183: High-risk cervicovaginal microbial communities and preterm birth: a multinomial model

Abstract

Community state IV (CST IV) is a high-risk cervicovaginal (CV) microbial community associated with preterm birth (PTB). Rigor of PTB phenotyping has varied among studies investigating the association of CST IV and PTB. We hypothesize that CST IV would be more strongly associated with spontaneous PTB (sPTB) than medically indicated PTB (mPTB). A prospective pregnancy cohort, Motherhood and Microbiome was performed. CV microbiota was analyzed by 16S rRNA sequencing and microbial communities were classified into community state types (CST) from CV swabs at 16-20 weeks. CV β-defensin (βD) levels were assessed by ELISA. Multinomial logistic regression was utilized to assess the association between CST IV and a 3-level birth outcome variable including sPTB, mPTB, and term birth as the reference group. The effect of immune marker βD on PTB and on the association between CST IV and birth outcome was assessed. The final cohort of 581 women included 103 sPTB, 57 mPTB, and 421 term births. In a logistic regression model adjusted for African American race and BMI, CST IV was significantly associated with all PTB (aOR 1.75; CI 1.18-2.61). In multinomial logistic regression models, CST IV was associated with sPTB (aOR 1.80; CI 1.13-2.88) and non-significantly with mPTB (aOR 1.67; CI 0.92-3.03). In adjusted multinomial models, there was no evidence of effect modification by low βD on the relationship between CST IV and sPTB (p=0.835) or CST IV and mPTB (p=0.971). The odds of sPTB for women with both CST IV and low βD were greater (aOR 3.05; CI 1.56-5.95) compared to women with neither factor (CST IV only aOR 1.80; CI 1.13-2.88 and low βD only aOR1.60; CI 1.05-2.45). CST IV increases the risk of all PTB, specifically sPTB. A high-risk CV microbial community and a poor immune response (low βD) are independent risk factors for sPTB. Further research is needed to determine if an unfavorable CV microbial-immune profile contributes to other adverse birth outcomes. Importantly, targeting the CV microbial-immune profile appears to be an important next step to reduce PTB. R01NR01478 (ME)View Large Image Figure ViewerDownload Hi-res image Download (PPT)