Global Burden of Neonatal Invasive Pneumococcal Disease: A Systematic Review and Meta-analysis

Background: This study aimed to estimate the global burden of invasive pneumococcal disease (IPD) incidence among neonates during the pre-pneumococcal conjugate vaccine era. Methods: A systematic search of published and unpublished data was undertaken. Bias assessment and qualitative synthesis of the included studies were carried out. Random effects models using the method of DerSimonian and Laird were constructed. Subgroup analyses, sensitivity analyses and meta-influence analysis were undertaken. Sources of heterogeneity were investigated. Results: From 26 neonatal IPD data points in the pre-pneumococcal conjugate vaccine era, the overall pooled neonatal IPD incidence, in the general population, combining all 3 United Nations (UN) country strata was estimated to be 36.0 per 100,000 live births [95% confidence interval (CI): 20.0-64.7 per 100,000]. The pooled neonatal IPD incidence in the general population in the less-developed UN country strata was estimated to be 16.0 per 100,000 live births (95% CI: 3.9-65.6 per 100,000) and in the more-developed stratum was 41.1 per 100,000 live births (95% CI: 29.1-58.1 per 100,000). This counter-intuitive finding is likely to have been affected by data quantity and confounding by time. A pooled estimate for the least-developed stratum was not computable as there was only 1 study in this stratum - A study from The Gambia with an unweighted IPD incidence of 369.5 per 100,000 (95% CI: 119.2-1138.5 per 100,000). Conclusions: Pneumococcus was a recognized pathogen among neonates in all development regions of the world. The burden of neonatal IPD, particularly in the least-developed UN country stratum, requires substantial further evaluation.