Early life vitamin D and neurocognitive abilities at age 6-8 years: a randomized clinical trial and observational...

Vitamin D is suggested to impact neurodevelopment, yet the current evidence is conflicting. We tested if vitamin D₃ supplementation during the first two years of life, maternal 25-hydroxy-vitamin D (25(OH)D) concentration during pregnancy, and child's 25(OH)D concentrations at 12 and 24 months are associated with neurocognitive abilities in 6.6-8.9-year-old children. Participants were from a Finnish vitamin D double-blind randomized clinical trial and classified themselves white. Children received either vitamin D₃ 400-IU (n = 189) or 1200-IU (n = 209) daily until 24 months of age. Serum 25(OH)D was analyzed from mothers at mean of 11.2 weeks of gestation, and from children at 12.0 and 23.9 months (25(OH)D, mean (SD) = 83.8 (21.7), 102.3 (30.1), 105.5 (28.6) nmol/L, respectively). Total Intelligence quotient (IQ) score was assessed with Wechsler Intelligence Scale for Children (WISC-IV) and executive functioning with A Developmental Neuropsychological Assessment (NEPSY-II) and parent-rated Behavior Rating Inventory of Executive Function (BRIEF) questionnaire. Neurocognitive abilities at age 6-8 years did not differ between the supplementation groups or according to 25(OH)D concentration at 12 or 24 months (total IQ: β = 1.14, 95% CI -1.69;3.97, p = 0.43, executive functioning, NEPSY-II: β =-0.07, 95% CI -0.14;0.28, p = 0.49, executive functioning, BRIEF: β =-0.42, 95% CI -5.13;4.28, p = 0.86). Maternal 25(OH)D was not associated with executive functioning. However, both lower and higher maternal 25(OH)D concentrations during pregnancy were associated with child's lower total IQ scores (vertex at 76.6 nmol/L, quadratic estimate p < 0.001) supporting the hypothesis of the role of vitamin D during fetal development. The study is registered with ClinicalTrials.gov (NCT01723852, 2012-11-07 and NCT04302987, 2020-03-06).