**1. Introduction**

The calciotropic role of vitamin D is well known from the early twentieth century. The recent advances in research opened a new perspective about vitamin D as prohormone with receptors in most tissues of the human body [1, 2]. This indicates additional non-calciotropic effects of vitamin D, such as its role in autoimmunity, chronic disease, infectious diseases, mental health issues, etc. [2]. However, the current dietary recommendations are based on only calciotropic effects of vitamin D although recent studies suggest that higher intakes are required to achieve the optimal vitamin in D status for both calciotropic and non-calciotropic benefits of vitamin D [2].

Pregnancy is a unique stage of life for women when the normal physiology of mother is changing in order to provide the nutritional needs for the growing fetus [3]. Those changes influence the vitamin D hemostasis and availability for the mother and the fetus. In this chapter, we provide an overview of the evidence about vitamin D metabolism during pregnancy, the association between maternal vitamin D status and pregnancy, fetal and postnatal outcomes. Further, we provide insight into the current recommendation for vitamin D intake to achieve optimal vitamin D status and the associated factors, particularly race and ethnicity. Finally, we review the existing policies and practices to assure optimal vitamin status in pregnant women and their offsprings.

### **2. Vitamin D metabolism during pregnancy**

Vitamin D homeostasis is altered during pregnancy in order to provide a successful delivery and optimal environment for the growth of the fetus. This section focuses on adaptive changes of vitamin D during pregnancy as a background for developing pregnancy and fetal related disorders.

Major vitamin D adaptations in pregnancy include: (1) maternal increase of calcitriol; (2) availability of maternal 25(OH)D for optimal neonatal 25(OH)D; (3) increased concentration of maternal vitamin D-binding protein (VDBP) and placental vitamin D receptor (VDR); and (4) increased activity of renal and placental 25(OH)D-1-α-hydroxylase (CYP27B1) [4, 5]. The first change is started in the first trimester, increasing the level of calcitriol in systemic circulation and placenta to 100–200% by the end of the third trimester [6]. It is originated mostly from the kidneys for the purpose of increased intestinal calcium absorption during pregnancy [7]. In fact, the activity of 1α hydroxylase increases while catabolism of calcitriol decreases leading to more intestinal calcium absorption and immune adaptation [8]. The additional contributors of increased maternal and placental calcitriol are prolactin, calcitonin, PTH-related peptide (PTH-rP), estradiol, placental lactogen [9], IGF-1 [10], and FGF23 [11]. Any dysregulation causing activation decrease and catabolism increase of 25(OH)D may lead to preeclamptic mothers, which will be discussed in this chapter [12].

The second adaptation is likely that the levels of 25(OH)D in cord blood are reduced on average 25% in comparison with maternal 25(OH)D [13]. Maternal 25(OH)D concentration remains constant during pregnancy, meaning that the increased level of calcitriol is not related to its precursor synthesis. Maternal 25(OH)D crosses the placenta barrier as the main source of vitamin D in the fetus [14]. Therefore, vitamin D insufficiency in pregnant mothers could affect the fetus. Other factors, including lifestyle, place of living, skin pigmentation, sunshine exposure, and obesity, contribute significantly to maternal vitamin D status during pregnancy [4]. Consequently, a low level of maternal vitamin D leads to impaired fetal 25(OH)D at birth.

The third adaptation is a 40–50% increase in the concentration of VDBP in both systemic circulation and placenta level compared to the non-pregnant woman reaching to a maximum level at the beginning of the third trimester, before starting to decrease by the end of gestation. This leads to a consistent decrease of free 25(OH)D from 15 to 36 weeks, since there is an inverse relationship between free 25(OH)D and VDBP concentration [15]. The mechanism has not fully understood, although studies suggested the high turnover rate of trophoblasts that are in contact with maternal blood directly leads to the increased expression of VDBP on the cell-surface of human placental trophoblasts during normal human pregnancy [16]. Studies conducted by Ma et al. and Liong et al. indicated that VDBP impairment,

**35**

D status.

**pregnancy**

population and individual level.

*Maternal Vitamin D Status among Different Ethnic Groups and Its Potential Contribution…*

either increase or decrease of its concentration, can contribute to the pathogenesis

Increased 1, 25(OH)D is attributed to the higher activity of CYP27B1 in maternal, kidney, placental trophoblasts, and decidua during pregnancy [22]. The mechanism by which CYP27B1 activity increases in pregnancy remains unclear. However, it has been suggested that PTH analog PTH-related peptide (PTH-rP), synthesized by fetal parathyroid and placenta, could be a potential regulatory factor

Vitamin D metabolism manifests significant changes in pregnant women compared to the non-pregnant state. In an optimal ongoing pregnancy, there are three striking alternation within a gestation; two-fold increase of calcitriol in the first trimester, versus about 25% reduction in the levels of 25(OH)D in cord blood as it crosses the placenta barrier and increase the expression of vitamin D receptor and regulatory metabolic enzymes in the placenta. Also, maternal increase of serum calcitriol and VDBP without changes in 25(OH)D and calcium concentration of mother indicates that neonatal vitamin D stores are dependent on maternal vitamin

**3. Current vitamin D intake recommendation guideline during** 

The role of vitamin D intake in pregnancy and its consequences for fetal growth

is the focus of current attention. The previous Dietary Reference Intake (DRI) review of vitamin D and Institute of Medicine (IOM) workshop on DRI research needs requested for research to evaluate the intake requirements for vitamin D as related to optimal circulating 25(OH)D concentrations across different life cycles and among different ethnic groups of Canadian and US populations [1]. **Table 1** summarizes different recommendations from various agencies which represents in

Health Canada [28] and IOM [1] have recommended dietary allowance of 600 IU/day and tolerable upper intake level of 4000 IU/day for pregnant women in the US and Canada would meet the daily need in 97.5% of the population. There is no consensus on the cut-off point for vitamin D insufficiency. To prevent rickets and osteomalacia, IOM recommended >50 nmol/L concentration of 25(OH)D. While, the Endocrine Society and Osteoporosis Canada suggested a target serum concentration >75 nmol/L based on the available evidence with the daily intake of 1500–2000 IU in order to achieve optimal benefits for skeletal and non-skeletal health [29, 30]. Accordingly, the Canadian Pediatric Society suggested 75 nmol/L as "sufficient" for pregnant and lactating women [31]. Moreover, several pilot studies have recommended that daily intake of 2000 [32], 4000 [33], or even 6400 IU [34] vitamin D would reduce vitamin D inadequacy without any toxicity sign in

The placenta is an important organ playing a pivotal role in the optimal embryonic improvement and healthy pregnancy. Placenta regulates vitamin D metabolism by its own mechanism [18]. In fact, 1-α-hydroxylase, 24-hydroxylase, VDBP, and VDR have all been detected in trophoblast cultures and in placenta tissue, resulting in local synthesis of 1,25(OH)2D in the maternal-fetal interface as extrarenal calcitriol. Moreover, in the placenta, VDR gene expression is higher within the first and second trimester compared to term placentas [19] and positively associated with transferring of calcium from mother-to-fetal. This indicates that VDR-dependent mechanisms in the placenta can affect fetal skeletal growth [20]. Vitamin D2 is metabolized in the placenta as well [21]. Thus, the placenta has its

*DOI: http://dx.doi.org/10.5772/intechopen.90766*

of preeclampsia (PET) and preterm birth [16, 17].

own mechanism in the regulation of vitamin D metabolism.

for CYP27B1 and augments during pregnancy [23].

#### *Maternal Vitamin D Status among Different Ethnic Groups and Its Potential Contribution… DOI: http://dx.doi.org/10.5772/intechopen.90766*

either increase or decrease of its concentration, can contribute to the pathogenesis of preeclampsia (PET) and preterm birth [16, 17].

The placenta is an important organ playing a pivotal role in the optimal embryonic improvement and healthy pregnancy. Placenta regulates vitamin D metabolism by its own mechanism [18]. In fact, 1-α-hydroxylase, 24-hydroxylase, VDBP, and VDR have all been detected in trophoblast cultures and in placenta tissue, resulting in local synthesis of 1,25(OH)2D in the maternal-fetal interface as extrarenal calcitriol. Moreover, in the placenta, VDR gene expression is higher within the first and second trimester compared to term placentas [19] and positively associated with transferring of calcium from mother-to-fetal. This indicates that VDR-dependent mechanisms in the placenta can affect fetal skeletal growth [20]. Vitamin D2 is metabolized in the placenta as well [21]. Thus, the placenta has its own mechanism in the regulation of vitamin D metabolism.

Increased 1, 25(OH)D is attributed to the higher activity of CYP27B1 in maternal, kidney, placental trophoblasts, and decidua during pregnancy [22]. The mechanism by which CYP27B1 activity increases in pregnancy remains unclear. However, it has been suggested that PTH analog PTH-related peptide (PTH-rP), synthesized by fetal parathyroid and placenta, could be a potential regulatory factor for CYP27B1 and augments during pregnancy [23].

Vitamin D metabolism manifests significant changes in pregnant women compared to the non-pregnant state. In an optimal ongoing pregnancy, there are three striking alternation within a gestation; two-fold increase of calcitriol in the first trimester, versus about 25% reduction in the levels of 25(OH)D in cord blood as it crosses the placenta barrier and increase the expression of vitamin D receptor and regulatory metabolic enzymes in the placenta. Also, maternal increase of serum calcitriol and VDBP without changes in 25(OH)D and calcium concentration of mother indicates that neonatal vitamin D stores are dependent on maternal vitamin D status.
