Cervicovaginal microbial communities deficient in Lactobacillus species are associated with second trimester short cervix

Abstract Background The cervix functions as a barrier to ascending pathogens in pregnancy. Short cervical length and lack of cervicovaginal Lactobacillus species are risk factors for spontaneous preterm birth; however, whether they interact to increase risk remains unknown. Objective We sought to examine the relationship between cervicovaginal microbiota and short cervix, as well as their combined impact on spontaneous preterm birth risk. Study Design This was a secondary analysis of a prospective nested, case-control pregnancy study. Cervical swabs were collected between 16 to 20 weeks of gestation. Cervical length was measured per standard clinical care during a clinically indicated ultrasound at approximately 20 weeks of gestation. Cervicovaginal microbiota were analyzed with 16S rRNA gene sequencing and classified into community state types among 67 cases of spontaneous preterm birth, 47 cases of medically-indicated preterm birth, and 358 cases of term births. Logistic regression was used to model associations of CST IV, a community characterized by a paucity of Lactobacillus species and a wide array of anaerobic bacteria, and short cervix ( Results Among the 472 women in the dataset, there were 38 (8.1%) with short cervix and 177 (37.5%) with CST IV. Short cervix was associated with spontaneous preterm birth (aOR 15.59; 95% CI: 6.77-35.92). Women with CST IV had higher odds of short cervix (aOR 2.17; 95% CI: 1.04-4.53) as well as spontaneous preterm birth (aOR 1.97; 95% CI: 1.06-3.65). While the interaction of CST IV and short cervix was not significant (p=0.771), women with both short cervix and CST IV (n=20) had higher odds of spontaneous preterm birth compared to women with both normal cervical length and CST I, II, III, or V (n=277) (aOR 21.8; 95% CI: 6.78-70.2). Conclusions CST IV, characterized by a diverse set of strict and facultative anaerobes and a paucity of Lactobacillus species, is associated with increased odds of short cervix. Women with both CST IV and short cervix have higher odds of spontaneous preterm birth than women with either factor alone. Determining the cascade of events leading to premature cervical shortening, including dysbiosis, may be critical in preventing spontaneous preterm birth.