Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials

Systematic review and meta-analysis of randomized trials in pregnant women receiving vitamin D supplementation across multiple countries and settings. A total of 43 trials with 8406 participants were eligible for meta-analyses, and most studies were small and conducted in low- or middle-income countries.

Vitamin D was given during pregnancy as either D2 or D3, by oral or intramuscular route, in regular or bolus regimens. Regular dosing was typically at least 2000 IU/day and commonly ranged from 400 IU/day to 4000 IU/day; bolus regimens ranged from 400 IU to 300,000 IU.

Prenatal vitamin D supplementation increased maternal and cord 25-hydroxyvitamin D concentrations and showed some favorable neonatal effects, including higher birth weight and lower risk of small-for-gestational-age birth. Pooled estimates showed serum 25(OH)D at/near delivery increased by 32.91 nmol/L and cord 25(OH)D increased by 27.73 nmol/L, while birth weight increased by 58.33 g. There was no clear benefit for gestational age at birth (-0.01 weeks), birth length, head circumference, or neonatal bone outcomes overall. Evidence for prevention of other maternal pregnancy outcomes and preterm birth was inconsistent, and the overall certainty was insufficient to guide clinical or policy recommendations.

Most included trials were small and of low quality, limiting confidence in the pooled findings. Many outcomes had missing or non-meta-analyzable data, and interventions, doses, and populations were heterogeneous across studies. Several clinically important outcomes remained uncertain despite the pooled analysis.