Vitamin D supplementation for the prevention of pre‐eclampsia? ‘First do no harm’

Sir, We read with interest the article by Wei et al. on longitudinal vitamin D status in pregnancy and the risk of preeclampsia. We commend the authors on performing the largest cohort study to address the issue to date and identifying that lower maternal 25(OH)D levels at late midtrimester were associated with an increased risk of preeclampsia. We would like to draw your readers’ attention to the fact that the clinical relevance of this remains uncertain. First, using maternal 25(OH)D levels at late mid-trimester as a test for predicting pre-eclampsia would have a sensitivity of 68% and a specificity of 62% (based on that cohort’s data). Second, in the latest Cochrane Systematic Review of the effects of vitamin D in pregnancy, the authors identified a single randomised controlled trial (from 1987) assessing the outcome of supplementation with vitamin D and calcium, and found no significant difference. On the other hand, the same systematic review identified a weak correlation between vitamin D supplementation and low birthweight, and teratogenicity of vitamin D remains a controversial issue. The British National Formulary 62 states that ‘high systemic doses [are] teratogenic in animals but therapeutic doses [are] unlikely to be harmful’, despite a very recent review arguing that vitamin D preparations are safe in pregnancy at even extremely high doses. Although current clinical trials in South Carolina and Bangladesh and Dhaka (NCT01126528) have shown no harmful effects of high-dose vitamin D supplementation, we believe more research is needed before arguing a case for the routine supplementation of pregnant women, particula in developed countries, with vitamin D. j