New insights into the vitamin D requirements during pregnancy.

Pregnancy represents a dynamic period with physical and physiological changes in both the mother and her developing fetus. The dramatic 2–3 fold increase in the active hormone 1,25(OH)2D concentrations during the early weeks of pregnancy despite minimal increased calcium demands during that time of gestation and which are sustained throughout pregnancy in both the mother and fetus suggests an immunomodulatory role in preventing fetal rejection by the mother. While there have been numerous observational studies that support the premise of vitamin D's role in maintaining maternal and fetal well-being, until recently, there have been few randomized clinical trials with vitamin D supplementation. One has to exhibit caution, however, even with RCTs, whose results can be problematic when analyzed on an intent-to-treat basis and when there is high non-adherence to protocol (as if often the case), thereby diluting the potential good or harm of a given treatment at higher doses. As such, a biomarker of a drug or in this case “vitamin” or pre-prohormone is better served. For these reasons, the effect of vitamin D therapies using the biomarker circulating 25(OH)D is a far better indicator of true “effect.” When pregnancy outcomes are analyzed using the biomarker 25(OH)D instead of treatment dose, there are notable differences in maternal and fetal outcomes across diverse racial/ethnic groups, with improved health in those women who attain a circulating 25(OH)D concentration of at least 100 nmol·L−1 (40 ng·mL−1). Because an important issue is the timing or initiation of vitamin D treatment/supplementation, and given the potential effect of vitamin D on placental gene expression and its effects on inflammation within the placenta, it appears crucial to start vitamin D treatment before placentation (and trophoblast invasion); however, this question remains unanswered. Additional work is needed to decipher the vitamin D requirements of pregnant women and the optimal timing of supplementation, taking into account a variety of lifestyles, body types, baseline vitamin D status, and maternal and fetal vitamin D receptor (VDR) and vitamin D binding protein (VDBP) genotypes. Determining the role of vitamin D in nonclassical, immune pathways continues to be a challenge that once answered will substantiate recommendations and public health policies. Larger amounts of vitamin D are needed during pregnancy than are currently recommended assert two experts. In a review article, Bruce Hollis and Carol Wagner from the Medical University of South Carolina in Charleston, USA, argue that current guidelines regarding vitamin D levels during pregnancy fail to take into account the latest research showing that vitamin D supplementation can help protect both the mother from pregnancy-related complications and the developing fetus from autoimmune disorders. The authors describe how, apart from its usual function as a calcium-regulating factor, vitamin D during pregnancy primarily helps maintain a proper immune balance. They argue that a lack of vitamin D during pregnancy or the early months of infancy may be responsible for certain diseases in later life, including asthma and multiple sclerosis.