1. Introduction
obesity, autism spectrum disorders, cancer, thyroid diseases, neuropsychiatric disorders, diabetes
OBESITY, SECONDARY, VITAMIN D DEFICIENCY, DIABETES
Introduction: Vitamin D (VitD) has been shown to impact neurodevelopment. Studies have shown that higher 25-hydroxy-vitamin D (25(OH)D) concentrations (the indicator of vitD status) may be associated with better neurodevelopmental outcomes, although current data are conflicting. This study examined the relationship between total circulating 25(OH)D concentrations and neurodevelopmental outcomes in 3–5-year-old (3–5 yo) children. Methods: In this study, pregnant women were randomized to receive 400 (standard dose), 2000, or 4000 IU vitDVitamin D is well known as a modulator of calcium and bone homeostasis, but recent studies suggest that it may play a larger role as a neuroactive steroid affecting brain development and adult brain function [In children, one condition having the most evidence for vitamin D’s relationship with neuropsychiatric disorders is autism spectrum disorders. A recent review details several studies that have found relationships between lower 25-hydroxy-vitamin D concentrations (25(OH)D) and an increased risk for the development of autism spectrum disorders in children and adolescents [There is also a growing body of evidence that hypothesizes that vitamin D status during pregnancy may impact offspring brain development and morphology. Animal studies have demonstrated links between maternal vitamin D depletion and changes to offspring brain morphology and reduced gene expression of the forkhead box protein P2 (Foxp2) in the brain, which is critical for the development of speech and language in humans [Several reports diverge from this hypothesis, however, including a systematic review that concluded that maternal vitamin D deficiency in the first or second trimester was associated with worsened socio-emotional development scores in offspring, while two others found that lower maternal 25(OH)D was associated with poorer language outcomes in children [Another factor that is important to consider when examining the effects of vitamin D is the vitamin D binding protein (VDBP) genotype. The majority of vitamin D in the body circulates bound to VDBP, and recent studies have suggested that VDBP, also called group-specific component (GC), may play an important role in various pathologies, including several forms of cancer, thyroid diseases, obesity, diabetes, and several other pathologies [Given the current discrepancy in the literature regarding the role of vitamin D in cognition and neurodevelopment and the potential impact of the VDBP genotype on 25(OH)D concentrations, vitamin D status, and various pathological states, we sought to determine if there is a link between vitamin D status and VDBP genotype on neurodevelopment. We hypothesized that (1) supplementation with higher doses of vitamin D during pregnancy and thus 25(OH)D concentrations (the marker of vitamin D status) in offspring would lead to better neurodevelopmental outcomes and (2) that children with the Gc1s allele would perform better on neurodevelopmental assessments than those with the Gc1f allele. In this post hoc analysis of offspring enrolled in a prospective follow-up study of maternal vitamin D supplementation during pregnancy, we examined whether maternal vitamin D supplementation during pregnancy and the subsequent 25(OH)D concentrations in offspring would impact scores on neurodevelopmental assessments performed at 3–5 years old. Therefore, our first endpoint was to determine whether there is a relationship between 25(OH)D concentration and child neurodevelopment, and the secondary endpoint was to determine whether VDBP genotype plays a role in this relationship.