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Preterm infants often have a reduced bone mineral content (BMC) with increased risk of metabolic bone disease. After birth it is difficult to supply calcium (Ca) and phosphorus (P) comparable to the high fetal accretion rate. It is not known whether high supplementation of minerals in the early postnatal period improves growth and bone mineralization. The aim of this study was to evaluate growth and bone mineralization at term corrected age (TCA) in very and extremely preterm infants who received different enteral Ca and P intakes during the first 10 days of life. Infants ( n = 109) with birth weights below 1500 g were randomly assigned to one of three groups that differed in the nutritional protocols delivered until day 10: Group A, mother's own milk (MOM) and donor milk (unfortified); Group B, MOM (unfortified) and preterm formula; Group C, MOM (start fortification >50 mL/day) and preterm formula. Due to the earlier commencement of fortification, Group C received higher intakes of calcium and phosphorus and protein ( p < 0.001) until day 10. At TCA weight, length, BMC and bone mineral density (BMD), measured by dual-X-ray absorptiometry, were not different between the groups. Nutritional intake of P was positively associated with length (β; (95% confidence interval (CI): 0.20 (0.001; 0.393); p -value = 0.048), whereas Ca intake was negatively associated with BMC (-1.94 (-2.78; -1.09); p -value < 0.001). A small interaction between Ca and P intake was only found for BMD (0.003 (0.00002; 0.00006); p -value = 0.036). The volume of human milk per kg provided during the first 10 days was positively associated with BMC (β; (95% CI): 0.013 (0.002; 0.023); p < 0.017). Higher intakes of Ca and P during the first 10 days, as provided in this study, did not improve bone mineralization at term corrected age., Competing Interests: The authors declare no conflict of interest. Johannes B. Van Goudoever reports grants outside the submitted work from Mead Johnson Nutrition, during the conduct of the study, grants from EU, FP-7 programme. Johannes B. Van Goudoever serves as director of the National Human Milk bank and as board member of the National Health Council and the National Breastfeeding Committee.

Magnesium (Mg) is an essential mineral in the body, impacting the synthesis of biomacromolecules, bone matrix development, energy production, as well as heart, nerve, and muscle function. Although the importance of Mg is evident, reference values for serum Mg (sMg) in pediatric patients (more specifically, in neonates) are not well established. This systematic literature review and meta-analysis (using 47 eligible studies) aims to quantify normal and tolerable ranges of sMg concentrations during the neonatal period and to highlight the factors influencing Mg levels and the importance of regulating sMg levels during pregnancy and birth. In newborns without Mg supplementation during pregnancy, magnesium levels at birth (0.76 (95% CI: 0.52, 0.99) mmol/L) were similar to that of mothers during pregnancy (0.74 (95% CI: 0.43, 1.04) mmol/L), but increased during the first week of life (0.91 (95% CI: 0.55, 1.26) mmol/L) before returning to adult levels. This pattern was also seen in newborns with Mg supplementation during pregnancy, where the average was 1.29 (95% CI: 0.50, 2.08) mmol/L at birth and 1.44 (95% CI: 0.61, 2.27) mmol/L during the first week of life. Factors influencing these levels include prenatal Mg supplementation, gestational age, birth weight, renal maturity/function, and postnatal Mg intake. Elevated Mg levels (>2.5 mmol/L) have been associated with an increased risk of mortality, admission into intensive care, hypotonia, hypotension, and respiratory depression but sMg concentrations up to 2.0 mmol/L appear to be well tolerated in neonates, requiring adequate survey and minimal intervention., Competing Interests: Jacques Rigo participated in the design and coordinated the multi-centric study on the multi-chamber bags of parenteral nutrition for preterm infants initiated by Baxter Healthcare Corporation. He received financial support from Baxter Healthcare Corporation for travel and conferencing related to this work. Sissel J. Moltu has participated as a speaker at the Baxter iCAN program. Catherine Pieltain, Viola Christmann, Francesco Bonsante, Silvia Iacobelli, and Stéphane Marret declare no conflicts of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; and in the decision to publish the results.

Preterm infants are at significant risk to develop reduced bone mineralization based on inadequate supply of calcium and phosphorus (Ca-P). Biochemical parameters can be used to evaluate the nutritional intake. The direct effect of nutritional intake on changes in biochemical parameters has not been studied. Our objective was to evaluate the effect of Ca-P supplementation on biochemical markers as serum (s)/urinary (u) Ca and P; alkaline phosphatase (ALP); tubular reabsorption of P (TrP); and urinary ratios for Ca/creatinin (creat) and P/creatinin in Very-Low-Birth-Weight infants on Postnatal Days 1, 3, 5, 7, 10, and 14. This observational study compared two groups with High ( n = 30) and Low ( n = 40) intake of Ca-P. Birth weight: median (IRQ) 948 (772-1225) vs. 939 (776-1163) grams; and gestational age: 28.2 (26.5-29.6) vs. 27.8 (26.1-29.4) weeks. Daily median concentrations of biochemical parameter were not different between the groups but linear regression mixed model analyses showed that Ca intake increased the uCa and TrP ( p = 0.04) and decreased ALP ( p = 0.00). Phosphorus intake increased sP, uP and uP/creat ratio and ALP ( p ≤ 0.02) and caused decrease in TrP ( p = 0.00). Protein intake decreased sP ( p = 0.000), while low gestational age and male gender increased renal excretion of P ( p < 0.03). Standardized repeated measurements showed that biochemical parameters were affected by nutritional intake, gestational age and gender., Competing Interests: The authors declare no conflict of interest. J.B.v.G. reports grants outside the submitted work from Mead Johnson Nutrition, during the conduct of the study, grants from Danone, grants and non-financial support from Hipp, personal fees and non-financial support from Nestle Institute and non-financial support from Baxter.