Comparison of vitamin D metabolites associated with preterm birth in a cohort of Black pregnant women.

Vitamin D deficiency during pregnancy has been associated with increased risk for preterm birth (PTB). However, it is unclear if total 25-hydroxyvitamin D [25(OH)D], the primary measure of vitamin D status in clinical practice, accurately reflects biological availability. Therefore, we investigated three specific measures of Vitamin D (circulating maternal total 25(OH)D, vitamin D binding protein (VDBP), free 25(OH)D levels) in relation to PTB in a cohort of pregnant Black women using a nested case-control analysis. Plasma 25(OH)D was quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and VDBP measured using ELISA methods. Free 25(OH)D levels were calculated using verified equations. PTB was defined as delivery < 37 completed weeks' gestation. Logistic regression models were used to estimate the odds of PTB per 1 ng/mL increase in plasma 25(OH)D, VDBP and free 25(OH)D. Adjusted models accounted for gestational age at blood draw, pre-pregnancy BMI, preeclampsia diagnosis, and seasonality of sampling. Each incremental ng/mL increase in 25(OH)D was associated with a reduction in PTB odds in the unadjusted model (OR 0.95; 95% CI 0.92-0.99; p = 0.023). This association remained significant following multivariable adjustment (OR 0.96; 95% CI 0.92-0.99; p = 0.047). Other measures of Vitamin D were not significantly associated with PTB in unadjusted or adjusted models. These findings support a role for maternal vitamin D stores in maintaining pregnancy duration and highlight the need for mechanistic studies addressing placental steroid metabolism, inflammatory regulation, and interactions between vitamin D-dependent signaling and early parturition pathways.