Impact of mode of birth and perinatal antibiotics on infant gut microbiota and health: a systematic review and meta-analysis

OBJECTIVE: To evaluate how the mode of birth and perinatal antibiotic exposure, independently and together, influence infant gut-microbiota composition, diversity and early health outcomes.

DESIGN: Systematic review and meta-analysis conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 and prospectively registered with PROSPERO (CRD42024536785).

DATA SOURCES: MEDLINE, Embase, Web of Science and Cochrane CENTRAL from inception to October 2024.

ELIGIBILITY CRITERIA: Randomised controlled trials, cohort or case-control studies of healthy term infants comparing vaginal versus caesarean birth and/or perinatal antibiotic exposure, with microbiota analysed by sequencing within 12 months post-delivery.

RESULTS: Eleven studies (n=5309 infants) were included, comprising ten prospective cohort studies and one randomised controlled trial across Europe, North America, Africa and Asia. Synthesis of six studies showed no statistically significant difference in bacterial abundance between vaginally delivered and caesarean-born infants (mean difference 3.44%, 95% CI -2.00 to 8.89; I² = 99%; very low certainty). Among antibiotic-exposed infants, the mean difference was -0.31% (95% CI -3.52 to 2.89), while among antibiotic-unexposed infants an exploratory trend towards higher bacterial abundance following vaginal delivery was observed. Narrative synthesis indicated consistent reductions in microbial diversity and depletion of Bacteroides and Bifidobacterium following caesarean birth or perinatal antibiotic exposure. Overall, caesarean delivery and perinatal antibiotic exposure were associated with differences in gut microbiota composition and diversity. Exclusive breastfeeding emerged as a modifying factor associated with partial restoration of microbial balance.

CONCLUSIONS: This review, the first to integrate both delivery mode and perinatal antibiotic exposure within a single analysis, suggests a consistent directional pattern of association between these exposures and early microbial assembly, with exclusive breastfeeding mitigating some potential negative effects. Due to imprecision in estimates and inherent limitations of observational data, pooled differences were not statistically significant, and overall certainty of evidence was very low. Long-term clinical consequences remain uncertain, highlighting the need for further study.

PROSPERO REGISTRATION NUMBER: CRD42024536785.