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

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 population and individual level.

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

*Vitamin D Deficiency*

women and their offsprings.

**2. Vitamin D metabolism during pregnancy**

developing pregnancy and fetal related disorders.

which will be discussed in this chapter [12].

fetal 25(OH)D at birth.

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

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

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,

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

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,

**34**


*25(OH)D, 25-hydroxyvitamin D; EAR, estimated average requirement; RI, recommended (individual) intake; AI, adequate intake; IOM, Institute of Medicine; NORDEN, Nordic Council of Ministers; SACN, Scientific Advisory Committee on Nutrition; EFSA, European Food Safety Authority. Table adapted from Kiely et al. [27].*

#### **Table 1.**

*Summary of the current dietary recommendations for vitamin D in pregnant women.*

pregnant women and their infants. The discrepancies in some factors, including different measurement tools of vitamin D levels, various patient populations and different sample sizes that were used in studies, might explain the differences in the recommendations. Because of conflicting evidences, identifying sufficient and upper-limit amount of vitamin D for pregnant women requires further research to be performed.
