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 the risk of autism and attention deficit hyperactivity disorder (ADHD).

Objective
The objective of this study was 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 (COPYCH) 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 wk 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.

Results
The psychopathologic evaluation was completed by 591 children aged 10 y, and 16 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, 12 children (2.4%) were diagnosed with autism and 58 (11.7%) with ADHD. Higher maternal preintervention 25(OH)D levels were associated with a decreased risk of autism [odd ratio (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 preintervention 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.
OriginalsprogEngelsk
TidsskriftThe American Journal of Clinical Nutrition
Vol/bind119
Udgave nummer2
Sider (fra-til)362-370
Antal sider9
ISSN0002-9165
DOI
StatusUdgivet - 2024

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