This study aimed to investigate the association between sexual activity during pregnancy and adverse birth outcomes among Black women, and to explore whether vaginal cytokine inflammation mediates this association. Data from 397 Black pregnant women through questionnaires on sexual activity and vaginal biosamples during early (8–14 weeks) and late (24–30 weeks) pregnancy, and birth outcomes were analyzed. Using a data-driven approach, the study found that vaginal sex during late pregnancy was associated with spontaneous early-term birth (sETB, 38–39 completed weeks’ gestation) (OR = 0.39, 95% CI: [0.21, 0.72], p-value = 0.003) but not with spontaneous preterm birth (sPTB) (OR = 1.08, p-value = 0.86) compared to full-term birth. Overall, despite vaginal sex in late pregnancy showing an overall positive effect on sETB (total effect = −0.1580, p-value = 0.015), we observed a negative effect of vaginal sex on sETB (indirect effect = 0.0313, p-value = 0.026) due to the fact that having vaginal sex could lead to elevated IL6 levels, which in turn increased the odds of sETB. In conclusion, the study found an overall positive association between sexual activity on ETB and a negative partial mediation effect via increased vaginal cytokine inflammation induced by vaginal sexual activity. This inconsistent mediation model suggested that vaginal sexual activity is a complex behavior that could have both positive and negative effects on the birth outcome.

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