High-dose vitamin D3 supplementation in pregnancy and risk of neurodevelopmental disorders in the children at age 10: A randomized clinical trial

Vitamin D deficiency in pregnancy may increase risk of autism and attention deficit hyperactivity disorder (ADHD). To estimate the effect of vitamin D3 supplementation in pregnancy on risk of autism and ADHD. This randomized clinical trial was part of the COpenhagen Prospective Study on Neuro-PSYCHiatric Development (COPSYCH) project nested within the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort comprising a population-based sample of 700 healthy mother-child pairs enrolled at week 24 of pregnancy. Maternal 25-hydroxy-vitamin D (25(OH)D) was measured at inclusion and 623 mothers were randomized 1:1 to either high-dose (2800 IU/d) or standard-dose (400 IU/d) vitamin D3 until 1 week postpartum (315 received high-dose, 308 standard dose). At age 10, diagnoses and symptom load of autism and ADHD, respectively, were established using the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). 591 children completed the psychopathological evaluation at age 10, sixteen children (2.7%) were diagnosed with autism and 65 (11.0%) with ADHD. Hereof, 496 children participated in the vitamin D3 trial (246 received high-dose, 250 standard dose). Of these, twelve children (2.4%) were diagnosed with autism and 58 (11.7%) with ADHD. Higher maternal pre-intervention 25(OH)D levels were associated with a decreased risk of autism (OR per 10 nmol/L 0.76 (0.59,0.97), p=0.034)), lower autistic symptom load (β per 10 nmol/L -0.03 (-0.05,0.00), p=0.024), and decreased risk of ADHD diagnosis (OR per 10 nmol/L 0.88 (0.78,0.99), p=0.033). High-dose vitamin D3 supplementation was not associated with risk of autism or ADHD. Higher maternal pre-intervention 25(OH)D was associated with a decreased risk of autism, lower autistic symptom load, and decreased risk of ADHD diagnosis, but high-dose vitamin D3 supplementation in pregnancy had no effect on risk of autism and ADHD. ClinicalTrials.gov Identifier: NCT00856947 URL: https://classic.clinicaltrials.gov/ct2/show/NCT00856947?term=NCT00856947&draw=2&rank=1