master thesis of neonatal sepsis

Early diagnosis and management of neonatal sepsis: a perspective

• Published: 31 March 2024
• Volume 20 , pages 303–306, ( 2024 )

Cite this article

• Li-Zhong Du 1  

837 Accesses

1 Altmetric

Explore all metrics

Avoid common mistakes on your manuscript.

Neonatal sepsis is an illness caused by bloodstream bacteria or fungal infections that affect newborn infants under 28 days of age. It stands as a significant contributor to morbidity and mortality in neonatal intensive care units (NICUs). With the improved survival rates of very low-birth-weight or extremely premature infants, a growing number of these vulnerable infants are receiving intensive care and undergoing invasive procedures, making nosocomial infections a persistent challenge in NICUs. The mortality rate associated with neonatal sepsis varies depending on factors such as birth weight, gestational age, and other co-morbidities. It can also lead to a range of long-term health consequences, including neurodevelopmental disabilities like cerebral palsy, visual or hearing impairments, and cognitive problems. Furthermore, neonatal sepsis is linked to various adverse outcomes, including respiratory complications, bronchopulmonary dysplasia, nutritional and growth issues, and immunological dysfunction [ 1 ]. Due to its atypical clinical presentation and the low rate of specific diagnostic indicators, such as a positive blood culture, accurately diagnosing neonatal sepsis is challenging. Consequently, the appropriateness of antibiotic treatment is often a matter of controversy.

Disease burden and epidemiology

The incidence of sepsis is most prevalent in neonates. Both bacterial early-onset sepsis (EOS) and late-onset sepsis (LOS) continue to pose serious complications in NICUs, resulting in high morbidity and mortality rates. In the USA, the overall incidence of EOS has remained relatively stable at about 0.8 cases per 1000 live births (LBs) over the past two decades [ 2 ]. However, the incidence of EOS among inborn infants of < 34 weeks’ gestation in 18 Chinese perinatal centers was notably higher at 9.7 cases per 1000 LBs [ 3 ].

The lack of standardization in diagnostic criteria and the definition of sepsis across available studies present obstacles to accurately estimating the global burden. A comprehensive study reviewed evidence from observational epidemiological studies to gauge the global burden and mortality of sepsis in neonates and children. The population-level estimate for neonatal sepsis was 2202 per 1,00,000 LBs, with mortality rates ranging from 11% to 19%. This would translate to an annual incidence of 3.0 million cases of neonatal sepsis globally [ 4 ]. In China, birth population-based surveys conducted in one region, which approximated national average levels, estimated the incidence of neonatal sepsis at 25.6 per 1000 LBs [ 5 ]. The case fatality rate of EOS in China was 19% (61 out of 321) [ 3 ].

As a middle-income country, China has limited population-based data on neonatal sepsis available in the literature. However, the recently launched national neonatal network, the Chinese Neonatal Network (CHNN), systematically collected multicenter qualified data from very low-birth-weight or very preterm infants in Chinese NICUs. Through the standardization of diagnostic criteria and the definition of sepsis, the incidence of LOS sepsis in very low-birth-weight infants in Chinese NICUs was determined to be 9.4% [ 6 ].

Screening and diagnosis

Clinical signs of neonatal sepsis encompass a spectrum from sub-clinical infection to severe manifestations of focal or systemic disease. Given that the clinical presentations of neonatal sepsis are non-specific, precise diagnosis is extremely important. Underdiagnosis may lead to the development of overwhelming infection or central nervous system involvement, while overdiagnosis can result in inappropriate antibiotic use. Various predictive models and scoring systems for neonatal sepsis have been developed and applied in diagnostic settings and retrospective studies. [ 7 , 8 , 9 ]. The clinical perinatal risk assessment program and the development guidelines for EOS, such as the National Institute for Health and Care Excellence (NICE) sepsis guideline [ 10 ], and Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics (AAP) guidelines for EOS risk assessment [ 11 ], play crucial roles in this regard. In 2019, China developed guidelines for the screening and diagnosis of neonatal sepsis in those at risk [ 12 ]. Both the NICE and the US sepsis guidelines emphasize clinical presentation and risk factor assessment, whereas the Chinese guideline incorporates laboratory non-specific markers such as C-reactive protein (CRP) or complete blood cell count (CBC) to a greater extent. Nevertheless, countries need to adapt these guidelines or screening procedures according to the local disease spectrum and health policy context. Whether these differences result in increased sensitivity for sepsis diagnosis or contribute to overdiagnosis requires further validation through study.

The American College of Obstetricians and Gynecologists (ACOG) recommends universal maternal screening through vaginal-rectal culture between 36 and 38 weeks of gestation as an effective measure to prevent Group B Streptococcus (GBS) EOS [ 13 ]. However, no standard guidelines currently exist for maternal GBS screening and neonatal GBS disease prevention in China. GBS is one of the leading causes of neonatal sepsis and maternal disease globally. Neonatal GBS infections have been increasingly reported in Chinese literature since the early twenty-first century. Recent studies, such as one in Shanghai involving 12,132 women in late pregnancy, revealed a GBS colonization rate of 6.52% [ 14 ]. A systematic review indicated that the maternal GBS colonization rate in mainland China ranged from 3.70% to 14.52%, with an incidence of invasive GBS disease in infants ranging from 0.55% to 1.79% per 1000 LBs and a case fatality risk between 6.45% and 7.10% [ 15 ]. Presently, universal prenatal screening for GBS carriage has not been implemented in China [ 16 ].

Surveillance and prevention of LOS are crucial issues. Advances in neonatal intensive care, coupled with an increased number of very to extremely preterm infants receiving care and undergoing invasive procedures or indwelling catheter use, contribute to a higher rate of nosocomial infections or LOS. Clinical management is further complicated by an increasing proportion of bacterial pathogens displaying in vitro resistance to commonly used first and second-line antibiotics for LOS treatment.

Neonatal sepsis work-up is essential for timely diagnosis and preventing adverse outcomes before the development of overwhelming sepsis or septic shock. Although a positive blood culture has traditionally been considered the gold standard, its yield is relatively low and can be influenced by factors such as sample volume, culture technique, and antibiotic usage prior to sampling [ 17 ]. Polymerase chain reaction and reverse hybridization of the 16S rRNA gene offer a fast and sensitive means of detecting the presence of bacteria and differentiating between Gram-positive and Gram-negative bacteria in clinical specimens [ 18 ]. Recently, metagenomic techniques using next-generation sequencing have enabled rapid, accurate, and unbiased identification of multiple microorganisms, particularly in cases with negative cultures or when identifying unusual microorganisms that are challenging to grow in culture, such as viruses, fungi, and parasites. However, current investigations using this technology are limited, and studies carry a high risk of bias. Further research employing this technique could enhance the rational use of antibiotics. One limitation is the difficulty in distinguishing between pathogens and commensals typical of each anatomical site [ 19 ].

In culture-independent sepsis work-up, non-specific biomarkers such as procalcitonin, CRP, white blood cell count, and absolute neutrophil count are commonly included. Some institutes also utilize serum cytokines to aid in the diagnosis [ 20 ]. However, these biomarkers are generally more reliable for negative predictivities than positive predictivities and should be used in conjunction with clinical presentations such as poor perfusion, heart rate variation, apnea, and poor feeding. It is noteworthy that in China, some institutes tend to over-rely on a CRP level of ≥ 8–10 mg/L as a cutoff for a positive predictive value, diagnosing sepsis even in the absence of significant clinical symptoms or signs, and initiating antibiotic treatment. Given the complexity of neonatal sepsis diagnosis, sepsis work-up should never replace clinical judgment and risk assessment.

Prevention and treatment

To prevent sepsis, several measures can be implemented to reduce infection rates, particularly for LOS. Practices such as hand hygiene, promoting enteral breastfeeding, minimizing the duration of central lines, and implementing care bundles for infection control have proven effective in sepsis prevention. Quality improvement programs introducing evidence-based practice have shown promise in reducing infections in Chinese neonatal intensive care units [ 21 ].

Empirical treatment of neonatal sepsis should be initiated promptly upon suspicion. However, challenges arise in finding the right balance, as both undertreating due to ineffective diagnosis and overtreating from overdiagnosis are concerns, with the latter being more pronounced in neonatal sepsis management. A recent multicenter study analyzed antibiotic prescription patterns for 2674 neonates from 15 hospitals in China, using the World Health Organization’s (WHO) Essential Medicines List Access, Watch, and Reserve (AWaRe), and the Management of Antibiotic Classification (MAC) Guidelines. The study revealed that meropenem was the most commonly prescribed antibiotic (11.8%), and broad-spectrum antibiotics, including those in the Watch and Special groups, were likely overused in Chinese neonates [ 22 ]. To address this issue, the Chinese Neonatal Society has developed regulations standardizing the application of meropenem in newborns, aiming to reduce inappropriate usage [ 23 ]. Implementation of the Smart Use of Antibiotics Program has also proven effective in reducing antibiotic exposure without compromising the quality of care [ 24 ].

A quality improvement program highlighted that among infants without infection, early antibiotic use was associated with an increased risk of developing bronchopulmonary dysplasia and late (after 7 days of age) antibiotic use [ 25 ]. These findings underscore the importance of careful consideration in antibiotic administration to neonates, emphasizing the need for judicious use to avoid potential adverse outcomes.

In summary, sepsis remains a significant challenge in NICUs. The increased survival of vulnerable very or extremely preterm infants who require intensive care complicates efforts in sepsis control. Advances in sepsis prevention, screening, diagnosis, and treatment have facilitated early recognition and intervention for neonates at risk. The development of neonatal quality improvement programs for sepsis control has shown promise.

Jiang S, Yang C, Yang C, Yan W, Shah V, Shah PS, REIN-EPIQ Study Group, et al. Epidemiology and microbiology of late-onset sepsis among preterm infants in China, 2015–2018: a cohort study. Int J Infect Dis. 2020;96:1–9.

Article   CAS   PubMed   Google Scholar  

Schrag SJ, Farley MM, Petit S, Reingold A, Weston EJ, Pondo T, et al. Epidemiology of invasive early-onset neonatal sepsis, 2005 to 2014. Pediatrics. 2016;138: e20162013.

Article   PubMed   Google Scholar  

Jiang S, Hong L, Gai J, Shi J, Yang Y, Lee SK, REIN-EPIQ Study Group, et al. Early-onset sepsis among preterm neonates in China, 2015 to 2018. Pediatr Infect Dis J. 2019;38:1236–41.

Fleischmann-Struzek C, Goldfarb DM, Schlattmann P, Schlapbach LJ, Reinhart K, Kissoon N. The global burden of paediatric and neonatal sepsis: a systematic review. Lancet Respir Med. 2018;6:223–30.

Wang H, Yue H, Sun B, Zhu X, Niu H, Qi T, et al. Birth population survey in Huai’an in 2015: perinatal-neonatal mortality and preterm birth rate in emerging regions in China. J Matern Fetal Neonatal Med. 2020;33:838–46.

Cao Y, Jiang S, Sun J, Hei M, Wang L, Zhang H, et al. Assessment of neonatal intensive care unit practices, morbidity, and mortality among very preterm infants in China. JAMA Netw Open. 2021;4:e2118904.

Article   PubMed   PubMed Central   Google Scholar  

Sahu P, Raj Stanly EA, Simon Lewis LE, Prabhu K, Rao M, Kunhikatta V. Prediction modelling in the early detection of neonatal sepsis. World J Pediatr. 2022;18:160–75.

Kopec G, Collin M, Das A. Application of Kaiser Sepsis Calculator in culture positive infants with early onset sepsis. World J Pediatr. 2021;17:429–33.

Zhao C, Xin MY, Li J, Zhao JF, Wang YJ, Wang W, et al. Comparing the precision of the pSOFA and SIRS scores in predicting sepsis-related deaths among hospitalized children: a multi-center retrospective cohort study. World J Emerg Med. 2022;13:259–65.

NICE guideline. Neonatal infection: antibiotics for prevention and treatment. https://www.nice.org.uk/guidance/ng195 . Accessed 18 Feb 2024.

Brady MT, Polin RA. Prevention and management of infants with suspected or proven neonatal sepsis. Pediatrics. 2013;132:166–8.

Subspecialty Group of Neonatology, the Society of Pediatric, Chinese Medical Association; Professional Committee of Infectious Diseases, Neonatology Society, Chinese Medical Doctor Association. Expert consensus on the diagnosis and management of neonatal sepsis (version 2019). Zhonghua Er Ke Za Zhi. 2019;57:252–7 ( in Chinese ).

Google Scholar  

Prevention of group B streptococcal early-Onset disease in newborns: ACOG committee opinion, number 797. Obstet Gynecol. 2020;135:e51–e72.

Ma H, Xu J, Zhang Y, Zhang R, Wu J. The current status of Group B Streptococcus infection in the reproductive tract of late-pregnancy women and its impact on pregnancy outcomes. Arch Gynecol Obstet. 2024. https://doi.org/10.1007/s00404-023-07343-8 .

Huang J, Lin XZ, Zhu Y, Chen C. Epidemiology of group B streptococcal infection in pregnant women and diseased infants in mainland China. Pediatr Neonatol. 2019;60:487–95.

Chen X, Cao S, Fu X, Ni Y, Huang B, Wu J, et al. The risk factors for Group B Streptococcus colonization during pregnancy and influences of intrapartum antibiotic prophylaxis on maternal and neonatal outcomes. BMC Pregnancy Child birth. 2023;23:207.

Article   Google Scholar  

Yaacobi N, Bar-Meir M, Shchors I, Bromiker R. A prospective controlled trial of the optimal volume for neonatal blood cultures. Pediatr Infect Dis J. 2015;34:351–4.

Shang S, Chen Z, Yu X. Detection of bacterial DNA by PCR and reverse hybridization in the 16S rRNA gene with particular reference to neonatal septicemia. Acta Paediatr. 2001;90:179–83.

Agudelo-Pérez S, Fernández-Sarmiento J, León DR, Peláez RG. Metagenomics by next-generation sequencing (mNGS) in the etiological characterization of neonatal and pediatric sepsis: a systematic review. Front Pediatr. 2023;11:1011723.

Genel F, Atlihan F, Gulez N, Kazanci E, Vergin C, Terek DT, et al. Evaluation of adhesion molecules CD64, CD11b and CD62L in neutrophils and monocytes of peripheral blood for early diagnosis of neonatal infection. World J Pediatr. 2012;8:72–5.

Cao Y, Jiang S, Zhou Q. Introducing evidence-based practice improvement in Chinese neonatal intensive care units. Transl Pediatr. 2019;8:257–61.

Zhang J, Lin L, Lu G, Wu K, Tian D, Tang L, et al. Patterns of antibiotic administration in Chinese neonates: results from a multi-center, point prevalence survey. BMC Infect Dis. 2024;24:186.

Guideline Development Group of Clinical Practice Guidelines for Meropenem Therapy in Neonatal Sepsis. Clinical Practice guidelines for meropenem therapy in neonatal sepsis. Zhongguo Dang Dai Er Ke Za Zhi. 2024;26:107–17.

Lu C, Liu Q, Yuan H, Wang L. Implementation of the smart use of antibiotics program to reduce unnecessary antibiotic use in a neonatal ICU: a prospective interrupted time-series study in a developing country. Crit Care Med. 2019;47:e1–7.

Yu W, Zhang L, Li S, Yan W, Bai R, Yang Z, et al. Early antibiotic use and neonatal outcomes among preterm infants without infections. Pediatrics. 2023;151:e2022059427.

Download references

Acknowledgements

The author thanks WJP editorial office for editing this manuscript.

This work was financially supported by National Natural Science Foundation of China (82241017).

Author information

Authors and affiliations.

Neonatal Intensive Care Unit, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310052, China

Li-Zhong Du

You can also search for this author in PubMed   Google Scholar

Contributions

DLZ wrote, revised, and approved the final version of the manuscript.

Corresponding author

Correspondence to Li-Zhong Du .

Ethics declarations

Conflict of interest.

The author declare that he has no financial or non-financial conflict of interest. Author Li-Zhong Du is a member of the Editorial Board for World Journal of Pediatrics . The paper was handled by the other Editor and has undergone a rigorous peer review process. Author Li-Zhong Du was not involved in the journal's review of, or decisions related to, this manuscript. Other authors have no conflict of interest to disclose.

Ethical approval

Not needed.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Du, LZ. Early diagnosis and management of neonatal sepsis: a perspective. World J Pediatr 20 , 303–306 (2024). https://doi.org/10.1007/s12519-024-00803-4

Download citation

Published : 31 March 2024

Issue Date : April 2024

DOI : https://doi.org/10.1007/s12519-024-00803-4

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Find a journal
• Publish with us
• Track your research

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here .

Loading metrics

Open Access

Peer-reviewed

Research Article

Treatment outcome of neonatal sepsis and associated factors among neonates admitted to neonatal intensive care unit in public hospitals, Addis Ababa, Ethiopia, 2021. Multi-center cross-sectional study

Roles Data curation, Investigation, Writing – original draft

Affiliation Yekatit 12 Hospital, Addis Ababa, Ethiopia

Contributed equally to this work with: Tefera Mulugeta, Fikertemariam Abebe, Yitayal Guadie, Dires Birhanu, Esmelealem Mihretu

Roles Software, Supervision

Affiliation College of Health Science, Addis Ababa University, Addis Ababa, Ethiopia

Roles Methodology, Visualization, Writing – review & editing

Roles Data curation, Formal analysis, Methodology, Validation

Affiliation Colleges of Medicine and Health Science, Debre Markos University, Debre Markos, Ethiopia

Roles Methodology, Software, Validation

Roles Data curation, Formal analysis, Software, Writing – review & editing

Affiliation College of Health Science, Dila University, Dilla, Ethiopia

Roles Conceptualization, Methodology, Writing – review & editing

* E-mail: [email protected]

• Asalef Endazanaw, 
• Tefera Mulugeta, 
• Fikertemariam Abebe, 
• Yohannes Godie, 
• Yitayal Guadie, 
• Dires Birhanu, 
• Esmelealem Mihretu

• Published: May 30, 2023
• https://doi.org/10.1371/journal.pone.0284983
• Peer Review
• Reader Comments

Globally, neonatal sepsis is the leading cause of neonatal mortality and morbidity, particularly in developing countries. Despite studies that revealed the prevalence of neonatal sepsis in developing countries, the outcome of the diseases, barriers for poor outcomes were inconclusive. The aim of this study was to assess the treatment outcome of neonatal sepsis and its associated factors among neonates admitted to neonatal intensive care unit in public hospitals, Addis Ababa, Ethiopia, 2021.

A cross-sectional study was carried out from February 15 to May 10, 2021 on 308 neonates admitted to neonatal intensive care units of Addis Ababa city public hospitals. Hospitals and study participants were selected by lottery and systematic random sampling techniques, respectively. Data were collected through face-to-face interviews with a structured, pretested questionnaire and by reviewing both the maternal and newborn profile cards. Epi-data version 4.6 was used to enter the collected data, which was then exported to SPSS version 26 for analysis. The 95% CI odds ratio is used to determine the direction and strength of the association between the dependent and independent variables.

Among the total study 308 neonates, 75(24.4%) were died. Regarding the poor treatment outcome of neonatal sepsis, neonates whose mothers <37 weeks of gestational age (AOR = 4.87, 95% CI: 1.23–19.22), Grunting (AOR 6.94: 1.48–32.54), Meconium amniotic stained (AOR = 3.03, 95% CI: 1.02–9.01), Duration of rupture of membrane >18hours (AOR = 3.66, 95% CI: (1.20–11.15), Hypertensive PIH/ Eclampsia (AOR = 3.54, 95% CI: 1.24–10.09), Meropenum (AOR = 4.16, 95% CI: 1.22–14.21) and CRP positive result (AOR = 5.87, 95% CI: 1.53–22.56) were significantly associated with poor treatment outcome of neonatal sepsis.

Conclusion and recommendation

The treatment outcomes of neonates were 75.6% recovered and 24.4% died. In this setting, empirical treatment was the cornerstone for managing neonatal sepsis. Professionals who are working in labor and delivery ward screened for mothers preeclampsia and duration of rupture of membrane >18hrs /PROM/ treated with antihypertensive drug and antibiotics for the prevention of neonatal sepsis.

Citation: Endazanaw A, Mulugeta T, Abebe F, Godie Y, Guadie Y, Birhanu D, et al. (2023) Treatment outcome of neonatal sepsis and associated factors among neonates admitted to neonatal intensive care unit in public hospitals, Addis Ababa, Ethiopia, 2021. Multi-center cross-sectional study. PLoS ONE 18(5): e0284983. https://doi.org/10.1371/journal.pone.0284983

Editor: Sanjoy Kumer Dey, Bangabandhu Sheikh Mujib Medical University (BSMMU), BANGLADESH

Received: August 1, 2022; Accepted: April 12, 2023; Published: May 30, 2023

Copyright: © 2023 Endazanaw 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 relevant data are within the paper.

Funding: The author(s) received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Neonatal sepsis is characterized as an infectious disease syndrome with a clinically suspected or culture-confirmed infection occurring within the first 28 days of life. It is a prevalent critical illness in the neonatal intensive care unit (NICU) [ 1 ]. One of the primary causes of morbidity and mortality in newborns is neonatal sepsis, a systemic infection that affects infants up to 28 days of age [ 2 ].

Around the world, newborn sepsis is thought to be the cause of 26% of fatalities in children under the age of five, with Sub-Saharan Africa (SSA) having the highest mortality rates. Neonatal mortality is unevenly distributed in Sub-Saharan Africa, where it is estimated that 49.6% of all under-five deaths occurred in 2013 [ 3 ]. Additionally, 30–50% of newborn mortality in underdeveloped nations and 15% of all neonatal deaths worldwide are attributable to neonatal sepsis. In Sub-Saharan Africa, neonatal sepsis is responsible for 17% of neonatal mortality. Neonatal sepsis, which causes over 37% of newborn mortality in Ethiopia and more than one-third of all neonatal deaths, is to blame [ 4 ].

One of the global initiatives of WHO is to reduce infant and under-five mortality in African countries to as low as 12/1000 and 25/1000, respectively, by the year 2030. The key to accomplishing this would be to improve the management and prevention of severe infections and preterm births [ 5 ].

In Ethiopia study shows that, small gestational age, being male, out born, not having breastfeed and lower Apgar score in the first 5 minute were identified as associated factors for the poor treatment outcome of preterm neonates admitted in NICU [ 6 ]. According to the 2019 Mini Ethiopian Demographic Health Survey (MEDHS) report, the neonatal mortality rate (NMR) is 30/1000 live births, a slight decrease from the 2011 EDHS report of 37/1000 live births. This high number of deaths is largely due to neonatal sepsis [ 5 , 7 ]. In a number of developing countries, identification of factors for neonatal sepsis and treatment of neonates with sepsis is not satisfactory. Moreover, reports from low income countries revealed inconsistencies in the prevalence, risk factors, and mortality from that of developed countries. Identification of risk factors and timely initiation of treatments can significantly decrease neonatal mortality and morbidity [ 8 ]. The outcomes of neonatal sepsis treatment vary between hospitals with different setups. Early detection and treatment are required to save the lives of our children and grandchildren. This may necessitate the use of expertise to identify common risk factors, antimicrobial use patterns, and clinical outcome treatment of neonatal sepsis. Therefore the purpose of this study was to assess treatment outcome and associated factors of neonatal sepsis among neonates admitted to neonatal intensive care unit in public hospitals, Addis Ababa, Ethiopia.

Methods and materials

Study design and setting.

This was a facility-based quantitative cross-sectional study carried out from February 15 to May 10, 2021 across Addis Ababa city public hospitals. Addis Ababa is the capital city of Ethiopia and seat of African Union and the United Nations World Economic Commission for Africa. It covers an area of 527 square kilometers and has 11 sub cities [ 9 ]. According to a population projection value for 2020 the city has an estimated population of 4.8 million.

The city has 12 public Hospitals among these, 11 hospitals having neonatal intensive care unit. Among these 6 were under Addis Ababa Health Bureau, 5 were under ministry of health and 1 was under Addis Ababa University (Tikur Anbessa Specialized Hospital) [ 10 ]. The study was conducted in four Addis Ababa public Hospitals (36%) selected by lottery method. These selected hospitals are Gandhi Memorial hospital (GMH), St peter Specialized hospital (SPSH), Tikur Anbessa special hospital (TASH) and Yekatit 12 hospital medical college (Y12HMC).

Sample size and sampling procedure

The sample size was determined using a single population–proportion formula by assuming a proportion (P) with culture-proven neonatal sepsis of 23.9%, the previous study in Ethiopia [ 11 ], a 5% margin of error (d), 10% nonresponse rate, n = ( Za /2) 2 p (1 − p )/( d ) 2 and the result was 308 neonates. Of the Eleven public hospitals in Addis Ababa city, four public hospitals (36%) were randomly selected for this study using a lottery method to.

Before the actual data collection started, the total number of neonates diagnosed as sepsis and admitted to NICU monthly was reviewed in each of the selected hospitals. Then the total sample size of the study was allocated proportionally to each selected hospital based on their previous number of neonates diagnosed as sepsis admitted to NICU. Neonates that fulfill eligibility criteria were recruited from respective study hospitals. Finally, 308 neonates diagnosed with sepsis were selected by using systematic random sampling technique from February 15, 2021 to May 10, 2021 with ‘k’ interval of 2. During the data collection, the first participant was selected by lottery method.

Study population.

During the study period, all neonate patients admitted to NICUs of Addis Ababa selected public hospitals were diagnosed with neonatal sepsis.

Inclusion criteria

The study included neonates with clinical diagnosis of sepsis based on the following two risk factors and/or clinical features of bacterial infections.

Risk factors include low birth weight (<2500 grams) or prematurity (<37 weeks of gestation age), febrile illness in the mother within 2 weeks prior to delivery, foul-smelling discharge and/or meconium stained amniotic liquid, prolonged rupture of membranes >18 hours, suspected chorioamnionitis, prolonged labor (> 24 hours), and perinatal asphyxia (Apgar score <4 at 1 minute).

Clinical features of sepsis include poor reflexes, lethargy, respiratory distress, bradycardia, apea, fever, convulsions, abdominal distension, and bleeding.

Data collection instrument and procedures

Data were gathered using a structured questionnaire and in face to face interviews. The data collection tools were adapted from various sources of information [ 3 , 10 – 13 ] and by reviewing both maternal and newborns profile cards. To ensure consistency, the questionnaire was created in English first, and then translated into Amharic and then back into English by language experts. The data was collected in day the day time shift from 8:00 a.m. to 5:30 p.m. after obtaining consent from each participant prior to data collection in the hospitals after finishing the services and returning home. Data was recruited by eight trained BSc nurses and they were supervised by four senior nurses having previous experience in data collection. Training was provided on data collection procedures; including how to conduct interviews, administer questionnaires, obtain consent, maintain confidentiality, and respect the rights of participants. Continuous follow up and supervision was made by principal investigator throughout the data collection period from February 15, 2021 to May 10, 202.

Data quality control

Supervisors and data collectors were trained on how and what information they should collect from the targeted data sources to ensure data quality. Expertise was given a tool to check the content’s validity and accuracy. It was pre-tested on 5% (n = 15) of similar mothers outside the study area at Zewditu Memorial Hospital to assess its completeness, clarity, length, skip patterns, and correctness of filled questioners. The questionnaire was modified based on the results of the pretest. Data was collected by trained health professionals from other units of the health facility.

Data analysis procedure

Data were entered into EPI Data version 4.6 and analyzed in SPSS Software version 26. Bi-variable analysis was used to examine the relationship between each independent variable and the outcome variable. To account for all potential confounders, all variables with p-values ≤ 0.25 were included in the multivariable model. The linear correlation among the independent variables was also examined using multi-co linearity. The degree of association between dependent and independent variables was determined using an odds ratio with a 95% confidence interval and a p-value ≤ 0.05.

Socio-demographic characteristics of respondents

All 308 required study participants were interviewed, with a 100% response rate. Among those who responded, 121 (39.3%) of the mothers were between the ages of 25 and 29. The mother’s average age was 29.37(±5.16) years. Almost all of the respondents, 296 (96.2%), were married. Around 267 (63.6%) of mothers had secondary or higher education. The average monthly household income of the study participants was 7501 Ethiopian Birr (136 (44.2%) of government employees and 84 (27.3%) of respondents. The mean and standard deviation of household income were 5775.8 (±3543.2) years.

Obstetric and neonatal health related factors of the study participants for their neonates

Almost all the respondents, 303 (98.4%), had an ANC follow-up. 221 (71.8%) of those who received ANC follow-up had four or more visits. The majority of mothers, 247 (80.2%), delivered their newborns in a hospital. Half of the 157 mothers with their newborns were 37 weeks gestational age ( Table 1 ).

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

https://doi.org/10.1371/journal.pone.0284983.t001

In terms of birth weight, 163 (52.9%) of neonates weighed 2.5 kg. The majority of neonates, 262 (85.1%), were admitted when they were older than 30 minutes ( Table 2 ).

https://doi.org/10.1371/journal.pone.0284983.t002

Treatment and laboratory findings of neonatal sepsis

Regarding the treatment outcomes, the majority of neonates 233 (75.6%) recovered from their condition with improvement, and 75 (24.4%) died ( Table 3 ).

https://doi.org/10.1371/journal.pone.0284983.t003

Almost all neonates were administered the combination of ampicillin and gentamicin as a first line ( Fig 1 ).

Others **: fluconazole, esomeprazole, TTC, phototherapy.

https://doi.org/10.1371/journal.pone.0284983.g001

In this study, the possible causes of neonatal deaths are 35(46.67%), cardio respiratory arrest secondary to respiratory problems and 14(18.67%) sepsis ( Fig 2 ).

https://doi.org/10.1371/journal.pone.0284983.g002

Predictor variable of treatment outcome of neonatal sepsis

The association of the independent and dependent variable were first tested by using bi-variable analysis which (P≤0.25) were tested in the final multivariable analysis to see their significant association with their treatment outcome of neonatal sepsis. Accordingly, as shown in Table 4 below those bi-variable regression associated with the crude odds ratios (COR) treatment outcome of neonatal sepsis such as education status of the mothers, place of delivery, gestational age < 37weeks, birth weight of the neonate, age of the neonate admitted to NICU, sever chest in drawing, grunting, un able to feed, temperature, Chorioamnaties, meconium amniotic stained, PROM, Hypertensive PIH/ Eclampsia, meropenum, vancomycin, metronidazole, CBC and CRP result.

https://doi.org/10.1371/journal.pone.0284983.t004

In Multivariable analysis results showed that, there was statistically significance association found between) Poor treatment outcome of neonatal sepsis parameters which showed p-value of below 0.05 were Preterm babies admitted to NICU (gestational age), grunting, meconium amniotic stained, duration of rupture of membrane >18hours (PROM), Hypertensive PIH/ Eclampsia, meropenum and CRP result.

This study aimed to assess treatment outcome of neonatal sepsis and its associated factors among newborns delivered in public hospitals in Addis Ababa, Ethiopia. In this study, the prevalence of poor neonatal sepsis treatment outcome was 24.4% with a 95% CI among newborns admitted to NICU in public hospitals in Addis Ababa (19.5–29.2). This finding is higher compared to a study conducted in Bahir dar (16%) [ 12 ]. This deference could be attributed to the way neonatal sepsis has been used to confirmatory blood culture to assert neonatal sepsis to the study that is done in some facility. In addition to this, NICU services at Felegehowot referral hospital are organized with personnel and equipment based on newborn conditions(severity) and classified as level-1(basic), level-2 (specialty) and level-3 (subspecialty) and study design (retrospective follow up that all deaths might not be documented. Many of the complications of preterm birth that result in poor in-hospital outcomes are related to gestational age, with premature infants being more vulnerable. This finding is nearly identical to a study conducted in Debrezeyt, Ethiopia, where 26% [ 13 ]. This finding is lower compared to a study conducted in Nigeria were (34%) [ 14 ]. This could be related with use of advanced confirmatory blood culture to establish neonatal sepsis in the Nigeria, which is difficult to apply in this study area due to the lack of some facilities. Another possible explanation for this variation is the variation in health facility and sample size across studies.

Neonatal sepsis treatment outcomes were 5 times more likely to be bad in newborns under 37 weeks of gestational age compared to newborns who were 37 weeks or older. This is consistent with research from Gondar [ 15 ], Tikur Anbessa Specialized Hospital, Ethiopia [ 16 ] and Kenya [ 17 ], which found that preterm newborns had a higher mortality rate than term newborns. This result is comparable to that of an Australian study, which discovered that a gestational age of one week enhanced the neonatal survival rate by more than 5% [ 18 ].

The odds of neonates born from mothers with developing Hypertensive PIH/ Eclampsia were 4 times higher than those of neonates born from who did not develop Hypertensive PIH/ Eclampsia. This finding is consistent with previous research that found chronic hypertension to be a risk factor for neonatal sepsis in Ethiopia. This could be because maternal hypertensive problems have a direct impact on fetal wellbeing in the uterus, which contributes to neonatal sepsis at birth.

PROM was statistically significantly associated with a poor treatment outcome of sepsis. Mothers who gave birth to neonates with PROM were 4 times more likely to suffer from sepsis compared with those neonates born from women who had not developed PROM. This finding is comparable with studies conducted in Nepal [ 19 ], Mexico [ 20 ] and USA [ 21 ]. These could be caused by aerobic and anaerobic pathogens colonizing the birth canal, resulting in ascending amniotic fluid infection and neonate colonization at birth. Mother-to-fetus transmission of bacterial agents infecting the amniotic fluid and birth canal during labor and delivery may occur more frequently, resulting in neonatal sepsis (EONS) [ 22 ].

Meconium amniotic stained were 3 times developed poor treatment outcome when compared to those neonates without history of Meconium amniotic stained. Which is similar with a study in Bahir dar [ 12 ], Uganda [ 23 ], Ghana [ 3 ], India [ 24 ] and Nepal [ 19 ]. This is revealed that after meconium aspiration strict follow up is needed for neonates. This may be due to neonates delivered from women with meconium stained amniotic fluid are more liable to aspirate it and fill smaller air ways and alveoli in the lung. And it increases the multiplication of microbes that cause sepsis and predisposes to late onset neonatal sepsis (LONS) [ 25 ].

A neonate who has at risk of respiratory problem was significantly associated with poor outcome of neonatal sepsis. Those neonates developed with grunting were 7 times developed poor outcome compared to neonates without respiratory distress syndrome. This is similar with a study in Bahir dar [ 12 ]. This result comparable with studies done in Uganda [ 23 ] and Sudan [ 26 ]. This may be due to health workers’ ignorance of the syndrome’s poor early detection of signs, and another explanation may be due to mothers’ delay coming in coming to health facilities or institutions.

C-reactive protein levels were found to be significantly associated with a poor sepsis outcome. Positive CRP laboratory results of neonates were 6 times they developed poor treatment outcomes when compared to those of neonates’ negative CRP results. This finding is similar with studies done in Nepal [ 19 ]. This could be because CRP is the most sensitive and widely used test, but it is necessary to consider a sepsis panel of at least three tests, at least two of which must be positive for one to suspect septicemia with reasonable certainty.

In most developing countries, including Ethiopia, empirical treatment is the primary method of managing neonatal sepsis. When compared to neonates who did not receive Meropenum, those who received it had a fourfold worse treatment outcome. In this hospital, antimicrobial use is primarily empirical. This may promote the development of resistant bacteria, influencing future drug selection in the treatment of neonatal sepsis.

The study found both maternal and neonatal factors as possible independent risk factors to have a strong association with the risk of poor outcome of neonatal sepsis. Preterm babies admitted to NICU, grunting, meconium amniotic stained (MSAF), duration of rupture of membrane >18hours (PROM), Hypertensive PIH/ Eclampsia, meropenum and CRP result were significantly associated with poor treatment outcome of neonatal sepsis. Researchers who are interested in conducting research on neonatal sepsis should have to include neonates in the community, which may increase the external validity of the study. It is also better to do a meta-analysis since the previous findings about the factors causing neonatal sepsis were inconsistent.

Acknowledgments

We would like to Acknowledge Addis Ababa University, college of health sciences, school of nursing and Midwifery and department of nursing for giving me the chance. In addition, we would like to extend our thanks to the study participants, data collectors, supervisors for their contribution and commitment throughout the study period.

Ethics approval and consent to participate

Ethical clearance was obtained from the institutional review board of Addis Ababa University, College of Health Sciences, School of Nursing and Midwifery, Department of Nursing (Protocol number: aau/chs/chnsg/18/21). Formal letters were obtained from Addis Ababa Public Health Research and Emergency Management Core Process in order to get permission to carry out the study. After explaining the purpose and procedure of the study, each respondent (mothers/care givers) signed a written informed consent form. No name or other identifying information was included with the instrument. The eligible study participants were enrolled in the study only after they gave written informed consent and will not be forced to participate. All the information given by the respondents was used for research purposes only; Confidentiality and privacy were maintained by omitting the names of the respondents during the data collection procedure and after the data collection was completed.

• View Article
• Google Scholar
• 5. WHO, World health Statistics. Monitoring health for the SDGs, sustainable development goals. WHO Library Cataloguing-in-Publication Data 2016.
• 7. Rockville, Maryland, USA. Mini Demographic and Health Survey Ethiopian Public Health Institute. 2019.
• 8. UNICEF. Committing to Child Survival: A Promise Renewed World Health Organ Tech Rep Ser. 2014.
• 9. World Population projections. Ethiopia Demographics Profile. CIA World. 2019.
• 10. Addis Ababa Health Service Information. General Hospital. Addis Ababa health Bureau 2019/20 (Unpublished)
• PubMed/NCBI
• 26. Khair k. Prevalence and outcome in a tertiary neonatal unit in Sudan. 2014.

Neonatal sepsis: A review of the literature

Article sidebar.

PlumX Metrics

Main Article Content

Neonatal sepsis contributes significantly to neonatal morbidity and mortality and is a major public health challenge around the world. Depending on the mode of occurrence, a distinction is made between maternal-transmitted infection and that acquired in the postnatal period. Although the etiologies maternally transmitted diseases are well understood, those of postnatal acquired infections are variable depending on the epidemiology of each hospital environment. On the one hand, risk factors for maternal-transmitted infections are maternal sepsis, prolonged premature rupture of membranes, chorioamnionitis, and bacteriuria in the mother during pregnancy. On the other hand, risk factors for postnatal acquired infections are prematurity, low birth weight, lack of hygiene, and invasive therapeutic interventions. The diagnosis is based on a series of anamnestic, clinical and biological features. Although the positive diagnosis is based on the isolation of the germ by culture on a body sample (blood, cerebrospinal fluid, urine, etc.); its low sensitivity leads to the use of markers of the acute phase of inflammation such as C-reactive protein, procalcitonin and interleukins. New molecular biology techniques are promising and offer precise diagnosis with rapid results. Empirical management is a function of microbial ecology while definitive treatment is guided by the results of microbial culture. This article presents the essential elements for understanding neonatal sepsis and discusses new diagnosis and therapeutic management. It offers a thorough reading based on the issue of infections in newborns.

Article Details

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License .

• Goldstein B, Giroir B, Randolph A, et al. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatric critical care medicine, 2005, 6(1): 2-8. https://doi.org/10.1097/01.PCC.0000149131.72248.E6
• Agnche Z, Yeshita HY and Gonete KA. Neonatal sepsis and its associated factors among neonates admitted to neonatal intensive care units in primary hospitals in central gondar zone, northwest ethiopia, 2019. Infect Drug Resist, 2020, 13: 3957-3967. https://doi.org/10.2147/IDR.S276678
• Shane AL, S´anchez PJ and Stoll BJ. Neonatal sepsis. Lancet, 2017, 390(10104): 1770-1780. https://doi.org/10.1016/S0140-6736(17)31002-4
• Tripathi S and Malik G. Neonatal Sepsis: past, present and future; a review article. Internet Journal of Medical Update, 2010, 5(2): 45-54. https://doi.org/10.4314/ijmu.v5i2.56163
• Ahirrao BM, Dravid N, Ahirrao M, et al. Diagnostic utility of Haematological scoring system (HSS) with clinicopathological and bacteriological evaluationin early diagnosis of neonatal sepsis. Annals of Pathology and Laboratory Medicine, 2017, 4(6): 721-726. https://doi.org/10.21276/APALM.1504
• Barton M, Shen A, Brien KO, et al. Early Onset Invasive Candidiasis in Extremely Low Birth Weight Infants: Perinatal Acquisition Predicts Poor Outcome. Clinical Infectious Diseases, 2017, 64(7): 921-927. https://doi.org/10.1093/cid/cix001
• Kaufman DA, Coggins SA, Zanelli SA, et al. Congenital Cutaneous Candidiasis: Prompt Systemic Treatment Is Associated with Improved Outcomes in Neonates. Clinical Infectious Diseases, 2017, 64(10): 1387-1395. https://doi.org/10.1093/cid/cix119
• Morriss F, Lindower J, Bartlett H, et al. Neonatal Enterovirus Infection: Case Series of Clinical Sepsis and Positive Cerebrospinal Fluid Polymerase Chain Reaction Test with Myocarditis and Cerebral White Matter Injury Complications. American Journal of Perinatology Reports, 2016, 6(3): 344-351. https://doi.org/10.1055/s-0036-1593406
• Chuang YY and Huang YC. Enteroviral infection in neonates. Journal of Microbiology, Immunology and Infection, 2019, 52(6): 851-857. https://doi.org/10.1016/j.jmii.2019.08.018
• Walker O, Kenny CB and Goel N. Neonatal sepsis. Paediatr Child Heal (United Kingdom), 2019, 29(6): 263-268. https://doi.org/10.1016/j.paed.2019.03.003
• Blond MH, Poulain P, Gold F, et al. Maternal-foetal bacterial infection. EMC - Gynecol, 2005, 2(1): 28-90. https://doi.org/10.1016/j.emcgo.2004.08.001
• Read JS, Cannon MJ, Stanberry LR, et al. Prevention of Mother-to-Child Transmission of Viral Infections. Curr Probl Pediatr Adolesc Health Care, 2008, 38(9): 274-297. https://doi.org/10.1016/j.cppeds.2008.08.001
• O’Keefe C. Viral infections in the neonate. Newborn and Infant Nursing Reviews, 2010, 10(4): 195-202. https://doi.org/10.1053/j.nainr.2010.09.008
• Al-Taiar A, Hammoud MS, Cuiqing L, et al. Neonatal infections in China, Malaysia, Hong Kong and Thailand. Archives of Disease in Childhood - Fetal and Neonatal Edition, 2012, 98(3): 249-255. https://doi.org/10.1136/archdischild-2012-301767
• Kim F, Polin RA and Hooven TA. Neonatal sepsis. The BMJ, 2020, 371: m3672. https://doi.org/10.1136/bmj.m3672
• Giannoni E, Agyeman PKA, Stocker M, et al. Neonatal Sepsis of Early Onset, and Hospital-Acquired and Community-Acquired Late Onset: A Prospective Population-Based Cohort Study. The Journal of Pediatrics, 2018, 201: 106-114. https://doi.org/10.1016/j.jpeds.2018.05.048
• Fleischmann-Struzek C, Goldfarb DM, Schlattmann P, et al. The global burden of paediatric and neonatal sepsis: a systematic review. The Lancet Respiratory Medicine, 2018, 6(3): 223-230. https://doi.org/10.1016/S2213-2600(18)30063-8
• Vergnano S, Sharland M, Kazembe P, et al. Neonatal sepsis: An international perspective. Archives of Disease in Childhood - Fetal and Neonatal Edition, 2005, 90(3): 220-225. https://doi.org/10.1136/adc.2002.022863
• Hyde TB, Hilger TM, Reingold A, et al. Population-Based Surveillance in San Francisco and Atlanta. Healthy San Francisco, 2011, 110(4): 1996-2003. https://doi.org/10.1542/peds.110.4.690
• Tallur SS, Kasturi AV, Nadgir SD, et al. Clinico-bacteriological study of neonatal septicemia in Hubli. The Indian Journal of Pediatrics, 2000, 67(3): 169-174. https://doi.org/10.1007/BF02723654
• Heath PT, Nik Yusoff NK and Baker CJ. Neonatal meningitis. Archives of Disease in Childhood - Fetal and Neonatal Edition, 2003, 88(3): 173-179. https://doi.org/10.1136/fn.88.3.F173
• Schuchat A, Zywicki SS, Dinsmoor MJ, et al. Risk factors and opportunities for prevention of early-onset neonatal sepsis: a multicenter case-control study. Pediatrics, 2000, 105(1): 21-26. https://doi.org/10.1542/peds.105.1.21
• Getabelew A, Aman M, Fantaye E, et al. Prevalence of Neonatal Sepsis and Associated Factors among Neonates in Neonatal Intensive Care Unit at Selected Governmental Hospitals in Shashemene Town, Oromia Regional State, Ethiopia, 2017. International Journal of Pediatrics, 2018, 2018: 1-7. https://doi.org/10.1155/2018/7801272
• Kanteng AW NM. Mortalit´e ´a L’unit´e de N´eonatologie des Cliniques Universitaires de Lubumbashi, Congo. Rev. m´ed. Gd. Lacs 2012, 1(4): 232-244.
• Ranjeva SL, Warf BC and Schiff SJ. Economic burden of neonatal sepsis in sub-Saharan Africa. BMJ global health, 2018, 3(1): e000347. https://doi.org/10.1136/bmjgh-2017-000347
• Chemsi M and Benomar S. Infections bact´eriennes n´eonatales pr´ecoces. Journal de P´ediatrie et de Pu´ericulture, 2015, 28(1): 29-37. https://doi.org/10.1016/j.jpp.2014.10.005
• Lawn J, Shibuya K and Stein C. No cry at birth: global estimates of intrapartum stillbirths and intrapartum-related neonatal deaths. Bulletin of the World Health Organization, 2005, 83: 409-417.
• Black RE, Cousens S, Johnson HL, et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet, 2010, 375(9730): 1969-1987. http://dx.doi.org/10.1016/S0140-6736(10)60549-1
• OMS. Nouveau n´es r´eduire la mortalit´e. Accessible sur, 2018.
• Sankar MJ, Natarajan CK, Das RR, et al. When do newborns die? A systematic review of timing of overall and cause-specific neonatal deaths in developing countries. Journal of Perinatology, 2016, 36(S1): 1-11. https://doi.org/10.1038/jp.2016.27
• Nyenga AM, Malonda BN AA, Assumani AN, et al. Trends in Neonatal Mortality in Lubumbashi (Democratic Republic of Congo) from 2011 to 2018, 2019, 2: 1-5.
• Russell NJ, Seale AC, O’Sullivan C, et al. Risk of Early-Onset Neonatal Group B Streptococcal Disease with Maternal Colonization Worldwide: Systematic Review and Meta-analyses. Clinical Infectious Diseases, 2017, 65: 152-159. https://doi.org/10.1093/cid/cix655
• Boghossian NS, Page GP, Bell EF, et al. Late-onset sepsis in very low birth weight infants from singleton and multiple-gestation births. The Journal of Pediatrics, 2013, 162(6): 4-9. https://doi.org/10.1016/j.jpeds.2012.11.089
• Doit C, Biran V and Aujard Y. Infections nosocomiales en n´eonatologie: Nosocomial infections in neonatal units. Infections n´eonatales. Elsevier Masson SAS, 2015, 91-106. http://dx.doi.org/10.1016/B978-2-294-74135-7/00009-7
• Downey LC, Smith PB and Benjamin DK. Risk factors and prevention of late-onset sepsis in premature infants. Early Human Development, 2010, 86(S1): 7-12. https://doi.org/10.1016/j.earlhumdev.2010.01.012
• Kuti BP, Ogunlesi TA, Oduwole O, et al. Hand hygiene for the prevention of infections in neonates. Cochrane Database of Systematic Reviews, 2019, 2019(5): CD013326. https://doi.org/10.1002/14651858.CD013326
• Turck D, Vidailhet M, Bocquet A, et al. Allaitement maternel: les b´en´efices pour la sant´e de l’enfant et de sa m`ere. Archives de p´ediatrie, 2013, 20(S2): 29-48. https://doi.org/10.1016/S0929-693X(13)72251-6
• Munblit D, Treneva M, Peroni DG, et al. Immune components in human milk are associated with early infant immunological health outcomes: A prospective three-country analysis. Nutrients, 2017, 9(6): 1-14. https://doi.org/10.3390/nu9060532
• Giannattasio A, Marra V, Zoccali S, et al. Nutrition and immunity in newborns. Italian Journal of Pediatrics, 2015, 41(S1): A33. https://doi.org/10.1186/1824-7288-41-S1-A33
• Field CJ. The immunological components of human milk and their effect on immune development in infants. The Journal of Nutrition, 2005, 135(1): 1-4. https://doi.org/10.1093/jn/135.1.1
• Donovan SM and Comstock SS. Human milk oligosaccharides influence neonatal mucosal and systemic immunity. Annals of Nutrition and Metabolism, 2017, 69(2): 42-51. https://doi.org/10.1159/000452818
• Marchant EA, Boyce GK, Sadarangani M, et al. Neonatal sepsis due to coagulase-negative staphylococci. Clinical and Developmental Immunology, 2013, 2013: 586076. https://doi.org/10.1155/2013/586076
• Bizzarro MJ, Shabanova V, Baltimore RS, et al. Neonatal sepsis 2004-2013: The rise and fall of coagulase-negative staphylococci. The Journal of Pediatrics, 2015, 166(5): 1193-1199. https://doi.org/10.1016/j.jpeds.2015.02.009
• Downie L, Armiento R, Subhi R, et al. Community-acquired neonatal and infant sepsis in developing countries: Efficacy of WHO’s currently recommended antibiotics - Systematic review and metaanalysis. Archives of Disease in Childhood, 2013, 98(2): 146-54. https://doi.org/10.1136/archdischild-2012-302033
• Janota J. Hand hygiene with alcohol hand rub and gloves reduces the incidence of late onset sepsis in preterm neonates. Acta Paediatrica, 2014, 103(10): 1053-1056 https://doi.org/10.1111/apa.12731
• Waters D, Jawad I, Ahmad A, et al. Aetiology of community-acquired neonatal sepsis in low and middle income countries. Journal of global health, 2011, 1(2): 154-170.
• Mve Koh Val`ere Salomon, Mengouna Jean-Rosaire and Essiben F´elix GKH. Colonisation G´enitale et Profil de Sensibilit´e du Streptocoque du Groupe B chez les Femmes Enceintes dans deux Hˆopitaux de Yaound´e. Health Sciences and Disease, 2017, 18: 21-25.
• Gbonon V, Guessan RN, Guessennd N, et al. Ecologie et sensibilit´e aux antibiotiques des bact´eries isol´ees d’infections materno-foetales au chu de yopougon (abidjan). Revue Bio-Africa, 2013, 12: 13-18.
• Habzi A and Benomar S. Les Infections Nosocomiales N´eonatales. Journal de P´ediatrie et de Pu´ericulture, 2001, 14(7): 419-424. https://doi.org/10.1016/S0987-7983(01)80115-8
• Griffin MP, Lake DE, O’Shea TM, et al. Heart rate characteristics and clinical signs in neonatal sepsis. Pediatric Research, 2007, 61(2): 222-227. https://doi.org/10.1203/01.pdr.0000252438.65759.af
• Fairchild KD. Predictive monitoring for early detection of sepsis in neonatal ICU patients. Current Opinion in Pediatrics, 2013, 25(2): 172-179. https://doi.org/10.1097/MOP.0b013e32835e8fe6
• De Felice C, Flori ML, Pellegrino M, et al. Predictive value of skin color for illness severity in the high-risk newborn. Pediatric Research, 2002, 51(1) : 100-105. https://doi.org/10.1203/00006450-200201000-00018
• Abourazzak S, Alaoui K, Oulmaati A, et al. L’approche de l’ict`ere dans l’infection urinaire n´eonatale. Archives de P´ediatrie, 2010, 17(6): 72. http://dx.doi.org/10.1016/S0929-693X(10)70488-7
• Kale A, Jaybhaye DL and Bonde V. Neonatal sepsis: An update. Iranian Journal of Neonatology, 2014, 4(4): 39-51.
• Nyenga A, Mukuku O, Mutombo AM ulang, et al. Neonatal infections: what is the place of obstetric history in the prevention of risk?The Pan African Medical Journal, 2014, 19: 133. https://doi.org/10.11604/pamj.2014.19.133.4432
• Adatara P, Afaya A, Salia SM, et al. Risk Factors Associated with Neonatal Sepsis: A Case Study at a Specialist Hospital in Ghana. Te Scientifc World Journal, 2019, 2019: 1-8. https://doi.org/10.1155/2019/9369051
• Kardana IM. Incidence and factors associated with mortality of neonatal sepsis. Paediatrica Indonesiana, 2011, 51(3): 144. https://doi.org/10.14238/pi51.3.2011.144-8
• Puopolo KM, Draper D, Wi S, et al. Estimating the probability of neonatal early-onset infection on the basis of maternal risk factors. Pediatrics, 2011, 128(5): 1155-1163. https://doi.org/10.1542/peds.2010-3464
• Mukhopadhyay S and Puopolo KM. Risk Assessment in Neonatal Early Onset Sepsis. Seminars in Perinatology, 2012, 36(6): 408-415. https://doi.org/10.1053/j.semperi.2012.06.002
• Kuzniewicz MW, Puopolo KM, Fischer A, et al. A quantitative, risk-based approach to the management of neonatal early-onset sepsis. JAMA Pediatr, 2017, 171(4): 365-371. https://doi.org/10.1001/jamapediatrics.2016.4678
• Ruoss JL and Wynn JL. Biomarkers in the Diagnosis of Neonatal Sepsis [Internet]. Infectious Disease and Pharmacology. Infectious Disease and Pharmacology, 2019, 103-112. https://doi.org/10.1016/B978-0-323-54391-0.00009-6
• Zea-Vera A and Ochoa TJ. Challenges in the diagnosis and management of neonatal sepsis. Journal of Tropical Pediatrics, 2015, 61(1): 1-13. https://doi.org/10.1093/tropej/fmu079
• Meem M, Modak JK, Mortuza R, et al. Biomarkers for diagnosis of neonatal infections: A systematic analysis of their potential as a point-of-care diagnostics.Journal of Global Health, 2011, 1(2): 201-109.
• Pammi M, Flores A, Leeflang M, et al. Molecular assays in the diagnosis of neonatal sepsis: A systematic review and meta-analysis. Pediatrics, 2011, 128(4): 973-985. https://doi.org/10.1542/peds.2011-1208
• Lutsar I, Telling K and Metsvaht T. Treatment option for sepsis in children in the era of antibiotic resistance. Expert Review of Anti-infective Therapy, 2014, 12(10): 1237-1252. https://doi.org/10.1586/14787210.2014.956093
• Sullins AK and Abdel-Rahman SM. Pharmacokinetics of antibacterial agents in the CSF of children and adolescents. Pediatric Drugs, 2013, 15(2): 93-117. https://doi.org/10.1007/s40272-013-0017-5
• Chiu CH, Michelow IC, Cronin J, et al. Effectiveness of a guideline to reduce vancomycin use in the neonatal intensive care unit. The Pediatric Infectious Disease Journal, 2011, 30(4): 273-278. https://doi.org/10.1097/INF.0b013e3182011d12
• Magers J, Prusakov P and Sanchez PJ. Evaluation of Nafcillin vs. Vancomycin as Empiric Therapy for Late-Onset Sepsis in the Neonatal Intensive Care Unit. Open Forum Infectious Diseases, 2019, 6(S2): 407-408. https://doi.org/10.1093/ofid/ofz360.1008
• Elbeldi A, Smaoui H, Hamouda S, et al. Les infections `a Listeria monocytogenes `a Tunis: `a propos de sept cas. Bulletin de la Societe de Pathologie Exotique, 2011, 104(1): 58-61. https://doi.org/10.1007/s13149-010-0110-8
• Furyk JS, Swann O and Molyneux E. Systematic review: Neonatal meningitis in the developing world. Tropical Medicine & International Health, 2011, 16(6): 672-679. https://doi.org/10.1111/j.1365-3156.2011.02750.x
• Awad HA, Mohamed MH, Badran NF, et al. Multidrug-resistant organisms in neonatal sepsis in two tertiary neonatal ICUs, Egypt. Journal of the Egyptian Public Health Association, 2016, 91(1): 31-38. https://doi.org/10.1097/01.EPX.0000482038.76692.3
• Shane AL and Stoll BJ. Neonatal sepsis: Progress towards improved outcomes. Journal of Infection, 2014, 68(S1): 24-32. http://dx.doi.org/10.1016/j.jinf.2013.09.011
• Alshaikh B, Yusuf K and Sauve R. Neurodevelopmental outcomes of very low birth weight infants with neonatal sepsis: Systematic review and meta-analysis. Journal of Perinatology, 2013, 33(7): 558-564. https://doi.org/10.1038/jp.2012.167
• Bakhuizen SE, De Haan TR, Teune MJ, et al. Meta-analysis shows that infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications. Acta Paediatrica, 2014, 103(12): 1211-1218. https://doi.org/10.1111/apa.12764
• Peroni DG, Pescollderungg L, Piacentini GL, et al. Neonatal sepsis and later development of atopy. Allergol Immunopathol (Madr), 2009, 37(6): 281-284. https://doi.org/10.1016/j.aller.2009.05.007
• Sobko T, Schi¨ott J, Ehlin A, et al. Neonatal sepsis, antibiotic therapy and later risk of asthma and allergy. Paediatr Perinat Epidemiol, 2010, 24(1): 88-92. https://doi.org/10.1111/j.1365-3016.2009.01080.x
• Aims & Scope
• Author Guidelines
• For Authors
• For Reviewers
• Editorial Team
• Editor-in-Chief
• Peer Reviewer
• Advertising
• Privacy Policy
• Ethical Policy
• Submission Policy
• Archiving Policy

Predictors of mortality among neonates hospitalized with neonatal sepsis: a case control study from southern Ethiopia

Affiliations.

• 1 Durame General Hospital, Durame, SNNPR, Ethiopia.
• 2 Department of Epidemiology, Institute of Health, Jimma University, Jimma, Ethiopia.
• 3 Department of nursing, Ambo University, Woliso Campus, Ambo, Ethiopia. [email protected].
• PMID: 34980043
• PMCID: PMC8722178
• DOI: 10.1186/s12887-021-03049-5

Background: Neonatal sepsis, which resulted from bacterial, viral, and fungal invasions of the bloodstream, is the major cause of neonatal mortality and neurodevelopmental impairment among neonates. It is responsible for more than one-third of neonatal deaths in Ethiopia. Frequently neonates referred to health facilities are at high risk of death. Hence, assessing and preventing the predictors of mortality in neonatal sepsis helps to reduce the burden of neonatal mortality.

Objectives: To determine predictors of mortality among neonates admitted with sepsis at Durame general hospital, southern Ethiopia, 2020.

Methods: Institution-based unmatched case-control study was carried out from March 8 to 30, 2020, among 219 neonates in Durame general hospital in southern Ethiopia. Neonates admitted with sepsis and died were considered as cases and neonates admitted with sepsis and survived (discharged alive) as controls. Cases were selected by taking the deaths of neonates consecutively among those neonates admitted with the diagnosis of neonatal sepsis. The next immediate three corresponding controls were selected by lottery method from the Neonatal Intensive Care Unit (NICU) case registration book. Data was collected by using structured pretested checklists from neonates' records and then entered into Epi data version 3.1 and exported to SPSS version 20. Logistic regression was used to identify the predictors of mortality. Statistical significance was declared at P < 0.05.

Results: A total of 55 cases and 164 controls were included in this study. More than three quarters (81.8%) of cases had early onset sepsis. The multivariable logistic regression analysis showed that predictors of mortality in this study were; poor feeding [AOR = 4.15; 95% CI (1.64, 10.49)], respiratory distress [AOR = 2.72; 95% CI (1.31, 5.61)], estimated gestational age less than 37 weeks [AOR = 4.64; 95% CI (2.17, 9.91)], and convulsion [AOR = 3.13; 95% CI (1.12, 8.76)].

Conclusion: This study showed that prematurity, convulsion, poor feeding, and respiratory distress were the predictors of sepsis-related neonatal mortality. It is important to pay attention to septicemic babies with any of the identified predictors to reduce sepsis-related mortality.

Keywords: Durame; Epidemiology; Ethiopia; Neonatal mortality; Neonatal sepsis.

© 2021. The Author(s).

• Case-Control Studies
• Ethiopia / epidemiology
• Infant Mortality
• Infant, Newborn
• Intensive Care Units, Neonatal
• Neonatal Sepsis* / diagnosis

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• JNMA J Nepal Med Assoc
• v.62(270); 2024 Feb
• PMC10924525

Sepsis among Neonates Admitted to a Neonatal Intensive Care Unit in a Tertiary Care Centre

Kanchan devkota.

1 Nepalgunj Medical College and Teaching Hospital, Nepalgunj, Banke, Nepal

Piush Kanodia

2 Department of Pediatrics, Nepalgunj Medical College and Teaching Hospital, Nepalgunj, Banke, Nepal

Bibek Joshi

Introduction:.

Neonatal sepsis is a condition that carries a high risk for mortality as neonates rapidly transition to extra-uterine life and are subjected to various risk factors. Sepsis prevalence can be reduced by good antenatal care, early detection and treatment of risk factors. The study aimed to find out the prevalence of sepsis among neonates admitted to a neonatal intensive care unit in a tertiary care centre.

This is a descriptive cross-sectional study conducted among neonates admitted to the neonatal care unit of a tertiary care centre after obtaining ethical approval from the Institutional Review Committee. Data of patients admitted from 12 December 2022 to 30 June 2023 was collected from hospital records. Symptomatic patients admitted to the neonatal intensive care unit were included and those with incomplete data were excluded from the study. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval.

Among 379 neonates, the prevalence of sepsis was 138 (36.41%) (28.38-44.44, 95% Confidence Interval). A total of 98 (71.01%) had early-onset neonatal sepsis and 40 (28.99%) had late-onset neonatal sepsis.

Conclusions:

The prevalence of neonatal sepsis was found to be lower than other studies done in similar settings.

INTRODUCTION

Neonatal Sepsis is a condition that carries a high risk for mortality in neonates. From acting as a unit with their mothers to initiating their defence mechanisms, neonates are subjected to various risk factors. The 2016 NDHS shows that the neonatal mortality rate (NMR) has moved from 33 per 1,000 live births to 21 per 1000. 1

The pattern of neonatal diseases varies with variations in geography. In developed countries, the main cause of morbidity and mortality in the neonatal period is congenital abnormalities which are mostly non-preventable, but in developing countries causes such as infections, birth asphyxia and pneumonia predominate. 2 Most of these are preventable by good antenatal care, early detection and treatment. 3 To improve neonatal survival, appropriate interventions should be directed towards illnesses and their prevention. 4

This study aimed to find out the prevalence of sepsis among neonates admitted to a neonatal intensive care unit in a tertiary care centre.

This descriptive cross-sectional study was conducted among patients admitted to the Neonatal Intensive Care Unit, Nepalgunj Medical College and Teaching Hospital, Nepalgunj, Banke, Nepal. Ethical approval was obtained from the Institutional Review Committee of the same institute (Reference number: NGMC-IRC/079/080-34). Data was collected from 12 December 2022 to 30 June 2023 from inpatient records at the hospital record system. Neonates admitted during study period is included in the study. Those with missing data were excluded from study. A convenience sampling method was used. The sample size was calculated by using the following formula:

• n = minimum required sample size
• Z = 1.96 at 95 % Confidence Interval (CI)
• p = prevalence taken as 50% for maximum sample size
• e = margin of error, 6%

The minimum required sample size was 267. However, the final sample size taken was 379.

Prematurity was diagnosed according to the WHO definition of live-born neonates delivered before 37 weeks of gestation and also by incorporating Ballard scoring. Birth weight 15002500 grams was categorized as low birth weight, 1000-1500 grams was categorized as very low birth weight and <1000 that was classified as extremely low birth weight. Neonatal sepsis was diagnosed based on clinical profile, blood culture and septic screening, onset in <72 hours was classified as early onset neonatal sepsis (EONNS) and >72 hours was late-onset neonatal sepsis (LONNS). 3

Data were entered in Microsoft Excel 2016 and analyzed using IBM SPSS Statistics version 25.0. The point estimate was calculated at a 95% CI.

Among 379 patients, the prevalence of neonatal sepsis was 138 (36.41%) (28.38-44.44, 95% CI). A total of 98 (71.01%) had early-onset neonatal sepsis and 40 (28.99%) had late-onset neonatal sepsis. The majority of neonates admitted to the NICU were male 85 (61.59%) and 53 (38.41%) were female. The most common mode of delivery was spontaneous vaginal delivery 86 (62.32%) ( Table 1 ).

A total of 91 (65.94%) neonates presented within 72 hours of life while 47 (34.06%) presented after 72 hours of life ( Figure 1 ).

In our study among 379 patients, the prevalence of neonatal sepsis was 138 (36.41%). A similar study listed major causes of admission of neonates as sepsis with prevalence of 36.9%. 3 The leading cause of death among neonates in Nepal was found to be neonatal sepsis followed by prematurity, low birth weight and birth asphyxia. 5 One of the significant causes of neonatal morbidity and mortality especially in preterm, low birth weight infants is neonatal sepsis. 6

Our study shows, the majority of neonates admitted to NICU were male, 85 (61.59%) while 53 (38.41%) were female. A total of 86 (62.32%) were delivered through spontaneous vaginal delivery and 52 (37.68%) by cesarean section. A total of 70 (50.72%) were term deliveries, 41 (29.71%) were delivered pre-term and 27 (19.57%) were post-term deliveries. A similar study showed similar demographics of 57.7% males and 42.3% females with the majority being term gestation 89.2% and 10.8% being pre-term. 3 The majority were born via spontaneous vaginal delivery (55%) while 39.4% were born via cesarean section. 3 Another research showed male predominance with 65.5% males and 34.4% females. 7 Male predominance may be because males are given more attention by caregivers and brought to seek health services more often in our country. 8

The most common predisposing factor for susceptibility to infection in neonates includes premature birth and low birth weight. 9 In this study, the majority of admissions were done within 72 hours of life 98 (71.01%) while some were after 72 hours of life 40 (28.99%). A total of 35 (25.36%) neonates were within the range of normal birth weight whereas, 35 (25.36%) were of low birth weight and 25 (18.12%) had very low birth weight. Another study shows 75.6% of neonates within the normal weight range and 24.4% below the range. 10 Likewise, 65.58% admissions within 72 hours of life and 34.41% after 72 hours, likewise 65.11% were within the normal range of weight while 34.89% were below the range in a similar study. 11 There is a 3-10-fold higher incidence of infection seen in preterm neonates than in full-term normal birth weight neonates. 12

There are also some limitations of this study as it is a single-centered study and might not be generalized to the entire population.

CONCLUSIONS

The prevalence of neonatal sepsis among neonates admitted to the neonatal intensive care unit was lower than other studies done in similar settings. Further studies involving multicentered research are needed to enhance the generalizability of findings and better understand the factors contributing to the neonatal sepsis in the neonates.

Conflict of Interest