**4.4 Bacterial vaginosis (BV)**

Bacterial vaginosis (BV) is a common vaginal infection in women in reproductive ages caused by the replacement of normal vaginal flora for mixed anaerobic bacteria [63]. Women diagnosed with BV are more likely to have preterm delivery [64]. Evidence indicates that vitamin D deficiency is an independent risk factor for bacterial vaginosis in pregnancy [65], and in several systematic reviews and metaanalysis articles, this association has been reported [5, 52, 55, 66]. The risk of BV increases from 3- to 5-fold for serum 25(OH)D values <75 to <30 nmol/L, respectively [67–69]. Therefore, several cross-sectional and observational studies consistently stated the plausible inverse association between vitamin D status and BV during pregnancy. A possible mechanism is related to immune responses regulated by calcitriol. In fact, as mentioned above, vitamin D activates potent antimicrobial peptide hCTD, an active peptide with broad-spectrum antimicrobial activity, in the placenta, macrophages and dendritic cells, inducing the innate immune responses [70]. These findings indicate that adequate vitamin D levels are crucial to enhance immunity, especially in pregnancy.

#### **4.5 Preterm delivery**

Preterm delivery is defined as birth completed before 37 weeks gestation [71]. Infection is the most common factor in preterm delivery [72]. Vitamin D plays as an anti-inflammatory and immunomodulatory factor, enabling to reduce the risk of preterm delivery in several plausible ways. One mechanism involves response reduction to microbial pathogens via cancelation of IL-1, IL-6, and TNF-alpha production by macrophages [73]. Uterine immune cells, such as dendritic cells, macrophages, and natural killer cells are modulated by vitamin D [74], and vitamin D receptors are expressed in the ovary, endometrium, and myometrium to maintain reproductive health [75].

There are conflicting findings regarding the effect of Vitamin D on preterm delivery. Some articles including critical and narrative reviews, reported no association between vitamin D deficiency and preterm delivery [43, 46, 76, 77], while single studies, systematic review, and meta-analysis showed significant relationship between them [45, 78–81]. Inconsistent findings can be explained by different designs of each study including the timing of 25(OH)D assessment, and different definition of preterm delivery. For instance, in two studies, ≤35 weeks gestation for preterm delivery was considered [78, 82], while in another study it was <37 weeks gestation [77].

Ethnicity appears to be an important factor regarding preterm birth. Bodnar et al. reported that the risk of preterm delivery increased only in non-white mothers compared to white women [82]. In a cohort study by Wagner et al., Hispanic women with serum 25(OH)D > 40 ng/ml had 79% reduced risk of preterm birth in comparison with those with serum 25(OH)D ≤ 20 ng/ml, while the reduced risk was

**39**

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

45% among black women [83]. Also, an increased risk of preterm birth associated with Vitamin D insufficiency in ethnic minority women in Canada [84] suggests the stratification of women based on their ethnicity in further studies. Another important thing should be considered in study design is the association of vitamin D status in different gestational age with pregnancy outcome. For instance, one study suggested that maternal vitamin D status closest to delivery time was the best indicator for preterm birth because of the more significant reduced risk in the third semester compared to serum concentrations of vitamin D in the first and second semesters [85]. Thus, vitamin D deficiency is likely to be associated with preterm birth, nevertheless, to investigate the explicit relationship between vitamin D status and preterm delivery several factors should be noted including the timing of 25(OH)D assessment (first, second, or third trimester), ethnicity, precise definition of preterm birth, different study design such as human interventional and cohort

Uterine muscle and skeletal muscle cells have VDR, which is a regulator of the contractile proteins of uterine myometrial cells [86]. Therefore, the strength of the contractile muscles is decreased with vitamin D deficiency as well as malformation of the pelvis, which are indications for C-section [87]. The indication of C-section can be related to vitamin D deficiency, but there is a mixture of results regarding this association. For example, prospective cohort studies suggested there was an inverse association with having a cesarean section and serum 25(OH)D levels [88–90], whereas others did not support this relationship [76, 87, 91]. Regarding ethnicity, in a cohort multi-ethnic Asian study, vitamin D deficiency was related to a higher risk of C-sections in Chinese and Indian women compared to Malay women [86]. Factors such as the different definition of C-section in terms of indication, primary or secondary, emergency or elective might be the reason of inconclusive findings [91]. Although observational studies mentioned above investigated a possible relationship between vitamin D and cesarean delivery, more studies are needed to verify this association along with biological and geographical factors.

Recurrent pregnancy losses (RPL) and repeated implantation failures (RIF) are two auto- and cellular immune abnormalities, and vitamin D deficiency is prevalent in women with RPL and RIF. Vitamin D plays a pivotal role in the regulation of auto- and cellular immune disorders [92]. Studies reported that 45% of RPL patients had vitamin D deficiency in one study, and increased risk of first-trimester miscarriage and recurrent pregnancy losses (RPL) was found with vitamin D insufficiency [93, 94]. Even this association has been found in early spontaneous pregnancy loss [95]. Studies show an inverse association between vitamin D deficiency and RPL; however, no conclusion can be drawn based on the findings of a few studies and more observational and

Other outcomes including spontaneous abortion [77, 96, 97] and stillbirth [77, 96], short gestational length [98], and low Apgar score [76, 96, 98] were not associated with vitamin D insufficiency, according to a systematic review and metaanalysis of longitudinal studies [99]. However, more studies with different designs such as clinical trials are necessary. Anemia, lipid disorders, periodontal disease,

interventional studies are necessary to confirm such association [43].

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

studies.

**4.6 Cesarean delivery**

**4.7 Recurrent pregnancy losses (RPL)**

**4.8 Other related outcomes**

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

45% among black women [83]. Also, an increased risk of preterm birth associated with Vitamin D insufficiency in ethnic minority women in Canada [84] suggests the stratification of women based on their ethnicity in further studies. Another important thing should be considered in study design is the association of vitamin D status in different gestational age with pregnancy outcome. For instance, one study suggested that maternal vitamin D status closest to delivery time was the best indicator for preterm birth because of the more significant reduced risk in the third semester compared to serum concentrations of vitamin D in the first and second semesters [85]. Thus, vitamin D deficiency is likely to be associated with preterm birth, nevertheless, to investigate the explicit relationship between vitamin D status and preterm delivery several factors should be noted including the timing of 25(OH)D assessment (first, second, or third trimester), ethnicity, precise definition of preterm birth, different study design such as human interventional and cohort studies.

#### **4.6 Cesarean delivery**

*Vitamin D Deficiency*

for more extensive studies in this regard.

**4.4 Bacterial vaginosis (BV)**

immunity, especially in pregnancy.

**4.5 Preterm delivery**

reproductive health [75].

gestation [77].

Furthermore, vitamin D protects the brain from oxidative stress by preserving the antioxidant glutathione in the brain [55, 56]. Most studies suggested there is an inverse association between vitamin D serum in different stages of gestation and postpartum depression [57–59]. In contrast, some studies indicate no association [60, 61], and even increased risk of PPD with sufficient vitamin D concentrations (≥50 nmol/L) [62]. However, in a systematic review study, a few studies reported the role of vitamin D in this pregnancy outcome [44]. Thus, although postpartum depression might be associated with vitamin D deficiency, inconsistent results need

Bacterial vaginosis (BV) is a common vaginal infection in women in reproductive ages caused by the replacement of normal vaginal flora for mixed anaerobic bacteria [63]. Women diagnosed with BV are more likely to have preterm delivery [64]. Evidence indicates that vitamin D deficiency is an independent risk factor for bacterial vaginosis in pregnancy [65], and in several systematic reviews and metaanalysis articles, this association has been reported [5, 52, 55, 66]. The risk of BV increases from 3- to 5-fold for serum 25(OH)D values <75 to <30 nmol/L, respectively [67–69]. Therefore, several cross-sectional and observational studies consistently stated the plausible inverse association between vitamin D status and BV during pregnancy. A possible mechanism is related to immune responses regulated by calcitriol. In fact, as mentioned above, vitamin D activates potent antimicrobial peptide hCTD, an active peptide with broad-spectrum antimicrobial activity, in the placenta, macrophages and dendritic cells, inducing the innate immune responses [70]. These findings indicate that adequate vitamin D levels are crucial to enhance

Preterm delivery is defined as birth completed before 37 weeks gestation [71]. Infection is the most common factor in preterm delivery [72]. Vitamin D plays as an anti-inflammatory and immunomodulatory factor, enabling to reduce the risk of preterm delivery in several plausible ways. One mechanism involves response reduction to microbial pathogens via cancelation of IL-1, IL-6, and TNF-alpha production by macrophages [73]. Uterine immune cells, such as dendritic cells, macrophages, and natural killer cells are modulated by vitamin D [74], and vitamin D receptors are expressed in the ovary, endometrium, and myometrium to maintain

There are conflicting findings regarding the effect of Vitamin D on preterm delivery. Some articles including critical and narrative reviews, reported no association between vitamin D deficiency and preterm delivery [43, 46, 76, 77], while single studies, systematic review, and meta-analysis showed significant relationship between them [45, 78–81]. Inconsistent findings can be explained by different designs of each study including the timing of 25(OH)D assessment, and different definition of preterm delivery. For instance, in two studies, ≤35 weeks gestation for preterm delivery was considered [78, 82], while in another study it was <37 weeks

Ethnicity appears to be an important factor regarding preterm birth. Bodnar et al. reported that the risk of preterm delivery increased only in non-white mothers compared to white women [82]. In a cohort study by Wagner et al., Hispanic women with serum 25(OH)D > 40 ng/ml had 79% reduced risk of preterm birth in comparison with those with serum 25(OH)D ≤ 20 ng/ml, while the reduced risk was

**38**

Uterine muscle and skeletal muscle cells have VDR, which is a regulator of the contractile proteins of uterine myometrial cells [86]. Therefore, the strength of the contractile muscles is decreased with vitamin D deficiency as well as malformation of the pelvis, which are indications for C-section [87]. The indication of C-section can be related to vitamin D deficiency, but there is a mixture of results regarding this association. For example, prospective cohort studies suggested there was an inverse association with having a cesarean section and serum 25(OH)D levels [88–90], whereas others did not support this relationship [76, 87, 91]. Regarding ethnicity, in a cohort multi-ethnic Asian study, vitamin D deficiency was related to a higher risk of C-sections in Chinese and Indian women compared to Malay women [86]. Factors such as the different definition of C-section in terms of indication, primary or secondary, emergency or elective might be the reason of inconclusive findings [91]. Although observational studies mentioned above investigated a possible relationship between vitamin D and cesarean delivery, more studies are needed to verify this association along with biological and geographical factors.

#### **4.7 Recurrent pregnancy losses (RPL)**

Recurrent pregnancy losses (RPL) and repeated implantation failures (RIF) are two auto- and cellular immune abnormalities, and vitamin D deficiency is prevalent in women with RPL and RIF. Vitamin D plays a pivotal role in the regulation of auto- and cellular immune disorders [92]. Studies reported that 45% of RPL patients had vitamin D deficiency in one study, and increased risk of first-trimester miscarriage and recurrent pregnancy losses (RPL) was found with vitamin D insufficiency [93, 94]. Even this association has been found in early spontaneous pregnancy loss [95]. Studies show an inverse association between vitamin D deficiency and RPL; however, no conclusion can be drawn based on the findings of a few studies and more observational and interventional studies are necessary to confirm such association [43].

#### **4.8 Other related outcomes**

Other outcomes including spontaneous abortion [77, 96, 97] and stillbirth [77, 96], short gestational length [98], and low Apgar score [76, 96, 98] were not associated with vitamin D insufficiency, according to a systematic review and metaanalysis of longitudinal studies [99]. However, more studies with different designs such as clinical trials are necessary. Anemia, lipid disorders, periodontal disease,

and HIV-related mortality are other pregnancy implications related to vitamin D deficiency. There is a mixture of results with regard to the vitamin D deficiency and anemia in pregnancy. Some studies indicated this relationship [100], while other studies failed to support it [76, 101]. The findings show a positive correlation between serum vitamin D and atherogenic factors such as total cholesterol and triglycerides [102, 103]. As vitamin D has immunomodulatory effects, it may have a protective role against mother-to-child transmission (MTCT) of the human immunodeficiency virus (HIV). A study on HIV-infected pregnant women conducted in Tanzania found that low maternal vitamin D level (<32 ng/mL) at 12–27 weeks gestation was associated with a 50% higher risk of MTCT of HIV [104]. Moreover, vitamin D insufficiency (serum 25[OH]D < 75 nmol/l) was associated with maternal periodontal disease during pregnancy, as reported by Boggess et al. [105].

Almost all the pregnancy complications related to vitamin D deficiency were discussed in this section. However, the results were contradictory due to small study samples in some studies, cross-sectional design, lack of adjustment for seasonal variation, race and ethnicity, various study design in terms of the trimester (first, second, or third trimester), different definition of some outcomes and even cut points to categorize vitamin D status. These inconsistencies justify the need for more large-scale prospective studies and interventional studies to evaluate these associations comprehensively.

## **5. Maternal vitamin D status across different ethnic groups**

Vitamin D deficiency has been reported among pregnant women globally, particularly among ethnic minorities and white women residents at high latitude [106]. Ethnic variety in vitamin D status of pregnant women can be relevant to large disparities in skin color, vitamin D intake, religion, culture, sun exposure (seasonal variation), and geographical location [107]. In ethnic minorities, the prevention of vitamin D deficiency on a population basis is challenging due to the shortage of clarity surrounding the metabolism and transport of vitamin D [108]. Due to lack of enough evidence regarding the nutritional requirements for vitamin D during pregnancy, there is no pregnancy-specific dietary recommendation for vitamin D. In addition, the question of specific dietary reference setting specifically for each ethnicity (for pregnant women) has not been addressed to date [109].

The best indicator of vitamin D status is the serum 25(OH)D concentration, because it is not regulated, and reflects both dietary intake and synthesis form of vitamin D [110]. However, there is no absolute agreement on normal range of vitamin D, although most authors have consensus that serum 25(OH)D concentration should be ≥50 nmol/L [110–112]. Ethnic differences in vitamin D status are in accordance with the ethnic differences in circulating vitamin D, where a mean value of 57 nmol/L has been reported for Caucasian pregnant women in Canada [113], a median value of 53 nmol/L has been reported for Belgian women [114], 57 nmol/L has been reported for pregnant women in Australia [115]. A cohort study in 2011 indicated that the mean 25(OH)D level in African-Americans was 38.75 nmol/L, Hispanics was 60.25 nmol/L, and Caucasians was 72.5 nmol/L [116]. African-American pregnant women had the lowest serum 25(OH)D in this study. However, in Southern Europe, Morales et al. demonstrated a median plasma value of 25(OH)D in pregnancy of 73.88 nmol/L [117]. Furthermore, a recent systematic review reported that mean 25(OH)D levels in the general populations were higher in America (North America) (75 nmol/L) than in the Middle East (50 nmol /L) or Europe (52 nmol/L) [118].

The absence of race- and pregnancy-specific dietary recommendations places pregnant women of the ethnic minority among the most vulnerable and

**41**

**Table 2.**

*\**

*Adopted by Saraf et al. [106].*

*Vitamin D deficiency. \*\*Severe vitamin D deficiency.*

*\*\*\*Not available.*

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

under-investigated population groups concerning vitamin D [106]. A review study indicated that pregnant women in Latin America, Asia, the Middle East, and Africa are at the danger of vitamin D deficiency and these are known as the topmost universally locations for occurrence of vitamin D deficiency and reported that incidence of vitamin D deficiency varied from 51.3 to 100% [119]. Recent studies in the United States, Canada, Australia, Iran, Sweden, and Pakistan reported that the range of vitamin D deficiency and insufficiency were 24–95.8% and 54–100% among pregnant women [116, 120–125]. The evidence for racial differences in vitamin D deficiency (**Table 2**) indicated that the global prevalence of 25(OH)D concentrations <50 nmol/L is 54% among pregnant women and 75% among newborns [106]. In other words, one in five pregnant women (18%) and one in three newborns (20%) had serum vitamin D concentration <25 nmol/L, which is a public health concern [106]. Vitamin D status is poorly defined in the South-East Asian, African, and Eastern Mediterranean regions and the non-European population in

Maternal vitamin D deficiency is also investigated for each trimester across different regions and ethnicities. For instance, in Thai pregnant women, high prevalence of vitamin D deficiency and inadequacy were reported in the first trimester: 26.7% (<50 nmol/l) and 56.7% (<75 nmol/l), respectively. Then, vitamin D inadequacy decreased to 30.9% (1.8% deficiency) in the second trimester and 27.4% (2.8% deficiency) in the third trimester [120]. Pregnant women were studied in the first trimester of pregnancy (gestational week 11–14) living in Mediterranean seacoast at latitude 36°N, therefore at a high sun exposure area, were classified as Spanish Caucasians and Arab immigrants [121]. The median serum 25(OH)D concentration for the whole sample was 68.39 nmol/L. Only 35.9% of the participants had adequate serum 25(OH)D concentrations (75 nmol/L), while these concentrations were found to be inadequate (50–75 nmol/L) in 41.4% and deficient (<50 nmol/L) in 22.7% of respondents. Vitamin D status was lower in Arab women in comparison to Caucasian women [121]. Another study reported that in second trimester 40.7% (<50 nmol/L) of Chinese pregnant women who lived at their urban locations had vitamin D deficiency [122]. According to a cross-sectional study in China, 74.9% of Chinese pregnant women had vitamin D shortage (25-hydroxyvi-

tamin D < 50 nmol/L) [123]. In one of the National Health and Nutrition

Examination Survey (NHANES) studies reported that among different factors, the largest magnitude of association was observed between race and 25(OH)D status. Those who were non-Hispanic whites in third trimester had a higher vitamin D levels (93 nmol/L) than non-Hispanic black (45 nmol/L) or Hispanic (69 nmol/L).

**WHO regions Percentage of 25-hydroxyvitamin D deficiency % < 25\***

Americas 64 9 European 57 23 Eastern Mediterranean 46 79 South-East Asian 87 N/A\*\*\* Western pacific 83 13

*Prevalence of maternal vitamin D deficiency classified by WHO region.*

**(nmol/L) % <50\*\* (nmol/L)**

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

the Western Pacific region (**Table 2**) [106].

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

under-investigated population groups concerning vitamin D [106]. A review study indicated that pregnant women in Latin America, Asia, the Middle East, and Africa are at the danger of vitamin D deficiency and these are known as the topmost universally locations for occurrence of vitamin D deficiency and reported that incidence of vitamin D deficiency varied from 51.3 to 100% [119]. Recent studies in the United States, Canada, Australia, Iran, Sweden, and Pakistan reported that the range of vitamin D deficiency and insufficiency were 24–95.8% and 54–100% among pregnant women [116, 120–125]. The evidence for racial differences in vitamin D deficiency (**Table 2**) indicated that the global prevalence of 25(OH)D concentrations <50 nmol/L is 54% among pregnant women and 75% among newborns [106]. In other words, one in five pregnant women (18%) and one in three newborns (20%) had serum vitamin D concentration <25 nmol/L, which is a public health concern [106]. Vitamin D status is poorly defined in the South-East Asian, African, and Eastern Mediterranean regions and the non-European population in the Western Pacific region (**Table 2**) [106].

Maternal vitamin D deficiency is also investigated for each trimester across different regions and ethnicities. For instance, in Thai pregnant women, high prevalence of vitamin D deficiency and inadequacy were reported in the first trimester: 26.7% (<50 nmol/l) and 56.7% (<75 nmol/l), respectively. Then, vitamin D inadequacy decreased to 30.9% (1.8% deficiency) in the second trimester and 27.4% (2.8% deficiency) in the third trimester [120]. Pregnant women were studied in the first trimester of pregnancy (gestational week 11–14) living in Mediterranean seacoast at latitude 36°N, therefore at a high sun exposure area, were classified as Spanish Caucasians and Arab immigrants [121]. The median serum 25(OH)D concentration for the whole sample was 68.39 nmol/L. Only 35.9% of the participants had adequate serum 25(OH)D concentrations (75 nmol/L), while these concentrations were found to be inadequate (50–75 nmol/L) in 41.4% and deficient (<50 nmol/L) in 22.7% of respondents. Vitamin D status was lower in Arab women in comparison to Caucasian women [121]. Another study reported that in second trimester 40.7% (<50 nmol/L) of Chinese pregnant women who lived at their urban locations had vitamin D deficiency [122]. According to a cross-sectional study in China, 74.9% of Chinese pregnant women had vitamin D shortage (25-hydroxyvitamin D < 50 nmol/L) [123]. In one of the National Health and Nutrition Examination Survey (NHANES) studies reported that among different factors, the largest magnitude of association was observed between race and 25(OH)D status. Those who were non-Hispanic whites in third trimester had a higher vitamin D levels (93 nmol/L) than non-Hispanic black (45 nmol/L) or Hispanic (69 nmol/L).


#### **Table 2.**

*Prevalence of maternal vitamin D deficiency classified by WHO region.*

*Vitamin D Deficiency*

associations comprehensively.

and HIV-related mortality are other pregnancy implications related to vitamin D deficiency. There is a mixture of results with regard to the vitamin D deficiency and anemia in pregnancy. Some studies indicated this relationship [100], while other studies failed to support it [76, 101]. The findings show a positive correlation between serum vitamin D and atherogenic factors such as total cholesterol and triglycerides [102, 103]. As vitamin D has immunomodulatory effects, it may have a protective role against mother-to-child transmission (MTCT) of the human immunodeficiency virus (HIV). A study on HIV-infected pregnant women conducted in Tanzania found that low maternal vitamin D level (<32 ng/mL) at 12–27 weeks gestation was associated with a 50% higher risk of MTCT of HIV [104]. Moreover, vitamin D insufficiency (serum 25[OH]D < 75 nmol/l) was associated with maternal periodontal disease during pregnancy, as reported by Boggess et al. [105]. Almost all the pregnancy complications related to vitamin D deficiency were discussed in this section. However, the results were contradictory due to small study samples in some studies, cross-sectional design, lack of adjustment for seasonal variation, race and ethnicity, various study design in terms of the trimester (first, second, or third trimester), different definition of some outcomes and even cut points to categorize vitamin D status. These inconsistencies justify the need for more large-scale prospective studies and interventional studies to evaluate these

**5. Maternal vitamin D status across different ethnic groups**

ethnicity (for pregnant women) has not been addressed to date [109].

Vitamin D deficiency has been reported among pregnant women globally, particularly among ethnic minorities and white women residents at high latitude [106]. Ethnic variety in vitamin D status of pregnant women can be relevant to large disparities in skin color, vitamin D intake, religion, culture, sun exposure (seasonal variation), and geographical location [107]. In ethnic minorities, the prevention of vitamin D deficiency on a population basis is challenging due to the shortage of clarity surrounding the metabolism and transport of vitamin D [108]. Due to lack of enough evidence regarding the nutritional requirements for vitamin D during pregnancy, there is no pregnancy-specific dietary recommendation for vitamin D. In addition, the question of specific dietary reference setting specifically for each

The best indicator of vitamin D status is the serum 25(OH)D concentration, because it is not regulated, and reflects both dietary intake and synthesis form of vitamin D [110]. However, there is no absolute agreement on normal range of vitamin D, although most authors have consensus that serum 25(OH)D concentration should be ≥50 nmol/L [110–112]. Ethnic differences in vitamin D status are in accordance with the ethnic differences in circulating vitamin D, where a mean value of 57 nmol/L has been reported for Caucasian pregnant women in Canada [113], a median value of 53 nmol/L has been reported for Belgian women [114], 57 nmol/L has been reported for pregnant women in Australia [115]. A cohort study in 2011 indicated that the mean 25(OH)D level in African-Americans was 38.75 nmol/L, Hispanics was 60.25 nmol/L, and Caucasians was 72.5 nmol/L [116]. African-American pregnant women had the lowest serum 25(OH)D in this study. However, in Southern Europe, Morales et al. demonstrated a median plasma value of 25(OH)D in pregnancy of 73.88 nmol/L [117]. Furthermore, a recent systematic review reported that mean 25(OH)D levels in the general populations were higher in America (North America) (75 nmol/L) than in the Middle East (50 nmol /L) or Europe (52 nmol/L) [118]. The absence of race- and pregnancy-specific dietary recommendations places pregnant women of the ethnic minority among the most vulnerable and

**40**

Vitamin D insufficiency in this study was 13%, 54% among whites, 80%, 95% among blacks, and 45%, 83% among Hispanics for 25(OH)D concentrations <50 and <75 nmol/L, respectively [124]. A recent cohort study reported that 44% of non-European pregnant women in the Netherland had vitamin D deficiency compared to European ones either with maternal serum or cord blood [125]. While from one of the Persian Gulf countries (United Arab Emirates (UAE)), 69% of vitamin D deficiency was reported among pregnant women [126].

Generally, previous recommendations have indicated that winter, higher latitude, dark pigmentation, season, limited sun exposure, and dressing style as risk factors for vitamin D deficiency. It can be difficult to describe the prevalence of pregnant women at risk to vitamin D deficiency because vitamin D status varies according to how deficiency is defined, as well as aforementioned risk factors [127–129]. These studies indicated that despite the geographical location of each region, vitamin D deficiency is highly prevalent among pregnant women because of the lifestyle and nutrition status of mothers. Future studies are required to investigate vitamin D deficiency of pregnant women among different ethnic groups based on similar cut-off values for vitamin D deficiency.

As we discussed in Section 4, vitamin D deficiency has a key role in the development of PET and GDM. In this section, we elaborate on the differences that the occurrence of these two diseases might have among different ethnic groups.

### **5.1 PET and GDM among ethnic disparities**

Pregnant minorities have been the least studied in vitamin D-related diseases such as PET and GDM. According to a meta-analysis, the occurrence of PET is seen at lower vitamin D levels due to the immunomodulation properties of vitamin D [52]. A recent study examined the evidence linking vitamin D deficiency in pregnancy to PET among different ethnic groups. Although prevalence of vitamin D deficiency differed significantly among African-Americans (72.3%), Hispanics (10.6%), and Caucasians (2.1%), there were no direct associations between low 25(OH)D levels and risk for PET among different ethnic groups [130]. While another recent study in UK indicated a greater prevalence of white British women developed GHT (12.0%) and PET (3.4%), compared to Pakistani women (the proportion of GHT and PET were 5.4 and 1.7%, respectively) [131]. The heterogeneity that exists among studies in terms of sun exposure (naturally occurring vitamin D synthesized from), geographical locations, considering different ethnic groups with divergent cultures, may lead to the differences in results.

It has been shown that maternal vitamin D concentration has inversely been linked to impaired glucose metabolism in pregnancy [132]. A few studies considered the effect of ethnicity on this relationship in pregnancy such as Clifton et al. study in Australia, which examined the association between serum 25(OH)D with GDM among five different ethnic groups including European (European Australian, English, German, Spanish), South-East Asian (Chinese, Japanese, Korean, Indonesian, Thai, Malaysian), Asian (Indian, Pakistani, Bangladeshi, Sri Lankan), Middle Eastern (Iranian, Iraqi, Lebanese, Syrian), and Other (Aboriginal Australian, Samoan, Papua New Guinean). They found no significant association between 25(OH)D and GDM in any ethnic group [132]. Generally, ethnicity was not an independent predictor of insulin resistance.

Overall, well-designed prospective cohort studies are needed to inform and update our knowledge regarding vitamin D deficiency and its association with PET and GDM among different ethnic minorities.

**43**

countries.

**5.3 Skin pigmentation**

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

Sun exposure decreases dramatically, with increasing latitude [129]. It seems logical that higher latitudes would report a higher proportion of vitamin D deficiency like Northern European countries, in comparison to the European South. In addition, almost all European Mediterranean countries are located at a high latitude (37–38°N), and previtamin D3 photosynthesis is lower during winter. Similar or even smaller proportion of vitamin D deficiency among pregnant women was reported from countries with higher latitudes in Western and Central Europe (latitudes 46–81°N) [133]; Slovenia with 46.5°N latitude, showed a high prevalence of severe vitamin D deficiency (23.6% with the threshold of <25 nmol/l) among pregnant women [134]. Even if in lower latitudes, the prevalence of maternal vitamin D deficiency is still high such as a study in China demonstrated that over 90% of pregnant women in urban northern China (39.9°N), had vitamin D deficiency (<50 nmol/l) and none had normal 25(OH)D concentrations (≥75 nmol/L) [135]. Although the Goulburn Valley in Northern Victoria (Australia) experiences abundant sunshine and located at 36° South of the equator, a place where vitamin D synthesis is possible during the year, 49.4% of pregnant women (<75 nmol/l) had vitamin D inadequacy and 12.2% (25–50 nmol/L) of pregnant women had a mild deficiency and 3.2% (<25 nmol/l) suffered a moderate/severe deficiency in summer [136]. A recent study from Bangkok, Thailand also revealed that 23.3% of Thai pregnant women had vitamin D deficiency in fall and 44.6% in winter (<50 nmol/L), despite the fact that this city is located at 13.45 N latitude and

Over the past few decades, several studies have reported a high prevalence of maternal vitamin D deficiency in countries where women wear concealing clothing such as India (31%) [138], Saudi Arabia (14.2%) [139], and Iran (5.7%) [140] and countries in northern latitudes such as the United Kingdom (21.2%) [141] and Norway (33% deficiency and 18% severe deficiency across three ethnic groups) [142]. Due to less sunlight exposure, these pregnant women are at high risk of vitamin D deficiency. The duration of sun exposure is directly associated with the concentration of 25(OH)D [135, 138]. Mothers with less than 0.5 h/day of sun exposure had a higher prevalence of vitamin D deficiency (38.4%) in China, which would worsen the situation in winter that the tendency toward outdoor physical activity decrease among pregnant women [135]. However, in sunny regions like Turkey, vitamin D deficiency among pregnant women is still a serious problem with the prevalence of 90% [143]. In addition, the prevalence of vitamin D deficiency (48%) was noted among pregnant women in South Carolina at latitude 32°N, where women lived in a sun-rich climate for most of the year [144]. Despite the longer duration of sunlight in UAE (ranges from 9 to 11 h), 69% of pregnant women suffer from vitamin D deficiency. It can be due to the decrease in time spent on outdoor activities and to the dressing style, which limits the surface area exposed to the sun [126]. Overall, latitude is an important factor but the other factors such as culture, belief, indoor lifestyle, etc., would play key roles in vitamin D deficiency in sun-rich

Skin pigmentation is the main determinant of ultraviolet B-rays (UV-B) absorp-

tion in humans [129]. The absorption of UV-B would be more when the skin is pale compared with the darker skin. In other words, the probability of vitamin D deficiency would be higher when skin pigmentation increases in critical periods

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

benefits sunlight throughout the year [137].

**5.2 Latitude**

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

#### **5.2 Latitude**

*Vitamin D Deficiency*

Vitamin D insufficiency in this study was 13%, 54% among whites, 80%, 95% among blacks, and 45%, 83% among Hispanics for 25(OH)D concentrations <50 and <75 nmol/L, respectively [124]. A recent cohort study reported that 44% of non-European pregnant women in the Netherland had vitamin D deficiency compared to European ones either with maternal serum or cord blood [125]. While from one of the Persian Gulf countries (United Arab Emirates (UAE)), 69% of vitamin D

Generally, previous recommendations have indicated that winter, higher latitude, dark pigmentation, season, limited sun exposure, and dressing style as risk factors for vitamin D deficiency. It can be difficult to describe the prevalence of pregnant women at risk to vitamin D deficiency because vitamin D status varies according to how deficiency is defined, as well as aforementioned risk factors [127–129]. These studies indicated that despite the geographical location of each region, vitamin D deficiency is highly prevalent among pregnant women because of the lifestyle and nutrition status of mothers. Future studies are required to investigate vitamin D deficiency of pregnant women among different ethnic groups based

As we discussed in Section 4, vitamin D deficiency has a key role in the development of PET and GDM. In this section, we elaborate on the differences that the occurrence of these two diseases might have among different ethnic groups.

Pregnant minorities have been the least studied in vitamin D-related diseases such as PET and GDM. According to a meta-analysis, the occurrence of PET is seen at lower vitamin D levels due to the immunomodulation properties of vitamin D [52]. A recent study examined the evidence linking vitamin D deficiency in pregnancy to PET among different ethnic groups. Although prevalence of vitamin D deficiency differed significantly among African-Americans (72.3%), Hispanics (10.6%), and Caucasians (2.1%), there were no direct associations between low 25(OH)D levels and risk for PET among different ethnic groups [130]. While another recent study in UK indicated a greater prevalence of white British women developed GHT (12.0%) and PET (3.4%), compared to Pakistani women (the proportion of GHT and PET were 5.4 and 1.7%, respectively) [131]. The heterogeneity that exists among studies in terms of sun exposure (naturally occurring vitamin D synthesized from), geographical locations, considering different ethnic groups with divergent cultures, may lead to the differences in

It has been shown that maternal vitamin D concentration has inversely been linked to impaired glucose metabolism in pregnancy [132]. A few studies considered the effect of ethnicity on this relationship in pregnancy such as Clifton et al. study in Australia, which examined the association between serum 25(OH)D with GDM among five different ethnic groups including European (European Australian, English, German, Spanish), South-East Asian (Chinese, Japanese, Korean, Indonesian, Thai, Malaysian), Asian (Indian, Pakistani, Bangladeshi, Sri Lankan), Middle Eastern (Iranian, Iraqi, Lebanese, Syrian), and Other (Aboriginal Australian, Samoan, Papua New Guinean). They found no significant association between 25(OH)D and GDM in any ethnic group [132]. Generally, ethnicity was not

Overall, well-designed prospective cohort studies are needed to inform and update our knowledge regarding vitamin D deficiency and its association with PET

deficiency was reported among pregnant women [126].

on similar cut-off values for vitamin D deficiency.

**5.1 PET and GDM among ethnic disparities**

an independent predictor of insulin resistance.

and GDM among different ethnic minorities.

**42**

results.

Sun exposure decreases dramatically, with increasing latitude [129]. It seems logical that higher latitudes would report a higher proportion of vitamin D deficiency like Northern European countries, in comparison to the European South. In addition, almost all European Mediterranean countries are located at a high latitude (37–38°N), and previtamin D3 photosynthesis is lower during winter. Similar or even smaller proportion of vitamin D deficiency among pregnant women was reported from countries with higher latitudes in Western and Central Europe (latitudes 46–81°N) [133]; Slovenia with 46.5°N latitude, showed a high prevalence of severe vitamin D deficiency (23.6% with the threshold of <25 nmol/l) among pregnant women [134]. Even if in lower latitudes, the prevalence of maternal vitamin D deficiency is still high such as a study in China demonstrated that over 90% of pregnant women in urban northern China (39.9°N), had vitamin D deficiency (<50 nmol/l) and none had normal 25(OH)D concentrations (≥75 nmol/L) [135]. Although the Goulburn Valley in Northern Victoria (Australia) experiences abundant sunshine and located at 36° South of the equator, a place where vitamin D synthesis is possible during the year, 49.4% of pregnant women (<75 nmol/l) had vitamin D inadequacy and 12.2% (25–50 nmol/L) of pregnant women had a mild deficiency and 3.2% (<25 nmol/l) suffered a moderate/severe deficiency in summer [136]. A recent study from Bangkok, Thailand also revealed that 23.3% of Thai pregnant women had vitamin D deficiency in fall and 44.6% in winter (<50 nmol/L), despite the fact that this city is located at 13.45 N latitude and benefits sunlight throughout the year [137].

Over the past few decades, several studies have reported a high prevalence of maternal vitamin D deficiency in countries where women wear concealing clothing such as India (31%) [138], Saudi Arabia (14.2%) [139], and Iran (5.7%) [140] and countries in northern latitudes such as the United Kingdom (21.2%) [141] and Norway (33% deficiency and 18% severe deficiency across three ethnic groups) [142]. Due to less sunlight exposure, these pregnant women are at high risk of vitamin D deficiency. The duration of sun exposure is directly associated with the concentration of 25(OH)D [135, 138]. Mothers with less than 0.5 h/day of sun exposure had a higher prevalence of vitamin D deficiency (38.4%) in China, which would worsen the situation in winter that the tendency toward outdoor physical activity decrease among pregnant women [135]. However, in sunny regions like Turkey, vitamin D deficiency among pregnant women is still a serious problem with the prevalence of 90% [143]. In addition, the prevalence of vitamin D deficiency (48%) was noted among pregnant women in South Carolina at latitude 32°N, where women lived in a sun-rich climate for most of the year [144]. Despite the longer duration of sunlight in UAE (ranges from 9 to 11 h), 69% of pregnant women suffer from vitamin D deficiency. It can be due to the decrease in time spent on outdoor activities and to the dressing style, which limits the surface area exposed to the sun [126].

Overall, latitude is an important factor but the other factors such as culture, belief, indoor lifestyle, etc., would play key roles in vitamin D deficiency in sun-rich countries.

#### **5.3 Skin pigmentation**

Skin pigmentation is the main determinant of ultraviolet B-rays (UV-B) absorption in humans [129]. The absorption of UV-B would be more when the skin is pale compared with the darker skin. In other words, the probability of vitamin D deficiency would be higher when skin pigmentation increases in critical periods

like pregnancy [126]. Pregnant women who live in southern Europe have more pigmented skin, probably with less efficient vitamin D synthesis [145]. In Italy, vitamin D deficiency of pregnant women (with different ethnic groups) was examined based on their skin color (fair, black, light brown). It was found that 22% had severe vitamin D deficiency (<25 nmol/L) in total and fair-skinned mothers had higher 25(OH)D concentrations [146]. Another study in Netherland observed several ethnic backgrounds who reside in The Hague in the Netherlands (52°N), that vitamin D deficiency is more common among most non-Western participants (dark-skinned) (59–84%) compare to western women (fair-skinned) (8%) [147]. In southwestern Sweden, vitamin D deficiency was examined among pregnant women from different backgrounds with various skin colors. The prevalence of vitamin D deficiency was 10% overall, and 2% among mothers born in north Europe, while vitamin D deficiency among women born in Africa was 50% (<30 nmol/L) and deficiency was common among Asian mothers as well [148]. A recent US study reported in the multi-ethnic population of pregnant women in the southeastern USA, non-Hispanic black pregnant women are most at risk for vitamin D insufficiency (91%) compare to non-Hispanic white women (47%) and Hispanic women (75%) [149]. The concentration of melanin in the skin determines vitamin D production. Melanin, which absorbs UV-B in the 290–320 nm range, functions as a light filter and therefore regulates the proportion of the vitamin D production [150]. Thus, skin pigmentation is a dominant variable controlling the production of vitamin D under circumstances of low levels of sun exposures because melanin absorbs UV photons in competition with 7-dehydrocholesterol [151, 152]. Overall, darker-skinned pregnant women need a greater duration of sun exposure (4–5 times) (they are more at risk in higher latitudes) in comparison to light-skinned ones to provide a comparable amount of vitamin D [153].
