How vitamin D and genetics shape early brain development

In a recent study published in Nutrients, a group of researchers examined the association between 25-hydroxy-vitamin D (25(OH)D) concentrations and neurodevelopmental outcomes in 3–5-year-old children, considering both maternal vitamin D (VitD) supplementation during pregnancy and vitamin D binding protein (VDBP) genotypes.

Study: Vitamin D and Child Neurodevelopment—A Post Hoc Analysis. Image Credit: Jane Vershinin / Shutterstock

Background 

VitD, traditionally linked to bone health, has emerged as a potential neuroactive steroid influencing brain development. In adults, it has been linked to Alzheimer’s and ADHD management, while in children, it is connected to autism spectrum disorders. Evidence shows that maternal VitD during pregnancy can affect offspring’s neurological health. Despite these findings, research is inconsistent; some suggest maternal VitD deficiency leads to poorer language skills in children, others see no impact. Another dimension is the VDBP genotype, influencing VitD circulation and possibly various diseases. Given these discrepancies and the potential role of VDBP, more research is crucial to discern VitD’s exact role in neurodevelopment.

About the study

The present study was a post hoc analysis examining the effects of VitD supplementation during pregnancy on child neurodevelopment, using data from a randomized clinical trial’s follow-up study. The preceding pregnancy study, conducted between 2004 and 2009, enrolled healthy pregnant women with singleton pregnancies between 12-16 weeks of gestation. Participants were given varying doses of VitD3 daily until delivery, and blood samples were taken regularly; of the initial 502 participants, 350 completed the study.

The subsequent follow-up study involved the children of the mothers from the initial study. From the 350 completing mothers, 172 permitted their children, aged 3-5 years, to participate in the research spanning 2009-2013. The children were examined yearly, collecting blood samples and conducting neurodevelopmental tests using the Brigance Screen II.

Sociodemographic data, including maternal race, education level, marital status, insurance type, and infant feeding method, were collected. The neurodevelopmental assessment, Brigance Screen II, covered language, motor, and academic domains. Blood samples from the children measured the total 25(OH)D concentrations, and VitD status was categorized based on the Endocrine Society’s standards. The VDBP genotype was also examined from blood samples. 

The statistical analysis focused on 156 children, scrutinizing neurodevelopmental scores in relation to treatment groups and VDBP genotype, among other factors. The primary outcomes revolved around the Brigance Screen scores in correlation with treatment. Secondary endpoints evaluated the relationship between VDBP genotype and neurodevelopmental scores. Various factors, like maternal education, race, and child’s sex, were included in the assessment.

Study results 

The study presented its findings on the sociodemographic and clinical characteristics of participants. From the baseline data, no notable disparities existed between groups in variables such as maternal race, marital status, education, insurance status, child’s gender, feeding choices, APGAR score, gestational age at delivery, and birth weight. Intriguingly, a notable correlation emerged between infant serum 25(OH)D concentration at birth and maternal 25(OH)D concentration from the initial prenatal visit and a month prior to delivery. When participants were revisited between ages 3 and 5, 19.2% of the children displayed a deficiency in VitD. Furthermore, a marked variation was detected in 25(OH)D concentrations across different VDBP genotypes.

As per the final models, higher concentrations of 25(OH)D in children aged 3-5 correlated with enhanced Brigance quotient scores. Furthermore, children of mothers with a college education also displayed higher Brigance quotient scores. Interestingly, Hispanic children recorded lower Brigance quotients. Additionally, both Hispanic and African American children showed lower Brigance academic scores. Variations in VDBP genotypes also influenced Brigance academic scores. 

Language scores on the Brigance test indicated higher scores among children whose mothers received a 2000 IU/day VitD regimen during their pregnancy. Additionally, children born to mothers with a college education outperformed their counterparts in the language domain. The season of testing also emerged as a factor, with children tested in the spring faring better in language scores. However, specific VDBP genotypes, such as Gc1f-1s or Gc1f-2 and Gc1s-1s, Gc1s-2, or Gc2,2, were linked with poorer language scores compared to the Gc1f-1f genotype.

Lastly, the Brigance motor assessment revealed that male children scored marginally lower than their female counterparts. Feeding practices also played a role, with breastfed children surpassing non-breastfed children in motor scores. In essence, the study’s results accentuate the multifaceted influences of sociodemographic factors, VitD levels, and genetic variables on early childhood neurodevelopmental outcomes.