Relationship Between Vitamin D During Perinatal Development and Health

Jovana Kaludjerovic, MSc; Reinhold Vieth, PhD

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

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.

(Enlarge Image)

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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Cite this: Relationship Between Vitamin D During Perinatal Development and Health - Medscape - Nov 01, 2010.

Abstract and Introduction
Vitamin D Metabolism
Vitamin D Metabolism During Pregnancy and Lactation
How Does Vitamin D Modulate Human Health?
Vitamin D Effects on Bone Health
Vitamin D Effects on Brain Development
Vitamin D Effects on Heart Disease
The Effects of Early Vitamin D Exposure on Type 1 Diabetes
Current Vitamin D Recommendations and Target Levels for Serum 25(OH)D
Conclusion
References

Table 1. Epidemiologic Evidence Linking Vitamin D and Disease
Disease Relationship	Variables Used in Epidemiology to Infer a Relationship to Vitamin D
Disease Relationship	Sun Exposure	Migration Away From High Sun Exposure	Season of Birth	Skin Pigmentation	Dietary Vitamin D
Osteomalacia and rickets	Decreased sun exposure in third trimester is associated with decreased bone mass²⁹	Afro-Caribbean immigrants in the UK are associated with an increased incidence of rickets⁶⁸	To our knowledge, no epidemiologic studies have shown this relationship	Children with darker skin have a higher prevalence of having poor bone health and rickets^17,69,70	Low maternal 25(OH)D concentrations during pregnancy are associated with decreased bone mineral content in children at 9 years of age²⁹ Vitamin D deficiency in early life is associated with rickets, mild respiratory distress, weak muscle tone, decreased calcium and increased parathyroid hormone levels⁷¹
Multiple sclerosis (MS)	Increased sun exposure during early life is associated with a decreased risk of MS⁷² MS relapse is inversely associated with UV exposure and 25(OH)D levels⁷³	Indian and Pakistani immigrants who enter the UK between 0–4 years of age are at increased risk of having MS⁷⁴ Second-generation Afro-Caribbean immigrants in the UK are associated with an increased MS risk⁷⁵	Data pooled from 4 countries shows that spring births are associated with an increased MS risk and fall births are associated with a decreased MS risk⁷⁶	Having white skin lowers the prevalence of MS disability⁷⁷	Consumption of fish 3–4 times a week is associated with a decreased MS risk⁷² Diets low in fish but high in meat and dairy products are associated with an increased prevalence of MS⁷⁸ Intake of vitamin D from supplements is inversely associated with MS risk⁷⁹
Schizophrenia	Increased sun exposure is associated with decreased risks of having schizophrenia, and schizophrenia-induced symptoms are weaker and less regular⁸⁰	Second-generation immigrants from Morocco and Surinam to the Netherlands are associated with an increased risk of schizophrenia⁸¹ Afro-Caribbean immigrants to the UK are associated with an increased risk of schizophrenia⁸²	Data pooled from 6 countries shows that winter births are associated with an increased incidence of schizophrenia^{83, 84}	Having black skin may be associated with an increased incidence of schizophrenia⁸⁵	Vitamin D supplementation during the first year of life lowered the risk of developing schizophrenia in males, but not females⁸⁶ Maternal 25(OH)D was not a risk factor for schizophrenia. But the results in the black subgroup raise the possibility that below a certain threshold low levels of 25(OH)D may be associated with an increased risk of schizophrenia⁸⁵
Type 1 diabetes	Monthly sunshine availability is inversely associated with having type 1 diabetes⁸⁷	Children who migrated to an area prevalent in diabetes (northern region) had a greater risk of developing type 1 diabetes⁸⁸	Winter and spring births are associated with higher frequency of type 1 diabetes^89–91 than summer births⁹¹	Children with black skin are at a higher risk of having type 1 diabetes than children with white skin⁹²	In a meta-analysis, vitamin D supplementation was associated with a decreased risk of type 1 diabetes⁹³ Children who consumed vitamin D supplements had an 80% lower risk of having type 1 diabetes⁵⁵ Use of cod liver oil by mothers during pregnancy and infants in the first year of life lowered the infants' risk of developing type 1 diabetes⁵⁶

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