Longitudinal changes in cervicovaginal antimicrobial peptides during pregnancy and association with spontaneous preterm birth

While immune responses in the cervicovaginal (CV) space are poorly studied, they undoubtedly play a role in premature cervical remodeling and spontaneous preterm birth (sPTB). Antimicrobial peptides (AMPs) are critical for mucosal and epithelial barrier integrity. The objectives of this study were to determine if AMPs in the CV space: 1) change during pregnancy 2) differ by race and 3) can predict sPTB. CV biospecimens were collected at 16-20 (V1), 20-24 (V2), and 24-28 (V3) weeks in a prospective cohort of singleton pregnancies (“M&M”; n=1,943). A nested case-control study of 92 healthy term deliveries and 43 sPTB was performed using all 3 time points. Controls were women delivering at term with no co-morbidities, obesity, or prior PTB. Two AMPs (B-defensin (BD) and SLPI) were examined for longitudinal changes using Wilcoxon signed ranks. Levels between cases and controls were compared using Wilcoxon rank sum. Odds of SPTB by AMP quartile were estimated using logistic regression adjusted for parity, age, obesity, intercourse ≤24hrs, and tobacco/antibiotic use. In term women, BD decreased >4-fold from V1 to V3 (P<0.001), but this same decrease was not observed in women having a sPTB (table). BD levels at V1 were significantly lower in cases vs. controls (p=0.02). SLPI levels did not differ over time. In stratifying by race, BD was higher in AA women at all 3 time points (p<0.001). After adjustment, an elevated risk of sPTB in AA women was observed with the lower quartiles of BD at V1: Q2 (aOR=2.88, 95% CI: 1.32-6.28) and Q1 (aOR: 3.18, 95% CI: 1.41-7.18) Sensitivity analysis revealed that intercourse ≤24hrs of visit coupled with a low BD may be associated with further increased risk Q2 (aOR=3.67) and Q1 (aOR=4.82). A unique immune profile exists in the CV space during normal pregnancy and perturbations of that profile early in pregnancy may play a role in sPTB. Racial differences in AMPs may provide insight into known disparities in sPTB. The influence of sexual intercourse on CV immune responses requires further research as to whether this serves to modify the risk of sPTB. Research exploring the immune response in the CV space during pregnancy could significantly advance our understanding of the pathogenesis of sPTB. (NRO14784 ME)View Large Image Figure ViewerDownload Hi-res image Download (PPT)