Regimens of vitamin D supplementation for women during pregnancy

Background Vitamin D deficiency during pregnancy increases the risk of pre‐eclampsia, gestational diabetes, preterm birth, and low birthweight. In a previous Cochrane Review we found that supplementing pregnant women with vitamin D alone compared to no vitamin D supplementation may reduce the risk of pre‐eclampsia, gestational diabetes, and low birthweight and may increase the risk of preterm births if it is combined with calcium. However the effects of different vitamin D regimens are not yet clear. Objectives To assess the effects and safety of different regimens of vitamin D supplementation alone or in combination with calcium or other vitamins, minerals or nutrients during pregnancy, specifically doses of 601 international units per day (IU/d) or more versus 600 IU/d or less; and 4000 IU/d or more versus 3999 IU/d or less. Search methods We searched the Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (12 July 2018), and the reference lists of retrieved studies. Selection criteria Randomised trials evaluating the effect of different vitamin D regimens (dose, frequency, duration, and time of commencement of supplementation during pregnancy), alone or in combination with other nutrients on pregnancy and neonatal health outcomes. We only included trials that compared 601 IU/d or more versus 600 IU/d or less and 4000 IU/d or more versus 3999 IU/d or less. We did not include in the analysis groups that received no vitamin D, as that comparison is assessed in another Cochrane Review. Data collection and analysis Two review authors independently: i) assessed the eligibility of studies against the inclusion criteria; ii) extracted data from included studies, and iii) assessed the risk of bias of the included studies. Our primary maternal outcomes were: pre‐eclampsia, gestational diabetes, and any adverse effects; our primary infant outcomes were preterm birth and low birthweight. Data were checked for accuracy. The certainty of the evidence was assessed using the GRADE approach. Main results In this review, we included data from 30 trials involving 7289 women. We excluded 11 trials, identified 16 ongoing/unpublished trials and two trials are awaiting classification. Overall risk of bias for the trials was mixed. Comparison 1. 601 IU/d or more versus 600 IU/d or less of vitamin D alone or with any other nutrient (19 trials; 5214 participants) Supplementation with 601 IU/d or