Serum 25-hydroxyvitamin D response to vitamin D supplementation in infants: a systematic review and meta-analysis of clinical intervention trials

Eur J Nutr. 2020 Feb;59(1):359-369. doi: 10.1007/s00394-019-01912-x. Epub 2019 Feb 5.

Abstract

Purpose: For the prevention of nutritional rickets, 400 IU vitamin D daily and circulating 25-hydroxyvitamin D (25OHD) concentrations > 50 nmol/L are recommended, whereas the toxicity threshold is set at 250 nmol/L. We synthesized the evidence for the effect of vitamin D supplementation on incremental 25OHD in infants up to 1 year of age.

Methods: We performed a systematic review and meta-analysis of intervention trials in several databases. A total of 87 records were identified for full-text review and 27 articles with 61 studies were included in the final analysis.

Results: The selected 61 studies included 1828 participants. Nineteen cohorts had already mean baseline 25OHD levels ≥ 50 nmol/L. The weighted mean difference in 25OHD following vitamin D supplementation was + 49.4 nmol/L (95% CI 43.6-55.3 nmol/L; P < 0.001). The increment was dose-dependent (P = 0.002), was higher in full-term than in pre-term infants (P < 0.001), was higher in infants with baseline 25OHD < 50 nmol/L as compared to ≥ 50 nmol/L (P = 0.001), and was marginally influenced by the 25OHD test procedure (P = 0.080). Vitamin D3 doses of 400 IU/day were sufficient to achieve 25OHD concentrations ≥ 50 nmol/L in most full-term infants. A 25OHD level of 250 nmol/L was not exceeded in ≥ 97.5% of infants at doses between 200 and 1200 IU/day, but potentially in ≥ 2.5% of infants at a dose of 1600 IU/day.

Conclusions: Vitamin D supplementation of 400 IU/day is sufficient for achieving 25OHD concentrations able to prevent nutritional rickets. A more personalized vitamin D dosing strategy would require 25OHD testing, but also assay standardization.

Keywords: 25-Hydroxyvitamin D; Infancy; Nutritional rickets prevention; Vitamin D2; Vitamin D3.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Clinical Trials as Topic
  • Dietary Supplements*
  • Humans
  • Infant
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D / therapeutic use*
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / prevention & control*
  • Vitamins / blood
  • Vitamins / therapeutic use*

Substances

  • Vitamins
  • Vitamin D
  • 25-hydroxyvitamin D