A prospective population-based study of gestational vitamin D status and brain morphology in preadolescents

Low vitamin D level during pregnancy has been associated with adverse neurodevelopmental outcomes such as autism spectrum disorders (ASD) in children. However, the underlying neurobiological mechanism remains largely unknown. This study investigated the association between gestational 25-hydroxyvitamin D [25(OH)D] concentration and brain morphology in 2597 children at the age of 10 years in the population-based Generation R Study. We studied both 25(OH)D in maternal venous blood in mid-gestation and in umbilical cord blood at delivery, in relation to brain volumetric measures and surface-based cortical metrics including cortical thickness, surface area, and gyrification using linear regression. We found exposure to higher maternal 25(OH)D concentrations in mid-gestation was associated with a larger cerebellar volume in children (b ​= ​0.02, 95%CI 0.001 to 0.04), however this association did not remain after correction for multiple comparisons. In addition, children exposed to persistently deficient (i.e., <25 ​nmol/L) 25(OH)D concentration from mid-gestation to delivery showed less cerebral gray matter and white matter volumes, as well as smaller surface area and less gyrification at 10 years than those with persistently sufficient (i.e., ≥50 ​nmol/L) 25(OH)D concentration. These results suggest temporal relationships between gestational vitamin D concentration and brain morphological development in children.