Abstract

The cervix functions as a physical and biochemical barrier to ascending pathogens in pregnancy. Short cervical length is a major risk factor for spontaneous preterm birth (sPTB). While the lack of lactobacillus species has been associated with an increased risk of sPTB, the relationship between cervicovaginal (CV) microbial communities and cervical length is unknown. We sought to examine the association between CV microbial communities and short cervix. This was a secondary analysis of a pregnancy cohort study, “Motherhood and Microbiome.” Cervical swabs were collected at 16-20 weeks’ gestation and cervical length was measured by transvaginal ultrasound at the time of the level 2 ultrasound (mean 20 weeks). We analyzed the CV microbiota with 16S rRNA sequencing and classified microbial communities into CSTs as previously reported (Ravel et al. PNAS 2011). CST IV is characterized by a preponderance of anaerobes and paucity of lactobacillus species. In women with cervical length measured, CV microbial data were available on 67 sPTBs, 47 medically-indicated PTBs (mPTBs), and 358 term births. We used log-binomial regression to model associations of CST IV and short cervix (<25 mm) and calculate adjusted risk ratios (aRR). Mean cervical length was 34.6 mm, 34.3 mm, and 26.2 mm among term births, mPTBs, and sPTBs, respectively (p<0.0001) and did not differ significantly among women with CST IV versus all other women (32.9 mm and 33.6 mm respectively, p=0.3); however, the prevalence of a short cervix was significantly higher (11.3% compared to 6.1%, p=0.04). After adjusting for race/ethnicity, body mass index, insurance status, and prior sPTB, women with CST IV had higher risk of short cervix (aRR 1.9, CI: 1.03-3.6). CST IV, which is characterized by anaerobes and a paucity of lactobacillus species, is associated with increased risk of short cervix during pregnancy, a major risk factor for sPTB. Determining the cascade of events that lead to premature cervical remodeling, potentially including dysbiosis, could be critical in preventing sPTB (R01NR014784; ME).

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