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

  • Kristina Aagaard
  • , Jens Richardt Møllegaard Jepsen
  • , Astrid Sevelsted
  • , David Horner
  • , Rebecca Vinding
  • , Julie Bøjstrup Rosenberg
  • , Nicklas Brustad
  • , Anders Eliasen
  • , Parisa Mohammadzadeh
  • , Nilofar Følsgaard
  • , María Hernández-Lorca
  • , Birgitte Fagerlund
  • , Birte Y Glenthøj
  • , Morten Arendt Rasmussen
  • , Niels Bilenberg
  • , Jakob Stokholm
  • , Klaus Bønnelykke
  • , Bjørn H. Ebdrup
  • , Bo Chawes

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Abstract

Background: Vitamin D deficiency in pregnancy may increase risk of autism and attention deficit hyperactivity disorder (ADHD). 
Objective: To estimate the effect of vitamin D3 supplementation in pregnancy on risk of autism and ADHD.
Design: 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).
Results: 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.
Conclusions: 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.  
Original languageEnglish
JournalAMERICAN JOURNAL OF CLINICAL NUTRITION
Volume119
Issue number2
Pages (from-to)362-370
ISSN0002-9165
DOIs
Publication statusPublished - 2024

Keywords

  • ADHD
  • Autism
  • Vitamin D
  • Neurodevelopment
  • Supplementation

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