Systematic analysis of global O-serotype prevalence of neonatal extraintestinal pathogenic Escherichia coli: A protocol integrating previous research and bioinformatics databases.

Abstract

Neonatal extraintestinal pathogenic Escherichia coli (ExPEC) severe threat to newborn health. O antigen is a highly variable component of lipopolysaccharide, serves as the main phenotypic marker for serotyping, and represents a promising target for vaccination. The global distribution of O-serotypes in neonatal ExPEC remains unclear, limiting epidemiological understanding and vaccine development. This study will integrate literature and genomic data to analyze the global distribution of O-serotypes in neonatal ExPEC systematically. We will systematically search PubMed, Embase, Web of Science, and Scopus for studies reporting neonatal ExPEC serotypes and published between database inception and December 2026. In parallel, neonatal ExPEC genomes will be retrieved from NCBI BioSample, ENA, and CNCB. Strain-level data, including serotype, host age, host disease, isolation site, isolation year, and geography, will be extracted. Serotypes from genomic data will be predicted using multiple bioinformatics tools. The primary outcome is global serotype prevalence; secondary outcomes include temporal trends, geographical variation, and associations with clinical syndromes. Risk of bias will be assessed at both study and strain levels. Descriptive synthesis will integrate literature and genome data, and subgroup or sensitivity analyses will explore heterogeneity if substantial. This study will clarify whether neonatal ExPEC is consistently driven by a limited number of dominant O-serotypes or whether substantial temporal and geographical heterogeneity exists. Defining these patterns is essential for evaluating the feasibility of O-antigen-targeted vaccines, particularly whether broad multivalent strategies or region-specific approaches are more appropriate. By integrating literature and genomic data, this study may also improve understanding of serotype associations with specific invasive syndromes, including sepsis and meningitis. The findings will provide a clearer epidemiological basis for vaccine prioritization, surveillance strategies, and future neonatal ExPEC research in the context of increasing antimicrobial resistance. PROSPERO CRD420251140604.