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

PurposeThis 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.MethodsA 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.ResultsEighteen 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.ConclusionsElevated 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.