Effect of breastfeeding on neonatal mortality : A systemic review and meta-analysis of observational studies in Ethiopia

Effect of breastfeeding on neonatal mortality : A systemic review and meta-analysis of observational studies in Ethiopia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Effect of breastfeeding on neonatal mortality : A systemic review and meta-analysis of observational studies in Ethiopia Fillmon Kidus, Demeke Tolira, Tesema Kecha This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7038235/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: This systematic review and meta analysis was conducted to determine the pooled effect size and examine the inconsistencies among the studies conducted in Ethiopia. Design: We conducted a systemic review and meta analysis of identified observational studies. Data Source: An electronic bibliographic search was conducted in PUB Med, MEDLINE, EMBASE, Cochran Library data base and Google scholar from September 05, 2024 until November 07, 2024. Eligibility Criteria for selected studies: We included observational studies conducted in Ethiopia and published in English language. Intervention : Exclusive breastfeeding of neonates. Primary outcome measure : The primary outcome was neonatal mortality. Data extraction and synthesis: data extraction was independently conducted by two reviewer and. investigate research bias using Risk of Bias in Non- Randomized Studies of Intervention tool. This study adhere with the guidelines of Meta-Analysis of Epidemiological observational studies and Preferred Report Items for Systemic Review and Meta-Analysis. Random effect model was employed and statistical heterogeneity was assessed using the Q and I 2 statistic. Result: Only 10 studies were included based on established criteria. The overall pooled effect measure demonstrated a statistically significant association [OR=0.24, 95%CI(0.03-0.45), P=0.02]. Heterogeneity, assessed using the Q statistical test, revealed [Q=97.46 , degree of freedom = 9 and P = 0.00] while, the I 2 statistic test showed [I 2 = 96%]. Publication bias of Begg’s funnel plot and Egger’s test , indicated an absence of publication bias [OR = 0.07, 95%CI ( -6.285 - 6.424) , P = 0.98]. Sensitivity analysis were deemed implausible. Certainty evidence of the studies was found to be moderate. Conclusion: Result of meta-analysis indicated that breastfeeding serves as a protective intervention to reduce risk of neonatal mortality in Ethiopia. Additionally, confirmed presence of heterogeneity among the studies. PROSPPRO protocol registration number : CRD42024599421 Pediatrics Neonatal mortality Breastfeeding Meta analysis Heterogeneity Observational study Figures Figure 1 Figure 2 Figure 3 Figure 4 STRENGTH AND LIMITAION OF THIS STUDY This study adhere with the guidelines of Meta-Analysis of Epidemiological observational studies(MOOSE) and Preferred Report Items for Systemic Review and Meta-Analysis(PRISMA) The study employ to assess the risk of bias and certainty of evidence of the studies using ROBINS-I(Risk of Bias in Non- Randomized Studies of Intervention tool).and GRADE approach(Grading of Recommendations Assessment Development and Evaluation) respectively. The evidence included in the study were heterogeneous due to variation in sample size, study design , sampling method, and study area. The quality of the evidence was also found moderate quality, which may impact the effect size. The review process was that the initiation time of breastfeeding was not measured or not taken in to account. Only exclusive breastfeeding was taken in to account in the review process. INTRODUCTION The neonatal period, defined as the first month (28 days) of life, is the most critical period for survival. Globally, 2017, there were 2.5 million neonatal deaths, which major which occurring early in the first days of life (1). Neonatal mortality contributed to 47% of under-five mortality (1). The global neonatal mortality rate (NMR) decreased from 37 per 1000 live births (LBs) in 1990 to 18 per 1000 LBs in 2017 (1). Although this overall reduction in mortality is exceed 50%, this decline was slower compared to children older than one month (2). The highest rates were found in sub-Saharan Africa (SSA) and South Asia (1). The majority of neonatal deaths were occur during the early neonatal period, which approximately about 1.7 million (75%) of the total neonatal deaths, and the majority (1 million) of early neonatal deaths occur within 24 hour of birth (3). Ethiopia has achieved the Millennium Development Goal (MDG) 4 by reducing under-five mortality by two-thirds, three years a head the 2015 deadline (1). Although neonatal mortality has declined, it remains high, and Ethiopia is one of the five countries where half of the world’s neonatal deaths are concentrated (1). Neonatal mortality in Ethiopia decreased from 39 to 29 between the 2005 and the 2016 Ethiopian Demographic and Health Survey (EDHS), but has remained stable since the 2016 EDHS and even increased to 33 deaths per 1,000 live births in the 2019 EDHS (4). Early initiation of breastfeeding protects newborns from infections and reduces mortality rate (5-7). It also strengthens the emotional bond between the newborn and the mother and positively impacts the duration of exclusive breastfeeding (8,9). The yellow or golden first milk produced in the first few days known as colostrum , is a vital source of nutrition and immune protection for the newborn (8, 9). Colostrum is a complex biological nutrient rich fluid produced by female mammals immediately after giving birth that provides essential immune support , growth, and tissue repair capabilities (10 , 11). Globally, an estimated 22% of early neonatal deaths 2018 were attributed to the late initiation of breastfeeding (12,13). The failure of to initiate early breast feeding( EIBF) in the first hour after birth is estimated to double the risk of neonatal death (14, 15). Although EIBF is a cost-effective and easily implementable practice with significant implications for saving newborn lives only 42% of mothers worldwide initiate breastfeeding within the first hour of birth (16). The Prevalence of EIBF varies across regions, with high-income countries having a higher practice of EIBF compared to low- and middle-income countries (17). Some observational studies conducted in Ethiopia indicated that, breastfeeding and neonatal mortality have a statistically significant association (18-23, 26-39). However, other studies indicated that, not statistical significant (24,25, 40). In past time , there is no meta analysis conducted in Ethiopia to review impact of breastfeeding on neonatal mortality. So that, to come up with concrete evidence regarding the effect of breast feeding on neonatal mortality, it is essential to have systematic review and meta-analysis of studies conducted in Ethiopia. The purpose of this systemic review and meta-analysis is to determine the pooled effect and assess the inconsistency of findings of related to breast feeding on neonatal mortality by reviewing observational studies conducted in Ethiopia. The findings of this study will help policy makers and stakeholders in the health sector to implement effective intervention of breastfeeding to reduce neonatal mortality at local and national level. METHOD This systemic review and Meta-Analysis was guided according the guide line of Preferred Reporting Items for Systemic Review and Meta- Analysis(PRISIMA)(41). Additionally, by the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) standard for epidemiological observational studies(42). Search Strategy We conducted an electronic bibliographic search in the following data base: PUBMed, MEDLINE, EMBASE, LILACS, Google scholar, and WHO journal data bases. We used search strategy in PUBMed and EMBASE as follow :(((((((breastfeeding [MeSH Terms]) AND (neonatal mortality[MeSH Terms])) ) OR (child mortality [MeSH Terms])) OR (infant mortality[MeSH Terms])) AND (Ethiopia [MeSH Terms]) Google scholar : "neonatal- mortality" "breast- feeding" "Ethiopia" "case- control" "cross- sectional" "cohort". Selection Process Two independent reviewers (FK and DT) initially scanned titles and abstracts to select potential full- text articles for further detailed review. When the titles and abstracts were accepted by reviewers, the full text of the articles was obtained through linked databases and carefully reviewed for inclusion by both reviewers. Studies published by the same researchers that examined the same factors were checked for potential duplicate data based on the year of publication and the study areas. In case of duplication the study with the largest data set was used for meta analysis. When there was disagreement, it was resolved through discussion with third reviewer (TK). Eligibility Criteria Study Type : Inclusion Criteria : Observational study designs published in any language from January , 2000 GC until November, 2024 GC and study conducted exclusively in Ethiopia. Exclusion Criteria: Studies that consist solely of with abstracts and studies conducted in other countries. Study population : Inclusion Criteria : All live neonates during the first 28 days of completed day of life and all neonate who died with in 28 completed days of life. Exclusion: Criteria: Neonates who died after 28 completed days of life. Outcome of Interest : Inclusion Criteria: The primary outcome was neonatal mortality, it defined as the death of a live born child before the 28 th day of life. Exclusion Criteria: Death of a live born child after the 28 th day of life. Exposure of Interest : Inclusion Criteria : Exclusive breastfeeding is defined as providing only breast milk to neonate during the first 28 completed days of life. Babies can be fed directly from their mother’s breast or breast milk can be pumped and administered to the baby using a bottle. Exclusion Criteria:: The provision of breast milk with other additional food to neonate during the first 28 days of completed life. Data Collection Process The data extraction form was developed by the investigator in Excel format based on a pilot review, the extraction and calibration of the included studies were conducted accordingly. Two reviewers independently extracted data from the eligible studies to assess quality of the study and synthesize the data. Any discrepancies identified were resolved through discussion with a third reviewer. Necessary information included the author, study setting, study population, and detail of exposure, study design, outcome, information for assessing of risk biases, sample size, and effect size measurements. Data Items of Outcome : The outcome domain and definition are as fellows: Neonatal death is defined as number of deaths of live born child during the first 28 completed days of life. Data Item Other variable : Author, country, Year of Publication, type of study design, sample population, effect size measurement type , sampling method and Standard Error Study Risk of Bias Assessment Two reviewers(FK and DT) independently evaluated the risk of bias in the included studies by assessing the quality of the studies. The overall risk of bias assessment was conducted using the ROBINS-I tool version 2, which is suitable for non- randomized studies based on seven domains of risk of bias and the results were categorized in to three levels of rating : low, moderate , and serious (43). In cases of disagreement between the reviewers regarding the risk of bias in specific studies, the issue was resolved through discussion, with the involvement of a third reviewer(TK). Over all, the findings from the assessment were utilized in data synthesis for the pre- planned sensitivity analysis to test the effect of removing poor quality studies. Synthesis Methods All meta- analyses were performed using IBM SPSS version 30. We employed random effect model, because of presence of heterogeneity with in the studies. The summery of effect size for each study was calculated using the Odds ratio (OR) with P value P< 0.05 as significant value , which is recommended for dichotomous categorical data with 95 % confidence interval. Statistical heterogeneity was assessed using cochran’s Q statistical test of and I 2 statistics test to quantify the level of heterogeneity between studies. We considered I 2 value greater than 50% to be indicative of substantial heterogeneity (44). Sensitivity analysis was conducted using leave -out -one study meta -analysis method to evaluate the influence of each stud on the pooled effect size. Subgroup and Meta-Regression Analysis : The impact of covariates on the pooled effect size and heterogeneity across studies was evaluated using meta-regression and subgroup analysis. The effect of covariates on the pooled effect size is deemed significant when the p-value is <0.05. Reporting Bias Assessment : We conducted Begg’s funnel plot and Egger‘s regression test to assess presence of publication bias (45), The strategies for addressing missing information on the methods used in the included studies authors was contacted using email address provided in the publication, or accessing phone directories from the author’s documented affiliated organizations. Certainty Assessment : The certainty assessment was conducted using GRADE approach method (Grading of Recommendation Assessment, Development, and Evaluation) (46) with the GRADEpro soft ware(47). The approach employs a four rating system high, moderate, low , and very low. RESULTS Study Selection A literature review was conducted from September 05, 2024 until November 07, 2024 using data bases such as MEDLINE, PubMed, LILACS, Google scholar, EMBASE, and the WHO journal. The review adhere to PRISMA 2020 statement (41) and MOOSE standard for epidemiological observational studies(42). A total of 767 records related to the review topic were identified with publication years ranging from January, 2000 GC. To July, 2024 GC. After removing duplicate of 217 record, 550 record remained but 466 were excluded during the initial assessment due to irrelevance their titles. The remaining 84 records were accessed and screened. However, 37 records were assessed for eligibility , 27 studies (20, 22,23 , 26,27, 30, 31, 33,34, 36,38, 48-62) were excluded because there were not relevant based on the exposure , outcome , study design, and effect measure . As a result , 10 studies published in English ( 18, 19, 21, 24,25, 29, 32, 35, 39,40) had their full- text articles were accessed and included in the review (Figure 1). Study Characteristics The studies were observational in nature, comprising five cross sectional, three case control and two prospective study design. Additionally, the studies were conducted in diverse region of Ethiopia (Table 1). Risk of Bias Assessment in Studies A risk of bias assessment was conducted for each study using the ROBINS I tool which evaluate seven domains of bias: confounding, classification of intervention, selection of participant into the study, deviation from the intended intervention, risk of bias due to missing data, measurement of outcomes and selection of reported results. The overall risk of bias assessment for each study was low risk of bias except for studies (21, 24, 39) moderate risk of bias. However; the overall judgement of risk of bias of the studies were moderate (Figure 2). Results of Synthesis The overall pooled effect measure indicated a 76% reduction in neonatal mortality due to breastfeeding interventions as determined by a random effects model meta -analysis [ OR= 0.24, 95%CI (0.03-0.45)],P=0.02]. Heterogeneity among studies was assessed using cochrane’s Q statistical test, which revealed that, [ Q=97.46 , DF (degree of freedom) = 9 and P = 0.00] . Additionally, Higgins I 2 statisticaltest showed that presence of heterogeneity [I 2 = 96%](Figure 3). Subgroup Analysis Subgroup analysis was conducted to identify the sources of heterogeneity in the reviewed studies. According to the subgroup analysis, multistage cluster sampling and two stage stratified cluster sampling did not statistically significant. Studies conducted in Benshangul, Northwestern Ethiopia, and nine region of Ethiopia revealed no statistically significant. Both cross sectional and prospective cohort study designs found no statistically significant. .More over, sample size greater than 5,000 did not statistically significant. However, The subgroup random effect meta analysis pooled result showed statistically significant with [OR= O.24, 95%CI: (0.03 - O.45), P = 0.02] : and the subgroup pooled effect measure also found consistent with the over all pooled meta analysis result of the all studies. Additionally, the subgroup I 2 and Q statistical test indicated heterogeneity with [I 2 = 96% ] (Table 2) . Meta Regression Analysis A meta-regression was conducted to examine the effect of certain covariates on impact of breastfeeding on neonatal mortality. The analysis was estimated using likely hood method of REML (Restricted Maximum Likelyhood ) and using Knapp -Hartung method the SE was adjusted and random effect meta regression model was employed. The effect of sample size relationship between breastfeeding and neonatal mortality was assessed and yielding Q statistic value [ Q= 59.87, df = 8 , P = <0.01] and [ I 2 =89.5%]. additionally, effect of study design on relationship between breastfeeding and neonatal mortality evaluated , result in a Q statistical test value [Q= 85.99, df =7, P = <0.01] and I 2 statistical test of heterogeneity was[I 2 = 97.1]. The third covarate was effect of sampling method on relationship between breastfeeding and neonatal mortality was reported that with a Q Statistical homogeneity was[Q= 46.09 , df =7, P = <0.001 ] and I 2 statistical test of heterogeneity was [I 2 = 99.4%]. Sensitivity Analysis To further investigate the influence of each study in the meta -analysis of the effect of breast feeding on neonatal mortality; we performed a leave- one- out sensitivity analysis. The result of our sensitivity analysis indicated that the point- estimated effect size obtained when each study was excluded from meta -analysis was fell with in confidence interval of the pooled effect size of the overall study, except for the meta -analysis that excluded studies ( 18, 19, 39, 40) which were out side the range of confidence interval of the pooled result of with out leave- out -one study but not exaggerated. Notably,, the heterogeneity result was the same or stable. Which the original pooled effect size was [OR=0.24, 95%CI(0.033-0.45)], while the leave out -one- study meta-analysis was indicated that the pooled effect measure ranged between [OR= 0.10 , 95%CI (0.01-0.19)] and [OR= 0.31, 95%CI(0.04 - 0.56)]. Therefore, these four studies were identified influential, and the results of the leave out- one -study meta- analysis were deemed implausible(Table 3). Publication Biases Begg’s funnel plot was indicated that it was symmetrical , and Egger’s regression test yielded an effect measure of [ OR= 0.07, 95%CI( -6.285 - 6.424) , P= 0.98]. Therefore, provided then no significant publication bias was observed with regard to effect of breastfeeding on neonatal mortality in observational studies conducted in Ethiopia( Figure 4). Certainty of Evidence We employed GRADE approach (46) and GRADEpro software (47) to analyze certainty of evidence regarding the study effect of breast feeding on neonatal mortality. The cafeterias used to assess certainty of evidence with neonatal mortality as outcome were number of studies included, study design, risk of bias, inconsistencies, indirectness, imprecision, publication bias, confounding , large effect size, and dose response prediction. The overall , result of the evidence assessment revealed that the quality of evidence was moderate . DISCUSSION This systematic review and meta- analysis, identified and assessed ten studies through data base search conducted from January 2000 - November 2024. However, the included studies were published between 2019 and 2024. Up on reviewing the individual studies, we found, that three were case control studies, five were cross sectional studies and two were prospective cohort observational studies. Seven studies reported that a statistically significant association between breastfeeding and neonatal mortality. In contrast, three studies reported not statistically significant association ( 24, 25, 40). A risk of bias assessment was conducted for each study using ROBINS I tool (46), using seven domains of bias. The overall risk of bias assessment for each study was classifies as low, except for three studies that were classified as moderate (21, 24, 39). Overall judgement of the risk bias across the studies were moderate. The pooled effect size of breastfeeding on neonatal mortality indicated that breastfeeding has a statistically significant effect on reducing neonatal mortality. The analysis revealed a 76% reduction of risk of neonatal mortality in Ethiopia, with a pooled effect of [ OR = 0.24, 95%CI(0.033–0.45), P = 0.02]. This finding is consistent with systematic review and meta- analysis conducted in different countries (63–65). Clinical evidence also suggests that the early initiation of exclusive breastfeeding significantly reduces neonatal mortality by providing crucial immunity and protection against pathogens. Colostrum, the first milk produced is richer in antibodies and immune factors providing the new born with crucial protection against infection and protection from pathogens. Heterogeneity among studies was assessed using cochrane’s Q statistical test which yielded the following result [ Q = 97.46, df = 9, P = 0.00]. Additionally, Higgins I 2 statistical test showed [ I 2 = 96%} confirming strong indicative of heterogeneity. Due to presence of heterogeneity we use random effect meta -analysis model for analysis of pooled effect size. Subgroup analysis and meta- regression analysis were performed to identify the sources of heterogeneity in the included studies. According to the subgroup analysis, multistage cluster sampling and two stage stratified cluster sampling did not yield statistically significant. Studies conducted in Benshangul, North Western Ethiopia, and nine region of Ethiopia indicated not statistically significant. A cross sectional and prospective cohort study found no statistically significant result. Moreover, a sample size greater than 5,000 reported as not statistically significant. Based on this evidence, the sources of heterogeneity included the sampling method, sample size, location, and study design type. Furthermore, a meta- regression analysis was performed to assess the influence of certain covariates on the effect of breastfeeding on neonatal mortality. The estimation method used was Restricted Maximum Likelyhood (REML) and employing a random effects meta- regression model and Knapp -Hartung adjusted standard error (SE). The influence of sample size on the effect of breastfeeding on neonatal mortality was reported as as statistically significant result with Q statistical test [ Q = 59.87, df = 8, P = < 0.01] and [ I 2 = 89.5%]. Additionally, the effect of study design on the relationship between breastfeeding and neonatal mortality indicated statistical significant with Q statistical test [Q = 85.99, df = 7, P = < 0.01], and I 2 statistical test of heterogeneity was [I 2 = 97.1]. The third covariate, the sampling method effect on association between breastfeeding and neonatal mortality indicated by the statistically significant Q statistical homogeneity test [Q = 46.09, df = 7, P = < 0.001 ], and I 2 statistical test for heterogeneity [ I 2 = 99.4%]. Therefore, these three characteristics of the studies were statistically significantly associated with an impact on effect measure size. The results of the sensitivity analysis revealed that the estimated effect sizes obtained through leave out -one -study meta- analysis method fell within the confidence interval for the overall pooled effect, except those excluded studies ( 18, 19, 39, 40). These were out side the range of the confidence interval for the pooled results of the overall studies, although there influence was not exaggerated. Furthermore, the heterogeneity remained stable. The original pooled effect size was [OR = 0.24, 95%CI(0.033–0.45), P = 0.02], but the leave out -one- study meta- analysis showed that the pooled effect measure ranges between [OR = 0.10, (95%CI (0.01–0.19)] and [OR = 0.31, 95%CI(0.04–0.56)]. Therefore, these four studies were identified as influential in the meta analysis. Consequently, the results of the leave out -one -study meta- analysis not deemed plausible. Regarding publication bias, a Begg’s funnel plot was generated, which appeared symmetrical. Additionally, Egger’s regression test yielded an effect measure of [ OR = 0.07, 95%CI( -6.285–6.424), P = 0.98], based on this evidence, no significant publication bias was observed concerning the effect of breastfeeding on neonatal mortality in observational studies conducted in Ethiopia. Finally, the quality from evidence of the studies was assessed using GRADE approach, which indicated a moderate quality of evidence. Conclusion and Recommendation The meta analysis indicated that breastfeeding practice as a protective intervention to reduce the risk of neonatal mortality in Ethiopia. Additionally, the studies included in the review found inconsistencies in their effect measures due to variation in study design, sampling method, and sample size. Therefore, policymakers should incorporate breastfeeding promotion as key component of child survival strategies to reduce the high neonatal mortality rate in Ethiopia. We also recommend that future study that can take in to account the initiation time of breastfeeding. Abbreviations CI : Confidence Interval, CM: Child Mortality , DF: Degree of Freedom , EDHS: Ethiopian Demographic Health Survey, EIBF: Early Initiation of Breastfeed, EMBASE: Excerpta Medica Data Base, GRADE: Grading of Recommendations Assessment Development and Evaluation , IM: Infant Mortality , LB: Live Birth, MDG: Millennium Development Goal , MEDLINE: Medical Literature Analysis and Retrieval System, NM: Neonatal Mortality , NMR: Neonatal Mortality Rate, OR: Odds Ratio, PRISMA: Preferred Reporting Item for Systemic review and Meta Analysis, PROSPERO: International Prospective Register of Systemic Review , REML: Restricted Maximum Likelihood, ROBINS-I: Risk of Bias in Non- Randomized Studies of Intervention, SSA: Sub Saharan Africa Declarations Ethical approval and consent to participate Not applicable Consent for publication Not applicable Ethical approval Not applicable Availability of data and materials All the data generated during this Meta-Analysis and review are included in this published article with in the figure, tables and supplementary material. Competing interests The authors declare that they have no competing interests. Funding Not applicable Authors Contributions FK was responsible from inception to design, protocol preparation, protocol registration, acquisition of data , analysis, and interpretation of data and preparing the manuscript. DT was responsible for acquisition of data and interpretation as second independent reviewer. TK was responsible for acquisition of data and interpretation of data as third independent reviewer. All author read and approved the final manuscript. Acknowledgment The authors would like to thank all the authors and publishers of original studies. Authors affilations 1 Tigray Regional Health Bureau, Researcher, Epidemiologist and surveillance specialists , Mekelle, Tigray Region, Ethiopia. 2 Clinton Health Access Initiative, Immunization Coordinator, Addis Ababa, Ethiopia. 2 United Nation Children Fund, Immunization and COVID -19 Consultant, Addis Ababa, Ethiopia. References United Nations Inter-agency Group for Child Mortality Estimation (UN IGME) . Levels & trends in child mortality: report 2017, estimates developed by the UN inter agency group for child mortality estimation. New York (NY): United Nations Children’s Fund; 2017. [ Google Scholar ] Hug L, Alexander M, You D, Alkema L.. National, regional, and global levels and trends in neonatal mortality between 1990 and 2017, with scenario-based projections to 2030: a systematic analysis. Lancet Glob Health . 2019;7:e710–8. doi: 10.1016/S2214-109X(19)30163-9; Epub 2019/05/18. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ] Assefa Y, Damme WV, Williams OD, Hill PS.. Successes and challenges of the millennium development goals in Ethiopia: lessons for the sustainable development goals. BMJ Global Health . 2017;2:e000318. doi: 10.1136/bmjgh-2017-000318; Epub 2017/10/31. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ] Ethiopia M. Demographic and Health Survey 2019 Edmond KM, Kirkwood BR, Amenga-Etego S, Owusu-Agyei S, Hurt LS. Effect of early infant feeding practices on infection-specific neonatal mortality: an investigation of the causal links with observational data from rural Ghana. Am J Clin Nutr . 2007;86: 1126–1131. doi: 10.1093/ajcn/86.4.1126 [ PubMed ] [ CrossRef ] [ Google Scholar ] Borg B, Gribble K, Courtney‐Haag K, Parajuli KR, Mihrshahi S. Association between early initiation of breastfeeding and reduced risk of respiratory infection: Implications for nonseparation of infant and mother in the COVID‐19 context. Matern Child Nutr . 2022;18. doi: 10.1111/mcn.13328 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ] Debes AK, Kohli A, Walker N, Edmond K, Mullany LC. Time to initiation of breastfeeding and neonatal mortality and morbidity: a systematic review. BMC Public Health . 2013;13: S19. doi: 10.1186/1471-2458-13-S3-S19 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ] Liu J, Leung P, Yang A. Breastfeeding and Active Bonding Protects against Children’s Internalizing Behavior Problems. Nutrients . 2013;6: 76–89. doi: 10.3390/nu6010076 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ] Else-Quest NM, Hyde JS, Clark R. Breastfeeding, Bonding, and the Mother-Infant Relationship. Merrill Palmer Q . 2003;49: 495–517. doi: 10.1353/mpq.2003.0020 [ CrossRef ] [ Google Scholar ] Thapa BR. Health factors in colostrum. Indian J Pediatr . 2005;72: 579–581. doi: 10.1007/BF02724182 [ PubMed ] [ CrossRef ] [ Google Scholar ] Uruakpa FO, Ismond MAH, Akobundu ENT. Colostrum and its benefits: a review . 2002. Available: www.elsevier.com/locate/nutres [ Google Scholar ] Edmond K. M., Kirkwood B. R., Amenga-Etego S., Owusu-Agyei S., Hurt L. S. Effect of early infant feeding practices on infection-specific neonatal mortality: an investigation of the causal links with observational data from rural Ghana. The American Journal of Clinical Nutrition . 2007;86(4):1126–1131. doi: 10.1093/ajcn/86.4.1126. [ PubMed ] [ CrossRef ] [ Google Scholar ] WHO. Breast Feeding . Geneva: World Health Organization; 2018. [ Google Scholar ] Khan J., Vesel L., Bahl R., Martines J. C. Timing of breastfeeding initiation and exclusivity of breastfeeding during the first month of life: effects on neonatal mortality and morbidity—a systematic review and meta-analysis. Maternal and Child Health Journal . 2015;19(3):468–479. doi: 10.1007/s10995-014-1526-8. [ PubMed ] [ CrossRef ] [ Google Scholar ] NEOVITA Study Group. Timing of initiation, patterns of breastfeeding, and infant survival: prospective analysis of pooled data from three randomised trials. The Lancet Global Health . 2016;4(4):e266–e275. doi: 10.1016/S2214-109X(16)00040-1. [ PubMed ] [ CrossRef ] [ Google Scholar ] World Health Organization. Health in 2015: from MDGs, Millennium Development Goals to SDGs, Sustainable Development goals . World Health Organization; 2015. [ Google Scholar ] Victora C. G., Bahl R., Barros A. J., et al. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet (London, England). . 2016;387(10017):475–490. doi: 10.1016/S0140-6736(15)01024-7. [ PubMed ] [ CrossRef ] [ Google Scholar ] Mitiku HD. Neonatal mortality and associated factors in Ethiopia: a cross-sectional population-based study. BMC Womens Health. 2021 Apr 16;21(1):156. doi:10.1186/s12905-021-01308-2. PMID: 33863331; PMCID: PMC8052649. Girma B, Nigussie J. Magnitude of preterm hospital neonatal mortality and associated factors in northern Ethiopia: a cross-sectional study. BMJ Open. 2021 Dec 3;11(12):e051161. doi: 10.1136/bmjopen-2021-051161. PMID: 34862286; PMCID: PMC8647539. Zelalem Ayichew M, Derseh Gezie L, Gelagay AA, Anmut Bitew D. Neonatal mortality and associated factors among neonates admitted to neonatal intensive care unit of Gandhi memorial hospital in Addis Ababa, Ethiopia, 2019. BMC Pediatr. 2022 May 12;22(1):266. doi: 10.1186/s12887-022-03339-6. PMID: 35550058; PMCID: PMC9097131. Fentaw KD, Fenta SM, Biresaw HB, Yalew MM. Factors associated with post-neonatal mortality in Ethiopia: Using the 2019 Ethiopia mini demographic and health survey. PLoS One. 2022 Jul 27;17(7):e0272016. doi: 10.1371/journal.pone.0272016. PMID: 35895632; PMCID: PMC9328495. Sahile A, Bekele D, Ayele H. Determining factors of neonatal mortality in Ethiopia: An investigation from the 2019 Ethiopia Mini Demographic and Health Survey. PLoS One. 2022 Dec 30;17(12):e0267999. doi:10.1371/journal.pone.0267999. PMID: 36584102; PMCID: PMC9803101. Kolola T, Ekubay M, Tesfa E, Morka W. Determinants of Neonatal Mortality in North Shoa Zone, Amhara Regional State, Ethiopia. PLoS One. 2016 Oct 14;11(10):e0164472. doi: 10.1371/journal.pone.0164472. PMID: 27741284; PMCID: PMC5065191. Kidus F, Woldemichael K, Hiko D. Predictors of neonatal mortality in Assosa zone, Western Ethiopia: a matched case control study. BMC Pregnancy Childbirth. 2019 Mar 29;19(1):108. doi: 10.1186/s12884-019-2243-5. PMID: 30925903; PMCID: PMC6441179. Bekele T, Merga H, Tesfaye T, Asefa H. Predictors of mortality among neonates hospitalized with neonatal sepsis: a case control study from southern Ethiopia. BMC Pediatr. 2022 Jan 3;22(1):1. doi: 10.1186/s12887-021-03049-5. PMID: 34980043; PMCID: PMC8722178. Birhanu D, Gebremichael B, Tesfaye T, Tadesse M, Belege F, Godie Y, Wodaje M, Tamiru E. Survival status and predictors of mortality among preterm neonates admitted to neonatal intensive care unit of Addis Ababa public hospitals, Ethiopia, 2021. A prospective cohort study. BMC Pediatr. 2022 Mar 23;22(1):153. doi: 10.1186/s12887-022-03176-7. PMID: 35321673; PMCID: PMC8941786. Alebel A, Wagnew F, Petrucka P, Tesema C, Moges NA, Ketema DB, Yismaw L, Melkamu MW, Hibstie YT, Temesgen B, Bitew ZW, Tadesse AA, Kibret GD. Neonatal mortality in the neonatal intensive care unit of Debre Markos referral hospital, Northwest Ethiopia: a prospective cohort study. BMC Pediatr. 2020 Feb 15;20(1):72. doi: 10.1186/s12887-020-1963-z. PMID: 32061260; PMCID: PMC7023807. Tolossa T, Wakuma B, Mengist B, Fetensa G, Mulisa D, Ayala D, Feyisa I, Fekadu G, Jara D, Bikila H, Getahun A. Survival status and predictors of neonatal mortality among neonates admitted to Neonatal Intensive care Unit (NICU) of Wollega University referral hospital (WURH) and Nekemte Specialized hospital, Western Ethiopia: A prospective cohort study. PLoS One. 2022 Jul 29;17(7):e0268744. doi: 10.1371/journal.pone.0268744. PMID: 35905094; PMCID: PMC9337704. Desalew A, Sintayehu Y, Teferi N, Amare F, Geda B, Worku T, Abera K, Asefaw A. Cause and predictors of neonatal mortality among neonates admitted to neonatal intensive care units of public hospitals in eastern Ethiopia: a facility-based prospective follow-up study. BMC Pediatr. 2020 Apr 14;20(1):160. doi: 10.1186/s12887-020-02051-7. PMID: 32290819; PMCID: PMC7155275. Roro EM, Tumtu MI, Gebre DS. Predictors, causes, and trends of neonatal mortality at Nekemte Referral Hospital, east Wollega Zone, western Ethiopia (2010-2014). Retrospective cohort study. PLoS One. 2019 Oct 9;14(10):e0221513. doi: 10.1371/journal.pone.0221513. PMID: 31596859; PMCID: PMC6785121. Orsido TT, Asseffa NA, Berheto TM. Predictors of Neonatal mortality in Neonatal intensive care unit at referral Hospital in Southern Ethiopia: a retrospective cohort study. BMC Pregnancy Childbirth. 2019 Feb 28;19(1):83. doi: 10.1186/s12884-019-2227-5. PMID: 30819143; PMCID: PMC6396455. Adem A, Dache A, Dona A. Determinants of neonatal mortality among newborns admitted in neonatal intensive care unit at Dilla University Referral Hospital in Gedeo Zone, Southern, Ethiopia: unmatched case control study. BMC Pediatr. 2021 Jul 8;21(1):307. doi: 10.1186/s12887-021-02780-3. PMID: 34238264; PMCID: PMC8265069. Mengesha HG, Wuneh AD, Lerebo WT, Tekle TH. Survival of neonates and predictors of their mortality in Tigray region, Northern Ethiopia: prospective cohort study. BMC Pregnancy Childbirth. 2016 Aug 2;16(1):202. doi:10.1186/s12884-016-0994-9. PMID: 27485138; PMCID: PMC4971662. Delele TG, Biks GA, Abebe SM, Kebede ZT. Prevalence of common symptoms of neonatal illness in Northwest Ethiopia: A repeated measure cross-sectional study. PLoS One. 2021 Mar 30;16(3):e0248678. doi: 10.1371/journal.pone.0248678. PMID: 33784322; PMCID: PMC8009397. Tewabe T, Mehariw Y, Negatie E, Yibeltal B. Neonatal mortality in the case of Felege Hiwot referral hospital, Bahir Dar, Amhara Regional State, North West Ethiopia 2016: a one year retrospective chart review. Ital J Pediatr. 2018 May 21;44(1):57. doi: 10.1186/s13052-018-0498-5. PMID: 29784060; PMCID: PMC5963133. Lindstrom DP, Berhanu B. The effects of breastfeeding and birth spacing on infant and early childhood mortality in Ethiopia. Soc Biol. 2000 Spring-Summer;47(1-2):1-17. doi: 10.1080/19485565.2000.9989006. PMID: 11521450. Jibro U, Desalew A, Ayana GM, Tura AK. Time to Death and Its Predictors among Neonates Hospitalized with Sepsis in Eastern Ethiopia. Biomed Res Int. 2024 Apr 5;2024:2594271. doi: 10.1155/2024/2594271. PMID: 38715713; PMCID: PMC11074904. Mekasha A, Tazu Z, Muhe L, Abayneh M, Gebreyesus G, Girma A, Berhane M, McClure EM, Goldenberg RL, Nigussie AK. Factors associated with the death of preterm babies admitted to neonatal intensive care units in Ethiopia: a prospective, cross-sectional, and observational study. Global pediatric health. 2020 Nov;7:2333794X20970005. Biya SA, Saketa D, Birhanu D, Gudeta T, Besho M, Getnet M, Tura G, Berhanu N, Siraneh Y, Abamecha F, Tamiru D. Trends and Determinants of Neonatal Mortality in Rural Ethiopia. medRxiv. 2024:2024-03. Zelka MA, Yalew AW, Debelew GT. The effects of completion of continuum of care in maternal health services on adverse birth outcomes in Northwestern Ethiopia: a prospective follow-up study. Reprod Health. 2022 Oct 8;19(1):200. doi: 10.1186/s12978-022-01508-5. PMID: 36209163; PMCID: PMC9548133. Page M J, McKenzie J E, Bossuyt P M, Boutron I, Hoffmann T C, Mulrow C D et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372 :n71. doi:10.1136/bmj.n71 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 Apr 19;283(15):2008-12. doi: 10.1001/jama.283.15.2008. PMID: 10789670. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND etal.. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016 Oct 12;355:i4919. doi: 10.1136/bmj.i4919. PMID: 27733354; PMCID: PMC5062054. Schroll JB, Moustgaard R, Gøtzsche PC. Dealing with substantial heterogeneity in Cochrane reviews. Cross-sectional study. BMC Med Res Methodol. 2011 Feb 24;11:22. doi: 10.1186/1471-2288-11-22. PMID: 21349195; PMCID: PMC3056846. Lifeng Lin, Haitao Chu, Mohammad Hassan Murad, Chuan Hong, Zhiyong Qu. Empirical Comparison of Publication Bias Tests in Meta-Analysis. J Gen Intern Med. 2018 Aug; 33(8): 12601267.doi: 10.1007/s11606-018-4425-7. PMCID: PMC6082203 PMID: 29663281 Schünemann H, Brożek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013 GRADEpro GDT: GRADEpro Guideline Development Tool [Software]. McMaster University and Evidence Prime, 2025. Available from gradepro.org. kefale BA, Woya AA, Tekile AK, Banti GM, Wubetu GY. Geographical disparties using EDHS data.BMC pediatr.2023 May 5, 23(1):221. dOi : 10.1186/s12887-023-04043-9. PMID: 37147651; PMCID: PMC10163692. Fenta SM, Ayenew GM, Fenta HM, Biresaw HB, Fentaw KD. Community and individual level determinants of infant mortality in rural Ethiopia using data from 2016 Ethiopian demographic and health survey. Sci Rep. 2022 Oct7;12(1):16879. doi: 10.1038/s41598-022-21438-3. PMID: 36207579; PMCID: PMC9546827. Shibesh BF, Yalew WA, Beyene MB, Minyiwab GW. Determinants of neonatal hypothermia among neonates admitted to neonatal intensive care unit northwest, Ethiopia, case-control study. J Matern Fetal Neonatal Med. 2022 Oct;35(20):3903-3908. doi: 10.1080/14767058.2020.1843153. Epub 2020 Nov 3. PMID: 33143494. Gobebo G. Determinant factors of under-five mortality in Southern Nations, Nationalities and People's region (SNNPR), Ethiopia. Ital J Pediatr. 2021 Oct 30;47(1):214. doi: 10.1186/s13052-021-01118-0. PMID: 34717721; PMCID: PMC8557013. Alebel A, Wagnew F, Petrucka P, Tesema C, Moges NA, Ketema DB, Yismaw L, Melkamu MW, Hibstie YT, Temesgen B, Bitew ZW, Tadesse AA, Kibret GD. Neonatal mortality in the neonatal intensive care unit of Debre Markos referral hospital, Northwest Ethiopia: a prospective cohort study. BMC Pediatr. 2020 Feb 15;20(1):72. doi: 10.1186/s12887-020-1963-z. PMID: 32061260; PMCID: PMC7023807. Tolossa T, Wakuma B, Mengist B, Fetensa G, Mulisa D, Ayala D, Feyisa I, Fekadu G, Jara D, Bikila H, Getahun A. Survival status and predictors of neonatal mortality among neonates admitted to Neonatal Intensive care Unit (NICU) of Wollega University referral hospital (WURH) and Nekemte Specialized hospital, Western Ethiopia: A prospective cohort study. PLoS One. 2022 Jul 29;17(7):e0268744. doi: 10.1371/journal.pone.0268744. PMID: 35905094; PMCID: PMC9337704. Tesfaw LM, Muluneh EK. Exploring and modeling recurrent birth events in Ethiopia: EMDHS 2019. BMC Pregnancy Childbirth. 2022 Aug 5;22(1):617. doi: 10.1186/s12884-022-04948-w. PMID: 35931977; PMCID: PMC9354376. Girma D, Abita Z, Fetene G, Birie B. Individual and community-level factors of perinatal mortality in the high mortality regions of Ethiopia: a multilevel mixed-effect analysis. BMC Public Health. 2022 Feb 7;22(1):247. doi: 10.1186/s12889-022-12695-y. PMID: 35130852; PMCID: PMC8819877. Shifa GT, Ahmed AA, Yalew AW. Maternal and child characteristics and health practices affecting under-five mortality: A matched case control study in Gamo Gofa Zone, Southern Ethiopia. PLoS One. 2018 Aug 15;13(8):e0202124. doi: 10.1371/journal.pone.0202124. PMID: 30110369; PMCID: PMC6093655. Roro EM, Tumtu MI, Gebre DS. Predictors, causes, and trends of neonatal mortality at Nekemte Referral Hospital, east Wollega Zone, western Ethiopia (2010-2014). Retrospective cohort study. PLoS One. 2019 Oct 9;14(10):e0221513. doi: 10.1371/journal.pone.0221513. PMID: 31596859; PMCID: PMC6785121. Tirore LL, Erkalo D, Abose S, Melaku LM, Mulugeta E, Shiferaw A, Habte A, Gebremeskel MG. Incidence of mortality and its predictors among preterm neonates in nigist eleni mohammed memmorial comprehensive specialized hospital, Hossana, Ethiopia: a prospective follow-up study. BMC Pediatr. 2024 Aug 9;24(1):511. doi: 10.1186/s12887-024-04992-9. PMID: 39123147; PMCID: PMC11312244. Tessema NS, Geda NR. Child health outcomes and associated factors among under five years children in Ethiopia: a population attributable fractions analysis of Ethiopia demographic and health survey (2005-2016). BMC Pediatr. 2024 Sep 4;24(1):560. doi: 10.1186/s12887-024-05019-z. PMID: 39232700; PMCID: PMC11373244. Wubneh CA, Endalamaw A, Tebeje NB. Predictors of mortality among HIV exposed infants at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. Ital J Pediatr. 2019 Nov 7;45(1):137. doi: 10.1186/s13052-019-0740-9. PMID: 31699137; PMCID: PMC6839236. Miller NP, Degefie T, Hazel E, Legesse H, Tolera T, Amouzou A. Coverage and equitability of interventions to prevent child mortality in rural Jimma and West Hararghe Zones, Oromia Region, Ethiopia. Ethiopia Med J. 2014 Oct;52 Suppl 3:37-45. PMID: 25845072. Hagos BT, Gebrerufael GG. Predictors of time to death among under-five children in pastoral regions of Ethiopia: A retrospective follow-up study. PLoS One. 2024 Jul 31;19(7):e0304662. doi: 10.1371/journal.pone.0304662. PMID: 39083551; PMCID: PMC11290679. Khan, J., Vesel, L., Bahl, R. et al. Timing of Breastfeeding Initiation and Exclusivity of Breastfeeding During the First Month of Life: Effects on Neonatal Mortality and Morbidity—A Systematic Review and Meta-analysis. Matern Child Health J 19 , 468–479 (2015). https://doi.org/10.1007/s10995-014-1526-8 Debes, A.K., Kohli, A., Walker, N. et al. Time to initiation of breastfeeding and neonatal mortality and morbidity: a systematic review. BMC Public Health 13 (Suppl 3), S19 (2013). https://doi.org/10.1186/1471-2458-13-S3-S19 Sandra L. Huffman, Elizabeth R. Zehner, Cesar Victora, Can improvements in breast-feeding practices reduce neonatal mortality in developing countries? Midwifery,Volume 17, Issue 2, 2001, Pages 80-92,ISSN0266-6138, https://doi.org/10.1054/midw.2001.0253. Additional Declarations The authors declare no competing interests. Supplementary Files PRISMA2020checklist.docx PRISMA Checklist MOOSEChecklist.doc MOOSE Checklist Extracteddata.xlsx Extracted data Screeningstudies.xlsx Screening studies Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7038235","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":480192180,"identity":"2bef7204-6119-4935-9370-66488ff60ed1","order_by":0,"name":"Fillmon Kidus","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+ElEQVRIiWNgGAWjYBAC9mbmxgNA2oCNIYGB+e8/GyCbESyCE/AcZmyAa2HgYUsDaWnAr+UAVAsDRMthsCh+LeyMDYduVNwx5mPPMf4gwXPebm37YaAhNTbROLUwMzYczjnzzIyN542ZhIHE7eRtZxKBWo6l5Tbg0GIP0pLbdtiGTSLHjCHB4Hay2QGgFpAgLi08SFqMPxxIOJdsdv4hcVrMgFoMJBsOHLAzu0GMLTlnDhuz8Twrk2ZsSE4wuwG0JQGPX3j4Dx98nFNx2HB+e/Lmz4wNdvZm59MfPvhQY4NTCwZIBKtMIFY5CNiTongUjIJRMApGBgAAd2RjUvesTMQAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-4090-0914","institution":"Tigray Regional Health Bureau","correspondingAuthor":true,"prefix":"","firstName":"Fillmon","middleName":"","lastName":"Kidus","suffix":""},{"id":480192181,"identity":"2111ac18-9010-4fd5-8f2e-d7f869d5ee63","order_by":1,"name":"Demeke Tolira","email":"","orcid":"","institution":"United Nations Children's fund","correspondingAuthor":false,"prefix":"","firstName":"Demeke","middleName":"","lastName":"Tolira","suffix":""},{"id":480192182,"identity":"c5c10a95-a3ff-4048-b55d-f30636a28e4d","order_by":2,"name":"Tesema Kecha","email":"","orcid":"","institution":"Clinton Health Access Initiative","correspondingAuthor":false,"prefix":"","firstName":"Tesema","middleName":"","lastName":"Kecha","suffix":""}],"badges":[],"createdAt":"2025-07-03 12:33:36","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7038235/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7038235/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":86143536,"identity":"e930cafb-b0ff-45ea-9fc2-285c5e1eab4a","added_by":"auto","created_at":"2025-07-07 08:42:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":723284,"visible":true,"origin":"","legend":"\u003cp\u003eFlow Chart of Study Search Results Adapted from the PRISMA Statement to Examine the Effect of Breastfeeding on Neonatal Mortality: A Meta-Analysis of Observational Studies in Ethiopia, January 2000 - 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November 2024\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-7038235/v1/431eaacfee785ecfe2e69a05.png"},{"id":86141627,"identity":"30f0832c-8ac0-4099-8eba-b19085167809","added_by":"auto","created_at":"2025-07-07 08:26:53","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":59420,"visible":true,"origin":"","legend":"\u003cp\u003eBegg’s Funnel Plot of the Effect of Breastfeeding on Neonatal Mortality: A Meta-Analysis of Observational Studies in Ethiopia , January 2000 -November 2025\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7038235/v1/a0a221fe5abd6d16a45d1814.png"},{"id":86143947,"identity":"47d0337a-c10f-4ecc-9cdc-7e361806179e","added_by":"auto","created_at":"2025-07-07 08:50:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3197189,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7038235/v1/95c75847-cf97-4c78-9935-6081229d19da.pdf"},{"id":86141620,"identity":"346cad71-e8a3-42da-a770-5668a136e492","added_by":"auto","created_at":"2025-07-07 08:26:53","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":273498,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA Checklist\u003c/p\u003e","description":"","filename":"PRISMA2020checklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-7038235/v1/7c82c84dbfdb9bb96a314a5f.docx"},{"id":86142210,"identity":"8617fc28-eeb7-48b0-bc92-df313793b6d3","added_by":"auto","created_at":"2025-07-07 08:34:53","extension":"doc","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":422912,"visible":true,"origin":"","legend":"\u003cp\u003eMOOSE Checklist\u003c/p\u003e","description":"","filename":"MOOSEChecklist.doc","url":"https://assets-eu.researchsquare.com/files/rs-7038235/v1/92e24deef61580bd04e1ec5c.doc"},{"id":86142212,"identity":"5503399c-13d2-4756-852a-c1e7a976f9c2","added_by":"auto","created_at":"2025-07-07 08:34:53","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":10058,"visible":true,"origin":"","legend":"\u003cp\u003eExtracted data\u003c/p\u003e","description":"","filename":"Extracteddata.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7038235/v1/2531c43e6b2029af13fbe6d9.xlsx"},{"id":86142213,"identity":"383aa93e-227e-4fda-ba2f-9737fca5f095","added_by":"auto","created_at":"2025-07-07 08:34:53","extension":"xlsx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":23841,"visible":true,"origin":"","legend":"\u003cp\u003eScreening studies\u003c/p\u003e","description":"","filename":"Screeningstudies.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7038235/v1/6469661d006f7bb5bbf11a41.xlsx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eEffect of breastfeeding on neonatal mortality : A systemic review and meta-analysis of observational studies in Ethiopia\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"STRENGTH AND LIMITAION OF THIS STUDY","content":"\u003cul\u003e\n \u003cli\u003eThis study adhere with \u0026nbsp;the guidelines of Meta-Analysis of Epidemiological observational studies(MOOSE) and Preferred Report Items for Systemic Review and Meta-Analysis(PRISMA)\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eThe study employ to \u0026nbsp;assess the risk of bias and certainty of evidence of the studies using ROBINS-I(Risk of Bias in Non- Randomized Studies of Intervention\u0026nbsp;tool).and GRADE approach(Grading of Recommendations Assessment Development and Evaluation)\u0026nbsp;respectively.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eThe evidence included in the study were heterogeneous due to variation in sample size, study design , sampling method, and study area.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eThe quality of the evidence was also found moderate quality, \u0026nbsp; which may impact the effect size. \u0026nbsp;\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;The review process was that the initiation time of breastfeeding was not measured or not taken in to account. Only exclusive breastfeeding was taken in to account \u0026nbsp; in the review process. \u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"INTRODUCTION","content":"\u003cp\u003eThe neonatal period, defined as the first month (28 days) of life, is the most critical period for survival. Globally, 2017, there were 2.5 million neonatal deaths, which major which occurring early in the first days of life (1). Neonatal mortality contributed to 47% of under-five mortality (1). The global neonatal mortality rate (NMR) \u0026nbsp;decreased from 37 per 1000 live births (LBs) in 1990 to 18 per 1000 LBs in 2017 (1). Although this overall reduction in mortality is exceed 50%, this decline was slower compared to \u0026nbsp;children older than one month (2). The highest rates were found \u0026nbsp; in sub-Saharan Africa (SSA) and South Asia (1). \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The majority of \u0026nbsp;neonatal deaths were occur during the early neonatal period, which approximately about 1.7 million (75%) of the total neonatal deaths, and the majority (1 million) of early neonatal deaths occur within 24 hour of birth \u0026nbsp;(3). \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEthiopia has achieved \u0026nbsp;the Millennium Development Goal (MDG) 4 by reducing under-five mortality by two-thirds, three years a head the 2015 deadline (1). Although neonatal mortality has declined, it remains high, and Ethiopia is one of \u0026nbsp;the five countries where half of the world’s neonatal deaths are concentrated (1). \u0026nbsp;\u0026nbsp;Neonatal mortality in Ethiopia decreased from 39 to 29 between the 2005 and the 2016 Ethiopian Demographic and Health Survey (EDHS), but has remained stable since the 2016 EDHS and even \u0026nbsp;increased to 33 deaths per 1,000 live births in the 2019 EDHS \u0026nbsp;(4).\u003c/p\u003e\n\u003cp\u003eEarly initiation of breastfeeding protects newborns from infections and reduces mortality rate (5-7). It \u0026nbsp;also strengthens the emotional bond between the newborn and the mother and positively impacts the duration of exclusive breastfeeding (8,9). The yellow or golden first milk produced in the first few days \u0026nbsp;known as colostrum , is a vital \u0026nbsp;source of nutrition and immune protection for the newborn (8, 9). Colostrum is a complex biological nutrient rich fluid produced by female mammals immediately after giving birth that provides \u0026nbsp;essential immune support , growth, and tissue repair capabilities (10 , 11).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGlobally, an estimated 22% of early neonatal deaths 2018 were attributed to the late initiation of breastfeeding (12,13). The failure of to initiate early breast feeding( EIBF) in the first hour after birth is estimated to double the risk of neonatal death (14, 15). Although EIBF is a cost-effective and easily implementable practice with significant implications for saving newborn lives only 42% of mothers \u0026nbsp;worldwide initiate breastfeeding within the first hour of birth (16). The Prevalence of \u0026nbsp; EIBF \u0026nbsp;varies across regions, with high-income countries having a higher practice of EIBF compared to low- and middle-income countries (17).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSome observational studies conducted in Ethiopia indicated that, breastfeeding and neonatal mortality have a statistically significant association (18-23, 26-39). However, other studies indicated that, not statistical significant (24,25, 40).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn past time , there is no meta analysis conducted in Ethiopia to review impact of breastfeeding on neonatal mortality. So that, \u0026nbsp;to come up with concrete evidence regarding the effect of breast feeding on neonatal mortality, it is essential to have systematic review and meta-analysis of studies conducted in Ethiopia. The purpose of this systemic review and meta-analysis is to determine the pooled effect and assess the inconsistency of \u0026nbsp; findings of \u0026nbsp;related to breast feeding on neonatal mortality by reviewing observational studies conducted in Ethiopia. The findings of this study will help policy makers and stakeholders \u0026nbsp;in the health sector to implement effective intervention of breastfeeding to reduce neonatal mortality at local and national level.\u0026nbsp;\u003c/p\u003e"},{"header":"METHOD ","content":"\u003cp\u003eThis systemic review and Meta-Analysis was guided according the guide line of Preferred Reporting Items for Systemic Review and Meta- Analysis(PRISIMA)(41). Additionally, by the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) standard for epidemiological observational studies(42). \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSearch Strategy \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted an electronic bibliographic search in the following data base: PUBMed, MEDLINE, EMBASE, LILACS, Google scholar, and WHO journal data bases. We used search strategy in PUBMed and EMBASE as follow :(((((((breastfeeding [MeSH Terms]) AND (neonatal mortality[MeSH Terms])) ) OR (child mortality [MeSH Terms])) OR (infant mortality[MeSH Terms])) AND (Ethiopia [MeSH Terms]) \u003c/p\u003e\n\u003cp\u003eGoogle scholar : \"neonatal- mortality\" \"breast- feeding\" \"Ethiopia\" \"case- control\" \"cross- sectional\" \"cohort\". \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSelection Process \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo independent reviewers (FK and DT) initially scanned titles and abstracts to select potential full- text articles for further detailed review. When the titles and abstracts were accepted by reviewers, the full text of the articles was obtained through linked databases and carefully reviewed for inclusion by both reviewers. Studies published by the same researchers that examined the same factors were checked for potential duplicate data based on the year of publication and the study areas. In case of duplication the study with the largest data set was used for meta analysis. When there was disagreement, it was resolved through discussion with third reviewer (TK).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEligibility Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Type : \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInclusion Criteria : Observational study designs published in any language from January , 2000 GC until November, 2024 GC and study conducted exclusively in Ethiopia. \u003c/p\u003e\n\u003cp\u003eExclusion Criteria: Studies that consist solely of with abstracts and studies conducted in other countries. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e Study population : \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInclusion Criteria : All live neonates during the first 28 days of completed day of life and all neonate who died with in 28 completed days of life. \u003c/p\u003e\n\u003cp\u003eExclusion: Criteria: Neonates who died after 28 completed days of life. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome of Interest : \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInclusion Criteria: The primary outcome was neonatal mortality, it defined as the death of a live born child before the 28\u003csup\u003eth\u003c/sup\u003e day of life. \u003c/p\u003e\n\u003cp\u003eExclusion Criteria: Death of a live born child after the 28\u003csup\u003eth\u003c/sup\u003e day of life. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExposure of Interest : \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInclusion Criteria : Exclusive breastfeeding is defined as providing only breast milk to neonate during the first 28 completed days of life. Babies can be fed directly from their mother’s breast or breast milk can be pumped and administered to the baby using a bottle. \u003c/p\u003e\n\u003cp\u003eExclusion Criteria:: The provision of breast milk with other additional food to neonate during the first 28 days of completed life. \u003c/p\u003e\n\u003ch2 id=\"_Toc1021\"\u003e Data Collection Process \u003c/h2\u003e\n\u003cp\u003eThe data extraction form was developed by the investigator in Excel format based on a pilot review, the extraction and calibration of the included studies were conducted accordingly. Two reviewers independently extracted data from the eligible studies to assess quality of the study and synthesize the data. Any discrepancies identified were resolved through discussion with a third reviewer. Necessary information included the author, study setting, study population, and detail of exposure, study design, outcome, information for assessing of risk biases, sample size, and effect size measurements. \u003c/p\u003e\n\u003cp id=\"_Toc18014\"\u003e\u003cstrong\u003eData Items of Outcome\u003c/strong\u003e: The outcome domain and definition are as fellows: Neonatal death is defined as number of deaths of live born child during the first 28 completed days of life. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Item Other variable :\u003c/strong\u003e Author, country, Year of Publication, type of study design, sample population, effect size measurement type , sampling method and Standard Error\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e Study Risk of Bias Assessment \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo reviewers(FK and DT) independently evaluated the risk of bias in the included studies by assessing the quality of the studies. The overall risk of bias assessment was conducted using the ROBINS-I tool version 2, which is suitable for non- randomized studies based on seven domains of risk of bias and the results were categorized in to three levels of rating : low, moderate , and serious (43). In cases of disagreement between the reviewers regarding the risk of bias in specific studies, the issue was resolved through discussion, with the involvement of a third reviewer(TK). Over all, the findings from the assessment were utilized in data synthesis for the pre- planned sensitivity analysis to test the effect of removing poor quality studies. \u003c/p\u003e\n\u003ch2 id=\"_Toc7099\"\u003eSynthesis Methods \u003c/h2\u003e\n\u003cp\u003eAll meta- analyses were performed using IBM SPSS version 30. We employed random effect model, because of presence of heterogeneity with in the studies. The summery of effect size for each study was calculated using the Odds ratio (OR) with P value P\u0026lt; 0.05 as significant value , which is recommended for dichotomous categorical data with 95 % confidence interval. Statistical heterogeneity was assessed using cochran’s Q statistical test of and I\u003csup\u003e2\u003c/sup\u003e statistics test to quantify the level of heterogeneity between studies. We considered I\u003csup\u003e2\u003c/sup\u003e value greater than 50% to be indicative of substantial heterogeneity (44). Sensitivity analysis was conducted using leave -out -one study meta -analysis method to evaluate the influence of each stud on the pooled effect size. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubgroup\u003c/strong\u003e\u003cstrong\u003e and Meta-Regression Analysis\u003c/strong\u003e : The impact of covariates on the pooled effect size and heterogeneity across studies was evaluated using meta-regression and subgroup analysis. The effect of covariates on the pooled effect size is deemed significant when the p-value is \u0026lt;0.05. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eReporting Bias Assessment \u003c/strong\u003e: We conducted Begg’s funnel plot and Egger‘s regression test to assess presence of publication bias (45), The strategies for addressing missing information on the methods used in the included studies authors was contacted using email address provided in the publication, or accessing phone directories from the author’s documented affiliated organizations. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCertainty Assessment\u003c/strong\u003e\u003cstrong\u003e :\u003c/strong\u003e The certainty assessment was conducted using GRADE approach method (Grading of Recommendation Assessment, Development, and Evaluation) (46) with the GRADEpro soft ware(47). The approach employs a four rating system high, moderate, low , and very low. \u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003eStudy Selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA literature review was conducted from September 05, 2024 until November 07, 2024 using data bases such as MEDLINE, PubMed, LILACS, Google scholar, EMBASE, and the WHO journal. The review adhere to PRISMA 2020 statement (41) and MOOSE standard for epidemiological observational studies(42).\u003c/p\u003e\n\u003cp\u003eA total of 767 records related to the review topic were identified with publication years ranging from January, 2000 GC. To July, 2024 GC. After removing duplicate of 217 record, 550 record remained but 466 were excluded during the initial assessment due to irrelevance their titles. The remaining 84 records were accessed and screened. However, 37 records were assessed for eligibility , 27 studies (20, 22,23 , 26,27, 30, 31, 33,34, 36,38, 48-62) were excluded because there were not relevant based on the exposure , outcome , study design, and effect measure . As a result , 10 studies published in English ( 18, 19, 21, 24,25, 29, 32, 35, 39,40) had their full- text articles were accessed and included in the review (Figure 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe studies were observational in nature, comprising five cross sectional, three case control and two prospective study design. Additionally, the studies were conducted in diverse region of Ethiopia (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRisk of Bias Assessment in Studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA risk of bias assessment was conducted for each study using the ROBINS I tool which evaluate seven domains of bias: confounding, classification of intervention, selection of participant into the study, deviation from the intended intervention, risk of bias due to missing data, measurement of outcomes and selection of reported results. The overall risk of bias assessment for each study was low risk of bias except for studies (21, 24, 39) moderate risk of bias. However; the overall judgement of risk of bias of the studies were moderate (Figure 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults of Synthesis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe overall pooled effect measure indicated a 76% reduction in neonatal mortality due to breastfeeding interventions as determined by a random effects model meta -analysis [ OR= 0.24, 95%CI (0.03-0.45)],P=0.02]. Heterogeneity among studies was assessed using cochrane\u0026rsquo;s Q statistical test, which revealed that, [ Q=97.46 , DF (degree of freedom) = 9 and P = 0.00] . Additionally, Higgins I \u003csup\u003e2\u0026nbsp;\u003c/sup\u003estatisticaltest showed that presence of heterogeneity [I\u003csup\u003e2\u0026nbsp;\u003c/sup\u003e= 96%](Figure 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubgroup Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSubgroup analysis was conducted to identify the sources of heterogeneity in the reviewed studies. According to the subgroup analysis, multistage cluster sampling and two stage stratified cluster sampling did not statistically significant. Studies conducted in Benshangul, Northwestern Ethiopia, and nine region of Ethiopia revealed no statistically significant. Both cross sectional and prospective cohort study designs found no statistically significant. .More over, sample size greater than 5,000 did not statistically significant. However, The subgroup random effect meta analysis pooled result showed statistically significant with [OR= O.24, 95%CI: (0.03 - O.45), P = 0.02] : and the subgroup pooled effect measure also found consistent with the over all pooled meta analysis result of the all studies. Additionally, the subgroup I \u003csup\u003e2\u0026nbsp;\u003c/sup\u003e and Q statistical test indicated heterogeneity with [I\u003csup\u003e2\u0026nbsp;\u003c/sup\u003e= 96% ] (Table 2) .\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeta Regression Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA meta-regression was conducted to examine the effect of certain covariates on impact of breastfeeding on neonatal mortality. The analysis was estimated using likely hood method of REML (Restricted Maximum Likelyhood ) and using Knapp -Hartung method the SE was adjusted and random effect meta regression model was employed. The effect of sample size relationship between breastfeeding and neonatal mortality was assessed and yielding Q statistic value [ Q= 59.87, df = 8 , P = \u0026lt;0.01] and [ I \u003csup\u003e2\u0026nbsp;\u003c/sup\u003e=89.5%]. additionally, effect of study design on relationship between breastfeeding and neonatal mortality evaluated , result in a Q statistical test value [Q= 85.99, df =7, P = \u0026lt;0.01] and I \u003csup\u003e2\u0026nbsp;\u003c/sup\u003e statistical test of heterogeneity was[I\u003csup\u003e2\u003c/sup\u003e= 97.1]. The third covarate was effect of sampling method on relationship between breastfeeding and neonatal mortality was reported that with a Q Statistical homogeneity was[Q= 46.09 , df =7, P = \u0026lt;0.001 ] and I\u003csup\u003e2\u0026nbsp;\u003c/sup\u003estatistical test of heterogeneity was [I\u003csup\u003e2\u0026nbsp;\u003c/sup\u003e= 99.4%].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSensitivity Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo further investigate the influence of each study in the meta -analysis of the effect of breast feeding on neonatal mortality; we performed a leave- one- out sensitivity analysis. The result of our sensitivity analysis indicated that the point- estimated effect size obtained when each study was excluded from meta -analysis was fell with in confidence interval of the pooled effect size of the overall study, except for the meta -analysis that excluded studies ( 18, 19, 39, 40) which were out side the range of confidence interval of the pooled result of with out leave- out -one study but not exaggerated. Notably,, the heterogeneity result was the same or stable. Which the original pooled effect size was [OR=0.24, 95%CI(0.033-0.45)], while the leave out -one- study meta-analysis was indicated that the pooled effect measure ranged between [OR= 0.10 , 95%CI (0.01-0.19)] and [OR= 0.31, 95%CI(0.04 - 0.56)]. Therefore, these four studies were identified influential, and the results of the leave out- one -study meta- analysis were deemed implausible(Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePublication Biases\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBegg\u0026rsquo;s funnel plot was indicated that it was symmetrical , and Egger\u0026rsquo;s regression test yielded an effect measure of [ OR= 0.07, 95%CI( -6.285 - 6.424) , P= 0.98]. Therefore, provided then no significant publication bias was observed with regard to effect of breastfeeding on neonatal mortality in observational studies conducted in Ethiopia( Figure 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCertainty of Evidence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe employed GRADE approach (46) and GRADEpro software (47) to analyze certainty of evidence regarding the study effect of breast feeding on neonatal mortality. The cafeterias used to assess certainty of evidence with neonatal mortality as outcome were number of studies included, study design, risk of bias, inconsistencies, indirectness, imprecision, publication bias, confounding , large effect size, and dose response prediction. The overall , result of the evidence assessment revealed that the quality of evidence was moderate .\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis systematic review and meta- analysis, identified and assessed ten studies through data base search conducted from January 2000 - November 2024. However, the included studies were published between 2019 and 2024. Up on reviewing the individual studies, we found, that three were case control studies, five were cross sectional studies and two were prospective cohort observational studies. Seven studies reported that a statistically significant association between breastfeeding and neonatal mortality. In contrast, three studies reported not statistically significant association ( 24, 25, 40). A risk of bias assessment was conducted for each study using ROBINS I tool (46), using seven domains of bias. The overall risk of bias assessment for each study was classifies as low, except for three studies that were classified as moderate (21, 24, 39). Overall judgement of the risk bias across the studies were moderate.\u003c/p\u003e\u003cp\u003eThe pooled effect size of breastfeeding on neonatal mortality indicated that breastfeeding has a statistically significant effect on reducing neonatal mortality. The analysis revealed a 76% reduction of risk of neonatal mortality in Ethiopia, with a pooled effect of [ OR = 0.24, 95%CI(0.033–0.45), P = 0.02]. This finding is consistent with systematic review and meta- analysis conducted in different countries (63–65). Clinical evidence also suggests that the early initiation of exclusive breastfeeding significantly reduces neonatal mortality by providing crucial immunity and protection against pathogens. Colostrum, the first milk produced is richer in antibodies and immune factors providing the new born with crucial protection against infection and protection from pathogens.\u003c/p\u003e\u003cp\u003eHeterogeneity among studies was assessed using cochrane’s Q statistical test which yielded the following result [ Q = 97.46, df = 9, P = 0.00]. Additionally, Higgins I \u003csup\u003e2\u003c/sup\u003e statistical test showed [ I\u003csup\u003e2\u003c/sup\u003e = 96%} confirming strong indicative of heterogeneity. Due to presence of heterogeneity we use random effect meta -analysis model for analysis of pooled effect size. Subgroup analysis and meta- regression analysis were performed to identify the sources of heterogeneity in the included studies. According to the subgroup analysis, multistage cluster sampling and two stage stratified cluster sampling did not yield statistically significant. Studies conducted in Benshangul, North Western Ethiopia, and nine region of Ethiopia indicated not statistically significant. A cross sectional and prospective cohort study found no statistically significant result. Moreover, a sample size greater than 5,000 reported as not statistically significant. Based on this evidence, the sources of heterogeneity included the sampling method, sample size, location, and study design type. Furthermore, a meta- regression analysis was performed to assess the influence of certain covariates on the effect of breastfeeding on neonatal mortality. The estimation method used was Restricted Maximum Likelyhood (REML) and employing a random effects meta- regression model and Knapp -Hartung adjusted standard error (SE). The influence of sample size on the effect of breastfeeding on neonatal mortality was reported as as statistically significant result with Q statistical test [ Q = 59.87, df = 8, P = \u0026lt; 0.01] and [ I \u003csup\u003e2\u003c/sup\u003e = 89.5%]. Additionally, the effect of study design on the relationship between breastfeeding and neonatal mortality indicated statistical significant with Q statistical test [Q = 85.99, df = 7, P = \u0026lt; 0.01], and I \u003csup\u003e2\u003c/sup\u003e statistical test of heterogeneity was [I\u003csup\u003e2\u003c/sup\u003e = 97.1]. The third covariate, the sampling method effect on association between breastfeeding and neonatal mortality indicated by the statistically significant Q statistical homogeneity test [Q = 46.09, df = 7, P = \u0026lt; 0.001 ], and I\u003csup\u003e2\u003c/sup\u003e statistical test for heterogeneity [ I\u003csup\u003e2\u003c/sup\u003e = 99.4%]. Therefore, these three characteristics of the studies were statistically significantly associated with an impact on effect measure size.\u003c/p\u003e\u003cp\u003eThe results of the sensitivity analysis revealed that the estimated effect sizes obtained through leave out -one -study meta- analysis method fell within the confidence interval for the overall pooled effect, except those excluded studies ( 18, 19, 39, 40). These were out side the range of the confidence interval for the pooled results of the overall studies, although there influence was not exaggerated. Furthermore, the heterogeneity remained stable. The original pooled effect size was [OR = 0.24, 95%CI(0.033–0.45), P = 0.02], but the leave out -one- study meta- analysis showed that the pooled effect measure ranges between [OR = 0.10, (95%CI (0.01–0.19)] and [OR = 0.31, 95%CI(0.04–0.56)]. Therefore, these four studies were identified as influential in the meta analysis. Consequently, the results of the leave out -one -study meta- analysis not deemed plausible.\u003c/p\u003e\u003cp\u003eRegarding publication bias, a Begg’s funnel plot was generated, which appeared symmetrical. Additionally, Egger’s regression test yielded an effect measure of [ OR = 0.07, 95%CI( -6.285–6.424), P = 0.98], based on this evidence, no significant publication bias was observed concerning the effect of breastfeeding on neonatal mortality in observational studies conducted in Ethiopia. Finally, the quality from evidence of the studies was assessed using GRADE approach, which indicated a moderate quality of evidence.\u003c/p\u003e"},{"header":"Conclusion and Recommendation","content":"\u003cp\u003eThe meta analysis indicated that breastfeeding practice as a protective intervention to reduce the risk of neonatal mortality in Ethiopia. Additionally, the studies included in the review found inconsistencies in their effect measures due to variation in study design, sampling method, and sample size. Therefore, policymakers should incorporate breastfeeding promotion as key component of child survival strategies to reduce the high neonatal mortality rate in Ethiopia. We also recommend that future study that can take in to account the initiation time of breastfeeding.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCI : Confidence Interval, CM: Child Mortality , \u0026nbsp;DF: Degree of Freedom , \u0026nbsp;EDHS: Ethiopian Demographic Health Survey, EIBF: Early Initiation of Breastfeed, \u0026nbsp;EMBASE: Excerpta Medica Data Base, GRADE: Grading of Recommendations Assessment Development and Evaluation , IM: Infant Mortality , LB: Live Birth, MDG: Millennium Development Goal , MEDLINE: Medical Literature Analysis and Retrieval System, \u0026nbsp; NM: Neonatal Mortality , \u0026nbsp;NMR: Neonatal Mortality \u0026nbsp;Rate, OR: Odds Ratio, PRISMA: Preferred Reporting Item for Systemic review and Meta Analysis, PROSPERO: International Prospective Register of Systemic Review , REML: Restricted Maximum Likelihood, \u0026nbsp;ROBINS-I: Risk of Bias in Non- Randomized Studies of Intervention, SSA: Sub Saharan Africa\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the data generated during this Meta-Analysis and review are included in this published article \u0026nbsp;with in the figure, tables and supplementary material.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors Contributions \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFK was responsible from inception to design, protocol preparation, protocol registration, acquisition of data , analysis, and interpretation of data and preparing the manuscript. DT was responsible for acquisition of data and interpretation as second independent reviewer. TK was responsible for acquisition of data and interpretation of data as third independent reviewer. All author read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all the authors and publishers of original studies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors affilations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003e\u0026nbsp; \u0026nbsp;Tigray Regional Health Bureau, Researcher, Epidemiologist and surveillance specialists , Mekelle, Tigray Region, \u0026nbsp;Ethiopia.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2 \u0026nbsp;\u003c/sup\u003eClinton Health Access Initiative, Immunization Coordinator, \u0026nbsp;Addis Ababa, Ethiopia.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003csup\u003e2 \u0026nbsp;\u003c/sup\u003e United Nation Children Fund, Immunization and COVID -19 \u0026nbsp;Consultant, Addis Ababa, Ethiopia.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eUnited Nations Inter-agency Group for Child Mortality Estimation (UN IGME) . Levels \u0026amp; trends in child mortality: report 2017, estimates developed by the UN inter agency group for child mortality estimation. New York (NY): United Nations Children\u0026rsquo;s Fund; 2017. [\u003cu\u003eGoogle Scholar\u003c/u\u003e]\u003c/li\u003e\n\u003cli\u003eHug L, Alexander M, You D, Alkema L.. National, regional, and global levels and trends in neonatal mortality between 1990 and 2017, with scenario-based projections to 2030: a systematic analysis. \u003cem\u003eLancet Glob Health\u003c/em\u003e. 2019;7:e710\u0026ndash;8. doi: 10.1016/S2214-109X(19)30163-9; Epub 2019/05/18. [\u003cu\u003ePMC free article\u003c/u\u003e] [\u003cu\u003ePubMed\u003c/u\u003e] [\u003cu\u003eCrossRef\u003c/u\u003e] [\u003cu\u003eGoogle Scholar\u003c/u\u003e]\u003c/li\u003e\n\u003cli\u003eAssefa Y, Damme WV, Williams OD, Hill PS.. Successes and challenges of the millennium development goals in Ethiopia: lessons for the sustainable development goals. \u003cem\u003eBMJ Global Health\u003c/em\u003e. 2017;2:e000318. doi: 10.1136/bmjgh-2017-000318; Epub 2017/10/31. [\u003cu\u003ePMC free article\u003c/u\u003e] [\u003cu\u003ePubMed\u003c/u\u003e] [\u003cu\u003eCrossRef\u003c/u\u003e] [\u003cu\u003eGoogle Scholar\u003c/u\u003e]\u003c/li\u003e\n\u003cli\u003eEthiopia M. Demographic and Health Survey 2019 \u003c/li\u003e\n\u003cli\u003eEdmond KM, Kirkwood BR, Amenga-Etego S, Owusu-Agyei S, Hurt LS. Effect of early infant feeding practices on infection-specific neonatal mortality: an investigation of the causal links with observational data from rural Ghana. \u003cem\u003eAm J Clin Nutr\u003c/em\u003e. 2007;86: 1126\u0026ndash;1131. doi: 10.1093/ajcn/86.4.1126 [\u003cu\u003ePubMed\u003c/u\u003e] [\u003cu\u003eCrossRef\u003c/u\u003e] [\u003cu\u003eGoogle Scholar\u003c/u\u003e]\u003c/li\u003e\n\u003cli\u003eBorg B, Gribble K, Courtney‐Haag K, Parajuli KR, Mihrshahi S. Association between early initiation of breastfeeding and reduced risk of respiratory infection: Implications for nonseparation of infant and mother in the COVID‐19 context. \u003cem\u003eMatern Child Nutr\u003c/em\u003e. 2022;18. doi: 10.1111/mcn.13328 [\u003cu\u003ePMC free article\u003c/u\u003e] [\u003cu\u003ePubMed\u003c/u\u003e] [\u003cu\u003eCrossRef\u003c/u\u003e] [\u003cu\u003eGoogle Scholar\u003c/u\u003e]\u003c/li\u003e\n\u003cli\u003eDebes AK, Kohli A, Walker N, Edmond K, Mullany LC. Time to initiation of breastfeeding and neonatal mortality and morbidity: a systematic review. \u003cem\u003eBMC Public Health\u003c/em\u003e. 2013;13: S19. doi: 10.1186/1471-2458-13-S3-S19 [\u003cu\u003ePMC free article\u003c/u\u003e] [\u003cu\u003ePubMed\u003c/u\u003e] [\u003cu\u003eCrossRef\u003c/u\u003e] [\u003cu\u003eGoogle Scholar\u003c/u\u003e]\u003c/li\u003e\n\u003cli\u003eLiu J, Leung P, Yang A. Breastfeeding and Active Bonding Protects against Children\u0026rsquo;s Internalizing Behavior Problems. \u003cem\u003eNutrients\u003c/em\u003e. 2013;6: 76\u0026ndash;89. doi: 10.3390/nu6010076 [\u003cu\u003ePMC free article\u003c/u\u003e] [\u003cu\u003ePubMed\u003c/u\u003e] [\u003cu\u003eCrossRef\u003c/u\u003e] [\u003cu\u003eGoogle Scholar\u003c/u\u003e]\u003c/li\u003e\n\u003cli\u003eElse-Quest NM, Hyde JS, Clark R. Breastfeeding, Bonding, and the Mother-Infant Relationship. \u003cem\u003eMerrill Palmer Q\u003c/em\u003e. 2003;49: 495\u0026ndash;517. doi: 10.1353/mpq.2003.0020 [\u003cu\u003eCrossRef\u003c/u\u003e] [\u003cu\u003eGoogle Scholar\u003c/u\u003e]\u003c/li\u003e\n\u003cli\u003eThapa BR. Health factors in colostrum. \u003cem\u003eIndian J Pediatr\u003c/em\u003e. 2005;72: 579\u0026ndash;581. doi: 10.1007/BF02724182 [\u003cu\u003ePubMed\u003c/u\u003e] [\u003cu\u003eCrossRef\u003c/u\u003e] [\u003cu\u003eGoogle Scholar\u003c/u\u003e]\u003c/li\u003e\n\u003cli\u003eUruakpa FO, Ismond MAH, Akobundu ENT. \u003cem\u003eColostrum and its benefits: a review\u003c/em\u003e. 2002. Available: \u003cu\u003ewww.elsevier.com/locate/nutres\u003c/u\u003e [\u003cu\u003eGoogle Scholar\u003c/u\u003e]\u003c/li\u003e\n\u003cli\u003eEdmond K. M., Kirkwood B. R., Amenga-Etego S., Owusu-Agyei S., Hurt L. S. Effect of early infant feeding practices on infection-specific neonatal mortality: an investigation of the causal links with observational data from rural Ghana. \u003cem\u003eThe American Journal of Clinical Nutrition\u003c/em\u003e\u003cem\u003e . \u003c/em\u003e2007;86(4):1126\u0026ndash;1131. doi: 10.1093/ajcn/86.4.1126. [\u003cu\u003ePubMed\u003c/u\u003e] [\u003cu\u003eCrossRef\u003c/u\u003e] [\u003cu\u003eGoogle Scholar\u003c/u\u003e]\u003c/li\u003e\n\u003cli\u003eWHO. \u003cem\u003eBreast Feeding\u003c/em\u003e\u003cem\u003e .\u003c/em\u003e Geneva: World Health Organization; 2018. [\u003cu\u003eGoogle Scholar\u003c/u\u003e]\u003c/li\u003e\n\u003cli\u003eKhan J., Vesel L., Bahl R., Martines J. C. Timing of breastfeeding initiation and exclusivity of breastfeeding during the first month of life: effects on neonatal mortality and morbidity\u0026mdash;a systematic review and meta-analysis. \u003cem\u003eMaternal and Child Health Journal\u003c/em\u003e\u003cem\u003e . \u003c/em\u003e2015;19(3):468\u0026ndash;479. doi: 10.1007/s10995-014-1526-8. [\u003cu\u003ePubMed\u003c/u\u003e] [\u003cu\u003eCrossRef\u003c/u\u003e] [\u003cu\u003eGoogle Scholar\u003c/u\u003e]\u003c/li\u003e\n\u003cli\u003eNEOVITA Study Group. Timing of initiation, patterns of breastfeeding, and infant survival: prospective analysis of pooled data from three randomised trials. \u003cem\u003eThe Lancet Global Health\u003c/em\u003e\u003cem\u003e . \u003c/em\u003e2016;4(4):e266\u0026ndash;e275. doi: 10.1016/S2214-109X(16)00040-1. [\u003cu\u003ePubMed\u003c/u\u003e] [\u003cu\u003eCrossRef\u003c/u\u003e] [\u003cu\u003eGoogle Scholar\u003c/u\u003e]\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. \u003cem\u003eHealth in 2015: from MDGs, Millennium Development Goals to SDGs, Sustainable Development goals\u003c/em\u003e\u003cem\u003e .\u003c/em\u003e World Health Organization; 2015. [\u003cu\u003eGoogle Scholar\u003c/u\u003e]\u003c/li\u003e\n\u003cli\u003eVictora C. G., Bahl R., Barros A. J., et al. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. \u003cem\u003eLancet (London, England).\u003c/em\u003e\u003cem\u003e . \u003c/em\u003e2016;387(10017):475\u0026ndash;490. doi: 10.1016/S0140-6736(15)01024-7. [\u003cu\u003ePubMed\u003c/u\u003e] [\u003cu\u003eCrossRef\u003c/u\u003e] [\u003cu\u003eGoogle Scholar\u003c/u\u003e]\u003c/li\u003e\n\u003cli\u003eMitiku HD. Neonatal mortality and associated factors in Ethiopia: a cross-sectional population-based study. BMC Womens Health. 2021 Apr 16;21(1):156. doi:10.1186/s12905-021-01308-2. PMID: 33863331; PMCID: PMC8052649. \u003c/li\u003e\n\u003cli\u003eGirma B, Nigussie J. Magnitude of preterm hospital neonatal mortality and associated factors in northern Ethiopia: a cross-sectional study. BMJ Open. 2021 Dec 3;11(12):e051161. doi: 10.1136/bmjopen-2021-051161. PMID: 34862286; PMCID: PMC8647539. \u003c/li\u003e\n\u003cli\u003eZelalem Ayichew M, Derseh Gezie L, Gelagay AA, Anmut Bitew D. Neonatal mortality and associated factors among neonates admitted to neonatal intensive care unit of Gandhi memorial hospital in Addis Ababa, Ethiopia, 2019. BMC Pediatr. 2022 May 12;22(1):266. doi: 10.1186/s12887-022-03339-6. PMID: 35550058; PMCID: PMC9097131.\u003c/li\u003e\n\u003cli\u003eFentaw KD, Fenta SM, Biresaw HB, Yalew MM. Factors associated with post-neonatal mortality in Ethiopia: Using the 2019 Ethiopia mini demographic and health survey. PLoS One. 2022 Jul 27;17(7):e0272016. doi: 10.1371/journal.pone.0272016. PMID: 35895632; PMCID: PMC9328495.\u003c/li\u003e\n\u003cli\u003eSahile A, Bekele D, Ayele H. Determining factors of neonatal mortality in Ethiopia: An investigation from the 2019 Ethiopia Mini Demographic and Health Survey. PLoS One. 2022 Dec 30;17(12):e0267999. doi:10.1371/journal.pone.0267999. PMID: 36584102; PMCID: PMC9803101.\u003c/li\u003e\n\u003cli\u003eKolola T, Ekubay M, Tesfa E, Morka W. Determinants of Neonatal Mortality in North Shoa Zone, Amhara Regional State, Ethiopia. PLoS One. 2016 Oct 14;11(10):e0164472. doi: 10.1371/journal.pone.0164472. PMID: 27741284; PMCID: PMC5065191.\u003c/li\u003e\n\u003cli\u003eKidus F, Woldemichael K, Hiko D. Predictors of neonatal mortality in Assosa zone, Western Ethiopia: a matched case control study. BMC Pregnancy Childbirth. 2019 Mar 29;19(1):108. doi: 10.1186/s12884-019-2243-5. PMID: 30925903; PMCID: PMC6441179.\u003c/li\u003e\n\u003cli\u003eBekele T, Merga H, Tesfaye T, Asefa H. Predictors of mortality among neonates hospitalized with neonatal sepsis: a case control study from southern Ethiopia. BMC Pediatr. 2022 Jan 3;22(1):1. doi: 10.1186/s12887-021-03049-5. PMID: 34980043; PMCID: PMC8722178.\u003c/li\u003e\n\u003cli\u003eBirhanu D, Gebremichael B, Tesfaye T, Tadesse M, Belege F, Godie Y, Wodaje M, Tamiru E. Survival status and predictors of mortality among preterm neonates admitted to neonatal intensive care unit of Addis Ababa public hospitals, Ethiopia, 2021. A prospective cohort study. BMC Pediatr. 2022 Mar 23;22(1):153. doi: 10.1186/s12887-022-03176-7. PMID: 35321673; PMCID: PMC8941786.\u003c/li\u003e\n\u003cli\u003eAlebel A, Wagnew F, Petrucka P, Tesema C, Moges NA, Ketema DB, Yismaw L, Melkamu MW, Hibstie YT, Temesgen B, Bitew ZW, Tadesse AA, Kibret GD. Neonatal mortality in the neonatal intensive care unit of Debre Markos referral hospital, Northwest Ethiopia: a prospective cohort study. BMC Pediatr. 2020 Feb 15;20(1):72. doi: 10.1186/s12887-020-1963-z. PMID: 32061260; PMCID: PMC7023807.\u003c/li\u003e\n\u003cli\u003eTolossa T, Wakuma B, Mengist B, Fetensa G, Mulisa D, Ayala D, Feyisa I, Fekadu G, Jara D, Bikila H, Getahun A. Survival status and predictors of neonatal mortality among neonates admitted to Neonatal Intensive care Unit (NICU) of Wollega University referral hospital (WURH) and Nekemte Specialized hospital, Western Ethiopia: A prospective cohort study. PLoS One. 2022 Jul 29;17(7):e0268744. doi: 10.1371/journal.pone.0268744. PMID: 35905094; PMCID: PMC9337704.\u003c/li\u003e\n\u003cli\u003eDesalew A, Sintayehu Y, Teferi N, Amare F, Geda B, Worku T, Abera K, Asefaw A. Cause and predictors of neonatal mortality among neonates admitted to neonatal intensive care units of public hospitals in eastern Ethiopia: a facility-based prospective follow-up study. BMC Pediatr. 2020 Apr 14;20(1):160. doi: 10.1186/s12887-020-02051-7. PMID: 32290819; PMCID: PMC7155275.\u003c/li\u003e\n\u003cli\u003eRoro EM, Tumtu MI, Gebre DS. Predictors, causes, and trends of neonatal mortality at Nekemte Referral Hospital, east Wollega Zone, western Ethiopia (2010-2014). Retrospective cohort study. PLoS One. 2019 Oct 9;14(10):e0221513. doi: 10.1371/journal.pone.0221513. PMID: 31596859; PMCID: PMC6785121.\u003c/li\u003e\n\u003cli\u003eOrsido TT, Asseffa NA, Berheto TM. Predictors of Neonatal mortality in Neonatal intensive care unit at referral Hospital in Southern Ethiopia: a retrospective cohort study. BMC Pregnancy Childbirth. 2019 Feb 28;19(1):83. doi: 10.1186/s12884-019-2227-5. PMID: 30819143; PMCID: PMC6396455.\u003c/li\u003e\n\u003cli\u003eAdem A, Dache A, Dona A. Determinants of neonatal mortality among newborns admitted in neonatal intensive care unit at Dilla University Referral Hospital in Gedeo Zone, Southern, Ethiopia: unmatched case control study. BMC Pediatr. 2021 Jul 8;21(1):307. doi: 10.1186/s12887-021-02780-3. PMID: 34238264; PMCID: PMC8265069.\u003c/li\u003e\n\u003cli\u003eMengesha HG, Wuneh AD, Lerebo WT, Tekle TH. Survival of neonates and predictors of their mortality in Tigray region, Northern Ethiopia: prospective cohort study. BMC Pregnancy Childbirth. 2016 Aug 2;16(1):202. doi:10.1186/s12884-016-0994-9. PMID: 27485138; PMCID: PMC4971662.\u003c/li\u003e\n\u003cli\u003eDelele TG, Biks GA, Abebe SM, Kebede ZT. Prevalence of common symptoms of neonatal illness in Northwest Ethiopia: A repeated measure cross-sectional study. PLoS One. 2021 Mar 30;16(3):e0248678. doi: 10.1371/journal.pone.0248678. PMID: 33784322; PMCID: PMC8009397.\u003c/li\u003e\n\u003cli\u003eTewabe T, Mehariw Y, Negatie E, Yibeltal B. Neonatal mortality in the case of Felege Hiwot referral hospital, Bahir Dar, Amhara Regional State, North West Ethiopia 2016: a one year retrospective chart review. Ital J Pediatr. 2018 May 21;44(1):57. doi: 10.1186/s13052-018-0498-5. PMID: 29784060; PMCID: PMC5963133.\u003c/li\u003e\n\u003cli\u003eLindstrom DP, Berhanu B. The effects of breastfeeding and birth spacing on infant and early childhood mortality in Ethiopia. Soc Biol. 2000 Spring-Summer;47(1-2):1-17. doi: 10.1080/19485565.2000.9989006. PMID: 11521450.\u003c/li\u003e\n\u003cli\u003eJibro U, Desalew A, Ayana GM, Tura AK. Time to Death and Its Predictors among Neonates Hospitalized with Sepsis in Eastern Ethiopia. Biomed Res Int. 2024 Apr 5;2024:2594271. doi: 10.1155/2024/2594271. PMID: 38715713; PMCID: PMC11074904.\u003c/li\u003e\n\u003cli\u003eMekasha A, Tazu Z, Muhe L, Abayneh M, Gebreyesus G, Girma A, Berhane M, McClure EM, Goldenberg RL, Nigussie AK. Factors associated with the death of preterm babies admitted to neonatal intensive care units in Ethiopia: a prospective, cross-sectional, and observational study. Global pediatric health. 2020 Nov;7:2333794X20970005. \u003c/li\u003e\n\u003cli\u003eBiya SA, Saketa D, Birhanu D, Gudeta T, Besho M, Getnet M, Tura G, Berhanu N, Siraneh Y, Abamecha F, Tamiru D. Trends and Determinants of Neonatal Mortality in Rural Ethiopia. medRxiv. 2024:2024-03.\u003c/li\u003e\n\u003cli\u003eZelka MA, Yalew AW, Debelew GT. The effects of completion of continuum of care in maternal health services on adverse birth outcomes in Northwestern Ethiopia: a prospective follow-up study. Reprod Health. 2022 Oct 8;19(1):200. doi: 10.1186/s12978-022-01508-5. PMID: 36209163; PMCID: PMC9548133. \u003c/li\u003e\n\u003cli\u003ePage M J, McKenzie J E, Bossuyt P M, Boutron I, Hoffmann T C, Mulrow C D et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. \u003cem\u003eBMJ \u003c/em\u003e2021; 372 :n71. doi:10.1136/bmj.n71\u003c/li\u003e\n\u003cli\u003eStroup 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 Apr 19;283(15):2008-12. doi: 10.1001/jama.283.15.2008. PMID: 10789670.\u003c/li\u003e\n\u003cli\u003eSterne JA, Hern\u0026aacute;n MA, Reeves BC, Savović J, Berkman ND etal.. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016 Oct 12;355:i4919. doi: 10.1136/bmj.i4919. PMID: 27733354; PMCID: PMC5062054.\u003c/li\u003e\n\u003cli\u003eSchroll JB, Moustgaard R, G\u0026oslash;tzsche PC. Dealing with substantial heterogeneity in Cochrane reviews. Cross-sectional study. BMC Med Res Methodol. 2011 Feb 24;11:22. doi: 10.1186/1471-2288-11-22. PMID: 21349195; PMCID: PMC3056846.\u003c/li\u003e\n\u003cli\u003eLifeng Lin, Haitao Chu, Mohammad Hassan Murad, Chuan Hong, Zhiyong Qu. Empirical Comparison of Publication Bias Tests in Meta-Analysis. J Gen Intern Med. 2018 Aug; 33(8): 12601267.doi: 10.1007/s11606-018-4425-7. PMCID: PMC6082203 PMID: 29663281 \u003c/li\u003e\n\u003cli\u003eSch\u0026uuml;nemann H, Brożek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013 \u003c/li\u003e\n\u003cli\u003eGRADEpro GDT: GRADEpro Guideline Development Tool [Software]. McMaster University and Evidence Prime, 2025. Available from gradepro.org. \u003c/li\u003e\n\u003cli\u003ekefale BA, Woya AA, Tekile AK, Banti GM, Wubetu GY. Geographical disparties using EDHS data.BMC pediatr.2023 May 5, 23(1):221. dOi : 10.1186/s12887-023-04043-9. PMID: 37147651; PMCID: PMC10163692. \u003c/li\u003e\n\u003cli\u003eFenta SM, Ayenew GM, Fenta HM, Biresaw HB, Fentaw KD. Community and individual level determinants of infant mortality in rural Ethiopia using data from 2016 Ethiopian demographic and health survey. Sci Rep. 2022 Oct7;12(1):16879. doi: 10.1038/s41598-022-21438-3. PMID: 36207579; PMCID: PMC9546827.\u003c/li\u003e\n\u003cli\u003eShibesh BF, Yalew WA, Beyene MB, Minyiwab GW. Determinants of neonatal hypothermia among neonates admitted to neonatal intensive care unit northwest, Ethiopia, case-control study. J Matern Fetal Neonatal Med. 2022 Oct;35(20):3903-3908. doi: 10.1080/14767058.2020.1843153. Epub 2020 Nov 3. PMID: 33143494.\u003c/li\u003e\n\u003cli\u003eGobebo G. Determinant factors of under-five mortality in Southern Nations, Nationalities and People\u0026apos;s region (SNNPR), Ethiopia. Ital J Pediatr. 2021 Oct 30;47(1):214. doi: 10.1186/s13052-021-01118-0. PMID: 34717721; PMCID: PMC8557013.\u003c/li\u003e\n\u003cli\u003eAlebel A, Wagnew F, Petrucka P, Tesema C, Moges NA, Ketema DB, Yismaw L, Melkamu MW, Hibstie YT, Temesgen B, Bitew ZW, Tadesse AA, Kibret GD. Neonatal mortality in the neonatal intensive care unit of Debre Markos referral hospital, Northwest Ethiopia: a prospective cohort study. BMC Pediatr. 2020 Feb 15;20(1):72. doi: 10.1186/s12887-020-1963-z. PMID: 32061260; PMCID: PMC7023807.\u003c/li\u003e\n\u003cli\u003eTolossa T, Wakuma B, Mengist B, Fetensa G, Mulisa D, Ayala D, Feyisa I, Fekadu G, Jara D, Bikila H, Getahun A. Survival status and predictors of neonatal mortality among neonates admitted to Neonatal Intensive care Unit (NICU) of Wollega University referral hospital (WURH) and Nekemte Specialized hospital, Western Ethiopia: A prospective cohort study. PLoS One. 2022 Jul 29;17(7):e0268744. doi: 10.1371/journal.pone.0268744. PMID: 35905094; PMCID: PMC9337704.\u003c/li\u003e\n\u003cli\u003eTesfaw LM, Muluneh EK. Exploring and modeling recurrent birth events in Ethiopia: EMDHS 2019. BMC Pregnancy Childbirth. 2022 Aug 5;22(1):617. doi: 10.1186/s12884-022-04948-w. PMID: 35931977; PMCID: PMC9354376.\u003c/li\u003e\n\u003cli\u003eGirma D, Abita Z, Fetene G, Birie B. Individual and community-level factors of perinatal mortality in the high mortality regions of Ethiopia: a multilevel mixed-effect analysis. BMC Public Health. 2022 Feb 7;22(1):247. doi: 10.1186/s12889-022-12695-y. PMID: 35130852; PMCID: PMC8819877. \u003c/li\u003e\n\u003cli\u003eShifa GT, Ahmed AA, Yalew AW. Maternal and child characteristics and health practices affecting under-five mortality: A matched case control study in Gamo Gofa Zone, Southern Ethiopia. PLoS One. 2018 Aug 15;13(8):e0202124. doi: 10.1371/journal.pone.0202124. PMID: 30110369; PMCID: PMC6093655. \u003c/li\u003e\n\u003cli\u003eRoro EM, Tumtu MI, Gebre DS. Predictors, causes, and trends of neonatal mortality at Nekemte Referral Hospital, east Wollega Zone, western Ethiopia (2010-2014). Retrospective cohort study. PLoS One. 2019 Oct 9;14(10):e0221513. doi: 10.1371/journal.pone.0221513. PMID: 31596859; PMCID: PMC6785121. \u003c/li\u003e\n\u003cli\u003eTirore LL, Erkalo D, Abose S, Melaku LM, Mulugeta E, Shiferaw A, Habte A, Gebremeskel MG. Incidence of mortality and its predictors among preterm neonates in nigist eleni mohammed memmorial comprehensive specialized hospital, Hossana, Ethiopia: a prospective follow-up study. BMC Pediatr. 2024 Aug 9;24(1):511. doi: 10.1186/s12887-024-04992-9. PMID: 39123147; PMCID: PMC11312244.\u003c/li\u003e\n\u003cli\u003eTessema NS, Geda NR. Child health outcomes and associated factors among under five years children in Ethiopia: a population attributable fractions analysis of Ethiopia demographic and health survey (2005-2016). BMC Pediatr. 2024 Sep 4;24(1):560. doi: 10.1186/s12887-024-05019-z. PMID: 39232700; PMCID: PMC11373244.\u003c/li\u003e\n\u003cli\u003eWubneh CA, Endalamaw A, Tebeje NB. Predictors of mortality among HIV exposed infants at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. Ital J Pediatr. 2019 Nov 7;45(1):137. doi: 10.1186/s13052-019-0740-9. PMID: 31699137; PMCID: PMC6839236.\u003c/li\u003e\n\u003cli\u003eMiller NP, Degefie T, Hazel E, Legesse H, Tolera T, Amouzou A. Coverage and equitability of interventions to prevent child mortality in rural Jimma and West Hararghe Zones, Oromia Region, Ethiopia. Ethiopia Med J. 2014 Oct;52 Suppl 3:37-45. PMID: 25845072. \u003c/li\u003e\n\u003cli\u003eHagos BT, Gebrerufael GG. Predictors of time to death among under-five children in pastoral regions of Ethiopia: A retrospective follow-up study. PLoS One. 2024 Jul 31;19(7):e0304662. doi: 10.1371/journal.pone.0304662. PMID: 39083551; PMCID: PMC11290679. \u003c/li\u003e\n\u003cli\u003eKhan, J., Vesel, L., Bahl, R. \u003cem\u003eet al.\u003c/em\u003e Timing of Breastfeeding Initiation and Exclusivity of Breastfeeding During the First Month of Life: Effects on Neonatal Mortality and Morbidity\u0026mdash;A Systematic Review and Meta-analysis. \u003cem\u003eMatern Child Health J\u003c/em\u003e \u003cstrong\u003e19\u003c/strong\u003e, 468\u0026ndash;479 (2015). https://doi.org/10.1007/s10995-014-1526-8\u003c/li\u003e\n\u003cli\u003eDebes, A.K., Kohli, A., Walker, N. \u003cem\u003eet al.\u003c/em\u003e Time to initiation of breastfeeding and neonatal mortality and morbidity: a systematic review. \u003cem\u003eBMC Public Health\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e (Suppl 3), S19 (2013). https://doi.org/10.1186/1471-2458-13-S3-S19 \u003c/li\u003e\n\u003cli\u003eSandra L. Huffman, Elizabeth R. Zehner, Cesar Victora, Can improvements in breast-feeding practices reduce neonatal mortality in developing countries? Midwifery,Volume 17, Issue 2, 2001, Pages 80-92,ISSN0266-6138, https://doi.org/10.1054/midw.2001.0253. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"N/A","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Neonatal mortality, Breastfeeding, Meta analysis, Heterogeneity, Observational study","lastPublishedDoi":"10.21203/rs.3.rs-7038235/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7038235/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e\u0026nbsp;This systematic review and meta analysis was conducted to determine the pooled effect size \u0026nbsp;and examine the inconsistencies among \u0026nbsp;the studies conducted in Ethiopia. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDesign:\u0026nbsp;\u003c/strong\u003eWe conducted a systemic review and meta analysis of identified observational studies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Source:\u003c/strong\u003e\u0026nbsp;An electronic bibliographic search was conducted in PUB Med, MEDLINE, EMBASE, Cochran Library data base and Google scholar from September 05, 2024 until November 07, 2024. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEligibility Criteria for selected studies:\u0026nbsp;\u003c/strong\u003eWe included observational studies conducted in Ethiopia and published in English language.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention\u003c/strong\u003e: Exclusive breastfeeding of neonates.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary outcome measure\u003c/strong\u003e: The primary outcome was neonatal mortality.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData extraction and synthesis: data extraction was independently conducted by two reviewer and. investigate research bias using \u0026nbsp;Risk of Bias in Non- Randomized Studies of Intervention\u0026nbsp;tool. This study adhere with \u0026nbsp;the guidelines of Meta-Analysis of Epidemiological observational studies and Preferred Report Items for Systemic Review and Meta-Analysis. Random effect model was employed and statistical heterogeneity was assessed using the Q and I\u003csup\u003e2\u003c/sup\u003e\u0026nbsp;statistic.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResult:\u003c/strong\u003e\u0026nbsp;Only 10 studies were included based on established criteria. The overall \u0026nbsp;pooled effect measure demonstrated a statistically significant association [OR=0.24, 95%CI(0.03-0.45), P=0.02]. Heterogeneity, assessed using the Q statistical test, \u0026nbsp;revealed [Q=97.46 , \u0026nbsp;degree of freedom = \u0026nbsp; 9 and P = \u0026nbsp; 0.00] \u0026nbsp;while, the I\u0026nbsp;\u003csup\u003e2 \u0026nbsp;\u003c/sup\u003estatistic\u003csup\u003e\u0026nbsp;\u0026nbsp;\u003c/sup\u003etest \u0026nbsp; showed [I\u003csup\u003e2 \u0026nbsp;\u003c/sup\u003e= 96%]. Publication bias of Begg’s funnel plot and Egger’s test , indicated an absence of publication bias [OR = 0.07, 95%CI ( -6.285 - 6.424) , P = 0.98]. Sensitivity analysis were deemed implausible. Certainty evidence of the studies was found to be moderate. \u0026nbsp;\u003cbr\u003e\n\u003cstrong\u003eConclusion:\u0026nbsp;\u003c/strong\u003eResult of meta-analysis indicated that breastfeeding serves as a protective intervention to reduce risk of neonatal mortality \u0026nbsp;in Ethiopia. Additionally, \u0026nbsp;confirmed presence of heterogeneity among the studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePROSPPRO \u0026nbsp;protocol registration number :\u003c/strong\u003e \u0026nbsp;CRD42024599421\u003c/p\u003e","manuscriptTitle":"Effect of breastfeeding on neonatal mortality : A systemic review and meta-analysis of observational studies in Ethiopia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-07 08:26:48","doi":"10.21203/rs.3.rs-7038235/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"449af1d6-0fb2-46b5-bdcc-b5fcceb7288d","owner":[],"postedDate":"July 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":50996192,"name":"Pediatrics"}],"tags":[],"updatedAt":"2025-07-07T08:26:48+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-07 08:26:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7038235","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7038235","identity":"rs-7038235","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}