Low maternal 25-hydroxyvitamin D concentration increases the risk of severe and mild preeclampsia

Ann Epidemiol. 2016 Dec;26(12):853-857.e1. doi: 10.1016/j.annepidem.2016.09.015. Epub 2016 Oct 8.


Purpose: The objective of this case-cohort study was to evaluate the relationship between maternal 25-hydroxyvitamin D (25(OH)D) concentration and preeclampsia overall and by severity.

Methods: From an eligible cohort of 12,861 women who had serum banked from aneuploidy screening in Pittsburgh, Pennsylvania from 1999 to 2010, we randomly sampled a subcohort of 2327 pregnancies and all remaining preeclampsia cases (n = 650 cases). Preeclampsia (defined as new-onset hypertension and proteinuria) and its mild and severe forms were identified using ICD-9 codes. Maternal serum collected at 20 weeks or less gestation was measured for 25(OH)D. We used log-binomial regression with restricted cubic splines to estimate the association between 25(OH)D and preeclampsia after adjusting for confounders.

Results: Approximately 21% of the randomly selected sample had 25(OH)D less than 50 nmol per L. We found that the adjusted risk of preeclampsia declined as serum 25(OH)D increased to 50 nmol per L and then plateaued (test of nonlinearity P < .05). The adjusted preeclampsia risk ratios (95% confidence intervals) for 25(OH)D less than 25 nmol per L, 25 to 49.9 nmol per L, and 50 to 74.9 nmol per L were 2.4 (1.2-4.8), 1.1 (0.69-1.7), and 1.3 (0.89-1.8), respectively, compared with those with 25(OH)D 75 nmol per L and over. Similar associations were observed with severe and mild preeclampsia.

Conclusions: Vitamin D deficiency increases risks of severe and mild forms of preeclampsia.

Keywords: 25-Hydroxyvitamin D; Hypertension; Preeclampsia; Pregnancy; Vitamin D deficiency.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Humans
  • Multivariate Analysis
  • Pre-Eclampsia / blood
  • Pre-Eclampsia / diagnosis
  • Pre-Eclampsia / etiology*
  • Pregnancy
  • Regression Analysis
  • Risk Factors
  • Severity of Illness Index
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / complications*
  • Vitamin D Deficiency / diagnosis


  • Biomarkers
  • Vitamin D
  • 25-hydroxyvitamin D