Effect of Higher vs Standard Dosage of Vitamin D3 Supplementation on Bone Strength and Infection in Healthy Infants: A Randomized Clinical Trial

Abstract

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 D3 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 D3 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/cm3; 95% CI, -8.3 to 14.2), cross-sectional area (mean difference, -0.9 mm2; 95% CI, -5.0 to 3.2), or polar moment of inertia (mean difference, -66.0 mm4, 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 ≥20.03 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 D3 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 D3 seems adequate in maintaining vitamin D sufficiency in children younger than 2 years.

Trial registration: ClinicalTrials.gov Identifier: NCT01723852.

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.. Participant Flow of the Vitamin D Intervention in Infants Study

Figure 2.. Serum 25-Hydroxyvitamin D, Ionized Calcium, and Intact Parathyroid Hormone Concentrations During the Vitamin D Intervention in Infants Study

A, Mean 25-hydroxyvitamin D (25[OH]D) concentrations with 95% CIs at baseline (cord blood), age 12 months, and age 24 months in infants randomized to vitamin D, 400 IU/d and 1200 IU/d. B through D, Crude values at 24-month follow-up by intervention group. Horizontal lines in panels B, C, and D represent median values. P values refer to differences between intervention groups as tested by the 2-tailed, unpaired, independent-samples t test. To convert serum 25(OH)D to nanomoles per liter, multiply by 2.496; ionized calcium to millimoles per liter, multiply by 0.25; and parathyroid hormone to nanograms per liter, multiply by 1.0.