Abstract:
Background: Early-life gut microbiota development is pivotal for immune and metabolic programming. Caesarean delivery and perinatal antibiotic exposure are common interventions that may disrupt maternal, infant microbial transmission, yet their combined effects remain poorly understood.
Objective: To examine how birth mode and perinatal antibiotic exposure, individually and jointly, influence infant gut microbiota composition, diversity, and early health outcomes.
Methods: A systematic review and meta-analysis was conducted following PRISMA 2020 and registered on PROSPERO (CRD42024536785). MEDLINE, Embase, Web of Science, and Cochrane CENTRAL were searched to October 2024. Eligible studies included healthy term infants comparing vaginal versus caesarean birth and/or perinatal antibiotic exposure, with microbiota assessed by sequencing within 12 months post-delivery.
Results: Eleven studies (n = 5,309 infants) were included: ten prospective cohorts and one randomized trial across Europe, North America, Africa, and Asia. Random-effects meta-analysis showed no significant pooled difference in bacterial abundance between vaginal and caesarean groups (mean difference 1.55%, 95% CI –2.50 to 5.61) or antibiotic-exposed infants (–0.31%, 95% CI –3.59 to 2.96). Narrative synthesis consistently reported reduced microbial diversity and depletion of Bacteroides and Bifidobacterium following caesarean birth or antibiotic exposure. Exclusive breastfeeding partially restored microbial balance and diversity.
Conclusions: This review, the first to integrate both delivery mode and perinatal antibiotic exposure, demonstrates consistent evidence that these interventions disrupt early microbial assembly, while exclusive breastfeeding mitigates these effects. Clinically, these findings reinforce the need for microbiome-conscious perinatal care, judicious antibiotic use, and breastfeeding support to optimize neonatal outcomes and inform future guidelines.
Keywords: Infant microbiota; Caesarean section; Perinatal antibiotics; Breastfeeding; Systematic review; Meta-analysis

