A comprehensive systematic review and meta-analysis published in the journal BIO Integration has found that routine vitamin D supplementation during pregnancy does not provide convincing evidence for preventing preterm birth. The analysis also highlighted that an apparent increase in preterm birth risk observed in one subgroup should be interpreted with caution because it was driven by a single clinical trial involving women living with HIV, rather than the broader pregnant population.
The researchers analyzed data from 38 randomized controlled trials (RCTs) involving 17,392 pregnant women. Among these, 19 trials including 7,959 women reported data on preterm birth, defined as delivery before 37 weeks of gestation. The investigators compared vitamin D supplementation with placebo, no treatment, or standard low-dose vitamin D (600 IU/day or less) to evaluate its effects on pregnancy outcomes.
The primary analysis showed a borderline increase in preterm birth risk among women receiving vitamin D supplements (Risk Ratio 1.13; 95% Confidence Interval 1.01–1.26). However, the authors emphasized that this finding was largely influenced by one large trial conducted among HIV-positive pregnant women. When this context was considered, the evidence did not support the conclusion that vitamin D supplementation increases preterm birth risk in healthy pregnant women.
Exploratory subgroup analyses suggested that women with baseline vitamin D levels of 30 nmol/L or higher appeared to have an increased risk of preterm birth after supplementation. However, this signal also originated almost entirely from the same HIV-focused study. No similar association was observed in women with lower baseline vitamin D levels, nor were there meaningful differences based on the dose of supplementation or the stage of pregnancy when vitamin D was initiated.
Beyond preterm birth, the researchers found no significant benefits or harms of vitamin D supplementation on maternal adverse events or neonatal outcomes, including birth weight and other anthropometric indicators.
The authors noted several limitations, including incomplete reporting of preterm births in some trials, reliance on findings from a single population-specific study, and the absence of individual participant-level data for more detailed analyses. They concluded that current evidence does not support universal vitamin D supplementation during pregnancy solely to prevent preterm birth. Instead, further large-scale, well-designed randomized trials and individual participant data meta-analyses are needed to determine whether vitamin D status before supplementation influences pregnancy outcomes. (doi=10.15212/bioi-2025-0224)
