New insights into the vitamin D requirements during pregnancy

Abstract

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.

Accounting for diverse evolutionary forces reveals the mosaic nature of selection on genomic regions associated with human preterm birth

“…The population-specific differentiation associated with the variant rs222016 is consistent with the differential evolution of the vitamin D system between populations—likely in response to different environments and associated changes in skin pigmentation 70,71 . Our results provide evolutionary context for the link between vitamin D and pregnancy outcomes 72 and suggest a role for variation in the gene GC in the ethnic disparities in pregnancy outcomes.…”

Efficacy of two different doses of oral vitamin D supplementation on inflammatory biomarkers and maternal and neonatal outcomes

“…Consistent with our findings, an open‐label randomized controlled trial showed that maternal vitamin D supplementation (2,000–4,000‐IU cholecalciferol) among women with VDD/insufficiency from 12 to 16 weeks of gestation until delivery prevents neonatal VDD (Rodda et al, ). It is likely that placental transportal sites, notably megalin–cubilin system, are saturated with taking a certain dose of vitamin D a day (Hollis & Wagner, ). Though vitamin D is not considered a teratogen, this may be a protective mechanism to regulate foetal vitamin D status.…”

“…Therefore, it seems crucial to initiating vitamin D supplementation earlier and eliminating VDD before pregnancy (Hollis & Wagner, 2017b). Moreover, it has been suggested that achieving serum 25(OH)D concentration of at least 100 nmol L −1 is required for optimizing the conversion of 25(OH)D to 1,25(OH)2D and reducing the adverse pregnancy outcomes (Hollis & Wagner, 2017a).…”

“…In most efficacy trials, changes of circulating 25(OH)D, pregnancy, and birth outcomes have been considered as the main outcomes (Curtis, Moon, Harvey, & Cooper, 2018;Roth et al, 2017). However, vitamin D can affect several health aspects including metabolism, inflammatory response, oxidative stress, and immunity (Hollis & Wagner, 2017a). To make a better evaluation of the possible effects of vitamin D supplementation during pregnancy, a clinical trial was designed to assess a wide spectrum of maternal, birth, and neonatal outcomes to compare two doses of vitamin D3 supplementation.…”

Maternal and Foetal Health Implications of Vitamin D Status during Pregnancy

“…Foetal hypercelcemia is an old concept that is confusing [26]; some reported hypercalcemias could have been not due to vitamin D excess leading to supravalvular aor-DOI: 10.1159/000487370 tic stenosis but due to a disease known as William' Syndrome in which patients exhibit an exaggerated response of circulating 25(OH)D to orally administrated vitamin D [27][28][29][30]. However, in the 1950s, the policy to fortify milk and cereals with Vitamin D in the United Kingdom increased the number of cases of Infantil Hypercalcemia that was half reduced when the fortification was limited [31].…”