Chemicals that accumulate in the vagina may contribute to spontaneous preterm birth

Chemicals that accumulate in the vagina, potentially originating from personal care products, may contribute to spontaneous preterm birth, according to a new study by researchers at Columbia University Vagelos College of Physicians and Surgeons.

The study of 232 pregnant women found that a handful of non-biological chemicals previously found in cosmetics and hygiene products are strongly associated with preterm birth.

“Our findings suggest that we need to look more closely at whether common environmental exposures are in fact causing preterm births and, if so, where these exposures are coming from,” says study co-leader Tal Korem, Ph.D., assistant professor in the Program for Mathematical Genomics and the Departments of Systems Biology and Obstetrics and Gynecology at Columbia. “The good news is that if these chemicals are to blame, it may be possible to limit these potentially harmful exposures.”

The study was published January 12 in Nature Microbiology.

In this study, we measured the second-trimester vaginal metabolome of 232 pregnant women. We show that it is associated with the vaginal microbiome, and that metabolite signatures are enriched for sPTB among Black women. We identify multiple metabolites that are associated with sPTB, across the cohort and separately for Black and White women.

Our results highlight exogenous metabolites with strong associations with sPTB, which we suggest constitute important risk factors. We further uncover intriguing interactions between TB-associated metabolites and potentially suboptimal microbes, and propose a difference in the vaginal metabolism of tyramine in White women who delivered preterm. Finally, we demonstrate that metabolome-based models can predict subsequent sPTB weeks to months in advance, potentially paving the way for early diagnostics.

We detected several sPTB-associated xenobiotics: DEA, ethyl glucoside, tartrate and EDTA, which prior literature and a functional analysis 37 suggest are of exogenous source. DEA, a chemical with no known natural source86, commonly used in drilling and metalworking fluids 35, and to which reproductive-aged women are highly exposed 87, and ethyl glucoside, present in alcohol-containing products 31, are both precursors or ingredients in hygienic and cosmetic products 30,33.

Tartrate and EDTA are used as food additives 32,58 and are also common in hygienic and cosmetic products 32,57. While we have not identified the sources of these metabolites, the fact that all are documented in hygienic and cosmetic products raises concern that some of these products may increase the risk of sPTB.

Our results coincide with recent studies raising concerns regarding environmental exposures in pregnancy 88,89, and identify these chemicals in the reproductive tract. Further study is warranted to identify the sources of these metabolites and to disentangle their effects on the host, microbiome and pregnancy outcomes, so that policy recommendations can be made regarding their use in various products and during pregnancy.

The cohort we analysed included a majority of Black women, offering an opportunity to study PTB in women who are disproportionately burdened by PTB and other adverse pregnancy outcomes, while also represented in small numbers in many studies. However, we urge caution in drawing conclusions from differences in associations between Black and White women, as maternal self-identified race represents a complex array of pre-existing differences, disparities and clinical covariates at the time of sampling.

Nevertheless, we note that the enrichment of sPTB associations among the xenobiotic metabolite set in Black women may potentially reflect disparities in environmental and exogenous exposures 90,91, consistent with reports that Black women have greater exposures to endocrine disrupting chemicals through personal care products 92,93 and with studies that identified exogenous chemicals as possible drivers of PTB94,95. Metabolomic exposure patterns could contribute to the association between racial disparities in prematurity rates and racial differences in the vaginal microbiome96.

We used community-scale metabolic models to investigate microbial tyramine metabolism, which have important limitations. Model curation is an ongoing effort, and thus models may not be tailored to each sample or may lack representation of niche-specific metabolic capabilities.

Another limitation stems from the resolution of 16S rRNA amplicon sequencing, which identifies taxa at the species or genus level, precluding strain-specific modelling. Despite these limitations, our models accurately predicted several metabolites, and offered insights regarding potential sources of tyramine.

Our predictive modelling approach has several noteworthy limitations: (1) our use of a case–control cohort enriched for sPTB limits our ability to assess population-level predictive value, and further validation is required in prospective studies. (2) As this cohort was focused on sPTB, we are unable to assess if our models are specific to sPTB or are detecting a general risk for adverse pregnancy outcomes. (3) The use of race in our models, while common throughout medicine 97, is controversial and creates issues in implementation 98.

This was driven by differences in both sample size and the vaginal metabolome itself between Black and White women in this cohort, and resulted in an overall increased accuracy. (4)

Finally, there is additional unexplored potential in using even earlier samples for prediction. A larger sample size, and combination with other sources of data, such as maternal urine or serum metabolomics, vaginal metagenomics or cell-free RNA measurements, could further improve prediction accuracy.

Our results demonstrate the utility of vaginal metabolites as early biomarkers of PTB, and identify xenobiotic metabolites as potentially modifiable sPTB risk factors, which may also disproportionately affect Black women. The strong associations we observe motivate the investigation of the vaginal microbiome and metabolome in the context of other adverse pregnancy outcomes such as pre-eclampsia, indicated PTB and BV.

More information: William F. Kindschuh et al, Preterm birth is associated with xenobiotics and predicted by the vaginal metabolome, Nature Microbiology (2023). DOI: 10.1038/s41564-022-01293-8