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Different doses of phosphorus, calcium, and vitamin D in premature infants and their effect on bone mineralization: systematic review and meta-analysis

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Abstract

Purpose

This systematic review and meta-analysis aims to assess the impact of different doses of Ca, P, and vitamin D on bone mineralization in premature infants.

Methods

A systematic search (1990–2022) of MEDLINE (Ovid), Cochrane Library, Scopus, EMBASE, and CINAHL (EBSCO) was conducted. Randomized control trials and cohort studies, involving premature infants with birthweight ≤2.5 kg, who received supplementation and underwent bone mineral content reassessment, were included. Impact on growth indicators was also evaluated, but not systematically. Following the critical evaluation process, using PEDro scale and JBI critical appraisal checklist, high-quality studies were reviewed. Random effect meta-analyses (standardized mean difference) were performed to assess the effect of increased doses of Ca, P, and Vitamin D on bone health indicators.

Results

Eighteen studies were included, fifteen with enteral and three with parenteral nutrition regimen. The included studies’ mineral intake ranges presented high heterogeneity. The beneficial effect of higher doses of Ca and P on bone mineralization was evident in most studies, and unanimous when accompanied with higher doses of vitamin D, indicating the synergist effect of the three elements. Higher enteral nutrition doses of (a) Ca and P or (b) Ca, P, and vitamin D resulted in increased bone mineralization (standardized mean difference: 0.39; 95% CI 0.09, 0.69, and 1.72; 0.81, 2.16), respectively, while higher supplementation of only vitamin D presented no such effect (−0.01; −0.59, 0.56). Higher parenteral nutrition doses of Ca and P proved beneficial for bone mineralization (0.88; 0.34, 1.43). Higher enteral doses of all elements indicated no additional effect on growth.

Conclusions

Elevated intake of Ca (daily doses: Ca 95–135 mg/100 kcal) and P (55–95 mg/100 kcal) throughout enteral nutrition together with sufficient vitamin D intake might prove beneficial towards enhancing bone mineralization in preterm infants.

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Abbreviations

AAP:

American Academy of Pediatrics

BTT:

Bone transmission time

Ca:

Calcium

DXA:

Dual-energy X-ray absorptiometry

ELBW:

Extremely low birth weight

EN:

Enteral nutrition

ESPGHAN:

European Society of Paediatric Gastroenterology, Hepatology and Nutrition

HG:

High-dose group

LBW:

Low birth weight

LG:

Low-dose group

MBD:

Metabolic bone disease

P:

Phosphorus

PN:

Parenteral nutrition

RCTs:

Randomized control trials

SOS:

Speed of sound

VLBW:

Very low birth weight

WHO:

World Health Organization

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Acknowledgements

We thank Professor Mary Hickson for her constructive suggestions and support of preparing this research project.

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Authors and Affiliations

  1. School of Health Professions, Faculty of Health, University of Plymouth, Plymouth, UK

    Aikaterini Vervesou, Kate Maslin & Jennifer H Carroll

  2. Institute of Preventive Medicine, Environmental and Occupational Health, Prolepsis, Greece

    Dimitrios V. Diamantis

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  1. Aikaterini Vervesou
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  3. Kate Maslin
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  4. Jennifer H Carroll
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Contributions

A Vervesou: conceptualization, methodology, data collection, data synthesis, meta-analysis, investigation, resources data curation, writing original draft, project administration. DV Diamantis: methodology, data collection, data synthesis, meta-analysis, investigation, data curation, writing review, and editing. K Maslin, JH Carroll: conceptualization, methodology, writing review and editing, supervision.

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Correspondence to Aikaterini Vervesou.

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Vervesou, A., Diamantis, D.V., Maslin, K. et al. Different doses of phosphorus, calcium, and vitamin D in premature infants and their effect on bone mineralization: systematic review and meta-analysis. Nutrire 48, 48 (2023). https://doi.org/10.1186/s41110-023-00235-6

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