In a large birth cohort in India maternal vitamin D deficiency predicted smaller muscle size (AMA) at 5 and 9.5 years of age, and higher insulin resistance at 9.5 years. Maternal vitamin D deficiency, defined at a higher 25(OH)D threshold, also predicted reduced insulin secretion. As far as we know, this is the first study to examine associations between maternal vitamin D status and cardiometabolic risk factors in children.
Major strengths of the study are detailed anthropometry and cardiovascular risk factors measured at two time points in a large group of healthy children, and prior measurements of maternal 25(OH)D status. Limitations were the lack of good data on maternal vitamin D supplement use, and no data on children’s serum 25(OH)D concentrations. Maternal lifestyle habits (diet, sun exposure) that could influence her own as well as her offspring’s vitamin D status and offspring outcomes were not measured. We used bioimpedance for body composition assessment and HOMA index for insulin resistance, which are not gold standard measurements. However, these methods are widely used and correlate well with more valid methods (29
Two recent studies have reported associations between maternal 25(OH)D concentrations and postnatal bone growth in the children. In the UK, lower maternal serum 25(OH)D concentrations in late pregnancy were associated with reduced bone mineral content in the children at 9 years of age (15
). In Lebanon, maternal veiling, a proxy for low maternal vitamin D status, was associated with lower bone mineral content and density in adolescent boys (31
). Neither study showed an association with height.
As in these studies, maternal vitamin D status was not related to height in the Mysore children. At 5 and 9.5 years of age, children of mothers without vitamin D deficiency had larger AMA. These associations were also continuous across the range of maternal 25(OH)D concentrations. There was no effect on grip-strength at 9.5 years. One explanation for this is that the association seen with AMA may be related to its bone component. Alternatively, intrauterine vitamin D status may influence muscle size but not function. Current vitamin D status is more likely to be associated with muscle performance (2
). We also observed an association between maternal vitamin D status and lean body mass (fat-free percentage) similar to a UK study that observed a trend towards higher lean body mass in children of mothers with higher vitamin D status (34
). Maternal vitamin D may have long-term effects on offspring muscle growth postnatally. Alternatively, these offspring may have similar lifestyle habits as their mothers, and thus better vitamin D status. Studies in animals suggest that vitamin D stimulates growth and differentiation of muscle tissue (9
). Bone growth may also be compromised in maternal deficiency due to intrauterine programming of endocrine mechanisms affecting calcium homeostasis (15
The association between low maternal vitamin D status and higher offspring fat percentage was alarming. Sex differences were a new finding. This may be related to more homogenous lifestyle habits in girls in this population (less out-door exposure) masking an association with maternal vitamin D status. This area needs further exploration.
Vitamin D is known to influence insulin secretion (35
), while hypovitaminosis D predicts insulin resistance, glucose intolerance and features of metabolic syndrome in normoglycaemic subjects (5
). We did not find an association in these Mysore mothers between vitamin D status and their own insulin resistance or risk of gestational diabetes (18
). There are no previous studies reporting long-term effects of maternal vitamin D status on risk of type 2 diabetes or metabolic syndrome in the offspring. We found that low concentrations of 25(OH)D in the pregnant mothers were associated with higher insulin resistance in their children at 9.5 years of age. Though the changes observed in our children are small and not currently clinically relevant, childhood HOMA tends to track to adulthood (39
). There were no associations with insulin secretion (30-minute increment). However, it was lower in children whose mothers had 25(OH)D concentrations <70 nmol/l. Seasonality of birth (a proxy for intrauterine vitamin D status) as well as maternal 25(OH)D concentrations have been shown to be associated with the prevalence of offspring type 1 diabetes in some studies (40
). However, a direct association between maternal vitamin D status and offspring β-cell functioning has not been reported. A recent study showed reduced β-cell secretion (HOMA-β) in adults with higher finger print ridge counts, which themselves were predicted by seasonality of conception (42
). There is still debate as to the optimal 25(OH)D concentrations for defining vitamin D deficiency, especially in pregnancy (11
). Current practice is based on the skeletal actions of the vitamin, and may not be applicable for its non-classic actions. Our study suggests that levels may differ for different parameters.
The mechanism by which maternal vitamin D predicts insulin resistance in late childhood is speculative. Our study suggests that neither fat nor muscle size are mediating factors in this association. The association was significant only at 9.5 years. Age related factors such as puberty and sedentary behaviours may have reduced the threshold for the risk factors to emerge in compromised children. The concept that maternal nutritional status influences the risk of chronic disorders in the offspring has attracted interest over the past 2 decades (43
). However, very few studies have been in a position to examine this association directly in humans. Recently, lower maternal vitamin B12 and higher folate status were shown to predict insulin resistance in Indian children (44
). Against the background of a high prevalence of vitamin D deficiency among Asian Indians, especially during pregnancy, this may be one factor that, through fetal programming, contributes to the rise of type 2 diabetes in the region.
An unexpected finding in our study was the association between maternal vitamin D deficiency and increased HDL-cholesterol in the male offspring. We do not have an explanation for this phenomenon. Past studies have reported an increase in serum LDL-cholesterol concentrations in post-menopausal women supplemented with long-term vitamin D3 (45
). More studies on this association are needed to understand the significance of our finding.
In conclusion, maternal vitamin D status may be an important micro-nutritional factor for post-natal musculo-skeletal development and glucose homeostasis in human offspring. This is alarming considering the high prevalence of vitamin D deficiency among pregnant women globally. This observation, therefore, warrants replication and further research to determine whether the association is causal and whether these adverse effects of maternal hypovitaminosis D on non-bony tissues in offspring can be prevented by vitamin D supplementation in pregnancy.