Epidemiology of necrotizing enterocolities and its predictors among preterm newborns in Ethiopia: a systematic review protocol

doi:10.21203/rs.3.rs-3963475/v1

Background

Necrotizing enterocolitis is a serious intestinal inflammation that can lead to tissue death in premature infants. It is most common in infants born before 37 weeks of pregnancy. Globally, a significant number of premature babies affected by this problem with the great variation across countries due to different factors. Evidence on the epidemiology and predictors of necrotizing enterocolitis is essential for policymakers and program planners to improve prevention and treatment strategies. Therefore, this systematic review aims to evaluate the epidemiology of necrotizing enterocolitis and its predictors among preterm newborns in Ethiopia.

Methods

This systematic review will search for and extract data from the JBI Database, Cochrane Database, MEDLINE, CINAHL, EMBASE, PEDro, POPLINE, Proquest, OpenGrey (SIGLE), Google Scholar, Google, APA PsycInfo, Web of Science, Scopus, and HINARI. Unpublished studies and grey literature will also be searched from different sources. The review will include quantitative observational studies and experimental studies that report on the prevalence or incidence of necrotizing enterocolitis in Ethiopia from January 1, 1990 to September 30, 2023. The Newcastle–Ottawa Quality Assessment Scale will be used to select eligible studies. Two researchers will independently assess the quality of the included studies and extract the data. They will resolve any discrepancies through discussion. Heterogeneity, or variation between the studies, will be assessed using forest plots and the I² statistic. If there is a lot of heterogeneity, a random-effects model will be used to pool the data. Subgroup analysis will be used to explore the possible sources of this heterogeneity. Publication bias, or the tendency for studies with positive results to be more likely to be published, will be assessed using funnel plots and Egger's regression test. The statistical software package STATA version 17 will be used to conduct the meta-analysis. An association will be considered statistically significant if the p-value is less than 0.05.

Discussion

Necrotizing enterocolitis is a significant problem in Ethiopia that affects premature newborns and can have severe consequences. More recent systematic reviews are needed to develop effective prevention and treatment strategies.

Systematic review registration number in PROSPERO:

CRD42023459199

Pediatrics

Epidemiology

Necrotizing enterocolities

Preterm

Predictors

Ethiopia

Necrotizing enterocolitis (NEC) is a serious inflammation of the intestines that can lead to tissue death. It is most common in premature infants, but can also occur in full-term infants[1, 2]. Globally, it affects about 7% of premature infants[3] with a mortality rate of 30–50%[4]. However, the incidence of NEC varies substantially across different parts of the world, likely due to differences in clinical and health settings. Larger and higher-quality studies on the incidence of NEC and associated factors, especially in low- and middle-income countries, are warranted [3]. Despite advances in neonatal care, there is still debate about the best way to treat NEC[4].

In Ethiopia, the incidence of NEC ranged from 6.8–25.4% in pocket studies [5–7]. The most commonly identified predictors were gestational age[5, 7], birth weight, preeclampsia [5–7], prolonged labor [5], APGAR score, chorioamnionitis, failure to breath, CPAP ventilation, mixed milk [5], length of hospital stay, initiating trophic feeding [6], premature rapture of membrane and perinatal asphyxia [7].

Evidence on the burden and epidemiology (prevalence, incidence, and magnitude) and predictors of NEC is essential for policymakers and program planners to improve prevention and treatment strategies. In Ethiopia, there is a dearth of evidence regarding the epidemiology and predictors of NEC, particularly considering the multitude of unique factors present in the country compared to other parts of the world. This systematic review aims to address these gaps in knowledge and provide valuable insights into NEC in the Ethiopian context.

A preliminary search of three electronic databases (MEDLINE, the Cochrane Database of Systematic Reviews, and JBI Evidence Synthesis) was conducted and no current or underway systematic review in Ethiopia on this topic. The objective of this systematic review is to evaluate the epidemiology of necrotizing enterocolitis and its predictors among preterm newborns in Ethiopia.

Protocol design and registration

The protocol is developed by following Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P)[8, 9] (Supplementary file 1). The findings of the systematic review will be reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline[10], and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group guidelines[11] (Supplementary file 2). The review title was registered in international prospective register of systematic reviews (PROSPERO) and the registration number is CRD42023459199.

Inclusion criteria

The inclusion criteria will be determined by the CoCoPop mnemonic (Condition, Context and Population) as this review will assess prevalence and incidence data.

Participants/Population

The participants for this systematic review will be preterm newborns.

Condition

This systematic review will consider studies that report on the prevalence and/or incidence, magnitude and predictors of NEC.

Context

The systematic review will include studies conducted in Ethiopia.

Types of studies

This systematic review will include observational studies (such as cohort studies and cross-sectional studies) and experimental studies that report on the prevalence or incidence.

Search strategy

This systematic review will search for both published and unpublished studies on the prevalence or incidence of NEC in Ethiopia. The search will be conducted in three steps. A limited search of MEDLINE and CINAHL will be conducted to identify relevant articles on NEC. The search terms will be based on the titles, abstracts, and index terms of relevant articles, and will use the Boolean logic operators AND and OR with MeSH terms, keywords, and word variants for NEC. The search terms identified in the initial search will be adapted to create a full search strategy for each included database and/or information source (Table 1). To identify additional relevant studies, the reference lists of all included studies will be screened. Only studies published in English from January 1, 1990 to September 30, 2023 will be included in this systematic review. All available data sources will be used to retrieve the needed information, including electronic databases, conference proceedings, websites, search engines, other online sources, and contact with study authors. The following databases will be searched: JBI Database, Cochrane Database, MEDLINE, CINAHL, EMBASE, PEDro, POPLINE, Proquest, OpenGrey (SIGLE), Google Scholar, Google, APA PsycInfo, Web of Science, Scopus, and HINARI. Unpublished studies and grey literature will be searched from institutional libraries and repositories, preprint websites, and personal contact with the authors.

Study selection

The first step is to find and remove duplicate citations. This can be done using a reference management software EndNote X8. Next, the reviewers (AM, NA and SS) will look at the titles and abstracts of all the citations to find the ones that might be relevant to the review. The inclusion criteria for the review will be used to decide if the citations are relevant. The full texts of the potentially relevant sources will then be retrieved. Two independent reviewers (AM and SS) will look at the full texts of the retrieved studies to decide if they meet the inclusion criteria for the review. If a study is excluded from the review, the reasons for exclusion will be recorded and reported in the systematic review. If the reviewers (AM and SS) disagree about whether a study should be included, the third reviewer (NA) will be involved and they will discuss it until they agree. The results of the search and the study inclusion process will be reported in full in the final systematic review and presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram[10] (Fig. 1).

Assessment of methodological quality

Eligible studies will be critically appraised by two independent reviewers (AM and SS) at the study level modify as appropriate if appraisal will occur at the outcome level for methodological quality in the review using Newcastle-Ottawa Scale (NOS)[12]. Authors of papers will be contacted to request missing or additional data for clarification, where necessary. Any disagreements that arise will be resolved through discussion. The results of the critical appraisal will be reported in narrative form and in a table. Studies will be scored using a quality appraisal checklist, and only studies with a score of 50% or higher will be included in the systematic review and meta-analysis of prevalence, incidence, or magnitude. If the two assessors (AM and SS) disagree on a score, they will review the study together to investigate the source of the disagreement. If they are still unable to agree, the third reviewer (NA) will be involved and the average of their scores will be used as the final decision. Studies that do not meet the quality threshold will be excluded from the systematic review and meta-analysis, but they will be reported in narrative form and in a table.

Data extraction

Two independent reviewers (AM and SS) will extract the data using a pre-defined Microsoft Excel 2016 spreadsheet that includes specific details about the condition, populations, study methods, and proportions of interest to the review question and specific objectives (Table 2). Any disagreements between the reviewers will be resolved through discussion. The authors of papers will be contacted to request missing or additional data, where necessary.

Data synthesis

Studies will be pooled in a statistical meta-analysis using STATA version 17, where possible. The effect size will be expressed as a proportion with a 95% confidence interval around the summary estimate. Forest plots and the I2 statistic will be used to assess heterogeneity, which is the variation in the results of the individual studies included in a meta-analysis. If there is a lot of heterogeneity, a random-effects model will be used to pool the data. This model takes into account the heterogeneity between the studies and produces a summary estimate that is more generalizable to the wider population. Subgroup analyses will be used to explore the potential sources of heterogeneity. This involves dividing the studies into different groups based on certain characteristics, such as the study population, study design, or method of measurement. Then the results of the subgroup analyses will be compared to see if there is a difference in the effect size between the groups. Funnel plots and Egger's regression test will be used to assess publication bias, which is the tendency for studies with positive results to be published more often than studies with negative results. A result will be considered statistically significant if the p-value is less than 0.05. If it is not possible to combine the results of the individual studies in a meta-analysis, the findings will be presented in a narrative form, including tables and figures to help visualize the data, where appropriate.

Assessing certainty in the findings

The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach will be used to evaluate the quality of the evidence that has been combined or summarized [13].

Necrotizing enterocolitis is a significant problem in Ethiopia that most commonly affects premature newborns and their families. The consequences of NEC can be severe and long-lasting. Some of the most common consequences include short bowel syndrome (SBS), intestinal strictures, intestinal perforation, sepsis, and death [1, 14]. Infants with NEC often require prolonged hospitalization, which can pose financial and emotional challenges for their families. Therefore, more recent systematic reviews are needed to assess the burden of NEC in Ethiopia and identify predictors of the disease in order to develop effective prevention and treatment strategies.

Amendments

The authors may believe that some amendments or modifications will be needed, but the details of any amendments or discrepancies and the reasons for them will be clearly reported in the systematic review.

NEC

Necrotizing enterocolitis

NOS

Newcastle-Ottawa Scale

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-analyses

PROSPERO

International Prospective Register of Systematic Reviews

SBS

Short bowel syndrome

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable

Availability of data and materials

Not applicable

Competing interests

The authors declare that they have no competing interests

Funding

The authors did not declare any grant for this research from any funding agency.

Authors' contributions

AM conceived the research question, wrote the methodology and introduction, and drafted the protocol. NA and SS assisted with the search process, and AM, NA and SS performed the critical revision, reviewed, and approved the final protocol for submission for publication.

Acknowledgements

The authors acknowledge Arba Minch University and Jimma University for all the supports.

Authors' information

Abera Mersha (BScN, MScN, Ph.D. Fellow), School of Nursing, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia, and School of Nursing, Faculty of Health Sciences, Institute of Health, Jimma University, Jimma, Ethiopia.

Nefsu Awoke (BScN, MScN, Ph.D. Fellow), School of Nursing, College of Health Science and Medicine, Wolaita Sodo University, Sodo, Ethiopia, and Department of Health Policy and Management, Public Health Faculty, Institute of Health, Jimma University, Jimma, Ethiopia.

Shitaye Shibiru (BScN, MScN, Ph.D. Fellow), School of Nursing, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia.

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Necrotizing Enterocolitis (NEC), 2023. Available at: https://www.nichd.nih.gov/health/topics/nec. Access Date [September 27, 2023].
Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med. 2011 Jan 20;364(3):255-64. doi: 10.1056/NEJMra1005408. PMID: 21247316; PMCID: PMC3628622.
Alsaied A, Islam N, Thalib L. Global incidence of Necrotizing Enterocolitis: a systematic review and Meta-analysis. BMC Pediatr. 2020 Jul 13;20(1):344. doi: 10.1186/s12887-020-02231-5. PMID: 32660457; PMCID: PMC7359006.
Zani A, Pierro A. Necrotizing enterocolitis: controversies and challenges. F1000Res. 2015 Nov 30;4:F1000 Faculty Rev-1373. doi: 10.12688/f1000research.6888.1. PMID: 26918125; PMCID: PMC4753995.
Mekonnen SM, Bekele DM, Fenta FA, Wake AD. The Prevalence of Necrotizing Enterocolitis and Associated Factors Among Enteral Fed Preterm and Low Birth Weight Neonates Admitted in Selected Public Hospitals in Addis Ababa, Ethiopia: A Cross-sectional Study. Global Pediatric Health. 2021;8. doi:10.1177/2333794X211019695.
Chekole Temere B, Aynalem Mewahegn A, Tefera Zewudie B, Alebel GebreEyesus F, Kassaw A, Gelaw Walle B, Geze Tenaw S, Mesfin Y, Argaw M, Abebe H, Tesfa S, Habte N, Birhanu R, Seid W. Necrotizing Enterocolitis and Its Predictors Among Preterm Neonates Admitted in Neonatal Intensive Care Units of Gurage Zone Public Hospitals, Southwest Ethiopia, 2021. Pediatric Health Med Ther. 2022;13:95-102. https://doi.org/10.2147/PHMT.S353663.
Alene T, Feleke MG, Yeshambel A, Amare AT, Tigabu A, Birlie TA, Aynalem YA, Kerebeh G, Eshetu K, Tsega TD, Wassihun B, Adella GA and Chichiabellu TY. Time to occurrence of necrotizing enterocolitis and its predictors among low birth weight neonates admitted at neonatal intensive care unit of felege hiwot compressive specialized hospital BahirDar, Ethiopia, 2021: A retrospective follow-up study. Front. Pediatr., 2022;10:959631. doi: 10.3389/fped.2022.959631.
Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA. Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4(1):1. doi: 10.1186/2046-4053-4-1.
Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA, the PRISMA-P Group. Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2015.349:g7647. doi: 10.1136/bmj.g7647.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. doi: 10.1136/bmj.n71. For more information, visit: http://www.prisma-statement.org/.
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000; 283(15):2008-2012.
Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Availabel at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed [September 27, 2023].
Schünemann H, Broek J, Guyatt G, Oxman A (editors). GRADE Handbook. Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach. Updated October 2013.
Federici S, De Biagi L. Long Term Outcome of Infants with NEC. Curr Pediatr Rev. 2019;15(2):111-114. doi: 10.2174/1573396315666181130144925. PMID: 30499415.

Table 1: Search strategy

CoCoPop components	Inclusion criteria	Search terms (keywords/Mesh terms/index terms/Free text words)	Limits
Population	Preterm newborns	preterm neonate[All Fields] OR pre-term infant[All Fields] OR preterm bab[All Fields] OR prematurity[All Fields] OR premature infant[All Fields] OR premature bab[All Fields] OR low birth weight[All Fields] OR LBW[All Fields] OR extremely premature bab[All Fields] OR extremely premature infant[All Fields] OR neonate [All Fields] OR newborn* [All Fields] OR baby[All Fields] OR babies[All Fields] OR infant[All Fields] OR newborn baby[All Fields] OR postnatal bab[All Fields] OR term infant[All Fields] OR term bab*[All Fields]	Language: English Publication date: January 1, 1990 to September 30, 2023
Condition	Prevalence and/or incidence, magnitude and predictors for NEC	prevalence[MeSH Terms] OR incidence[MeSH Terms] OR magnitude* [All Fields] OR contributing factor[MeSH Terms] OR associated factor[MeSH Terms] OR risk factor[MeSH Terms] OR predictor[All Fields] OR necrotizing enterocolitis [All Fields] OR NEC*[MeSH Terms]
Context	Studies in Ethiopia	Ethiopia
Combine a single search strategy: (((((((((((((((((((((((((((((preterm neonate[All Fields]) OR (pre-term infant[All Fields])) OR (preterm bab[All Fields])) OR (prematurity[All Fields])) OR (premature infant[All Fields])) OR (premature bab[All Fields])) OR (low birth weight[All Fields])) OR (LBW[All Fields])) OR (extremely premature bab[All Fields])) OR (extremely premature infant[All Fields])) OR (neonate [All Fields])) OR (newborn* [All Fields])) OR (baby[All Fields])) OR (babies[All Fields])) OR (infant[All Fields])) OR (newborn baby[All Fields])) OR (postnatal bab[All Fields])) OR (term infant[All Fields])) OR (term bab[All Fields])) AND (prevalence[MeSH Terms])) OR (incidence[MeSH Terms])) OR (magnitude [All Fields])) OR (contributing factor[MeSH Terms])) OR (associated factor[MeSH Terms])) OR (risk factor[MeSH Terms])) OR (predictor[All Fields])) OR (necrotizing enterocolitis [All Fields])) OR (NEC*[MeSH Terms])) AND (Ethiopia)) AND (("1990/1/1"[Date - Publication] : "2023/9/30"[Date - Publication]))
Number of records retrieved by the search: 8,699
Database used: MEDLINE (Ovid)
Search conducted on: Date: September 27, 2023; Time: 10:02:04

Table 2: Sample data extraction form

Authors	Publication year	Region	Study setting	Study design	Participants	Sample size	Prevalence or incidence or magnitude	Event	Predictors or associated factors or risk factors

The authors declare no competing interests.

Supplementaryfile1PRISMAPchecklist.doc
Supplementary file 1: Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) 2015 checklist (word)
Supplementaryfile2ISSMMOOSEChecklist.pdf
Supplementary file 2: Meta-analyses Of Observational Studies in Epidemiology (MOOSE) Checklist (pdf)

Epidemiology of necrotizing enterocolities and its predictors among preterm newborns in Ethiopia: a systematic review protocol

Status:

Version 1

Abstract

Background

Methods

Discussion

Systematic review registration number in PROSPERO:

Figures

Background

Methods

Protocol design and registration

Inclusion criteria

Search strategy

Study selection

Assessment of methodological quality

Data extraction

Data synthesis

Assessing certainty in the findings

Discussion

Amendments

List Of Abbreviations

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Version 1