Preconception vitamin D status and subsequent risk of preeclampsia: A secondary cohort analysis from the EAGeR trial

OBJECTIVE: To evaluate associations between maternal serum 25-hyroxyvitamin D [25(OH)D] measured at both preconception and 8 weeks gestation and the risk of preeclampsia. STUDY DESIGN: A secondary analysis of the EAGeR Trial (2006-2012), which was a multisite, prospective, double-blind, block-randomized, placebo-controlled clinical trial of women with regular menstrual cycles and 1-2 prior pregnancy losses. Analyses were restricted to participants who conceived and had a live birth (N = 552) and serum 25(OH)D measured at preconception and 8 weeks' gestation. MAIN OUTCOME MEASURES: Log-binomial regression with robust standard errors estimated risk ratios (RR) and 95% confidence intervals (CI) for preeclampsia across 25(OH)D categories. Inverse probability weighting accounted for selection bias from restricting analyses to live births. RESULTS: Overall, 55 (10.0%) women developed preeclampsia. In adjusted models excluding body mass index (BMI), deficient preconception 25(OH)D levels (≤20 ng/ml) were associated with an increased preeclampsia risk (RR: 2.32, 95% CI: 1.09, 4.95) compared with sufficient levels (≥30 ng/ml). These associations were attenuated after adjusting for BMI and other covariates (RR: 1.45, 95% CI: 0.64, 3.29). No significant associations were observed for insufficient 25(OH)D or for concentrations measured at 8 weeks' gestation. CONCLUSION: Deficient preconception 25(OH)D levels may be associated with an increased risk of preeclampsia, although this relationship appears partly mediated by BMI. These findings highlight the preconception period as a potentially critical window for optimizing maternal vitamin D status and reducing future preeclampsia risk. Addressing maternal nutritional status before conception may offer a novel prevention strategy warranting confirmation in larger and more diverse populations.