Effects of vaccinations of newborn on neonatal mortality: A systematic review and meta-analysis of randomized controlled trials studies in low and low- to middle-income countries

Background: Newborn vaccination can significantly lower neonatal mortality by protecting against infectious disease and offering nonspecific protective effects, which may include in all-cause mortality. Studies conducted on new born vaccination and neonatal mortality in low and low-to middle-income countries have shown inconsistency results. Therefore, the objectives of this study were to produce concrete pooled evidence and to identify the source of inconsistency in the studies’ results. Methods : The protocol of this study was registered in the International Prospective Register of Systematic Review with registration number CRD420251164676. Moreover, this study adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Studies were identified through databases searchs in PubMed, MEDLINE, Embase, and Google Scholar. All the meta-analyses were conducted via Review manager 5.4.1. Statistical tests were conducted by applying random effect model of pooled effect measures, heterogeneity, subgroup analyses and sensitivity analyses. Furthermore, risk bias, publication bias ,and certainty evidence assessments were performed. Results: Nine studies, with total sample size 40772 were included in the review, on the basis of established criteria. The pooled effect measure revealed that vaccination of newborns with BCG only or BCG-plus-OPV or OPV alone significantly decrease the risk of neonatal mortality by 22% [HR= 0.78 , 95% CI (0.67 - 0.90), P <0.001]. Moreover, heterogeneity was detected with the Higgins I ² statistical test [I ² = 61%], and the Cochran's Q statistical test [Q=20.44, DF= 8, P = 0.009]. Sample size, intervention type, and study setting variation were the sources of the heterogeneity. The sensitivity analysis indicated that the absence of influential studies was plausible. Furthermore, the study revealed the absence of publication bias. The certainty evidence of the studies was high grade. Conclusions: The study results showed that newborns vaccinated with BCG alone or BCG-plus-OPV, or OPV alone had a 22% lower risk of neonatal death. Moreover, the source of inconsistency in the included studies was due to variation in sample size, intervention type, and study setting. Therefore, all stakeholders should promote increasing coverage of new born vaccination. Future research should focus on other newborn vaccines such as hepatitis B. PROSPERO Protocol registration : CRD420251164676