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

  • Armin ZittermannEmail author
  • Stefan Pilz
  • Heiner K. Berthold
Original Contribution

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

Vitamin D2 Vitamin D3 Infancy 25-Hydroxyvitamin D Nutritional rickets prevention 

Notes

Author contributions

AZ designed the study. AZ and HKB analyzed the data. ÁZ, SP, and HKB interpreted the data. AZ draft the manuscript. SP and HKB participated in the writing and critical revision of the manuscript. AZ, SP, and HKB read and approved the version of the manuscript being submitted.

Funding

None.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

394_2019_1912_MOESM1_ESM.pdf (18 kb)
Supplementary material 1 (PDF 17 KB)
394_2019_1912_MOESM2_ESM.pptx (52 kb)
Supplementary material 2 (PPTX 52 KB)
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Supplementary material 3 (PDF 1636 KB)
394_2019_1912_MOESM4_ESM.docx (18 kb)
Supplementary material 4 (DOCX 17 KB)
394_2019_1912_MOESM5_ESM.docx (16 kb)
Supplementary material 5 (DOCX 16 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Clinic for Thoracic and Cardiovascular SurgeryHerz- und Diabeteszentrum NRW, Ruhr University BochumBad OeynhausenGermany
  2. 2.Division of Endocrinology and Diabetology, Department of Internal MedicineMedical University of GrazGrazAustria
  3. 3.Department of Internal Medicine and GeriatricsBethel Clinic (EvKB)BielefeldGermany

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