Calcium Intake and Metabolism in Infants and Young Children: A Systematic Review of Balance Studies for Supporting the Development of Calcium Requirements

Statement of Significance: A systematic review on calcium balance studies was commissioned by the WHO/FAO to support an international expert group tasked with updating calcium requirements for infants and children aged 0-4 y. This review provides a comprehensive evidence base for setting calcium requirements, using the factorial approach, in this population and highlights the future work needed in pediatric calcium balance design. Determining calcium requirements for infants and children is vital due to high calcium needs for growth. Balance studies enable comprehensive measurement of calcium metabolism and can support nutrient requirement development. This systematic review summarizes evidence from mass balance and isotopic studies in children aged 0-4 y to address key questions on calcium loss and absorption/retention identified by an expert group developing calcium requirements. Literature searches were implemented in multiple electronic databases to June 2020. Balance studies assessing calcium intake, loss, absorption, or retention in healthy children were eligible. A newly developed risk-of-bias assessment tool was used for balance studies, and a modified Grades of Recommendation, Assessment, Development, and Evaluation approach determined strength of evidence. Altogether, 23 studies (15 mass balance; 8 isotope) with 485 total participants were included. Only 3 studies were of children >6 mo. Mass balance studies suggested infant feed components may influence calcium balance. The random-effects model meta-regression on 42 mass balance study arms showed an average net calcium retention of 40.4% among infants aged 0-6 mo (beta = 0.404 [95% CI: 0.302, 0.506]). Isotope studies suggested calcium intake of 240 to 400 mg/d may promote optimal calcium absorption with minimal loss, and intake from human milk may lead to greater absorption and retention efficacy than formula or solid foods. Most studies had low risk of bias. Strength of evidence was low due to variability in infant feedings, limited endogenous and dermal calcium loss measures, and few studies isolating calcium effects. To improve certainty of the body of evidence, more balance studies isolating effects of calcium intake in this age group are needed. Future work on calcium needs should incorporate both balance measures and biological endpoints of importance (e.g. bone mineral density or content) to determine adequate calcium intake for growth in infants and children.

Automated summary

This systematic review examines calcium balance studies in infants and children aged 0-4 y to determine calcium requirements for this population. The review highlights the influence of factors such as calcium intake and absorption on calcium balance. However, more research is needed to address the limitations and isolate the effects of calcium intake in this age group.