IMPORTANCE Although guidelines for vitamin D supplementation in infants have been widely implemented, they are mostly based on studies focusing on prevention of rickets. The optimal dose for bone strength and infection prevention in healthy infants remains unclear. OBJECTIVE To determine whether daily supplementation with 1200 IU of vitamin D 3 increases bone strength or decreases incidence of infections in the first 2 years of life compared with a dosage of 400 IU/d. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial involving a random sample of 975 healthy term infants at a maternity hospital in Helsinki, Finland. Study recruitment occurred between January 14, 2013, and June 9, 2014, and the last follow-up was May 30, 2016. Data analysis was by the intention-to-treat principle. INTERVENTIONS Randomization of 489 infants to daily oral vitamin D 3 supplementation of 400 IU and 486 infants to 1200 IU from age 2 weeks to 24 months. MAIN OUTCOMES AND MEASURES Primary outcomes were bone strength and incidence of parent-reported infections at 24 months. RESULTS Of the 975 infants who were randomized, 485 (49.7%) were girls and all were of Northern European ethnicity. Eight hundred twenty-three (84.4%) completed the 24-month follow-up. We found no differences between groups in bone strength measures, including bone mineral content (mean difference, 0.4 mg/mm; 95% CI, −0.8 to 1.6), mineral density (mean difference, 2.9 mg/cm 3 ; 95% CI, −8.3 to 14.2), cross-sectional area (mean difference,-0.9 mm 2 ; 95% CI, −5.0 to 3.2), or polar moment of inertia (mean difference,-66.0 mm 4 , 95% CI, −274.3 to 142.3). Incidence rates of parent-reported infections did not differ between groups (incidence rate ratio, 1.00; 95% CI, 0.93-1.06). At birth, 914 of 955 infants (95.7%) were vitamin D sufficient (ie, 25-hydroxyvitamin D [25(OH)D] concentration Ն20.03 ng/mL). At 24 months, mean 25(OH)D concentration was higher in the 1200-IU group than in the 400-IU group (mean difference, 12.50 ng/mL; 95% CI, 11.22-13.78). CONCLUSIONS AND RELEVANCE A vitamin D 3 supplemental dose of up to 1200 IU in infants did not lead to increased bone strength or to decreased infection incidence. Daily supplementation with 400 IU vitamin D 3 seems adequate in maintaining vitamin D sufficiency in children younger than 2 years.

Objective To investigate the effect of vitamin D supplementation dose on allergic sensitization and allergic diseases in infants, and to evaluate whether vitamin D status in pregnancy and at birth are associated with infant allergy outcomes. Study design Altogether, 975 infants participated in a randomized, controlled trial of daily vitamin D supplementation of 10 mg (400 IU) or 30 mg (1200 IU) from the age of 2 weeks. At 12 months of age, food and aeroallergen IgE antibodies were measured, and the occurrence of allergic diseases and wheezing were evaluated. Results We found no differences between the vitamin D supplementation groups in food (OR, 0.98; 95% CI, 0.66-1.46) or aeroallergen sensitization at 12 months (OR, 0.76; 95% CI,0.34-1.71). Allergic diseases or wheezing did not differ between groups, except for milk allergy which occurred more often in infants administered 30 mg vitamin D compared with the 10 mg dose (OR, 2.23; 95% CI, 1.00-4.96). Infants with high cord blood 25-hydroxyvitamin D (³100 nmol/L) had a higher risk of food allergen sensitization compared with those with lower 25(OH)D concentration (75-99.9 nmol/L; OR, 2.00; 95% CI, 1.19-3.39). Conclusions High-dose vitamin D supplementation did not prevent allergic sensitization, allergic diseases, or wheezing during the first year of life. In contrast, we observed an increased risk of milk allergy in infants randomized to higher vitamin D supplementation, and an increased risk of allergic sensitization in infants with high cord blood vitamin D status, indicating a possible adverse effect of high concentrations of vitamin D.