Vitamin D insufficiency is associated with increased risk of first-trimester miscarriage in the Odense Child Cohort

Am J Clin Nutr. 2015 Sep;102(3):633-8. doi: 10.3945/ajcn.114.103655. Epub 2015 Jul 15.

Abstract

Background: Miscarriage is the most common negative outcome of pregnancy, and identification of modifiable risk factors is potentially of great importance for public health. Low vitamin D concentrations in pregnancy are widespread worldwide, and vitamin D deficiency is implicated in immune cell regulation at the feto-maternal interface and several diseases of pregnancy.

Objective: We investigated whether 25-hydroxyvitamin D serum concentration was a modifiable risk factor for early miscarriage.

Design: In a prospective cohort study of 1683 pregnant women donating serum before gestational week 22, we investigated the association between maternal serum concentrations of serum 25-hydroxyvitamin D [25(OH)D] and the risk of subsequent miscarriage (n = 58).

Results: The adjusted hazard of first-trimester miscarriage was lower with higher 25(OH)D concentrations (HR: 0.98; 95% CI: 0.96, 0.99). Concentrations of 25(OH)D <50 nmol/L were associated with a >2-fold increased adjusted HR for miscarriage (HR: 2.50; 95% CI: 1.10, 5.69). Concentrations of 25(OH)D were not associated with an increased risk of second-trimester miscarriage.

Conclusions: We found an association between 25(OH)D and first-trimester miscarriages, suggesting vitamin D as a modifiable risk factor for miscarriage. To test this hypothesis, randomized controlled trials should investigate the possible effect of vitamin D supplementation to increase 25(OH)D concentrations in early pregnancy, or before conception, to decrease risk of miscarriage. This trial was registered at clinicaltrials.gov as NCT02434900.

Keywords: cohort study; endocrinology; miscarriage; pregnancy; spontaneous abortion; vitamin D.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Spontaneous / blood*
  • Abortion, Spontaneous / epidemiology*
  • Adult
  • Denmark / epidemiology
  • Dietary Supplements
  • Female
  • Gestational Age
  • Humans
  • Pregnancy
  • Pregnancy Trimester, First*
  • Pregnancy Trimester, Second
  • Prospective Studies
  • Risk Factors
  • Vitamin D / blood*
  • Vitamin D Deficiency / blood*
  • Vitamin D Deficiency / epidemiology*
  • Young Adult

Substances

  • Vitamin D

Associated data

  • ClinicalTrials.gov/NCT02434900