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

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).