Association between innate immunity gene polymorphisms and neonatal sepsis development:a systematic review and meta-analysis

Background The aim of this meta-analysis was to analyze all available data from studies investigating associations between polymorphisms in genes responsible for innate immunity and neonatal sepsis development.Methods A comprehensive literature search,reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-S guidelines,was performed with no language restriction.Studies derived using the PICO(population,intervention,comparison and outcomes)strategy,with data on the genotype distribution for innate immunity gene polymorphisms in newborns with and without sepsis.Data were analyzed using Review Manager.The Cochran–Mantel–Haenszel test was used to calculate odds ratios with 95%confidence intervals.Heterogeneity was tested using the I2 index.Results From a total of 9428 possibly relevant articles,33 qualified for inclusion in this systematic review.According to the STrengthening the REporting of Genetic Association Studies,23 studies were found to be of moderate quality,while 10 were of low quality.The results showed an association of the mannose-binding lectin(MBL)exon 1 genetic polymorphism with the risk of culture-proven sepsis.Toll-like receptor(TLR)4 rs4986791 genotype distribution suggests its association with the increased risk of culture-proven sepsis.The certainty of evidence per GRADE(Grading of Recommendations,Assessment,Development,and Evaluation)varied from very low to low.Publication bias was not detected.Conclusions Out of the 11 investigated single-nucleotide polymorphisms,this meta-analysis found a possible association between the risk for culture-proven sepsis and MBL exon 1 and TLR4 rs4986791 polymorphisms.There is an evident need for larger well-designed,multicentric observational studies investigating inflammatory gene polymorphisms in neonatal sepsis.