Vitamin D Metabolism in Pregnancy: Determinants and Impact on Vitamin D Supplementation

Vitamin D is known to exert important non-calcemic effects during mammalian pregnancy. Furthermore, vitamin D deficiency has been associated with pregnancy disorders such as gestational diabetes, preeclampsia and fetal growth restriction. Remarkably, equivocal data from randomized clinical trials on vitamin D supplementation have created significant debate on the timing, vitamin D supplementation dose, and patient subpopulations that would benefit the most. This review focuses on environmental and physiological determinants that may regulate maternal-, placental-, and fetal-vitamin D metabolism in health and disease. We will cover the physiological adaptations of vitamin D metabolism in uncomplicated pregnancies and emphasize important similarities and differences between humans and mammalian species commonly used in reproductive research that include mice, rats, guinea pigs, sheep, and baboons. Then, we will examine observational studies on vitamin D metabolism in maternal obesity and pregnancy disorders focusing on consistent differences with uncomplicated pregnancies, followed by animal model research on vitamin D deficiency/sufficiency. The data reviewed herein will strengthen the current notion that vitamin D supplementation is unlikely to increase functional vitamin D status equally in all subjects and support the need for future research on strategies to restore dysfunctional vitamin D homeostasis in pregnancy.