Vitamin D Supplementation in Pregnancy Does Not Prevent Preterm Birth, Meta-Analysis Finds
核心洞察
A meta-analysis of 38 RCTs involving 17,392 pregnant women found vitamin D supplementation was associated with a borderline increase in preterm birth (搜索) risk (RR, 1.13; 95% CI, 1.01-1.26; P = 0.04).
The increased risk signal was largely driven by a single large trial among women living with HIV and should not be generalized to healthy pregnant women.
No significant effects were observed for maternal adverse events or neonatal anthropometric indicators as secondary outcomes.
A comprehensive systematic review and meta-analysis published in BIO Integration has concluded that current evidence does not support universal vitamin D supplementation during pregnancy to prevent preterm birth (搜索). The analysis, which pooled data from 38 randomized controlled trials (RCTs) encompassing 17,392 pregnant women, found that vitamin D supplementation was associated with a borderline increase in preterm birth risk rather than a protective effect.
The findings challenge long-held assumptions about the role of vitamin D in pregnancy outcomes and underscore the need for more nuanced, individualized approaches to supplementation.
Primary Analysis Reveals Unexpected Risk Signal
In the primary analysis, which included 19 RCTs involving 7,959 pregnant women who reported preterm birth (搜索) outcomes, vitamin D supplementation was associated with a modest but statistically significant increase in preterm birth risk (RR, 1.13; 95% CI, 1.01–1.26; P = 0.04; I² = 0%). The low heterogeneity (I² = 0%) indicates consistency across the included trials, though the authors caution that this association was largely driven by one large RCT conducted among women living with HIV.
The systematic review searched PubMed, Web of Science, Medline, Cochrane Library, and Embase from inception to April 2023 with no language restrictions, comparing vitamin D supplementation with placebo, no treatment, or standard low-dose vitamin D (≤ 600 IU/day) in pregnant women.
Subgroup Analyses and the HIV Trial Influence
Exploratory subgroup analyses revealed an increased preterm birth (搜索) signal among participants with a baseline 25(OH)D level of 30 nmol/L or higher (OR, 1.25; 95% CI, 1.05–1.48). However, the authors emphasize that this signal was entirely derived from the same HIV-positive trial population. No significant subgroup associations were detected in the below 30 nmol/L subgroup, nor were significant differences observed when stratifying by supplementation dose or timing of initiation.
"The possible increased risk of preterm birth (搜索) 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," the authors stated.
Secondary Outcomes Show No Significant Effects
Beyond preterm birth (搜索), the meta-analysis examined maternal adverse events and neonatal anthropometric indicators as secondary outcomes. No significant effects were noted for either maternal or neonatal secondary outcomes, suggesting that vitamin D supplementation during pregnancy does not confer measurable benefits or harms on these parameters based on current evidence.
Study Limitations Acknowledged
The authors identified several important limitations in their analysis. These included incomplete reporting of preterm births across trials, reliance on a risk signal derived from a single population-specific trial, dichotomization of baseline 25(OH)D status, and the lack of individual participant data for more refined subgroup analyses.
Clinical Implications and Future Directions
Preterm birth (搜索) complications remain among the leading causes of mortality in neonates and children under 5 years of age worldwide, making the identification of effective preventive strategies a global health priority. The association between prenatal vitamin D supplementation and preterm birth risk has been controversial based on prior RCTs, and this meta-analysis provides the most comprehensive assessment to date.
The authors call for further large-scale RCTs and individual participant data meta-analyses to clarify whether baseline vitamin D status modifies the effects of vitamin D supplementation. Until such evidence emerges, the findings suggest that universal vitamin D supplementation specifically for preterm birth (搜索) prevention is not warranted.