**6.5 Immunity and allergies**

Some studies are suggesting that low maternal or cord blood 25(OH)D concentrations are associated with an increased risk of developing atopic disorders, including atopic dermatitis or eczema, allergic rhinitis, asthma, and food allergy [206–209]. A study conducted in 270 mother-child pairs showed that a higher cord blood 25(OH)D concentration was associated with reduced risk of eczema in children at 1 and 3 years of age. However, no significant associations were found between cord blood 25(OH)D concentration and the development of allergic rhinitis, allergic sensitization, or asthma [206]. In another study, cord serum 25(OH)D levels were found to be inversely associated with the risk of atopic dermatitis by the age of 5 years, but no association was reported with allergic rhinitis and asthma [207]. Chiu et al. observed a significant association between low cord blood 25(OH) D levels and increased risk of milk sensitization but not eczema, allergic rhinitis, or asthma in early childhood [208]. In another study with the same authors, it was revealed that lower maternal 25(OH)D levels (<20 ng/ml) were associated with a higher prevalence of allergen sensitization before age 2, and higher maternal 25(OH)D levels were associated with lower risk of eczema and asthma at age 4 [209]. Wei et al. conducted a meta-analysis of prospective cohort studies to examine the association between maternal vitamin D status and childhood allergic diseases. They found an inverse association between maternal vitamin D status during pregnancy and risk of childhood eczema but not childhood asthma or wheeze [200]. However, a recent meta-analysis of observational studies reported no significant associations between 25(OH)D levels in cord blood at birth or maternal blood in

**49**

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

pregnancy and the risk of atopic disorders [203]. Taken together, these studies indicate that lower maternal 25(OH)D concentration may be associated with an

Here, we discuss the role of intrauterine vitamin D exposure on the risk of two common autoimmune diseases—type 1 diabetes and multiple sclerosis. Type 1 diabetes mellitus is an autoimmune disease characterized by the destruction of the insulin-producing pancreatic β-cells of the Langerhans islets [210]. Staples et al. found an inverse association between annual ambient UV radiation exposure and prevalence of type 1 diabetes in Australia, which was suggested to be due to the role of UV radiation in vitamin D synthesis [211]. In a case-control study conducted in 109 cases and 219 control women, it was observed that lower levels of vitamin D during pregnancy were associated with a higher risk of developing type 1 diabetes in offspring before 15 years of age [212]. In contrast, in another case-control study conducted in Finnish women, Miettinen et al. found no difference between serum 25(OH)D levels during early pregnancy between mothers whose children later on developed type 1 diabetes, and mothers of healthy children [213]. Thorsen and colleagues showed that normal variation in maternal or neonatal 25(OH)D levels has no significant effect on the risk of childhood type 1 diabetes [214]. Jacobsen et al. also failed to find an association between 25(OH)D levels around the time of birth and the risk of developing type 1 diabetes before the age of 18 years [215]. As these studies found inconsistent results, more research is still needed before any conclusions can be drawn on the relationship between maternal vitamin D status and risk

Multiple sclerosis (MS) is an autoimmune disease, in which the immune system attacks the myelin sheaths surrounding nerve cells [216]. Accumulating evidence suggests an association between the month of birth and risk of MS [217–219], possibly due to variation in UV exposure, which in turn determines maternal vitamin D levels during pregnancy. In support of this hypothesis, Munger et al. reported that maternal vitamin D deficiency (<30.0 nmol/L) during early pregnancy was associated with increased risk of MS (almost 2-fold) in the offspring compared with women with normal 25(OH)D levels [220]. A nested case-control study demonstrated that exposure to high 25(OH)D levels during the years preceding disease onset was associated with decreased risk of MS in the offspring. However, no decrease in risk of MS was observed in the offspring exposed to high levels of 25(OH)D *in utero* (≥75 vs. <75 nmol/L) [221]. Nielsen et al. also carried out a matched case-control study and found an association between lower levels of 25(OH)D in neonates and increased risk of MS [222]. However, in another population-based case-control study conducted in Sweden, Ueda et al. failed to find such as association [223]. These results suggest that exposure to low levels of 25(OH)D prenatal and in early postnatal life may act as a risk factor for developing MS.

A growing body of evidence suggests that low maternal 25(OH)D levels during pregnancy are associated with impaired neurodevelopmental and neurocognitive outcomes during infancy and childhood [117, 224–228]; however, not all studies are in agreement [229, 230]. In this regard, several studies have shown a significant association between suboptimal maternal vitamin D status and reduced language

Accumulating evidence also suggests a link between maternal vitamin D levels and the risk of developing neuropsychiatric disorders such as attention deficit hyperactivity disorder (ADHD) [231, 232], autism spectrum disorder (ASD) [233–236], and schizophrenia [237]. Results from a prospective pregnancy cohort

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

increased risk of developing atopic disorders.

of developing type 1 diabetes in offspring.

**6.6 Offspring brain development and function**

developmental outcomes in the offspring [224–226].

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

pregnancy and the risk of atopic disorders [203]. Taken together, these studies indicate that lower maternal 25(OH)D concentration may be associated with an increased risk of developing atopic disorders.

Here, we discuss the role of intrauterine vitamin D exposure on the risk of two common autoimmune diseases—type 1 diabetes and multiple sclerosis. Type 1 diabetes mellitus is an autoimmune disease characterized by the destruction of the insulin-producing pancreatic β-cells of the Langerhans islets [210]. Staples et al. found an inverse association between annual ambient UV radiation exposure and prevalence of type 1 diabetes in Australia, which was suggested to be due to the role of UV radiation in vitamin D synthesis [211]. In a case-control study conducted in 109 cases and 219 control women, it was observed that lower levels of vitamin D during pregnancy were associated with a higher risk of developing type 1 diabetes in offspring before 15 years of age [212]. In contrast, in another case-control study conducted in Finnish women, Miettinen et al. found no difference between serum 25(OH)D levels during early pregnancy between mothers whose children later on developed type 1 diabetes, and mothers of healthy children [213]. Thorsen and colleagues showed that normal variation in maternal or neonatal 25(OH)D levels has no significant effect on the risk of childhood type 1 diabetes [214]. Jacobsen et al. also failed to find an association between 25(OH)D levels around the time of birth and the risk of developing type 1 diabetes before the age of 18 years [215]. As these studies found inconsistent results, more research is still needed before any conclusions can be drawn on the relationship between maternal vitamin D status and risk of developing type 1 diabetes in offspring.

Multiple sclerosis (MS) is an autoimmune disease, in which the immune system attacks the myelin sheaths surrounding nerve cells [216]. Accumulating evidence suggests an association between the month of birth and risk of MS [217–219], possibly due to variation in UV exposure, which in turn determines maternal vitamin D levels during pregnancy. In support of this hypothesis, Munger et al. reported that maternal vitamin D deficiency (<30.0 nmol/L) during early pregnancy was associated with increased risk of MS (almost 2-fold) in the offspring compared with women with normal 25(OH)D levels [220]. A nested case-control study demonstrated that exposure to high 25(OH)D levels during the years preceding disease onset was associated with decreased risk of MS in the offspring. However, no decrease in risk of MS was observed in the offspring exposed to high levels of 25(OH)D *in utero* (≥75 vs. <75 nmol/L) [221]. Nielsen et al. also carried out a matched case-control study and found an association between lower levels of 25(OH)D in neonates and increased risk of MS [222]. However, in another population-based case-control study conducted in Sweden, Ueda et al. failed to find such as association [223]. These results suggest that exposure to low levels of 25(OH)D prenatal and in early postnatal life may act as a risk factor for developing MS.

### **6.6 Offspring brain development and function**

A growing body of evidence suggests that low maternal 25(OH)D levels during pregnancy are associated with impaired neurodevelopmental and neurocognitive outcomes during infancy and childhood [117, 224–228]; however, not all studies are in agreement [229, 230]. In this regard, several studies have shown a significant association between suboptimal maternal vitamin D status and reduced language developmental outcomes in the offspring [224–226].

Accumulating evidence also suggests a link between maternal vitamin D levels and the risk of developing neuropsychiatric disorders such as attention deficit hyperactivity disorder (ADHD) [231, 232], autism spectrum disorder (ASD) [233–236], and schizophrenia [237]. Results from a prospective pregnancy cohort

*Vitamin D Deficiency*

is involved in the process of maturation of the fetal lung including type II alveolar cells maturation and the alveolarization [199]. Currently, there are four metaanalyses published within a 3-year period from 2016 to 2018, which examined the association between maternal 25(OH)D levels during pregnancy and the offspring's respiratory conditions [200–203]. The first meta-analysis included eight studies on the association between maternal vitamin D status and childhood asthma or wheeze. This meta-analysis showed no statistical association between maternal vitamin D during pregnancy and risk of childhood asthma or childhood wheeze [200]. In contrast, the second meta-analysis included 15 prospective studies with 12,758 participants and found a U-shaped relationship between 25(OH)D levels during pregnancy and risk of childhood asthma, with the lowest risk at approximately 70 nmol/L [201]. The third meta-analysis assessed the association of both cord blood and maternal 25(OH)D levels with the risk of offspring's asthma, wheeze, and respiratory tract infections. The results revealed borderline significant inverse associations between *in utero* exposure to vitamin D and risk of asthma and wheeze, but not the risk of respiratory tract infections in offspring [202]. In the final and most recent meta-analysis, Pacheco-González et al. found an inverse association between prenatal exposure to 25(OH)D and the risk of respiratory tract infections. The authors also observed a positive borderline association between maternal or cord blood 25(OH)D levels and lung function at school age. However, no associations were found for asthma and wheeze [203]. The apparently conflicting results of meta-analyses may be partly explained by differences in inclusion criteria, the number of studies, the characteristics of participants and the methodology used. Further, the results of two other meta-analyses revealed that higher maternal intake of vitamin D was associated with lower odds of wheeze during childhood [204, 205]. Taken together, these results suggest the role of maternal vitamin D status as a protective factor for the development of offspring respiratory

Some studies are suggesting that low maternal or cord blood 25(OH)D concentrations are associated with an increased risk of developing atopic disorders, including atopic dermatitis or eczema, allergic rhinitis, asthma, and food allergy [206–209]. A study conducted in 270 mother-child pairs showed that a higher cord blood 25(OH)D concentration was associated with reduced risk of eczema in children at 1 and 3 years of age. However, no significant associations were found between cord blood 25(OH)D concentration and the development of allergic rhinitis, allergic sensitization, or asthma [206]. In another study, cord serum 25(OH)D levels were found to be inversely associated with the risk of atopic dermatitis by the age of 5 years, but no association was reported with allergic rhinitis and asthma [207]. Chiu et al. observed a significant association between low cord blood 25(OH) D levels and increased risk of milk sensitization but not eczema, allergic rhinitis, or asthma in early childhood [208]. In another study with the same authors, it was revealed that lower maternal 25(OH)D levels (<20 ng/ml) were associated with a higher prevalence of allergen sensitization before age 2, and higher maternal 25(OH)D levels were associated with lower risk of eczema and asthma at age 4 [209]. Wei et al. conducted a meta-analysis of prospective cohort studies to examine the association between maternal vitamin D status and childhood allergic diseases. They found an inverse association between maternal vitamin D status during pregnancy and risk of childhood eczema but not childhood asthma or wheeze [200]. However, a recent meta-analysis of observational studies reported no significant associations between 25(OH)D levels in cord blood at birth or maternal blood in

**48**

disorders.

**6.5 Immunity and allergies**

conducted in 487 mother-child pairs revealed that children born to mothers in the high 25(OH)D tertile (>50.7 nmol/l) had decreased risk of developing ADHD-like symptoms at 4 years of age, compared to children of women in the low 25(OH)D tertile (<38.4 nmol/l) [231]. In another prospective study conducted in 1650 mother-child pairs, Morales et al. found an inverse association between maternal circulating levels of 25(OH)D in pregnancy and risk of developing ADHD-like at ages 4–5 years [232]. Using a case-control design study, Chen and colleagues reported that low maternal first-trimester serum levels of 25(OH)D was associated with increased odds of ASD diagnosis at age 3–7 years in the offspring [233]. Another study also found an increased risk of ASD in children who were born to mothers with vitamin D deficiency at mid-gestation [234]. In a large populationbased cohort of mothers and their children, gestational vitamin D deficiency was associated with a continuous measure of autism-related traits at 6 years [235]. Magnusson et al. also observed a relationship between maternal vitamin D deficiency and risk of ASD with, but not without, intellectual disability [236]. Further, it has been demonstrated that low maternal vitamin D levels are associated with increased risk of schizophrenia within the subgroup of black but not white individuals [237]. Although more robust studies needed, these results highlight the importance of maternal vitamin D status in offspring brain development and function.
