378: Cervicovaginal MMP-9 is associated with high-risk microbial communities and spontaneous preterm birth

Abstract

Cervicovaginal (CV) microbial communities and host responses have been implicated in cervical remodeling leading to spontaneous preterm birth (sPTB). We hypothesize that disruption of the CV epithelial barrier leads to an increase in matrix metalloproteinase 9 (MMP-9), contributing to degradation of the cervical extracellular matrix, cervical shortening, and sPTB. A nested case-control was performed from a prospective pregnancy cohort, Motherhood and Microbiome which included African American women who had sPTB (n=40) or term birth (n=40). CV microbiota was characterized by 16S rRNA gene sequencing, and we classified microbial communities into community state types (CST) from CV swabs at 20-24 weeks. CST IV is a high-risk community characterized by anaerobes and a lack of Lactobacillus. Cervical length was assessed at the anatomy ultrasound with short cervix < 25mm. MMP-9 was quantified by ELISA. Standard analytical approaches and multivariable logistic regression were used to determine differences in MMP-9 and associations with outcomes. Demographic characteristics are in Table 1. MMP-9 was 4.7-fold higher in sPTB v. term birth (p=0.0013). MMP-9 was 7.3-fold higher in women with CST IV v. non-CST IV (p< 0.0001) and 4.71-fold higher in women with short cervix v. normal cervical length (p=0.01). Women with both CST IV and short cervix had a 14.5-fold increase in MMP-9 v. women with non-CST IV and normal cervical length (p< 0.0001). High MMP-9 was associated with 2.8-fold higher odds of CST IV (CI 1.05-7.63), 3.1-fold higher odds of short cervix (CI 1.05-9.17), and 3.8-fold higher odds of sPTB (CI 1.41-10.09). These findings begin to ascribe a biological link between high-risk CV microbial communities, short cervix, and sPTB through increased expression of MMP-9, which may serve to degrade the cervical matrix. Additional studies are warranted to determine the efficacy of targeting this pathway to prevent sPTB. Incorporating CV MMP-9 levels into risk stratification for sPTB may have clinical utility. (Danielle Peress MD Memorial Fund; KG & R01NR01478; ME)View Large Image Figure ViewerDownload Hi-res image Download (PPT)