Relationship Between Vitamin D During Perinatal Development and Health

Jovana Kaludjerovic, MSc; Reinhold Vieth, PhD


J Midwifery Womens Health. 2010;55(6):550-560. 

In This Article

Vitamin D Metabolism During Pregnancy and Lactation

At 4 weeks of gestation, the placenta is formed, allowing nutrients to be transferred from the mother to the fetus (Figure 1). From 4 weeks of gestation to term, 25(OH)D easily diffuses across the placenta, allowing the 25(OH)D concentrations in fetal cord blood to reach 87% that of the mother's concentrations.[10] The physiologically active metabolite 1,25(OH)2D does not readily cross the placenta.[11] However, the placenta and the fetal kidney express the enzyme 1α-hydroxylase that converts 25(OH)D to 1,25(OH)2D in these tissues, which may contribute to fetal circulating levels of 1,25(OH)2D.[11] In both the mother and the fetus, total 1,25(OH)2D concentrations increase by 100% to 200% starting in the first trimester, but most of this vitamin D is bound to vitamin D–binding protein. It is widely assumed that the nonprotein bound free hormone reflects the more biologic active form of vitamin D. Free 1,25(OH)2D concentrations have only been shown to be elevated in the last trimester[12] and may be implicated in labor initiation. Most recent studies have shown that 1,25(OH)2D regulates the secretion of placental hormones (i.e., estradiol and progesterone)[13] and prevents the induction of inflammatory cytokines that stimulate preeclampsia and premature labor.[14] These findings at least in part explain the observation that vitamin D–deficient women have a fivefold increased risk of developing preeclampsia.[15] After birth, maternal serum 25(OH)D and 1,25(OH)2D concentrations drop significantly, which is partially why breastfed infants need to be supplemented with vitamin D.

Figure 1.

Vitamin D effects on fetal development. In pregnancy, the fertilized egg undergoes a series of reproductive cell divisions to form three germ layers (i.e., endoderm, mesoderm, and ectoderm) that give rise to different types of cells, many of which express vitamin D receptors (VDR; denoted by a star). Different types of cells give rise to different organs through a process called organogenesis that extends from 4 to 10 weeks of gestation. During this time, localized concentrations of diverse nutrient (i.e., vitamin D) and their metabolites [i.e., 25(OH)D and 1,25(OH)2D] can interact with various signalling systems to regulate organ development. If we examine the timeline in Figure 2, the placenta is formed at 4 weeks of gestation. Placenta permits the transfer of 25(OH)D from the mother to the fetus. The placenta also produces 1α-OHase, allowing it to locally synthesize 1,25(OH)2D. The biologically active hormone 1,25(OH)2D binds to VDR in specialized cells to induce genomic and nongenomic responses that stimulate organ development. By 10 weeks of gestation, the organs are formed (i.e., heart, brain, liver, kidney, and intestine).


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