Periconception Maternal-Serum Vitamin D, Vaginal Bleeding, and Subchorionic Hemorrhage in Early Pregnancy

Background/Objectives: To examine relationships between maternal-serum 25(OH)D levels at preconception and 8 weeks' gestation and the risk of vaginal bleeding and subchorionic hemorrhage during pregnancy. Methods: A secondary analysis of the EAGeR Trial, which is a prospective, multisite, randomized controlled trial that enrolled 1228 women with 1-2 prior pregnancy losses. Analyses were restricted to participants who became pregnant and had 25(OH)D measured at preconception (n = 747) and 8 weeks' gestation (n = 605). Vaginal bleeding and subchorionic hemorrhage were assessed via medical record extraction, which captured clinically recognized symptoms at medical visits measured at any point throughout pregnancy. Symptom severity of vaginal bleeding was assessed via time-varying self-reported symptoms across early pregnancy through 3-8 weeks gestation using daily diaries. Logistic regression models evaluated associations between maternal-serum 25(OH)D levels (deficient ≤ 20 ng/mL; insufficient 21-29 ng/mL; sufficient ≥ 30 ng/mL) and vaginal bleeding and subchorionic hemorrhage, while generalized estimating equations (GEE) models were used to evaluate time-varying symptom severity of vaginal bleeding from daily diary data. Results: Those who remained 25(OH)D deficient/insufficient had increased odds of having a subchorionic hemorrhage (aOR: 2.18; 95% CI: 1.13, 4.20) compared to those who had sufficient levels at both time points. In longitudinal GEE models, women with deficient preconception 25(OH)D had greater odds of moderate-to-heavy bleeding (vs. none) (aOR: 3.02; 95% CI: 1.13, 8.13), but no association was observed for light bleeding (aOR: 1.07; 95% CI: 0.58, 2.00). Findings were directionally similar, yet less precise when restricted to pregnancies resulting in a live birth. Conclusions: Persistently low vitamin D from preconception to early pregnancy is associated with increased risk of subchorionic hemorrhage and moderate/heavy vaginal bleeding, highlighting the importance of vitamin D sufficiency for implantation and early placental development.