Vaginal microbiome structure in pregnancy and host factors predict preterm birth: Results from the ECHO Cohort

Abstract

Purpose: The vaginal microbiome is dynamic, typically shifting during pregnancy toward enrichment of Lactobacillus. However, proliferation of Lactobacillus may be absent among women with preterm births (PTBs). We sought to identify robust vaginal microbiota signatures along with host factors that predicted PTB across diverse U.S. cohorts.

Methods: We meta-analyzed 16S rRNA gene amplicon sequence data from the Environmental influences on Child Health Outcomes Cohort. We classified community state types (CSTs) and employed penalized logistic regression models to assess the association between vaginal CST and PTB. We generated supervised random forest models and validated them using a train-and-test approach to identify the most predictive vaginal taxa and host factors.

Results: Of 683 births, 12 % were preterm. Overall, 26 % had a non- L. iners Lactobacillus-dominant CST (I, II, V), 43 % had a L. iners-dominant CST (III), and 30 % had a diverse, non-Lactobacillus-dominant (IV-B, IV-C) CST. Vaginal CST was strongly associated with PTB (adjusted odds ratio [aOR], 3.86, 95 % confidence interval [CI], 1.57-11.3 for diverse, non-Lactobacillus-dominant communities and aOR, 3.03, 95 % CI, 1.25-8.78 for L. iners-dominant compared to L. crispatus-dominant communities). The model with the highest area under the curve (AUC=.77) included Gardnerella vaginalis, age, Prevotella timonensis, and L. crispatus.

Conclusions: Along with host factors, vaginal microbiota could be used for predictive risk scoring for PTB across different U.S. cohorts.

Keywords: Microbiota; Pregnancy; Preterm birth.