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Spontaneous Preterm Birth Clues Identified in Cervicovaginal Microbiome

NEW YORK (GenomeWeb) – A University of Pennsylvania and University of Maryland team has identified microbial community features and host immune features in the cervix and vagina that appear to coincide with spontaneous preterm birth risk.

Based on targeted sequence data and enzyme-linked immunosorbent assay (ELISA) data that provided a look at cervicovaginal microbial community members and immune protein levels, respectively, in hundreds of women with or without preterm birth, the researchers pinned down half a dozen microbial community types and identified seven taxa with apparent ties to spontaneous preterm birth.

Together with host immune protein levels, the microbiome data provided clues to preterm birth biology, the authors noted in its study, out in Nature Communications today. Moreover, they suggested that it may eventually be possible to develop therapeutic approaches that tap into microbiome or immune features associated with the condition.

"Studies such as this one will lead to novel [spontaneous preterm birth] prevention strategies based on appropriate risk stratification of pregnant women and informed personal counseling," senior and co-corresponding author Jacques Ravel, a genome sciences, microbiology, and immunology researcher at the University of Maryland School of Medicine, and his colleagues wrote. "Most importantly, this work will lead to innovative therapeutic opportunities to prevent [spontaneous preterm birth], including [a] combination of microbiome-based therapeutics and immune modulators earlier in pregnancy."

Starting with a group of some 2,000 pregnant women enrolled for the Motherhood & Microbiome study, the team identified a few hundred women for a nested case-control study of spontaneous preterm birth — a group that included 107 extensively phenotyped women who gave birth prior to 37 weeks of gestation and 432 unaffected women who delivered their babies at term. Nearly three-quarters of the participants were African American, the authors noted, and the median age of the mothers was 28 years old.

The investigators had access to cervicovaginal swab samples and anthropometric measurements collected at three points during pregnancy: at 16 to 20 weeks gestation, 20 to 24 weeks gestation, and between 24 and 28 weeks gestation.

When they compared microbial community members in cervicovaginal samples from those cases and controls, which were profiled with 16S ribosomal RNA gene sequencing, the researchers saw seven bacterial taxa that appeared to be associated with spontaneous preterm birth, particularly in women with African-American ancestry.

The team dug into that association further using ELISA-based immunological profiling, focused on host-derived anti-microbial peptides known as beta-defensin-2 that have previously been described in studies of the genital tract, both in healthy women and those suffering from bacterial infections.

Those experiments indicated that the presence of Lactobacillus bacteria that are normally considered beneficial did not necessary coincide with diminished risk of spontaneous preterm birth. Instead, the data suggested that enhanced beta-defensin-2 levels in cervicovaginal samples typically coincided with decreased spontaneous preterm birth risk, while lower-than-usual levels of the protein tended to track with increased risk, even when high levels of bacteria belonging to Lactobacillus species were present.

That beta-defensin-2 effect was especially pronounced in the African-American women, but was not significant when the team analyzed data for non-African-American women alone. Likewise, African-American women who delivered their infants at term also had increased beta-defensin-2 levels compared to non-African-American women with at-term deliveries.

On the other hand, although levels of Lactobacillus bacteria appeared less prominent in general in samples from the African-American women, the researchers reported, levels of those microbes did not track consistently with earlier-than-usual delivery by African-American moms. 

The authors noted that these and other findings from their study "hold promise for diagnostics to accurately identify women at risk for [spontaneous preterm birth] early in pregnancy."

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