Early-Life Effects of Vitamin D: A Focus on Pregnancy and Lactation

Abstract

Vitamin D is an endocrine regulator of calcium and bone metabolism. Yet, its effects include other systems, such as innate and adaptive immunity. Unique to pregnancy, circulating 1,25-dihydroxyvitamin D (1,25[OH]₂D) increases early on to concentrations that are 2–3 times prepregnant values. At no other time during the lifecycle is the conversion of 25-hydroxyvitamin D (25[OH]D) to 1,25(OH)₂D directly related and optimized at ≥100 nmol/L. Vitamin D deficiency appears to affect pregnancy outcomes, yet randomized controlled trials of vitamin D supplementation achieve mixed results depending on when supplementation is initiated during pregnancy, the dose and dosing interval, and the degree of deficiency at the onset of pregnancy. Analysis of trials on an intention-to-treat basis as opposed to the use of 25(OH)D as the intermediary biomarker of vitamin D metabolism yields differing results, with treatment effects often noted only in the most deficient women. Immediately after delivery, maternal circulating 1,25(OH)₂D concentrations return to prepregnancy baseline, at a time when a breastfeeding woman has increased demands of calcium, beyond what was needed during the last trimester of pregnancy, making one question why 1,25(OH)₂D increases so significantly during pregnancy. Is it to serve as an immune modulator? The vitamin D content of mother’s milk is directly related to maternal vitamin D status, and if a woman was deficient during pregnancy, her milk will be deficient unless she is taking higher doses of vitamin D. Because of this relative “deficiency,” there is a recommendation that all breastfed infants receive 400 IU vitamin D₃/day starting a few days after birth. The alternative – maternal supplementation with 6,400 IU vitamin D₃/day, effective in safely raising maternal circulating vitamin D, that of her breast milk, and effective in achieving sufficiency in her recipient breastfeeding infant – remains a viable option. Additional research is needed to understand vitamin D’s influence on pregnancy health and the effect of maternal supplementation on breast milk’s immune signaling.