Vitamin D, pre-eclampsia, and preterm birth among pregnancies at high risk for pre-eclampsia: an analysis of data from a low-dose aspirin trial

Objective: To examine the relation between maternal vitamin D status and risk of pre-eclampsia and preterm birth in women at high risk for pre-eclampsia. Design: Analysis of prospectively collected data and blood samples from a trial of prenatal low-dose aspirin. Setting: Thirteen sites across the USA. Population: Women at high risk for pre-eclampsia. Methods: We measured 25-hydroxyvitamin D [25(OH)D] concentrations in stored maternal serum samples drawn at 12–26 weeks’ gestation (n = 822). We used mixed effects models to examine the association between 25(OH)D and risk of pre-eclampsia and preterm birth, controlling for confounders including prepregnancy BMI and race. Main outcome measures: Pre-eclampsia and preterm birth. Results: Twelve percent of women were vitamin D deficient [25(OH)D <30 nmol/l]. Women with 25(OH)D <30 versus ≥75 nmol/l had a 2.4-fold (95% CI 1.0–5.6) higher risk of early-onset pre-eclampsia (<35 weeks’ gestation) after confounder adjustment. Women with 25(OH)D <50 nmol/l had a 1.8-fold (95% CI 1.0–3.2) increased risk of preterm birth at <35 weeks compared with women who had 25(OH)D ≥75 nmol/l, which was driven by indicated preterm births at <35 weeks’ gestation [25(OH)D <50 versus ≥75 nmol/l adjusted RR 2.5 (95% CI 1.1–5.8)]. There was no association between vitamin D status and pre-eclampsia or preterm birth at <37 weeks. Conclusion: Maternal vitamin D status in the second trimester was inversely associated with risk of early-onset pre-eclampsia and preterm birth at <35 weeks in women at high risk for pre-eclampsia. Tweetable abstract: Vitamin D is inversely related to risk of pre-eclampsia and preterm birth at <35 weeks in high-risk pregnancies.