A cross-sectional pilot study of birth mode and vaginal microbiota in reproductive-age women

Recent studies suggest that birth mode (Cesarean section [C-section] or vaginal delivery) is an important event in the initial colonization of the human microbiome and may be associated with long-term health outcomes. We sought to determine the association between a woman's birth mode and her vaginal microbiota in adulthood. We re-contacted 144 adult women from two U.S. studies and administered a brief survey. Vaginal microbiota was characterized on a single sample by amplicon sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene and clustered into community state types (CSTs). We evaluated the association between birth mode and a CST with low relative abundance of Lactobacillus spp. ("molecular bacterial vaginosis" [Molecular-BV]) compared to Lactobacillus-dominated CSTs in logistic regression modeling which adjusted for body mass index, a confounder in this analysis. Twenty-seven women (19%) reported C-section. Overall, C-section showed a non-significant trend towards increased odds of Molecular-BV (aOR = 1.22, 95% CI: 0.45, 3.32), and Prevotella bivia was the strongest single taxa associated with C-section. However, because the two archived studies had different inclusion criteria (interaction p = 0.048), we stratified the analysis by study site. In the study with a larger sample size (n = 88), women born by C-section had 3-fold higher odds of Molecular-BV compared to vaginally-delivered women (aOR = 3.55, p = 0.06, 95% CI: 0.97-13.02). No association was found in the smaller study (n = 56, aOR = 0.19, p = 0.14, 95% CI: 0.02-1.71). This pilot cross-sectional study suggests a possible association between C-section and Molecular-BV in adulthood. However, the analysis is limited by small sample size and lack of comparability in participant age and other characteristics between the study sites. Future longitudinal studies could recruit larger samples of women, address the temporal dynamics of vaginal microbiota, and explore other confounders, including maternal factors, breastfeeding history, and socioeconomic status, which may affect the relationship between birth mode and vaginal microbiota.