Changes in Biochemical Parameters of the Calcium-Phosphorus Homeostasis in Relation to Nutritional Intake in Very-Low-Birth-Weight Infants

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

Growth and Bone Mineralization of Very Preterm Infants at Term Corrected Age in Relation to Different Nutritional Intakes in the Early Postnatal Period

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 (; (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 (; (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 ag

Evaluation of bone mineralization in former preterm born children: Phalangeal quantitative ultrasound cannot replace dual-energy X-ray absorptiometry

Background: Preterm infants are at risk of impaired bone health in later life. Dual-energy X-ray absorptiometry-scan (DXA) is the gold standard to determine bone mineralization. Phalangeal quantitative ultrasound (pQUS) is an alternative technique that is inexpensive, easy to use and radiation-free. The aim of this study was to investigate whether both techniques reveal equivalent results. Materials and methods: Sixty former preterm infants (31 boys; 29 girls) received a DXA and pQUS at age 9 to 10 years. DXA measured bone mineral content (BMC) and bone mineral density (BMD) for total body and lumbar spine (L1-4), while pQUS measured the amplitude dependent speed of sound (AD-SoS) and bone transit time (BTT) at metacarpals II-IV providing continuous values and Z-scores based on age and sex. Four statistical methods evaluated the association between both techniques: Pearson's correlation coefficients, partial correlation coefficients adjusted for gestational age, height and BMI, Bland-Altman analysis and cross tabulation. Results: Both techniques showed a statistically significant weak correlation for continuous values as well as Z-scores (0.291–0.462, p < 0.05). Boys had significant and relatively high correlations (0.468–0.585, p < 0.05). In comparison, the correlations for girls were not significant. Correlation coefficients further decreased while calculating the partial correlations. The Bland-Altman plots showed poor agreement. Sensitivity ranged from 33% to 92% and specificity from 16% to 68%. Positive and negative predictive values ranged from 4% to 38% and 82% to 97%, respectively. Conclusions: We found statistically significant weak correlations and poor agreement between DXA and pQUS measurements. DXA is not equivalent to pQUS and therefore not replaceable by this technique in former preterm born children at the age of 9 to 10 years

Effect of Donor Milk on Severe Infections and Mortality in Very Low-Birth-Weight Infants The Early Nutrition Study Randomized Clinical Trial

IMPORTANCE Infections and necrotizing enterocolitis, major causes of mortality and morbidity in preterm infants, are reduced in infants fed their own mother's milk when compared with formula. When own mother's milk is not available, human donor milk is considered a good alternative, albeit an expensive one. However, most infants at modern neonatal intensive care units are predominantly fed with own mother's milk. The benefits of add-on donor milk over formula are not clear. OBJECTIVE To determine whether providing donor milk instead of formula as supplemental feeding whenever own mother's milk is insufficiently available during the first 10 days of life reduces the incidence of serious infection, necrotizing enterocolitis, and mortality. DESIGN, SETTINGS, AND PARTICIPANTS The Early Nutrition Studywas a multicenter, double-blind randomized clinical trial in very low-birth-weight infants (birth weight <1500 g) admitted to 1 of 6 neonatal intensive care units in the Netherlands from March 30, 2012, through August 17, 2014. Intent-to-treat analysis was performed. INTERVENTIONS Infants received pasteurized donor milk or preterm formula during the first 10 days of life if own mother's milk was not (sufficiently) available. MAIN OUTCOMES AND MEASURES The primary end point was cumulative occurrence of serious infection (sepsis or meningitis), necrotizing enterocolitis, or mortality during the first 60 days of life. RESULTS A total of 930 infants were screened for inclusion; 557 were excluded, resulting in 373 infants (183 receiving donor milk and 190 receiving formula) who were evaluated by intent-to-treat analysis (median birth weight, 1066 g; mean gestational age, 28.4 weeks). Own mother's milk comprised 89.1% and 84.5% of total mean intake during the intervention period for the donor milk and formula groups, respectively. The incidence of the combined outcome was not different (85 [44.7%] [formula] vs 77 [42.1%] [donor milk]; mean difference, 2.6%; 95% CI, -12.7% to 7.4%). The adjusted hazard ratio was 0.87 (95% CI, 0.63-1.19; P =.37). CONCLUSIONS AND RELEVANCE In the current study, pasteurized donor milk and preterm formula as supplemental feeding during the first 10 days of life yielded similar short-term outcomes in very low-birth-weight infants regarding safety and efficacy when own mother's milk availability was insufficient. Future studies investigating longer duration of use of human donor milk on short-term and long-term outcomes are necessary