**6.3 Offspring soft tissue body composition**

A growing body of evidence suggests that maternal vitamin D status in pregnancy may play a part in the offspring adipogenesis [185–189]; however, not all studies are in agreement [190, 191]. Tint et al. conducted a study to examine the association between maternal 25(OH)D status at mid-gestation and neonatal abdominal adipose tissue (AT) compartments. The findings indicated an inverse liner correlation between maternal 25(OH)D and both superficial and deep subcutaneous AT compartments measured by magnetic resonance imaging (MRI). In addition, compared to neonates born to mothers with 25(OH)D sufficiency

**47**

**6.4 Respiratory health**

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

obese individuals, partly due to the sequestration of vitamin D by AT [193].

tions are required to draw a firm conclusion on this matter.

D status on offspring lean mass or muscle strength [194, 195]. Using data from Mysore Parthenon Study, Krishnaveni et al. reported that Indian children born to vitamin D-deficient mothers (serum 25(OH)D < 50 nmol/L) had a smaller armmuscle area at ages 5 and 9.5 years in comparison with children born to mothers without deficiency. However, no difference in grip strength was observed between the offspring of mothers with and without vitamin D deficiency [194]. In contrast, a study conducted in 678 mother-child pairs showed that maternal serum 25(OH)D concentration in pregnancy was positively associated with height-adjusted hand grip strength but not muscle mass in offspring at 4 years of age [195]. These results suggest that low maternal vitamin D status may be associated with the smaller armmuscle area and lower muscle strength in the offspring. However, more observa-

In humans, lung development starts *in utero* with the formation of two endodermally derived lung buds and continues through childhood, adolescence, and early adulthood [196]. A growing body of evidence suggests that the origins of respiratory disorders such as asthma can be traced back to the fetal period when the lung is undergoing rapid development [197, 198]. It has been shown that vitamin D

A limited number of studies have investigated the influence of maternal vitamin

(>75.0nmol/L), neonates with maternal 25(OH)D inadequacy had higher superficial and deep subcutaneous AT volumes, despite similar birth weight [185]. However, in a prospective observational study, Godang et al. reported a positive association between neonatal total body fat mass (FM) and umbilical cord plasma, but not maternal, 25(OH)D [190]. This was confirmed in another study where a positive correlation between cord blood 25(OH)D levels and neonatal percentage body fat was observed [192]. Using data from the Southampton Women's Survey, Crozier et al. found that lower maternal vitamin D status at 34-week gestation was associated with lower FM in the offspring at birth but with greater FM at ages 4 and 6 years [186]. Similarly, a prospective pregnancy cohort conducted by Daraki et al. showed that offspring of mothers in the low 25(OH)D tertile (<37.7 nmol/L) had higher BMI and waist circumference at preschool age, compared with the offspring of women with higher 25(OH)D concentrations, and this relationship persisted at age 6 years [187]. Results from a recent prospective cohort conducted in 476 mother/infant dyads also demonstrated that reduced maternal 25(OH)D (first quartile compared to the fourth quartile) was associated with lower birth weight for gestational age z-scores (−0.43 units) but higher 1-year weight-for-length (0.78 units) and 3-year BMI z-scores (0.83units) in offspring [188]. In another study, maternal deficit of 25(OH)D (<50 nmol/L) was reported to be associated with increased risk of fetal overweight defined as abdominal circumference ≥90th percentile or either as the estimated fetal weight ≥90th percentile. Moreover, a significant association was found between deficit of 25(OH)D in pregnancy and increased risk of overweight in offspring at age 1 year. However, this association was attenuated at age 4 years [189]. In contrast to these studies, Ong and colleagues, in a mother-offspring cohort in Singapore, observed no significant associations between maternal vitamin D status and any of the adiposity outcomes (i.e., BMI and skinfold thickness) at birth or postnatally. This was partly explained by the low prevalence of severe maternal vitamin D deficiency in the studied population (mean maternal vitamin D concentration of 81.3 nmol/L) [191]. These findings suggest that intrauterine exposure to low 25(OH)D concentrations may be linked to lower FM at birth but greater FM during childhood. A higher FM may also contribute to decreased 25(OH)D levels in

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

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

(>75.0nmol/L), neonates with maternal 25(OH)D inadequacy had higher superficial and deep subcutaneous AT volumes, despite similar birth weight [185]. However, in a prospective observational study, Godang et al. reported a positive association between neonatal total body fat mass (FM) and umbilical cord plasma, but not maternal, 25(OH)D [190]. This was confirmed in another study where a positive correlation between cord blood 25(OH)D levels and neonatal percentage body fat was observed [192]. Using data from the Southampton Women's Survey, Crozier et al. found that lower maternal vitamin D status at 34-week gestation was associated with lower FM in the offspring at birth but with greater FM at ages 4 and 6 years [186]. Similarly, a prospective pregnancy cohort conducted by Daraki et al. showed that offspring of mothers in the low 25(OH)D tertile (<37.7 nmol/L) had higher BMI and waist circumference at preschool age, compared with the offspring of women with higher 25(OH)D concentrations, and this relationship persisted at age 6 years [187]. Results from a recent prospective cohort conducted in 476 mother/infant dyads also demonstrated that reduced maternal 25(OH)D (first quartile compared to the fourth quartile) was associated with lower birth weight for gestational age z-scores (−0.43 units) but higher 1-year weight-for-length (0.78 units) and 3-year BMI z-scores (0.83units) in offspring [188]. In another study, maternal deficit of 25(OH)D (<50 nmol/L) was reported to be associated with increased risk of fetal overweight defined as abdominal circumference ≥90th percentile or either as the estimated fetal weight ≥90th percentile. Moreover, a significant association was found between deficit of 25(OH)D in pregnancy and increased risk of overweight in offspring at age 1 year. However, this association was attenuated at age 4 years [189]. In contrast to these studies, Ong and colleagues, in a mother-offspring cohort in Singapore, observed no significant associations between maternal vitamin D status and any of the adiposity outcomes (i.e., BMI and skinfold thickness) at birth or postnatally. This was partly explained by the low prevalence of severe maternal vitamin D deficiency in the studied population (mean maternal vitamin D concentration of 81.3 nmol/L) [191]. These findings suggest that intrauterine exposure to low 25(OH)D concentrations may be linked to lower FM at birth but greater FM during childhood. A higher FM may also contribute to decreased 25(OH)D levels in obese individuals, partly due to the sequestration of vitamin D by AT [193].

A limited number of studies have investigated the influence of maternal vitamin D status on offspring lean mass or muscle strength [194, 195]. Using data from Mysore Parthenon Study, Krishnaveni et al. reported that Indian children born to vitamin D-deficient mothers (serum 25(OH)D < 50 nmol/L) had a smaller armmuscle area at ages 5 and 9.5 years in comparison with children born to mothers without deficiency. However, no difference in grip strength was observed between the offspring of mothers with and without vitamin D deficiency [194]. In contrast, a study conducted in 678 mother-child pairs showed that maternal serum 25(OH)D concentration in pregnancy was positively associated with height-adjusted hand grip strength but not muscle mass in offspring at 4 years of age [195]. These results suggest that low maternal vitamin D status may be associated with the smaller armmuscle area and lower muscle strength in the offspring. However, more observations are required to draw a firm conclusion on this matter.

#### **6.4 Respiratory health**

In humans, lung development starts *in utero* with the formation of two endodermally derived lung buds and continues through childhood, adolescence, and early adulthood [196]. A growing body of evidence suggests that the origins of respiratory disorders such as asthma can be traced back to the fetal period when the lung is undergoing rapid development [197, 198]. It has been shown that vitamin D

*Vitamin D Deficiency*

the first study, Wei et al. carried out a meta-analysis on six studies and found that pregnant women with circulating 25(OH)D levels less than 50 nmol/L experienced an about 1.5-fold increased risk of SGA [45]. These results were confirmed in another meta-analysis of 13 prospective cohort studies, in which a significant positive association was found between maternal vitamin D deficiency and risk of SGA infants (pooled odds ratio 1.58; 95% CI 1.14–2.22) in the random effects model [180]. Similar results were obtained in subgroup analyses by study quality (high vs. low), gestational week for blood sampling (first trimester vs. second trimester vs. mixed), cut-off vitamin D levels (<10 ng/mL vs. <15 ng/mL vs. <20 ng/mL), sample size (N > 1000 vs. N < 1000), adjustment for critical confounders (Yes vs. No), and method for measuring vitamin D (liquid chromatography with tandem mass spectrometry vs. others) [180]. There results suggest that maternal vitamin D deficiency

A meta-analysis conducted in 2013 showed that insufficient serum levels of 25(OH)D in pregnant women was associated with increased risk of having SGA infants (pooled odds ratio 1.85; 95% CI 1.52–2.26) [52]. In terms of birth weight, the authors used data from four observational studies and found infants of mothers with low 25(OH)D concentrations during pregnancy (<37.5 nmol/L) had lower birth weight (random weighted mean difference −130.9 g). However, no significant difference was observed between maternal vitamin D status and other anthropometric outcomes such as birth length and head circumference [52]. The most recent meta-analysis conducted by Tous et al. included 54 eligible studies and reported that vitamin D-deficient mothers (<30 nmol/L) had offspring with lower birth-weight (mean difference −87.82 g), head circumference (mean difference −0.19 cm), and a higher risk of SGA infants (odds ratio 1.59; 95% CI 1.24–2.03) compared to mothers with concentrations ≥30 nmol/L. However, no difference was observed in terms of infants' length [181]. The results also revealed a significant association between vitamin D insufficiency (<50 nmol/L) and increased risk of SGA (odds ratio 1.43; 95% CI 1.08–1.91). The authors found no significant differences in birth-weight and SGA between offspring born to mothers with 25(OH)D concentrations <75 nmol/L and those born to mothers with 25(OH)D concentrations ≥75 nmol/L [181]. Further, a meta-analysis of 13 interventional studies revealed that vitamin D supplementation during pregnancy was associated with significantly higher circulating 25(OH)D levels (mean difference: 66.5 nmol/L), birth weight (mean difference: 107.6 g), and birth length (mean difference: 0.3 cm), when compared to the control group [182]. Neonates exposed to low levels of vitamin D *in utero* (<30 nmol/L) showed accelerated growth in length and weight during the first year of life to compensate for their small initial size [183, 184]. There results suggest that maternal vitamin D deficiency is associated not only with increased risk of SGA infants but also with lower birth-weight. However, more studies are required to draw a firm conclusion on the relationship

between maternal vitamin D status and other anthropometric outcomes.

A growing body of evidence suggests that maternal vitamin D status in pregnancy may play a part in the offspring adipogenesis [185–189]; however, not all studies are in agreement [190, 191]. Tint et al. conducted a study to examine the association between maternal 25(OH)D status at mid-gestation and neonatal abdominal adipose tissue (AT) compartments. The findings indicated an inverse liner correlation between maternal 25(OH)D and both superficial and deep subcutaneous AT compartments measured by magnetic resonance imaging (MRI). In addition, compared to neonates born to mothers with 25(OH)D sufficiency

**6.3 Offspring soft tissue body composition**

may be associated with an increased risk of SGA infants.

**46**

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 disorders.
