Disentangling race, environment and the microbiome in a study of preterm birth risk

Abstract Previous studies have investigated the associations between the vaginal microbiome and preterm birth (PTB), with the aim of determining whether differences in community patterns meaningfully alter risk, and could therefore be the target of intervention. We report on vaginal microbial analysis on a subset of the Pregnancy, Infection, and Nutrition (PIN) Study, a prospectively enrolled cohort of women in central North Carolina between 1995-2001. We selected a nested case-control subset of this cohort, including 464 White women (375 term birth and 89 spontaneous PTB, sPTB) and 360 Black women (276 term birth and 84 sPTB). Microbial DNA was extracted from genital track swabs collected mid-pregnancy, and subjected to 16S rRNA taxonomic profiling. We found that microbial community structure is associated with race and sPTB, although the influence of race is stronger than the influence of sPTB. The microbiome of Black women has higher alpha-diversity, higher abundance of Lactobacillus iners and lower abundance of Lactobacillus crispatus. These differences were obscured once maternal douching behavior was considered—specifically, among women who douche, there were no significant differences in microbiome by race. The sPTB associated microbiome exhibited a lower abundance of L. crispatus, while alpha diversity and L. iners were not significantly different. Associations between the microbiome and sPTB were only significant in women who do not douche. While race was a strong predictor of microbial community structure, we also observed strong intercorrelations between a range of maternal factors, including poverty, education, marital status, age, douching and race, with microbiome effect sizes in the range of 1.8-5.2% in univariate models. Therefore, race may simply be a proxy for other socially driven factors that differentiate microbiome community structures. Future work will continue to refine reliable microbial biomarkers for preterm birth across diverse cohorts.