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

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, ma