High maternal vitamin D levels in early pregnancy may protect against behavioral difficulties at preschool age: the Rhea mother-child cohort, Crete, Greece

Animal studies suggest that prenatal vitamin D status may affect fetal brain growth. However, human studies are scarce with conflicting results. We aimed to investigate the association of maternal 25-hydroxyvitamin D [25(OH) D] levels with multiple neurodevelopmental outcomes at 4 years of age. We included 487 mother-child pairs from the prospective pregnancy cohort, "Rhea" in Crete, Greece. Maternal serum 25(OH) D concentrations were measured at the first prenatal visit (13 +/- 2.4 weeks). Cognitive functions at 4 years were assessed by means of the McCarthy Scales of Children's Abilities. Behavioral difficulties were assessed by means of Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Children of women in the high 25(OH) D tertile (> 50.7 nmol/l) had 37% decreased number of hyperactivity-impulsivity symptoms (IRR 0.63, 95% CI 0.39, 0.99, p (trend) = 0.05) and 40% decreased number of total ADHD-like symptoms (IRR 0.60, 95% CI 0.37, 0.95, p (trend) = 0.03) at 4 years of age, compared to children of women in the low 25(OH) D tertile (< 38.4 nmol/l), after adjustment for several confounders. Similar associations were found with the hyperactivity/inattention score of the SDQ questionnaire. Children of mothers with high 25(OH) D levels had also fewer total behavioral difficulties (beta-coeff: -1.25, 95% CI -2.32, -0.19) and externalizing symptoms (beta-coeff: -0.87, 95% CI -1.58, -0.15) at preschool age. The observed associations were stronger in girls than in boys (p (for interaction) < 0.1). No association was observed between maternal 25(OH) D concentrations and cognitive function in preschoolers. Our results suggest that high maternal vitamin D levels in early pregnancy may protect against behavioral difficulties, especially ADHD-like symptoms at preschool age.