Preterm birth remains one of the most consequential complications of pregnancy, particularly in South Asia where vitamin D deficiency is nearly universal. If a low-cost, widely available supplement could meaningfully reduce risk, the implications for neonatal outcomes in resource-limited settings would be substantial — making this trial design worth scrutinizing closely.
This registered double-blind RCT, published in BMJ Open as a study protocol, will enroll 902 singleton-pregnant Indian women under 18 weeks gestation who have confirmed 25-hydroxyvitamin D insufficiency (below 20 ng/mL). Participants will be randomized to either 500 IU/day (the current standard-of-care dose) or 2,000 IU/day of vitamin D3, both combined with 1,000 mg elemental calcium, continuing until delivery. The primary comparison targets preterm birth rates and premature rupture of membranes, with monthly compliance monitoring and serial blood sampling. The design explicitly excludes women with chronic illness, certain infections, or assisted conception, which will constrain generalizability but improves internal validity.
The existing evidence on vitamin D and preterm birth is mixed. Several meta-analyses suggest modest reductions in preterm birth risk with supplementation above standard doses, but effect sizes are heterogeneous and few trials have been conducted in populations where baseline deficiency is as profound as India's estimated 90% prevalence. The 2,000 IU dose tested here is notably conservative compared to some intervention arms in prior trials, which have used 4,000 IU or higher. This choice may limit the detectable signal if a threshold effect exists at higher serum 25(OH)D concentrations. As a protocol publication, no outcome data are yet available — the trial's value lies in its pre-specified design and powered sample size. If results confirm even a modest protective effect, the cost-benefit argument for raising prenatal vitamin D recommendations in deficiency-endemic regions would become considerably stronger. This is a confirmatory trial in character, not paradigm-shifting at the protocol stage.