Vitamin D Supplementation and the Effects on Glucose Metabolism During Pregnancy: A Randomized Controlled Trial

Abstract

OBJECTIVEVitamin D deficiency in pregnancy is associated with an increased risk of gestational diabetes mellitus (GDM) and neonatal vitamin D deficiency. We conducted a doubleblind, 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 METHODSWomen 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. RESULTSThere 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 6 11 vs. 29 6 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. CONCLUSIONSHD 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.Vitamin D deficiency has become a common problem globally. It has been estimated that one billion people worldwide are vitamin D deficient (1). In the U.S., vitamin D deficiency is prevalent across populations of all age-groups (2). Even in a country with high ultraviolet exposure like Australia, the prevalence of vitamin D deficiency (25-hydroxyvitamin D [25OHD] level ,20 ng/mL [,50 nmol/L]) was 31% among

Vitamin D supplementation during pregnancy: Updated meta-analysis on maternal outcomes

“…1). We excluded 27 studies, mainly because the comparisons were among different doses of vitamin D without a placebo or control group [7[15], [24], [35], [40], [45], [51], [55], [57], [58], [29], [64], [65], [68]. Also, four trials were not randomised [2], [12], [14], [33] and three were done in pregnant women with chronic conditions [3], [4], [20].…”

Vitamin D and Parathyroid Hormone Status in Pregnancy: Effect on Insulin Sensitivity, β-cell Function, and Gestational Diabetes Mellitus

“…In a double-blind, randomized controlled trial of 54 women with GDM, treatment with two doses of 50 000 IU vitamin D had beneficial effects on fasting glucose and insulin resistance compared with placebo, although it should be noted that these parameters differed between the treatment arms at baseline (37). Most recently, a trial in which 179 women with vitamin D deficiency were randomly assigned to either high-dose or standard vitamin D supplementation from mean 14 weeks' gestation onward found no effect on glucose levels at the OGTT at 26 -28 weeks' gestation (38). In the context of this modest conflicted literature, the current study raises the possibility that previous trials may have failed to detect a robust effect of vitamin D supplementation on glucose metabolism because they were not performed in the specific patient population that might most benefit from this intervention-namely, women whose 25-OH-D levels are unable to suppress PTH.…”

Potential impact of maternal vitamin D status on obstetric well-being

“…In Europe, a randomized controlled trial, for preventive measures against the development of GDM in overweight and obese women, is exploring the potential effectiveness of VD supplementation on the risk of developing GDM combined by lifestyle [72]. In contrast, in Australia, a double-blind, randomized controlled trial of low vs. high dose of VD supplementation, concluded that high dose does not improve glucose levels in pregnancy [73].…”