Vaginal metabolites may be early predictors of spontaneous preterm birth


In a recent study, an association was found between vaginal metabolites and spontaneous preterm birth.

Vaginal metabolites may be early predictors of spontaneous preterm birth (sPTB), according to a recent study.

Despite sPTB being a leading cause of maternal and neonatal morbidity, there are few options for early risk identification and prevention. While the vaginal microbiome has been associated with sPTB, the relationship between these 2 factors remains unclear.

Metabolites have been observed to cause local and systemic effects, having associations with the microbiome, inflammation, and preterm birth. Investigators conducted a study to further understand the role of metabolites on sPTB.

The second-trimester vaginal metabolome was measured in 232 pregnant women. Of these, 80 pregnancies ended preterm. There were 635 metabolites identified, 549 of which were seen in over half of the study population, and 108 of which were seen in the entire population. 

Associations were found between the metabolome and microbiome, but community state types (CSTs) were not well separated. Microbiomes however were well separated. This indicated a strong but imperfect correlation between the vaginal microbiome and metabolome.

Six metabolite clusters (MC) were found, without as significant of separation as that between the vaginal microbiome and CSTs. Polyamine metabolism was the most enriched metabolite sub-pathway within each MC. Also, investigators found various enrichments of CSTs in MCs.

There was a significant difference between the metabolome of Black and White women, but only mild differences when looking at the correlation to MCs. Several MCs were significantly associated with sPTB in Black women but not White women. This indicated prematurity in Black women rather than with the microbiome structure.

Four metabolites were significantly associated with sPTB, 3 of which were of exogenous source. These 3 were ethyl β-glucopyranoside, tartrate, and diethanolamine. Investigators found these metabolites in over 95% of the study population.

Choline, an essential nutrient, was found to have lower levels in women with subsequent sPTB. Low levels of choline have also been linked to low betaine levels. As diethanolamine has been associated with disrupted choline metabolism, investigators hypothesized higher diethanolamine levels in sPTB may lower choline and betaine levels.

There were 13 vaginal metabolites associated with earlier sPTB. This included sugar or sugar alcohol metabolites found to be higher in early preterm birth. Interactions were found with both race and sPTB timing, with an additional sPTB-associated xenobiotic found as well.

These results showed enriched metabolite signatures among Black women with sPTB. Exogenous metabolites were also strongly associated with sPTB, indicating important risk factors.


Kindschuh WF, Baldini F, Liu MC, Liao J, Meydan Y, Lee HH, et al. Preterm birth is associated with xenobiotics and predicted by the vaginal metabolome. Nat Microbiol. 2023. doi:10.1038/s41564-022-01293-8

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