A Nested Case-Control Study of Midgestation Vitamin D Deficiency and Risk of Severe Preeclampsia

Context: Vitamin D may be important in the pathogenesis of severe preeclampsia. Given the few effective preventive strategies for severe preeclampsia, studies establishing this link are needed so that effective interventions can be developed. Objective: Our objective was to assess whether midgestation vitamin D deficiency is associated with development of severe preeclampsia. Design and Setting: We conducted a nested case-control study of pregnant women who had previously given blood for routine genetic multiple marker screening and subsequently delivered at a tertiary hospital between January 2004 and November 2008. Patients: Participants included women with singleton pregnancies in the absence of any chronic medical illnesses. From an overall cohort of 3992 women, 51 cases of severe preeclampsia were matched by race/ethnicity with 204 women delivering at term with uncomplicated pregnancies. Banked maternal serum was used to measure maternal 25-hydroxyvitamin D [25(OH)D]. Main Outcome Measure: The main outcome was severe preeclampsia. Results: Midgestation maternal 25(OH)D concentration was lower in women who subsequently developed severe preeclampsia compared with controls [median (interquartile range), 75 (47-107) nmol/liter vs. 98 (68-113) nmol/liter; P = 0.01]. Midgestation maternal 25(OH)D of less than 50 nmol/liter was associated with an almost 4-fold odds of severe preeclampsia (unadjusted odds ratio, 3.63; 95% confidence interval, 1.52-8.65) compared with midgestation levels of at least 75 nmol/liter. Adjustment for known confounders strengthened the observed association (adjusted odds ratio, 5.41; 95% confidence interval, 2.02-14.52). Conclusion: Maternal midgestation vitamin D deficiency was associated with increased risk of severe preeclampsia. Vitamin D deficiency may be a modifiable risk factor for severe preeclampsia. (J Clin Endocrinol Metab 95: 5105-5109, 2010)