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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

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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.

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Authors and Affiliations

  1. Clinic for Thoracic and Cardiovascular Surgery, Herz- und Diabeteszentrum NRW, Ruhr University Bochum, Georghstraße 11, 32545, Bad Oeynhausen, Germany

    Armin Zittermann

  2. Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, 8036, Graz, Austria

    Stefan Pilz

  3. Department of Internal Medicine and Geriatrics, Bethel Clinic (EvKB), 33611, Bielefeld, Germany

    Heiner K. Berthold

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  1. Armin Zittermann
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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.

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Correspondence to Armin Zittermann.

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The authors declare that they have no conflict of interest.

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Zittermann, A., Pilz, S. & Berthold, H.K. Serum 25-hydroxyvitamin D response to vitamin D supplementation in infants: a systematic review and meta-analysis of clinical intervention trials. Eur J Nutr 59, 359–369 (2020). https://doi.org/10.1007/s00394-019-01912-x

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  • DOI: https://doi.org/10.1007/s00394-019-01912-x

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