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

Abstract

Vitamin D and its active metabolite, 1,25-dihydroxyvitamin D (25(OH)D), may play an important role in the pathogenesis of preeclampsia. A number of investigators have reported lower maternal vitamin D concentrations in women after diagnosis of preeclampsia. Moreover, there is evidence that supplementation with vitamin D may reduce the risk of preeclampsia. Previous studies showing an association between vitamin D deficiency early in pregnancy and preeclampsia did not focus on women with severe disease. This nested case-control study tested the hypothesis that midgestation vitamin D deficiency is associated with an increased risk of developing severe preeclampsia compared with healthy women delivering at term. The participants were a cohort of 3992 singleton pregnant women who had previously provided blood samples for routine genetic multiple marker screening. Women with term pregnancies who developed severe preeclampsia (n = 51) were matched by race and ethnicity with those without preeclampsia (n = 204). All participants were healthy and had no chronic medical illnesses. Three maternal serum vitamin D concentrations were measured: 25(OH)D ≥ 75 nmol/L (reference group), 50–74.9 nmol/L, and ≤50 nmol/L. Multivariable logistical regression analysis was used to adjust for covariates. The midgestation serum 25(OH)D concentration was 23% lower among women who developed severe preeclampsia compared with control women (median interquartile range: 75 [95% confidence interval {CI}, 47–107] vs. 98 [95% CI, 68–113] nmol/L; P = 0.01). There was an inverse association between midgestation maternal 25(OH)D concentration and risk of severe preeclampsia in unadjusted models: 25(OH)D ≤50 nmol/L was associated with an almost 4-fold increased odds of severe preeclampsia compared with ≥75 nmol/L; the odds ratio was 3.63, with a 95% CI of 1.52–8.65. This association strengthened after adjustment for covariates (adjusted odds ratio, 5.41; 95% CI, 2.02–14.52). These findings support an association between maternal midgestation vitamin D deficiency and severe preeclampsia. The investigators suggest that supplementing vitamin D in deficient women during the preconception period or early pregnancy could be potentially effective to prevent severe preeclampsia.