Vitamin D supplementation and the effects on glucose metabolism during pregnancy: a randomized controlled trial

Abstract

Objective: Vitamin D deficiency in pregnancy is associated with an increased risk of gestational diabetes mellitus (GDM) and neonatal vitamin D deficiency. We conducted a double-blind, randomized controlled trial of low-dose (LD) versus high-dose (HD) vitamin D supplementation to investigate the effects of vitamin D supplementation on glucose metabolism during pregnancy.

Research design and methods: Women with plasma 25-hydroxyvitamin D (25OHD) levels <32 ng/mL before 20 weeks' gestation were randomized to oral vitamin D3 at 5,000 IU daily (HD) (n = 89) or the recommended pregnancy dose of 400 IU daily (LD) (n = 90) until delivery. The primary end point was maternal glucose levels on oral glucose tolerance test (OGTT) at 26-28 weeks' gestation. Secondary end points included neonatal 25OHD, obstetric and other neonatal outcomes, and maternal homeostasis model assessment of insulin resistance. Analysis was by intention to treat.

Results: There was no difference in maternal glucose levels on OGTT. Twelve LD women (13%) developed GDM versus seven (8%) HD women (P = 0.25). Neonatal cord 25OHD was higher in HD offspring (46 ± 11 vs. 29 ± 12 ng/mL, P < 0.001), and deficiency was more common in LD offspring (24 vs. 10%, P = 0.06). Post hoc analysis in LD women showed an inverse relationship between pretreatment 25OHD and both fasting and 2-h blood glucose level on OGTT (both P < 0.001). Baseline 25OHD remained an independent predictor after multiple regression analysis.

Conclusions: HD vitamin D supplementation commencing at a mean of 14 weeks' gestation does not improve glucose levels in pregnancy. However, in women with baseline levels <32 ng/mL, 5,000 IU per day was well tolerated and highly effective at preventing neonatal vitamin D deficiency.