Exposure to maternal vaginal flora during labor and long-term infectious morbidity of the offspring

PURPOSE: Cesarean delivery (CD) has been linked to increased long-term infectious morbidity in offspring, potentially due to limited exposure to the maternal vaginal microbiome, which may influence immune development. We hypothesized that the degree of exposure to vaginal microbiota during labor would be associated with differences in long-term infectious morbidity. METHODS: We conducted a population-based cohort study including 348,332 singleton deliveries. Offspring were classified into four groups: vaginal delivery (VD, reference), CD for non-progressive labor in the first stage (NPL1), CD for non-progressive labor in the second stage (NPL2), and elective (pre-labor) CD. Infectious-related hospitalizations up to age 18 were assessed. Kaplan-Meier curves compared cumulative incidence between the groups and a Cox proportional hazards model adjusted for various potential confounders. RESULTS: Of the cohort, 89.2% were VD, 1.4% NPL1, 0.6% NPL2, and 8.8% elective CD. Infectious-related hospitalization rates were higher for NPL1 and elective CD (26.2% each) compared to NPL2 (24.3%) and VD (23.8%) (p < 0.001). Kaplan-Meier analysis demonstrated a dose-response pattern, with the lowest cumulative incidence in VD, followed by NPL2, NPL1, and highest in elective CD (log-rank p < 0.001). In adjusted analysis, NPL1 (aHR 1.10) and elective CD (aHR 1.13) were associated with increased long-term infectious morbidity, whereas NPL2 was not significantly different from VD. CONCLUSION: Reduced exposure to vaginal microbiota, as in elective CD and NPL1, is associated with increased long-term infectious morbidity in offspring, while exposure during the second stage of labor (NPL2) may confer immunological benefits.