Background: Emerging evidence suggests that vitamin D status in pregnancy may be associated with the development of gestational diabetes (GDM). However, the temporal relationship remains unclear due to the lack of prospective data with serial measurements of maternal vitamin D levels. We prospectively examined longitudinal changes in vitamin D biomarkers in relation to subsequent GDM risk.

Methods: A nested case-control study of 107 GDM cases and 214 controls (matched on age, race/ethnicity, and gestational week (GW) at blood draw) was conducted within the NICHD Fetal Growth Studies-Singleton Cohort (2009-2013). Plasma concentrations of D2 and D3 25-hydroxyvitamin D (25(OH)D) and vitamin D binding protein were measured at GWs 10-14, 15-26, 23-31, and 33-39; we further calculated total, free, and bioavailable 25(OH)D. Linear mixed-effects models and conditional logistic regression models were used adjusting for confounders.

Results: Compared with controls, women who developed GDM appeared to have lower concentrations of total 25(OH)D as early as GWs 10-14 (median: 25.59 vs. 27.46 ng/mL) and had a greater longitudinal increase in total 25(OH)D levels from GWs 10-14 to 15-26 (LS mean difference in log-scale: 0.10 vs. 0.04, p=0.046). We found no linear associations between vitamin D biomarkers at GWs 10-14 or GWs 15-26 and GDM risk. However, vitamin D deficiency (<20 ng/mL) at GWs 10-14 was associated with a 2.82-fold increased GDM risk (adjusted OR=2.82, 95% CI: 1.15-6.93). Furthermore, women with persistent vitamin D deficiency at both weeks 10-14 and weeks 15-26 had more than 4-fold elevated risk for GDM compared to those persistently non-deficient (adjusted OR=4.46, 95% CI: 1.15-17.3).

Conclusions: Our findings suggest that maternal vitamin D deficiency in the first trimester of pregnancy may be implicated in the development of GDM. Assessment of vitamin D status in early pregnancy may be clinically important and valuable for the primary prevention of GDM.


J. Xia: None. Y. Song: None. S. Rawal: None. J. Wu: None. S. Hinkle: None. M.Y. Tsai: None. C. Zhang: None.

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