TY - JOUR
T1 - High-dose vitamin D3 supplementation in pregnancy and risk of neurodevelopmental disorders in the children at age 10 - A randomized clinical trial
AU - Aagaard, Kristina
AU - Møllegaard Jepsen, Jens Richardt
AU - Sevelsted, Astrid
AU - Horner, David
AU - Vinding, Rebecca
AU - Rosenberg, Julie Bøjstrup
AU - Brustad, Nicklas
AU - Eliasen, Anders
AU - Mohammadzadeh, Parisa
AU - Følsgaard, Nilofar
AU - Hernández-Lorca, María
AU - Fagerlund, Birgitte
AU - Glenthøj, Birte Y
AU - Rasmussen, Morten Arendt
AU - Bilenberg, Niels
AU - Stokholm, Jakob
AU - Bønnelykke, Klaus
AU - Ebdrup, Bjørn H
AU - Chawes, Bo
N1 - Copyright © 2023. Published by Elsevier Inc.
PY - 2024/2
Y1 - 2024/2
N2 - 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. This trial was registered at clinicaltrials.gov as NCT00856947.
AB - 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. This trial was registered at clinicaltrials.gov as NCT00856947.
KW - ADHD
KW - Autism
KW - neurodevelopment
KW - supplementation
KW - vitamin D
UR - http://www.scopus.com/inward/record.url?scp=85182884241&partnerID=8YFLogxK
U2 - 10.1016/j.ajcnut.2023.12.002
DO - 10.1016/j.ajcnut.2023.12.002
M3 - Journal article
C2 - 38072183
SN - 0002-9165
VL - 119
SP - 362
EP - 370
JO - The American journal of clinical nutrition
JF - The American journal of clinical nutrition
IS - 2
ER -