Post-Hoc Comparison of Vitamin D Status at Three Time Points During Pregnancy Demonstrates Lower Risk of Preterm Birth with Higher Vitamin D Closer to Delivery

Carol L. Wagner, Carole Baggerly, Sharon L. McDonnell, Leo Baggerly, Stuart A. Hamilton, Joyce Winkler, Gloria Warner, Carolina Rodriguez Cook, Judy R. Shary, Pamela G. Smith, Bruce W. Hollis

There have been observational reports that maternal vitamin D status at baseline and not closest to delivery is a better predictor of pregnancy outcomes, suggesting that a cascade of events is set into motion that is not modiable by vitamin D supplementation during later pregnancy. To address this issue, in this exploratory post-hoc analysis using correlation and logistic regression, we sought to measure the strength of the association between serum 25(OH)D concentrations at 3 time points during pregnancy: baseline, 1st trimester (<16 weeks); 2nd trimester (16–26 weeks); and 3rd trimester (27 weeks) and preterm birth. I twas hypothesized that the 25(OH)D value closest to delivery would be most significantly associated with preterm birth. To accomplish this objective, the data sets from NICHD (n=333) and Thrasher Research Fund (n = 154) vitamin D supplementation pregnancy studies were combined.

The results of this analysis were that 25(OH)D values closer to delivery were more strongly correlated with gestational age at delivery than earlier values: 1st trimester: r = 0.11 (p = 0.02); 2nd trimester: r = 0.08 (p = 0.09); and 3rd trimester: r =0.15 (p = 0.001). When logistic regression was performed with preterm birth (<37 weeks) as the outcome and 25(OH)D quartiles as the predictor variable, adjusting for study and participant race/ethnicity, as with the correlation analysis, the measurements closer to delivery were more significantly associated and had a higher magnitude of effect. That is, at baseline, those who had serum concentrations <50 nmol/L (20ng/mL) had 3.3 times of odds of a preterm birth compared to those with serum concentrations 100 nmol/L (40 ng/mL; p = 0.27). At 2nd trimester, the odds were 2.0 fold (p = 0.21) and at the end of pregnancy, the odds were 3.8 fold (p = 0.01). The major ndings from this exploratory analysis were: (1) maternal vitamin D status closest to delivery date was more signicantly associatedwith pretermbirth, suggesting that later intervention as a rescue treatment may positively impact the risk of preterm delivery, and (2) a serum concentration of 100 nmol/L (40 ng/mL) in the 3rd trimester was associated with a 47% reduction in preterm births.

This article is part of a Special Issue entitled ‘17th Vitamin D Workshop’.

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