University of Oulu

Sandboge S, Räikkönen K, Lahti-Pulkkinen M, et al. Effect of Vitamin D₃ Supplementation in the First 2 Years of Life on Psychiatric Symptoms at Ages 6 to 8 Years: A Randomized Clinical Trial. JAMA Netw Open. 2023;6(5):e2314319. doi:10.1001/jamanetworkopen.2023.14319

Effect of vitamin D₃ supplementation in the first 2 years of life on psychiatric symptoms at sges 6 to 8 years : a randomized clinical trial

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Author: Sandboge, Samuel1,2; Räikkönen, Katri3; Lahti-Pulkkinen, Marius2,3,4;
Organizations: 1Psychology/Welfare Sciences, Faculty of Social Sciences, University of Tampere, Tampere, Finland
2Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland
3Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
4Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
5Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
6Research Unit for Pediatrics, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
7Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
8Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
9Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
10Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
11Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
12Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, Canada
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.9 MB)
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Language: English
Published: American Medical Association, 2023
Publish Date: 2023-09-29


Importance: Vitamin D is associated with neurodevelopment, but causality, critical windows, and potentials for modification remain unknown.

Objective: To determine the impact of high-dose (1200 IU) vs standard-dose (400 IU) vitamin D₃ supplementation during the first 2 years on psychiatric symptoms at ages 6 to 8 years and whether the impact is different in children with lower vs higher maternal vitamin D₃ levels; lower vs higher levels were defined as 25-hydroxyvitamin D (25[OH]D) less than 30 ng/mL vs 30 ng/mL or greater.

Design, Setting, and Participants: This study was a long-term follow-up of the double-blind randomized clinical trial (RCT) Vitamin D Intervention in Infants (VIDI) conducted at a single center in Helsinki, Finland, at 60 degrees north latitude. Recruitment for VIDI took place in 2013 to 2014. Follow-up data for secondary data analysis were collected 2020 to 2021. VIDI originally included 987 term-born infants; 546 of these individuals participated in the follow-up at ages 6 to 8 years, among whom 346 individuals had data on parent-reported psychiatric symptoms. Data were analyzed from June 2022 to March 2023.

Interventions: There were 169 infants randomized to receive 400-IU and 177 infants randomized to receive 1200-IU oral vitamin D3 supplementation daily from ages 2 weeks to 24 months.

Main Outcomes and Measures Primary outcomes were internalizing, externalizing, and total problems scores, with clinically significant problems defined as T scores of 64 or greater in the Child Behavior Checklist questionnaire.

Results: Among 346 participants (164 females [47.4%]; mean [SD] age, 7.1 [0.4] years), the vitamin D₃ dose was 400 IU for 169 participants and 1200 IU for 177 participants. Clinically significant internalizing problems occurred in 10 participants in the 1200-IU group (5.6% prevalence) compared with 20 participants (11.8%) in the 400-IU group (odds ratio, 0.40; 95% CI, 0.17-0.94; P = .04) after adjustment for sex, birth season, maternal depressive symptoms at birth, and parental single status at follow-up. In a post hoc subgroup analysis, 48 children in the 400-IU group with maternal 25(OH)D concentrations less than 30 ng/mL had higher internalizing problems scores compared with children in the 1200-IU group, including 44 children with maternal 25(OH)D concentrations below 30 ng/mL (adjusted mean difference, 0.49; 95% CI, 0.09-0.89; P = .02) and 91 children with maternal concentrations above 30 ng/mL (adjusted mean difference, 0.37; 95% CI, 0.03-0.72; P = .04). Groups did not differ in externalizing or total problems.

Conclusions and Relevance: This randomized clinical trial found that higher-than-standard vitamin D₃ supplementation in the first 2 years decreased risk of internalizing problems at ages 6 to 8 years.

Trial Registration: Identifiers: NCT01723852 (VIDI) and NCT04302987 (VIDI2)

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Series: JAMA network open
ISSN: 2574-3805
ISSN-E: 2574-3805
ISSN-L: 2574-3805
Volume: 6
Issue: 5
Article number: e2314319
DOI: 10.1001/jamanetworkopen.2023.14319
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Funding: This work was supported by the Academy of Finland, Sigrid Jusélius Foundation, Signe and Ane Gyllenberg Foundation, Finland Foundation for Pediatric Research, Yrjö Jahnsson Foundation, Novo Nordisk Foundation, Finska Läkaresällskapet, Finland Special Governmental Subsidy for Clinical Research, Juho Vainio Foundation, and Päivikki and Sakari Sohlberg Foundation. Orion Pharmaceuticals is acknowledged for providing vitamin D3 supplements gratis for the study.
Copyright information: © The Author(s) 2023. This is an open access article distributed under the terms of the CC-BY License.