Lower maternal vitamin D concentrations may be associated with earlier gestational age at delivery, according to a retrospective cohort study.
Investigators conducted an 8-year retrospective review of electronic health records from women who delivered at the Medical University of South Carolina between January 2016 and March 2024. The cohort included 15,506 women with at least 1 maternal 25-hydroxyvitamin D (25[OH]D) measurement during pregnancy. The investigators used the first documented measurement prior to delivery to reduce potential bias.
The primary outcome was preterm birth, defined as delivery prior to 37 weeks. Preterm birth prior to 32 weeks and etiologic subtypes were also examined. Maternal 25(OH)D concentration was evaluated continuously and according to predefined thresholds of less than 10, 20, 30, and 40 ng/mL. Multivariable models accounted for race and ethnicity, insurance status, and maternal age.
Mean maternal 25(OH)D concentration was 34.8 ng/mL among women delivering at term (n = 13,451) compared with 31.3 ng/mL among those delivering at 32 to 36 weeks (n = 1,652), a difference of 3.46 ng/mL. The difference was greater among women delivering before 32 weeks (n = 385), whose mean concentration was 26.2 ng/mL.
The inverse association between maternal 25(OH)D concentration and preterm birth persisted following adjustment for race and ethnicity, insurance status, and maternal age. Higher concentrations were associated with lower odds of delivery before both 37 weeks and 32 weeks. Because the secondary outcomes represented overlapping, nonindependent subsets of preterm birth, the investigators considered those analyses exploratory and emphasized the consistency of the associations rather than formal comparisons across outcomes.
Lower vitamin D concentrations were also common in the cohort. Overall, 45% of women had at least 1 measured 25(OH)D concentration below 30 ng/mL, and 66% had at least 1 concentration below 40 ng/mL. Mean concentrations varied across racial and ethnic groups, from 24.4 ng/mL among Black women to 40.8 ng/mL among White women. The clinical significance of a 40-ng/mL threshold remains debated and evidence supporting a universal threshold during pregnancy is inconsistent, according to the investigators.
The study's retrospective design precluded causal inference, and information on potential confounders including maternal body mass index, diet, vitamin D supplementation, and detailed socioeconomic measures was incomplete or unavailable. The timing of vitamin D measurements also varied during pregnancy. In addition, measurements were available only among women who underwent clinical testing, limiting generalizability to the broader obstetric population. Residual confounding could not be excluded.
The investigators said prospective studies and randomized trials are needed to clarify causality, appropriate thresholds, and which populations might benefit from targeted interventions.
“Although these findings do not establish causality, they contribute real-world evidence from a large, diverse US population to a growing literature suggesting that maternal vitamin D status may be relevant to pregnancy outcomes,” wrote lead study author Anjali G. Borsum, of the College of Medicine at the Medical University of South Carolina, and colleagues.
The study authors reported no conflicts of interest.
Source: Journal of Perinatology
