Evidence does not support universal vitamin D supplementation to prevent preterm birth

Announcing a new article publication in BIO Integration. Preterm birth complications are among leading causes of mortality in neonates and children under 5 years of age worldwide. The association between prenatal vitamin D supplementation and risk of preterm birth is controversial based on randomized controlled trials (RCTs). The authors of this article aimed to determine the effect of vitamin D supplementation during pregnancy on preterm birth and maternal and neonatal secondary outcomes, and to ascertain whether the effects of vitamin D supplementation on preterm birth differed by baseline 25(OH)D status, supplementation dose, and timing of initiation. PubMed, Web of Science, Medline, Cochrane Library, and Embase were searched from inception to April 2023 with no language restrictions.

RCTs comparing vitamin D supplementation with placebo, no treatment, or standard low-dose vitamin D (≤ 600 IU/day) in pregnant women were included. The primary outcome was preterm birth (<37 weeks' gestation) and secondary outcomes included maternal adverse events and neonatal anthropometric indicators.

Thirty-eight RCTs involving 17,392 pregnant women were included. Nineteen RCTs involving 7959 pregnant women reported preterm birth. Vitamin D supplementation was associated with a borderline increase in preterm birth risk in the primary analysis (RR, 1.13; 95% CI, 1.01-1.26; P = 0.04; I² = 0%) but this association was modest and largely driven by one large RCT among women living with HIV. An increased preterm birth signal was noted among participants with a baseline 25(OH)D ≥ 30 nmol/L (OR, 1.25; 95% CI, 1.05-1.48) in exploratory subgroup analyses presented as ORs and this signal was entirely derived from the same HIV trial. No significant subgroup associations were detected in the < 30 nmol/L subgroup or by supplementation dose or initiation timing. No significant effects were noted for maternal or neonatal secondary outcomes.

The main study limitations included incomplete reporting of preterm births across trials, reliance on the risk signal on a single population-specific risk signal, dichotomization of baseline 25(OH)D status, and lack of individual participant data for refined subgroup analyses.

Current evidence does not support universal vitamin D supplementation to prevent preterm birth. A possible increased risk of preterm birth among participants with a baseline 25(OH)D ≥ 30 nmol/L should be interpreted cautiously because this finding was driven by a single trial in HIV-positive pregnant women and should not be generalized to healthy pregnant women. Further large-scale RCTs and individual participant data meta-analyses are warranted to clarify whether baseline vitamin D status modifies effects of vitamin D supplementation.