Vitamin D supplementation during pregnancy: safety considerations in the design and interpretation of clinical trials

J Perinatol. 2011 Jul;31(7):449-59. doi: 10.1038/jp.2010.203. Epub 2011 Jan 20.


Maternal-child health benefits of optimizing vitamin D status during pregnancy may include a reduced risk of pre-eclampsia, improved fetal growth and beneficial effects on infant immune function. These hypotheses require evaluation by randomized controlled antenatal vitamin D supplementation trials using doses that are high enough to elevate serum 25-hydroxyvitamin D concentrations into the range believed to be associated with improved health outcomes. Such doses may be considerably higher than the current recommended dietary allowance (600 IU day(-1)) or standard prenatal supplement dose (400 IU day(-1)), and may even be higher than the tolerable upper intake level (4000 IU day(-1)) advised by the Institute of Medicine (2010). A critical review of the published literature yielded limited data regarding the safety of antenatal vitamin D regimens. There have been no published reports of the teratogenic effects of vitamin D on humans. Some animal studies have suggested the potential for dose-dependent fetal toxicities (for example, growth impairment, skeletal malformations and cardiovascular anomalies), but the relevance of these observations to humans is unknown. Antenatal vitamin D supplementation trials should incorporate a range of methods for objectively establishing maternal and fetal safety, and aim to identify the lowest doses of vitamin D required to achieve target outcomes.

Publication types

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

MeSH terms

  • Animals
  • Dietary Supplements*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Maternal Welfare*
  • Maximum Tolerated Dose
  • Pregnancy / physiology*
  • Pregnancy Complications / prevention & control*
  • Pregnancy, Animal / physiology*
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Safety Management
  • Treatment Outcome
  • Vitamin D / administration & dosage*
  • Vitamin D / adverse effects


  • Vitamin D