4. Discussion
nonadherence
SECONDARY
The primary aim of this study was to examine the relationship between vitamin D status early in life and neurodevelopmental outcomes. The secondary outcome was to examine the relationship between VDBP genotype and neurodevelopmental outcomes. In this study, we demonstrated that even when controlling for several factors that may affect vitamin D status, both maternal vitamin D supplementation and child vitamin D status were associated with higher scores on neurodevelopmental testing.Specifically, we demonstrate that higher child 25(OH)D at the time of testing was associated with higher Brigance quotient scores even when controlling for socioeconomic factors, including maternal education, marital status, race, and VDBP genotype. These results agree with a recently published study which found that vitamin D status was associated with better problem-solving abilities [This study also found evidence to support the important role that maternal vitamin D status during pregnancy may play in child neurodevelopment. We found that children born to mothers who received the 2000 IU/day dose of vitamin D during pregnancy scored higher on the Brigance language section than those born to mothers receiving the standard prenatal dose of 400 IU/day, even after controlling for several factors, which may also impact vitamin D status. Interestingly, this pattern did not extend to children born to mothers in the 4000 IU/day group.In the design of the original study, the 4000 IU vitamin DIn this study, it is unclear why the neurodevelopmental benefit was limited to the 2000 IU/day group since supplementation is only a surrogate for increasing circulating 25(OH)D concentration. Similar findings of benefit were noted when the association of 25(OH)D concentration and neurodevelopment was analyzed. Supplementing pregnant women with 4000 IU/day with further investigation of this neurodevelopment is necessary to resolve this question.It is also important to note that in this post hoc analysis, 38% of the original cohort was seen in longitudinal follow-up at 3-to-5 years of age, and as such, the groups in this post hoc analysis were not complete. Analyzing neurodevelopmental outcomes on the basis of 25(OH)D concentration during pregnancy, at birth, and at the time of follow-up in the offspring as a continuous variable is a more accurate assessment of vitamin D’s influence that is not seen with treatment groups that are plagued by nonadherence to protocol [This pattern also agrees with previously published animal data, which found that maternal vitamin D depletion was associated with morphological changes in the regions of the brain that in humans responsible for speech and language production [The present study also found an association between VDBP genotype and performance on several measures of the neurodevelopmental screening tool, even when controlling for vitamin D status, supporting the idea that VDBP genotype has a role in neurodevelopment that is independent of its effect on vitamin D concentration. Previous research has shown that the Gc1f allele is associated with the lowest levels of vitamin D status, while the presence of the Gc1s allele is associated with the highest levels of vitamin D status [Together, these results suggest that there is a relationship between vitamin D status and neurodevelopment in children and support the notion that a higher dose of vitamin D during pregnancy would be beneficial for child neurodevelopment, specifically within the language domain. Additionally, our results support the idea that the VDBP genotype may affect child neurodevelopment. Interestingly, our study shows that VDBP genotype affects each domain of neurodevelopment in different ways and independently from vitamin D status, with the Gc1f-1s or Gc1f-2 having both a positive effect on academic domain scores and a negative effect on language domain scores. Together, these results add to the growing body of literature surrounding vitamin D and neurodevelopment and speak to the importance of vitamin D on the developing brain.