sample case study pregnancy induced hypertension

Pregnant women’s experiences with the management of hypertensive disorders of pregnancy: a qualitative study

• Amyna Helou 1 ,
• Kay Stewart 1 ,
• Kath Ryan 2 &
• Johnson George 1  

BMC Health Services Research volume  21 , Article number:  1292 ( 2021 ) Cite this article

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Hypertensive disorders are a leading cause of mortality and morbidity during pregnancy. Despite multiple national and international clinical guidelines and a plethora of research in the field of optimising management, there has been limited research describing the perspectives and experiences of pregnant women with the management of hypertensive disorders of pregnancy (HDP). Understanding these perceptions and experiences is imperative to the optimisation of HDP management.

A qualitative study involving face-to-face, in-depth interviews were undertaken with 27 pregnant women diagnosed with and being treated for HDP to explore their perspectives of and experiences with clinical management. Written consent was obtained individually from each participant, and the interviews ranged from 16 to 54 min. Inductive codes were generated systematically for the entire data set. Line-by-line analysis was then performed and nodes were created within NVivo, a qualitative data management software. Data collection was continued until thematic saturation was reached. Thematic analysis was employed to interpret the data.

Three major descriptive themes were discerned regarding the women’s perspectives on and experiences with the management of HDP: attitudes towards monitoring of HDP, attitudes and perceptions towards development and management of complications, and perceptions of pregnant women with chronic hypertension. Trust in the hospital system, positive attitudes towards close blood pressure monitoring as well as self-monitoring of blood pressure, and a realistic approach to emergency antenatal hospital admissions contributed to a positive attitude towards monitoring of HDP. Women with prior experiences of HDP complications, including pre-eclampsia, were more confident in their clinical management and knew what to expect. Those without prior experience were often in shock when they developed pre-eclampsia. Some women with chronic hypertension displayed limited understanding of the potential risks that they may experience during pregnancy and thus lacked comprehension of the seriousness of the condition.

Conclusions

The clinical management experiences of pregnant women with HDP were varied. Many women did not feel that they were well informed of management decisions and had a desire to be more informed and involved in decision-making. Clear, concise information about various facets of HDP management including blood pressure monitoring, prescription of the appropriate antihypertensive agent, and planning for potential early delivery are required .

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Introduction

Hypertensive disorders of pregnancy (HDP) affect around 10% of pregnancies in Australia and around the world [ 1 ]. Combined, they are the second largest cause of maternal death, after haemorrhage, in the developed world [ 1 ].

In Australia, the public health system provides maternity care from pre-conception to postpartum. The main health professionals who care for the pregnant women are obstetricians, midwives, general practitioners (GP) and obstetric physicians [ 1 ]. The GP has an important role in pre-conception counselling, especially with women who have chronic diseases such as hypertension or asthma. It is also the responsibility of the GP to confirm the pregnancy and refer the woman to the relevant maternal hospital service.

Initially, the choice of model of care is given to the woman. The Midwifery Group Practice model [ 1 ] allows for one-to-one maternal care, often with the same midwife throughout the term of pregnancy, which is a suitable option for women without complications. Pregnant women with complications such as chronic hypertension or a previous pregnancy complicated by hypertensive disorders of pregnancy (HDP), however, need to be cared for by an obstetrician, who can monitor the progress of the pregnancy, blood pressure (BP), signs of pre-eclampsia, and fetal growth. The obstetric physician is usually involved in prescribing and monitoring antihypertensive medication and BP control. Pregnant women who have had pre-eclampsia previously or who have chronic hypertension are at risk of developing pre-eclampsia. Timely administration of low-dose (81-100 mg) aspirin before 16 weeks gestation has been found to reduce risk of pre-eclampsia [ 2 ].

Monitoring of BP occurs at each antenatal visit. If her BP is elevated, the woman may be referred to a day assessment unit for 4-h assessment of BP, which involves taking BP readings every half an hour for 4 h to observe the pattern of the BP and decide whether a diagnosis of HDP and/or prescription of an antihypertensive medication is warranted. In addition, test for urinary protein, full blood examination, renal function tests and fetal monitoring are performed [ 3 ]. This 4-h assessment is seen as a favourable alternative to overnight inpatient stays, both in terms of patient satisfaction and public health economics [ 3 ].

The timing of delivery in women with HDP is dependent on many maternal and fetal factors, including inability to stabilise BP, deteriorating liver and/or renal function, placental abruption, and severe fetal growth restriction [ 4 ]. Fetal morbidity and mortality are linked to the gestational age at delivery [ 4 ], so there is always a desire to prolong the pregnancy as close as possible to term (37 weeks) in the absence of an emergency. HYPITAT was a multicentre, open-label randomised controlled trial investigating induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks’ gestation [ 5 ]. The study reported a reduction in the incidence of severe hypertension as result of induction of labour at 36 weeks gestation. No significant clinical differences were found in outcomes such as thromboembolism, eclampsia or placental abruption [ 5 ]. This study was followed by HYPITAT-II, which found that delivery should be deferred until 37 weeks as opposed to 36 weeks, unless maternal deterioration supervenes [ 6 ].

Despite multiple clinical guidelines [ 4 , 7 , 8 ] and a plethora of research in the field of optimising HDP management, there have been limited published studies describing the experiences of pregnant women with the management of HDP, as distinct from medication treatment.

A survey of women with pre-eclampsia or their partners, friends or relatives found that many had no knowledge of pre-eclampsia prior to diagnosis and once diagnosed, did not appreciate how serious or life threatening it was [ 9 ]. Women wanted access to information about pre-eclampsia and their experience contributed substantial anxiety towards future pregnancies. Partners/friends/relatives also had no prior understanding of pre-eclampsia and expressed fear for the woman and/or her baby [ 9 ]. A qualitative study of pregnant Moroccan women in the Netherlands or Morocco found that knowledge of symptoms related to hypertensive disorders of pregnancy was limited or absent [ 10 ]. The limited knowledge of hypertension-related symptoms and complications was based on their own experiences or on those of some family members or stories from their social network or internet, with little or no information on symptoms from their midwives or obstetricians [ 10 ]. The experiences, perceptions and behaviours of pregnant women with regard to the management of HDP during pregnancy remain largely unexplored. Understanding these perceptions and experiences is imperative to the optimisation of HDP management.

To explore pregnant women’s perspectives of and experiences with clinical management of HDP.

Study design

A qualitative study using in-depth interviews was conducted, with pregnant women in their second or third trimester, recruited from antenatal clinics in two large tertiary hospitals in Melbourne, Australia.

Participants were sourced via a larger mixed-methods study, which included 100 pregnant women with HDP. Eligible participants were identified by one researcher (AH), who reviewed the medical records of pregnant women attending antenatal clinics, and then approached them individually. Participants were provided with written information for the larger study and on receipt of written informed consent, a questionnaire was given for self-completion. At the end of the questionnaire, participants were asked to indicate their interest in undertaking an interview. Of the 98 women who responded to the questionnaire, 65 expressed interest in being interviewed. Combined convenience and purposive sampling was conducted among these 65 women to seek a breadth of views. All of the women who were invited accepted to participate in an interview. Informed written consent was obtained prior to each interview, which included permission to audio record the conversation and to use quotations when anonymously reporting and publishing the results.

Study sample

Face-to-face, qualitative in-depth interviews were conducted with 27 pregnant women who were diagnosed with HDP and had a prescription for an antihypertensive medication, in either the second or third trimester of pregnancy, recruited from the antenatal outpatient clinics of two large tertiary maternity hospitals in Melbourne, Australia. Together, these hospitals provide antenatal care to approximately 13,000 women annually. They were identified using hospital records and approached during subsequent clinic visits. Participation was voluntary and involved informed consent.

The study sample size was determined based on theme saturation during analysis and was not predetermined. Recruitment ceased when no new information was forthcoming from the last three interviews, with regard to replication of data relating to attitudes towards HDP monitoring, perceptions of the development and management of complications (including early delivery) and perceptions of the women who had chronic hypertension.

Data collection

Interviews were conducted face to face by a single researcher (AH) a female Pharmacist (who was a PhD candidate at the time) after receiving training in in-depth interviewing prior to the commencement of the study using an interview guide developed based on the literature [ 11 , 12 ] and was agreed upon by the authors (Table  1 ). Open-ended questions, such as “Tell me about …? ”, followed by appropriate prompts, such as “How did that make you feel?” or “Can you explain that in more detail?” were used to guide the interview and encourage the interviewee to speak freely and in-depth about their experiences and thoughts. As the interviewer had met the participants during the larger study, some rapport had been established prior to the interview. The interviewer did not disclose their healthcare background to participants to avoid requests for health advice during the interviews. Interviews on average lasted 35 min (range 16 to 54 min) and were conducted in a private room near the antenatal clinics. No repeat interviews were performed.

Socio-demographic and self-reported health information was collected from participants through the questionnaire. Health information was verified, with consent, through medical records.

All interviews were audio-recorded, transcribed verbatim and de-identified. Interviews continued until data saturation was reached, deemed to be the point after which no new information for analysis was forthcoming [ 13 ]. The transcripts were not returned to the participants for comments or correction.

Data analysis

Data analysis occurred concurrently with the interviews. Initial coding was completed by AH using the qualitative data management software QSR NVivo 10 (QSR International) [ 14 ]. Inductive codes were generated systematically for the entire data set. Line-by-line analysis was then performed and nodes were created within NVivo. To ensure reliability, a random selection of 20% of the transcripts were coded independently by another member of the research team (KS). KS and KR read all the transcripts and any differences were discussed among all three to reach consensus. The researchers were all pharmacists; KS and KR had extensive experience in conducting qualitative research. Transcripts were reread by AH and KS to ensure that coding was accurate and all relevant data were included.

Thematic analysis was employed [ 15 ]. This was done across all HDP subtypes and severities to obtain a wide range of views. AH read and reread the codes, collapsed them into potential themes, compared the developing themes with the intact transcripts and cross referenced to HDP subtypes. When a pattern was seen within a certain subtype, coding was grouped specifically for that subgroup. Codes were arranged into potential themes. Themes were reviewed, refined and prepared into a final set with KS; sub-themes were identified within this process.

Participants

Of the 98 women who responded to the questionnaire, 65 expressed interest in being interviewed. A combination of convenience and purposive sampling was conducted among these women to seek a wide breadth of views. All participants had a diagnosis of HDP and were prescribed antihypertensive medication. Interviews occurred during pregnancy except for one, which happened 1 day postpartum. All participants were aged 18 years or over and were fluent in English. Twenty-seven women were interviewed to reach data saturation. Their demographics, clinical and obstetric characteristics are shown in Table  2 . Family members were present for some interviews but none of them participated in the interview or made comments. Field notes were taken by the interviewer during the interviews. No participants dropped out of the study or refused participation.

Eight participants were primigravidae, the remainder were multigravidae, including six who had previous miscarriages. One participant had an assisted pregnancy (in vitro fertilisation). Twelve were prescribed aspirin for the prevention of pre-eclampsia. Participants ranged in age from 26 to 42 years. The annotations at the end of each quote give a description of the participant’s age, parity, gestational trimester and subtype of HDP at the time of the interview. The participants did not provide feedback on the findings.

Interview themes

Three major descriptive themes were discerned regarding the women’s experiences with the management of HDP:

attitudes towards monitoring of hypertensive disorders of pregnancy;

attitudes and perceptions towards development and management of complications; and

perceptions of pregnant women with chronic hypertension.

Theme 1: Attitudes towards monitoring of hypertensive disorders of pregnancy.

Most women had general trust in the hospital system. Some felt extra confidence knowing that they were being managed at a maternity hospital:

“Hospital is for saving lives of people...as soon as I see the hospital I know that I am in safe hands.” (#14, 40 years, 2nd pregnancy, second trimester, severe pre-eclampsia).

“I felt very comfortable here...it seems like they are well prepared for these things...I was in the section of the hospital where all women were in the same [hypertension] situation.” (#9, 30 years, 1st pregnancy, second trimester, chronic hypertension).

One woman expressed some distrust in general hospitals, which she perceived as not managing her BP well:

“My own GP at that time increased it [methyldopa] to six a day … the hospital … increased to 10 a day … but I couldn’t lift my head up … so I ended up coming to the women’s hospital to Emergency, because I felt like no one’s helping me.” (# 71, 37 years, 3rd pregnancy, third trimester, severe pre-eclampsia superimposed on chronic hypertension).

Self-monitoring of BP was often recommended to women treated with antihypertensives. For some, it gave reassurance, but for others it was a source of confusion, with different messages coming from various members of the treating team:

“I take up to eight [methyldopa tablets] a day...I take two and then I’ll see what my readings are...at home, myself...I also do it if I have any other symptoms.....” (# 71, 37 years old, 3rd pregnancy, third trimester, severe pre-eclampsia superimposed on chronic hypertension).

“One of the physicians I saw told me to do it three times a day … three times in a row and then she said take the average of the second two readings each time...Then I told the obstetrician my readings and she said the machine that I had at home is under-measuring...but...the physician, he was quite interested...he wanted to see my readings because he likes to compare his machine to home machines.” (#53, 40 years, 6th pregnancy, third trimester, secondary chronic hypertension).

Some women had milder HDP in previous pregnancies, which gave them a sense that the monitoring and management was overstated. Others with more severe cases and their prior experience brought back memories initiating action to make plans:

“With [child 1] it was really bad during pregnancy. With [child 2] it was bad just in the last couple of weeks and straight afterwards...[child 3] was bad, but not really bad enough. They just called it hypertension, pregnancy induced hypertension and they just left it at that. They didn’t make a big song and dance about it...They made a big song and dance last time [child 4] and then this time [they said] ‘You’re going for your monitoring’...come back a week later...’You’re going for your monitoring’, couple of hours later – ‘You’re being admitted’...Then a couple of hours later...’You’re starting on medicine’.” (#6, 28 years, 4th pregnancy, 1 day postpartum, gestational hypertension).

“Last Wednesday when they [found] blood pressure’s up … it just brought back memories from last time because same thing. I just went in for an appointment and I never came home...Ten days later I came home with a baby. So I think those aspects freak me out a bit because it’s like ‘Oh, it’s happening again’ … every appointment...even this appointment, we’ve got contingency plans, just in case.” (#74, 36 years, 2nd pregnancy, third trimester, chronic hypertension).

Some women wondered about why they were not told their BP readings unless they asked:

“I find it funny that when they take your blood pressure they don’t tell it to you. I always have to ask, always, no matter who it is, midwife, physician, obstetrician. They take it and they walk away. It’s my body but they don’t tell me.” (#53, 40 years, 6th pregnancy, third trimester, secondary chronic hypertension).

Close monitoring was perceived as frustrating, but also as part of the life adjustments that come with having a baby. Some women considered spending four hours in the day assessment centre for monitoring their BP better than being an inpatient and staying overnight, whilst others saw it as an annoyance:

“I am happy to come back every day as long as I don’t have to spend overnight here. I am happy to be here for 12 hours a day, but I just can’t be away from my children at night time.” (#29, 26 years, 3rd pregnancy, second trimester, secondary chronic hypertension).

“They just monitor me at that perinatal care...you just sit here four hours a day...it’s shocking...worse than taking the tablet.” (#90, 35 years, 7th pregnancy, third trimester, chronic hypertension).

“The only thing that was slightly frustrating was [that] four hours is a long time to sit around, but again, you’re having a baby so you’ve got to make a few adjustments to your life.” (#99, 34 years, 1st pregnancy, third trimester, pre-eclampsia).

Some of the women required a short inpatient stay to stabilise their BP and avert an emergency premature delivery. For many, it was an emotional experience filled with apprehension and uncertainty about the future:

“It was very emotional, very scary, and at the same time still trying to stay strong. So that when my husband and my kids came in, I was like ‘I’ve just got a little bit high blood pressure, everything’s alright’...I didn’t know that a possible side effect of having the blood pressure is that they may have to deliver the baby [early].” (#32, 42 years, 3rd pregnancy, third trimester, severe early onset pre-eclampsia).

“B.P. at first was around 160...she came back 15 minutes – 170, another 15 minutes 180, within 10 minutes 190...I got nervous … After 160 they gave me ...labetalol...but [the BP] did not go down...There were other tablets they gave to me but [the BP still] didn’t go down...All the doctors came up...surrounded with those with scrub suits, I panic...blood pressure...went to 210..they were panicked...one just looked at me and said “AAAH”. I cried...of course you feel anxious, you feel sad...worried... what’s going on with me? I cried and cried. It was just like a movie, they push my bed out from the room and sent me quickly down to the birthing suite [in case delivery was imminent].” (#14, 40 years, 2nd pregnancy, second trimester, severe pre-eclampsia).

Theme 2: Attitudes and perceptions towards development and management of complications.

For many women, the diagnosis of pre-eclampsia came as a shock. Those with prior experience knew what to expect and were hesitant to cease antihypertensive treatment even if their BP was low. One woman without prior experience self-educated about pre-eclampsia, became concerned about the symptoms and developed anxiety about developing it:

“It was a shock and it was a bit scary...I thought ‘I’ve heard of pre-eclampsia but I don’t really know what it is’...but all the staff, they explained everything quite well... [I could see] how they were being very concerned about it, so that was making me realise this isn’t just a small thing, this is obviously a serious situation.” (#32, 42 years, 3rd pregnancy, third trimester, severe early onset pre-eclampsia).

“I didn’t want to stop the medication altogether, only because I just didn’t want to go through the path of having the high blood pressure affect the baby [intra-uterine growth restriction].” (#8, 36 years, 2nd pregnancy, third trimester, chronic hypertension).

“I was reading that if you do develop pre-eclampsia... it is a risk for the baby and the mother as well. Upon reading all that information...I became a bit paranoid, swollen foot, swollen hands, they’re part of the symptoms, headaches, generally not feeling well...I became quite paranoid looking at my symptoms and [thinking] have I got this, have I not got this? But the doctors actually did say that I have got borderline pre-eclampsia, so they were waiting to see if I was going to develop it. However, they haven’t been able to reassure me that I’m not going to develop it and...that was quite scary for me.” (# 24, 35 years, 1st pregnancy, third trimester, chronic hypertension diagnosed during pregnancy).

Some women understood that low-dose aspirin was being used for prevention of pre-eclampsia, whereas others did not always perceive it as being effective for this purpose. Many women thought that aspirin helped with controlling the BP rather than for prevention of pre-eclampsia:

“I started on aspirin throughout the pregnancy … just to...prevent mild pre-eclampsia happening again.” (#64, 30 years, 3rd pregnancy, third trimester, chronic hypertension).

“Obstetrician put me on one aspirin a day which is supposed to help control blood pressure. So perhaps that’s also why my blood pressure is being well controlled.” (#21, 35 years, 1st pregnancy, second trimester, chronic hypertension).

Most women had a general understanding that the only way to stop the direct effects of pre-eclampsia was to deliver the baby for the safety of both mother and child. The level of comfort with such a decision varied depending on the gestational stage of diagnosis of pre-eclampsia:

“I was really disappointed and very worried about the effect it [pre-eclampsia] would have on the baby [at 21 weeks] and whether or not I would be able to carry the baby to a safe week. I just thought...if something had happened and I was forced, like accidentally went into labour too early or something like that, the baby’s chances of survival would be very low and I was really upset.” (#21, 35 years, 1st pregnancy, second trimester, chronic hypertension).

“All I know is that you just need to get the baby out...I mean plenty of women and plenty of babies survive it...but you need to detect it pretty quickly before it turns into the full...is it eclampsia?” (#41, 34 years, 1st pregnancy, third trimester, chronic hypertension).

Although many women understood that they would not continue to full-term, their perceptions and fears about the potential for a premature delivery were related to their week of gestation, concern about the welfare of the baby, and fear of separation after the birth:

“I know from my reading that 24 weeks, it’s still not ideal obviously, but if you had the baby at 24 weeks that the chance of survival was higher. I think it was 43% chance of survival from this...prior to that it was like 16% chance of survival...My sister-in–law, who is a midwife, had said...they consider 26 weeks more viable. So after that it was like, right (a) to get to 24, (b) get to 26.”. (#21, 35 years, 1st pregnancy, second trimester, chronic hypertension).

“I am just worried about my baby [having] to be delivered earlier because you see the consequences...you see things happen in the future...they are still very weak...no sucking reflex yet, the lungs are not fully developed, so many things not developed...she may live but maybe there are some disabilities...I am just hoping that I will reach even up to 30 weeks or 32 weeks. That would make me feel better.” (#14, 40 years, 2nd pregnancy, second trimester, severe pre-eclampsia).

“I was 28 weeks [when I developed severe pre-eclampsia]...they gave me steroid injections to increase the lung capacity of the baby...One of the doctors came from the NICU with a leaflet about possibly having a premature baby...that was very upsetting...and to think of having the baby...then me going home with the baby staying here is just a very scary thought.”(#32, 42 years, 3rd pregnancy, third trimester, severe early onset pre-eclampsia).

Intervention with the delivery process was a likely reality for many women who had a prospect of early delivery. Some women were apprehensive about the prospect of induction of labour or caesarean section but understood that it was for their benefit and that of their child. Others were hesitant to allow for intervention unless the risks were made clear:

“So a little bit scary, but in a way I want it to, because I’m starting to feel the uncomfortable risk that’s associated with pregnancy in this condition. Knowing that she’s at full term now at 37 weeks and she’s fine and healthy, I don’t want to develop pre-eclampsia if I can help it.” (# 24, 35 years, 1st pregnancy, third trimester, chronic hypertension diagnosed during pregnancy).

“I’m trying to push it off because I don’t want to do it. I like to have the baby when the baby’s ready, not when they tell me to. But if they tell me to because it’s really dangerous for me then I’ll listen to them obviously ….” (#53, 40 years, 6th pregnancy, third trimester, secondary chronic hypertension).

Concerns about lack of information sharing by health professionals led some women to feel that they were left out of the planning for potential intervention in the delivery, whilst others voiced concern about having low-dose aspirin in the context of a possible emergency caesarean section:

“I even asked her last time actually because she said...I’m happy with the baby’s growth, but the blood pressure’s going up so … she said ‘I’m formulating a plan in my mind’ but she doesn’t like to disclose it. I don’t know why. It’s about me; I don’t know why she just doesn’t tell me.” (#53, 40 years, 6th pregnancy, third trimester, secondary chronic hypertension).

“I also thought...what if I have an emergency caesarean tomorrow and I haven’t gotten off the aspirin? Is it going to cause me issues?” (#29, 26 years, 3rd pregnancy, second trimester, secondary chronic hypertension).

Theme 3: Perceptions of pregnant women with chronic hypertension.

Many women with chronic hypertension were already on antihypertensive medication not deemed safe during pregnancy when they found out they were pregnant. For some, it was changed to a safer alternative as soon as possible, whilst for others, the decision to change the medication was delayed and the patient’s assessment of potential risks was downplayed:

“I was on medication [telmisartan]...then when I had the kidney scan and I found out [that I was pregnant], my G.P. said ‘You’ve got to stop taking that medication because it’s not safe...so then she gave me another one to take.” (#2, 30 years, 1st pregnancy, third trimester, secondary chronic hypertension).

“The first time I found out I was pregnant I went to a GP...I told the GP that I’m taking atenolol, and then she told me that...atenolol is not recommended for pregnancy... so I asked....What medication do you think that I should take?’...she said she doesn’t dare to prescribe me any medicine because she knows she is going to refer me to a hospital.” (#59, 34 years, 1st pregnancy, second trimester, chronic hypertension).

Other women had their antihypertensive changed during the pre-pregnancy planning stage:

“[To be safe during pregnancy] I would just have to change my medications. The medication I was on I couldn’t be on while being pregnant. So when we decided to try for our first child, I went on the Aldomet and oxprenolol and that’s what I pretty much stayed on because we always wanted a second child.” (#1, 39 years, 2nd pregnancy, third trimester, secondary chronic hypertension).

Some women with chronic hypertension had concerns about lack of information sharing by health professionals and felt that they were not well informed of the potential risks that their hypertension may have on the pregnancy. Some mentioned that they may have ‘taken it more seriously’ if they had known about the risk of premature delivery associated with uncontrolled hypertension, whilst others had some limited awareness of pre-eclampsia:

“When they told me I had protein in my urine, I was a bit scared because I don’t know if it’s related to my BP.” (#4, 33 years, 1st pregnancy, third trimester, chronic hypertension).

One woman was very anxious about her diagnosis of severe, early-onset pre-eclampsia so she did some ‘self-research’. Unfortunately, she misinterpreted the information and caused herself extra unwarranted fear:

“I read on [US website found on Google] and found that 80% die after/during birth that have pre-eclampsia. That was really scary.” (#71, 37 years, 2nd pregnancy, third trimester, severe pre-eclampsia superimposed on chronic hypertension).

The information on the US Preeclampsia Foundation website actually states that “Nearly 80% of women who die from pre-eclampsia die post-partum” [ 16 ].

For some women with chronic hypertension, lack of knowledge of the seriousness of the condition resulted in lack of comprehension of the importance of BP monitoring and treatment:

“I think it was about 140 over 110 or something like that … which is pretty normal for me but they think it’s high … I feel alright. It’s all good.” (#90, 35 years, 7th pregnancy, third trimester, chronic hypertension).

“I really tried for weeks not to go on [the antihypertensive], but then when she said that maybe you could have a stroke, I got a bit scared, a lot scared … I got really worried because then they said … you could have problems, the baby could die. And I got really upset when she said the baby could not get enough oxygen. I just felt, oh just have whatever it is.” (#22, 37 years, 3rd pregnancy, third trimester, chronic hypertension).

Most women who had chronic hypertension were under a model of care involving both an obstetrician and a physician. One was triaged to midwife-only care, despite having a diagnosis of chronic hypertension and being prescribed an antihypertensive medication. This then caused a delay in the change of the antihypertensive to a safer alternative:

“Actually, I asked the midwife whether it [atenolol] is safe or not [at 18 weeks gestation]...and then she said that...it should be okay, but to be safe discuss with the physician. And so, because she said it should be okay, I presumed that ‘Oh that is okay’ ... but then the physician said ‘No, it’s better not to...so from now onwards you have to take this medicine [oxprenolol]’.” (#59, 34 years, 1st pregnancy, second trimester, chronic hypertension).

Many women had their first antenatal appointment at the hospital between 16 and 20 weeks gestation. Some women, especially those with chronic hypertension, had concerns about the timing of this appointment:

“It takes a long time now for women to get their first appointment through the hospital. It wasn’t like that, I think, about 10 years ago, must’ve changed by now … Now you have to wait ‘til you’re about 18, 20 weeks before you get your first actual appointment...and if you’ve got other health issues, things can go wrong, which it did with me.” (#71, 37 years, 2nd pregnancy, third trimester, severe pre-eclampsia superimposed on chronic hypertension).

Some women did not know that they had high BP before pregnancy. This may have been because they did not get regular check-ups with the GP or that their BP was not routinely checked at regular GP visits:

“I think if I had never gotten pregnant, I definitely would not have had [high BP], would not have to be on medication … because I wouldn’t be under the strain that I am. And also I wouldn’t be in with the doctor. I don’t think I would’ve gone to the doctor and said put me on medication … because I didn’t, want anything to change. But my lifestyle is changing now so I don’t have a choice.” (#18, 35 years, 2nd pregnancy, second trimester, chronic hypertension).

“It [BP] was quite normal before the pregnancy, so obviously it’s pregnancy-related according to the doctors [despite having been diagnosed at 7 weeks].” (#24, 35 years, 1st pregnancy, third trimester, chronic hypertension diagnosed during pregnancy).

Many women had developed chronic hypertension after a previous pregnancy that involved either gestational hypertension or pre-eclampsia. Some of them had routine follow-up for their hypertension postpartum and understood that it was now chronic hypertension, whilst others did not:

“Once I’d had the baby they changed my medication to the perindopril...I was then checking my BP at home...the readings were fine...when they did get too high, I’d go back to my local GP who would then once again adjust the dosage accordingly...I have been told by my local GP that generally once you’re on a blood pressure medication, you’re on it for life, whether it’s a minimal dosage or, depending on what the readings are, what they need to give...I’m happy to stay on that.” (#8, 36 years, 2nd pregnancy, third trimester, chronic hypertension).

“I got increased blood pressure at the end [of the previous pregnancy] and they put me in perinatal care, but then afterwards it was okay....I honestly just didn’t go to the doctor, and I haven’t gone to the doctor since I fell pregnant with this one.” (#90, 35 years, 7th pregnancy, third trimester, chronic hypertension).

One woman described having been prescribed an antihypertensive during her previous pregnancy and never told to stop it, so she continued with no formal review of her hypertension until the current pregnancy:

“They never told me to stop taking the tablet [labetalol] after I had him [first child] so I just kept continuing with it ... I saw the physician [during this current pregnancy] and he just said just keep taking it...he actually questioned ‘Did they ask you to stop it?...I said no one spoke to me about anything...I was here for a week after I had him [first child]...no one ever discussed it.” (#58, 38 years, 2nd pregnancy, third trimester, chronic hypertension).

Trust in the hospital system, positive attitudes towards close BP monitoring as well as self-monitoring of BP (SMBP) and a realistic approach to emergency antenatal hospital admissions contributed to a positive attitude towards monitoring of HDP. Most of the women in our study had a general trust in the healthcare system. Distrust surfaced when health services outside the women’s hospital were not seen as able to control hypertension early in the pregnancy, triggering patient-initiated referral to the women’s hospital. Trust of healthcare systems in western countries is generally declining [ 17 ]. It is, however, important to note that pregnant women with HDP are considered to be in a high-risk pregnancy and are thus more vulnerable than the general population. Therein lies dependence on the hospital system, especially in urgent situations such as needing to lower BP or planning for an early delivery, similar to the dependence reported in patients with coronary heart disease [ 18 ].

Anecdotally, it is common for healthcare professionals to mention that the BP reading is ‘good’ or ‘too high’ without telling the patient the systolic/diastolic numbers. An important factor relating to patient evaluation of care is their involvement in decision-making [ 19 ]. Most of the women in our study were not involved in decision-making, leaving some to wonder why this was so. This suggests that pregnant women with HDP would like to be better informed of their situation and be part of the decision-making process when deemed appropriate. This is consistent with the women’s views from the pilot of the CHIPS study who enjoyed being heavily involved in their BP management [ 20 ]. One way to have women more involved in their BP management is to encourage SMBP. SMBP in the general population has been shown to reduce BP [ 21 ] and improve adherence to antihypertensive medication [ 22 ]. In our study, SMBP was often recommended to women who were prescribed antihypertensive medications. This was taken up well by most, similar to the CHIPS pilot study [ 20 ]. SMBP during pregnancy has also been shown to be reassuring and not anxiety provoking [ 23 ] which was seen in our study. A recent survey of 5555 pregnant women from antenatal clinics in 16 hospitals in England, found that nearly half of the 389 hypertensive women reported SMBP, and that the majority of them (79%) shared their BP readings with their treating doctor [ 24 ]. Such partnership has been shown to improve patient adherence in the general population [ 25 ]. There is however an assumption that because these women are in a high-risk pregnancy, the healthcare professionals (HCP) tend to take over and do not acknowledge that the women are quite competent and that with the correct information can be involved in SMBP in collaboration with the HCPs. It is thus important to have a good doctor-patient relationship to reduce confusion, instil confidence in SMBP and complete the circle of care.

Those with prior experience with HDP and monitoring had varied views, often depending on the severity of disease in the previous pregnancy (ies). Good communication about how HDP can vary from one pregnancy to another, being either worse or better, may assist in reducing the cynicism of some and reassure others. Similarly, those who had prior experience with pre-eclampsia were a lot more confident in their management and knew what to expect. Those who did not have prior experience were often in shock and were at times anxious about the diagnosis, a finding similar to another study relating to the understanding of pre-eclampsia [ 26 ]. Moreover, the use of low-dose aspirin to prevent pre-eclampsia was only partially understood by women in our study. This indication should be communicated clearly to women who are at high risk of developing pre-eclampsia. The plan for the cessation of aspirin before delivery should also be communicated clearly to reduce any anxiety that may be present, especially in terms of a potential emergency delivery.

At times, antenatal inpatient admission was required to stabilise BP and closely monitor both the mother and baby. This was a particularly apprehensive time, especially for women who had not experienced HDP during a previous pregnancy. It is important to have good, clear communication with women about the need for close monitoring, affirmation concerning their status as worthy of hospital care, provision of consistent information, inclusion in decision-making and good social support [ 27 ]. A possible alternative to inpatient admission can be pregnancy day assessment monitoring. Despite limited research into this model of care, pregnant women have been found to prefer a four-hour stay rather be admitted to hospital for one or more nights, if the situation is deemed safe to do so [ 3 ]. This is consistent with our findings. Once again, clear consistent information regarding the need for this type of monitoring should be given to women who require it. Recent advancements in the integration of telemedicine into antenatal care [ 28 ] have encouraged early research into the feasibility of incorporating this for women with HDP to reduce the burden of multiple antenatal hospital visits [ 29 ]. The unpredictable course of worsening BP and the development of pre-eclampsia pose specific challenges to this monitoring and would require a holistic approach. A recent single centre study in the UK [ 29 ] developed and trialled an innovative SMBP intervention including a downloadable mobile app in for women with HDP to monitor for signs of pre-eclampsia or worsening hypertension. Although this study showed positive acceptance and compliance from the women, further research is required to meet the standard of care required for them [ 29 ].

In general, most women desire to labour spontaneously and have a natural birth [ 30 ]. When the reality that the only way to stop the direct effects of pre-eclampsia is to deliver the baby at any given gestational week is revealed to some women, it is received with disappointment. Good communication by the treating doctor about the intention to preserve the pregnancy for as close as possible to term is required. Likewise, sound communication about the need for a premature delivery should be communicated clearly. Moreover, it has been shown that pregnant women who require induction of labour or caesarean section often feel left out of the decision-making process [ 30 ]. An Australian study of women’s experiences of decision-making and attitudes in relation to induction of labour, reported a clear need for women to be provided with more information and agency when making decisions about their timing of birth, particularly when there are multiple reasonable treatment options [ 30 ]. Furthermore, emergency caesarean sections have been found to negatively contribute to several psychosocial outcomes for women, in particular post-traumatic stress [ 31 ]. There is, thus, a need for careful consideration and counselling for women after an emergency caesarean delivery. This can involve the members of the antenatal treating team but also counsellors or psychologists. Moreover, counselling of pregnant women who are at risk of emergency caesarean, either because of their HDP or otherwise, about this possibility may help to pre-empt potential trauma.

Research into the management experiences of pregnant women with chronic hypertension, as distinct from medication treatment, is scant. Our study has highlighted the need for extra attention to be given to improve management pre-conception, during the pregnancy and postpartum. A qualitative study exploring knowledge and attitudes related to pregnancy and preconception health in women with chronic medical conditions, including chronic hypertension, found that the women had limited knowledge of the specific potential complications of pregnancy [ 32 ]. Some women in our study also displayed limited understanding of the potential risks that they may endure during pregnancy and thus had a lack of comprehension of the seriousness of the condition. Counselling women pre-conception regarding potential risks during pregnancy allows them to be more aware of what to expect [ 33 ]. Moreover, an open conversation about the information that the pregnant woman may have either from prior experience or ‘self-research’ would help to improve understanding as well as avoiding confusion and unnecessary anxiety. The provision of written material so that the women can refer to it when necessary would also be appropriate. Another facet of management of chronic hypertension pre-conception is the initial diagnosis of hypertension. Some women in our study were not aware of their BP readings before pregnancy and were diagnosed with hypertension quite early in pregnancy and thus classed as having chronic hypertension. Regular checking of BP in women of reproductive age at routine GP visits may help to identify chronic hypertension earlier. This can help in the planning of a pregnancy, or ensure that the BP is under control in the case of an unexpected pregnancy. Similarly, for those who have chronic hypertension and are prescribed antihypertensives, switching the medication to one that is safer during pregnancy, either pre-conception or as early as possible, can help to reduce fetal exposure and reduce the mother’s anxiety. Both GPs and community pharmacists have a role in counselling women of reproductive age who are prescribed an antihypertensive. A simple question as to whether the women is planning a pregnancy can help initiate the necessary conversation and trigger the switch to a safer alternative in a timely manner. Various resources are available to help make the decision to change the antihypertensive, including drug information lines at maternity hospitals. Moreover, a large number of women who had entered our study with chronic hypertension had developed the condition after a previous pregnancy that was affected by gestational hypertension or pre-eclampsia. Furthermore, our study found that many women developed chronic hypertension soon after a pregnancy complicated by HDP. This is supported by a recent systematic review and meta-analysis which reported that the risk of developing hypertension after HDP is highest in the early postpartum period [ 34 ]. The authors also suggested that diagnosis and targeted interventions to improve maternal cardiovascular health may need to be commenced in the immediate postpartum period [ 33 ]. We agree with this and call for a more integrated follow up with women in the postpartum period and beyond. This may involve the GP and the community pharmacist for easy accessibility for the women.

Although most women with chronic hypertension in our study were under a model of care involving an obstetrician and a physician, one was under midwifery care despite having chronic hypertension and being prescribed an antihypertensive. Although it is recognised by Australian guidelines for the management of HDP that midwives play a role in a multidisciplinary team in relation to management of HDP [ 4 , 35 ], they are not qualified to independently prescribe medication and manage cases of pregnant women with chronic hypertension requiring treatment. Similarly, a recent scoping review found that practising midwives worldwide lack knowledge on several aspects of pre-eclampsia diagnosis and care and have called for an increase in in-service training to increase midwives’ knowledge in this area [ 36 ]. It is therefore important that all pregnant women who have chronic hypertension be under the doctor model of care to monitor both mother and baby throughout the pregnancy.

Recommendations for practice

Good communication between the HCP and the patient is important to optimise management. Clear, direct and concise information about various facets of the management of HDP should be provided for all women who experience HDP.

Women who experience any form of HDP during pregnancy should be invited to be part of the decision-making pertaining to the monitoring of BP and progression to pre-eclampsia as well as the timing and mode of delivery when appropriate.

There should be a priority for women with chronic hypertension to be seen at the hospital under an obstetrician led model of care before 18 weeks, not only for the regular monitoring of BP and fetal progress but also for the timely prescription of low-dose aspirin before 16 weeks gestation for the prevention of pre-eclampsia. Furthermore, other health professionals, including psychologists and pharmacists, can be involved in the prenatal care of these women to address potential fear and anxiety as well as the optimal use of medication.

Women who have chronic hypertension and are of reproductive age should be informed of the potential risks of pregnancy and be switched to a pregnancy safe antihypertensive in the preconception stage.

Women who experience gestational hypertension or pre-eclampsia during pregnancy should have their BP monitored postpartum by the GP or the community pharmacist to identify any risk of developing severe cardiovascular events.

Recommendations for future research

Currently, much of the monitoring of HDP requires a hospital visit. Further research into the feasibility of telehealth for the monitoring of HDP, especially in mild cases will help to include patients in the decision-making. Moreover, future research into the role of the GP and the community pharmacist in the pre-pregnancy planning stage for those with chronic hypertension and postpartum for those with gestational hypertension or pre-eclampsia is warranted.

Strengths and limitations

This qualitative study is the first to use in-depth interviews to explore pregnant women’s experiences, perceptions and behaviours with regard to the management of HDP during pregnancy. Our study included women with all forms of HDP except HELLP and eclampsia, as the interviews were done when the women were in a comfortable, non-emergency situation. Participants varied in gestation stage, subtype of HDP, severity of HDP, ethnicity and socioeconomic status allowing for a wide range of views. The interviews were conducted during pregnancy thus reducing recall bias. This is in contrast to other qualitative studies which explored aspects of HDP in retrospect [ 27 , 35 , 37 ]. Recruitment was from two major public maternity referral hospitals in Melbourne with a widespread combined catchment including metropolitan, regional and rural areas. Participants did not include those in the first trimester of pregnancy, as most were scheduled to attend the antenatal clinics after 12 weeks gestation. Views of women with chronic hypertension during the first trimester of pregnancy may vary from those in the second and third trimesters and they were not captured . Women with poor English skills were excluded from the study, therefore, caution should be taken in the extrapolation of our findings to women from non-English speaking backgrounds.

The clinical management experiences of pregnant women with HDP were varied. Many women did not feel that they were well informed of treatment and management decisions and had a desire to be more informed and more involved in decision-making. Clear, concise information about various facets of HDP management including BP monitoring, administration of low dose aspirin in women with a high risk of developing pre-eclampsia, prescription of the appropriate antihypertensive, and planning for potential early delivery are required. In addition, cardiovascular pre-pregnancy planning and postpartum follow-up should be routinely offered to women.

Availability of data and materials

The datasets generated and/or analysed during the current study are not publicly available due to privacy surrounding participant information as stipulated in the written consent form, but are available from the corresponding author on reasonable request.

Royal Australian and New Zealand College of Obstetrians and Gynaecologists. Maternity Care in Australia. 1st ed; 2017.

Google Scholar  

Roberge S, Nicolaides K, Demers S, Hyett J, Chaillet N, Bujold E. The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis. Am J Obstet Gynecol. 2017;216(2):110–20 e6.

Article   CAS   Google Scholar  

Dunlop L, Umstad M, McGrath G, Reidy K, Brennecke S. Cost-effectiveness and patient satisfaction with pregnancy day care for hypertensive disorders of pregnancy. Aust NZ J Obstet Gyn. 2003;43(3):207–12.

Article   Google Scholar  

Lowe SA, Bowyer L, Lust K, McMahon LP, Morton MR, North RA, et al. The SOMANZ guidelines for the Management of Hypertensive Disorders of pregnancy 2014. Aust NZ J Obstet Gyn. 2015;55(1):11–6.

Koopmans CM, Bijlenga D, Groen H, Vijgen SMC, Aarnoudse JG, Bekedam DJ, et al. Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks’ gestation (HYPITAT): a multicentre, open-label randomised controlled trial. Lancet. 2009;374(9694):979–88.

Broekhuijsen K, van Baaren GJ, van Pampus MG. Immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy between 34 and 37 weeks of gestation (HYPITAT-II): a multicentre, open-label randomised controlled trial (vol 385, pg 2492, 2015). Lancet. 2016;387(10021):848.

Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. Hypertensive disorders of pregnancy ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension. 2018;72(1):24–43.

Magee LA, Pels A, Helewa M, Rey E, von Dadelszen P, Pr CHD. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy. Pregnancy Hypertens. 2014;4(2):105–45.

East C, Conway K, Pollock W, Frawley N, Brennecke S. Women’s experiences of preeclampsia: Australian action on preeclampsia survey of women and their confidants. J Pregnancy. 2011. Article number 375653.

Ouasmani F, Engeltjes B, Haddou Rahou B, Belayachi O, Verhoeven C. Knowledge of hypertensive disorders in pregnancy of Moroccan women in Morocco and in the Netherlands: a qualitative interview study. BMC Pregnancy Childbirth. 2018;18(1):344.

Sawicki E, Stewart K, Wong S, Leung L, Paul E, George J. Medication use for chronic health conditions by pregnant women attending an Australian maternity hospital. Aust NZ J Obstet Gynaecol. 2011;51(4):333–8.

Lim AS, Stewart K, Abramson MJ, Ryan K, George J. Asthma during pregnancy: the experiences, concerns and views of pregnant women with asthma. J Asthma. 2012;49(5):474–9.

Fusch PI, Ness LR. Are we there yet? Data saturation in qualitative research. Qual Rep. 2015;20(9):1408–16.

Microsoft Windows NVivo 10. [Available from: http://help-nv10.qsrinternational.com/desktop/concepts/about_nodes.htm .] Accessed 21 Feb 2020.

Braun VC, V. Using thematic analysis in psychology. Qual Res Psychol. 2006;3(2):77–101.

Preeclampsia Foundation 2021 [Available from: https://www.preeclampsia.org/health-information ]. Accessed 11/02/2021.

Ward PR, Rokkas P, Cenko C, Pulvirenti M, Dean N, Carney S, et al. A qualitative study of patient (dis) trust in public and private hospitals: the importance of choice and pragmatic acceptance for trust considerations in South Australia. BMC Health Serv Res. 2015;15:297.

Meyer SB, Ward PR. Differentiating between trust and dependence of patients with coronary heart disease: furthering the sociology of trust. Health Risk Soc. 2013;15(3):279–93.

Hodnett ED. Pain and women’s satisfaction with the experience of childbirth: a systematic review. Am J Obstet Gynecol. 2002;186(5):S160–S72.

Magee LA, von Dadelszen P, Chan S, Gafni A, Gruslin A, Helewa M, et al. Women’s views of their experiences in the CHIPS (control of hypertension in pregnancy study) pilot trial. Hypertension Pregnancy. 2007;26(4):371–87.

Tucker KL, Sheppard JP, Stevens R, Bosworth HB, Bove A, Bray EP, et al. Self-monitoring of blood pressure in hypertension: a systematic review and individual patient data meta-analysis. PLoS Med. 2017;14(9):e1002389. https://doi.org/10.1371/journal.pmed.1002389 .

Ogedegbe G, Schoenthaler A. A systematic review of the effects of home blood pressure monitoring on medication adherence. J Clin Hypertens (Greenwich). 2006;8(3):174–80.

Hinton L, Tucker KL, Greenfield SM, Hodgkinson JA, Mackillop L, McCourt C, et al. Blood pressure self-monitoring in pregnancy (BuMP) feasibility study; a qualitative analysis of women’s experiences of self-monitoring. BMC Pregnancy Childbirth. 2017;17(1):427. https://doi.org/10.1186/s12884-017-1592-1 .

Tucker KL, Hodgkinson J, Wilson HM, Crawford C, Stevens R, Lay-Flurrie S, et al. Current prevalence of self-monitoring of blood pressure during pregnancy: the BUMP survey. J Hypertens. 2021;39(5):994–1001.

Sabate E, editor. Adherence to long-term therapies: evidence for action. Geneva: World Health Organization; 2003.

You WB, Wolf M, Bailey SC, Pandit AU, Waite KR, Sobel RM, et al. Factors associated with patient understanding of preeclampsia. Hypertens Pregnancy. 2012;31(3):341–9.

Barlow JHHJ. Thornton S Women’s experiences of hospitalisation with hypertension during pregnancy: feeling a fraud. J Reprod Infant Psychol. 2008;26(3):157–67.

Zairina E, Abramson MJ, McDonald CF, Li J, Dharmasiri T, Stewart K, et al. Telehealth to improve asthma control in pregnancy: a randomized controlled trial. Respirology. 2016;21(5):867–74.

Sheehan EKA, Kay L. Using a smartphone app to identify signs of pre-eclampsia and/or worsening blood pressure. Br J Midwifery. 2019;27(2):92–9.

Coates D, Goodfellow A, Sinclair L. Induction of labour: experiences of care and decision-making of women and clinicians. Women Birth. 2020;33(1):e1–e14.

Benton M, Salter A, Tape N, Wilkinson C, Turnbull D. Women’s psychosocial outcomes following an emergency caesarean section: a systematic literature review. BMC Pregnancy Childbirth. 2019;19(1):535.

Chuang CH, Velott DL, Weisman CS. Exploring knowledge and attitudes related to pregnancy and preconception health in women with chronic medical conditions. Matern Child Hlth J. 2010;14(5):713–9.

Seely EW, Ecker J. Chronic hypertension in pregnancy. Circulation. 2014;129(11):1254–61.

Giorgione V, Ridder A, Kalafat E, Khalil A, Thilaganathan B. Incidence of postpartum hypertension within 2 years of a pregnancy complicated by pre-eclampsia: a systematic review and meta-analysis. BJOG. 2021;128(3):495–503.

Roberts LM, Davis GK, Homer CS. Pregnancy with gestational hypertension or preeclampsia: a qualitative exploration of women’s experiences. Midwifery. 2017;46:17–23.

Garti I, Gray M, Tan JY, Bromley A. Midwives’ knowledge of pre-eclampsia management: a scoping review. Women Birth. 2021;34(1):87–104.

Shanmugalingam R, Mengesha Z, Notaras S, Liamputtong P, Fulcher I, Lee G, et al. Factors that influence adherence to aspirin therapy in the prevention of preeclampsia amongst high-risk pregnant women: a mixed method analysis. PLoS One. 2020;15(2):e0229622. https://doi.org/10.1371/journal.pone.0229622 .

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Acknowledgements

We would like to thank the staff at both the Mercy Hospital for Women and the Royal Women’s Hospital for their help with this study. We would also like to thank all the women who participated.

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All authors contributed to the conception and design of the study. Patient recruitment and in-depth interviews were undertaken by AH. Data analyses and interpretation were performed by AH, KS and KR. The manuscript was written by AH and critically reviewed by all authors. All authors read and approved the final manuscript.

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Ethical approval was obtained from Mercy Health Human Research Ethics Committee Heidelberg-Melbourne (R12/62) 08/01/2013, The Royal Women’s Hospital Research and Human Research Ethics Committee Parkville-Melbourne (R13/18) 12/07/2013 and Monash University Human Research Ethics Committee Clayton-Melbourne (CF13/117) 18/01/2013. Informed written consent was obtained prior to each interview, which included permission to audio record the conversation and use quotations when anonymously reporting and publishing the results. All methods were carried out in accordance with relevant guidelines and regulations of the ethics committees.

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Helou, A., Stewart, K., Ryan, K. et al. Pregnant women’s experiences with the management of hypertensive disorders of pregnancy: a qualitative study. BMC Health Serv Res 21 , 1292 (2021). https://doi.org/10.1186/s12913-021-07320-4

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A CASE STUDY ON LIFE-THREATENING PREGNANCY-INDUCED HYPERTENSION IN PRETERM PREGNANCY AND MANAGEMENT CHALLENGES

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Introduction: Hypertensive disorders of pregnancy are the most common causes of adverse maternal & perinatal outcomes. Such investigations in resource limited settings would help to have great design strategies in preventing maternal and perinatal morbidity and mortality. All women who presented with hypertensive disorders of pregnancy and delivered in the hospital and whose records were complete, were included in the study and divided into 5 groups namely, Gestational hypertension (GH), Mild pre-eclampsia (PE), Severe pre-eclampsia, Eclampsia and Chronic hypertension with superimposed pre-eclampsia (CHPE) based on their clinical presentation at admission. After excluding all incomplete data entries, the sample size was finalized at 200. Results: In this study, records of 2,989 women who delivered in our tertiary hospital were reviewed and of these, 256 women had hypertensive disorders of pregnancy. Fifty six of these women had either left the hospital against medical advice or their records were incomplete so their outcome could not be followed and hence were excluded from the study. Conclusion: Pre-eclampsia and Eclampsia still remains a major problem in developing countries. Pregnancy induced hypertension is one of the most extensively researched subjects in obstetrics. Still the etiology remains an enigma to us. Though the incidence of pre-eclampsia and eclampsia is on the decline, still it remains the major contributor to poor maternal and foetal outcome. The fact that pre-eclampsia, eclampsia is largely a preventable disease is established by the negligible incidence of pre-eclampsia and eclampsia with proper antenatal care and prompt treatment of pre-eclampsia. In preclampsia and eclampsia, pathology should be understood and that i-involves multiorgan dysfunction should be taken into account. The early use of antihypertensive drugs, optimum timing of delivery and strict fluid balance, anticonvulsants in cases of eclampsia will help to achieve successful outcome. Early transfer to specialist centre is important and the referral the referral centers should be well equipped to treat such critically ill patients.

IOSR Journals

Back Ground: Aim: The Aim of the study was to find out the incidence of PIH & Preeclampsia and to evaluate the risk factors, predictors of severity and obstetrical and perinatal outcome in severe preeclampsia and Eclampsia.. Place and duration Methodology: Out of total 8800 deliveries 880 were diagnosed to have pregnancy induced hypertension. Out of these 580 (66%) had gestational hypertension. 80(0.9%) cases had preeclampsia without severe features, 220(2.5%) cases had preeclampsia with severe features. The present study was conducted in 200 cases of preeclampsia with severe features. The cases were evaluated and managed as per the existing protocol in the department and Obstetrical and perinatal outcome were recorded and analyzed. Results: The incidence of pregnancy induced hypertension was 10% and preeclampsia 3.5% in our study. 50% had anemia and 30% had obesity as risk factors. Materanl mortality was seen in 12cases of severe preeclamsia, accounting to 50% of total maternal deaths in our centre. Other maternal complications were seen in 60% of cases.Most common was Eclamsia in 30% of cases followed by Abruption in 20% & DIC in 18% and 20% of cases required transfusion of blood & Blood components for thrombocytopenia and coagulation failure. 10% cases required ventilator support for dyspneoa. Perinatal mortality was seen in 16% of cases. Perinatal morality is due to premaurity, low birth weight and abruption. NICU admissions were required in 20% of cases because of severe birth Asphyxia. Conclusion: Regular antenatal checkup and regular blood pressure measurement will help in early detection of hypertensive cases. Treating anemia and educating women on significance of alarming symptoms will improve maternal and perinatal outcome. Hospitalisation, regular BP monitoring, investigations and timely delivery will improve significantly the maternal and perinatal outcome. A good maternal intensive care unit and neonatal intensive care unit will help to improve obstetrical and perinatal outcome in hypertensive disorders of pregnancy.

Hypertension in Pregnancy

Altaf shaikh

Corine Koopmans

https://www.ijhsr.org/IJHSR_Vol.11_Issue.1_Jan2021/IJHSR_Abstract.041.html

International Journal of Health Sciences and Research (IJHSR)

Background: Hypertension is one of the common medical complications of pregnancy & contributes significantly to maternal & perinatal morbidity & mortality. The World Health Organization estimates that at least one woman dies every seven minutes from complications of hypertensive disorders of pregnancy. Hence a study was undertaken to assess the impact of Pregnancy Induced Hypertension on fetal outcomes among mothers with PIH who delivered at tertiary care hospital, Dadra & Nagar Haveli. Method: It was a cross sectional study conducted at Shri Vinoba Bhave Civil Hospital, Silvassa, Dadra & Nagar Haveli from September to November 2020.The sample size of the study was 32. The data regarding demographic variables, obstetric history, clinical details & examinations, investigations & fetal outcomes was collected using Structured Interview Schedule. Result: In the present study, Gestational Hypertension was found to be 65.62%, Pre eclampsia was 28.12% and Eclampsia was found to be 6.25%. It was more prevalent among multipara mothers. The clinical representation of PIH showed that 71.87% mothers had pain in lower abdomen, 37.3% had pedal edema followed by 15.62% headache & 9.37% blurring of vision. Antihypertensive drugs (93.75%) were given to almost all the mothers whereas 9.37% were treated with anticonvulsant medicines. The most common fetal complications found were preterm births (43.75%) & LBW (37.5%). 28.12% babies required NICU admission due to various reasons whereas 6.25% neonatal deaths were reported. Conclusion: Pregnancy-related hypertensive disorders are common and adversely impact perinatal outcomes. Efforts should be made at both the community and hospital levels to increase awareness regarding hypertensive disorder of pregnancy and reduce its associated morbidity and mortality.

Clinical & Biomedical Research

Francisco Maximiliano Pancich Gallarreta

Scholar Science Journals

Background: Preeclampsia and eclampsia have been recognized as clinical entities since the times of Hippocrates. Pregnancy induced hypertension (PIH) is one of the commonest disorders associated with the increased risk of maternal and fetal complications. It is reported in the world literature that the incidence of eclampsia is on the decline, but still a menace in developing countries. Objectives: To study the maternal and foetal outcome in pregnancy induced hypertension. Material and Methods: A prospective randomized study was carried out A total of 100 pregnant women with PIH were enrolled in the study. A pre-tested interview tool was used to collect necessary information such as detailed history, clinical examination findings and investigations performed. Results were analysed using SPSS 13.0 Results: In the present study, the overall incidence of PIH was 8.96%, which includes preeclampsia in 7.26% and eclampsia in 1.70%. Preterm labour was the commonest maternal obstetrical complication observed in 18% of mild PIH and 48% of severe PIH cases. Prematurity was the commonest foetal complication seen in 17.99%, 47.62% and 52.63% of mild PIH, severe PIH and Eclampsia cases respectively. Conclusion: Pregnancy induced hypertension is a common medical disorder seen associated with pregnancy in the rural population, especially among young primigravidas, who remain unregistered during pregnancy. Maternal and fetal morbidity and mortality can be reduced by early recognition and institutional management.

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Archives of Gynecology and Obstetrics

Eray Çalışkan

Objective: The aim of the study was to determine the risk factors, prevalance, epidemiological parameters and maternal-perinatal outcome in pregnant women with hypertensive disorder. Materials and methods: A retrospective analysis was undertaken on 255 consecutive cases of hypertensive disorder in pregnancy who were managed at Kocaeli University, School of Medicine, Department of Obstetrics and Gynecology from June 1997 to November 2004. Demographic data involving age, parity, gestational week, clinical and laboratory findings were recorded from the medical files. Additionally delivery route, indications of cesarean section, fetal and maternal complications were determined. Statistical analysis was performed by SPSS programme using Kruskal Wallis nonparametric test, ANOVA (Analysis of variance) and chi-square tests. Results: Of 5,155 deliveries in our clinic during the defined period, 438 cases (8.49%) were managed as hypertensive disorder of pregnancy. Medical records of 255 cases could be avaliable. Of 255 cases, 138 patients (54.11%) were found to have severe preeclampsia while 88 cases (34.50%) were diagnosed as mild preeclampsia. Twenty-nine patients (11.37%) were suffering from chronic hypertension. Of 138 severely preeclamptic cases, 28 cases (11%) had eclamptic convulsion and another 28 patients (11%) were demonstrated to have HELLP syndrome. Intrauterine growth restriction, oligohydramnios, placental ablation were the obstetric complications in 75 (29.4%), 49 (19.2%), 19 (7.5%) cases, respectively. Additionally multiple pregnancy and gestational diabetes mellitus were noted in 5.9% (n:15) and 3.9% (n:10) of the patients. Delivery route was vaginal in 105 patients (41.2%) while 150 patients (58.8%) underwent cesarean section with the most frequent indication to be fetal distress in 69 cases (46%). Cesarean section rate seemed to be the lowest (48.3%) in chronic hypertensive women while the highest (63.8%) in severe preeclamptic patients. Maternal mortality occured in 3 cases (1.2%) and all of those cases were complicated with HELLP syndrome. Intracranial bleeding was the cause of maternal death in one case while the other two cases were lost due to acute renal failure and disseminated intravascular coagulation, respectively. Intrauterine fetal demise was recorded in 24 cases on admission. Ten fetuses died during the intrapartum period. Mean gestational age and birth weight were 28±3.5 and 1000±416 g, respectively in this group. In these ten women, five cases were diagnosed as HELLP syndrome, two were severely preeclamptic and three were eclamptic. Perinatal mortality rate was found to be 144/1,000 births Conclusion: Hypertensive disorder of pregnancy is associated with increased risk of maternal-perinatal adverse outcome. The complications of severe preeclampsia and eclampsia could be prevented by more widespread use of prenatal care, education of primary medical care personnel, prompt diagnosis of high-risk patients and timely referral to tertiary medical centers.

South African Family Practice

Nnabuike Chibuoke Ngene

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Determinants of pregnancy-induced hypertension on maternal and foetal outcomes in Hossana town administration, Hadiya zone, Southern Ethiopia: Unmatched case-control study

Affiliations.

• 1 Department of Nursing College of Medicine and Health Science, Wachemo University, Hossana, Ethiopia.
• 2 Department of Public Health College of Medicine and Health Science, Wachemo University, Hossana, Ethiopia.
• 3 Department of Health Management and Economics, School of Public Health, Tehran University of Medical Science, Tehran, Iran.
• PMID: 33979338
• PMCID: PMC8115896
• DOI: 10.1371/journal.pone.0250548

Background: Globally, 292,982 women die due to the complications of pregnancy and childbirth per year, out of those deaths 85% occurs in Sub Saharan Africa. In Ethiopia, pre-eclampsia accounts for 11% of direct maternal deaths.

Objective: To determine maternal and foetal outcomes of pregnancy-induced hypertension among women who gave birth at health facilities in Hossana town administration.

Methods: Institutional based unmatched case-control study was conducted among women, who gave birth at health facilities from May 20 to October 30, 2018. By using Epi-Info version 7; 207 sample size was estimated, for each case two controls were selected. Two health facilities were selected using a simple random sampling method. Sample sizes for each facility were allocated proportionally. All cleaned & coded data were entered into Epi-info version 3.5.1 and analysis was carried out using SPSS version 20. Multivariate analysis was performed to determine predictors of pregnancy-induced hypertension at a p-value of <0.05.

Result: Women between 18 to 41 years old had participated in the study with the mean age of 26.00(SD ±4.42), and 25.87(SD ±5.02) for cases and controls respectively. Out of participants 21(30.4%) among cases and 21(15.2%) among controls had developed at least one complication following delivery. 12 (17.4%) and 8 (5.7%) foetal deaths were found in cases and controls groups respectively whereas 15.6% from cases and 3.6% from controls groups women gave birth to the foetus with intra-uterine growth retardation. Women gravidity AOR = 0.32 [95% CI (0.12 0.86)], Previous history of pregnancy-induced hypertension AOR = 22.50 [95% CI (14.95 16.52)] and educational status AOR = 0.32[95% CI (0.12, 0.85)] were identified as predictor of pregnancy-induced hypertension.

Conclusion: Women with a previous history of pregnancy-induced hypertension had increased risk of developing pregnancy-induced hypertension, whilst ≥ 3 previous pregnancies and informal educational status decrease odds of developing pregnancy-induced hypertension.

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Conflict of interest statement

The authors declare that no competing interests.

Fig 1. Conceptual frame work of PIH…

Fig 1. Conceptual frame work of PIH and factors (source from literature review).

Legend: PIH:…

Fig 2. Sampling procedure scheme of mother…

Fig 2. Sampling procedure scheme of mother who gave birth in public health facility, Hossana…

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Peer-reviewed

Research Article

Determinants of pregnancy-induced hypertension on maternal and foetal outcomes in Hossana town administration, Hadiya zone, Southern Ethiopia: Unmatched case-control study

Roles Writing – original draft

* E-mail: [email protected]

Affiliation Department of Nursing College of Medicine and Health Science, Wachemo University, Hossana, Ethiopia

Roles Writing – review & editing

Roles Data curation

Affiliation Department of Public Health College of Medicine and Health Science, Wachemo University, Hossana, Ethiopia

Affiliation Department of Health Management and Economics, School of Public Health, Tehran University of Medical Science, Tehran, Iran

• Getachew Ossabo Babore, 
• Tsegaye Gebre Aregago, 
• Tadesse Lelago Ermolo, 
• Mangistu Handiso Nunemo, 
• Teshome Tesfaye Habebo

• Published: May 12, 2021
• https://doi.org/10.1371/journal.pone.0250548
• Peer Review
• Reader Comments

Globally, 292,982 women die due to the complications of pregnancy and childbirth per year, out of those deaths 85% occurs in Sub Saharan Africa. In Ethiopia, pre-eclampsia accounts for 11% of direct maternal deaths.

To determine maternal and foetal outcomes of pregnancy-induced hypertension among women who gave birth at health facilities in Hossana town administration.

Institutional based unmatched case-control study was conducted among women, who gave birth at health facilities from May 20 to October 30, 2018. By using Epi-Info version 7; 207 sample size was estimated, for each case two controls were selected. Two health facilities were selected using a simple random sampling method. Sample sizes for each facility were allocated proportionally. All cleaned & coded data were entered into Epi-info version 3.5.1 and analysis was carried out using SPSS version 20. Multivariate analysis was performed to determine predictors of pregnancy-induced hypertension at a p-value of <0.05.

Women between 18 to 41 years old had participated in the study with the mean age of 26.00(SD ±4.42), and 25.87(SD ±5.02) for cases and controls respectively. Out of participants 21(30.4%) among cases and 21(15.2%) among controls had developed at least one complication following delivery. 12 (17.4%) and 8 (5.7%) foetal deaths were found in cases and controls groups respectively whereas 15.6% from cases and 3.6% from controls groups women gave birth to the foetus with intra-uterine growth retardation. Women gravidity AOR = 0.32 [95% CI (0.12 0.86)], Previous history of pregnancy-induced hypertension AOR = 22.50 [95% CI (14.95 16.52)] and educational status AOR = 0.32[95% CI (0.12, 0.85)] were identified as predictor of pregnancy-induced hypertension.

Women with a previous history of pregnancy-induced hypertension had increased risk of developing pregnancy-induced hypertension, whilst ≥ 3 previous pregnancies and informal educational status decrease odds of developing pregnancy-induced hypertension.

Citation: Babore GO, Aregago TG, Ermolo TL, Nunemo MH, Habebo TT (2021) Determinants of pregnancy-induced hypertension on maternal and foetal outcomes in Hossana town administration, Hadiya zone, Southern Ethiopia: Unmatched case-control study. PLoS ONE 16(5): e0250548. https://doi.org/10.1371/journal.pone.0250548

Editor: Frank T. Spradley, University of Mississippi Medical Center, UNITED STATES

Received: May 1, 2020; Accepted: April 9, 2021; Published: May 12, 2021

Copyright: © 2021 Babore et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All the necessary data and materials are incorporated in the article and Supporting Information . Any further requests will be addressed by the corresponding author upon reasonable request.

Funding: The authors received no specific funding for this work from any source. all of us doing for academic qualification and put finger print for scientific society.

Competing interests: The authors declare that no competing interests.

Introduction

Pregnancy and childbirth are natural processes, which comes up with multiple consequences. A hypertensive disorder is one of the pregnancy consequences which is a major alarming cause for maternal, perinatal morbidity and mortalities [ 1 ]. The term hypertension in pregnancy is commonly used to describe a wide spectrum of the patient who may have only mild elevations in blood pressure to severe organ dysfunction. Thus, it is accompanied by minor to major complications. Worldwide hypertensive disorder in pregnancy/HDP affects 5–22% and it is responsible for 5–10% of complications in all pregnancies [ 2 – 4 ] .

Among four classes of HDP, preeclampsia remains a leading cause, which needs rigorous public intervention for better outcome of foetus and mother, and Preeclampsia affects up to 5–8% out of all pregnancies [ 5 ]. Also, preeclampsia is a unique form of hypertension during pregnancy which usually occurs after 20 weeks of gestation. If the early investigation and appropriate management are not undertaken for the women diagnosed with pre-eclampsia. It progress to a severe form called eclampsia, which end-up with maternal as well as foetal adverse outcomes like abruption placenta, acute renal failure/ARF, intravascular coagulation, intra-uterine growth retardation/IUGR, and stillbirth [ 6 ]. Therefore, the origin for eclampsia is pre-eclampsia (Eclampsia is the definition of Preeclampsia plus ≥ +2 proteinuria plus the occurrence of convulsion or coma) [ 7 ].

Studies suggested that either pre-existing pregnancy-induced hypertension/PIH or pregnancy changes could be responsible for the occurrence of pre-eclampsia. In a multicentre study approximately, 30% of hypertensive disorders of pregnancy were occurred due to chronic hypertension while 70% of the cases were diagnosed as gestational hypertension or pre-eclampsia [ 8 ]. Regardless of new-onset or pre-existing occurrences, the harmful effects of preeclampsia and eclampsia upraised from mother to child, family to the country and its severity is from trivial to life-threatening. Still, it has remained a significant public health threat in both developed and developing countries [ 9 ].

PIH denotes women’s systolic blood pressure/SBP ≥ 140mmHg, and diastolic blood pressure/DBP ≥ 90mmHg on two or more consecutive measures without proteinuria after 20 weeks of gestation; pre-eclampsia is characterized as when pregnant women presented with SBP ≥ 140mmHg and DBP ≥ 90mmHg on two or more consecutive measures within 4 hours interval with the presence of proteinuria that occurs after 20 weeks of gestation whereas eclampsia denotes the occurrence of convulsion plus proteinuria +2 or more and sign and symptom of severe pre-eclampsia for the women who fulfil the definition of PIH [ 10 – 12 ].

Pre-eclampsia and eclampsia are the second direct cause for maternal death which accounts for 10 to 15% of maternal deaths worldwide [ 13 ]. The incidence of pre-eclampsia has significant variation in different parts of the continents. For instance, 4% in Africa, 3.8% in Europe, and 4.2% in the western Pacific region [ 14 ]. Moreover, the prevalence of pre-eclampsia throughout the country has vast variation, in Jima University specialized hospital, it was 51.8%, three southwest Ethiopia hospitals 6.3% [ 15 ], and in seven Tigray hospitals 50% [ 16 ].

Globally, 292,982 women died due to the complications of pregnancy and childbirth. Out of those deaths, 85% have occurred in Sub Saharan Africa/ SSA, yet the majority of those deaths occurred in low resource settings, and most of them could have been preventable [ 17 , 18 ]. Furthermore, the highest share of maternal death has been reported in Africa as compared to other regions. Maternal death due to pregnancy-related causes is 1 in 4,000 in Europe and 1 in 16 in African countries [ 18 , 19 ]. Likewise, The probability of a 15 year-old girl eventually dying from a maternal cause in Africa was as high as 1 in 37- as compared to 1 in 3400 in the European region [ 20 ].

According to the latest joint trend review study in maternal mortality conducted by United Nation Population Division/UNPD, World health organization/WHO and World Bank, the proportion of mothers dying per 100,000 live births has declined from 380 to 210 in 1990 to 2013 [ 21 ]. Besides, there was a slight reduction in maternal mortalities in the last three consecutive Ethiopian demographic health surveys/EDHs; MMR was 667, 665 and 412 per 100,000 life birth and all those deaths might have happened as a result of direct or indirect causes [ 22 ]. On the other hand, a trend review study from 1980 to 2012 in Ethiopia, on maternal death reported that as a result of hypertensive disorder of pregnancy/HDP, maternal death has increased from 4%-29%. In-addition to the death trend, the review pointed out the major direct obstetric complications (sepsis, haemorrhage, unsafe abortion, obstructed labour) including pre-eclampsia, accounts for 85% of maternal death. Whereas pre-eclampsia solely accounts for 11% of maternal death [ 23 , 24 ]. Whilst pre-eclampsia and Eclampsia contribute to 53% of maternal and 62.7% of perinatal complications during pregnancy and birth [ 25 ].

HDP especially preeclampsia, in primigravida women is 2 times more risky than multigravida [ 26 , 27 ]. Impacts of pre-eclampsia and eclampsia are disproportional in both developed and developing countries which are seven times higher in developing countries than in developed worldwide [ 28 ].

Impacts of Pre-eclampsia and eclampsia on maternal and foetal outcomes are enormous, which results in life-threatening events to death. For instance, it increases the risk of placenta abruption, postpartum haemorrhage/PPH and intra-uterine growth retardation. According to the WHO multicentre survey, the risk of perinatal death among women with preeclampsia and eclampsia increased 3 and 5 folds respectively, as compared to women with no preeclampsia or eclampsia [ 26 , 29 , 30 ]. Still, preeclampsia is one of the major causes of perinatal death in developing countries, accounts for 20–50% of deaths [ 31 ]. In Ethiopia, eclampsia accounts for 35.7% of maternal death [ 32 , 33 ].

Studies were done abroad and our country revealed that pregnancy-induced hypertension has been associated with poor maternal and prenatal outcomes and loos of life [ 34 ]. Case control hospital-based study done in India reported that 10, 8, 3 and 2 complications of Haemolysis, Elevated Liver enzymes, and Low Platelet count/HELLP syndrome, PPH, Infection and ARF respectively [ 35 ]. On another case control study conducted by Guduri GB revealed that there were 18%, 2% PPH and 36%, 7% preterm complication, among cases and controls respectively [ 36 ].

Studies done in different regional hospitals, Ethiopia reported various proportions of maternal complications and deaths following delivery occurred as a result of pre-eclampsia/eclampsia. The Eastern part of, Ethiopia finding revealed that 53% maternal and 62.7% perinatal complication with a fatality rate of 11% [ 25 ], in Woliata Sodo University teaching Hospital 48.89% perinatal complication and 8.89% perinatal deaths [ 37 ]. In Zewuditu Memorial Hospital, among women had developed PIH, 131 (52.4%) of them developed complication whilst 31.1% of them experienced with HELLP syndrome [ 38 ].

Different studies noted that previous history of pregnancy-induced hypertension, age, and educational status were independent risk factors for the development of preeclampsia. In addition to these, occupation, gravidity, family history of hypertension, gestational diabetic Mellitus and residence had a significant statistical association with preeclampsia [ 39 – 42 ].

Yet, there have been different studies conducted to explore PIH in Ethiopia, but there was no study conducted on predictors of pregnancy-induced hypertension in the study area. Thus, to come up with effective public as well as clinical intervention approach and strong policy development direction, conducting root cause identification research is essential. Therefore, the main objective of this study is to determine maternal and foetal outcomes of pregnancy-induced hypertension among women who gave birth at Public health facility in Hossana town administration, Hadiya zone, Southern Ethiopia: unmatched case control [ Fig 1 ].

• PPT PowerPoint slide
• PNG larger image
• TIFF original image

Legend: PIH: Pregnancy-induced hypertension, HDP: hypertensive disorder of pregnancy, Hx: history, ANC: antenatal care, GA: gestational age.

https://doi.org/10.1371/journal.pone.0250548.g001

Methods and material

The study was conducted in Hossan town administration, Hadiya Zone, South Nation Nationality and People Regional state/SNNPR, Ethiopia. Hadiya zone has ten woredas and two town administrations. According to the Hadiya Zone Finance and Economic Development office statistics, the total population of the zone was 2,486,242 of which 1,218,258 were men whereas 1,267,983 of them were female.

Hossana town is located in the northern part of SNNPR state. It is 232 KM far from the country’s capital city to the south and 120 KM from the regional capital town. The town administration is classified into 3 subs administrative with a total of 8 kebeles. According to the Hossana town administrative office, the current (2018/2019) projection estimated total population was 104,053 whereas 50,986 males and 53, 067 of them were females. Among the total town population, women within the reproductive age group encompass 24,244 from them the estimated number of women who are eligible to be pregnant in the current physical year were 8,388 [ 43 ].

The town has one teaching hospital which has been serving more than 3, 548,800 million people from the entire Hadiya Zone and partial part of kembeta and Silte Zone. As well, the town has three health centres, one private surgical hospital, and more than 15 private clinics.

Study design and period

Institutional based unmatched case control study was conducted in OB/GYN department of the selected public health facilities, from May 20/2018 to October 30/2018.

All pregnant women who were on follow up after 20 weeks gestational age and visit health facilities for delivery service and screened as of having pregnancy-induced hypertension registered in the OB/GYN departments of the respective facilities.

Pregnant women who have no PIH in the same period and the same health facilities and who came for delivery service after 20 weeks of gestational age.

Source population

The source population of the study were all women, who have been on follow-up care unit and visit facilities for delivery service in Public Health facilities those resided in Hossana town administration.

Study population

All women who were selected using systematic sampling method applying population proportionate to sample size (PPS) from randomly selected public health facilities among women who had been on follow-up care unit and visit the health facility for delivery service whose gestational age above 20 weeks.

Eligibility criteria

Inclusion criteria..

All pregnant women who were on flow up and visited selected public health facility for delivery service whose gestational age above 20 weeks were included. For women representing cases, they diagnosed having Pregnancy-induced hypertension as of her SBP ≥140mmHg and DBP ≥90 mmHg on two separate reading which measure within at least four hours apart, plus a dipstick reading +1 and above. For women represent Controls, women within the same health facilities who were attending delivery care was not diagnosed as having Pregnancy-induced hypertension.

Exclusion criteria.

Women who didn’t indweller in respective town administrative sub towns and no longer stay at Hossan town administration for more than six months.

Women with a known diagnosis for Epilepsy and women who were not voluntary to give consent also excluded from the study.

Simple size and sampling technique

Sample size..

The sample size for this study was computed based on the comparison of proportion for case control study by using Epi-info version 7 for windows. According to a study conducted by Eskeziaw Agedew [ 39 ], by considering the factors gravidity and maternal age had an association with PIH. Being multigravida and age during current pregnancy between 25–30 years which have a significant association with pregnancy-induced hypertension with case to control ratio 1:2 and Odds ratio (OR) = 4 and using the following assumptions: power 80%, confidence level 95% ( Table 1 ). The final sample size was taken from the women who were multigravida by adding 10% non-response rate. Thus, an estimated sample was employed for case 69 and 138 for controls yielding a total sample of 207.

https://doi.org/10.1371/journal.pone.0250548.t001

Sampling technique

To select a study unit two Public Health facilities were selected randomly among four facilities. Considering the two months report data from the health management information system/HMIS office sample size allocated proportionally by using proportionate to population size for cases and controls. All newly registered pregnant women who were more than 20 gestational weeks suffered from pregnancy-induced hypertension were selected representing the cases. For each case, women who registered for ANC follow up and had given delivery whose gestational age ≥20 weeks, but hadn’t experienced with PIH at the same time in the same facilities were taken as control. To select controls, a list of total women the MCH department registration book for those who have ANC follow up after 20 weeks of gestation age was considered as a sampling frame. The estimated sample size for this study (n) was divided by a total number of women (N) registered in randomly selected HFs during the last two months which yield proportionate (P). Then through multiplying proportionate value with two months sample, a proportional sample was allocated for each selected health facilities. Finally, by employing a systematic sampling method based on the k th value sampling unit was traced in respective facilities. The sampling procedure was presented ( Fig 2 ).

HC: health centre, NEMMTH: Nigest Eleni Mohomod Memorial Teaching Hospital, n: proportional allocated sample size.

https://doi.org/10.1371/journal.pone.0250548.g002

Data collection method, tools and procedures

Structured and pretested questionnaires which was prepared in English and translated to Amharic and then translated back into English again to assure consistency of tool, which developed from reviewing different literature was used in this study.

Data were collected by 4 BSc midwives, 2 BSc Nurses supervised and monitored during the data collection phase by using structured questionnaires whereas the principal investigator undertakes the overall coordination. Data were collected from women who gave birth in the OB/GYN department, for each case, two controls were interviewed on the same day and health facilities. Participant’s medical charts were also reviewed to obtain biomedical laboratory data at the same time.

Data quality control measures and management

Before the actual data collection date, data collectors & supervisors were trained concerning the overall issue of data collection format like, in time data collection following delivery, completeness, participant confidentiality and consistency.

One week before the actual data collection date, research tool was tested on 13 women who gave birth at Doyogena primary hospital, validity checked then a lot amendment was undertaken.

Every day, the principal investigator and supervisors were checked data for completeness and incomplete questionnaires were discarded. Cross-checked and coded data were entered into Epi-info software version 3.5.1. For further analysis and data cleaning, it was exported to SPSS (statistical package for social science) version 20.

Data analysis

To identify the proportion of the pregnancy induce hypertension impact on maternal and foetal outcome in-relation to outcome variable cross-tabulation frequencies were done. Cross tabulation was also employed to test the relation of variables against with outcome variable. Bivariate logistic regression was conducted to select candidate variables for multivariate analysis at P-value < 0.05. Finally, to determine predictors of outcome variables multivariate analysis was employed.

Data was described and presented using cross-tabulation value to for descriptive findings and interpreted by looking at a variable that has an association with outcome variables on multivariate analysis with a 95% confidence interval for AOR.

Study variables

Dependent variable..

Foeto-maternal outcomes of Pregnancy Induced Hypertension

Independent variable.

Socio demographic variables . Maternal age, residence, educational status, occupation and monthly income.

Obstetrics variables . Gravidity, number of parity, gestational age at delivery, number ANC follow up, number of babies (twin).

Medical variables . Previous history of pregnancy induced HTN, History of D/M, anaemia and renal disease.

Hypertensive disorder sign and symptoms of pregnancies on admission . Level of blood pressure during admission/presentation, vomiting, proteinuria, typical symptoms (oedema, blurred vision, headache and epigastric pain).

Ethical consideration

Ethical approval was obtained from IRB of WCU, Official letter for zonal/woreda health department was written from University research and community service V/P office and a cooperation letter was written from respective woreda office managers to the randomly selected health facilities.

Operational definitions of terms

Hypertensive disorders of pregnancy..

Includes chronic hypertensive and pregnancy induced hypertension, regardless of previous history of hypertensive disorder.

Pregnancy-induced hypertension.

Hypertension developed after 20 weeks of gestation where SBP ≥ 140mmHg and DBP ≥ 90mmHg, within two consecutive reading which measured 4–6 hours apart without proteinuria among mothers who were attended delivery unit at health facilities among previously normotensive women.

Preeclampsia.

The new onset of hypertension with SBP ≥ 140 and DBP ≥ 90 mmHg, within two reading which measured 4–6 hours interval with the presence of proteinuria with or without oedema which occurred after 20 weeks of gestation.

Mother with DBP greater than or equal to 110mmHg after 20 weeks of gestation and in-addition to the features of pre-eclampsia having one or more episode of convulsion or coma plus proteinuria + 2 or more.

Pregnancy outcome.

Any women who had at least one prenatal as well as maternal unfavourable outcome after delivery

Maternal complication.

Any mothers had at least one complication among who had attended delivery at Hospital.

Gestational age.

The duration of gestation is measured from the first day of last menstrual period more than 20 weeks for this study.

Foetal outcomes.

Any diagnosed complication or death confirmed after delivery.

Socio-demographic characteristics

Among a total of 207 participants, 69 cases and 139 controls women have participated in the study. Women from the age of 18–41 participated in the study while their mean age was 26.00 (SD ± 4.42), 25.87 (SD ± 5.02) for cases and controls respectively. Two women were participated in the study where their age was below legally eligible for marriage. The majority 97 (47.3%) participants’ were house-hold wives, 9(4.3% of them were students and 69 (42.9%) had no formal education.

Reproductive history and pre-existing medical illness during current pregnancy

Among women who had ANC visits three and above, 34 (52.3%) from cases and 72 (55.0%) from control were not developed PIH. Women with a high frequency of ANC follow-Up had a low proportion of becoming hypertensive on current pregnancy while among women who had no ANC follow-up, 4 from cases and 10 from controls groups had developed pregnancy-induced hypertension.

More than one-third of the study participants were primigravida among them 34 (31.5%) were not know their LNMP. However, 180 (86.9%) didn’t attend the minimum expected ANC follow up, only 16 (7.7%) had four and above ANC follow up. Seven women among cases and 44 women from control groups gave birth by caesarean section, but the largest proportion 62 (89.8%) of women from cases gave birth via spontaneous vaginal delivery/SVD as compared with controls 94 (68.1%).

Among all interviewed women, 29 (14.0%) were experienced with pre-existing medical illness includes: diabetic Mellitus, anaemia and non-pregnancy induced hypertension 4.3%, 5.3% and 3.9% respectively. A high proportion of women from cases 14 (20.3%) had medical problems as compared to controls 15 (10.9%). Out of the total cases that participated in this study; twenty-four women had a previous history of PIH. On the occasion of health facility arrival, 120 (57.9%) women were admitted with pushing labour pain, but the remaining were came up with one or more features rather than labour pain ( Table 2 ).

https://doi.org/10.1371/journal.pone.0250548.t002

Even though the DBP range from 90 to 144 mmHg among cases the mean DBP, 104.13 (SD ± 9.20) was above the cut-off point of the normotensive women. Perinatal delivered from women with cases experienced with an average of 0.7 complications. On the occasion of reception for delivery service and follow-up care in addition to having high blood pressure, every woman from cases was admitted with at least of two suggestive clinical features for PIH whereas controlled had less than 1 clinical feature ( Table 3 ).

https://doi.org/10.1371/journal.pone.0250548.t003

Maternal and fetal outcomes

A total of 69 women with cases participated in the study and showed a potential effect on maternal and perinatal health. Among the interviewed cases, 11 (15.9%) of them were developed eclampsia. On the occasion of the arrival to health facility among women who had developed eclampsia, only 3 (27.2%) of them were comatose on the occasion of the arrival of health facility. For all Women who developed PIH urine test was performed and a test result had shown a minimum +1 proteinuria for the dipstick test.

Among the total of interviewed cases, 21(30.4%) women have developed at least one complication following delivery. The majority of complications were 13 PPH and 7 disseminated intravascular coagulopathy/DIC. Moreover, PIH has a potential effect on maternal as well as perinatal outcomes; perinatal borne from women with PIH more likely to develop complication than normotensive women. Out of 55, alive births among cases 32 (58.2%) had at least one complication, but out of total alive births, 32.9% (n = 68) perinatal hadn’t any complication. From 20 perinatal deaths, 12 (17.4%) was reported from women who had developed PIH. Among 13 foetal IUGR, 8 of them were from cases as far as women diagnosed for PIH 3.7 times more risky to causes foetal IUGR than normotensive women ( Table 4 ).

https://doi.org/10.1371/journal.pone.0250548.t004

Pregnancy-induced hypertension and associated factors

Binary logistic regression with a confidence level of 95%, (α = 0.05) was conducted and variables which have statistically significant at p-value < 0.05 were selected as candidate variable for the last model that determine predictors of pregnancy-induced hypertension among women gave birth at health facilities.

Finally, variables entered into the last model and multivariate analysis was performed. The Previous history of pregnancy-induced hypertension increased odds of developing pregnancy-induced hypertension by 22 folds, [95% CI (6.313, 80.204)], three and above previous pregnancies decreases odds of pregnancy-induced hypertension AOR = 0.32 [95% CI (0.12, 0.86)] and women who had no formal education, 68.4% [95% CI (0.12, 0.85)] less likely to develop PIH than women had primary and above educational status. Thus, the model was identified; gravidity, educational status, and previous history of pregnancy-induced hypertension were determinant factors for pregnancy-induced hypertension. Furthermore, Pregnancy-induced hypertension had an impact on inducing maternal complication, perinatal death and Intra-Uterine growth retardation/IUGR ( Table 5 ).

https://doi.org/10.1371/journal.pone.0250548.t005

This study revealed that 21(30.4%) among cases and 21(15.2%) women in control groups had developed at least one complication following delivery. The finding is supported by the study conducted in India 54% among case and 9% from controls developed maternal complications [ 36 ]. Also, a study done by Kapil Dev revealed that among cases 24% of women developed at least one maternal complication, but there was no maternal complication in controls [ 37 ]. A lower proportion of maternal complication in this study could be due to living style and women in the study area had less history of medical complications.

The commonest maternal complications in this study were postpartum haemorrhage/PPH 13 (18.8%), which is higher than the study done in India [ 35 ]. The lower proportion reported from elsewhere might be a better management approach and health care setups in those facilities were more intensive and organized as compared to our study area.

This study showed that perinatal complications were more prevalent among controls (63.4%) as compared to cases (58.2%). The finding is supported by the study done by Aleem Arshad, only 1 and 13 low birth weight reported from cases and control, respectively [ 44 ]. In this study, neonatal death was the second leading outcome of PIH, 17.4% from cases and 5.7% controls deaths were reported. Concerning perinatal complications, this study reported that 15.6% IUGR from cases and 3.6% from control which was lower than a study conducted in India; 29% and 71% IUGR were reported from women who had developed PIH and normotensive, respectively [ 36 ]. The possible reason for the low proportion could be socio-demographic factors and women in our study area affected by low superimposed medical problems.

Out of the cases, group preeclampsia accounted for 58(84.1%) whereas eclampsia comprises 11(15.9%). A study was done in Harare, Zimbabwe reported the proportion of pre-eclampsia and eclampsia were 1.7% & 0.3% respectively [ 9 ], but the proportion was lower than a study conducted by Selemawit, 121 women developed Pre-eclampsia and 17 of them Eclampsia [ 45 ]. The difference might be due to early identification and alerting women during ANC visits which decrease the possible occurrences of preeclampsia and eclampsia. Other study carried in three south-west hospitals, Ethiopia and tertiary care hospital of Visakhapatnam, India reported in the prevalence of pre-eclampsia and eclampsia were 7.9%, 3% and 16%, 36% respectively among cases [ 36 , 46 ].

In this study gravidity has an association with PIH, women with gravidity 3 and above were 68% [95% CI (0.12, 0.86)], less likely to develop Pregnancy-induced hypertension as compared to their counterparts. This study is in-line with a study done in Darashe Special woreda [ 39 ] and Kombolicha, Ethiopia [ 41 ]. Whereas, the finding is in contrast with the study done in Addis Ababa, Ethiopia and Colombia; primigravida women were 2.7 times more likely to develop PIH than multigravida [ 24 ], and 36.9% of primigravida women among cases had developed PIH [ 47 ], the possible reason might be due to difference in assigning the reference group.

History of previous pregnancy-induced hypertension was significantly associated with PIH. In our study previous history of pregnancy-induced hypertension had 22 times increased odds of pregnancy-induced hypertension as compared to previous normotensive women. Out of the total interviewed women who had previous history of pregnancy-induced hypertension, 34.8% in cases and 2.9% in controls groups developed PIH in the current pregnancy. This finding is in-line with the studies done in Addis Ababa, Ethiopia and Karnataka, India. Women with a previous history of pregnancy-induced hypertension were 4 times more likely to develop PIH during current conception, which reported 28.95% women among cases and 10.9% among control had developed PIH in Karnataka, India. Women with a previous history of PIH were 58 times odds of developing PIH, out of the total interviewed cases 60% and controls 2.50% of women developed PIH during current pregnancy [ 36 ]. However, the finding of this study contradicts with the study done in Jaipur, India [ 40 ].

In this study, multivariable analysis revealed that previous history of medical illness had no statistical association with PIH, but studies conducted in Tigray, Kombolicha in Ethiopia, and Southern India reported that women with diabetic Mellitus were 5.4, 11 and 5 times more likely to develop PIH respectively [ 16 , 41 , 48 ]. The possible reason for this discrepancy could be that the number of women with a pre-existing medical problem in this study was fewer than those studies conducted elsewhere.

In addition to the maternal complication, this study singled-out that perinatal complications such as low birth weight, IUGR, and pre-term were higher in the cases than controls. Also, the study demonstrated that there was no association between PIH and birth weight which is in contrast with the study done in Zimbabwe where women with PIH were 3 times more likely to have a baby with low birth weight [ 9 ]. However, this study is in-line with a study done by Eskzyiaw [ 39 ]. Major perinatal complications reported in this study were LBW (31.1%), IUGR (6.9%) and preterm (6.8%).

Conclusion and recommendation

Pregnancy-induced hypertension yet has been seen as a burning issue, which provokes adverse health impact on mothers and their babies. In this study, both maternal and perinatal outcomes were significantly different in both groups (cases & control). Women with PIH were at higher risk for a maternal and perinatal adverse outcome as compared to normotensive women. Women with a previous history of PIH had increased risk of developing PIH whilst women who had ≥ 3 previous pregnancies and with informal education were less likely to develop pregnancy-induced hypertension.

Recommendation

For women diagnosed with a previous history of pregnancy-induced hypertension, health care providers should have taken especial attention and focused care to tackle the adverse effect of PIH on their current conception. Furthermore, concerning governing bodies and partners engaged in maternal service should have facilitated basic setups like on-job training on early screening skills and managements, tax-free transportation. When gravidity increased women may not caution as like the first conception so that clinical expertise gave attention to alerting women regarding early warning sign and improve health service delivery strategies. Principal governing bodies and concern partners should have facilitated maternal waiting room/village for better health, good perinatal and maternal outcome.

Supporting information

https://doi.org/10.1371/journal.pone.0250548.s001

https://doi.org/10.1371/journal.pone.0250548.s002

Acknowledgments

First, of all, I would like to Praise and give thanks to God for his grace and blessings over this work. Secondly, I would like to thanks Wachamo University research and community service and vice President Office and College of Health science and medicine for overall coordination since preparation to finalizing the research project. Finally, my greatest gratitude extends to my NEMMRH MCH departments professionals and Hossana town administration health office for giving the baseline data for this study.

• 1. Malawi M., Baseline Survey of Management at Lilongwe Central Hospital , Malawi . Boston, MA, MSH, 2004.
• View Article
• PubMed/NCBI
• Google Scholar
• 13. Duley L. The global impact of pre-eclampsia and eclampsia . in Seminars in perinatology . 2009. Elsevier. https://doi.org/10.1053/j.semperi.2009.02.010 pmid:19464502
• 14. Nwanodi O.B. Preeclampsia-eclampsia adverse outcomes reduction : the preeclampsia-eclampsia checklist . in Healthcare . 2016. Multidisciplinary Digital Publishing Institute. https://doi.org/10.3390/healthcare4020026 pmid:27417614
• 21. Alkema L., et al., Trends in maternal mortality : 1990 to 2013-estimates by WHO , UNICEF , UNFPA , the World Bank , and the United Nations population division . 2014, The World Bank.
• 22. ICF E.E.M.D., Health Survey , 2019 . Key Indicators . Rockville, Maryland, USA: EPHI and ICF, 2019.
• 28. Organization W.H., The World health report : 2005 : make every mother and child count . 2005: World Health Organization.
• 38. Dufera S., Maternal and Perinatal Outcomes of Pregenancies Complecated by Preeclampsia/Eclampsia at Zewditu Memorial Hospital . 2015, Addis Ababa University.
• 43. Hossan town finace and economic office., annual plan of the town, Hossana, Ethipia 2018 (unpublished)
• 45. Selamawit D. and Sisay T., Maternal and Perinatal outcomes of pregenancies complecated by preeclampsia/eclampsia at zewditu memorial hospital . Addis Ababa Aniversity school of graduate studies faculty of Medicine, 2015.

• Open access
• Published: 30 August 2024

Hypertension subtypes and adverse maternal and perinatal outcomes - a retrospective population-based cohort study

• Daniel Perejón 1 , 2 , 3 ,
• Anna Bardalet 4 ,
• Iñaki Gascó 5 ,
• Júlia Siscart 1 , 2 , 6 ,
• Maria Catalina Serna 1 , 2 , 7 &
• Míriam Orós 1 , 2 , 8  

BMC Pregnancy and Childbirth volume  24 , Article number:  568 ( 2024 ) Cite this article

Metrics details

This study aims to examine risk of adverse pregnancy outcomes and mothers’ characteristics in patients with chronic hypertension, gestational hypertension and preeclampsia.

The study included all births born from women aged 15–45 years, in Lleida, Spain from 2012 to 2018. Pregnancy outcomes were retrieved by regional administrative databases. Logistic regression analysis was used to calculate adjusted odds ratios (OR) (OR 95% CI) for maternal characteristics or neonatal outcomes.

Among 17,177 pregnant women, different types of hypertension present varying risks for both the mother and fetus. There is an increased risk of cesarean section in patients with preeclampsia (OR 2.04, 95% CI: 1.43–2.88). For the newborn, a higher risk of preterm birth is associated with maternal chronic hypertension (OR 3.09, 95% CI: 1.91–4.83) and preeclampsia (OR 5.07, 95% CI: 3.28–7.65). Additionally, there is a higher risk of low birth weight in cases of maternal chronic hypertension (OR 3.2, 95% CI: 2.04–4.88), preeclampsia (OR 5.07, 95% CI: 3.34–7.52), and gestational hypertension (OR 2.72, 95% CI: 1.49–4.68). Furthermore, only newborns of patients with preeclampsia had a higher risk of an Apgar score lower than 7 in the first minute (OR 2.95, 95% CI: 1.45–5.38).

Conclusions

In the study population adjusted for body weight, the different types of hypertension represent different risks in the mother and foetus. These complications were mostly associated with preeclampsia.

Peer Review reports

Introduction

Hypertensive disorders in pregnancy (HDP) are significant contributors to elevated maternal morbidity and mortality rates [ 1 , 2 ], along with neonatal morbidity [ 1 , 2 ], as well as neonatal morbidity. HDP refers to gestational hypertension, preeclampsia and eclampsia, chronic hypertension complicated with preeclampsia, and chronic hypertension [ 3 , 4 ]. According to the International Society for the Study of Hypertension in Pregnancy in 2021, HDP is classified into chronic hypertension, which exists or is diagnosed before 20 weeks’ gestation, and de novo hypertension, which typically occurs from 20 weeks’ gestation onwards. This second one has many manifestations including hypertension alone, known as gestational hypertension; pre-eclampsia (PE), hypertension with proteinuria and maternal organ dysfunction (haematological, liver, renal and neurological) and eclampsia, characterised by seizures [ 5 , 6 ].

Most guidelines around the world agree on the definition of hypertension in pregnancy, consisting in blood pressure (BP) ≥ 140/90 mmHg. At the same time, there is variability in the threshold for initiating antihypertensive treatment attributable to uncertainty about the maternal benefits of lowering BP and the potential foetal risks from reductions in utero-placental circulation and in utero exposure to drugs [ 7 ].

Hypertension in pregnancy is associated with an increased risk of placental abruption, intrauterine growth restriction, preterm birth, renal failure, postpartum haemorrhage, perinatal and maternal death and newborn morbidity [ 8 , 9 , 10 ]. In this sense, it has been estimated that hypertension during pregnancy is one of the main causes of maternal and foetal morbidity and mortality in the world [ 11 ].

Therefore, the aim of this study is to determine the difference in pregnancy outcomes in women with chronic hypertension, gestational hypertension and preeclampsia compared to women with normal pregnancies using populations data.

Materials and methods

Study design and data collection.

A retrospective observational cohort study was conducted among pregnant women in the health region of Lleida from 2012 to 2018.

The data of women who had given birth at the Arnau de Vilanova Hospital between January 1st, 2012 and December 31st, 2018 were obtained through the (“Conjunt Minim de Base de Dades”) CMBD database. Data of all the eligible patients assigned to a primary care unit derived from the computerized clinical history database E-CAP of the Catalan Health Institute; and data from Social Security prescriptions obtained from the database of the ServeiCatalà de Salut.

This article is part of the Iler Pregnancy project, a retrospective cohort study conducted in Lleida with the aim of evaluating the prevalence of chronic pathologies in pregnancy (hypothyroidism, depression, diabetes mellitus and obesity) and therapeutic adherence to prescribed drugs [ 12 , 13 ].

Study population

Women who have had a birth at the Arnau de Vilanova University Hospital in Lleida between January 1st, 2012, and December 31st, 2018, were included in the study. Women who did not belong to Lleida health region were excluded. To evaluate the representativeness of the sample, we calculated the percentage of pregnant women studied compared to the total of pregnant women in the health region of Lleida. Data was obtained from the database of “Instituto Statistics of Catalonia” (Idescat) (Table  1 ).

Variables recorded

The following variables were recorded: region of origin (Sub Saharan Africa, Latin America, Asia and the Middle East, West Europe, Eastern Europe, and Maghreb) [ 12 ]; body mass index (BMI) which is classified according to low weigh (BMI under 18.5 Kg/m2), overweigh (BMI between 25 and 29.9) and obesity (BMI more than 30); number of pregnancy and twin pregnancy; risk during pregnancy; diabetes and mellitus (code O24.9 at CIE-10.); arterial hypertension (code I10-I16 at l’ICD-10); dyslipidemia (code E78 at l’ICD-10); depression (codes F32.0-F32.9, F33.0-F33.3, F33.8, F33.9, F34.1, or F41.2 at l’ICD-10). Other variables taken into account were risk of the pregnancy; duration of the pregnancy (miscarriage, preterm, term, prolonged); caesarean section; birth weight (< 2500 g = underweight, between 2500 g and 3999 g = normal weight, and ≥ 4000 g = macrosomia), 1-minute and 5-minute Apgar score; and preeclampsia.

Data analysis

We performed a descriptive analysis. Based on delivery status, the cohort was divided into four groups: (1) without HDP, (2) chronic hypertension, (3) gestational hypertension, and (4) preeclampsia. Maternal and neonatal characteristics were compared between groups. Continuous variables were expressed as mean and SD and analyzed using ANOVA with post hoc Scheffé test. Ordinal variables were expressed as median and IQR and analyzed using Kruskal–Wallis H test. Categorical variables were expressed as percentages and analyzed using χ² or Fisher’s exact test. Relative risks of HDP phenotypes and outcomes were estimated using multinomial logistic regression. The model-building process was conducted in two blocks: the first included HDP, and the second included covariates (maternal age, BMI, hypothyroidism, maternal diabetes). Adjusted relative risks were expressed as odds ratios (OR) with 95% confidence intervals (95% CI). The “No hypertension” group served as the reference. Superimposed hypertension was excluded from the analysis.

Ethical aspects

This study was approved by the ethics and clinical research committee at the Institut d’Investigació IDIAP Jordi Gol under the code 19/195-P and carried out in accordance with the principles of the Declaration of Helsinki. Information was obtained from electronic medical records stored in the centralized ECAP database and extracted by the Department of Healthcare Evaluation and Research Management. Therefore, it was not necessary to ask participants to sign an informed consent. The variables in the ECAP database were processed anonymously and with full confidentiality guarantees as established by national Spanish law and Regulation 2016/679 of the European Parliament and of the Council on the protection of natural people regarding the processing of personal data, and to the free movement of such data. Ethics committee of (Idiap Jordi Gol i Gurina) waived the need for informed consent due to retrospective observational cohort study.

The study was started with a sample of 21,375 women who had given birth at the Arnau de Vilanova Hospital in Lleida between 2012 and 2018 (both included). From this sample, 1625 patients were excluded because they did not have a personal identification code (CIP), and 2573 because multiple data from the clinical history was missing. The final study sample included 17,177 patients (Fig.  1 ).

Sample of pregnant women studied

Characteristics of the study population

Among the total sample, 533 (3.10%) women had a diagnosis of high blood pressure. 263 (1.53%) pregnant women were diagnosed of chronic hypertension, 111 (0.65%) pregnant women were diagnosed with gestational hypertension and 134 (0.78%) were diagnosed with preeclampsia. Preeclampsia superimposed on chronic hypertension occurred in 25 cases (0.14%).

It was observed that in pregnant women with chronic arterial hypertension (263), the mean age was 33.9 (± 6.00) years, compared to 30.6 (± 5.85) years in the non-hypertensive population. Regarding BMI, 38.4% of patients with chronic hypertension were obese, 44.1% of patients with gestational hypertension, and 26.6% in case of preeclampsia. However, only 14% of non-hypertensive women were obese. Among maternal complications, the percentage of caesarean sections was 28.5% in the case of chronic hypertension, 30.8% in preeclampsia, 23.4% in gestational hypertension compared to 17% in non-hypertensive women. Among the newborn complications, 7.6% in the case of mothers with preeclampsia had an Apgar score lower than 7 in the first minute compared to 2.4% in the case of mothers without hypertension. Respect preterm birth, 18.3% were preterm in the case of chronic hypertension, 24.4% in preeclampsia, 10.7% in gestational hypertension and 5.5% in the case of absence of maternal hypertension. Low birth weight occurred in 17.6% in cases of chronic hypertension, 14.8% in gestational hypertension, 22.9% in preeclampsia and in 5.6% newborns of mothers without hypertension during pregnancy. In the case of chronic hypertension, it was classified as high or very high risk of pregnancy to a greater extent, affecting 31% and 16.3% respectively (Table  2 ).

In the multivariate analysis of the different phenotypes of hypertension during pregnancy adjusted for the covariates (maternal age, BMI, hypothyroidism, maternal diabetes) showed statistically significant associations in the risk of cesarean section in patients with preeclampsia (OR 2.04 95% CI: 1.43–2.88). For the newborn, higher risk of preterm birth was associated with maternal chronic hypertension (OR 3.09, 95% CI: 1.91–4.83) or preeclampsia (OR 5.07, 95% CI: 3.28–7.65) and higher risk of low birth weight in case of maternal chronic hypertension (OR 3.2, 95% CI: 2.04–4.88), preeclampsia (OR 5.07, 95% CI: 3.34–7.52) and in the case of gestational hypertension (OR 2.72, 95% CI: 1.49–4.68). On the other hand, only newborns of patients with preeclampsia had higher risk of having an Apgar score lower than 7 in the first minute (OR 2.95, 95% CI: 1.45–5.38). Patients classified as high or very high risk were primarily those who presented chronic hypertension (OR 5.45, 95% CI: 2.77–10.22) and followed by preeclampsia (OR 1.21, 95% CI: 0.36–3.22) (Fig.  2 ).

Multivariate analysis of types of hypertension in pregnancy and outcomes in the mother and baby, adjusted for body weight

This study, including 17,177 pregnant women, provides valuable information on the risk factors, prevalence and outcomes of a range of HDP adjusted for body weight, which demonstrates that the different subtypes of hypertension represent different risks to the mother and the foetus. There is an increased risk of caesarean section in patients with preeclampsia (OR 2.04 95% CI: 1.43–2.88). For the newborn, higher risk of preterm birth was associated with maternal chronic hypertension (OR 3.09, 95% CI: 1.91–4.83) or preeclampsia (OR 5.07, 95% CI: 3.28–7.65) and higher risk of low birth weight in case of maternal chronic hypertension (OR 3.2, 95% CI: 2.04–4.88), preeclampsia (OR 5.07, 95% CI: 3.34–7.52) and in the case of gestational hypertension (OR 2.72, 95% CI: 1.49–4.68). On the other hand, only newborns of patients with preeclampsia had higher risk of having an Apgar score lower than 7 in the first minute (OR 2.95, 95% CI: 1.45–5.38). Patients categorized as high or very high risk predominantly include those with chronic hypertension (OR 5.45, 95% CI: 2.77–10.22), followed by those with preeclampsia (OR 1.21, 95% CI: 0.36–3.22).

Analysing risk factors individually, gestational age was significantly higher in patients with chronic hypertension with a median of 33.9 (± 6.19) years of age; being 3 years older in comparison to preeclampsia and non-hypertensive women. BMI average for hypertensive women was 28.8 (± 6.28) and 25.9 (± 5.75) in women with preeclampsia. For the rest of the pregnant women, BMI was 24.8 (± 4.85). In a retrospective cohort study carried out in Southern Spain [ 14 ], it was concluded that overweight and obesity increase the risk of suffering from hypertensive disorders during pregnancy; the risk is significantly higher as BMI increases. In multiple population studies it was identified that obesity increases 2 to 4 times the risk of developing preeclampsia [ 15 , 16 ].

Relationship of chronic hypertension (OR 3.09) and preeclampsia (OR 5.07) with a risk of preterm birth in our study has been observed, as described in other publications. According to Sibai et al., the rates of preterm delivery in a large population of women with chronic hypertension while comparing them with those in a healthy control woman, the overall rates of preterm delivery were significantly higher among women with diabetes mellitus (38%) and hypertension (33.1%) than among control women (13.9%) [ 17 ]. An et al., in a prospective cohort study done in China, after adjusting for potential confounders, observed higher levels of preterm birth in women with gestational hypertension 1.04 (95% CI 0.98 to 1.11) and pre-eclampsia 1.39 (95% CI 1.25 to 1.55), respect control women [ 18 ]. Other medical publications also showed an increased risk of preterm birth in a population with hypertension during pregnancy [ 19 , 20 ].

Delivery methods studies demonstrate higher rate of caesarean section in all women with hypertension: 28.5% in chronic hypertension, 23.4% in gestational hypertension and 30.8% in preeclampsia; compared to 17% in women without hypertension in pregnancy. A systematic review and meta-analysis of hypertension and pregnancy outcomes showed a combined incidence of cesarean section of 41.4% (35.5-47.7%) higher than the rate observed in our study [ 21 ]. Moreover, high incidence of adverse outcomes, were described. Therefore, patient-level analysis should be conducted to assess the reasons for cesarean section to provide and guarantee clear indication in each instance.

Study results are comparable to another study from a maternity hospital in Brazil [ 22 ] that reveals the existence of statistically significant differences between the proportion of c-sections, preterm infants and low birth weight infants for pregnant women with and without hypertensive disorders.

All types of hypertensive disorders were associated with low birth weight. The rate observed for patients with chronic hypertension was 17.6%, 22.9% in patients with preeclampsia, 14.8% in patients with gestational hypertension and 5.6% in women not diagnosed with hypertension.

The study conducted by Fang et al. describes similar results comparing women with and without chronic hypertension; reporting rates of low birth weight among hypertensive mothers for white (16.8%), black (24.4%), and Hispanic (19.5%) populations respectively. Trends were similar for chronic and pregnancy-related hypertension, as well as preeclampsia/eclampsia [ 23 ]. The study completed by Wu et al. evaluates the relationship of stage 1 hypertension detected early in gestation (< 20 weeks) and risks of adverse pregnancy outcomes, stratified by pre-pregnancy BMI. Data indicates that women classified at stage 1a (systolic blood pressure 130–134 mm Hg; diastolic BP, 80–84 mm Hg; or both) and stage 1b hypertension (systolic BP, 135–139 mm Hg; diastolic BP, 85–90 mm Hg; or both) show slightly higher but significant rates and risks of gestational diabetes mellitus, preterm birth, and low birth weight (< 2500 g) in both groups compared with normotensive controls [ 24 ].

Results of this study show that only newborns of patients with preeclampsia had a higher risk of having an Apgar score lower than 7 in the first minute (OR 3.3). However, this was not observed in other hypertensive disorders, where Apgar score was normalizing at 5 min. In a large Chinese population study both maternal hypertension and preeclampsia increased risks for low Apgar score at 1 min (aRR: 1.20, 95%CI: 1.13–1.27; aRR: 1.53, 95%CI: 1.41–1.67, respectively), and for low Apgar score at 5 min (aRR: 1.30, 95%CI: 1.17–1.45; aRR: 1.70, 95%CI: 1.46–1.99, respectively). The risk for neonatal respiratory disorders increased with severity of maternal hypertension [ 25 ]. Moreover, Gu et al. proved that higher diastolic blood pressure was associated with an increased risk of 1-minute Apgar score ≤ 7 when extreme quartiles were compared. However, no significant association was found between systolic blood pressure and 1-minutes or 5-minutes Apgar score ≤ 7, which implies that diastolic blood pressure, has a better prognostic value [ 26 ].

Bronfield et al. [ 27 ]. found in a retrospective study in 14 US states worse outcomes for both mothers and babies in mothers with preeclampsia or superimposed preeclampsia compared to the non-hypertensive population, the population with chronic hypertension also had a higher risk of childbirth premature birth, respiratory distress, low birth weight compared to women without hypertension, but the risk was lower than that of mothers with preeclampsia and, as a last group, women with gestational hypertension had a somewhat higher risk of complications compared to non-hypertensive women but more similar to the healthy population. These data are similar to those reported in our study.

Limitations

The main limitation of this study if the fact of using a retrospective design based on administrative data, thus reducing important information on both maternal and neonatal outcomes. The effect of different antihypertensive treatments on maternal and perinatal outcomes have not been evaluated.

Adequate blood pressure control can modify these adverse outcomes. Minas et cols. [ 28 ] Show that more uncontrollable blood pression patients had superimposed preeclampsia with severe features (54.6% vs. 25.0%; p  = 0.01) and preterm delivery (40.9% vs. 10.7%; p  = 0.002) than controlled blood pressure patients. The results of CHAP trial [ 29 ] and the meta-analysis carried out by Atta et al. [ 30 ] suggest the beneficence of pharmacologic treatment of mild chronic hypertension during pregnancy to a blood pressure goal below140/90 mm Hg, which is also supported by the Society for Maternal-Fetal Medicine (SMFM) [ 31 ]. Conversely, in our study, we did not analyze the potential complications of eclampsia or HELLP syndrome in a detailed manner, as these conditions are encompassed within the diagnoses of preeclampsia. Furthermore, superimposed preeclampsia was excluded because it involves patients from two distinct groups. Some instances of gestational hypertension may correspond to previously undetected chronic hypertension due to the presence of masked hypertension. This condition has been associated with an increased risk of developing preeclàmpsia [ 32 ].

Finally, another limitation to be considered is the lack of socioeconomic data on the population, which may also influence several factors and health outcomes.

Future research

All types of hypertension have been found to be related to adverse events on pregnancy. This study supports the need to further investigate the pathophysiological knowledge of hypertension in pregnancies to improve the preventive and therapeutic approaches.

Hypertension in pregnancy is associated with higher incidence of adverse pregnancy outcomes. The different types of hypertension represent different risks in the mother and foetus. These complications were mostly associated with preeclampsia. This finding should be interpreted within the limitations of the study.

The use of sensitive diagnostic criteria facilitates solid foundation in epidemiological study, general practise, and clinical research. To address hypertension, Public Health interventions are necessary in addition to clinical management that act at different levels to improve lifestyle habits and early diagnosis before and during pregnancy.

Data availability

The data used in this study are only available for the participating researchers, in accordance with current European and national laws. Thus, the distribution of the data is not allowed. However, researchers from public institutions can request data from SIDIAP.

1, Boulet SL, Platner M, Joseph NT, Campbell A, Williams R, Stanhope KK, Jamieson DJ. Hypertensive Disorders of Pregnancy, Cesarean Delivery, and Severe Maternal Morbidity in an Urban Safety-Net Population. Am J Epidemiol. 2020;189(12):1502–1511. https://doi.org/10.1093/aje/kwaa135 . PMID: 32639535.

Wu P, Chew-Graham CA, Maas AH, Chappell LC, Potts JE, Gulati M, Jordan KP, Mamas MA. Temporal Changes in Hypertensive Disorders of Pregnancy and Impact on Cardiovascular and Obstetric Outcomes. Am J Cardiol. 2020;125(10):1508–1516. doi: 10.1016/j.amjcard.2020.02.029. Epub 2020 Mar 5. PMID: 32273052.

Li F, Qin J, Zhang S, Chen L. Prevalence of hypertensive disorders in pregnancy in China: a systematic review and meta-analysis. Pregnancy Hypertens. 2021;24:13–21. https://doi.org/10.1016/j.preghy.2021.02.001 . Epub 2021 Feb 14. PMID: 33626437.

Article   PubMed   Google Scholar  

ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstet Gynecol. 2019;133(1):1. https://doi.org/10.1097/AOG.0000000000003018 . PMID: 30575675.

Magee LA, Brown MA, Hall DR, Gupte S, Hennessy A, Karumanchi SA, Kenny LC, McCarthy F, Myers J, Poon LC, Rana S, Saito S, Staff AC, Tsigas E, von Dadelszen P. The 2021 International Society for the Study of Hypertension in Pregnancy classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2022;27:148–69. Epub 2021 Oct 9. PMID: 35066406.

Corrigan L, O’Farrell A, Moran P, Daly D. Hypertension in pregnancy: prevalence, risk factors and outcomes for women birthing in Ireland. Pregnancy Hypertens. 2021;24:1–6. https://doi.org/10.1016/j.preghy.2021.02.005 . Epub 2021 Feb 14. PMID: 33618054.

American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 203: Chronic Hypertension in Pregnancy. Obstet Gynecol. 2019;133(1):e26-e50. https://doi.org/10.1097/AOG.0000000000003020 . PMID: 30575676.

Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol. 2020;135(6):e237-e260. https://doi.org/10.1097/AOG.0000000000003891 . PMID: 32443079.

Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R, Pre-eclampsia. Lancet. 2010;376(9741):631–44. https://doi.org/10.1016/S0140-6736(10)60279-6 . Epub 2010 Jul 2. PMID: 20598363.

Cruz MO, Gao W, Hibbard JU. Obstetrical and perinatal outcomes among women with gestational hypertension, mild preeclampsia, and mild chronic hypertension. Am J Obstet Gynecol. 2011;205(3):260. .e1-260.e9.

Article   Google Scholar  

Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB, Daniels J, Gülmezoglu AM, Temmerman M, Alkema L. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014;2(6):e323–33. https://doi.org/10.1016/S2214-109X(14)70227-X . Epub 2014 May 5. PMID: 25103301.

12, Orós M, Siscart J, Perejón D, Serna MC, Godoy P, Salinas-Roca B. Ethnic disparities and obesity risk factors in pregnant women: a Retrospective Observational Cohort Study. Nutrients. 2023;15(4):926. https://doi.org/10.3390/nu15040926 . PMID: 36839284; PMCID: PMC9961767.

Siscart J, Orós M, Serna MC, Perejón D, Galván L, Ortega M. Adherence to treatment for hypothyroidism in pregnancy and relationship with thyrotropin control: a retrospective observational cohort study. BMC Pregnancy Childbirth. 2022;22(1):168. https://doi.org/10.1186/s12884-022-04483-8 . PMID: 35232385; PMCID: PMC8886742.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Fernández Alba JJ, Mesa Páez C, Vilar Sánchez Á, Soto Pazos E, González Macías M, del Serrano Negro C. Overweight and obesity at risk factors for hypertensive states of pregnancy: a retrospective cohort study. Nutr Hosp. 2018;35(4):874–80.

Spradley FT, Palei AC, Granger JP. Increased risk for the development of preeclampsia in obese pregnancies: weighing in on the mechanisms. Am J Physiol Regul Integr Comp Physiol. 2015;309(11):R1326–43. https://doi.org/10.1152/ajpregu.00178.2015 . Epub 2015 Oct 7. PMID: 26447211; PMCID: PMC4698403.

Robillard PY, et al. Increased BMI has a linear association with late-onset preeclampsia: a population-based study. PLoS ONE. 2019;14:e0223888.

Sibai BM, Caritis SN, Hauth JC, MacPherson C, VanDorsten JP, Klebanoff M, Landon M, Paul RH, Meis PJ, Miodovnik M, Dombrowski MP, Thurnau GR, Moawad AH, Roberts J. Preterm delivery in women with pregestational diabetes mellitus or chronic hypertension relative to women with uncomplicated pregnancies. The National institute of Child health and Human Development Maternal- Fetal Medicine Units Network. Am J Obstet Gynecol. 2000;183(6):1520-4. https://doi.org/10.1067/mob.2000.107621 . PMID: 11120521.

An H, Jin M, Li Z, Zhang L, Li H, Zhang Y, Ye R, Li N. Impact of gestational hypertension and pre-eclampsia on preterm birth in China: a large prospective cohort study. BMJ Open. 2022;12(9):e058068. https://doi.org/10.1136/bmjopen-2021-058068 . PMID: 36167382; PMCID: PMC9516080.

Article   PubMed   PubMed Central   Google Scholar  

Berhe AK, Ilesanmi AO, Aimakhu CO, et al. Effect of pregnancy induced hypertension on adverse perinatal outcomes in Tigray regional state, Ethiopia: a prospective cohort study. BMC Pregnancy Childbirth. 2019;20:7.

Mulualem G, Wondim A, Woretaw A. The effect of pregnancy induced hypertension and multiple pregnancies on preterm birth in Ethiopia: a systematic review and meta-analysis. BMC Res Notes. 2019;12:91.

Bramham K, Parnell B, Nelson-Piercy C, Seed PT, Poston L, Chappell LC. Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis. BMJ. 2014;348:g2301. https://doi.org/10.1136/bmj.g2301 . PMID: 24735917; PMCID: PMC3988319.

Ramos Filho FL, Antunes CMF. Hypertensive Disorders: Prevalence, Perinatal Outcomes and Cesarean Section Rates in Pregnant Women Hospitalized for Delivery. Rev Bras Ginecol Obstet. 2020;42(11):690–696. doi: 10.1055/s-0040-1714134. Epub 2020 Nov 30. PMID: 33254262; PMCID: PMC10309246.

23, Fang J, Madhavan S, Alderman MH. The influence of maternal hypertension on low birth weight: differences among ethnic populations. Ethn Dis. 1999 Autumn;9(3):369 – 76. PMID: 10600059.

Wu DD, Gao L, Huang O, Ullah K, Guo MX, Liu Y, Zhang J, Chen L, Fan JX, Sheng JZ, Lin XH, Huang HF. Increased Adverse Pregnancy Outcomes Associated With Stage 1 Hypertension in a Low-Risk Cohort: Evidence From 47 874 Cases. Hypertension. 2020;75(3):772–780. doi: 10.1161/HYPERTENSIONAHA.119.14252. Epub 2020 Feb 3. PMID: 32008433.

25, Tian T, Wang L, Ye R, Liu J, Ren A. Maternal hypertension, preeclampsia, and risk of neonatal respiratory disorders in a large-prospective cohort study. Pregnancy Hypertens. 2020;19:131–7. https://doi.org/10.1016/j.preghy.2020.01.006 . Epub 2020 Jan 14. PMID: 31982835.

Gu Y, Shi H, Zeng W, Zheng Y, Yang M, Sun M, Shi H, Gu W. Association between gestational visit-to-visit blood pressure variability and adverse neonatal outcomes. J Clin Hypertens (Greenwich). 2022;24(6):779–88. https://doi.org/10.1111/jch.14500 . Epub 2022 May 14. PMID: 35567772; PMCID: PMC9180330.

Article   CAS   PubMed   Google Scholar  

Bromfield SG, Ma Q, DeVries A, Inglis T, Gordon AS. The association between hypertensive disorders during pregnancy and maternal and neonatal outcomes: a retrospective claims analysis. BMC Pregnancy Childbirth. 2023;23(1):514. https://doi.org/10.1186/s12884-023-05818-9 . PMID: 37452285; PMCID: PMC10347833.

Minhas R, Young D, Naseem R, Mueller A, Chinthala S, Perdigao JL, Yeo KJ, Chan SL, Tung A, White JB, Shahul S, Rana S. Association of antepartum blood pressure levels and angiogenic profile among women with chronic hypertension. Pregnancy Hypertens. 2018;14:110–114. doi: 10.1016/j.preghy.2018.09.003. Epub 2018 Sep 5. PMID: 30527096.

Tita AT, Szychowski JM, Boggess K, Dugoff L, Sibai B, Lawrence K, Hughes BL, Bell J, Aagaard K, Edwards RK, Gibson K, Haas DM, Plante L, Metz T, Casey B, Esplin S, Longo S, Hoffman M, Saade GR, Hoppe KK, Foroutan J, Tuuli M, Owens MY, Simhan HN, Frey H, Rosen T, Palatnik A, Baker S, August P, Reddy UM, Kinzler W, Su E, Krishna I, Nguyen N, Norton ME, Skupski D, El-Sayed YY, Ogunyemi D, Galis ZS, Harper L, Ambalavanan N, Geller NL, Oparil S, Cutter GR, Andrews WW. Chronic hypertension and pregnancy (CHAP) Trial Consortium. Treatment for mild chronic hypertension during pregnancy. N Engl J Med. 2022;386(19):1781–92. https://doi.org/10.1056/NEJMoa2201295 . Epub 2022 Apr 2. PMID: 35363951; PMCID: PMC9575330.

Attar A, Hosseinpour A, Moghadami M. The impact of antihypertensive treatment of mild to moderate hypertension during pregnancy on maternal and neonatal outcomes: An updated meta-analysis of randomized controlled trials. Clin Cardiol. 2023;46(5):467–476. doi: 10.1002/clc.24013. Epub 2023 Mar 28. PMID: 369873Society for Maternal-Fetal Medicine. Society for Maternal‐Fetal Medicine statement: antihypertensive therapy for mild chronic hypertension in pregnancy—the chronic hypertension and preg-nancy trial. Am J Obstet Gynecol. 2022;227(2):B24‐B2790; PMCID: PMC10189071.

Society for Maternal-Fetal Medicine. Publications Committee. Electronic address: [email protected]. Society for maternal-fetal Medicine Statement: antihypertensive therapy for mild chronic hypertension in pregnancy-the chronic hypertension and pregnancy trial. Am J Obstet Gynecol. 2022;227(2):B24–7. https://doi.org/10.1016/j.ajog.2022.04.011 . Epub 2022 Apr 19. PMID: 35710594.

Espeche WG, Salazar MR, Minetto J, Leiva Sisnieguez CE, Cerri G, Balbín E, Stavile RN, Carrera Ramos P, Soria A, Santillan C, Grassi F, Torres S, Carbajal HA. Hypertension arising after 20 weeks of gestation: gestational hypertension or masked chronic hypertension? J Hum Hypertens. 2023;37(9):813–7. https://doi.org/10.1038/s41371-022-00767-w . Epub 2022 Oct 12. PMID: 36224324.

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Acknowledgements

The authors would like to acknowledge Dr. Miquel Butí for his valuable contribution and support to design and build the database. Joaquim Sol for his contribution to the statistics analysis, and Gol i Gurina Foundation.

The authors declare no contribution from any organization for the submitted work; no financial relationships with organizations that might have an interest in the submitted work for the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

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Hospital Trueta, Catalan Institute of Health, Anna Bardalet Hospital Trueta, Institut Català de la Salut (ICS), Avda de Francia s/n 17007, Girona, Spain

Anna Bardalet

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AB and DP conceptualized the study, analysed the data, and wrote the first draft of the manuscript; MCS, JS, IG contributed to the design of the study, data management, and manuscript development and review; MO also contributed to the design of the study, and to the creation of data bases and data analysis. All authors read and approved the final manuscript.

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This study was approved by the ethics and clinical research committee at the Institut d’Investigació IDIAP Jordi Gol under the code 19/195-P and conducted in accordance with the principles of the Declaration of Helsinki. Information was obtained from electronic medical records stored in the centralized ECAP (computerized clinical history) database and extracted by the Department of Healthcare Evaluation and Research Management. Accordingly, it was not necessary to ask participants for their informed consent. The variables in the ECAP database were processed anonymously and with full confidentiality guarantees as established by Spanish national law and Regulation 2016/679 of the European Parliament and the Council on the protection of natural persons with regard to the processing of personal data, and to the free distribution of such data. The data used in this study are only available for the participating researchers, in accordance with current European and national laws. Thus, the distribution of the data is not allowed. However, researchers from public institutions can request data from SIDIAP. Ethics committee of (Idiap Jordi Gol i Gurina) waived the need for informed consent due to retrospective observational cohort study.

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Perejón, D., Bardalet, A., Gascó, I. et al. Hypertension subtypes and adverse maternal and perinatal outcomes - a retrospective population-based cohort study. BMC Pregnancy Childbirth 24 , 568 (2024). https://doi.org/10.1186/s12884-024-06754-y

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Pregnacy Induced Hypertension (PIH) Case Study

Pregnancy-induced hypertension (PIH) is one of the most common complications of pregnancy. This occurs during the 20 th week of gestation or late in the second trimester of pregnancy. This is a health condition wherein there is a rise in the blood pressure and disappears after the termination of pregnancy or delivery. PIH was formerly called toxaemia or the presence of toxins in the blood. This is because its occurrence was not well understood in the clinical field. Its common manifestations are hypertension, proteinuria (presence of protein in the urine), and edema. There are 2 main types of pregnancy-induced hypertension namely: pre-eclampsia and eclampsia.

• Pre-eclampsia— this is the non-convulsive form of PIH. This affects 7% of all pregnant women. Its incidence is higher in lower socio-economic groups. It may be classified either mild or severe.
• Eclampsia— this is the convulsive form of PIH. It occurs with 5% of all pre-eclampsia cases. The mortality rate among mothers is nearly 20% and fetal mortality is also high due to premature delivery.

NORMAL ANATOMY AND PHYSIOLOGY

There are a lot of bodily changes that happen during a normal pregnancy. There are external changes that are noticeable, and there are internal changes that can only be appreciated through thorough clinical examinations. Most of the changes are the body’s response to the changes in levels of hormones and the growing demands of the fetus.

The two dominant female hormones, estrogen and progesterone , change in a normal level. Along with this, a significant rise/appearance of 4 more major hormones take place; these are 1. human chorionic gonadotropin (HCG), 2. human placental lactogen, 3. prolactin, and 4. oxytocin. All these 6 hormones interact with each other simultaneously to maintain a normal pregnancy as it progresses.

The following are the major effects of these hormones in the body:

The exact cause of pregnancy-induced hypertension is unknown; however, it is highly linked to angiotensin gene T235 and the existence of other risk factors. Malnutrition and inadequate prenatal care are the greatest risk factors. The history and presence of diabetes mellitus (DM), multifetal gestation (twin pregnancies), polyhydramnios (excessive amniotic fluid), and renal diseases are also among the major contributory factors in the development of PIH. In the past, the mystery revolving around PIH postulated a lot of theories on its true origin, most of them were believed to be of toxic nature. Among these are placental infarcts, autointoxication, uremia, pyelonephritis, and maternal sensitization to total proteins.

The i ncidence of PIH among pregnant women is very high (8%), costing hundreds and thousands of lives of both mothers and fetus around the world. This commonly affects first-time pregnancies due to the presence of functioning tropoblasts (develops after the 20 th week of gestation and stays evident until after 48 hours after delivery. Age is also an important indicator in the development of PIH. Too early, as in teenage pregnancies and old primigravidas (first-time pregnancy) as in over 35 years of age put a woman higher chances of having pregnancy-induced hypertension . 

PATHOPHYSIOLOGY

SIGNS AND SYMPTOMS

The signs and symptoms of the type of PIH present in a pregnant woman are based on the presentation of evident clinical manifestations. These are shown in the table below:

COMPLICATIONS

Based on the severity of the PIH present to a person or the extent of damage left/occurred, a list of possible complications can be drawn.

• Abruption placenta
• Disseminated intravascular coagulation (DIC)
• Prematurity
• Intrauterine growth retardation (IUGR)
• HELLP syndrome
• Maternal and/or fetal death  

The changes of the mother and/or fetus to survive after an episode of convulsion or until delivery depends on the threshold on the effects of PIH and its complications. This can be:

• Good— if the symptoms are mild or those that are with mild pre-eclampsia and is responding well to the treatment regimen
•   Poor— if there are multiple and long episodes of convulsions that are associated or lead to the development of persistent coma, hyperthermia, cyanosis, tachycardia, and liver damage.
• Congestive heart failure (CHF)
• Pulmonary edema
• Cerebral hemorrhage
• Renal failure

DIAGNOSTIC EVALUATIONS

            Diagnostic evaluations are performed after episodes of convulsions or after the client has been rushed to a health care facility. These are routinely done to assess the damages and will serve as the basis for the plan of treatment.

• 24-hour urine-protein— health problem through protein determination from the involvement of the renal system.
• Serum BUN and creatinine— to evaluate renal functioning.
• Ophthalmic examination— to assess spasm, papilledema, retinal edema/detachment, and/or hemorrhages.
• Ultrasonography with stress and non- stress test— to evaluate fetal well-being after.
• Stress test —fetalheart tone (FHT) and fetal activity are electronically monitored after oxytocin induction which causes uterine contraction.
• Non-stress test —fetal heart tone (FHT) and fetal activity are electronically monitored during fetal activity (no oxytocin induction).  

NURSING DIAGNOSES

• Fluid volume excess related to altered blood osmolarity and sodium/water retention.
• Altered nutrition, less than body requirements related to loss through damaged renal membrane.
• Altered tissue perfusion related to increased peripheral resistance and vasospasm in renal and cardiovascular system.
• Altered urinary elimination related to hypovolemia.
• Sensory/perceptual alterations: visual related to cerebral edema and decreased oxygenation of the brain.
• Diversional activity deficit related to decreased time for rest and sleep from stimulating environment.
• Risk for injury related to seizure episodes.
• Anxiety-related to fear of the unknown.    

            The overall goal of management in pregnancy-induced hypertension is directed towards the control of hypertension and the correction of developed health problems that might leadto other serious complications. Among the specially-designed treatment course for PIH are the following:

• Use of antihypertensive drugs (hydralazine-drug of choice)
• Diet-high protein, high calories
•   Magnesium sulphate (MgSO4) treatment
• Diazepam and amobarbital sodium (if convulsions don’t respond to MgSO4)
• Beta-adrenergic blockers (used for acute hypertension)
• Delivery (if all treatment regimen don’t work)

NURSING MANAGEMENT

A.   Assessment

•   Monitor blood pressure in sitting or side-lying position.
• Monitor fetal heart tone (FHT) and fetal heart rate (FHR).
• Check for deep tendon reflexes (DTR) and clonus.
•   Monitor intake and output (I&O) and proteinuria.
• Monitor daily weight and edema.
• Assess for signs of labor (possibility of abruption placenta).
• Assess for emotional status.

B.  Interventions

1.  Fluid balance

• Maintain patent and regulated IVF
• Strict I&O monitoring
• Monitor hematocrit level
• Vital signs monitoring every hour
• Assess breath sounds for signs of pulmonary edema

  2.  Tissue perfusion

•  Position on left-lateral position
• Monitor fetal activity (stress and fetal activity)

3.   Preventing injury

• Monitor cerebral signs and symptoms (headache, visual disturbances, and dizziness)
• Lie on left-lateral position if cerebral symptoms are present
• Secure padded side rails
• Keep oxygen suction set, tongue blade, and emergency medications (diazepam and magnesium sulphate) at all times
• Never leave an unstable patient

4.   Anxiety

 Discuss the health condition and planned treatment

• PIH is not lifetime
• PIH is only for the first pregnancy
• All medications and its maternal and fetal effects

Allow to ask questions and answer it truthfully

Provide emotional support to the client and family

C.   Educative

• Reinforce the importance of rest and sleep
• Encourage family cooperation with the treatment course
• Discuss the laboratory procedures and alternative managements
• Include medical team, client, and significant others in the discussion
• Be realistic in discussing the possibilities of premature delivery  
• No sign of pulmonary edema
• Adequate urine output
• No episode of seizure
• Stable and normal heart rate

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Characteristics, physiopathology and management of dyslipidemias in pregnancy: a narrative review.

1. Introduction

2. lipid physiology in pregnancy, 3. hyperlipidemia and possible adverse maternal and neonatal outcomes, lipid metabolism and pregestational conditions.

4. Dietary and Lifestyle Approaches in Pregnancy

4.1. macronutrients in pregnancy, 4.2. micronutrients: minerals and vitamins, 5. nutritional strategies for managing dyslipidemias in pregnancy, 6. pharmacological approach, 6.1. familial hypercholesterolemia: treatment in pregnancy, 6.1.1. bile acid sequestrants, 6.1.2. fibrates, nicotinic acid, ezetimibe, 6.1.3. statins, 6.1.4. new therapies, 6.2. lipoprotein apheresis for managing dyslipidemia in pregnancy, 6.3. severe hypertriglyceridemia: treatment in pregnancy, 6.3.1. statins, 6.3.2. fibrates, 6.3.3. omega-3, 6.3.4. nicotinic acid (niacin), 6.3.5. bile acid sequestrants, 6.3.6. new therapies, 6.3.7. plasmapheresis, 7. conclusions, author contributions, institutional review board statement, informed consent statement, data availability statement, conflicts of interest.

• Roeters Van Lennep, J.E.; Tokgözoǧlu, L.S.; Badimon, L.; Dumanski, S.M.; Gulati, M.; Hess, C.N.; Holven, K.B.; Kavousi, M.; Kaylkçloǧlu, M.; Lutgens, E.; et al. Women, Lipids, and Atherosclerotic Cardiovascular Disease: A Call to Action from the European Atherosclerosis Society. Eur. Heart J. 2023 , 44 , 4157–4173. [ Google Scholar ] [ CrossRef ]
• Liu, T.; Zhao, D.; Qi, Y. Global Trends in the Epidemiology and Management of Dyslipidemia. J. Clin. Med. 2022 , 11 , 6377. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Yanai, H.; Yoshida, H. Secondary Dyslipidemia: Its Treatments and Association with Atherosclerosis. Glob. Health Med. 2021 , 3 , 15–23. [ Google Scholar ] [ CrossRef ]
• Cho, S.M.J.; Lee, H.J.; Shim, J.S.; Song, B.M.; Kim, H.C. Associations between Age and Dyslipidemia Are Differed by Education Level: The Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC) Cohort. Lipids Health Dis. 2020 , 19 , 12. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Formisano, E.; Pasta, A.; Cremonini, A.L.; Di Lorenzo, I.; Sukkar, S.G.; Pisciotta, L. Effects of a Mediterranean Diet, Dairy, and Meat Products on Different Phenotypes of Dyslipidemia: A Preliminary Retrospective Analysis. Nutrients 2021 , 13 , 1161. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Schienkiewitz, A.; Truthmann, J.; Ernert, A.; Wiegand, S.; Schwab, K.O.; Scheidt-Nave, C. Age, Maturation and Serum Lipid Parameters: Findings from the German Health Survey for Children and Adolescents. BMC Public Health 2019 , 19 , 1627. [ Google Scholar ] [ CrossRef ]
• Sharma, J.; McAlister, J.; Aggarwal, N.R.; Wei, J.; Mehta, P.K.; Quesada, O.; Mattina, D.; Scott, N.S.; Michos, E.D.; Mahmoud, Z.; et al. Evaluation and Management of Blood Lipids through a Woman’s Life Cycle. Am. J. Prev. Cardiol. 2022 , 10 , 100333. [ Google Scholar ] [ CrossRef ]
• Upmeier, E.; Lavonius, S.; Heinonen, P.; Viitanen, M.; Isoaho, H.; Arve, S.; Lehtonen, A. Longitudinal Changes in Serum Lipids in Older People the Turku Elderly Study 1991–2006. Age Ageing 2011 , 40 , 280–283. [ Google Scholar ] [ CrossRef ]
• Mulder, J.W.C.M.; Kusters, D.M.; van Lennep, J.E.R.; Hutten, B.A. Lipid Metabolism during Pregnancy: Consequences for Mother and Child. Curr. Opin. Lipidol. 2024 , 35 , 133–140. [ Google Scholar ] [ CrossRef ]
• Li, C.; Li, X.; Wu, D.; Chen, Q.; Xiao, Z.; Wen, D.; Zhai, L.; Jia, L. Influence of Dietary Behaviors on Dyslipidemia in Pregnant Women and Its Effects on Physical Development of Fetuses and Infants: A Bidirectional Cohort Study. Nutrients 2021 , 13 , 3398. [ Google Scholar ] [ CrossRef ]
• Graves, M.; Howse, K.; Pudwell, J.; Smith, G.N. Pregnancy-Related Cardiovascular Risk Indicators: Primary Care Approach to Postpartum Management and Prevention of Future Disease. Can. Fam. Physician 2019 , 65 , 883–889. [ Google Scholar ] [ PubMed ]
• Tabacu, C.; Manolea, M.-M.; Novac, L.; Dijmarescu, A.L.; Boldeanu, M.V. Maternal Lipid Profile as a Risk Factor for Gestational Diabetes Mellitus in Obese Women. Curr. Health Sci. J. 2021 , 47 , 209–214. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Spracklen, C.N.; Smith, C.J.; Saftlas, A.F.; Robinson, J.G.; Ryckman, K.K. Maternal Hyperlipidemia and the Risk of Preeclampsia: A Meta-Analysis. Am. J. Epidemiol. 2014 , 180 , 346–358. [ Google Scholar ] [ CrossRef ]
• Mach, F.; Baigent, C.; Catapano, A.L.; Koskina, K.C.; Casula, M.; Badimon, L.; Chapman, M.J.; De Backer, G.G.; Delgado, V.; Ference, B.A.; et al. 2019 ESC/EAS Guidelines for the Management of Dyslipidaemias: Lipid Modification to Reduce Cardiovascular Risk. Atherosclerosis 2019 , 290 , 140–205. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Makarem, N.; Chau, K.; Miller, E.C.; Gyamfi-Bannerman, C.; Tous, I.; Booker, W.; Catov, J.M.; Haas, D.M.; Grobman, W.A.; Levine, L.D.; et al. Association of a Mediterranean Diet Pattern With Adverse Pregnancy Outcomes Among US Women. JAMA Netw. Open 2022 , 5 , E2248165. [ Google Scholar ] [ CrossRef ]
• Dai, F.C.; Wang, P.; Li, Q.; Zhang, L.; Yu, L.J.; Wu, L.; Tao, R.X.; Zhu, P. Mediterranean Diet during Pregnancy and Infant Neurodevelopment: A Prospective Birth Cohort Study. Front. Nutr. 2023 , 9 , 1078481. [ Google Scholar ] [ CrossRef ]
• Richardson, L.A.; Izuora, K.; Basu, A. Mediterranean Diet and Its Association with Cardiovascular Disease Risk Factors: A Scoping Review. Int. J. Environ. Res. Public Health 2022 , 19 , 12762. [ Google Scholar ] [ CrossRef ]
• Escobar, C.; Anguita, M.; Arrarte, V.; Barrios, V.; Cequier, Á.; Cosín-Sales, J.; Egocheaga, I.; López de Sa, E.; Masana, L.; Pallarés, V.; et al. Recommendations to Improve Lipid Control. Consensus Document of the Spanish Society of Cardiology. Rev. Esp. Cardiol. (Engl. Ed.) 2020 , 73 , 161–167. [ Google Scholar ] [ CrossRef ]
• Pasta, A.; Formisano, E.; Cremonini, A.L.; Maganza, E.; Parodi, E.; Piras, S.; Pisciotta, L. Diet and Nutraceutical Supplementation in Dyslipidemic Patients: First Results of an Italian Single Center Real-World Retrospective Analysis. Nutrients 2020 , 12 , 2056. [ Google Scholar ] [ CrossRef ]
• Mauricio, R.; Khera, A. Statin Use in Pregnancy: Is It Time For a Paradigm Shift? Circulation 2022 , 145 , 496–498. [ Google Scholar ] [ CrossRef ]
• Bohn, M.K.; Adeli, K. Physiological and Metabolic Adaptations in Pregnancy: Importance of Trimester-Specific Reference Intervals to Investigate Maternal Health and Complications. Crit. Rev. Clin. Lab. Sci. 2022 , 59 , 76–92. [ Google Scholar ] [ CrossRef ]
• Zeng, Z.; Liu, F.; Li, S. Metabolic Adaptations in Pregnancy: A Review. Ann. Nutr. Metab. 2017 , 70 , 59–65. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Herrera, E. Lipid Metabolism in Pregnancy and Its Consequences in the Fetus and Newborn. Endocrine 2002 , 19 , 43–55. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Lain, K.Y.; Catalano, P.M. Metabolic Changes in Pregnancy. Clin. Obstet. Gynecol. 2007 , 50 , 938–948. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Rung, E.; Friberg, P.A.; Shao, R.; Larsson, D.G.J.; Nielsen, E.C.; Svensson, P.A.; Carlsson, B.; Carlsson, L.M.S.; Billig, H. Progesterone-Receptor Antagonists and Statins Decrease de Novo Cholesterol Synthesis and Increase Apoptosis in Rat and Human Periovulatory Granulosa Cells in Vitro. Biol. Reprod. 2005 , 72 , 538–545. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Duttaroy, A.K.; Basak, S. Maternal Fatty Acid Metabolism in Pregnancy and Its Consequences in the Feto-Placental Development. Front. Physiol. 2022 , 12 , 787848. [ Google Scholar ] [ CrossRef ]
• Ghio, A.; Bertolotto, A.; Resi, V.; Volpe, L.; Di Cianni, G. Triglyceride Metabolism in Pregnancy. Adv. Clin. Chem. 2011 , 55 , 133–153. [ Google Scholar ] [ CrossRef ]
• Goldberg, I.J.; Eckel, R.H.; Abumrad, N.A. Regulation of Fatty Acid Uptake into Tissues: Lipoprotein Lipase- and CD36-Mediated Pathways. J. Lipid Res. 2009 , 50 , S86–S90. [ Google Scholar ] [ CrossRef ]
• Bowman, C.E.; Arany, Z.; Wolfgang, M.J. Regulation of Maternal-Fetal Metabolic Communication. Cell Mol. Life Sci. 2021 , 78 , 1455–1486. [ Google Scholar ] [ CrossRef ]
• Herrera, E.; Desoye, G. Maternal and Fetal Lipid Metabolism under Normal and Gestational Diabetic Conditions. Horm. Mol. Biol. Clin. Investig. 2016 , 26 , 109–127. [ Google Scholar ] [ CrossRef ]
• Melchior, J.T.; Swertfeger, D.K.; Morris, J.; Street, S.E.; Warshak, C.R.; Welge, J.A.; Remaley, A.T.; Catov, J.M.; Davidson, W.S.; Woollett, L.A. Pregnancy Is Accompanied by Larger High Density Lipoprotein Particles and Compositionally Distinct Subspecies. J. Lipid Res. 2021 , 62 , 100107. [ Google Scholar ] [ CrossRef ]
• Piechota, W.; Staszewski, A. Reference Ranges of Lipids and Apolipoproteins in Pregnancy. Eur. J. Obstet. Gynecol. Reprod. Biol. 1992 , 45 , 27–35. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Wang, C.; Kong, L.; Yang, Y.; Wei, Y.; Zhu, W.; Su, R.; Lin, L.; Yang, H. Recommended Reference Values for Serum Lipids during Early and Middle Pregnancy: A Retrospective Study from China. Lipids Health Dis. 2018 , 17 , 246. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Perrine, C.G.; Nelson, J.M.; Corbelli, J.; Scanlon, K.S. Lactation and Maternal Cardio-Metabolic Health. Annu. Rev. Nutr. 2016 , 36 , 627–645. [ Google Scholar ] [ CrossRef ]
• Lu, F.; Ferriero, D.M.; Jiang, X. Cholesterol in Brain Development and Perinatal Brain Injury: More than a Building Block. Curr. Neuropharmacol. 2022 , 20 , 1400–1412. [ Google Scholar ] [ CrossRef ]
• Wong, B.; Ooi, T.C.; Keely, E. Severe Gestational Hypertriglyceridemia: A Practical Approach for Clinicians. Obstet. Med. 2015 , 8 , 158–167. [ Google Scholar ] [ CrossRef ]
• Dalfrà, M.G.; Burlina, S.; Ragazzi, E.; Pastrolin, S.; Sartore, G.; Lapolla, A. Lipid Profile in Women of Different Ethnicity with Gestational Diabetes: Relationship with Fetal Growth. J. Diabetes Investig. 2024 , 15 , 355–363. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Wang, Y.; Chen, Z.; Zhang, F. Association between Maternal Lipid Levels during Pregnancy and Delivery of Small for Gestational Age: A Systematic Review and Meta-Analysis. Front. Pediatr. 2022 , 10 , 934505. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Toleikyte, I.; Retterstøl, K.; Leren, T.P.; Iversen, P.O. Pregnancy Outcomes in Familial Hypercholesterolemia: A Registry-Based Study. Circulation 2011 , 124 , 1606–1614. [ Google Scholar ] [ CrossRef ]
• Pasta, A.; Cremonini, A.L.; Formisano, E.; Fresa, R.; Bertolini, S.; Pisciotta, L. Long Term Follow-up of Genetically Confirmed Patients with Familial Hypercholesterolemia Treated with First and Second-Generation Statins and Then with PCSK9 Monoclonal Antibodies. Atherosclerosis 2020 , 308 , 6–14. [ Google Scholar ] [ CrossRef ]
• Casula, M.; Gazzotti, M.; Capra, M.E.; Olmastroni, E.; Galimberti, F.; Catapano, A.L.; Pederiva, C.; Anesi, A.; Arca, M.; Auricchio, R.; et al. Refinement of the Diagnostic Approach for the Identification of Children and Adolescents Affected by Familial Hypercholesterolemia: Evidence from the LIPIGEN Study. Atherosclerosis 2023 , 385 , 117231. [ Google Scholar ] [ CrossRef ]
• Graham, D.F.; Raal, F.J. Management of Familial Hypercholesterolemia in Pregnancy. Curr. Opin. Lipidol. 2021 , 32 , 370–377. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Amundsen, Å.L.; Khoury, J.; Iversen, P.O.; Bergei, C.; Ose, L.; Tonstad, S.; Retterstøl, K. Marked Changes in Plasma Lipids and Lipoproteins during Pregnancy in Women with Familial Hypercholesterolemia. Atherosclerosis 2006 , 189 , 451–457. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Abu-Awwad, S.A.; Craina, M.; Boscu, L.; Bernad, E.; Ciordas, P.D.; Marian, C.; Iurciuc, M.; Abu-Awwad, A.; Iurciuc, S.; Bernad, B.; et al. Lipid Profile Variations in Pregnancies with and without Cardiovascular Risk: Consequences for Both Mother and Newborn. Children 2023 , 10 , 1521. [ Google Scholar ] [ CrossRef ]
• Li, G.; Kong, L.; Zhang, L.; Fan, L.; Su, Y.; Rose, J.C.; Zhang, W. Early Pregnancy Maternal Lipid Profiles and the Risk of Gestational Diabetes Mellitus Stratified for Body Mass Index. Reprod. Sci. 2015 , 22 , 712–717. [ Google Scholar ] [ CrossRef ]
• Ryckman, K.K.; Spracklen, C.N.; Smith, C.J.; Robinson, J.G.; Saftlas, A.F. Maternal Lipid Levels during Pregnancy and Gestational Diabetes: A Systematic Review and Meta-Analysis. BJOG 2015 , 122 , 643–651. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Rahnemaei, F.A.; Pakzad, R.; Amirian, A.; Pakzad, I.; Abdi, F. Effect of Gestational Diabetes Mellitus on Lipid Profile: A Systematic Review and Meta-Analysis. Open Med (Wars). 2021 , 17 , 70–86. [ Google Scholar ] [ CrossRef ]
• O’Malley, E.G.; Reynolds, C.M.E.; Killalea, A.; O’Kelly, R.; Sheehan, S.R.; Turner, M.J. Maternal Obesity and Dyslipidemia Associated with Gestational Diabetes Mellitus (GDM). Eur. J. Obstet. Gynecol. Reprod. Biol. 2020 , 246 , 67–71. [ Google Scholar ] [ CrossRef ]
• Hardy, O.T.; Czech, M.P.; Corvera, S. What Causes the Insulin Resistance Underlying Obesity? Curr. Opin. Endocrinol. Diabetes Obes. 2012 , 19 , 81–87. [ Google Scholar ] [ CrossRef ]
• Stadler, J.T.; Lackner, S.; Mörkl, S.; Trakaki, A.; Scharnagl, H.; Borenich, A.; Wonisch, W.; Mangge, H.; Zelzer, S.; Meier-Allard, N.; et al. Obesity Affects HDL Metabolism, Composition and Subclass Distribution. Biomedicines 2021 , 9 , 242. [ Google Scholar ] [ CrossRef ]
• Formisano, E.; Proietti, E.; Borgarelli, C.; Sukkar, S.G.; Albertelli, M.; Boschetti, M.; Pisciotta, L. The Impact of Overweight on Lipid Phenotype in Different Forms of Dyslipidemia: A Retrospective Cohort Study. J. Endocrinol. Investig. 2024 . [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Wojcik-Baszko, D.; Charkiewicz, K.; Laudanski, P. Role of Dyslipidemia in Preeclampsia—A Review of Lipidomic Analysis of Blood, Placenta, Syncytiotrophoblast Microvesicles and Umbilical Cord Artery from Women with Preeclampsia. Prostaglandins Other Lipid Mediat. 2018 , 139 , 19–23. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Roberts, J.M.; Escudero, C. The Placenta in Preeclampsia. Pregnancy Hypertens. 2012 , 2 , 72–83. [ Google Scholar ] [ CrossRef ]
• Yang, Y.; Wang, Y.; Lv, Y.; Ding, H. Dissecting the Roles of Lipids in Preeclampsia. Metabolites 2022 , 12 , 590. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Gallos, I.D.; Sivakumar, K.; Kilby, M.D.; Coomarasamy, A.; Thangaratinam, S.; Vatish, M. Pre-Eclampsia Is Associated with, and Preceded by, Hypertriglyceridaemia: A Meta-Analysis. BJOG 2013 , 120 , 1321–1332. [ Google Scholar ] [ CrossRef ]
• Kleess, L.E.; Janicic, N. Severe hypertriglyceridemia in pregnancy: A case report and review of the literature. AACE Clin. Case Rep. 2019 , 5 , e99. [ Google Scholar ] [ CrossRef ]
• Dash, S.; Tiwari, M.; Dash, P.; Kar, K.; Mohakud, N.K. Complications of Hypertriglyceridemia in Pregnancy and Its Impact on Neonates: A Hospital-Based Study from Odisha. Cureus 2022 , 14 , e28399. [ Google Scholar ] [ CrossRef ]
• Wang, J.; Moore, D.; Subramanian, A.; Cheng, K.K.; Toulis, K.A.; Qiu, X.; Saravanan, P.; Price, M.J.; Nirantharakumar, K. Gestational Dyslipidaemia and Adverse Birthweight Outcomes: A Systematic Review and Meta-Analysis. Obes. Rev. 2018 , 19 , 1256–1268. [ Google Scholar ] [ CrossRef ]
• Calina, D.; Docea, A.O.; Golokhvast, K.S.; Sifakis, S.; Tsatsakis, A.; Makrigiannakis, A. Management of Endocrinopathies in Pregnancy: A Review of Current Evidence. Int. J. Environ. Res. Public Health 2019 , 16 , 781. [ Google Scholar ] [ CrossRef ]
• Alexopoulos, A.S.; Blair, R.; Peters, A.L. Management of Preexisting Diabetes in Pregnancy: A Review. JAMA 2019 , 321 , 1811–1819. [ Google Scholar ] [ CrossRef ]
• Hui, D.; Hladunewich, M.A. Chronic Kidney Disease and Pregnancy. Obstet. Gynecol. 2019 , 133 , 1182–1194. [ Google Scholar ] [ CrossRef ]
• Baumfeld, Y.; Novack, L.; Wiznitzer, A.; Sheiner, E.; Henkin, Y.; Sherf, M.; Novack, V. Pre-Conception Dyslipidemia Is Associated with Development of Preeclampsia and Gestational Diabetes Mellitus. PLoS ONE 2015 , 10 , e0139164. [ Google Scholar ] [ CrossRef ]
• Huhtala, M.; Rönnemaa, T.; Tertti, K. Insulin Resistance Is Associated with an Unfavorable Serum Lipoprotein Lipid Profile in Women with Newly Diagnosed Gestational Diabetes. Biomolecules 2023 , 13 , 470. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Wu, S.A.; Kersten, S.; Qi, L. Lipoprotein Lipase and Its Regulators: An Unfolding Story. Trends Endocrinol. Metab. 2021 , 32 , 48–61. [ Google Scholar ] [ CrossRef ]
• Toescu, V.; Nuttall, S.L.; Martin, U.; Nightingale, P.; Kendall, M.J.; Brydon, P.; Dunne, F. Changes in Plasma Lipids and Markers of Oxidative Stress in Normal Pregnancy and Pregnancies Complicated by Diabetes. Clin. Sc. (Lond.) 2004 , 106 , 93–98. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Oros Ruiz, M.; Perejón López, D.; Serna Arnaiz, C.; Siscart Viladegut, J.; Àngel Baldó, J.; Sol, J. Maternal and Foetal Complications of Pregestational and Gestational Diabetes: A Descriptive, Retrospective Cohort Study. Sci. Rep. 2024 , 14 , 9017. [ Google Scholar ] [ CrossRef ]
• Malaza, N.; Masete, M.; Adam, S.; Dias, S.; Nyawo, T.; Pheiffer, C. A Systematic Review to Compare Adverse Pregnancy Outcomes in Women with Pregestational Diabetes and Gestational Diabetes. Int. J. Environ. Res. Public Health 2022 , 19 , 10846. [ Google Scholar ] [ CrossRef ]
• Jiang, X.; Lu, X.; Cai, M.; Liu, Y.; Guo, Y. Impact of Dyslipidemia on the Cumulative Pregnancy Outcomes after First Ovarian Stimulation. Front. Endocrinol. 2022 , 13 , 915424. [ Google Scholar ] [ CrossRef ]
• Morón-Díaz, M.; Saavedra, P.; Alberiche-Ruano, M.P.; Rodríguez-Pérez, C.A.; López-Plasencia, Y.; Marrero-Arencibia, D.; González-Lleó, A.M.; Boronat, M. Correlation between TSH Levels and Quality of Life among Subjects with Well-Controlled Primary Hypothyroidism. Endocrine 2021 , 72 , 190–197. [ Google Scholar ] [ CrossRef ]
• Liu, H.; Peng, D. Update on Dyslipidemia in Hypothyroidism: The Mechanism of Dyslipidemia in Hypothyroidism. Endocr. Connect. 2022 , 11 , e210002. [ Google Scholar ] [ CrossRef ]
• Moon, J.H.; Kim, H.J.; Kim, H.M.; Choi, S.H.; Lim, S.; Park, Y.J.; Jang, H.C.; Cha, B.S. Decreased Expression of Hepatic Low-Density Lipoprotein Receptor–Related Protein 1 in Hypothyroidism: A Novel Mechanism of Atherogenic Dyslipidemia in Hypothyroidism. Thyroid 2013 , 23 , 1057–1065. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Vella, K.; Vella, S.; Savona-Ventura, C.; Vassallo, J. Thyroid Dysfunction in Pregnancy—A Retrospective Observational Analysis of a Maltese Cohort. BMC Pregnancy Childbirth 2022 , 22 , 941. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Palomba, S.; Falbo, A.; Chiossi, G.; Muscogiuri, G.; Fornaciari, E.; Orio, F.; Tolino, A.; Colao, A.; La Sala, G.B.; Zullo, F. Lipid Profile in Nonobese Pregnant Women with Polycystic Ovary Syndrome: A Prospective Controlled Clinical Study. Steroids 2014 , 88 , 36–43. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Wild, R.A.; Rizzo, M.; Clifton, S.; Carmina, E. Lipid Levels in Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis. Fertil. Steril. 2011 , 95 , 1073–1079.e11. [ Google Scholar ] [ CrossRef ]
• Farland, L.V.; Stern, J.E.; Liu, C.L.; Cabral, H.J.; Coddington, C.C.; Diop, H.; Dukhovny, D.; Hwang, S.; Missmer, S.A. Polycystic Ovary Syndrome and Risk of Adverse Pregnancy Outcomes: A Registry Linkage Study from Massachusetts. Hum. Reprod. 2022 , 37 , 2690–2699. [ Google Scholar ] [ CrossRef ]
• August, P. Obstetric Nephrology: Pregnancy and the Kidney--Inextricably Linked. Clin. J. Am. Soc. Nephrol. 2012 , 7 , 2071–2072. [ Google Scholar ] [ CrossRef ]
• Oliverio, A.L.; Hladunewich, M.A. End Stage Kidney Disease and Dialysis in Pregnancy. Adv. Chronic Kidney Dis. 2020 , 27 , 477–485. [ Google Scholar ] [ CrossRef ]
• Piccoli, G.B.; Zakharova, E.; Attini, R.; Hernandez, M.I.; Guillien, A.O.; Alrukhaimi, M.; Liu, Z.H.; Ashuntantang, G.; Covella, B.; Cabiddu, G.; et al. Pregnancy in Chronic Kidney Disease: Need for Higher Awareness. A Pragmatic Review Focused on What Could Be Improved in the Different CKD Stages and Phases. J. Clin. Med. 2018 , 7 , 415. [ Google Scholar ] [ CrossRef ]
• Hladunewich, M.A.; Hou, S.; Odutayo, A.; Cornelis, T.; Pierratos, A.; Goldstein, M.; Tennankore, K.; Keunen, J.; Hui, D.; Chan, C.T. Intensive Hemodialysis Associates with Improved Pregnancy Outcomes: A Canadian and United States Cohort Comparison. J. Am. Soc. Nephrol. 2014 , 25 , 1103–1109. [ Google Scholar ] [ CrossRef ]
• Visconti, L.; Benvenga, S.; Lacquaniti, A.; Cernaro, V.; Bruzzese, A.; Conti, G.; Buemi, M.; Santoro, D. Lipid Disorders in Patients with Renal Failure: Role in Cardiovascular Events and Progression of Chronic Kidney Disease. J. Clin. Transl. Endocrinol. 2016 , 6 , 8–14. [ Google Scholar ] [ CrossRef ]
• Lluesa, J.H.; López-Romero, L.C.; Monzó, J.J.B.; Marugán, M.R.; Boyano, I.V.; Rodríguez-Espinosa, D.; Gómez-Bori, A.; Orient, A.S.; Such, R.D.; Perez, P.S.; et al. Lipidic Profiles of Patients Starting Peritoneal Dialysis Suggest an Increased Cardiovascular Risk beyond Classical Dyslipidemia Biomarkers. Sci. Rep. 2022 , 12 , 16394. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Lloyd-Jones, D.M.; Morris, P.B.; Ballantyne, C.M.; Birtcher, K.K.; Covington, A.M.; DePalma, S.M.; Minissian, M.B.; Orringer, C.E.; Smith, S.C.; Waring, A.A.; et al. 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Solution Set Oversight Committee. J. Am. Coll. Cardiol. 2022 , 80 , 1366–1418. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Bashir, M.; Navti, O.B.; Frcog, M.; Ahmed, B.; Konje, J.C.; Frcog, F. Hyperlipidaemia and Severe Hypertriglyceridaemia in Pregnancy. Obstet. Gynaecol. 2023 , 25 , 196–209. [ Google Scholar ] [ CrossRef ]
• Szatmary, P.; Grammatikopoulos, T.; Cai, W.; Huang, W.; Mukherjee, R.; Halloran, C.; Beyer, G.; Sutton, R. Acute Pancreatitis: Diagnosis and Treatment. Drugs 2022 , 82 , 1251–1276. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Gangopadhyay, D.; Roy, M.; Laha, S.; Nandi, D.; Sengupta, R.; Chattopadhyay, A. Hyperviscosity Syndrome Revisited. Ann. Pediatr. Cardiol. 2022 , 15 , 284–290. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Zhu, Y.; Zhu, H.; Dang, Q.; Yang, Q.; Huang, D.; Zhang, Y.; Cai, X.; Yu, H. Changes in Serum TG Levels during Pregnancy and Their Association with Postpartum Hypertriglyceridemia: A Population-Based Prospective Cohort Study. Lipids Health Dis. 2021 , 20 , 119. [ Google Scholar ] [ CrossRef ]
• D’Erasmo, L.; Bini, S.; Casula, M.; Gazzotti, M.; Bertolini, S.; Calandra, S.; Tarugi, P.; Averna, M.; Iannuzzo, G.; Fortunato, G.; et al. Contemporary Lipid-Lowering Management and Risk of Cardiovascular Events in Homozygous Familial Hypercholesterolaemia: Insights from the Italian LIPIGEN Registry. Eur. J. Prev. Cardiol. 2024 , 31 , 1038–1047. [ Google Scholar ] [ CrossRef ]
• Blaha, M.; Lanska, M.; Blaha, V.; Boudys, L.; Zak, P. Pregnancy in Homozygous Familial Hypercholesterolemia--Importance of LDL-Apheresis. Atheroscler. Suppl. 2015 , 18 , 134–139. [ Google Scholar ] [ CrossRef ]
• Fanshawe, A.E.; Ibrahim, M. The Current Status of Lipoprotein (a) in Pregnancy: A Literature Review. J. Cardiol. 2013 , 61 , 99–106. [ Google Scholar ] [ CrossRef ]
• Cremonini, A.L.; Pasta, A.; Carbone, F.; Visconti, L.; Casula, M.; Elia, E.; Bonaventura, A.; Liberale, L.; Bertolotto, M.; Artom, N.; et al. Lipoprotein(a) Modulates Carotid Atherosclerosis in Metabolic Syndrome. Front. Mol. Biosci. 2022 , 9 , 854624. [ Google Scholar ] [ CrossRef ]
• Sattar, N.; Clark, P.; Greer, I.A.; Shepherd, J.; Packard, C.J. Lipoprotein (a) Levels in Normal Pregnancy and in Pregnancy Complicated with Pre-Eclampsia. Atherosclerosis 2000 , 148 , 407–411. [ Google Scholar ] [ CrossRef ]
• Golawski, M.; Lejawa, M.; Osadnik, T.; Mickiewicz, A.; Gierlotka, M.; Jozwiak, J.; Pawlas, N.; Banach, M. Genetically Determined Lipoprotein(a) Levels Do Not Cause an Increased Risk of Preeclampsia—A Two-Sample Mendelian Randomization Study. Eur. Heart J. 2023 , 44 , ehad655.2728. [ Google Scholar ] [ CrossRef ]
• Romagnuolo, I.; Sticchi, E.; Attanasio, M.; Grifoni, E.; Cioni, G.; Cellai, A.P.; Abbate, R.; Fatini, C. Searching for a Common Mechanism for Placenta-Mediated Pregnancy Complications and Cardiovascular Disease: Role of Lipoprotein(a). Fertil. Steril. 2016 , 105 , 1287–1293.e3. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Rutherford, J.D. Maternal Heterozygous Familial Hypercholesterolemia and Its Consequences for Mother and Child. Circulation 2011 , 124 , 1599–1601. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Cuchel, M.; Bruckert, E.; Ginsberg, H.N.; Raal, F.J.; Santos, R.D.; Hegele, R.A.; Kuivenhoven, J.A.; Nordestgaard, B.G.; Descamps, O.S.; Steinhagen-Thiessen, E.; et al. Homozygous Familial Hypercholesterolaemia: New Insights and Guidance for Clinicians to Improve Detection and Clinical Management. A Position Paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur. Heart J. 2014 , 35 , 2146–2157. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Fahed, A.C.; Nassar, A.H. Pregnancy in a Woman with Homozygous Familial Hypercholesterolemia Not on Low-Density Lipoprotein Apheresis. AJP Rep. 2012 , 2 , 33–36. [ Google Scholar ] [ CrossRef ]
• Coronado Arroyo, J.C.; Concepción Zavaleta, M.J.; García Villasante, E.J.; Kcomt Lam, M.; Concepción Urteaga, L.A.; Zavaleta Gutiérrez, F.E. Familial Chylomicronemia Syndrome-Induced Acute Necrotizing Pancreatitis during Pregnancy. RBGO Gynecol. Obstet. 2021 , 43 , 220–224. [ Google Scholar ] [ CrossRef ]
• Jaafar, B.; Chaaya, J.A.; Ammar, S.; Salti, I. Acute Pancreatitis in Pregnancy and Familial Chylomicronemia Syndrome: Case Report and Literature Review. Metab. Target. Organ. Damage 2023 , 3 , 21. [ Google Scholar ] [ CrossRef ]
• Cetin, I.; Berti, C.; Calabrese, S. Role of Micronutrients in the Periconceptional Period. Hum. Reprod. Update 2010 , 16 , 80–95. [ Google Scholar ] [ CrossRef ]
• Lorite Mingot, D.; Gesteiro, E.; Bastida, S.; Sánchez-Muniz, F.J. Epigenetic Effects of the Pregnancy Mediterranean Diet Adherence on the Offspring Metabolic Syndrome Markers. J. Physiol. Biochem. 2017 , 73 , 495–510. [ Google Scholar ] [ CrossRef ]
• Yee, L.M.; Silver, R.M.; Haas, D.M.; Parry, S.; Mercer, B.M.; Iams, J.; Wing, D.; Parker, C.B.; Reddy, U.M.; Wapner, R.J.; et al. Quality of Periconceptional Dietary Intake and Maternal and Neonatal Outcomes. Am. J. Obstet. Gynecol. 2020 , 223 , 121.e1–121.e8. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• De Giuseppe, R.; Bocchi, M.; Maffoni, S.; Del Bo, E.; Manzoni, F.; Cerbo, R.M.; Porri, D.; Cena, H. Mediterranean Diet and Lifestyle Habits during Pregnancy: Is There an Association with Small for Gestational Age Infants? An Italian Single Centre Experience. Nutrients 2021 , 13 , 1941. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Eckl, M.R.; Brouwer-Brolsma, E.M.; Küpers, L.K. Maternal Adherence to the Mediterranean Diet during Pregnancy: A Review of Commonly Used a Priori Indexes. Nutrients 2021 , 13 , 582. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Flor-Alemany, M.; Migueles, J.H.; Alemany-Arrebola, I.; Aparicio, V.A.; Baena-García, L. Exercise, Mediterranean Diet Adherence or Both during Pregnancy to Prevent Postpartum Depression—GESTAFIT Trial Secondary Analyses. Int. J. Environ. Res. Public Health 2022 , 19 , 4450. [ Google Scholar ] [ CrossRef ]
• Schoenaker, D.A.J.M.; Soedamah-Muthu, S.S.; Callaway, L.K.; Mishra, G.D. Prepregnancy Dietary Patterns and Risk of Developing Hypertensive Disorders of Pregnancy: Results from the Australian Longitudinal Study on Women’s Health. Am. J. Clin. Nutr. 2015 , 102 , 94–101. [ Google Scholar ] [ CrossRef ]
• Winter, H.G.; Rolnik, D.L.; Mol, B.W.J.; Torkel, S.; Alesi, S.; Mousa, A.; Habibi, N.; Silva, T.R.; Oi Cheung, T.; Thien Tay, C.; et al. Can Dietary Patterns Impact Fertility Outcomes? A Systematic Review and Meta-Analysis. Nutrients 2023 , 15 , 2589. [ Google Scholar ] [ CrossRef ]
• Ricci, E.; Bravi, F.; Noli, S.; Somigliana, E.; Cipriani, S.; Castiglioni, M.; Chiaffarino, F.; Vignali, M.; Gallotti, B.; Parazzini, F. Mediterranean Diet and Outcomes of Assisted Reproduction: An Italian Cohort Study. Am. J. Obstet. Gynecol. 2019 , 221 , 627.e1–627.e14. [ Google Scholar ] [ CrossRef ]
• Esquivel, M.K. Nutritional Status and Nutrients Related to Pre-Eclampsia. Am. J. Lifestyle Med. 2023 , 17 , 41–45. [ Google Scholar ] [ CrossRef ]
• Gómez-Pinilla, F. Brain Foods: The Effects of Nutrients on Brain Function. Nat. Rev. Neurosci. 2008 , 9 , 568–578. [ Google Scholar ] [ CrossRef ]
• Guasch-Ferré, M.; Willett, W.C. The Mediterranean Diet and Health: A Comprehensive Overview. J. Intern. Med. 2021 , 290 , 549–566. [ Google Scholar ] [ CrossRef ]
• Wang, P.; Xie, J.; Jiao, X.C.; Ma, S.S.; Liu, Y.; Yin, W.J.; Tao, R.X.; Hu, H.L.; Zhang, Y.; Chen, X.X.; et al. Maternal Glycemia During Pregnancy and Early Offspring Development: A Prospective Birth Cohort Study. J. Clin. Endocrinol. Metab. 2021 , 106 , 2279–2290. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Dominguez, L.J.; Veronese, N.; Di Bella, G.; Cusumano, C.; Parisi, A.; Tagliaferri, F.; Ciriminna, S.; Barbagallo, M. Mediterranean Diet in the Management and Prevention of Obesity. Exp. Gerontol. 2023 , 174 , 112121. [ Google Scholar ] [ CrossRef ]
• Romaguera, D.; Bamia, C.; Pons, A.; Tur, J.A.; Trichopoulou, A. Food Patterns and Mediterranean Diet in Western and Eastern Mediterranean Islands. Public Health Nutr. 2009 , 12 , 1174–1181. [ Google Scholar ] [ CrossRef ]
• Bach-Faig, A.; Berry, E.M.; Lairon, D.; Reguant, J.; Trichopoulou, A.; Dernini, S.; Medina, F.X.; Battino, M.; Belahsen, R.; Miranda, G.; et al. Mediterranean Diet Pyramid Today. Science and Cultural Updates. Public Health Nutr. 2011 , 14 , 2274–2284. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Martínez-González, M.Á.; Hershey, M.S.; Zazpe, I.; Trichopoulou, A. Transferability of the Mediterranean Diet to Non-Mediterranean Countries. What Is and What Is Not the Mediterranean Diet. Nutrients 2017 , 9 , 1226. [ Google Scholar ] [ CrossRef ]
• Cruz, J.A.A. Dietary Habits and Nutritional Status in Adolescents over Europe--Southern Europe. Eur. J. Clin. Nutr. 2000 , 54 (Suppl. S1), S29–S35. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Estruch, R.; Ros, E.; Salas-Salvadó, J.; Covas, M.-I.; Corella, D.; Arós, F.; Gómez-Gracia, E.; Ruiz-Gutiérrez, V.; Fiol, M.; Lapetra, J.; et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N. Engl. J. Med. 2018 , 378 , e34. [ Google Scholar ] [ CrossRef ]
• Estruch, R.; Martínez-González, M.A.; Corella, D.; Salas-Salvadó, J.; Fitó, M.; Chiva-Blanch, G.; Fiol, M.; Gómez-Gracia, E.; Arós, F.; Lapetra, J.; et al. Effect of a High-Fat Mediterranean Diet on Bodyweight and Waist Circumference: A Prespecified Secondary Outcomes Analysis of the PREDIMED Randomised Controlled Trial. Lancet Diabetes Endocrinol. 2019 , 7 , e6–e17. [ Google Scholar ] [ CrossRef ]
• Babio, N.; Toledo, E.; Estruch, R.; Ros, E.; Martínez-González, M.A.; Castañer, O.; Bulló, M.; Corella, D.; Arós, F.; Gómez-Gracia, E.; et al. Mediterranean Diets and Metabolic Syndrome Status in the PREDIMED Randomized Trial. CMAJ 2014 , 186 , E649–E657. [ Google Scholar ] [ CrossRef ]
• Salas-Salvadó, J.; Bulló, M.; Estruch, R.; Ros, E.; Covas, M.-I.; Ibarrola-Jurado, N.; Corella, D.; Arós, F.; Gómez-Gracia, E.; Ruiz-Gutiérrez, V.; et al. Prevention of Diabetes with Mediterranean Diets: A Subgroup Analysis of a Randomized Trial. Ann. Intern. Med. 2014 , 160 , 43–46. [ Google Scholar ] [ CrossRef ]
• Mousa, A.; Naqash, A.; Lim, S. Macronutrient and Micronutrient Intake during Pregnancy: An Overview of Recent Evidence. Nutrients 2019 , 11 , 443. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Kominiarek, M.A.; Rajan, P. Nutrition Recommendations in Pregnancy and Lactation. Med. Clin. N. Am. 2016 , 100 , 1199–1215. [ Google Scholar ] [ CrossRef ]
• LARN Livelli Di Assunzione Di Riferimento Di Nutrienti Ed Energia per La Popolazione Italiana ; SICS Editore; IV Revisione. 2014. Available online: https://air.uniud.it/handle/11390/1041183?mode=complete (accessed on 25 July 2024).
• Rasmussen, K.M.; Yaktine, A.L. Weight Gain During Pregnancy: Reexamining the Guidelines ; National Academies Press: Washington, DC, USA, 2009. [ Google Scholar ] [ CrossRef ]
• EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on Dietary Reference Values for Energy. EFSA J. 2013 , 11 , 3005. [ Google Scholar ] [ CrossRef ]
• Serra-Majem, L.; Tomaino, L.; Dernini, S.; Berry, E.M.; Lairon, D.; de la Cruz, J.N.; Bach-Faig, A.; Donini, L.M.; Medina, F.X.; Belahsen, R.; et al. Updating the Mediterranean Diet Pyramid towards Sustainability: Focus on Environmental Concerns. Int. J. Environ. Res. Public Health 2020 , 17 , 8758. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Koletzko, B.; Cremer, M.; Flothkötter, M.; Graf, C.; Hauner, H.; Hellmers, C.; Kersting, M.; Krawinkel, M.; Przyrembel, H.; Röbl-Mathieu, M.; et al. Diet and Lifestyle Before and During Pregnancy—Practical Recommendations of the Germany-Wide Healthy Start—Young Family Network. Geburtshilfe Frauenheilkd. 2018 , 78 , 1262–1282. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Ruchat, S.M.; Davenport, M.H.; Giroux, I.; Hillier, M.; Batada, A.; Sopper, M.M.; Hammond, J.M.S.; Mottola, M.F. Nutrition and Exercise Reduce Excessive Weight Gain in Normal-Weight Pregnant Women. Med. Sci. Sports Exerc. 2012 , 44 , 1419–1426. [ Google Scholar ] [ CrossRef ]
• Deierlein, A.L.; Siega-Riz, A.M.; Evenson, K.R. Physical Activity during Pregnancy and Risk of Hyperglycemia. J. Womens Health 2012 , 21 , 769–775. [ Google Scholar ] [ CrossRef ]
• Barakat, R.; Zhang, D.; Sánchez-Polán, M.; Silva-José, C.; Gil-Ares, J.; Franco, E. Is Exercise during Pregnancy a Risk for Gestational Age and Preterm Delivery? Systematic Review and Meta-Analysis. J. Clin. Med. 2023 , 12 , 4915. [ Google Scholar ] [ CrossRef ]
• EFSA (European Food Safety Authority). Dietary Reference Values for Nutrients Summary Report. EFSA Support. Publ. 2017 , 14 , e15121. [ Google Scholar ] [ CrossRef ]
• Eilander, A.; Harika, R.K.; Zock, P.L. Intake and Sources of Dietary Fatty Acids in Europe: Are Current Population Intakes of Fats Aligned with Dietary Recommendations? Eur. J. Lipid Sci. Technol. 2015 , 117 , 1370–1377. [ Google Scholar ] [ CrossRef ]
• Danielewicz, H.; Myszczyszyn, G.; Dębińska, A.; Myszkal, A.; Boznański, A.; Hirnle, L. Diet in Pregnancy—More than Food. Eur. J. Pediatr. 2017 , 176 , 1573–1579. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Genuis, S.J.; Genuis, R.A. Preconception Care: A New Standard of Care within Maternal Health Services. Biomed. Res. Int. 2016 , 2016 , 6150976. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Alibrandi, A.; Zirilli, A.; Le Donne, M.; Giannetto, C.; Lanfranchi, M.; De Pascale, A.; Politi, C.; Incognito, G.G.; Ercoli, A.; Granese, R. Association between Fish Consumption during Pregnancy and Maternal and Neonatal Outcomes: A Statistical Study in Southern Italy. J. Clin. Med. 2024 , 13 , 2131. [ Google Scholar ] [ CrossRef ]
• McGuire, S. WHO Guideline: Vitamin A Supplementation in Pregnant Women. Geneva: WHO, 2011; WHO Guideline: Vitamin A Supplementation in Postpartum Women. Geneva: WHO, 2011. Adv. Nutr. 2012 , 3 , 215–216. [ Google Scholar ] [ CrossRef ]
• Morse, N.L. Benefits of Docosahexaenoic Acid, Folic Acid, Vitamin D and Iodine on Foetal and Infant Brain Development and Function Following Maternal Supplementation during Pregnancy and Lactation. Nutrients 2012 , 4 , 799. [ Google Scholar ] [ CrossRef ]
• World Health Organization Guideline: Calcium Supplementation in Pregnant Women ; World Health Organization: Geneva, Switzerland, 2013; Volume 24.
• Iacone, R.; Iaccarino Idelson, P.; Russo, O.; Donfrancesco, C.; Krogh, V.; Sieri, S.; Macchia, P.E.; Formisano, P.; Lo Noce, C.; Palmieri, L.; et al. Iodine Intake from Food and Iodized Salt as Related to Dietary Salt Consumption in the Italian Adult General Population. Nutrients 2021 , 13 , 3486. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Alexander, E.K.; Pearce, E.N.; Brent, G.A.; Brown, R.S.; Chen, H.; Dosiou, C.; Grobman, W.A.; Laurberg, P.; Lazarus, J.H.; Mandel, S.J.; et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid 2017 , 27 , 315–389. [ Google Scholar ] [ CrossRef ]
• Sofi, F.; Macchi, C.; Abbate, R.; Gensini, G.F.; Casini, A. Mediterranean Diet and Health Status: An Updated Meta-Analysis and a Proposal for a Literature-Based Adherence Score. Public Health Nutr. 2014 , 17 , 2769–2782. [ Google Scholar ] [ CrossRef ]
• Herrera, E.; Ortega-Senovilla, H. Disturbances in Lipid Metabolism in Diabetic Pregnancy—Are These the Cause of the Problem? Best Pract. Res. Clin. Endocrinol. Metab. 2010 , 24 , 515–525. [ Google Scholar ] [ CrossRef ]
• Barbour, L.A.; Hernandez, T.L. Maternal Lipids and Fetal Overgrowth: Making Fat from Fat. Clin. Ther. 2018 , 40 , 1638–1647. [ Google Scholar ] [ CrossRef ]
• Luna-Castillo, K.P.; Olivares-Ochoa, X.C.; Hernández-Ruiz, R.G.; Llamas-Covarrubias, I.M.; Rodríguez-Reyes, S.C.; Betancourt-Núñez, A.; Vizmanos, B.; Martínez-López, E.; Muñoz-Valle, J.F.; Márquez-Sandoval, F.; et al. The Effect of Dietary Interventions on Hypertriglyceridemia: From Public Health to Molecular Nutrition Evidence. Nutrients 2022 , 14 , 1104. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Mentella, M.C.; Scaldaferri, F.; Ricci, C.; Gasbarrini, A.; Miggiano, G.A.D. Cancer and Mediterranean Diet: A Review. Nutrients 2019 , 11 , 2059. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Zelber-Sagi, S.; Salomone, F.; Mlynarsky, L. The Mediterranean Dietary Pattern as the Diet of Choice for Non-Alcoholic Fatty Liver Disease: Evidence and Plausible Mechanisms. Liver Int. 2017 , 37 , 936–949. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Flor-Alemany, M.; Acosta-Manzano, P.; Migueles, J.H.; Baena-García, L.; Aranda, P.; Aparicio, V.A. Association of Mediterranean Diet Adherence during Pregnancy with Maternal and Neonatal Lipid, Glycemic and Inflammatory Markers: The GESTAFIT Project. Matern. Child. Nutr. 2023 , 19 , e13454. [ Google Scholar ] [ CrossRef ]
• Melero, V.; Arnoriaga, M.; Barabash, A.; Valerio, J.; del Valle, L.; Martin O’Connor, R.; de Miguel, M.P.; Diaz, J.A.; Familiar, C.; Moraga, I.; et al. An Early Mediterranean-Based Nutritional Intervention during Pregnancy Reduces Metabolic Syndrome and Glucose Dysregulation Rates at 3 Years Postpartum. Nutrients 2023 , 15 , 3252. [ Google Scholar ] [ CrossRef ]
• Amati, F.; Hassounah, S.; Swaka, A. The Impact of Mediterranean Dietary Patterns During Pregnancy on Maternal and Offspring Health. Nutrients 2019 , 11 , 1098. [ Google Scholar ] [ CrossRef ]
• Ribeiro, M.M.; Andrade, A.; Nunes, I. Physical Exercise in Pregnancy: Benefits, Risks and Prescription. J. Perinat. Med. 2021 , 50 , 4–17. [ Google Scholar ] [ CrossRef ]
• Eapen, D.J.; Valiani, K.; Reddy, S.; Sperling, L. Management of Familial Hypercholesterolemia during Pregnancy: Case Series and Discussion. J. Clin. Lipidol. 2012 , 6 , 88–91. [ Google Scholar ] [ CrossRef ]
• Glueck, C.J.; Christopher, C.; Tsang, R.C.; Mellies, M.J. Cholesterol-Free Diet and the Physiologic Hyperlipidemia of Pregnancy in Familial Hypercholesterolemia. Metabolism 1980 , 29 , 949–955. [ Google Scholar ] [ CrossRef ]
• Trautwein, E.A.; McKay, S. The Role of Specific Components of a Plant-Based Diet in Management of Dyslipidemia and the Impact on Cardiovascular Risk. Nutrients 2020 , 12 , 2671. [ Google Scholar ] [ CrossRef ]
• Popova, S.; Dozet, D.; Shield, K.; Rehm, J.; Burd, L. Alcohol’s Impact on the Fetus. Nutrients 2021 , 13 , 3452. [ Google Scholar ] [ CrossRef ]
• Do Rego, A.T.; Klop, B.; Birnie, E.; Elte, J.W.F.; Cachofeiro Ramos, V.; Walther Alvarez-Sala, L.A.; Castro Cabezas, M. Diurnal Triglyceridemia in Relation to Alcohol Intake in Men. Nutrients 2013 , 5 , 5114. [ Google Scholar ] [ CrossRef ]
• Williams, L.; Rhodes, K.S.; Karmally, W.; Welstead, L.A.; Alexander, L.; Sutton, L. Familial Chylomicronemia Syndrome: Bringing to Life Dietary Recommendations throughout the Life Span. J. Clin. Lipidol. 2018 , 12 , 908–919. [ Google Scholar ] [ CrossRef ]
• Goldberg, A.S.; Hegele, R.A. Severe Hypertriglyceridemia in Pregnancy. J. Clin. Endocrinol. Metab. 2012 , 97 , 2589–2596. [ Google Scholar ] [ CrossRef ]
• Nguyen, N.T.; Nath, P.V.; Mai, V.Q.; Shakir, M.K.M.; Hoang, T.D. Treatment of Severe Hypertriglyceridemia During Pregnancy With High Doses of Omega-3 Fatty Acid and Plasmapheresis. AACE Clin. Case Rep. 2021 , 7 , 211–215. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Papamandjaris, A.A.; Macdougall, D.E.; Jones, P.J.H. Medium Chain Fatty Acid Metabolism and Energy Expenditure: Obesity Treatment Implications. Life Sci. 1998 , 62 , 1203–1215. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Jadhav, H.B.; Annapure, U.S. Triglycerides of Medium-Chain Fatty Acids: A Concise Review. J. Food Sci. Technol. 2023 , 60 , 2143–2152. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Nangrahary, M.; Graham, D.F.; Pang, J.; Barnett, W.; Watts, G.F. Familial Hypercholesterolaemia in Pregnancy: Australian Case Series and Review. Aust. N. Z. J. Obstet. Gynaecol. 2023 , 63 , 402–408. [ Google Scholar ] [ CrossRef ]
• Soma-Pillay, P.; Nelson-Piercy, C.; Tolppanen, H.; Mebazaa, A. Physiological Changes in Pregnancy. Cardiovasc. J. Afr. 2016 , 27 , 89–94. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Mauri, M.; Calmarza, P.; Ibarretxe, D. Dyslipemias and Pregnancy, an Update. Clin. Investig. Arterioscler. 2021 , 33 , 41–52. [ Google Scholar ] [ CrossRef ]
• Watts, G.F.; Gidding, S.S.; Hegele, R.A.; Raal, F.J.; Sturm, A.C.; Jones, L.K.; Sarkies, M.N.; Al-Rasadi, K.; Blom, D.J.; Daccord, M.; et al. International Atherosclerosis Society Guidance for Implementing Best Practice in the Care of Familial Hypercholesterolaemia. Nat. Rev. Cardiol. 2023 , 20 , 845–869. [ Google Scholar ] [ CrossRef ]
• Bruckert, E.; Giral, P.; Tellier, P. Perspectives in Cholesterol-Lowering Therapy: The Role of Ezetimibe, a New Selective Inhibitor of Intestinal Cholesterol Absorption. Circulation 2003 , 107 , 3124–3128. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Wang, Y.; Zhan, S.; Du, H.; Li, J.; Khan, S.U.; Aertgeerts, B.; Guyatt, G.; Hao, Q.; Bekkering, G.; Li, L.; et al. Safety of Ezetimibe in Lipid-Lowering Treatment: Systematic Review and Meta-Analysis of Randomised Controlled Trials and Cohort Studies. BMJ Med. 2022 , 1 , e000134. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Parker, B.A.; Thompson, P.D. Effect of statins on skeletal muscle: Exercise, myopathy, and muscle outcomes. Exerc. Sport Sci. Rev. 2012 , 40 , 188–194, Erratum in Exerc. Sport Sci. Rev . 2013 , 41 , 71. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Cuchel, M.; Raal, F.J.; Hegele, R.A.; Al-Rasadi, K.; Arca, M.; Averna, M.; Bruckert, E.; Freiberger, T.; Gaudet, D.; Harada-Shiba, M.; et al. 2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: New Treatments and Clinical Guidance. Eur. Heart J. 2023 , 44 , 2277–2291. [ Google Scholar ] [ CrossRef ]
• Harada-Shiba, M.; Ohtake, A.; Sugiyama, D.; Tada, H.; Dobashi, K.; Matsuki, K.; Minamino, T.; Yamashita, S.; Yamamoto, Y. Guidelines for the Diagnosis and Treatment of Pediatric Familial Hypercholesterolemia 2022. J. Atheroscler. Thromb. 2023 , 30 , 531–557. [ Google Scholar ] [ CrossRef ]
• Döbert, M.; Varouxaki, A.N.; Mu, A.C.; Syngelaki, A.; Ciobanu, A.; Akolekar, R.; De Paco Matallana, C.; Cicero, S.; Greco, E.; Singh, M.; et al. Pravastatin Versus Placebo in Pregnancies at High Risk of Term Preeclampsia. Circulation 2021 , 144 , 670–679. [ Google Scholar ] [ CrossRef ]
• Edison, R.J.; Muenke, M. Central Nervous System and Limb Anomalies in Case Reports of First-Trimester Statin Exposure. N. Engl. J. Med. 2004 , 350 , 1579–1582. [ Google Scholar ] [ CrossRef ]
• Ghidini, A.; Sicherer, S.; Willner, J. Congenital Abnormalities (VATER) in Baby Born to Mother Using Lovastatin. Lancet 1992 , 339 , 1416–1417. [ Google Scholar ] [ CrossRef ]
• Bateman, B.T.; Hernandez-Diaz, S.; Fischer, M.A.; Seely, E.W.; Ecker, J.L.; Franklin, J.M.; Desai, R.J.; Allen-Coleman, C.; Mogun, H.; Avorn, J.; et al. Statins and Congenital Malformations: Cohort Study. BMJ 2015 , 350 , h1035. [ Google Scholar ] [ CrossRef ]
• Maierean, S.M.; Mikhailidis, D.P.; Toth, P.P.; Grzesiak, M.; Mazidi, M.; Maciejewski, M.; Banach, M. The Potential Role of Statins in Preeclampsia and Dyslipidemia during Gestation: A Narrative Review. Expert. Opin. Investig. Drugs 2018 , 27 , 427–435. [ Google Scholar ] [ CrossRef ]
• Vahedian-Azimi, A.; Makvandi, S.; Banach, M.; Reiner, Ž.; Sahebkar, A. Fetal Toxicity Associated with Statins: A Systematic Review and Meta-Analysis. Atherosclerosis 2021 , 327 , 59–67. [ Google Scholar ] [ CrossRef ]
• Vahedian-Azimi, A.; Bianconi, V.; Makvandi, S.; Banach, M.; Mohammadi, S.M.; Pirro, M.; Sahebkar, A. A Systematic Review and Meta-Analysis on the Effects of Statins on Pregnancy Outcomes. Atherosclerosis 2021 , 336 , 1–11. [ Google Scholar ] [ CrossRef ]
• Wu, T.; Shi, Y.; Zhu, B.; Li, D.; Li, Z.; Zhao, Z.; Zhang, Y. Pregnancy-Related Adverse Events Associated with Statins: A Real-World Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS). Expert. Opin. Drug Saf. 2024 , 23 , 313–321. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Karalis, D.G.; Hill, A.N.; Clifton, S.; Wild, R.A. The Risks of Statin Use in Pregnancy: A Systematic Review. J. Clin. Lipidol. 2016 , 10 , 1081–1090. [ Google Scholar ] [ CrossRef ]
• Chang, J.C.; Chen, Y.J.; Chen, I.C.; Lin, W.S.; Chen, Y.M.; Lin, C.H. Perinatal Outcomes After Statin Exposure During Pregnancy. JAMA Netw. Open 2021 , 4 , e2141321. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• FDA Requests Removal of Strongest Warning against Using Cholesterol-Lowering Statins during Pregnancy; Still Advises Most Pregnant Patients Should Stop Taking Statins. Available online: https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-removal-strongest-warning-against-using-cholesterol-lowering-statins-during-pregnancy (accessed on 20 July 2024).
• Pollack, P.S.; Shields, K.E.; Burnett, D.M.; Osborne, M.J.; Cunningham, M.L.; Stepanavage, M.E. Pregnancy Outcomes after Maternal Exposure to Simvastatin and Lovastatin. Birth Defects Res. A Clin. Mol. Teratol. 2005 , 73 , 888–896. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Botha, T.C.; Pilcher, G.J.; Wolmarans, K.; Blom, D.J.; Raal, F.J. Statins and Other Lipid-Lowering Therapy and Pregnancy Outcomes in Homozygous Familial Hypercholesterolaemia: A Retrospective Review of 39 Pregnancies. Atherosclerosis 2018 , 277 , 502–507. [ Google Scholar ] [ CrossRef ]
• Zarek, J.; Koren, G. The Fetal Safety of Statins: A Systematic Review and Meta-Analysis. J. Obstet. Gynaecol. Can. 2014 , 36 , 506–509. [ Google Scholar ] [ CrossRef ]
• Grześk, G.; Dorota, B.; Wołowiec, Ł.; Wołowiec, A.; Osiak, J.; Kozakiewicz, M.; Banach, J. Safety of PCSK9 Inhibitors. Biomed. Pharmacother. 2022 , 156 , 113957. [ Google Scholar ] [ CrossRef ]
• Pasta, A.; Cremonini, A.L.; Pisciotta, L.; Buscaglia, A.; Porto, I.; Barra, F.; Ferrero, S.; Brunelli, C.; Rosa, G.M. PCSK9 Inhibitors for Treating Hypercholesterolemia. Expert. Opin. Pharmacother. 2020 , 21 , 353–363. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Harada-Shiba, M.; Arai, H.; Ohmura, H.; Okazaki, H.; Sugiyama, D.; Tada, H.; Dobashi, K.; Matsuki, K.; Minamino, T.; Yamashita, S.; et al. Guidelines for the Diagnosis and Treatment of Adult Familial Hypercholesterolemia 2022. J. Atheroscler. Thromb. 2023 , 30 , 558–586. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Macchi, C.; Iodice, S.; Persico, N.; Ferrari, L.; Cantone, L.; Greco, M.F.; Ischia, B.; Dozio, E.; Corsini, A.; Sirtori, C.R.; et al. Maternal Exposure to Air Pollutants, PCSK9 Levels, Fetal Growth and Gestational Age—An Italian Cohort. Environ. Int. 2021 , 149 , 106163. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Ardissino, M.; Slob, E.A.W.; Reddy, R.K.; Morley, A.P.; Schuermans, A.; Hill, P.; Williamson, C.; Honigberg, M.C.; De Marvao, A.; Ng, F.S. Genetically Proxied Low-Density Lipoprotein Cholesterol Lowering via PCSK9-Inhibitor Drug Targets and Risk of Congenital Malformations. Eur. J. Prev. Cardiol. 2024 , 31 , 955–965. [ Google Scholar ] [ CrossRef ]
• Gouni-Berthold, I.; Berthold, H.K. Mipomersen and Lomitapide: Two New Drugs for the Treatment of Homozygous Familial Hypercholesterolemia. Atheroscler. Suppl. 2015 , 18 , 28–34. [ Google Scholar ] [ CrossRef ]
• Wong, E.; Goldberg, T. Mipomersen (Kynamro): A Novel Antisense Oligonucleotide Inhibitor for the Management of Homozygous Familial Hypercholesterolemia. Pharm. Ther. 2014 , 39 , 119. [ Google Scholar ]
• Stefanutti, C.; Thompson, G.R. Lipoprotein Apheresis in the Management of Familial Hypercholesterolaemia: Historical Perspective and Recent Advances. Curr. Atheroscler. Rep. 2015 , 17 , 465. [ Google Scholar ] [ CrossRef ]
• Schwartz, J.; Padmanabhan, A.; Aqui, N.; Balogun, R.A.; Connelly-Smith, L.; Delaney, M.; Dunbar, N.M.; Witt, V.; Wu, Y.; Shaz, B.H. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Seventh Special Issue. J. Clin. Apher. 2016 , 31 , 149–162. [ Google Scholar ] [ CrossRef ]
• Connelly-Smith, L.; Alquist, C.R.; Aqui, N.A.; Hofmann, J.C.; Klingel, R.; Onwuemene, O.A.; Patriquin, C.J.; Pham, H.P.; Sanchez, A.P.; Schneiderman, J.; et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice—Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Ninth Special Issue. J. Clin. Apher. 2023 , 38 , 77–278. [ Google Scholar ] [ CrossRef ]
• Nugent, A.K.; Gray, J.V.; Gorby, L.K.; Moriarty, P.M. Lipoprotein Apheresis: First FDA Indicated Treatment for Elevated Lipoprotein(a). J. Clin. Cardiol. 2020 , 1 , 16–21. [ Google Scholar ] [ CrossRef ]
• Russi, G. Severe Dyslipidemia in Pregnancy: The Role of Therapeutic Apheresis. Transfus. Apher. Sci. 2015 , 53 , 283–287. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Shapero, K.; Countouris, M.; Chibisov, I.; Jeyabalan, A.; Berlacher, K. Peripartum Lipid Apheresis: Novel Management of Familial Hyperlipidemia in Pregnancy. JACC Case Rep. 2023 , 27 , 102052. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Ogura, M.; Makino, H.; Kamiya, C.; Yoshimatsu, J.; Soran, H.; Eatough, R.; Perrone, G.; Harada-Shiba, M.; Stefanutti, C. Lipoprotein Apheresis Is Essential for Managing Pregnancies in Patients with Homozygous Familial Hypercholesterolemia: Seven Case Series and Discussion. Atherosclerosis 2016 , 254 , 179–183. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Stefanutti, C.; Julius, U.; Watts, G.F.; Harada-Shiba, M.; Cossu, M.; Schettler, V.J.; De Silvestro, G.; Soran, H.; Van Lennep, J.R.; Pisciotta, L.; et al. Toward an International Consensus-Integrating Lipoprotein Apheresis and New Lipid-Lowering Drugs. J. Clin. Lipidol. 2017 , 11 , 858–871.e3. [ Google Scholar ] [ CrossRef ]
• Reijman, M.D.; Kusters, D.M.; Groothoff, J.W.; Arbeiter, K.; Dann, E.J.; de Boer, L.M.; de Ferranti, S.D.; Gallo, A.; Greber-Platzer, S.; Hartz, J.; et al. Clinical Practice Recommendations on Lipoprotein Apheresis for Children with Homozygous Familial Hypercholesterolaemia: An Expert Consensus Statement from ERKNet and ESPN. Atherosclerosis 2024 , 392 , 117525. [ Google Scholar ] [ CrossRef ]
• Gupta, M.; Liti, B.; Barrett, C.; Thompson, P.D.; Fernandez, A.B. Prevention and Management of Hypertriglyceridemia-Induced Acute Pancreatitis During Pregnancy: A Systematic Review. Am. J. Med. 2022 , 135 , 709–714. [ Google Scholar ] [ CrossRef ]
• Dittrich, E.; Schmaldienst, S.; Langer, M.; Jansen, M.; Hörl, W.H.; Derfler, K. Immunoadsorption and Plasma Exchange in Pregnancy. Kidney Blood Press. Res. 2002 , 25 , 232–239. [ Google Scholar ] [ CrossRef ]
• Lindkvist, B.; Appelros, S.; Regnér, S.; Manjer, J. A Prospective Cohort Study on Risk of Acute Pancreatitis Related to Serum Triglycerides, Cholesterol and Fasting Glucose. Pancreatology 2012 , 12 , 317–324. [ Google Scholar ] [ CrossRef ]
• Preiss, D.; Tikkanen, M.J.; Welsh, P.; Ford, I.; Lovato, L.C.; Elam, M.B.; LaRosa, J.C.; DeMicco, D.A.; Colhoun, H.M.; Goldenberg, I.; et al. Lipid-Modifying Therapies and Risk of Pancreatitis: A Meta-Analysis. JAMA 2012 , 308 , 804–811. [ Google Scholar ] [ CrossRef ]
• Toskes, P.P. Hyperlipidemic Pancreatitis. Gastroenterol. Clin. N. Am. 1990 , 19 , 783–791. [ Google Scholar ] [ CrossRef ]
• Berglund, L.; Brunzell, J.D.; Goldberg, A.C.; Goldberg, I.J.; Sacks, F.; Murad, M.H.; Stalenhoef, A.F.H. Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 2012 , 97 , 2969–2989. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Vallejo-Vaz, A.J.; Fayyad, R.; Matthijs Boekholdt, S.; Kees Hovingh, G.; Kastelein, J.J.; Melamed, S.; Barter, P.; Waters, D.D.; Ray, K.K. Triglyceride-Rich Lipoprotein Cholesterol and Risk of Cardiovascular Events Among Patients Receiving Statin Therapy in the TNT Trial. Circulation 2018 , 138 , 770–781. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Edison, R.J.; Muenke, M. Mechanistic and Epidemiologic Considerations in the Evaluation of Adverse Birth Outcomes Following Gestational Exposure to Statins. Am. J. Med. Genet. A 2004 , 131 , 287–298. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Godfrey, L.M.; Erramouspe, J.; Cleveland, K.W. Teratogenic Risk of Statins in Pregnancy. Ann. Pharmacother. 2012 , 46 , 1419–1424. [ Google Scholar ] [ CrossRef ]
• Visseren, F.; Mach, F.; Smulders, Y.M.; Carballo, D.; Koskinas, K.C.; Bäck, M.; Benetos, A.; Biffi, A.; Boavida, J.M.; Capodanno, D.; et al. 2021 ESC Guidelines on Cardiovascular Disease Prevention in Clinical Practice. Eur. Heart J. 2021 , 42 , 3227–3337. [ Google Scholar ] [ CrossRef ]
• Poornima, I.G.; Pulipati, V.P.; Brinton, E.A.; Wild, R.A. Update on Statin Use in Pregnancy. Am. J. Med. 2023 , 136 , 12–14. [ Google Scholar ] [ CrossRef ]
• Costantine, M.M.; Cleary, K. Pravastatin for the Prevention of Preeclampsia in High-Risk Pregnant Women. Obstet. Gynecol. 2013 , 121 , 349–353. [ Google Scholar ] [ CrossRef ]
• Klevmoen, M.; Bogsrud, M.P.; Retterstøl, K.; Svilaas, T.; Vesterbekkmo, E.K.; Hovland, A.; Berge, C.; Roeters van Lennep, J.; Holven, K.B. Loss of Statin Treatment Years during Pregnancy and Breastfeeding Periods in Women with Familial Hypercholesterolemia. Atherosclerosis 2021 , 335 , 8–15. [ Google Scholar ] [ CrossRef ]
• Holmsen, S.T.; Bakkebø, T.; Seferowicz, M.; Retterstøl, K. Statins and Breastfeeding in Familial Hypercholesterolaemia. Tidsskr. Nor. Laegeforen 2017 , 137 , 686–687. [ Google Scholar ] [ CrossRef ]
• Laufs, U.; Parhofer, K.G.; Ginsberg, H.N.; Hegele, R.A. Clinical Review on Triglycerides. Eur. Heart J. 2020 , 41 , 99–109. [ Google Scholar ] [ CrossRef ]
• Brunzell, J.D. Clinical Practice. Hypertriglyceridemia. N. Engl. J. Med. 2007 , 357 , 1009–1017. [ Google Scholar ] [ CrossRef ]
• Magarian, G.J.; Lucas, L.M.; Colley, C. Gemfibrozil-Induced Myopathy. Arch. Intern. Med. 1991 , 151 , 1873–1874. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Ward, N.C.; Watts, G.F.; Eckel, R.H. Response by Ward et al. to Letter Regarding Article, “Statin Toxicity: Mechanistic Insights and Clinical Implications”. Circ. Res. 2019 , 124 , e121–e122. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Miller, D.B.; Spence, J.D. Clinical Pharmacokinetics of Fibric Acid Derivatives (Fibrates). Clin. Pharmacokinet. 1998 , 34 , 155–162. [ Google Scholar ] [ CrossRef ]
• Pierce, L.R.; Wysowski, D.K.; Gross, T.P. Myopathy and Rhabdomyolysis Associated With Lovastatin-Gemfibrozil Combination Therapy. JAMA 1990 , 264 , 71–75. [ Google Scholar ] [ CrossRef ]
• Jones, P.H.; Davidson, M.H. Reporting Rate of Rhabdomyolysis with Fenofibrate + Statin versus Gemfibrozil + Any Statin. Am. J. Cardiol. 2005 , 95 , 120–122. [ Google Scholar ] [ CrossRef ]
• Tsai, E.C.; Brown, J.A.; Veldee, M.Y.; Anderson, G.J.; Chait, A.; Brunzell, J.D. Potential of Essential Fatty Acid Deficiency with Extremely Low Fat Diet in Lipoprotein Lipase Deficiency during Pregnancy: A Case Report. BMC Pregnancy Childbirth 2004 , 4 , 27. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Abu Musa, A.A.; Usta, I.M.; Rechdan, J.B.; Nassar, A.H. Recurrent Hypertriglyceridemia-Induced Pancreatitis in Pregnancy: A Management Dilemma. Pancreas 2006 , 32 , 227–228. [ Google Scholar ] [ CrossRef ]
• Saadi, H.F.; Kurlander, D.J.; Erkins, J.M.; Hoogwerf, B.J. Severe Hypertriglyceridemia and Acute Pancreatitis during Pregnancy: Treatment with Gemfibrozil. Endocr. Pract. 1999 , 5 , 33–36. [ Google Scholar ] [ CrossRef ]
• Goldenberg, I.; Benderly, M.; Goldbourt, U. Update on the use of fibrates: Focus on bezafibrate. Vasc Health Risk Manag. 2008 , 4 , 131–141. [ Google Scholar ] [ CrossRef ]
• Bachmann, C.M.; Janitschke, D.; Lauer, A.A.; Erhardt, T.; Hartmann, T.; Grimm, M.O.W.; Grimm, H.S. Gemfibrozil-Induced Intracellular Triglyceride Increase in SH-SY5Y, HEK and Calu-3 Cells. Int. J. Mol. Sci. 2023 , 24 , 2972. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Harris, W.S.; Connor, W.E.; Illingworth, D.R.; Rothrock, D.W.; Foster, D.M. Effects of Fish Oil on VLDL Triglyceride Kinetics in Humans. J. Lipid Res. 1990 , 31 , 1549–1558. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Simha, V. Management of Hypertriglyceridemia. BMJ 2020 , 371 , m3109. [ Google Scholar ] [ CrossRef ]
• Skulas-Ray, A.C.; Wilson, P.W.F.; Harris, W.S.; Brinton, E.A.; Kris-Etherton, P.M.; Richter, C.K.; Jacobson, T.A.; Engler, M.B.; Miller, M.; Robinson, J.G.; et al. Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association. Circulation 2019 , 140 , E673–E691. [ Google Scholar ] [ CrossRef ]
• Bays, H.E.; Ballantyne, C.M.; Kastelein, J.J.; Isaacsohn, J.L.; Braeckman, R.A.; Soni, P.N. Eicosapentaenoic Acid Ethyl Ester (AMR101) Therapy in Patients with Very High Triglyceride Levels (from the Multi-Center, PlAcebo-Controlled, Randomized, Double-BlINd, 12-Week Study with an Open-Label Extension [MARINE] Trial). Am. J. Cardiol. 2011 , 108 , 682–690. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Wierzbicki, A.S.; Kim, E.J.; Esan, O.; Ramachandran, R. Hypertriglyceridaemia: An Update. J. Clin. Pathol. 2022 , 75 , 798–806. [ Google Scholar ] [ CrossRef ]
• Nordgren, T.M.; Lyden, E.; Anderson-Berry, A.; Hanson, C. Omega-3 Fatty Acid Intake of Pregnant Women and Women of Childbearing Age in the United States: Potential for Deficiency? Nutrients 2017 , 9 , 197. [ Google Scholar ] [ CrossRef ]
• Emmett, P.M.; Jones, L.R.; Golding, J. Pregnancy Diet and Associated Outcomes in the Avon Longitudinal Study of Parents and Children. Nutr. Rev. 2015 , 73 (Suppl. S3), 154–174. [ Google Scholar ] [ CrossRef ]
• Middleton, P.; Gomersall, J.C.; Gould, J.F.; Shepherd, E.; Olsen, S.F.; Makrides, M. Omega-3 Fatty Acid Addition during Pregnancy. Cochrane Database Syst. Rev. 2018 , 11 , CD003402. [ Google Scholar ] [ CrossRef ]
• Olsen, S.F.; Secher, N.J. A Possible Preventive Effect of Low-Dose Fish Oil on Early Delivery and Pre-Eclampsia: Indications from a 50-Year-Old Controlled Trial. Br. J. Nutr. 1990 , 64 , 599–609. [ Google Scholar ] [ CrossRef ]
• Olsen, S.F.; Østerdal, M.L.; Salvig, J.D.; Weber, T.; Tabor, A.; Secher, N.J. Duration of Pregnancy in Relation to Fish Oil Supplementation and Habitual Fish Intake: A Randomised Clinical Trial with Fish Oil. Eur. J. Clin. Nutr. 2007 , 61 , 976–985. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Olsen, S.F.; Secher, N.J. Low Consumption of Seafood in Early Pregnancy as a Risk Factor for Preterm Delivery: Prospective Cohort Study. BMJ 2002 , 324 , 447–450. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Yokoyama, M.; Origasa, H.; Matsuzaki, M.; Matsuzawa, Y.; Saito, Y.; Ishikawa, Y.; Oikawa, S.; Sasaki, J.; Hishida, H.; Itakura, H.; et al. Effects of Eicosapentaenoic Acid on Major Coronary Events in Hypercholesterolaemic Patients (JELIS): A Randomised Open-Label, Blinded Endpoint Analysis. Lancet 2007 , 369 , 1090–1098. [ Google Scholar ] [ CrossRef ]
• Manson, J.E.; Cook, N.R.; Lee, I.-M.; Christen, W.; Bassuk, S.S.; Mora, S.; Gibson, H.; Albert, C.M.; Gordon, D.; Copeland, T.; et al. Marine N-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N. Engl. J. Med. 2019 , 380 , 23–32. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Bhatt, D.L.; Steg, P.G.; Miller, M.; Brinton, E.A.; Jacobson, T.A.; Ketchum, S.B.; Doyle, R.T.; Juliano, R.A.; Jiao, L.; Granowitz, C.; et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N. Engl. J. Med. 2019 , 380 , 11–22. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Nakao, J.; Ohba, T.; Takaishi, K.; Katabuchi, H. Omega-3 Fatty Acids for the Treatment of Hypertriglyceridemia during the Second Trimester. Nutrition 2015 , 31 , 409–412. [ Google Scholar ] [ CrossRef ]
• Goldie, C.; Taylor, A.J.; Nguyen, P.; McCoy, C.; Zhao, X.Q.; Preiss, D. Niacin Therapy and the Risk of New-Onset Diabetes: A Meta-Analysis of Randomised Controlled Trials. Heart 2016 , 102 , 198–203. [ Google Scholar ] [ CrossRef ]
• Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline ; The National Academies Press: Washington, DC, USA, 1998. [ Google Scholar ] [ CrossRef ]
• Rader, J.I.; Calvert, R.J.; Hathcock, J.N. Hepatic Toxicity of Unmodified and Time-Release Preparations of Niacin. Am. J. Med. 1992 , 92 , 77–81. [ Google Scholar ] [ CrossRef ]
• Lewek, J.; Bielecka-Dabrowa, A.; Toth, P.P.; Banach, M. Dyslipidaemia Management in Pregnant Patients: A 2024 Update. Eur. Heart J. Open 2024 , 4 , oeae032. [ Google Scholar ] [ CrossRef ]
• Crouse, J.R. Hypertriglyceridemia: A Contraindication to the Use of Bile Acid Binding Resins. Am. J. Med. 1987 , 83 , 243–248. [ Google Scholar ] [ CrossRef ]
• Tsuang, W.; Navaneethan, U.; Ruiz, L.; Palascak, J.B.; Gelrud, A. Hypertriglyceridemic Pancreatitis: Presentation and Management. Am. J. Gastroenterol. 2009 , 104 , 984–991. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Basar, R.; Uzum, A.K.; Canbaz, B.; Dogansen, S.C.; Kalayoglu-Besisik, S.; Altay-Dadin, S.; Aral, F.; Ozbey, N.C. Therapeutic Apheresis for Severe Hypertriglyceridemia in Pregnancy. Arch. Gynecol. Obstet. 2013 , 287 , 839–843. [ Google Scholar ] [ CrossRef ]
• Papadakis, E.P.; Sarigianni, M.; Mikhailidis, D.P.; Mamopoulos, A.; Karagiannis, V. Acute Pancreatitis in Pregnancy: An Overview. Eur. J. Obstet. Gynecol. Reprod. Biol. 2011 , 159 , 261–266. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Chen, Z.; Huang, X.; Zhang, M.; Han, N.; Ning, Y. Rapid Reduction in Triglyceride Levels by Therapeutic Plasma Exchange in Patients with Hypertriglyceridemic Pancreatitis. J. Clin. Apher. 2022 , 37 , 82–90. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Stefanutti, C.; Labbadia, G.; Morozzi, C. Severe Hypertriglyceridemia-Related Acute Pancreatitis. Ther. Apher. Dial. 2013 , 17 , 130–137. [ Google Scholar ] [ CrossRef ]
• Ewald, N.; Kloer, H.U. Treatment Options for Severe Hypertriglyceridemia (SHTG): The Role of Apheresis. Clin. Res. Cardiol. Suppl. 2012 , 7 , 31–35. [ Google Scholar ] [ CrossRef ]
• Syed, H.; Bilusic, M.; Rhondla, C.; Tavaria, A. Plasmapheresis in the Treatment of Hypertriglyceridemia-Induced Pancreatitis: A Community Hospital’s Experience. J. Clin. Apher. 2010 , 25 , 229–234. [ Google Scholar ] [ CrossRef ]
• Gavva, C.; Sarode, R.; Agrawal, D.; Burner, J. Therapeutic Plasma Exchange for Hypertriglyceridemia Induced Pancreatitis: A Rapid and Practical Approach. Transfus. Apher. Sci. 2016 , 54 , 99–102. [ Google Scholar ] [ CrossRef ]
• Kadikoylu, G.; Yavasoglu, I.; Bolaman, Z. Plasma Exchange in Severe Hypertriglyceridemia a Clinical Study. Transfus. Apher. Sci. 2006 , 34 , 253–257. [ Google Scholar ] [ CrossRef ]
• Lennertz, A.; Parhofer, K.G.; Samtleben, W.; Bosch, T. Therapeutic Plasma Exchange in Patients with Chylomicronemia Syndrome Complicated by Acute Pancreatitis. Ther. Apher. 1999 , 3 , 227–233. [ Google Scholar ] [ CrossRef ]
• Yeh, J.H.; Chen, J.H.; Chiu, H.C. Plasmapheresis for Hyperlipidemic Pancreatitis. J. Clin. Apher. 2003 , 18 , 181–185. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Kandemir, A.; Coşkun, A.; Yavaşoğlu, İ.; Bolaman, Z.; Ünübol, M.; Yaşa, M.H.; Kadıköylü, G. Therapeutic Plasma Exchange for Hypertriglyceridemia Induced Acut Pancreatitis: The 33 Cases Experience from a Tertiary Reference Center in Turkey. Turk. J. Gastroenterol. 2018 , 29 , 676–683. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Piolot, A.; Nadler, F.; Cavallero, E.; Coquard, J.L.; Jacotot, B. Prevention of Recurrent Acute Pancreatitis in Patients with Severe Hypertriglyceridemia: Value of Regular Plasmapheresis. Pancreas 1996 , 13 , 96–99. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Wind, M.; Gaasbeek, A.G.A.; Oosten, L.E.M.; Rabelink, T.J.; van Lith, J.M.M.; Sueters, M.; Teng, Y.K.O. Therapeutic Plasma Exchange in Pregnancy: A Literature Review. Eur. J. Obstet. Gynecol. Reprod. Biol. 2021 , 260 , 29–36. [ Google Scholar ] [ CrossRef ]
• Perrone, G.; Brunelli, R.; Marcoccia, E.; Zannini, I.; Candelieri, M.; Gozzer, M.; Stefanutti, C. Therapeutic Apheresis in Pregnancy: Three Differential Indications With Positive Maternal and Fetal Outcome. Ther. Apher. Dial. 2016 , 20 , 677–685. [ Google Scholar ] [ CrossRef ]
• Perrone, S.; Brunelli, R.; Perrone, G.; Zannini, I.; Galoppi, P.; Di Giacomo, S.; Morozzi, C.; Pisciotta, L.; Stefanutti, C. A Successful Term Pregnancy with Severe Hypertriglyceridaemia and Acute Pancreatitis. Clinical Management and Review of the Literature. Atheroscler. Suppl. 2019 , 40 , 117–121. [ Google Scholar ] [ CrossRef ]
• Altun, D.; Eren, G.; Cukurova, Z.; Hergünsel, O.; Yasar, L. An Alternative Treatment in Hypertriglyceridemia-Induced Acute Pancreatitis in Pregnancy: Plasmapheresis. J. Anaesthesiol. Clin. Pharmacol. 2012 , 28 , 252–254. [ Google Scholar ] [ CrossRef ]
• Safi, F.; Toumeh, A.; Qadan, M.A.A.; Karaz, R.; AlAkdar, B.; Assaly, R. Management of Familial Hypertriglyceridemia-Induced Pancreatitis during Pregnancy with Therapeutic Plasma Exchange: A Case Report and Review of Literature. Am. J. Ther. 2014 , 21 , e134–e136. [ Google Scholar ] [ CrossRef ]
• Rawla, P.; Sunkara, T.; Thandra, K.C.; Gaduputi, V. Hypertriglyceridemia-Induced Pancreatitis: Updated Review of Current Treatment and Preventive Strategies. Clin. J. Gastroenterol. 2018 , 11 , 441–448. [ Google Scholar ] [ CrossRef ]

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Formisano, E.; Proietti, E.; Perrone, G.; Demarco, V.; Galoppi, P.; Stefanutti, C.; Pisciotta, L. Characteristics, Physiopathology and Management of Dyslipidemias in Pregnancy: A Narrative Review. Nutrients 2024 , 16 , 2927. https://doi.org/10.3390/nu16172927

Formisano E, Proietti E, Perrone G, Demarco V, Galoppi P, Stefanutti C, Pisciotta L. Characteristics, Physiopathology and Management of Dyslipidemias in Pregnancy: A Narrative Review. Nutrients . 2024; 16(17):2927. https://doi.org/10.3390/nu16172927

Formisano, Elena, Elisa Proietti, Giuseppina Perrone, Valentina Demarco, Paola Galoppi, Claudia Stefanutti, and Livia Pisciotta. 2024. "Characteristics, Physiopathology and Management of Dyslipidemias in Pregnancy: A Narrative Review" Nutrients 16, no. 17: 2927. https://doi.org/10.3390/nu16172927

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• Review Article
• Special issue: Topics from The 45 the Annual Scientific meeting of the Japanese Society of Hypertension (JSH 2024)
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• Published: 29 August 2024

Obstructive sleep apnea -related hypertension: a review of the literature and clinical management strategy

• Kazuki Shiina 1  

Hypertension Research ( 2024 ) Cite this article

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Obstructive Sleep Apnea (OSA) and hypertension have a high rate of co-occurrence, with OSA being a causative factor for hypertension. Sympathetic activity due to intermittent hypoxia and/or fragmented sleep is the most important mechanisms triggering the elevation in blood pressure in OSA. OSA-related hypertension is characterized by resistant hypertension, nocturnal hypertension, abnormal blood pressure variability, and vascular remodeling. In particular, the prevalence of OSA is high in patients with resistant hypertension, and the mechanism proposed includes vascular remodeling due to the exacerbation of arterial stiffness by OSA. Continuous positive airway pressure therapy is effective at lowering blood pressure, however, the magnitude of the decrease in blood pressure is relatively modest, therefore, patients often need to also take antihypertensive medications to achieve optimal blood pressure control. Antihypertensive medications targeting sympathetic pathways or the renin-angiotensin-aldosterone system have theoretical potential in OSA-related hypertension, Therefore, beta-blockers and renin-angiotensin system inhibitors may be effective in the management of OSA-related hypertension, but current evidence is limited. The characteristics of OSA-related hypertension, such as nocturnal hypertension and obesity-related hypertension, suggests potential for angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucose-dependent insulinotropic polypeptide receptor/ glucagon-like peptide-1 receptor agonist (GIP/GLP-1 RA). Recently, OSA has been considered to be caused not only by upper airway anatomy but also by several non-anatomic mechanisms, such as responsiveness of the upper airway response, ventilatory control instability, and reduced sleep arousal threshold. Elucidating the phenotypic mechanisms of OSA may potentially advance more personalized hypertension treatment strategies in the future.

Clinical characteristics and management strategy of OSA-related hypertension. OSA obstructive sleep apnea, BP blood pressure, ABPM ambulatory blood pressure monitoring, CPAP continuous positive airway pressure, LVH left ventricular hypertrophy, ARB: angiotensin II receptor blocker, SGLT2i Sodium-glucose cotransporter 2 inhibitors, ARNI angiotensin receptor-neprilysin inhibitor, CCB calcium channel blocker, GIP/GLP-1 RA glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist.

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Recent advances in the management of secondary hypertension—obstructive sleep apnea

Obstructive sleep apnea and ambulatory blood pressure monitoring: current evidence and research gaps

Obstructive sleep apnoea heterogeneity and cardiovascular disease

Introduction.

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of complete or partial collapse of the upper airway during sleep, resulting in apnea or hypopnea, and is recognized as an independent risk factor for cardiovascular disease such as hypertension, heart failure, arrhythmia, and coronary heart disease [ 1 , 2 ]. OSA increases blood pressure (BP) by enhancing various risk factors including the sympathetic nervous system, renin-angiotensin-aldosterone system (RAAS), and inflammation through mechanisms such as obesity, decreased intrathoracic pressure, pulmonary stretch receptor stimulation, chemoreceptor stimulation, hypoxemia, and hypercapnia [ 3 , 4 ]. The 2023 European Society of Hypertension (ESH) Guidelines for the diagnosis and treatment of hypertension emphasize the importance of the obese state and of the metabolic syndrome, one of the causes of hypertension, as the main partially reversible risk factors for OSA [ 5 ].

The presence of OSA has been related to an increase in the prevalence and incidence of hypertension, regardless of other factors (OR: 1.5–2.9) [ 6 , 7 ]. In fact, approximately 30–50% of hypertensive patients have OSA, whereas 50% of patients with OSA present hypertension [ 6 ], especially about 80% of patients with resistant hypertension have OSA. Therefore, screening for OSA is recommended in patients with resistant hypertension [ 8 , 9 ].

This review aims to summarize the latest findings on the clinical features of OSA-related hypertension to its treatment strategies.

Symptoms and clinical findings in OSA

In patients with OSA, extremely loud snoring and sleep apnea are typical symptoms, often prompting visits based on the partner’s observations (Table  1 ). However, the rational clinical examination systematic review by Myers, et al. [ 10 ] reported that the most useful observation for identifying patients with OSA was nocturnal choking or gasping (summary likelihood ratio [LR], 3.3; 95% CI, 2.1–4.6) when the diagnosis was established by apnea-hypopnea index: AHI ≥ 10/h). Snoring is common in OSA patients but is not useful for establishing the diagnosis (summary LR, 1.1; 95% CI, 1.0–1.1). Daytime excessive sleepiness is a common subjective clinical symptom, although it has been reported that awareness of symptoms is often lacking [ 11 ], particularly among patients with cardiovascular diseases [ 12 , 13 ]. As there is controversy regarding the association of morning headache and obstructive sleep apnea syndrome (OSAS), Goksan, et al. demonstrated that prevalence of morning headache increases with increasing OSAS severity [ 14 ]. Atrial stretch due to the large negative pressure swings by OSA results in secretion of atrial natriuretic peptide, causing nocturia. The prevalence of OSA increases with factors such as obesity and aging, but in Asia, there are many non-obese OSA patients related to craniofacial bony restriction [ 15 ].

Therefore, when examining hypertensive patients, it is important to pay attention to typical symptoms such as sleepiness and abnormalities in facial and pharyngeal morphology, even in non-obese patients, and to actively perform OSA screening tests when these abnormalities are suspected. Additionally, it is necessary to actively suspect OSA in patients with left ventricular hypertrophy (LVH), aortic disease, atrial fibrillation (AF), and those undergoing dialysis [ 9 ].

New concept of mechanisms in OSA

Recently, OSA has been considered to be caused not only by upper airway anatomy but also by several non-anatomic mechanisms [ 16 ]. These factors include the responsiveness of the upper airway responce, ventilatory control instability [ 17 ], and reduced sleep arousal threshold [ 18 ]. The relative contributions of these processes may vary from one patient to another and have therapeutic implications [ 19 ]. For example, upper-airway stimulation device is a new treatment for OSA that targets the responsiveness of the upper airway response [ 20 ]. Future treatments for OSA-related hypertension may need to consider these phenotypes.

Hypertension Risk and OSA

OSA and hypertension are not merely comorbidities; OSA itself can potentially be a causative factor for hypertension. The Wisconsin Sleep Cohort study, a prospective, community-based study, it has been demonstrated that an increase in AHI independently of age and body mass index (BMI) is associated with the new-onset hypertension [ 6 ]. In contrast, the 5-year follow-up study of the Sleep Heart Health Study, conducted with 2470 participants without hypertension at admission, found that after adjusting for BMI, AHI was no longer a significant predictor of hypertension [ 21 ]. The findings that do not support the relationship between OSA and hypertension were attributed to the lower rate of participants with moderate to severe OSA. Indeed, the vast majority of the participants included in the 5-year follow-up of the Sleep Heart Health Study had mild OSA [ 21 ]. On the other hand, Marin, et al. demonstrated that the presence of OSA was associated with increased adjusted risk of incident hypertension in a large prospective cohort study (median follow-up periods 12.2 years) without hypertension [ 22 ]. The incidence of hypertension increased with severity of OSA. These findings suggest that untreated “severe” OSA is independently of BMI associated with an increased risk for developing new-onset hypertension, and there is a “dose–response” relation between OSA and the risk of developing hypertension.

Pathogenesis of Hypertension in OSA

The mechanisms promoting hypertension in OSA are multifactorial and complex. Sympathetic activity due to intermittent hypoxia and/or fragmented sleep is the most important mechanisms triggering the elevation in BP in OSA. The pathophysiology begins with obstructed airfow into the lungs, which causes transient hypoxia and hypercapnia. The sympathetic nervous system is activated simultaneously by these repetitive blood gas derangements, which stimulate both central and peripheral chemoreceptors, apnea-induced cessation of pulmonary stretch receptor-mediated inhibition of central sympathetic outflow, and silencing of sympathoinhibitory input from carotid sinus baroreceptors by reductions in stroke volume and BP during obstructive apneas. When the apnea is interrupted by arousal from sleep, the latter process simultaneously augments sympathetic nervous activity and reduces cardiac vagal activity [ 3 , 4 , 23 ]. The result is a postapneic surge in BP [ 24 ].

These acute adverse effects of OSA on the autonomic nervous system are not confined to sleep. Patients with OSA and cardiac dysfunction also have elevated sympathetic nervous activity and depressed cardiac vagal activity when awake [ 23 ]. The mechanisms for such daytime carryover effects remain unclear but may relate to the adaptation of chemoreceptor reflexes or central processes governing autonomic outflow.

Consequently, RAAS is activated, the endothelin-1 level is increased, and the nitric oxide level is decreased, all of which contribute to the increase in vascular resistance and the development of hypertension [ 25 , 26 ]. Sympathetic hyperactivity leads to a proinflammatory state, resulting in endothelial dysfunction and increased arterial stiffness [ 27 , 28 , 29 ].

Characteristics of OSA-related HT

Resistant hypertension.

Resistant hypertension is defined as BP that is uncontrolled despite using ≥3 medications of different classes (Table  2 ), commonly a long-acting calcium channel blocker (CCB), angiotensin converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) and a diuretic (Fig.  1 ). Multiple studies have demonstrated a high prevalence of OSA in patients with resistant hypertension. The prevalence is reported to be 70–80% [ 30 , 31 , 32 , 33 , 34 ]. Several mechanisms may exlain the potential role of OSA in promoting resistant hypertension [ 35 ]. These include sympathetic nervous system activation, endothelial dysfunction, increased arterial stiffness, and fluid retention due to OSA. Among these mechanisms, increased arterial stiffness due to OSA is a major cause of resistant hypertension. Roderjan et al. reported that among resistant hypertensives, the more severe the apnea was associated with the greater the arterial stiffness, and that patients with increased pulse wave velocity (PWV) have an adverse clinical and polysomnographic profile pointing to a higher cardiovascular risk, especially women, patients with true resistant hypertension [ 36 ]. We have demonstrated that OSA and metabolic syndrome were independently associated with elevated PWV in large Sleep Cohort [ 29 ]. Although it is not clear what the roles of arterial stiffness in contributing to resistant hypertension are, it is reasonable to speculate that the vascular remodeling promoted by OSA may exacerbate BP in patients with hypertension [ 37 ].

Proposed pathways through which OSA may contribute to the development of resistant hypertension. OSA obstructive sleep apnea, RAAS RAAS: renin–angiotensin– aldosterone system, T2DM type 2 diabetes mellitus, CKD chronic kidney disease, ASCVD atherosclerotic cardiovascular disease

Non-dipper phenomenon

OSA-related hypertension is predominantly nocturnal and characterized by a non-dipping pattern [ 38 , 39 , 40 ]. Systolic BP (SBP) and diastolic BP (DBP) reduce by ~10 mmHg (about 10–20%) during sleep, but this dipping phenomenon is reversed in those with OSA. The prevalence of non-dipping was 84% in a population of untreated patients with mild to severe OSA [ 41 ]. OSA increases sympathetic nerve activity due to arousals in sleep, which counteracts the normal nocturnal BP dip and results in increased intravascular pressure. This chronic hypertension leads to vascular remodeling, decreased endothelial production of vasodilatory nitric oxide, and insensitive baroreceptors, further inhibiting the reflex of nocturnal BP dip [ 28 , 42 , 43 ]. In patients with severe OSA, positive airway pressure (CPAP) turns a non-dipping into a dipping BP profile [ 44 ].

BP variability (BPV)

In OSA, BP variability (BPV) has been studied mainly as very short-term (beat-to-beat) and short-term (24-hour BP profile) variability [ 45 , 46 ].

BP measured on consecutive heartbeats has been demonstrated to be highly variable, due to repeated peaks during sleep, so that an accurate assessment of nocturnal BP levels in OSA may require peculiar methodologies [ 47 , 48 , 49 , 50 ].

Consistent evidence indicates that the presence of OSA may be associated with increased short-term BPV, but the information on its relationship with long-term BPV, assessed on a visit-to-visit variability (VVV) is limited [ 51 ]. We observed that patients with severe OSA had significantly higher systolic VVV than controls matched for age, BMI and SBP [ 52 ]. Moreover, in this study, the plasma noradrenaline level and the AHI were independently and positively correlated with VVV and VVV was significantly reduced by CPAP. In a different study, Kansui et al. demonstrated the impact of OSA on long-term (yearly) BPV in Japanese work-site population [ 53 ].

Inter-arm BP difference

Inter-arm SBP difference (IAD) is a non-invasively and easily measurable parameter. Recent evidence suggests the existence of correlations between IAD and the risk of cardiovascular events and mortality in patients with hypertension, diabetes mellitus, and coronary artery disease, as also in the general population [ 54 ]. IAD of BP is important but the measurement methodology has a major influence on IAD results. According to a meta-analysis, the number of subjects with a systolic and diastolic IAD ≥ 10 mmHg was significantly lower when BP measurements were performed simultaneously instead of sequentially [ 55 ]. This could have overestimated the prevalence of IAD ≥ 10 mmHg. The results from Tokyo Sleep Heart Study, moderate to severe OSA was independently associated with the IAD accessed by simultaneously BP measurements [ 56 ]. The plausible explanation is that the negative intrathoracic pressure caused by OSA may exert an adverse impact on the structural properties of the thoracic aorta.

Cardiovascular damage by OSA-related HT

Cardiac morphology and function, left ventricular hypertrophy (lvh).

Several studies have observed an association between OSA and LVH [ 57 , 58 , 59 ], but it has been difficult to demonstrate an association between OSA and higher LVH independent of obesity and hypertension. Indeed, Usui, et al. demonstrated that no significant differences in left ventricular mass index by OSA severity in 74 healthy non-obese men [ 60 ]. However, recent meta-analysis showed that OSA was significantly associated with an increased risk of LVH (OR = 1.70, 95% CI 1.44–2.00, P < 0.001) [ 61 ]. Although significant variability in prevalence estimates exists between studies, recent meta-analysis suggests that in the OSA setting concentric LVH is more frequent than eccentric LVH [ 62 ].

Left ventricular systolic function

Literature reports concerning left ventricular systolic function in OSA patients are controversial. The meta-analysis by Yu, et al. demonstrated that significant decreases in left ventricular ejection fraction (LVEF) were observed in OSAS patients [ 63 ], however, the alterations in LVEF seemed not to be remarkable enough to induce obvious clinical symptoms of LV dysfunction. Recent study demonstrated that global longitudinal strain (GLS), a more sensitive measurement of LV systolic function, is impaired in patients with OSA, thus allowing to identify subclinical alterations of the systolic function not captured by LVEF [ 64 ].

Left ventricular diastolic function

Several studies demonstrated the association between OSA and　echocardiographic parameters of left ventricular diastolic dysfunction. Wachter, et al. reported that moderate-to-severe OSA is independently associated with diastolic dysfunction in a primary care cohort of 352 patients with cardiovascular risk factors [ 65 ]. OSA may be independently associated with left ventricular diastolic dysfunction perhaps due to higher LV mass [ 66 ]. Usui, et al. reported that coexistence of OSA and metabolic syndrome is independently associated with LVH and diastolic dysfunction in Japanese sleep cohort [ 67 ]. Clinicians should pay attention to the significance of the coexistence of these disorders so as to prevent the development of heart failure with preserved LVEF.

Based on these results, although comorbidities such as hypertension play a role in OSA, it is particularly associated with LVH and decreased left ventricular diastolic function. Therefore, it is important to consider the presence of OSA in patients with hypertension that exhibits these characteristics.

Atrial fibrillation (AF)

The prevalence of OSA in patients with atrial fibrillation (AF) is extremely high [ 68 , 69 ], making screening for OSA essential in these patients. The high-frequency intermittent hypoxia, negative intrathoracic pressure, atrial stretching, neurohumoral activation, and chronic concomitant conditions, such as hypertension, metabolic syndrome, and obesity, associated with OSA create progressive structural remodeling of the atrium [ 69 ]. This progressive atrial structural remodeling, along with the electrophysiological changes contributes to the reentry mechanism for AF and establishes an arrhythmogenic substrate in the atrium.

Recently, we reported that nutritional status and sleep quality are associated with AF in patients with OSA [ 70 ]. Undernutrition, as assessed by the CONtrolling NUTritional status (CONUT) score [ 71 ], and reduced slow-wave sleep were factors significantly related to the presence of AF. The CONUT scores were calculated from total peripheral lymphocyte counts, the serum albumin levels, and total cholesterol levels. On the other hand, several meta-analyses have demonstrated that CPAP therapy [ 72 , 73 ] suppresses the recurrence of pulmonary vein isolation for AF. Therefore, CPAP therapy should also be actively considered in managing BP and preventing AF recurrence in OSA-related hypertension with AF.

Vascular remodeling

A potential pathophysiological role linking OSA to vascular remodeling (i.e., progressive aortic dilatation, increased risk for aneurysms, and aortic dissection) has been reported by several clinical studies [ 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 ]. Pathophysiological conditions associated with the development of these vascular remodeling in OSA include negative intrathoracic pressure, increased BP via sympathetic hyperactivity, and oxidative stress via cyclical hypoxemia-reoxygenation due to OSA (Fig.  2 ). Recent meta-analysis actually showed that aortic size was higher in patients with OSA than in their counterparts without OSA [ 75 ]. However, the results of this meta-analysis should be considered in the context of some limitations, such as the paucity of available data, and the methodological differences of the various studies.

Vascular Damage by OSA. OSA: obstructive sleep apnea, FMD Flow mediated dilation, PWV pulse wave velocity

Regarding the relationship between aortic dissection (AD) and OSA severity, a greater relation was found between moderate-to-severe OSA and AD (OR 4.43; 95% CI 2.59–7.59) [ 79 ]. Gaisl, et al. demonstrated the strong evidence for a positive association of thoracic aortic aneurysms (TAA) expansion with AHI [ 80 ]. On the other hand, in abdominal aortic aneurysms (AAA) patients, the rate of aortic diameter enlargement was significantly higher by 2.2 mm/year in the population with an AHI ≥ 30/h compared with an AHI 0–5/h [ 81 ]. We also demonstrated that patients with TAA, AAA, and AD showed high incidences of moderate to severe OSA [ 82 ]. Negative intrathoracic pressure could theoretically dilate the thoracic aorta via increased stress in the aortic wall, but would have little effect on the abdominal aorta. However, it is inconclusive which of the thoracic and abdominal vasculatures OSA more strongly impacts.

Treatment of OSA-related hypertension

Among the treatment modalities that come to the fore in OSA-related hypertension are CPAP, antihypertensive medications (beta-blocker, diuretics, ARB and CCB), and renal denervation (RDN). There are currently no specific clinical recommendations on whether to prioritize CPAP or antihypertensive medications in OSA-related hypertension. However, in hypertensive patients with moderate to severe OSA accompanied by sleepiness, it is common to prioritize CPAP therapy to improve sleep quality. Weight loss, physical exercise, reducing alcohol consumption, and smoking cessation are among the primary lifestyle changes recommended for OSA-related hypertension [ 83 ].

CPAP therapy

A number of studies have demonstrated that CPAP has modest but significant BP-lowering effects of 2–7 mmHg in SBP and of 2–5 mmHg in DBP in OSA-related hypertension [ 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 ] (Fig.  3 ). The effect of CPAP on BP varies among patients (Fig.  3 ). Higher BMI, severe OSA (AHI ≥ 30), hypersomnolence, higher BP values, untreated hypertension, nocturnal hypertension, treatment-resistant hypertension and adherence to CPAP are variables that have been associated with a greater improvement in BP in several studies [ 92 , 93 , 94 , 95 , 96 , 97 ]. HIPARCO RCT found a significant correlation between CPAP usage and reductions in 24-h mean BP, SBP, and DBP [ 98 ]. Best results for quality of life improvements and optimal reductions in BP occur when CPAP usage exceeds 4 hour/night [ 87 , 99 ]. Furthermore, recent meta-analyses suggest an even higher degree of daily CPAP adherence (at least 4.0–5.5 hour/night) to improve BP in patients with resistant hypertension and sleepiness [ 100 ].

Recent meta-analyses regarding the effect of CPAP treatment on blood pressure. CPAP Continuous positive airway pressure, SBP Systolic blood pressure, DBP Diastolic blood pressure

In the patients with non-sleepy OSA, CPAP therapy have no overall beneficial effects on subjective sleepiness, SBP, or cardiovascular risk compared with no active therapy. OSA patients who were less sleepy had lower BMI and lower CPAP adherence. This probably might be due to a lower respiratory arousal threshold. Comprehensive management including an active lifestyle and regular support of CPAP use is key to managing this kind of OSA [ 101 ]. Furthermore, CPAP withdrawal results in a clinically relevant increase in BP (office SBP): +5.4 mm Hg, home SBP : +9.0 mm Hg), which is considerably higher than in conventional CPAP trials [ 102 ].

In patients with nocturnal hypertension (non-dipper/riser types), CPAP often selectively lowers BP during sleep, leading to a normal dipper pattern [ 103 ]. In the aforementioned studies, HIPARCO RCT, among patients with OSA and resistant hypertension, CPAP treatment for 12 weeks compared with control resulted in a decrease in 24 h mean (−3.1 mmHg) and DBP (−3.2 mmHg) and an improvement in the nocturnal BP pattern [ 98 ].

As mentioned above, the antihypertensive effects of CPAP are modest. However, CPAP therapy exert beneficial effects on sympathovagal balance and arterial stiffness, independent of BP lowering [ 104 ]. Therefore, patients with moderate-to- severe OSA-related hypertension should undergo CPAP therapy as a first-line treatment.

Antihypertensive medications

CPAP therapy is effective at lowering BP, however, the magnitude of the decrease in BP is relatively modest, therefore, patients often need to also take antihypertensive medications to achieve optimal BP control (Table  3 ). However, current guidelines do not specify what type of antihypertensive therapy should be offered to patients with OSA and concomitant hypertension [ 5 , 8 ]. An earlier study conducted by Kraiczi et al. compared the effects of atenolol, hydrochlorothiazide, amlodipine, enalapril, and losartan on office and ambulatory BP in 40 OSA-related hypertension patients [ 105 ]. Compared with the other four medications, atenolol lowered the office DBP as well as mean night-time ambulatory SBP and DBP. These findings support the hypothesis that overactivity of the sympathetic nervous system is the most important mechanism involved in the development of hypertension in patients with OSA. Kario, et al. reported the BP-lowering effects of CCBs and beta-blockers using a trigger sleep BP monitor with an oxygen-triggered function in OSA-related hypertension [ 106 ]. The BP-lowering effects of nifedipine on the mean and minimum sleep SBP were stronger than those of carvedilol, but sleep SBP surge was only significantly reduced by carvedilol.

On the other hand, in terms of suppressing organ damage, RAAS inhibitors, such as ARB, may be useful in patients with OSA-related hypertension, especially in obese patients, because the RAAS is hyperactive and LVH is a common complication [ 107 , 108 ].

Fluid retension from the lower extremities to the upper body during sleep is strongly associated with OSA in hypertensive patients. Therefore, in OSA patients with obesity and a fluid retention, diuretics may be beneficial. Spironolactone reduced the severity of OSA and reduced BP in resistant hypertension patients with moderate-to-severe OSA [ 109 , 110 ]. A propensity score-matched cohort analysis of data from the French national sleep apnea registry demonstrated that diuretics appear to have a positive impact on OSA severity in overweight or moderately obese patients with hypertension [ 111 ].

Recently, Svedmyr, et al. investigated 5970 hypertensive patients with OSA on current antihypertensive treatment from the European Sleep Apnea Database (ESADA) cohort [ 112 ]. Monotherapy with beta-blocker was associated with lower SBP, particularly in non-obese middle-aged males with hypertension. Conversely, the combination of a beta-blocker and a diuretic was associated with lower SBP and DBP in hypertensive patients with moderate–severe OSA. Furthermore, another report in ESADA cohort suggests that ACEI or ARB, alone or in combination with other drug classes, provides a particularly strong reduction of BP and better BP control when combined with CPAP in OSA [ 113 ]. Considering that CPAP will remove repetitive hypoxia, most arousals, and the chronic sympathetic activation, it is likely that other mechanisms, such as RAAS activation, may play a dominant role following OSA treatment. This is speculated to be the reason why ACEI or ARB were effective in the CPAP treated OSA.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i)

A recent series of mega-scale clinical trials for sodium-glucose cotransporter 2 inhibitor (SGLT2i) indicated cardio-renal protective effects of SGLT2i [ 114 , 115 , 116 , 117 , 118 ], and some SGLT2is have now become the first-line treatment for T2DM with comorbid atherosclerotic cardiovascular disease (ASCVD) and heart failure. Furthermore, several studies have reported a lowering effect of SGLT2i on BP [ 119 , 120 ]. Although mechanisms underlying the BP-lowering effects of SGLT2i are unclear, SGLT2i presumably acts primarily by decreasing circulating plasma volume through osmotic and natriuretic diuresis in the early stages of administration and later by suppressing sympathetic nerve activity in the long term [ 121 , 122 ]. Wojeck, et al. reported that Ertugliflozin reduced incident OSA [ 123 ]. In the meta-analysis, Lin, et al. demonstrated that SGLT2i was shown to reduce AHI [ 124 ]. These results suggest that SGLT2i may not only have beneficial effects on OSA-related hypertension but also on OSA itself [ 125 ].

Angiotensin receptor-neprilysin inhibitor (ARNI)

The angiotensin receptor neprilysin inhibitor (ARNI) has recently been approved in Japan to treat hypertension [ 126 ]. Reductions in 24-hour, daytime, and nighttime BP have been documented during treatment with ARNI in patients with hypertension [ 127 , 128 , 129 ]. This potent 24-hour BP-lowering effects of ARNI may be effective for OSA-related hypertension characterized by resistant, nocturnal, and non-dipper hypertension [ 130 ]. Additionally, as previously mentioned, since OSA-related hypertension is associated with LVH [ 57 , 58 , 59 , 61 , 62 ] and left ventricular diastolic dysfunction [ 65 , 66 , 67 ], ARNI, which is characterized by so-called “reverse remodeling”, may be useful for OSA-related hypertension. Furthermore, in chronic heart failure patients with sleep apnea, ARNI treatment for 3 months in patients with OSA decreased the severity of OSA itself (the ENTRESTO-SAS study) [ 131 ].

However, both ARNI and SGLT2i are used in the United States to treat heart failure. In addition, there may be considerably less research on antihypertensive in OSA. Future research is needed to investigate the effect of ARNI and SGLT2i on BP in patients with OSA-related hypertension.

Glucose-dependent insulinotropic polypeptide receptor/ glucagon-like peptide-1 receptor agonist (GIP/GLP-1 RA)

Recently, a study evaluating the safety and efficacy of tirzepatide for the treatment of OSA and obesity was published (The SURMOUNT-OSA trials) [ 132 ]. Tirzepatide is a long-acting glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist that selectively binds to and activates both the GIP and GLP-1 receptors. The SURMOUNT-OSA trials were two 52-week, phase 3, multicenter, parallel-group, double-blind, randomized, controlled trials that were conducted at 60 sites across nine countries to evaluate the efficacy and safety of the maximum tolerated dose of weekly tirzepatide (10 mg or 15 mg) in adults with moderate-to-severe OSA and obesity. In this trial, tirzepatide reduced the AHI, body weight, hypoxic burden, high-sensitivity C-reactive protein concentration, and SBP [Estimated treatment differences :−7.6 mmHg (95% CI, −10.5 to −4.8), P  < 0.001, not receiving CPAP group]. The effect of tirzepatide on OSA-related hypertension is expected in the future.

Renal denervation

Increased sympathetic activity, consistently evident in patients with OSA, plays a key role in the development of resistant hypertension [ 35 ]. Therefore, OSA-related hypertension may represent a promising indication for RDN. In an RCT conducted with moderate-to-severe OSA patients with resistant hypertension, Warchol-Celinska, et al. demonstrated that RDN safely provided significant BP reduction compared with the control group [ 133 ]. However, the effect of RDN for OSA-related hypertension remains unclear due to differences in research design and other factors, such as sham procedure, ablations catheter, treatment adherence, sample size, observational periods, etc. Further large scale studies are warranted to assess the impact of RDN on OSA and its relation to BP decline and cardiovascular risk.

Future directions

As previously mentioned, it has become clear that OSA is caused not only by upper airway anatomic factors but also by several non-anatomic mechanisms [ 16 , 17 , 18 , 19 ]. Therefore, it is hypothesized that the pathophysiology of OSA-related hypertension is also not a single condition but is divided into several phenotypes. Elucidating the phenotypic mechanisms of OSA may potentially advance more personalized hypertension treatment strategies in the future.

Conclusions

OSA occurs at a high prevalence in hypertensive patients, particularly those with resistant hypertension. Additionally, it is highly prevalent among AF patients, warranting OSA screening. OSA-related hypertension is characterized by morning hypertension, nocturnal hypertension, non-dipper pattern, increased BPV, and pronounced arterial remodeling. CPAP therapy is the gold standard therapy for OSA but its effects on BP are relatively modest, often requiring combination therapy with antihypertensive medications. While there is insufficient evidence regarding the choice of antihypertensive medications, beta-blockers, diuretics, and ARBs may be used as monotherapy or in combination therapy depending on individual cases. Further evaluation of the efficacy of novel agents such as SGLT2i and ARNI, and GIP/GLP-1 RA is necessary. Elucidating the phenotypic mechanisms of OSA may potentially advance more personalized hypertension treatment strategies in the future.

Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005;365:1046–53.

Article   PubMed   Google Scholar  

Yeghiazarians Y, Jneid H, Tietjens JR, Redline S, Brown DL, El-Sherif N, et al. Obstructive Sleep Apnea and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation 2021;144:e56–e67.

Article   CAS   PubMed   Google Scholar  

Javaheri S, Barbe F, Campos-Rodriguez F, Dempsey JA, Khayat R, Javaheri S, et al. Sleep Apnea: Types, Mechanisms, and Clinical Cardiovascular Consequences. J Am Coll Cardiol. 2017;69:841–58.

Article   PubMed   PubMed Central   Google Scholar  

Cowie MR, Linz D, Redline S, Somers VK, Simonds AK. Sleep Disordered Breathing and Cardiovascular Disease: JACC State-of-the-Art Review. J Am Coll Cardiol. 2021;78:608–24.

Mancia G, Kreutz R, Brunstrom M, Burnier M, Grassi G, Januszewicz A, et al. 2023 ESH Guidelines for the management of arterial hypertension. J Hypertens. 2023;41:1874–2071.

Peppard PE, Young T, Palta M, et al. Prospective study of the association between sleep-disordered breathing and hypertension. N. Engl J Med. 2000;342:1378–84.

Hou H, Zhao Y, Yu W, Dong H, Xue X, Ding J, et al. Association of obstructive sleep apnea with hypertension: a systematic review and meta-analysis. J Glob Health. 2018;8:010405.

Umemura S, Arima H, Arima S, Asayama K, Dohi Y, Hirooka Y, et al. The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019). Hypertens Res. 2019;42:1235–481.

Kasai T, et al. JCS 2023 Guideline on Diagnosis and Treatment of Sleep Disordered Breathing in Cardiovascular Disease. Circ J. (in press).

Myers KA, Mrkobrada M, Simel DL. Does this patient have obstructive sleep apnea?: The Rational Clinical Examination systematic review. JAMA 2013;310:731–41.

Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328:1230–5.

Hastings PC, Vazir A, O’Driscoll DM, Morrell MJ, Simonds AK. Symptom burden of sleep-disordered breathing in mild-to-moderate congestive heart failure patients. Eur Respir J. 2006;27:748–55.

Kadhim K, Middeldorp ME, Elliott AD, Jones D, Hendriks JML, Gallagher C, et al. Self-Reported Daytime Sleepiness and Sleep-Disordered Breathing in Patients With Atrial Fibrillation: SNOozE-AF. Can J Cardiol. 2019;35:1457–64.

Goksan B, Gunduz A, Karadeniz D, Ağan K, Tascilar FN, Tan F, et al. Morning headache in sleep apnoea: clinical and polysomnographic evaluation and response to nasal continuous positive airway pressure. Cephalalgia 2009;29:635–41.

Lee RW, Vasudavan S, Hui DS, Prvan T, Petocz P, Darendeliler MA, et al. Differences in craniofacial structures and obesity in Caucasian and Chinese patients with obstructive sleep apnea. Sleep 2010;33:1075–80.

Carberry JC, Amatoury J, Eckert DJ. Personalized Management Approach for OSA. Chest 2018;153:744–55.

Wellman A, Jordan AS, Malhotra A, Fogel RB, Katz ES, Schory K, et al. Ventilatory control and airway anatomy in obstructive sleep apnea. Am J Respir Crit Care Med. 2004;170:1225–32.

Eckert DJ, Owens RL, Kehlmann GB, Wellman A, Rahangdale S, Yim‐Yeh S, et al. Eszopiclone increases the respiratory arousal threshold and lowers the apnoea/hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold. Clin Sci. 2011;120:505–14.

Article   Google Scholar  

Tietjens JR, Claman D, Kezirian EJ, De Marco T, Mirzayan A, Sadroonri B, et al. Obstructive Sleep Apnea in Cardiovascular Disease: A Review of the Literature and Proposed Multidisciplinary Clinical Management Strategy. J Am Heart Assoc. 2019;8:e010440.

Strollo PJ Jr, Soose RJ, Maurer JT, de Vries N, Cornelius J, Froymovich O, et al. Upper-airway stimulation for obstructive sleep apnea. N. Engl J Med. 2014;370:139–49.

O’Connor GT, Caffo B, Newman AB, Quan SF, Rapoport DM, Redline S, et al. Prospective study of sleep-disordered breathing and hypertension: the Sleep Heart Health Study. Am J Respir Crit Care Med. 2009;179:1159–64.

Marin JM, Agusti A, Villar I, Forner M, Nieto D, Carrizo SJ, et al. Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA 2012;307:2169–76.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Floras JS. Sympathetic nervous system activation in human heart failure: clinical implications of an updated model. J Am Coll Cardiol. 2009;54:375–85.

Kasai T, Floras JS, Bradley TD. Sleep apnea and cardiovascular disease: a bidirectional relationship. Circulation 2012;126:1495–510.

Jin ZN, Wei YX. Meta-analysis of effects of obstructive sleep apnea on the renin-angiotensin-aldosterone system. J Geriatr Cardiol. 2016;13:333–43.

CAS   PubMed   PubMed Central   Google Scholar  

Harańczyk M, Konieczyńska M, Płazak W. Endothelial dysfunction in obstructive sleep apnea patients. Sleep Breath. 2022;26:231–42.

Drager LF, Togeiro SM, Polotsky VY, Lorenzi-Filho G. Obstructive sleep apnea: a cardiometabolic risk in obesity and the metabolic syndrome. J Am Coll Cardiol. 2013;62:569–76.

Wang J, Yu W, Gao M, Zhang F, Gu C, Yu Y, et al. Impact of Obstructive Sleep Apnea Syndrome on Endothelial Function, Arterial Stiffening, and Serum Inflammatory Markers: An Updated Meta-analysis and Metaregression of 18 Studies. J Am Heart Assoc. 2015;4:e002454.

Shiina K, Tomiyama H, Takata Y, Usui Y, Asano K, Hirayama Y, et al. Concurrent presence of metabolic syndrome in obstructive sleep apnea syndrome exacerbates the cardiovascular risk: a sleep clinic cohort study. Hypertens Res. 2006;29:433–41.

Logan AG, Perlikowski SM, Mente A, Tisler A, Tkacova R, Niroumand M, et al. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens. 2001;19:2271–7.

Martínez-García MA, Gómez-Aldaraví R, Gil-Martínez T, Soler-Cataluña JJ, Bernácer-Alpera B, Román-Sánchez P. Sleep-disordered breathing in patients with difficult-to-control hypertension. Arch Bronconeumol. 2006;42:14–20.

Gonçalves SC, Martinez D, Gus M, de Abreu-Silva EO, Bertoluci C, Dutra I, et al. Obstructive sleep apnea and resistant hypertension: a case-control study. Chest 2007;132:1858–62.

Shiina K. Obstructive sleep apnea and cardiovascular disease. J Cardiol Jpn Ed. 2012;7:38–43.

Google Scholar  

Muxfeldt ES, Margallo VS, Guimarães GM, Salles GF. Prevalence and associated factors of obstructive sleep apnea in patients with resistant hypertension. Am J Hypertens. 2014;27:1069–78.

Genta-Pereira DC, Pedrosa RP, Lorenzi-Filho G, Drager LF. Sleep disturbances and resistant hypertension: association or causality? Curr Hypertens Rep. 2014;16:459.

Roderjan CN, de Hollanda Cavalcanti A, Cortez AF, Chedier B, Oliveira de Carvalho Carlos F, et al. Association between arterial stiffness and sleep apnoea in patients with resistant hypertension. J Hum Hypertens. 2022;36:1078–84.

Pickering TG. Arterial stiffness as a cause of resistant hypertension? J Clin Hypertens (Greenwich). 2007;9:390–5.

Baguet JP, Hammer L, Lévy P, Pierre H, Rossini E, Mouret S, et al. Night-time and diastolic hypertension are common and underestimated conditions in newly diagnosed apnoeic patients. J Hypertens. 2005;23:521–7.

Wolf J, Hering D, Narkiewicz K. Non-dipping pattern of hypertension and obstructive sleep apnea syndrome. Hypertens Res. 2010;33:867–71.

Seif F, Patel SR, Walia HK, Rueschman M, Bhatt DL, Blumenthal RS, et al. Obstructive sleep apnea and diurnal nondipping hemodynamic indices in patients at increased cardiovascular risk. J Hypertens. 2014;32:267–75.

Loredo JS, Ancoli-Israel S, Dimsdale JE. Sleep quality and blood pressure dipping in obstructive sleep apnea. Am J Hypertens. 2001;14:887–92.

Hla KM, Young T, Finn L, Peppard PE, Szklo-Coxe M, Stubbs M. Longitudinal association of sleep-disordered breathing and nondipping of nocturnal blood pressure in the Wisconsin sleep chort study. Sleep 2008;31:795–800.

Brown J, Yazdi F, Jodari-Karimi M, Owen JG, Reisin E. Obstructive Sleep Apnea and Hypertension: Updates to a Critical Relationship. Curr Hypertens Rep. 2022;24:173–84.

Bischof F, Egresits J, Schulz R, Randerath WJ, Galetke W, Budweiser S, et al. Effects of continuous positive airway pressure therapy on daytime and nighttime arterial blood pressure in patients with severe obstructive sleep apnea and endothelial dysfunction. Sleep Breath. 2020;24:941–51.

Marrone O, Bonsignore MR. Blood-pressure variability in patients with obstructive sleep apnea: current perspectives. Nat Sci Sleep. 2018;10:229–42.

Cheng YB, Guo QH, Xia JH, Zhang J, Xu TY, Li Y, et al. Obstructive sleep apnea in relation to beat-to-beat, reading-to-reading, and day-to-day blood pressure variability. Hypertens Res. 2024;47:1391–1400.

Kario K. Nocturnal Hypertension: New Technology and Evidence. Hypertension. 2018;71:997–1009.

Sasaki N, Nagai M, Mizuno H, Kuwabara M, Hoshide S, Kario K. Associations Between Characteristics of Obstructive Sleep Apnea and Nocturnal Blood Pressure Surge. Hypertension. 2018;72:1133–40.

Kario K. Management of Hypertension in the Digital Era: Small Wearable Monitoring Devices for Remote Blood Pressure Monitoring. Hypertension 2020;76:640–50.

Hoshide S, Yoshihisa A, Tsuchida F, Mizuno H, Teragawa H, Kasai T, et al. Pulse transit time-estimated blood pressure: a comparison of beat-to-beat and intermittent measurement. Hypertens Res. 2022;45:1001–7.

Bilo G, Pengo MF, Lombardi C, Parati G. Blood pressure variability and obstructive sleep apnea. A question of phenotype? Hypertens Res. 2019;42:27–28.

Shiina K, Tomiyama H, Takata Y, Matsumoto C, Odaira M, Kato K, et al. Obstructive Sleep Apnea as Possible Causal Factor for Visit-to-Visit Blood Pressure Variability. Circ J. 2016;80:1787–94.

Kansui Y, Matsumura K, Morinaga Y, Inoue M, Sakata S, Oishi E, et al. Impact of obstructive sleep apnea on long-term blood pressure variability in Japanese men: a cross-sectional study of a work-site population. Hypertens Res. 2018;41:957–64.

Clark CE, Taylor RS, Shore AC, Ukoumunne OC, Campbell JL. Association of a difference in systolic blood pressure between arms with vascular disease and mortality: a systematic review and meta-analysis. Lancet 2012;379:905–14.

Verberk WJ, Kessels AG, Thien T. Blood pressure measurement method and inter-arm differences: a meta-analysis. Am J Hypertens. 2011;24:1201–8.

Shiina K, Takata Y, Nakano H, Fujii M, Iwasaki Y, Kumai K, et al. Moderate to severe obstructive sleep apnea is independently associated with inter-arm systolic blood pressure difference: Tokyo Sleep Heart Study. J Hypertens. 2022;40:318–26.

Chami HA, Devereux RB, Gottdiener JS, Mehra R, Roman MJ, Benjamin EJ, et al. Left ventricular morphology and systolic function in sleep-disordered breathing: the Sleep Heart Health Study. Circulation 2008;117:2599–607.

Sekizuka H, Osada N, Akashi YJ. Impact of obstructive sleep apnea and hypertension on left ventricular hypertrophy in Japanese patients. Hypertens Res. 2017;40:477–82.

Cabrini ML, Macedo TA, Castro E, de Barros S, Azam I, Pio-Abreu A, et al. Obstructive sleep apnea and hypertension-mediated organ damage in nonresistant and resistant hypertension. Hypertens Res. 2023;46:2033–43.

Usui Y, Takata Y, Inoue Y, Tomiyama H, Kurohane S, Hashimura Y, et al. Severe obstructive sleep apnea impairs left ventricular diastolic function in non-obese men. Sleep Med. 2013;14:1–5.

Cuspidi C, Tadic M, Sala C, Gherbesi E, Grassi G, Mancia G. Obstructive sleep apnoea syndrome and left ventricular hypertrophy: a meta-analysis of echocardiographic studies. J Hypertens. 2020;38:1640–9.

Cuspidi C, Tadic M, Sala C, Gherbesi E, Grassi G, Mancia G. Targeting Concentric Left Ventricular Hypertrophy in Obstructive Sleep Apnea Syndrome. A Meta-analysis of Echocardiographic Studies. Am J Hypertens. 2020;33:310–5.

Yu L, Li H, Liu X, Fan J, Zhu Q, Li J, et al. Left ventricular remodeling and dysfunction in obstructive sleep apnea : Systematic review and meta-analysis. Herz 2020;45:726–38.

Tadic M, Gherbesi E, Faggiano A, Sala C, Carugo S, Cuspidi C. Is myocardial strain an early marker of systolic dysfunction in obstructive sleep apnoea? Findings from a meta-analysis of echocardiographic studies. J Hypertens. 2022;40:1461–8.

Wachter R, Lüthje L, Klemmstein D, Lüers C, Stahrenberg R, Edelmann F, et al. Impact of obstructive sleep apnoea on diastolic function. Eur Respir J. 2013;41:376–83.

Al-Sadawi M, Theodoropoulos K, Saeidifard F, Kiladejo A, Al-Ajam M, Salciccioli L, et al. Sleep Apnea as a Risk Factor for Diastolic Dysfunction: A Systematic Review and Meta-Analysis. Respiration 2022;101:1051–68.

Usui Y, Takata Y, Inoue Y, Shimada K, Tomiyama H, Nishihata Y, et al. Coexistence of obstructive sleep apnoea and metabolic syndrome is independently associated with left ventricular hypertrophy and diastolic dysfunction. Sleep Breath. 2012;16:677–84.

Tanaka N, Tanaka K, Hirao Y, Okada M, Ninomiya Y, Yoshimoto I, et al. Home Sleep Apnea Test to Screen Patients With Atrial Fibrillation for Sleep Apnea Prior to Catheter Ablation. Circ J. 2021;85:252–60.

Linz D, McEvoy RD, Cowie MR, Somers VK, Nattel S, Lévy P, et al. Associations of Obstructive Sleep Apnea With Atrial Fibrillation and Continuous Positive Airway Pressure Treatment: A Review. JAMA Cardiol. 2018;3:532–40.

Shiina K, Takata Y, Takahashi T, Kani J, Nakano H, Takada Y, et al. Nutritional Status and Sleep Quality Are Associated with Atrial Fibrillation in Patients with Obstructive Sleep Apnea: Results from Tokyo Sleep Heart Study. Nutrients 2023;15:3943.

Ignacio de Ulíbarri J, González-Madroño A, de Villar NG, González P, González B, Mancha A, et al. CONUT: a tool for controlling nutritional status. First validation in a hospital population. Nutr Hosp. 2005;20:38–45.

PubMed   Google Scholar  

Ng CY, Liu T, Shehata M, Stevens S, Chugh SS, Wang X. Meta-analysis of obstructive sleep apnea as predictor of atrial fibrillation recurrence after catheter ablation. Am J Cardiol. 2011;108:47–51.

Shukla A, Aizer A, Holmes D, Fowler S, Park DS, Bernstein S, et al. Effect of Obstructive Sleep Apnea Treatment on Atrial Fibrillation Recurrence: A Meta-Analysis. JACC Clin Electrophysiol. 2015;1:41–51.

Gaisl T, Bratton DJ, Kohler M. The impact of obstructive sleep apnoea on the aorta. Eur Respir J. 2015;46:532–44.

Gherbesi E, Tadic M, Faggiano A, Sala C, Carugo S, Cuspidi C. Sleep Apnea Syndrome and Large Artery Subclinical Damage: Targeting Thoracic Aortic Dilatation. Am J Hypertens. 2022;35:543–50.

Tomita Y, Kasai T, Ishiwata S, Daida H, Narui K. Aortic Knob Width as a Novel Indicator of Atherosclerosis and Obstructive Sleep Apnea. J Atheroscler Thromb. 2020;27:501–8.

Shiina K, Tomiyama H, Takata Y, Chikamori T. Aortic Knob Width: A Possible Marker of Vascular Remodeling in Obstructive Sleep Apnea. J Atheroscler Thromb. 2020;27:499–500.

Sampol G, Romero O, Salas A, Tovar JL, Lloberes P, Sagalés T, et al. Obstructive sleep apnea and thoracic aorta dissection. Am J Respir Crit Care Med. 2003;168:1528–31.

Zhou X, Liu F, Zhang W, Wang G, Guo D, Fu W, et al. Obstructive sleep apnea and risk of aortic dissection: A meta-analysis of observational studies. Vascular 2018;26:515–23.

Gaisl T, Rejmer P, Roeder M, Baumgartner P, Sievi NA, Siegfried S, et al. Obstructive sleep apnoea and the progression of thoracic aortic aneurysm: a prospective cohort study. Eur Respir J. 2021;57:2003322.

Mason RH, Ruegg G, Perkins J, Hardinge M, Amann-Vesti B, Senn O, et al. Obstructive sleep apnea in patients with abdominal aortic aneurysms: highly prevalent and associated with aneurysm expansion. Am J Respir Crit Care Med. 2011;183:668–74.

Saruhara H, Takata Y, Usui Y, Shiina K, Hashimura Y, Kato K, et al. Obstructive sleep apnea as a potential risk factor for aortic disease. Heart Vessels. 2012;27:166–73.

Kario K, Hettrick DA, Prejbisz A, Januszewicz A. Obstructive Sleep Apnea-Induced Neurogenic Nocturnal Hypertension: A Potential Role of Renal Denervation? Hypertension 2021;77:1047–60.

Fava C, Dorigoni S, Dalle Vedove F, Danese E, Montagnana M, Guidi GC, et al. Effect of CPAP on blood pressure in patients with OSA/hypopnea a systematic review and meta-analysis. Chest 2014;145:762–71.

Iftikhar IH, Valentine CW, Bittencourt LR, Cohen DL, Fedson AC, Gíslason T, et al. Effects of continuous positive airway pressure on blood pressure in patients with resistant hypertension and obstructive sleep apnea: a meta-analysis. J Hypertens. 2014;32:2341–50.

Schein AS, Kerkhoff AC, Coronel CC, Plentz RD, Sbruzzi G. Continuous positive airway pressure reduces blood pressure in patients with obstructive sleep apnea; a systematic review and meta-analysis with 1000 patients. J Hypertens. 2014;32:1762–73.

Bratton DJ, Gaisl T, Wons AM, Kohler M. CPAP vs Mandibular Advancement Devices and Blood Pressure in Patients With Obstructive Sleep Apnea: A Systematic Review and Meta-analysis. JAMA 2015;314:2280–93.

Liu L, Cao Q, Guo Z, Dai Q. Continuous Positive Airway Pressure in Patients With Obstructive Sleep Apnea and Resistant Hypertension: A Meta-Analysis of Randomized Controlled Trials. J Clin Hypertens (Greenwich). 2016;18:153–8.

Labarca G, Schmidt A, Dreyse J, Jorquera J, Enos D, Torres G, et al. Efficacy of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) and resistant hypertension (RH): Systematic review and meta-analysis. Sleep Med Rev. 2021;58:101446.

Shang W, Zhang Y, Liu L, Chen F, Wang G, Han D. Benefits of continuous positive airway pressure on blood pressure in patients with hypertension and obstructive sleep apnea: a meta-analysis. Hypertens Res. 2022;45:1802–13.

Sun L, Chang YF, Wang YF, Xie QX, Ran XZ, Hu CY, et al. Effect of Continuous Positive Airway Pressure on Blood Pressure in Patients with Resistant Hypertension and Obstructive Sleep Apnea: An Updated Meta-analysis. Curr Hypertens Rep. 2024;26:201–11.

Bazzano LA, Khan Z, Reynolds K, He J. Effect of nocturnal nasal continuous positive airway pressure on blood pressure in obstructive sleep apnea. Hypertension 2007;50:417–23.

Baguet JP, Barone-Rochette G, Pépin JL. Hypertension and obstructive sleep apnoea syndrome: current perspectives. J Hum Hypertens. 2009;23:431–43.

Logan AG, Tkacova R, Perlikowski SM, Leung RS, Tisler A, Floras JS, et al. Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex. Eur Respir J. 2003;21:241–7.

Martínez-García MA, Gómez-Aldaraví R, Soler-Cataluña JJ, Martínez TG, Bernácer-Alpera B, Román-Sánchez P. Positive effect of CPAP treatment on the control of difficult-to-treat hypertension. Eur Respir J. 2007;29:951–7.

Konecny T, Kara T, Somers VK. Obstructive sleep apnea and hypertension: an update. Hypertension 2014;63:203–9.

Montesi SB, Edwards BA, Malhotra A, Bakker JP. The effect of continuous positive airway pressure treatment on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Clin Sleep Med. 2012;8:587–96.

Martínez-García MA, Capote F, Campos-Rodríguez F, Lloberes P, Díaz de Atauri MJ, Somoza M, et al. Effect of CPAP on blood pressure in patients with obstructive sleep apnea and resistant hypertension: the HIPARCO randomized clinical trial. JAMA 2013;310:2407–15.

McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, et al. CPAP for prevention of cardiovascular events in obstructive sleep apnea. N. Engl J Med. 2016;375:919–31.

Oh A, Grivell N, Chai-Coetzer CL. What is a Clinically Meaningful Target for Positive Airway Pressure Adherence? Sleep Med Clin. 2021;16:1–10.

Altintas N, Riha RL. Non-sleepy obstructive sleep apnoea: to treat or not to treat? Eur Respir Rev. 2019;28:190031.

Schwarz EI, Schlatzer C, Rossi VA, Stradling JR, Kohler M. Effect of CPAP Withdrawal on BP in OSA: Data from Three Randomized Controlled Trials. Chest 2016;150:1202–10.

Akashiba T, Minemura H, Yamamoto H, Kosaka N, Saito O, Horie T. Nasal continuous positive airway pressure changes blood pressure “non-dippers” to “dippers” in patients with obstructive sleep apnea. Sleep 1999;22:849–53.

Shiina K, Tomiyama H, Takata Y, Yoshida M, Kato K, Saruhara H, et al. Effects of CPAP therapy on the sympathovagal balance and arterial stiffness in obstructive sleep apnea. Respir Med. 2010;104:911–6.

Kraiczi H, Hedner J, Peker Y, Grote L. Comparison of atenolol, amlodipine, enalapril, hydrochlorothiazide, and losartan for antihypertensive treatment in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2000;161:1423–8.

Kario K, Kuwabara M, Hoshide S, Nagai M, Shimpo M. Effects of nighttime single-dose administration of vasodilating vs sympatholytic antihypertensive agents on sleep blood pressure in hypertensive patients with sleep apnea syndrome. J Clin Hypertens (Greenwich). 2014;16:459–66.

Pépin JL, Tamisier R, Barone-Rochette G, Launois SH, Lévy P, Baguet JP. Comparison of continuous positive airway pressure and valsartan in hypertensive patients with sleep apnea. Am J Respir Crit Care Med. 2010;182:954–60.

Thunström E, Manhem K, Rosengren A, Peker Y. Blood Pressure Response to Losartan and Continuous Positive Airway Pressure in Hypertension and Obstructive Sleep Apnea. Am J Respir Crit Care Med. 2016;193:310–20.

Yang L, Zhang H, Cai M, Zou Y, Jiang X, Song L, et al. Effect of spironolactone on patients with resistant hypertension and obstructive sleep apnea. Clin Exp Hypertens. 2016;38:464–8.

Kasai T, Bradley TD, Friedman O, Logan AG. Effect of intensified diuretic therapy on overnight rostral fluid shift and obstructive sleep apnoea in patients with uncontrolled hypertension. J Hypertens. 2014;32:673–80.

Revol B, Jullian-Desayes I, Bailly S, Tamisier R, Grillet Y, Sapène M, et al. Who May Benefit From Diuretics in OSA?: A Propensity Score-Match Observational Study. Chest 2020;158:359–64.

Svedmyr S, Hedner J, Bonsignore MR, Lombardi C, Parati G, Ludka O, et al. Hypertension treatment in patients with sleep apnea from the European Sleep Apnea Database (ESADA) cohort - towards precision medicine. J Sleep Res. 2023;32:e13811.

Svedmyr S, Hedner J, Bailly S, Fanfulla F, Hein H, Lombardi C, et al. Blood pressure control in hypertensive sleep apnoea patients of the European Sleep Apnea Database cohort - effects of positive airway pressure and antihypertensive medication. Eur Heart J Open. 2023;3:oead109.

Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. EMPA-REG OUTCOME investigators: empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N. Engl J Med. 2015;373:2117–28.

Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. CANVAS program collaborative group: canagliflozin and cardiovascular and renal events in type 2 diabetes. N. Engl J Med. 2017;377:644–57.

Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N. Engl J Med. 2019;380:347–57.

Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, et al. Dapagliflozin in Patients with Chronic Kidney Disease. N. Engl J Med. 2020;383:1436–46.

Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, et al. Empagliflozin in Patients with Chronic Kidney Disease. N. Engl J Med. 2023;388:117–27.

Kario K, Okada K, Kato M, Nishizawa M, Yoshida T, Asano T, et al. 24-Hour blood pressurelowering effect of an SGLT-2 inhibitor in patients with diabetes and uncontrolled nocturnal hypertension: results from the randomized, placebo-controlled SACRA study. Circulation 2018;139:2089–97.

Tsukamoto S, Kobayashi K, Toyoda M, Hatori N, Kanaoka T, Wakui H, et al. Pretreatment body mass index affects achievement of target blood pressure with sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus and chronic kidney disease. Hypertens Res. 2024;47:628–38.

van Ruiten CC, Smits MM, Kok MD, Serné EH, van Raalte DH, Kramer M, et al. Mechanisms underlying the blood pressure lowering effects of dapagliflozin, exenatide, and their combination in people with type 2 diabetes: a secondary analysis of a randomized trial. Cardiovasc Diabetol. 2022;21:63.

Shiina K, Tomiyama H, Tanaka A, Imai T, Hisauchi I, Taguchi I, et al. Canagliflozin independently reduced plasma volume from conventional diuretics in patients with type 2 diabetes and chronic heart failure: a subanalysis of the CANDLE trial. Hypertens Res. 2023;46:495–506.

Wojeck BS, Inzucchi SE, Neeland IJ, Mancuso JP, Frederich R, Masiukiewicz U, et al. Ertugliflozin and incident obstructive sleep apnea: an analysis from the VERTIS CV trial. Sleep Breath. 2023;27:669–72.

Lin R, Yan W, He M, Liu B, Su X, Yi M, et al. The benefits of hypoglycemic therapy for patients with obstructive sleep apnea. Sleep Breath. 2024 https://doi.org/10.1007/s11325-024-03015-2 .

Kario K, Weber M, Ferrannini E. Nocturnal hypertension in diabetes: Potential target of sodium/glucose cotransporter 2 (SGLT2) inhibition. J Clin Hypertens (Greenwich). 2018;20:424–8.

Otsuka Pharmaceutical Co Ltd. Otsuka announces that Novartis Pharma’s ENTRESTO(R) received a new indication for treatment of hypertension in Japan [media release]. Accessed Feb 26, 2024. https://www.otsuka.co.jp/en/company/newsreleases/2021/20210927_2.html .

Williams B, Cockcroft JR, Kario K, Zappe DH, Brunel PC, Wang Q, et al. Effects of sacubitril/valsartan versus olmesartan on central hemodynamics in the elderly with systolic hypertension: the PARAMETER study. Hypertension 2017;69:411–20.

Kario K, Sun N, Chiang FT, Supasyndh O, Baek SH, Inubushi-Molessa A, et al. Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension: a randomized, double-blind, placebo controlled study. Hypertension 2014;63:698–705.

Kario K, Rakugi H, Yarimizu D, Morita Y, Eguchi S, Iekushi K. Twenty-Four-Hour Blood Pressure-Lowering Efficacy of Sacubitril/Valsartan Versus Olmesartan in Japanese Patients With Essential Hypertension Based on Nocturnal Blood Pressure Dipping Status: A Post Hoc Analysis of Data From a Randomized, Double-Blind Multicenter Study. J Am Heart Assoc. 2023;12:e027612.

Kario K, Williams B. Nocturnal Hypertension and Heart Failure: Mechanisms, Evidence, and New Treatments. Hypertension 2021;78:564–77.

Jaffuel D, Nogue E, Berdague P, Galinier M, Fournier P, Dupuis M, et al. Sacubitril-valsartan initiation in chronic heart failure patients impacts sleep apnea: the ENTRESTO-SAS study. ESC Heart Fail. 2021;8:2513–26.

Malhotra A, Grunstein RR, Fietze I, Weaver TE, Redline S, Azarbarzin A, et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. N Engl J Med. 2024 https://doi.org/10.1056/NEJMoa2404881 .

Warchol-Celinska E, Prejbisz A, Kadziela J, Florczak E, Januszewicz M, Michalowska I, et al. Renal Denervation in Resistant Hypertension and Obstructive Sleep Apnea: Randomized Proof-of-Concept Phase II Trial. Hypertension 2018;72:381–90.

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Shiina, K. Obstructive sleep apnea -related hypertension: a review of the literature and clinical management strategy. Hypertens Res (2024). https://doi.org/10.1038/s41440-024-01852-y

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Pregnancy Induced Hypertension and Associated Factors among Women Attending Delivery Service at Mizan-Tepi University Teaching Hospital, Tepi General Hospital and Gebretsadik Shawo Hospital, Southwest, Ethiopia

Tesfaye abera gudeta.

1 MizanTepi University, College of Health science, Department of Nursing, Maternal Health Nursing Unit

Tilahun Mekonnen Regassa

2 MizanTepi University, College of Health Science, Department of Nursing, adult Health Hursing Unit

Disorders of pregnancy induced hypertensive are a major health problem in the obstetric population as they are one of the leading causes of maternal and perinatal morbidity and mortality. The World Health Organization estimates that at least one woman dies every seven minutes from complications of hypertensive disorders of pregnancy. The objective of this study is to assess pregnancy induced hypertension and its associated factors among women attending delivery service at Mizan-Tepi University Teaching Hospital, Gebretsadikshawo Hospital and Tepi General Hospital.

A health facility based cross-sectional study was carried out from October 01 to November 30/2016. The total sample size (422) was proportionally allocated to the three hospitals. Systematic sampling technique was used to select study participants. Variables with p-value of less than 0.25 in binary logistic regression were entered into the multivariable logistic regression to control cofounding. Odds ratio with 95% confidence interval was used. P-value less than 0.05 was considered as statistically significant.

The prevalence of pregnancy induced hypertension was 33(7.9%); of which 5(15.2%) were gestational hypertension, 12 (36.4%) were mild preeclampsia, 15(45.5%) were severe preeclampsia and 1 (3%) eclampsia. Positive family history of pregnancy induced hypertension [AOR5.25 (1.39–19.86)], kidney diseases (AOR 3.32(1.04–10.58)), having asthma [AOR 37.95(1.41–1021)] and gestational age (AOR 0.096(0.04-.23)) were predictors of pregnancy induced hypertension.

The prevalence of pregnancy induced hypertension among women attending delivery service was 7.9%. Having family history of pregnancy induced hypertension, chronic kidney diseases and gestational age were predictors of pregnancy induced hypertension.

Introduction

Hypertension in pregnancy is a systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or both. Both systolic and diastolic blood pressure raises are important in the identification of Pregnancy induced hypertension ( 1 ). Pregnancy induced hypertension (PIH) is hypertension that occurs after 20 weeks of gestation in women with previously normal blood pressure. The broad classification of pregnancy-induced hypertension during pregnancy is gestational hypertension, pre-eclampsia and eclampsia ( 2 ).

Severe preeclampsia in pregnancy is a systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg or both. Eclampsia is a severe type of pregnancy induced hypertension, and it happens in about one in 1,600 pregnancies and develops near the end of pregnancy ( 4 ). The three primary characteristics of pregnancy induced hypertension conditions are high blood pressure, protein in the urine and pathologic edema ( 3 – 5 ).

Pregnancy induced hypertension is a major contributors to maternal and perinatal morbidity and mortality. In the United States, about 15% of maternal deaths are attributable to hypertension, making it the second leading cause of maternal mortality. Severe hypertension increases the mother's risk of cardiac failure, heart attack, renal failure and cerebral vascular accidents. In addition, the fetus is at increased risk from complications like poor placental transfer of oxygen, growth restriction, preterm birth, placental abruption, stillbirth and neonatal death ( 2 ). Hypertensive disorders represent the most common medical complications of pregnancy with a reported incidence of 5–10% ( 6 , 7 ).

Globally, preeclampsia is a leading cause of maternal and neonatal mortality and morbidity, predominantly in developing countries. The disorder is usually diagnosed in late pregnancy by the presence of high blood pressure with proteinuria and/or edema. Prevention of any disease process needs awareness of its prevalence, etiology and pathogenesis ( 8 ). The World Health Organization estimates that at least one woman dies every seven minutes from complications of pregnancy induced hypertension disorders. Pregnancy complicated with hypertensive disorder is related with increased risk of adverse fetal, neonatal and maternal outcome ( 9 ).

Null parity, multiple pregnancies, history of chronic hypertension, gestational diabetes, fetal malformation , obesity, extreme maternal age (less than 20 or over 40 years), history of PIH in previous pregnancies and chronic diseases like renal disease, diabetes mellitus, cardiac disease, unrecognized chronic hypertension, positive family history of PIH which shows genetic susceptibility, psychological stress, alcohol use, rheumatic arthritis, extreme underweight and overweight, asthma and low level of socioeconomic status are the risk factors for PIH ( 5 , 10 , 11 ). According to a study in South Africa, the incidence of hypertensive disorders of pregnancy was 12%, and it was the commonest cause of maternal death which contributed 20.7% of maternal deaths ( 12 ).

As the Ethiopian Demographic Health survey (EDHS) 2016 reported, maternal mortality ratio is 412 deaths per 100,000 live births, and pregnancy induced hypertension has a countless role for this maternal death ( 13 ). A review study conducted on the causes of maternal mortality in Ethiopia indicated that the proportion of maternal mortality in Ethiopia due to hypertensive disorders between the year of 1980 and 2012 was in an increased trend from 4%–29% ( 14 ).

The Federal Ministry of Health has applied multi-pronged approaches to reducing maternal and newborn morbidity and mortality by improving access to and strengthening facility-based maternal and newborn services but the maternal morbidity and mortality due to pregnancy induced hypertension was in an increasing trend ( 15 ).

Despite the fact that pregnancy induced hypertension is a leading causes of maternal morbidity and mortality during pregnancy, little is known about the current magnitude of PIH, its associated factors among women attending delivery service in Ethiopia and specifically in study areas. Therefore, the objective of this study was to assess pregnancy induced hypertension and its associated factors among women attending delivery service at Mizan Tepi University Teaching Hospital, Gebretsadikshawo Hospital and Tepi General Hospital, Southwest Ethiopia.

Materials and Methods

Study area and period : The study was conducted in Mizan Tepi University Teaching Hospital, Tepi General Hospital and Gebretsadikshawo Hospital found in Benchi Maji, Sheka and Kefa zones from October 01-November 30/2016. Mizan Tepi University Teaching Hospital is located in Bench Maji Zone 560 kms far from Addis Ababa, and Gebretsadikshawo is found 441 kms from Addis Ababa in Kefa Zone and Tepi General Hospital is located in Sheka Zone 565 kms from the capital city of Ethiopia, Addis Ababa.

Study design: Health facility based cross-sectional study design with quantitative data collection method was used.

Source and study population : All women who attended delivery service in Mizan Tepi University teaching Hospital, Tepi General Hospital and Gebretsadikshawo Hospital were considered as source population whereas all sampled women were considered as study population.

Inclusion and exclusion criteria : All admitted women in delivery ward with gestational age greater than 28 weeks were included to the study whereas women with known chronic hypertension and those who were critically ill and unable to communicate after full course of treatment were excluded from the study. A woman who was critically ill due to PIH was waited until she recovered from her illness.

Sample size and sampling technique : The sample size was calculated by using a single population proportion sample size calculation formula by considering the following assumptions: d = margin of error of 5% with 95% confidence interval and P=50% in order to maximized the sample size. By considering 10% none response rate, the final sample size became 422.

The total sample size was proportionally allocated to the three public hospitals based on their source population from each hospital. The source population of each hospital was taken from six-month delivery reports. Then, the average was considered as source population (1030). Afterwards, the study participants were systematically selected from each hospital, and admitted mothers for delivery who were eligible to the study were included until the required sample size was obtained ( Figure 1 ).

Schematic presentation of sampling procedure

Pregnancy induced hypertension (PIH) : A pregnant women attending delivery service with high blood pressure (≥140/90mmHg) after 28 weeks of gestation was measured two times six hours apart by trained data collectors and with or without proteinuria. The diagnosis of PIH was confirmed by a physician working in labour ward. Pregnancy induced hypertension includes gestational hypertension, pre-eclampsia and eclampsia.

Psychological stress : A woman who scored greater than the mean score was considered as psychologically stressed.

Data collection instruments : The data was collected by using pre-tested structured questionnaire adapted from a validated questionnaire ( 16 , 17 ). The questionnaire was first adapted in English and translate into Amharic by an expert and translated back to English to see the consistency of the item. The questionnaire contains sections for assessing demographics and associated factors. The questions and statements were grouped and arranged according to the particular objectives that they were aimed to address. Six data collectors who were degree-holding midwives in qualification fluent in speaking, writing and reading Amharic language were recruited purposefully from their respective facilities to maintain the quality of the data. also Three supervisors were recruited for the same purpose.

Data collection procedure : Data was collected through face-to-face interview, measurements and reviewing of medical records of the mother using pretested structured questionnaire by trained data collectors. Data were collected day and night in order not to miss the cases. Blood pressure reading was taken while the woman was seated in the upright position and supine position using a mercury sphygmomanometer apparatus, and for referred women, BP and protein urea at time of diagnosis were taken from referral form.

Data processing and analysis : EPI data statistical software version 3.1 and Statistical Package for Social Sciences (SPSS) software version 21.0 were used for data entry and analysis. After organizing and cleaning the data, frequencies and percentages were calculated to all variables that were related to the objectives of the study. Variables with p-value less than 0.25 in binary logistic regression analysis were entered into the multivariable logistic regression analysis to control confounders. Odds ratio with 95% confidence interval was used to examine associations between dependent and independent variables. P-value less than 0.05 was considered significant. Finally, the result was presented by using tables and narrative forms.

Data quality control measures : The quality of the data was assured by using validated and pretested questionnaire. Prior to the actual data collection, pre-testing was done on 5% of the total study subjects at Chena Hospital which was not included in the actual study, and based on the findings necessary amendments were made. Reliability of the questions used to measure psychological stress of mothers was tested by Cronbach's alpha test (0.89). Data collectors were trained for one day intensively on the study instrument and data collection procedure that included the relevance of the study, the objective of the study, confidentiality of the information, informed consent and interview technique. The data collectors worked under close supervision of the supervisors to ensure adherence to correct data collection procedures. The supervisors reviewed the filled questionnaires at the end of data collection every day for completeness.

Every morning, the supervisors and the data collectors conducted a morning session to solve problem, if encountered, as early as possible and to take corrective measures accordingly. Moreover, the data was carefully entered and cleaned before the analysis.

Ethical considerations : The study did not involve any experiment, and no harm was expected on human subjects, exception of benefit. Ethical clearance from Mizan Tepi University and permission from respective authorities and written consent of respondents' were obtained before the data collection. To get full co-operation, respondents were reassured about the confidentiality of their responses. They were also informed their voluntarily participation and right to take part or terminate at any time they wanted. Since the subjects of the study could raise ethical issues, care was taken in the design of the questionnaire.

Socio-demographic characteristics : Among the total study participants, 155(37.3%) were aged between 20–24 years, more than half 236(56.7%)of the respondents were orthodox in religion, and 403(96.9%) were married. Almost half of the participants were from rural areas, 214(51.4%). Regarding their educational level, 150(36.1%) of the respondents attended primary school, the majority 276(66.3%) were housewives, and 230(55.3) of the family sizes of the participants were between 3–4 ( Table 1 ).

Distribution of the study participants by their socio- demographic characteristics at MTUTH, Tepi and Gebretsadikshawo hospitals, south west Ethiopia, Nov, 2016

Prevalence of pregnancy induced hypertension : The prevalence of pregnancy induced hypertension among women attending delivery service in the three hospitals of this study was 33(7.9%). The mean of systolic blood pressure was 110.72±15.315 with range of 90 mmHg to 210 mmHg, and the mean of diastolic blood pressure was 72.71±13.093 with range of 50 mmHg to160 mmHg. The result of proteinuria ranged from negative to 3+ in dipstick test. Out of the total of women who had pregnancy induced hypertension, 5(15.2%) were gestational hypertension, 12(36.4%) were mild preeclampsia, 15(45.5%) were severe preeclampsia and 1(3%) were eclampsia.

Variables related to obstetric conditions : Out of the pregnant women who participated in study, 408(98.1%) of the pregnancy were wanted, and 224(53.8%) of pregnancy were multigravida. Regarding parity of the women, 261(62.7%) had parity of 1–4, and the majority, 309(74.3%) of gestational ages were between 37 and 42 weeks. Only 5(1.3%) of the pregnant mothers who were admitted for delivery had previous history of PIH, only 3(0.8) of them had history of gestational diabetic mellitus while 20(4.8%) of the pregnancies were multiple ones ( Table 2 ).

Frequency distribution of variables related to obstetric conditions among women attending delivery service at MTUTH, Tepi and Gebretsadikshawo hospitals, southwest Ethiopia, 2016

NB : GDM=Gestational Diabetic Mellitus

Medical and family history related variables : Regarding medical and family histories of illness, out of the total, 43(10.3%) had family history of chronic hypertension, 16(3.8%) of them had family history of pregnancy induced hypertension commonly from their mothers, 11(84.6). Regarding kidney diseases, 32(7.7%) of the respondents had history of kidney diseases during the current pregnancy, and only 7(1.7%) of them had history of chronic diabetic mellitus. From the study participants, only 36(8.7%) of them had family history of diabetic mellitus and 2 (0.5%) of them had history of asthma ( Table 3 ).

Distributions of medical and family history risk factors among delivered women at MTUTH, Tepi and Gebretsadikshawo hospitals, South west Ethiopia, 2016

Variables related to personal risks : Among the respondents, 9(2.2%) had history of smoking cigarette, of which 2(0.5%) were current smokers while 23(5.5%) of the family members smoked cigarette, mostly the husbands, 20 (87%). From the total of the mothers attending delivery service, 350(84.1%) had mid upper arm circumference ≥21cm whereas 66(15.9%) them were <21cm.

Regarding sleeping pattern of women during current pregnancy, more than half, 250(60.1%), of them sleep ≥9 hours per night, and 164(39.4%) of women were doing scheduled regular physical exercise during their current pregnancy. Based on the nine items used to assess psychological stress, 171(41.1%) of the women had psychological stress during current pregnancy ( Table 4 ).

Distribution of the study subjects by their personal risk factors among women attending delivery service at MTUTH, Tepi and Gebretsadikshawo hospitals, Southwest Ethiopia, Nov, 2016

Variables related to health facility utilization : According to this study, 406(97.6%) of the pregnant mothers utilized health facility for ANC follow-up, of which 8(2%) attended first visit of their routine ANC follow-up and 398 (98%) attended ANC more than twice. Regarding utilization of health facilities for health problems other than the current pregnancy, only 132(31.7%) utilized health facilities for gynecology, surgical and medical problems.

Predictors of pregnancy induced hypertension : In the multivariable logistic regression analysis, factors contributing to pregnancy induced hypertension were identified: Positive family history of pregnancy induced hypertension, kidney diseases during pregnancy, asthma and gestational age had statistically significant associations with pregnancy induced hypertension ( Table 5 ).

Multivariable logistic regression analysis of pregnancy induced hypertension and associated factors among women attending delivery service at MTUTH, Tepi and Gebretsadikshawo hospital, Southwestern 11 Ethiopia, 2016

The pregnant women attending delivery service with family history of pregnancy induced hypertension were five times more likely to develop pregnancy induced hypertension than those who did not have family history of pregnancy induced hypertension (AOR=5.25 at 95%CI= (1.39–19.86).

As this study showed, having kidney diseases during pregnancy was 3.25 times more likely to develop pregnancy induced hypertension as compared to pregnant mothers who did not have kidney diseases during pregnancy (AOR=3.32 at 95%CI= (1.04–10.58). Women who had asthma more likely develop pregnancy induced hypertension by 38 times as compared with women those attending delivery service did not have asthma (at 95% CI, AOR=37.95(1.41–1021).

In this study, gestational was age identified as predictor, indicating that women with gestational age greater than or equal to 37 weeks were less likely to develop pregnancy induced hypertension by 9.6% as compared to women gestational age less than 37 weeks (AOR=0.096 at 95% CI(0.04–0.23) ( Table 5 ).

The prevalence of pregnancy induced hypertension among women attending delivery service in this study was 33(7.9%). This might increase the morbidity and mortality of the mother and the fetus. If appropriate preventive measures are not taken for the risk of pregnant women, in long term, it might be the first cause of maternal mortality. The prevalence of PIH in this study is similar with the study conducted in India which was 7.8 % ( 18 ). However, it is slightly lower than the findings of studies done in Iran 9.8% ( 19 ), in Jimma University Specialized Hospital (8.48%) and Dessie Referal Hospital, 8.4%( 20 , 21 ).

This difference might be attributed to differences in the study period and study design. The population might also be different in lifestyle and culture. However, the prevalence in this study is still greater than the study done in Ethiopia at Tikur Anbessa Hospital which was 5.3% and Mettu Karl Hospital, 2.4% ( 7 , 22 ).

This discrepancy might be because of differences in the study period, study design and health seeking behaviors of pregnant women. In addition, the gap might be due to current health policy which focuses on implementation of focused ANC and exempted service for maternal care which increases the health care seeking behavior of pregnant women and delivery at health facility which increases detection of the case.

In this study, some associated factors of pregnancy induced hypertension were also identified. Having family history of pregnancy induced hypertension had about five times greater odds of developing pregnancy induced hypertension. This is consistent with the study conducted in Ghana ( 23 ) and in the textbook of current diagnosis and treatment in obstetrics and gynecology ( 2 ). This might have occurred due to genetic factors that contribute to the physiologic predisposition of pregnancy induced hypertension.

This study revealed that having kidney diseases during pregnancy increases the likelyhood of pregnancy induced hypertension. This finding was similar with the study conducted in Public Health facility of Dirashe Woreda which showed that preexisting renal diseases had statistically significant associations with pregnancy induced hypertension ( 24 ). Other theories also support that renal physiological function had direct relationship with cardiovascular system ( 2 ).

This study also showed that women who had asthma are at more risk to develop pregnancy induced hypertension than those who did not have asthma. This is in line with the study conducted in New York and Canada ( 25 , 26 ). The other variable associated with PIH in this study was gestational age, which showed that women with gestational age greater than or equal to 37 weeks were less likely to develop pregnancy induced hypertension than women with gestational age less than 37 weeks. However this is inconsistent with the literature. This might be due to the fact that the population of this study was women attending delivery service so that more women with PIH might be delivered before and around 37 weeks of gestational age to reduce the risk of maternal and fetal complication.

As any other cross-sectional study, this study has strength and weakness. The possible limitations may arise from women's readiness and ability to provide every information about themselves and their family correctly based on which PIH was related and; recall and social desirability bias may be introduced during data collection from the pregnant women as they were self-referred. However, measure has been taken to minimize these limitations by using targeted questions.

The other limitation of this study was few variables have small observation which causes lower precision, so it was carefully interpreted. Inclusion of all hospitals from the three zones was strength of this study.

The prevalence of pregnancy induced hypertension among women attending delivery service was 7.9% which indicates that a significant number of women attending delivery services at Mizan Tepi Teaching Hospital, Gebretsadikshawo and Tepi Hospital developed pregnancy induced hypertension. Among pregnancy induced hypertensions, severe preeclampsia was the most common. Having family history of pregnancy induced hypertension, chronic renal diseases (kidney diseases) and gestational age were the factors associated with pregnancy induced hypertension.

Acknowledgment

We are extremely grateful to the Mizan Tepi University for grant fund, study subjects involved in the study, data collectors and supervisors.

• Research article
• Open access
• Published: 02 September 2024

Cruciferous vegetables lower blood pressure in adults with mildly elevated blood pressure in a randomized, controlled, crossover trial: the VEgetableS for vaScular hEaLth (VESSEL) study

• Emma L. Connolly 1 ,
• Alex H. Liu 1 ,
• Simone Radavelli-Bagatini 1 ,
• Armaghan Shafaei 2 ,
• Mary C. Boyce 3 ,
• Lisa G. Wood 4 ,
• Lyn McCahon 1 ,
• Henrietta Koch 5 ,
• Marc Sim 1 , 6 ,
• Caroline R. Hill 1 ,
• Benjamin H. Parmenter 1 ,
• Nicola P. Bondonno 1 , 7 ,
• Amanda Devine 1 ,
• Kevin D. Croft 5 ,
• Richard Mithen 8 ,
• Seng Khee Gan 6 , 9 ,
• Carl J. Schultz 6 , 10 ,
• Richard J. Woodman 11 ,
• Catherine P. Bondonno 1 , 6 ,
• Joshua R. Lewis 1 , 6 , 12 ,
• Jonathan M. Hodgson 1 , 6 &
• Lauren C. Blekkenhorst 1 , 6  

BMC Medicine volume  22 , Article number:  353 ( 2024 ) Cite this article

Metrics details

Higher cruciferous vegetable intake is associated with lower cardiovascular disease risk in observational studies. The pathways involved remain uncertain. We aimed to determine whether cruciferous vegetable intake (active) lowers 24-h brachial systolic blood pressure (SBP; primary outcome) compared to root and squash vegetables (control) in Australian adults with mildly elevated BP (SBP 120–160 mmHg inclusive).

In this randomized, controlled, crossover trial, participants completed two 2-week dietary interventions separated by a 2-week washout. Cruciferous vegetables were compared to root and squash vegetables (~ 300 g/day) consumed with lunch and dinner meals. Participants were blinded to which interventions were the active and control. Adherence was assessed using food diaries and biomarkers (S-methyl cysteine sulfoxide (SMCSO, active) and carotenoids (control)). Twenty-four-hour brachial ambulatory SBP and secondary outcomes were assessed pre- and post each intervention. Differences were tested using linear mixed effects regression.

Eighteen participants were recruited (median (IQR) age: 68 (66–70); female: n  = 16/18; mean ± SD clinic SBP: 135.9 ± 10.0 mmHg). For both interventions, 72% participants had 100% adherence (IQR: 96.4–100%). SMCSO and carotenoids were significantly different between interventions (mean difference active vs. control SMCSO: 22.93 mg/mL, 95%CI 15.62, 30.23, P  < 0.0001; carotenoids: − 0.974 mg/mL, 95%CI − 1.525, − 0.423, P  = 0.001). Twenty-four-hour brachial SBP was significantly reduced following the active vs. control (mean difference − 2.5 mmHg, 95%CI − 4.2, − 0.9, P  = 0.002; active pre: 126.8 ± 12.6 mmHg, post: 124.4 ± 11.8 mmHg; control pre: 125.5 ± 12.1 mmHg, post: 124.8 ± 13.1 mmHg, n  = 17), driven by daytime SBP (mean difference − 3.6 mmHg, 95%CI − 5.4, − 1.7, P  < 0.001). Serum triglycerides were significantly lower following the active vs. control (mean difference − 0.2 mmol/L, 95%CI − 0.4, − 0.0, P  = 0.047).

Conclusions

Increased intake of cruciferous vegetables resulted in reduced SBP compared to root and squash vegetables. Future research is needed to determine whether targeted recommendations for increasing cruciferous vegetable intake benefits population health.

Trial registration

Clinical trial registry ACTRN12619001294145.  https://www.anzctr.org.au

Peer Review reports

Increasing vegetable intake is widely recommended to reduce cardiovascular disease (CVD) risk [ 1 , 2 , 3 ]. Historically researched for their anti-cancer properties, one group of vegetables that have been proposed to have superior benefits on CVD are cruciferous vegetables (e.g., arugula, bok choy, broccoli, Brussels sprouts, cabbage, cauliflower, collard greens, horseradish, kale, radish, turnips, and watercress) [ 4 , 5 , 6 ]. Whilst these vegetables are commonly consumed globally, cruciferous vegetables typically make up a small proportion of total vegetable intake (5–24%) [ 7 ]. Cruciferous vegetable intake was found to be inversely associated with CVD risk in a dose–response meta-analysis of prospective cohort studies [ 8 ]. Similar results were observed when objective markers of cruciferous vegetable intake (i.e., urinary thiocyanate) were considered [ 9 ]. More research is required to establish any causal pathways through which cruciferous vegetables benefit cardiovascular health.

Hypertension is the leading risk factor for CVD with its prevalence increasing with age [ 10 ]. Glucosinolates are found almost exclusively in cruciferous vegetables and have been shown to lower blood pressure in animals, but evidence in humans is limited [ 4 ]. These compounds have been proposed to exhibit cardiovascular health benefits, such as reduced glycemic-related complications, improved endothelial function, and reduced formation and progression of atherosclerotic plaques [ 4 ]. Additionally, cruciferous vegetables also contain several other components that likely influence blood pressure, such as nitrate and vitamin K [ 11 , 12 ].

Few intervention studies have been conducted in humans to investigate the effects of cruciferous vegetables on risk factors for CVD, such as elevated blood pressure. As previously described in the published protocol [ 13 ], the primary objective of the VEgetableS for vaScular hEaLth (VESSEL) study was to determine if daily consumption of cruciferous vegetables results in lower 24-h brachial systolic blood pressure (SBP) in middle-aged and older adults with mildly elevated blood pressure compared to root and squash vegetables. Our a priori hypothesis was that daily consumption of cruciferous vegetables, in comparison to root and squash vegetables, would result in a greater reduction in ambulatory blood pressure. Secondary objectives were to determine if cruciferous vegetables were superior in improving other brachial and arterial ambulatory blood pressures, arterial stiffness, and circulating biomarkers of oxidative stress and inflammation and other CVD risk factors.

The Edith Cowan University Human Research Ethics Committee granted ethics approval for the VESSEL Study (2019–00356-BLEKKENHORST) and the trial was registered at www.anzctr.org.au (ACTRN12619001294145). Written informed consent was obtained from all participants. Procedures were followed in accordance with institutional guidelines.

Study design

The VESSEL study was a randomized, controlled, crossover trial with two 2-week dietary intervention periods, as previously described in the protocol [ 13 ]. Intervention periods were separated by a 2-week washout (Fig.  1 ). The study was conducted at the Royal Perth Hospital Research Foundation, Perth, Australia.

Overview of study design

Participants

Six newspaper advertisements were placed at varying intervals between August 2019 and March 2021 to recruit men and women aged 50 to 75 years with mild to moderately elevated blood pressure (SBP 120–160 mmHg, inclusive, and diastolic (DBP) < 100 mmHg) from the general population of Perth, Australia. Detailed inclusion and exclusion criteria are shown in Additional File 1: Table S1 [ 2 , 14 ].

Screening blood pressure was assessed using a CARESCAPE Dinamap v100 Vital Signs Monitor (GE Healthcare, Buckinghamshire, UK). After resting in a supine position for 5 min, five blood pressure and heart rate measurements were taken at 1-min intervals. The first measurement was excluded, and the next four readings were averaged to calculate mean resting blood pressure.

Randomization

Using computer-generated random numbers, eligible participants were randomly assigned to one of two intervention sequence orders (1:1 allocation). The intervention sequence orders were placed in opaque sealed envelopes by a study investigator and opened in consecutive order as participants were enrolled in the study.

Dietary intervention

Participants completed two 2-week dietary interventions in random order, as follows:

Active: four serves (~ 300 g/day) of cruciferous vegetables (broccoli, kale, cauliflower, and cabbage) consumed as two soups: one at lunch and one at dinner (~ 600 mL soup/day, ~ 600 kJ/day).

Control: four serves (~ 300 g/day) of root and squash vegetables (potato, sweet potato, carrot, and pumpkin) consumed as two soups: one at lunch and one at dinner (~ 600 mL soup/day, ~ 600 kJ/day).

All soups were prepared at Edith Cowan University, Joondalup Campus, Perth, Australia, using standardized recipes, as detailed in the protocol [ 13 ]. Vegetables were chopped and boiled prior to blending into a soup and were immediately frozen at − 18 °C for storage. Soup was generally consumed within the week, but could be stored for up to 6 weeks at − 18 °C. The active soup contained 40% broccoli, 25% cauliflower, 25% cabbage, and 10% kale, and the control soup contained 40% potato, 30% pumpkin, 20% carrot, and 10% sweet potato. Root and squash vegetables were chosen as the control intervention as these vegetables are commonly consumed in Australia [ 15 ]. The macronutrient content of the soups was closely matched, as previously reported in the protocol [ 13 ]. Participants were instructed not to add salt to their soups and were blinded to which interventions were the active and control.

Standard lunch and dinner meals were provided throughout both interventions to minimize background diet variation amongst participants. These meals provided approximately 1–4 serves (75–450 g) of vegetables per day, excluding the additional vegetable serves provided in the soups. Cruciferous vegetables were avoided when selecting these meals by checking the listed ingredients. Participants were able to select meals based on personal preference and meal orders were duplicated for each intervention to limit variation in the diet between intervention periods. All meals for each participant were ordered and stored at − 18 °C at the beginning of the study period to mitigate potential disruptions to stock availability due to the COVID-19 pandemic.

Participants were instructed to consume their usual breakfast foods and snacks but were asked to avoid consuming any snacks in the 2-h window after soup was consumed. Participants were required to complete food diaries, including the timing of all meals and snacks. Participant food diaries were checked by a dietitian (ELC) and Foodworks software using the AusBrands 2019 and AusFoods 2019 databases was used for dietary assessment (FoodWorks 10 Professional, v10.0. Brisbane: Xyris Pty Ltd, 2019). Intervention adherence was assessed using self-reported (i.e., food diaries) and objective biomarkers of intake (i.e., serum carotenoids and urinary and plasma S-methyl cysteine sulfoxide (SMCSO)). Percent self-reported adherence was calculated by dividing the number of soups consumed by the number of total soups that should have been consumed (28 soups per intervention) and multiplying that number by 100. Urinary and plasma SMCSO were used as objective markers of adherence to the active intervention as SMCSO is found in higher concentrations in cruciferous vegetables, but not root and squash vegetables [ 16 ]. Conversely, root and squash vegetables contain higher concentrations of carotenoids than cruciferous vegetables; therefore, serum carotenoids were measured as an objective marker of control intervention adherence [ 17 ]. Please see “ Biochemical analyses ” for methodology used for objective measures of adherence.

Baseline dietary assessment

To assess baseline habitual dietary intake, participants completed the Dietary Questionnaire for Epidemiological Studies (DQES v3.2), a validated food frequency questionnaire, under the supervision of a trained dietitian or nutritionist (ELC, CRH, BHP) [ 18 ]. A dietitian (ELC) looked at outliers for implausible energy intakes with respect to factors such as BMI, sex, and age and reviewed for unrealistic energy intakes to support body function and lifestyle. All vegetables (including legumes and potatoes cooked without fat) were included in the analysis of baseline total vegetable intake (g/day). Intake of Asian greens (e.g., bok choy), coleslaw, Brussels sprouts, cauliflower, and broccoli (i.e., available cruciferous vegetables in the DQES v3.2) were combined to create the cruciferous vegetable (g/day) variable for baseline analysis of cruciferous vegetable intake.

Outcome measurements

Ambulatory blood pressure and arterial stiffness.

Trained study investigators (AHL, ELC) fitted participants with the Oscar 2 Ambulatory Blood Pressure Monitor (ABPM) system (SunTech Medical Inc., Morrisville, NC, USA) to assess 24-h ambulatory blood pressure at pre- and post-intervention visits (i.e., beginning and end of each 2-week period), as previously described [ 13 ]. The ABPM system measured brachial and aortic blood pressure every 20 min during daytime hours (6 am until 10 pm) and every 30 min during nighttime hours (10 pm until 6 am). Participants used the same ABPM for all visits. Participants were instructed to avoid vigorous activity whilst wearing the monitor and to continue with regular daily activities. Participants were excluded if they were missing more than 20% of measurements or if there were more than four hours with no blood pressure measurements. Ambulatory arterial stiffness was assessed using the aortic augmentation index (AIx, %) [ 19 ]. The ambulatory AIx data was obtained using the SphygmoCor component of the Oscar 2 ABPM at pre- and post-intervention visits.

Anthropometry

Body composition (weight, height, body mass index (BMI), waist and hip circumference, body fat mass) was assessed according to standard protocols at each pre- and post-intervention visit [ 13 ].

Online self-administered questionnaires were used to assess lifestyle factors known to influence blood pressure. These factors included physical activity (assessed using the Community Healthy Activities Model Program for Seniors (CHAMPS) [ 20 ]) and stress (assessed using the Perceived Stress Scale (PSS) [ 14 ]). CHAMPS and PSS questionnaires were completed pre- and post-intervention to assess any changes in physical activity and stress levels, as these lifestyle factors have been shown to influence blood pressure [ 21 ].

Biochemical analyses

Blood and urine samples were collected at pre- and post-intervention visits. Fasting blood samples were collected by venipuncture into serum-separating tubes (SST) and ethylenediaminetetraacetic acid (EDTA)-coated vacutainers. SST vacutainers were immediately covered in aluminum foil to protect the tubes from light, due to the light sensitivity of carotenoids [ 17 ], and sat upright for 30 min prior to centrifugation. Whole blood was centrifuged at 4 °C at 3500 rpm for 10 min. All aliquots were stored at − 80 °C until analysis. Twenty-four-hour urine samples were collected in sterilized containers the day before pre- and post-intervention visits. After participants returned their sample to the clinic, samples were weighed and urine aliquots were stored at − 80 °C until analysis.

SMCSO was measured in urine and plasma samples. Sulforaphane, the isothiocyanate of the glucosinolate, glucoraphanin, was also measured in plasma samples. For the urinary SMCSO analysis, urine samples were thawed on ice and 50 µL of samples were diluted with liquid chromatography mass spectrometry (LC–MS) grade water (1:2 dilution). The diluted samples (50 µL) were transferred to a 1.5 mL centrifuge tube. The acetonitrile (ACN) solution (150 µL) containing 2 µg/mL internal standards (SMCSO-d3) was added, and the samples were vortexed for 2 min and centrifuged at 14,000 rpm and 4 °C for 10 min. A 100 μL aliquot of supernatant was transferred to a 2 mL high-performance liquid chromatography (HPLC) vial for analysis using liquid chromatography tandem mass spectrometry (LC–MS/MS). Chromatographic separation was performed on an UltiMate 3000 Liquid Chromatograph (Thermo Scientific, CA, USA) coupled to a Thermo Scientific TSQ Quantiva Triple Quadrupole Mass Spectrometer equipped with an electrospray ionization (ESI) source. The optimal separation was achieved on ACQUITY UPLC BEH Amide column (100 mm × 2.1 mm ID; Waters) with 1.7 μm particles and a mobile phase of water and ACN containing 10 mM ammonium formate and 50 nM formic acid at pH 3. The flow rate was 0.5 mL/min and the column temperature was maintained at 35 °C with an injection volume of 4 µL. The detection was performed in positive mode (3500 V) and the spectra were acquired in multiple reaction monitoring (MRM) mode. Argon gas was selected as the collision gas and nitrogen as the nebulizer and heater gas.

For the plasma SMCSO and sulforaphane analysis, plasma samples were thawed on ice and 50 µL of samples were transferred to a 1.5 mL centrifuge tube. The methanol solution (150 μL) containing 0.75 µg/mL internal standards (SMCSO-d3 and SFN-d8) was added, and the samples were vortexed for 2 min and centrifuged at 4000 rpm and 4 °C for 10 min. An 80 μL aliquot of supernatant was transferred to a 2 mL HPLC vial for analysis using the LC–MS/MS. The optimal separation was achieved on XBridge C18 column (100 × 3.0 mm packed with 3.5µm particles; Waters) and using a mobile phase of water and ACN both containing 0.1% formic acid. The flow rate was 0.4 mL/min and the column temperature was maintained at 35 °C with an injection volume of 6 µL. As with the urine analysis, the detection was performed in positive mode (3500 V) and the spectra were acquired in MRM mode. Argon gas was selected as the collision gas and nitrogen as the nebulizer and heater gas.

Serum carotenoids were measured using HPLC, as previously described [ 22 ]. Briefly, ethanol, ethyl acetate, and hexane were used to extract carotenoids, with canthaxanthin as an internal standard. Dichloromethane:methanol (1:2 vol) was used to reconstitute the dried extract after evaporation of the solvents. Using a Hypersil ODS column (100 mm × 2.1 mm × 5 μm) (Thermo Scientific, CA, USA), chromatography was performed on an Agilent 1200 HPLC system (Agilent Technologies, CA, USA). A mobile phase of ACN:dichloromethane:methanol 0.05% ammonium acetate (85:10:5 vol:vol) at a flow rate of 0.3 mL/min with the use of a diode array detector (450 nm) was used to analyze carotenoids [ 22 ].

Plasma F 2 -isoprostanes, a biomarker of oxidative lipid damage, were measured using electron-capture negative-ion gas chromatography–mass spectrometry as total (free plus esterified) F 2 -isoprostanes, as previously described [ 23 ]. Serum high sensitivity interleukin-6 (hsIL-6), a marker of inflammation, was analyzed using a commercially available enzyme-linked immunosorbent assay (ELISA) kit (R&D Systems, Inc., Minneapolis, MN, USA). Urinary concentrations of creatinine, sodium, and potassium (markers of sodium and potassium intakes) and serum concentrations of triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, calculated low-density lipoprotein (LDL) cholesterol, glucose, creatinine, high sensitivity C-reactive protein (hsCRP), sodium, and potassium were analyzed by PathWest Laboratories (Fiona Stanley Hospital, Perth, Australia).

Statistical analysis

Sample size.

Based on 24-h ambulatory SBP as the primary outcome, a desired sample size of 25 participants was calculated. This sample size was calculated to provide > 90% power to detect a 2.5 mmHg difference in mean 24-h ambulatory SBP, assuming a standard deviation (SD) of 14 mmHg for SBP, a within-period correlation between SBP measurements of 0.6, a between period correlation of mean SBP of 0.6, and a minimum of 40 blood pressure measurements over each 24-h period [ 24 ], as described in the published protocol [ 13 ]. The estimated change of 2.5 mmHg was based on plausible values for changes in SBP following a nutritional intervention, such as those described previously from the ingestion of black tea [ 24 ], as well as also constituting a clinically meaningful change.

Statistical methods

All data were analyzed using IBM SPSS Statistics for Windows, version 29.0 (IBM Corp., Armonk, NY, USA) and STATA, version 15.1 (Statacorp, College Station, TX, USA). Statistical significance was set at a two-sided type 1 error rate of P  < 0.05. The Shapiro–Wilk normality test was used to assess the normality of distributions of continuous variables. Descriptive statistics of normally distributed variables are expressed as mean ± SD, non-normally distributed continuous variables as median and interquartile range (IQR), and categorical variables as number and proportion (%). Paired t tests and Wilcoxon signed rank tests were used to compare pre- and post-intervention measurements within the intervention groups for normally and non-normally distributed variables, respectively.

The primary analyses were conducted according to a modified intention-to-treat protocol, including all participants for which pre-intervention visit data for both interventions were obtained. Secondary per-protocol analyses were conducted on participants who completed the study and had complete data. Intention-to-treat and per-protocol analyses were the same for all outcomes except for hsCRP (extreme outlier removed) and ambulatory aortic blood pressure and arterial stiffness (> 10% missing data). Differences between treatments for ambulatory brachial and aortic blood pressure and arterial stiffness were tested using linear mixed effects regression with fixed effects for treatment, pre vs. post treatment, hour, intervention order, and a treatment X pre-post interaction. In this analysis, “hour” referred to the blood pressure readings aggregated for each hour over the 24-h period. Participant ID was included as a random intercept with a random slope for treatment and pre- vs. post treatment. Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to determine the best model fit. For all other outcomes, differences between treatments were tested using the same model without a time variable (hour). Due to ABPM error, there was > 10% missing data for aortic blood pressure (11% missing data) and arterial stiffness (13% missing data), and therefore, multiple imputation was utilized as per the published protocol [ 13 ]. Ten imputations were generated using a chained regression equation including the following variables in the imputation model: visit, hour, daytime/nighttime hours, treatment, intervention order, age, sex, weight, height, and screening blood pressure. ELC and LCB had full access to all data in the study and took responsibility for its integrity and the data analysis.

Recruitment

A total of 76 individuals underwent physical screening to be assessed for eligibility. Of these, 21 participants were randomly assigned. Three participants withdrew after randomization: two withdrew due to scheduling difficulties before pre-intervention visit data was collected and one withdrew as they were unwilling to follow study requirements. The CONSORT flow diagram for participant recruitment is shown in Fig.  2 . Due to the global COVID-19 pandemic and restrictions put in place in Western Australia, recruitment was paused in March 2020 and later recommenced in October 2020 in a limited capacity.

CONSORT diagram

Baseline demographic and clinical characteristics

Participants were aged 56 to 72 years and had a BMI range of 21.2 to 35.1 kg/m 2 (Table 1 ). Most participants were Caucasian (94%). At screening, participants presented with mean ± SD brachial SBP of 135.9 ± 10.0 mmHg and a DBP of 76.4 ± 7.9 mmHg. Two participants used blood pressure-lowering medication, which remained unaltered throughout the trial. Median (IQR) baseline habitual daily intake of cruciferous vegetable was 26.0 g (18.5–52.9 g) and most people consumed at least 3.5 servings of vegetables per day (Additional File 1: Table S2).

For both soups, 72% of participants had 100% soup adherence (median (IQR) adherence: 100% (96.4–100%) for both interventions). No adverse events were reported. Energy, macronutrient, and food group consumption during both intervention periods is presented in Additional File 1: Table S3. Only protein was significantly different between interventions ( P  = 0.001). Median (IQR) intake of total vegetables per day was 481 g (458–526 g) and 493 g (458–503 g) for the control and active interventions, respectively. Median (IQR) intake of cruciferous vegetables was 0 g/day (0–0 g/day) during the control intervention; four participants reported consuming cruciferous vegetables ranging from 0.3–12.3 g/day during their control intervention. During the active intervention, median (IQR) intake of cruciferous vegetables was 300 g/day (293–300 g/day); three participants reported consuming cruciferous vegetables outside of the intervention soups ranging from 2.1 to 10 g/day during their active intervention.

Ambulatory blood pressure

Twenty-four-hour brachial SBP was significantly reduced in the active intervention compared to the control intervention (mean difference active vs. control: − 2.5 mmHg, 95% CI − 4.1, − 0.9, P  = 0.002) (Table  2 ). This result was driven by the daytime period (mean difference active vs. control: − 3.6 mmHg, 95% CI − 5.4, − 1.7, P  < 0.001). No significant difference was seen for nighttime SBP nor 24-h, daytime, and nighttime brachial DBP between interventions (Table  2 ). Figure  3 shows 24-h brachial SBP at the pre- and post-intervention visit for both interventions. No carryover effects were seen for 24-h brachial SBP ( P  = 0.877) or DBP ( P  = 0.556).

24-h ambulatory systolic blood pressure (SBP) aggregated hourly for the control ( A ) and active ( B ) interventions at the pre- and post-intervention visits

Between interventions, 24-h and daytime aortic SBP were significantly reduced in the active intervention compared to the control intervention (mean difference active vs. control: − 2.1 mmHg, 95% CI − 3.7, -0.5, P  = 0.010 and − 3.2 mmHg, 95% CI − 5.0, − 1.4, P  = 0.001, respectively) (Table  3 ). Nighttime aortic DBP was significantly increased in the active compared to the control intervention between interventions (mean difference active vs. control: 2.9 mmHg, 95% CI 0.6, 5.2, P  = 0.014). Ambulatory aortic blood pressure prior to multiple imputations is shown in Additional File 1: Table S4.

Relative to control, there was a significant increase in 24-h and nighttime heart rate for the active intervention (mean difference active vs. control: 2.1 beats/min, 95% CI 1.1, 3.2, P  < 0.001 and 2.0 beats/min, 95% CI 0.6, 3.3, P  = 0.004, respectively; Table  2 ). However, this difference was driven by significant reductions in the control intervention for 24-h ( P  = 0.048) and nighttime heart rate ( P  = 0.004) from pre- to post-intervention visits, which appeared to cause the significant between-group differences.

Arterial stiffness

The mean difference in AIx was not significantly different between interventions for 24-h, daytime, or nighttime measurements (Table  3 ). AIx prior to multiple imputations is shown in Supplementary Table 4. No carryover effects were noted ( P  = 0.645).

Biomarkers of oxidative stress and inflammation

There was no overall difference in the mean F 2 -isprostanes between interventions (Table  4 ). Plasma F 2 -isoprostanes were significantly lower at the post-intervention visit compared with the pre-intervention visit within the active intervention ( P  = 0.013). However, a similar non-significant drop in F 2 -isprostanes was seen in the control intervention. There was no significant difference in hsCRP and hsIL-6 between interventions (Table  4 ). One participant was excluded from the per-protocol analysis of hsCRP due to an extreme outlier (hsCRP value: 89.6 mg/L; mean difference active vs. control 0.2 mg/L, 95% CI − 0.9, 1.4, P  = 0.708). No carryover effects were seen for either F 2 -isprostanes ( P  = 0.901) or hsCRP ( P  = 0.553).

Markers of adherence and metabolism

Urinary/plasma smcso and plasma sulforaphane.

The mean differences in urinary and plasma SMCSO (mean difference active vs. control: 22.93 mg/mL, 95% CI 15.62, 30.23, P  < 0.0001 and 5.46 mg/mL, 95% CI 4.40, 6.51, P  < 0.0001, respectively) and plasma sulforaphane concentrations were significantly higher following the active intervention compared to the control intervention (mean difference active vs. control: 0.15 ng/mL, 95% CI 0.06, 0.23, P  < 0.001) (Table  5 ). Urinary and plasma SMCSO concentrations, as well as plasma sulforaphane, were significantly higher at the post-intervention visit compared with the pre-intervention visit in the active group ( P  < 0.05 for all) (Table  5 ).

Serum carotenoids

Mean differences in total carotenoids, lutein, lycopene, a-carotene, and b-carotene were significantly higher following the control intervention compared to the active intervention ( P  < 0.05 for all) (Table  6 ). Total and individual carotenoids, excluding b-cryptoxanthin, were significantly higher at the post-intervention visit compared with the pre-intervention visit in the control intervention ( P  < 0.05 for all). In the active intervention, only a-carotene was significantly different at the post-intervention visit compared with the pre-intervention visit.

Serum and urinary sodium, potassium, and creatinine

Between interventions, there were no significant mean differences for serum sodium, potassium, or creatine. Urinary sodium, potassium, and creatinine were also not significantly different between interventions (Table  7 ).

Serum lipids and glucose

Serum triglycerides were significantly lower in the active intervention compared to the control intervention (mean difference active vs. control: − 0.2 mmol/L, 95% CI − 0.4, − 0.0, P  = 0.047) (Table  7 ). No carryover effects were noted ( P  = 0.7897). There were no significant mean differences between interventions for serum total cholesterol, LDL cholesterol, HDL cholesterol, or serum glucose. However, serum total, LDL, and HDL cholesterol and serum glucose were significantly decreased at the post-intervention visit compared with the pre-intervention visit for both interventions ( P  < 0.05 for all).

Anthropometry, energy expenditure from physical activity, and stress

There were no significant mean differences between interventions for any anthropometric measures, energy expenditure from physical activity, or perceived stress ( P  > 0.05 for all) (Additional File 1: Table S5). However, weight, BMI, and body fat mass were significantly reduced at the post-intervention visit compared with the pre-intervention visit for both interventions.

In this randomized, controlled, crossover trial, we found that consumption of four serves per day of cruciferous vegetables (active intervention) resulted in a statistically significant reduction in SBP compared with four serves per day of root and squash vegetables (control intervention), supporting our hypothesis. This reduction in SBP is clinically relevant; in a meta-analysis of randomized controlled trials involving pharmacological interventions, a reduction in SBP of 5 mmHg was found to reduce the risk of major cardiovascular events by ~ 10% [ 25 ]. Therefore, the 2.5 mmHg reduction in SBP resulting from increasing cruciferous vegetable intake could translate to a 5% lower risk of major cardiovascular events.

Weight reduction is an important component of non-pharmacological management of hypertension [ 26 ], with a loss of 1 kg weight associated with approximately 1 mmHg reduction in SBP [ 27 ]. Both interventions resulted in a statistically significant reduction in weight post-intervention (control: 1.9 kg; active: 1.3 kg). However, there was no significant difference seen between interventions. Therefore, the improvements in SBP seen with the cruciferous vegetable intervention are likely independent of weight reduction. In addition, there was no significant difference in urinary sodium or potassium excretion between interventions, indicating that the reduction in SBP was independent of dietary sodium and potassium intake.

This blood pressure result is in alignment with other research investigating the breakdown products of cruciferous vegetables, which include glucosinolates and isothiocyanates [ 28 ]. Research into the cardio-protective properties of these compounds has largely focused on glucoraphanin, a major glucosinolate found in broccoli, and its isothiocyanate, sulforaphane [ 5 ]. Previous studies have investigated the effects of glucosinolates and isothiocyanates on blood pressure in animal models (i.e., rats), with results demonstrating blood pressure-lowering effects [ 29 , 30 , 31 , 32 ]. However, studies involving humans have been inconsistent. In a study including 40 participants with hypertension (baseline mean blood pressure: control group = 158.6/98; active group = 158.5/96 mmHg), daily ingestion of 10 g dried broccoli sprouts for 4 weeks did not improve blood pressure or endothelial function [ 33 ]. Conversely, a 4-week study including participants with type two diabetes and positive for H. Pylori (baseline mean blood pressure: standard triple therapy group ( n  = 33) 130/80.4; broccoli sprouts powder group ( n  = 28) 125/80.4; combination group ( n  = 25) 136/89.8 mmHg) found that there was a significant reduction in SBP and DBP in participants who received 6 g/day broccoli sprout powder in combination with standard triple therapy for H. Pylori (14 mmHg and 9.4 mmHg reduction in SBP and DBP, respectively) [ 34 ]. In a dose escalation study including 12 pregnant women with preeclampsia, activated broccoli extract equivalent to 32 mg or 64 mg of sulforaphane resulted in a trend towards an approximately 10% decrease in DBP ( P  = 0.05) but not SBP [ 35 ].

Plasma sulforaphane was significantly higher after the active intervention compared with the control, indicating that glucosinolates (i.e., glucoraphanin) were present in the soup and may explain the beneficial effect seen on blood pressure. These compounds have been proposed to have anti-inflammatory and antioxidant properties due to involvement in increasing Nrf2 activity and inhibition of NF-ĸB [ 36 ]. Whilst our findings show that cruciferous vegetable intake did not have a significant effect on our marker of oxidative lipid damage, relative to root and squash vegetables, plasma F 2 -isoprostanes were significantly lower after the active intervention. This highlights the potential efficacy for the antioxidant capabilities of cruciferous vegetables [ 37 ], although our study does not provide evidence that this explains the observed difference in SBP. Evidence for cruciferous vegetables altering oxidative stress and inflammation has been inconsistent [ 38 , 39 , 40 ] and further studies are needed to investigate the anti-inflammatory and antioxidant capacity of cruciferous vegetables when consumed as part of the diet. Although there were no significant differences in oxidative stress and inflammatory biomarkers between interventions in our study, this could be due to similar benefits of other vegetables in the control treatment. The control soup contained carotenoid-rich vegetables, which also have both antioxidant and anti-inflammatory properties [ 41 ]. Furthermore, these biomarkers were within normal expected ranges [ 42 , 43 , 44 ], which may also explain this result.

Whilst we report SMCSO as a biomarker of adherence to cruciferous vegetable intake in this study, SMCSO has also been recently identified as a key metabolite associated with the antihypertensive benefits of the Dietary Approaches to Stop Hypertension (DASH) diet [ 45 ]. SMCSO contributes a greater proportion of sulfur in cruciferous vegetables than glucosinolates, yet whether SMCSO mediates some of the therapeutic benefits of these vegetables in humans remains largely unexplored [ 46 ]. Sulfur-rich vegetables (i.e., cruciferous) are a good source contributing to hydrogen sulfide (H 2 S): the third most important gaseous signaling molecule. As such, this may be a potential mechanism through which these vegetables modulate endothelial function [ 47 ]. The contribution of H 2 S to the anti-hypertensive benefits of sulfur-rich allium vegetables (e.g., onion, garlic) has been recently explored [ 48 ]; however, more research is required. Both SMCSO and glucosinolates may act as H 2 S donors [ 45 , 47 ], and the subsequent vasodilation may be partly responsible for the reduction in blood pressure observed in the active intervention.

We also found that serum triglycerides were significantly lower after the active intervention compared with the control intervention. Although pre-clinical evidence suggests that cruciferous vegetables and their glucosinolates may play a role in the reduction of blood lipids [ 49 , 50 , 51 , 52 ], there is limited evidence in humans. Human trials have shown that broccoli sprouts and glucoraphanin-rich broccoli can improve HDL cholesterol [ 53 ] and reduce LDL cholesterol [ 54 ], respectively. There were no significant differences in biomarkers of total cholesterol, LDL, HDL, and glucose between interventions in our study. However, this could be due to similar benefits of other vegetables in the control treatment, as there were significant within-group changes in these biomarkers following both interventions.

This study had multiple strengths. First, to our knowledge, our study is the only intervention study in humans to show improvements in blood pressure in middle-aged and older adults with mildly elevated blood pressure after increased short-term consumption of cruciferous vegetables compared to commonly consumed root and squash vegetables. Furthermore, this study is also novel in that the study design included a dietary intervention utilizing a combination of cruciferous vegetables as whole foods (not extracts of cruciferous vegetables or their bioactives). Second, the study had a crossover design which allowed all participants to act as their own control, mitigating potential differences between participants. A 2-week washout period was selected between interventions to avoid potential carryover effects, as this was considered enough time for objective markers of intake to be adequately excreted (i.e., urinary SMCSO in the active intervention and serum carotenoids in the control intervention). This washout period has been used in prior studies, demonstrating that these biomarkers return to normal levels within 2 weeks [ 55 , 56 ]. Third, in addition to self-reported food diaries, objective markers of intake were measured to corroborate adherence to both dietary interventions. Additionally, we carefully controlled the background diet of participants. The provision of lunch and dinner meals throughout the study likely substantially reduced the background variation in vegetable intake and other foods.

This study also has limitations. Although a significant reduction in our primary outcome of 24-h SBP was observed, we did not reach our desired sample size. The reduced sample size resulting from COVID-19-related issues may be relevant for secondary outcomes in this study. As we were unable to recruit the desired sample size of 25 participants (28 to account for participant drop-out) due to the COVID-19 pandemic, this study may be considered a pilot RCT rather than a phase 2 trial. However, despite this, we were still able to demonstrate a statistically significant result for our primary outcome, brachial 24-h ambulatory SBP, thereby eliminating the possibility of making a type-2 error for the primary outcome. We were aiming to have roughly an equal distribution of males and females; however, this was not possible due to limitations resulting from the COVID-19 pandemic (e.g., logistical and financial) and led to mostly female participants. Most participants were also Caucasian. Therefore, these results may not be as generalizable to males and other ethnicities. Second, participants included in this study had a baseline reported intake of vegetables higher than that of the general population (327 g vs.195 g per day) [ 57 ], which may reduce the generalizability of these results. However, this may also be seen as a strength by reinforcing that the type of vegetable consumed matters. Nonetheless, investigation of cruciferous vegetable intake in individuals with lower baseline intake of vegetables is warranted to determine if there is a more profound effect with a greater increase from baseline habitual intake. Third, given the nature of the dietary interventions, participants were unable to be completely blinded, as the different soups had clear differences in color and taste. However, participants were not informed which soup was the active or control or what vegetables were included in each soup. Lastly, self-reported protein intake was significantly different between interventions (7 g higher in the active group in comparison to the control, P  = 0.001), and increasing protein intake has been shown to influence blood pressure. However, this difference is unlikely to have an effect, based on results of a meta-analysis that indicate amounts of approximately 40 g per day are needed to have a similar effect on blood pressure [ 58 ]. It is important to note that cruciferous vegetables do not contain only glucosinolates and SMCSO at higher concentrations than root and squash vegetables. Cruciferous vegetables also contain higher nitrate and vitamin K levels. In addition, they also provide smaller but higher levels of other nutrients and phytochemicals such as magnesium, flavonoids, vitamin C, and folate, all of which have potential to contribute to benefits on blood pressure [ 11 , 12 ]. As such, we are not able to fully elucidate which specific components are responsible for the beneficial effects that we observed.

Daily consumption of four serves of cruciferous vegetables over a 2-week period resulted in reduced SBP in middle-aged and older adults with mildly elevated blood pressure compared with root and squash vegetables. Increased intake of a variety of different vegetables has many health benefits due to the presence of vitamins, minerals, and many other bioactive compounds. Future research is needed to inform whether targeted recommendations to increase cruciferous vegetable intake within a healthy diet that includes a variety of vegetables can reduce the public health burden of CVD. Furthermore, the study could be implemented in other regions worldwide to obtain multi-ethnic data.

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Liu RH. Health-promoting components of fruits and vegetables in the diet. Adv Nutr. 2013;4(3):384s-s392.

Article   PubMed   PubMed Central   CAS   Google Scholar  

National Health and Medical Research Council. Australian Dietary Guidelines. Canberra, Australia: National Health and Medical Research Council; 2013.

Wallace TC, Bailey RL, Blumberg JB, Burton-Freeman B, Chen CO, Crowe-White KM, et al. Fruits, vegetables, and health: a comprehensive narrative, umbrella review of the science and recommendations for enhanced public policy to improve intake. Crit Rev Food Sci Nutr. 2020;60(13):2174–211.

Article   PubMed   CAS   Google Scholar  

Connolly EL, Sim M, Travica N, Marx W, Beasy G, Lynch GS, et al. Glucosinolates from cruciferous vegetables and their potential role in chronic disease: investigating the preclinical and clinical evidence. Front Pharmacol. 2021;12: 767975.

Mazarakis N, Snibson K, Licciardi PV, Karagiannis TC. The potential use of l-sulforaphane for the treatment of chronic inflammatory diseases: a review of the clinical evidence. Clin Nutr. 2020;39(3):664–75.

Zurbau A, Au-Yeung F, Blanco Mejia S, Khan TA, Vuksan V, Jovanovski E, et al. Relation of different fruit and vegetable sources with incident cardiovascular outcomes: a systematic review and meta-analysis of prospective cohort studies. J Am Heart Assoc. 2020;9(19): e017728.

Article   PubMed   PubMed Central   Google Scholar  

IARC Working Group of the Evaluation of Cancer Preventive Strategies. Cruciferous vegetables, isothiocyanates and indoles. Lyon, France2003.

Aune D, Giovannucci E, Boffetta P, Fadnes LT, Keum N, Norat T, et al. Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality-a systematic review and dose-response meta-analysis of prospective studies. Int J Epidemiol. 2017;46(3):1029–56.

Wang Q, King L, Wang P, Jiang G, Huang Y, Dun C, et al. Higher Levels of urinary thiocyanate, a biomarker of cruciferous vegetable intake, were associated with lower risks of cardiovascular disease and all-cause mortality among non-smoking subjects. Front Nutr. 2022;9.

Oliveros E, Patel H, Kyung S, Fugar S, Goldberg A, Madan N, et al. Hypertension in older adults: assessment, management, and challenges. Clin Cardiol. 2020;43(2):99–107.

Article   PubMed   Google Scholar  

Ağagündüz D, Şahin T, Yılmaz B, Ekenci KD, Duyar Özer Ş, Capasso R. Cruciferous vegetables and their bioactive metabolites: from prevention to novel therapies of colorectal cancer. Evid Based Complement Alternat Med. 2022;2022:1534083.

Blekkenhorst LC, Sim M, Bondonno CP, Bondonno NP, Ward NC, Prince RL, et al. Cardiovascular health benefits of specific vegetable types: a narrative review. Nutrients. 2018;10(5).

Connolly EL, Bondonno CP, Sim M, Radavelli-Bagatini S, Croft KD, Boyce MC, et al. A randomised controlled crossover trial investigating the short-term effects of different types of vegetables on vascular and metabolic function in middle-aged and older adults with mildly elevated blood pressure: the VEgetableS for vaScular hEaLth (VESSEL) study protocol. Nutr J. 2020;19(1):41.

Cohen S. Perceived stress in a probability sample of the United States. In: Oskamp SSS, editor. The social psychology of health. Thousand Oaks, CA, USA: Sage Publications Inc.; 1988. p. 31–67.

Google Scholar  

Australian Bureau of Statistics. Australian Health Survey: consumption of food groups from the Australian Dietary Guidelines, 2011–12. Canberra, Australia: Australian Bureau of Statistics; 2016.

Edmands WM, Beckonert OP, Stella C, Campbell A, Lake BG, Lindon JC, et al. Identification of human urinary biomarkers of cruciferous vegetable consumption by metabonomic profiling. J Proteome Res. 2011;10(10):4513–21.

Woodside JV, Draper J, Lloyd A, McKinley MC. Use of biomarkers to assess fruit and vegetable intake. Proceedings of the Nutrition Society. 2017;76(3):308–15.

Hodge A, Patterson AJ, Brown WJ, Ireland P, Giles G. The Anti Cancer Council of Victoria FFQ: relative validity of nutrient intakes compared with weighed food records in young to middle-aged women in a study of iron supplementation. Aust N Z J Public Health. 2000;24(6):576–83.

Safar ME. Pulse pressure, arterial stiffness and wave reflections (augmentation index) as cardiovascular risk factors in hypertension. Ther Adv Cardiovasc Dis. 2008;2(1):13–24.

Stewart AL, Mills KM, King AC, Haskell WL, Gillis D, Ritter PL. CHAMPS physical activity questionnaire for older adults: outcomes for interventions. Med Sci Sports Exerc. 2001;33(7):1126–41.

Tomitani N, Kanegae H, Suzuki Y, Kuwabara M, Kario K. Stress-induced blood pressure elevation self-measured by a wearable watch-type device. Am J Hypertens. 2021;34(4):377–82.

Wood LG, Garg ML, Smart JM, Scott HA, Barker D, Gibson PG. Manipulating antioxidant intake in asthma: a randomized controlled trial. Am J Clin Nutr. 2012;96(3):534–43.

Tsai IJ, Croft KD, Mori TA, Falck JR, Beilin LJ, Puddey IB, et al. 20-HETE and F2-isoprostanes in the metabolic syndrome: the effect of weight reduction. Free Radic Biol Med. 2009;46(2):263–70.

Hodgson JM, Puddey IB, Woodman RJ, Mulder TP, Fuchs D, Scott K, et al. Effects of black tea on blood pressure: a randomized controlled trial. Arch Intern Med. 2012;172(2):186–8.

Rahimi K, Bidel Z, Nazarzadeh M, Copland E, Canoy D, Ramakrishnan R, et al. Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis. Lancet. 2021;397(10285):1625–36.

Article   Google Scholar  

Hall ME, Cohen JB, Ard JD, Egan BM, Hall JE, Lavie CJ, et al. Weight-loss strategies for prevention and treatment of hypertension: a scientific statement From the American Heart Association. Hypertension. 2021;78(5):e38–50.

Neter JE, Stam BE, Kok FJ, Grobbee DE, Geleijnse JM. Influence of weight reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension. 2003;42(5):878–84.

Kissen R, Rossiter JT, Bones AM. The ‘mustard oil bomb’: not so easy to assemble?! Localization, expression and distribution of the components of the myrosinase enzyme system. Phytochem Rev. 2009;8(1):69–86.

Article   CAS   Google Scholar  

Salma U, Khan T, Shah AJ. Antihypertensive effect of the methanolic extract from Eruca sativa Mill., (Brassicaceae) in rats: muscarinic receptor-linked vasorelaxant and cardiotonic effects. J Ethnopharmacol. 2018;224:409–20.

Senanayake GV, Banigesh A, Wu L, Lee P, Juurlink BH. The dietary phase 2 protein inducer sulforaphane can normalize the kidney epigenome and improve blood pressure in hypertensive rats. Am J Hypertens. 2012;25(2):229–35.

Elbarbry F, Moshirian N. The modulation of arachidonic acid metabolism and blood pressure-lowering effect of honokiol in spontaneously hypertensive rats. Molecules. 2022;27(11).

Prado NJ, Ramirez D, Mazzei L, Parra M, Casarotto M, Calvo JP, et al. Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables. Heliyon. 2022;8(2): e08989.

Christiansen B, Bellostas Muguerza N, Petersen AM, Kveiborg B, Madsen CR, Thomas H, et al. Ingestion of broccoli sprouts does not improve endothelial function in humans with hypertension. PLoS ONE. 2010;5(8): e12461.

Mirmiran P, Bahadoran Z, Golzarand M, Zojaji H, Azizi F. A comparative study of broccoli sprouts powder and standard triple therapy on cardiovascular risk factors following H.pylori eradication: a randomized clinical trial in patients with type 2 diabetes. J Diabetes Metab Disord. 2014;13:64.

Langston-Cox AG, Anderson D, Creek DJ, Palmer KR, Marshall SA, Wallace EM. Sulforaphane bioavailability and effects on blood pressure in women with pregnancy hypertension. Reprod Sci. 2021;28(5):1489–97.

Esteve M. Mechanisms underlying biological effects of cruciferous glucosinolate-derived isothiocyanates/indoles: a focus on metabolic syndrome. Front Nutr. 2020;7:111.

Griendling KK, Camargo LL, Rios FJ, Alves-Lopes R, Montezano AC, Touyz RM. Oxidative stress and hypertension. Circ Res. 2021;128(7):993–1020.

Fowke JH, Morrow JD, Motley S, Bostick RM, Ness RM. Brassica vegetable consumption reduces urinary F2-isoprostane levels independent of micronutrient intake. Carcinogenesis. 2006;27(10):2096–102.

Navarro SL, Schwarz Y, Song X, Wang CY, Chen C, Trudo SP, et al. Cruciferous vegetables have variable effects on biomarkers of systemic inflammation in a randomized controlled trial in healthy young adults. J Nutr. 2014;144(11):1850–7.

Wirth MD, Murphy EA, Hurley TG, Hébert JR. Effect of cruciferous vegetable intake on oxidative stress biomarkers: differences by breast cancer status. Cancer Invest. 2017;35(4):277–87.

Kaulmann A, Bohn T. Carotenoids, inflammation, and oxidative stress—implications of cellular signaling pathways and relation to chronic disease prevention. Nutr Res. 2014;34(11):907–29.

Camfield DA, Nolidin K, Savage K, Timmer J, Croft K, Tangestani Fard M, et al. Higher plasma levels of F2-isoprostanes are associated with slower psychomotor speed in healthy older adults. Free Radic Res. 2019;53(4):377–86.

Nehring SM, Goyal A, Patel BC. C Reactive Protein. StatPearls. Treasure Island, FL: StatPearls Publishing; 2023.

Said EA, Al-Reesi I, Al-Shizawi N, Jaju S, Al-Balushi MS, Koh CY, et al. Defining IL-6 levels in healthy individuals: a meta-analysis. J Med Virol. 2021;93(6):3915–24.

Chan Q, Wren GM, Lau CE, Ebbels TMD, Gibson R, Loo RL, et al. Blood pressure interactions with the DASH dietary pattern, sodium, and potassium: The International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP). Am J Clin Nutr. 2022;116(1):216–29.

Edmands WMB, Gooderham NJ, Holmes E, Mitchell SC. S-Methyl-l-cysteine sulphoxide: the Cinderella phytochemical? Toxicol Res. 2012;2(1):11–22.

Hill CR, Shafaei A, Balmer L, Lewis JR, Hodgson JM, Millar AH, et al. Sulfur compounds: from plants to humans and their role in chronic disease prevention. Crit Rev Food Sci Nutr. 2022:1–23.

Ali A, Kouvari M, Riaz S, Naumovski N, Liao L, Khan A, et al. Potential of Allium sativum in blood pressure control involves signaling pathways: A narrative review. Food Front.

Du K, Fan Y, Li D. Sulforaphane ameliorates lipid profile in rodents: an updated systematic review and meta-analysis. Sci Rep. 2021;11(1):7804.

Huang H, Jiang X, Xiao Z, Yu L, Pham Q, Sun J, et al. Red cabbage microgreens lower circulating low-density lipoprotein (ldl), liver cholesterol, and inflammatory cytokines in mice fed a high-fat diet. J Agric Food Chem. 2016;64(48):9161–71.

Melega S, Canistro D, De Nicola GR, Lazzeri L, Sapone A, Paolini M. Protective effect of Tuscan black cabbage sprout extract against serum lipid increase and perturbations of liver antioxidant and detoxifying enzymes in rats fed a high-fat diet. Br J Nutr. 2013;110(6):988–97.

Thomaz FS, Tan YP, Williams CM, Ward LC, Worrall S, Panchal SK. Wasabi (Eutrema japonicum) reduces obesity and blood pressure in diet-induced metabolic syndrome in rats. Foods. 2022;11(21).

Murashima M, Watanabe S, Zhuo XG, Uehara M, Kurashige A. Phase 1 study of multiple biomarkers for metabolism and oxidative stress after one-week intake of broccoli sprouts. BioFactors. 2004;22(1–4):271–5.

Armah CN, Derdemezis C, Traka MH, Dainty JR, Doleman JF, Saha S, et al. Diet rich in high glucoraphanin broccoli reduces plasma LDL cholesterol: evidence from randomised controlled trials. Mol Nutr Food Res. 2015;59(5):918–26.

Coode-Bate J, Sivapalan T, Melchini A, Saha S, Needs PW, Dainty JR, et al. Accumulation of dietary S-methyl cysteine sulfoxide in human prostate tissue. Mol Nutr Food Res. 2019;63(20): e1900461.

Pezdirc K, Hutchesson MJ, Williams RL, Rollo ME, Burrows TL, Wood LG, et al. Consuming high-carotenoid fruit and vegetables influences skin yellowness and plasma carotenoids in young women: a single-blind randomized crossover trial. J Acad Nutr Diet. 2016;116(8):1257–65.

Australian Bureau of Statistics. Dietary behaviour Canberra: Australian Bureau of Statistics; 2020–21 [Available from: https://www.abs.gov.au/statistics/health/health-conditions-and-risks/dietary-behaviour/latest-release .

Rebholz CM, Friedman EE, Powers LJ, Arroyave WD, He J, Kelly TN. Dietary protein intake and blood pressure: a meta-analysis of randomized controlled trials. Am J Epidemiol. 2012;176(Suppl 7):S27-43.

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Acknowledgements

We would like to thank Kim Luu, a lab technician for Nutrition & Dietetics, for the preparation of the intervention soups.

This research was funded by Edith Cowan University Early Career Researcher Grant 2019 (grant number G1004405) and Department of Health Western Australia Near Miss Merit Awards 2019 (grant number G1004519). Funding sources had no involvement in the study design; collection, analysis, and interpretation of the data; or writing of the manuscript, and there are no restrictions regarding publication. EC is supported by an Australian Government Research Training Program Scholarship at Edith Cowan University. MS is supported by a Royal Perth Hospital Research Foundation Fellowship (ID: CAF 130/2020) and an Emerging Leader Fellowship from the Western Australian Future Health Research and Innovation Fund. CPB is supported by a Royal Perth Hospital Research Foundation ‘Lawrie Beilin’ Career Advancement Fellowship (ID: CAF 127/2020) and the Western Australian Future Health Research and Innovation Fund (ID: IG2021/5). LCB is supported by a National Health and Medical Research Council of Australia Emerging Leadership Investigator Grant (ID: 1172987) and a National Heart Foundation of Australia Post-Doctoral Research Fellowship (ID: 102498). JRL is supported by a National Heart Foundation Future Leader Fellowship (ID: 102817).

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Emma L. Connolly, Alex H. Liu, Simone Radavelli-Bagatini, Lyn McCahon, Marc Sim, Caroline R. Hill, Benjamin H. Parmenter, Nicola P. Bondonno, Amanda Devine, Catherine P. Bondonno, Joshua R. Lewis, Jonathan M. Hodgson & Lauren C. Blekkenhorst

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LCB, RM, and JMH designed the research. ELC conducted the study with assistance from AHL, LM, SRB, AD, MS, CRH, BHP, SKG, CJS, CPB, JRL, JMH, and LCB. AS, MCB, KDC, LGW, LM, and HK conducted the laboratory analysis. ELC performed statistical analysis in consultation with NPB, RJW, JMH, and LCB. ELC wrote the original draft manuscript in consultation and with editing from LCB. ELC and LCB had primary responsibility for the final content. All authors critically revised the manuscript, provided intellectual contribution to the interpretation of results, and read and approved the final manuscript.

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12916_2024_3577_moesm1_esm.docx.

Additional file 1. Table S1 Detailed inclusion and exclusion criteria. Table S2 Dietary intakes of study participants at baseline obtained using a food frequency questionnaire. Table S3 Comparison of energy, macronutrients, and food groups consumed during both interventions for all participants who completed the study ( n = 18). Table S4 Ambulatory aortic blood pressure and arterial stiffness by intervention and between intervention differences. Table S5 Anthropometric measurements, energy expenditure from physical activity, and perceived stress by intervention.

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Connolly, E.L., Liu, A.H., Radavelli-Bagatini, S. et al. Cruciferous vegetables lower blood pressure in adults with mildly elevated blood pressure in a randomized, controlled, crossover trial: the VEgetableS for vaScular hEaLth (VESSEL) study. BMC Med 22 , 353 (2024). https://doi.org/10.1186/s12916-024-03577-8

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Received : 30 November 2023

Accepted : 22 August 2024

Published : 02 September 2024

DOI : https://doi.org/10.1186/s12916-024-03577-8

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• Cruciferous
• Hypertension
• Blood pressure
• Older adults
• Glucosinolates
• Oxidative stress
• Inflammation
• Cardiovascular disease
• Randomized controlled trial

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