Vitamin D supplementation during pregnancy: safety considerations in the design and interpretation of clinical trials.
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.
Division of Pediatric Medicine, The Hospital for Sick Children, Toronto, ON, Canada. daniel.roth@sickkids.ca
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D000818:Animals; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008429:Maternal Welfare; D020714:Maximum Tolerated Dose; D011247:Pregnancy / Q000502:physiology*; D011248:Pregnancy Complications / Q000517:prevention & control*; D011270:Pregnancy, Animal / Q000502:physiology*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D017751:Safety Management; D016896:Treatment Outcome; D014807:Vitamin D / Q000008:administration & dosage* / Q000009:adverse effects
D014807:Vitamin D