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

  • Meta-analysis
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Abstract

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.

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Data availability

All additional data are available in supplementary material of the manuscript.

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Funding

This research was supported by the Ministry of Education, Science and Technological Development of Republic of Serbia (No. 451-03-9/2021-14/200129).

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Authors and Affiliations

  1. Department of Neonatology, The Obstetrics and Gynecology Clinic “Narodni Front”, Belgrade, Serbia

    Tamara Sljivancanin Jakovljevic & Tanja Lazić Mitrović

  2. School of Medicine, University of Belgrade, Belgrade, Serbia

    Jelena Martic

  3. Department of Neonatology, Mother and Child Health Care Institute of Serbia “Dr Vukan Cupic”, Belgrade, Serbia

    Jelena Martic

  4. Central Library, School of Dental Medicine, University of Belgrade, Belgrade, Serbia

    Jelena Jacimovic

  5. Department of Human Genetics, School of Dental Medicine, University of Belgrade, Belgrade, Serbia

    Nadja Nikolic & Jelena Milasin

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  1. Tamara Sljivancanin Jakovljevic
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Contributions

SJT contributed to conceptualization, data curation, formal analysis, investigation, methodology, project administration, writing of the original draft, reviewing and editing. MJ contributed to data curation, investigation, supervision, validation, writing of the original draft, reviewing and editing. JJ contributed to formal analysis, investigation, methodology, validation, visualization, and writing of the original draft. NN contributed to formal analysis, investigation, methodology, visualization, and writing of the original draft. MJ contributed to investigation, supervision, validation, writing of the original draft, reviewing and editing. LMT contributed to investigation, supervision, validation, writing of the original draft, reviewing and editing. All the authors approved the final version of the manuscript.

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Correspondence to Tamara Sljivancanin Jakovljevic.

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Sljivancanin Jakovljevic, T., Martic, J., Jacimovic, J. et al. Association between innate immunity gene polymorphisms and neonatal sepsis development: a systematic review and meta-analysis. World J Pediatr 18, 654–670 (2022). https://doi.org/10.1007/s12519-022-00569-7

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