Vaginal Microbiome Composition in Early Pregnancy and Risk of Spontaneous Preterm and Early Term Birth Among African American Women

Abstract

ObjectiveTo evaluate the association between the early pregnancy vaginal microbiome and spontaneous preterm birth (sPTB) and early term birth (sETB) among African American women.MethodsVaginal samples collected in early pregnancy (8-14 weeks’ gestation) from 436 women enrolled in the Emory University African American Vaginal, Oral, and Gut Microbiome in Pregnancy Study underwent 16S rRNA gene sequencing of the V3-V4 region, taxonomic classification, and community state type (CST) assignment. We compared vaginal CST and abundance of taxa for women whose pregnancy ended in sPTB (N = 44) or sETB (N= 84) to those who delivered full term (N = 231).ResultsNearly half of the women had a vaginal microbiome classified as CST IV (Diverse CST), while one-third had CST III (L. iners dominated) and just 16% had CST I, II, or V (non-iners Lactobacillus dominated). Compared to vaginal CST I, II, or V (non-iners Lactobacillus dominated), both CST III (L. iners dominated) and CST IV (Diverse) were associated with sPTB with an adjusted odds ratio (95% confidence interval) of 4.1 (1.1, infinity) and 7.7 (2.2, infinity), respectively, in multivariate logistic regression. In contrast, no vaginal CST was associated with sETB. The linear decomposition model (LDM) based on amplicon sequence variant (ASV) relative abundance found a significant overall effect of the vaginal microbiome on sPTB (p=0.034) but not sETB (p=0.320), whereas the LDM based on presence/absence of ASV found no overall effect on sPTB (p=0.328) but a significant effect on sETB (p=0.030). In testing for ASV-specific effects, the LDM found that no ASV was significantly associated with sPTB considering either relative abundance or presence/absence data after controlling for multiple comparisons (FDR 10%), although in marginal analysis the relative abundance of Gardnerella vaginalis (p=0.011), non-iners Lactobacillus (p=0.016), and Mobiluncus curtisii (p=0.035) and the presence of Atopobium vaginae (p=0.049), BVAB2 (p=0.024), Dialister microaerophilis (p=0.011), and Prevotella amnii (p=0.044) were associated with sPTB. The LDM identified the higher abundance of 7 ASVs and the presence of 13 ASVs, all commonly residents of the gut, as associated with sETB at FDR < 10%.ConclusionsIn this cohort of African American women, an early pregnancy vaginal CST III or IV was associated with an increased risk of sPTB but not sETB. The relative abundance and presence of distinct taxa within the early pregnancy vaginal microbiome was associated with either sPTB or sETB.

Association Between Vaginal Gardnerella and Tubal Pregnancy in Women With Symptomatic Early Pregnancies in China: A Nested Case-Control Study

“…Firstly, we included a well-defined study population, so the results would be limited to pregnant women with abdominal pain and/or uterine bleeding. Secondly, because the composition of vaginal microbiota can be affected by ethnicity (Fettweis et al, 2019;Dunlop et al, 2021), further studies should be performed to verify whether the results of our study are applicable to women with symptomatic early pregnancies outside of China. Thirdly, our study involved association analysis research and focused specifically on describing the association between vaginal microbiota and the incidence of TP.…”

Vaginal Atopobium is Associated with Spontaneous Abortion in the First Trimester: a Prospective Cohort Study in China

“…Recently, growing evidence has come to support the idea that abnormal alterations in the vaginal microbiota are related to several female reproductive disorders ( 18 , 19 ). Although epidemiological research showed that women with disorders of the vaginal microbiota rarely manifest symptoms of infection ( 20 ), the unremarkable and common microorganisms in play in such an environment remain dangerous and can lead to preterm delivery ( 13 , 21 ), failure of in vitro fertilization ( 22 , 23 ), infertility ( 18 ), and so on.…”

Microbiota of the pregnant mouse: characterization of the bacterial communities in the oral cavity, lung, intestine, and vagina through culture and DNA sequencing

“…These Lactobacillusdominant CSTs (CSTs I-III, and V) are generally perceived as being conducive to reproductive health. Conversely, the relationship between human reproductive health and the non-Lactobacillus-dominant, and thus species rich and diverse, CST IV is more ambiguous (45,(55)(56)(57)(63)(64)(65). This disparity in health outcome potentially related to the structure of the vaginal microbiota is highlighted by the observation that women who do not have a Lactobacillus-dominant vaginal microbiota prior to or during early pregnancy typically transition to a vaginal microbiota of Lactobacillus-dominance as gestation progresses (50,51,66), suggesting that pregnancy entails selective pressures for Lactobacillus-dominance in the vaginal microenvironment.…”