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Maternal Vitamin D Deficiency Increases the Risk of Preeclampsia

Department of Epidemiology (L.M.B., J.M.C., J.M.R.), University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania 15261; Department of Obstetrics, Gynecology, and Reproductive Sciences (L.M.B., J.M.C., H.N.S., R.W.P., J.M.R.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261; Magee-Womens Research Institute (L.M.B., J.M.C., H.N.S., R.W.P., J.M.R.), Pittsburgh, Pennsylvania 15213; and Vitamin D Laboratory (M.F.H.), Section of Endocrinology, Nutrition and Diabetes, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Lisa M. Bodnar, Ph.D., M.P.H., R.D., Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, A742 Crabtree Hall, 130 DeSoto Street, Pittsburgh, Pennsylvania, 15261. E-mail: bodnar{at}edc.pitt.edu.

Context: Vitamin D has direct influence on molecular pathways proposed to be important in the pathogenesis of preeclampsia, yet the vitamin D-preeclampsia relation has not been studied.

Objectives: We aimed to assess the effect of maternal 25-hydroxyvitamin D [25(OH)D] concentration on the risk of preeclampsia and to assess the vitamin D status of newborns of preeclamptic mothers.

Design and Setting: We conducted a nested case-control study of pregnant women followed from less than 16 wk gestation to delivery (1997–2001) at prenatal clinics and private practices.

Patients: Patients included nulliparous pregnant women with singleton pregnancies who developed preeclampsia (n = 55) or did not develop preeclampsia (n = 219). Women’s banked sera were newly measured for 25(OH)D.

Main Outcome Measure: The main outcome measure was preeclampsia (new-onset gestational hypertension and proteinuria for the first time after 20 wk gestation). Our hypotheses were formulated before data collection.

Results: Adjusted serum 25(OH)D concentrations in early pregnancy were lower in women who subsequently developed preeclampsia compared with controls [geometric mean, 45.4 nmol/liter, and 95% confidence interval (CI), 38.6–53.4 nmol/liter, vs. 53.1 and 47.1–59.9 nmol/liter; P < 0.01]. There was a monotonic dose-response relation between serum 25(OH)D concentrations at less than 22 wk and risk of preeclampsia. After confounder adjustment, a 50-nmol/liter decline in 25(OH)D concentration doubled the risk of preeclampsia (adjusted odds ratio, 2.4; 95% CI, 1.1–5.4). Newborns of preeclamptic mothers were twice as likely as control newborns to have 25(OH)D less than 37.5 nmol/liter (adjusted odds ratio, 2.2; 95% CI, 1.2–4.1).

Conclusions: Maternal vitamin D deficiency may be an independent risk factor for preeclampsia. Vitamin D supplementation in early pregnancy should be explored for preventing preeclampsia and promoting neonatal well-being.

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