Zinc Supplementation Trial in Pediatric Chronic Kidney Disease: Effects on Circulating FGF-23 and Klotho.

Background: Zinc status, its role in bone metabolism and efficacy of deficiency correction has not been well studied in children with chronic kidney disease (CKD). Objectives: The primary objective was to investigate whether 3 months of oral zinc supplementation corrects zinc deficiency in children with CKD who have native or transplanted kidneys. The secondary objective was to compare circulating intact FGF-23 (iFGF-23), c-terminal FGF-23 (cFGF-23), and Klotho between zinc-sufficient and zinc-deficient children with CKD and to assess the relationship between circulating zinc, iFGF-23, cFGF-23, Klotho, bone biomarkers, copper, and phosphate excretion pre-supplementation and post-supplementation of zinc. Methods: Forty-one children (25 male and 16 female, age 12.94 ± 4.13 years) with CKD in native or transplanted kidneys were recruited through 2 pediatric nephrology divisions in Ontario, Canada. Of those, 14 patients (9 native CKD, 5 transplant CKD) with identified zinc deficiency (64% enrollment rate) received zinc citrate supplement for 3 months: 10 mg orally once (4-8 years) or twice (9-18 years) daily. Results: Zinc deficiency (plasma concentration < 11.5 µmol/L) was found in 22 patients (53.7%). A linear regression model suggested that zinc concentration reduced by 0.026 µmol/L (P = .04) for every 1-unit of estimated glomerular filtration rate (eGFR) drop. Zinc deficiency status was associated with higher serum iFGF-23; however, this was predominantly determined by the falling GFR. Zinc deficient and sufficient children had similar circulating c-FGF-23 and alpha-Klotho. Normalization of plasma zinc concentration was achieved in 8 (5 native CKD and 3 transplant CKD) out of 14 treated patients rising from 10.04 ± 1.42 to 12.29 ± 3.77 µmol/L (P = .0038). There were no significant changes in other biochemical measures in all treated patients. A statistically significant (P = .0078) rise in c-FGF-23 was observed only in a subgroup of 11 children treated with zinc but not receiving calcitriol. Conclusions: Zinc status is related to kidney function and possibly connected to bone metabolism in patients with CKD. However, it plays a minor role in fine-tuning various metabolic processes. In this exploratory non-randomized study, 3 months supplementation with zinc corrected deficiency in just over half of patients and only modestly affected bone metabolism in asymptomatic CKD patients.

Contexte: Le statut du zinc, son rôle dans le métabolisme osseux et l'efficacité de la correction d'une carence n'ont pas encore été bien étudiés chez les enfants atteints d'insuffisance rénale chronique (IRC). Objectifs: L'objectif principal était d'examiner si une supplémentation orale en zinc pendant trois mois pouvait corriger une carence chez les enfants atteints d'IRC avec des reins natifs ou transplantés. Les objectifs secondaires étaient de comparer les taux circulants de FGF-23 intact (iFGF-23), de FGF-23 c-terminal (cFGF-23) et de Klotho d'enfants atteints d'IRC et ayant des niveaux corrects ou déficients en zinc, puis d'évaluer la relation entre le zinc circulant, l'iFGF-23, le cFGF-23, le Klotho, les biomarqueurs osseux et l'excrétion de cuivre et de phosphate avant et après la supplémentation en zinc. Méthodologie: Un total de 41 enfants (25 garçons et 16 filles, âgés de 12,94 ±4,13 ans) atteints d'IRC avec reins natifs ou transplantés ont été recrutés par deux divisions de néphrologie pédiatrique en Ontario, au Canada. De ceux-ci, 14 patients (9 avec reins natifs; 5 avec reins transplantés) qui présentaient une carence en zinc (taux d'inclusion de 64 %) ont reçu un supplément de citrate de zinc pendant trois mois à raison de 10 mg par voie orale une fois (4 à 8 ans) ou deux fois (9 à 18 ans) par jour. Résultats: Une carence en zinc (concentration plasmatique < 11,5 µmol/L) a été constatée chez 22 patients (53,7 %). Un modèle de régression linéaire a suggéré que la concentration de zinc diminue de 0,026 µmol/L (P = 0,04) pour chaque chute d'une unité de DFGe. Le statut de carence en zinc était associé à un taux sérique d'iFGF-23 plus élevé; cependant, cela était principalement déterminé par la baisse du DFG. Tous les enfants, avec ou sans carence en zinc, avaient des taux circulants similaires de c-FGF-23 et d'alpha-Klotho. La normalisation de la concentration plasmatique de zinc a été obtenue chez 8 patients (5 avec reins natifs; 3 avec reins transplantés) sur les 14 qui ont été traités, passant de 10,04 ±1,42 à 12,29 ±3,77 µmol/L (P = 0,003 8). Aucun changement significatif n'a été observé dans les autres mesures biochimiques chez les patients traités. Une augmentation statistiquement significative (P = 0,007 8) du taux de c-FGF-23 a été observée uniquement dans un sous-groupe de 11 enfants traités avec du zinc, mais ne recevant pas de calcitriol. Conclusion: Le statut du zinc est lié à la fonction rénale et peut être lié au métabolisme osseux chez les patients atteints d'IRC. Il joue toutefois un rôle mineur dans le réglage fin de divers processus métaboliques. Dans cet essai exploratoire non randomisé, une supplémentation en zinc pendant trois mois a permis de corriger la carence chez un peu plus de la moitié des patients et n'a eu qu'un effet modeste sur le métabolisme osseux chez les patients asymptomatiques atteints d'IRC.

Parental and child genetic contributions to obesity traits in early life based on 83 loci validated in adults: the FAMILY study.

BACKGROUND: The genetic influence on child obesity has not been fully elucidated. OBJECTIVE: This study investigated the parental and child contributions of 83 adult body mass index (BMI)-associated single-nucleotide polymorphisms (SNPs) to obesity-related traits in children from birth to 5 years old. METHODS: A total of 1402 individuals were genotyped for 83 SNPs. An unweighted genetic risk score (GRS) was generated by the sum of BMI-increasing alleles. Repeated weight and length/height were measured at birth, 1, 2, 3 and 5 years of age, and age-specific and sex-specific weight and BMI Z-scores were computed. RESULTS: The GRS was significantly associated with birthweight Z-score (P = 0.03). It was also associated with weight/BMI Z-score gain between birth and 5 years old (P = 0.02 and 6.77 × 10-3 , respectively). In longitudinal analyses, the GRS was associated with weight and BMI Z-score from birth to 5 years (P = 5.91 × 10-3 and 5.08 × 10-3 , respectively). The maternal effects of rs3736485 in DMXL2 on weight and BMI variation from birth to 5 years were significantly greater compared with the paternal effects by Z test (P = 1.53 × 10-6 and 3.75 × 10-5 , respectively). CONCLUSIONS: SNPs contributing to adult BMI exert their effect at birth and in early childhood. Parent-of-origin effects may occur in a limited subset of obesity predisposing SNPs.

Prenatal and early-life predictors of atopy and allergic disease in Canadian children: results of the Family Atherosclerosis Monitoring In earLY life (FAMILY) Study.

Prenatal and early-life environmental exposures play a key role in the development of atopy and allergic disease. The Family Atherosclerosis Monitoring In earLY life Study is a general, population-based Canadian birth cohort that prospectively evaluated prenatal and early-life traits and their association with atopy and/or allergic disease. The study population included 901 babies, 857 mothers and 530 fathers. Prenatal and postnatal risk factors were evaluated through questionnaires collected during the antenatal period and at 1 year. The end points of atopy and allergic diseases in infants were evaluated through questionnaires and skin prick testing. Key outcomes included atopy (24.5%), food allergy (17.5%), cow's milk allergy (4.8%), wheezing (18.6%) and eczema (16%). The association between infant antibiotic exposure [odds ratio (OR): 2.04, 95% confidence interval (CI): 1.45-2.88] and increased atopy was noted in the multivariate analysis, whereas prenatal maternal exposure to dogs (OR: 0.60, 95% CI: 0.42-0.84) and acetaminophen (OR: 0.68, 95% CI: 0.51-0.92) was associated with decreased atopy. This population-based birth cohort in Canada demonstrated high rates of atopy, food allergy, wheezing and eczema. Several previously reported and some novel prenatal and postnatal exposures were associated with atopy and allergic diseases at 1 year of age.

Validation of surrogate limb analysis for body composition in children by dual energy X-ray absorptiometry (DXA).

BACKGROUND/OBJECTIVES: Dual energy X-ray absorptiometry (DXA) is a recognized tool for measurement of body composition and provides benefits of low dose radiation, quick scan time and multiple measurement options. Challenges arise in scanning children, particularly with limb movement. We aimed to validate the use of surrogate limb substitutions compared with whole-body scans by DXA for measuring fat, lean and bone mass in children. SUBJECTS/METHODS: DXA scans were obtained from 3-year-old children who had normal positioning and no limb movement (n=246) or movement of a single limb (n=55). By replacing the measurements of one scanned limb with those of the opposite limb, we obtained an estimate value that was compared with the original whole-body scan measures for fat, lean and bone mass, percent whole-body fat and total mass for scans without or with movement. RESULTS: Original normal scan analyses were highly correlated with estimates using substitution of the surrogate limb for all body compartments (R(2)=0.986-0.999, P<0.005). The Bland-Altman analysis demonstrated high levels of agreement between the estimates using surrogate limb and original whole-body measurements. Differences in estimate values and variance were greater with limb substitution in scans with movement compared to without movement. CONCLUSIONS: Use of limb surrogate methodology for fat mass, lean mass, bone mineral content, percent fat and total mass, is a valid alternative that minimizes variation in estimates of body composition from DXA scans in young children in which a single limb is affected by movement. This will allow inclusion of scans with movement artifact in a single limb for data analysis.

Bone mineralization is elevated and less heterogeneous in adults with type 2 diabetes and osteoarthritis compared to controls with osteoarthritis alone.

PURPOSE: The purpose of this study was to determine whether trabecular bone mineralization differed in adults with type 2 diabetes compared to adults without type 2 diabetes. METHODS: Proximal femur specimens were obtained following a total hip replacement procedure from men and women ≥65 years of age with and without type 2 diabetes. A scanning electron microscope was used for quantitative backscattered electron imaging (qBEI) analysis of trabecular bone samples from the femoral neck. Gray scale images (pixel size=5.6 µm(2)) were uploaded to ImageJ software and gray level (GL) values were converted to calcium concentrations (weight [wt] % calcium [Ca]) using data obtained with energy dispersive X-ray spectrometry. The following bone mineralization density distribution (BMDD) outcomes were collected: the weighted mean bone calcium concentration (CaMEAN), the most frequently occurring bone calcium concentration (CaPEAK) and mineralization heterogeneity (CaWIDTH). Differences between groups were assessed using the Student's t-test for normally distributed data and Mann-Whitney U-test for non-normally distributed data. An alpha value of <0.05 was considered significant. RESULTS: Thirty-five Caucasian participants were recruited (mean [standard deviation, SD] age, 75.5 [6.5]years): 14 adults with type 2 diabetes (years since type 2 diabetes diagnosis, 13.5 [7.4]years) and 21 adults without type 2 diabetes. In the adults with type 2 diabetes, bone CaMEAN was 4.9% greater (20.36 [0.98]wt.% Ca versus 19.40 [1.07]wt.% Ca, p=0.015) and CaWIDTH was 9.4% lower (median [interquartile range] 3.55 [2.99-4.12]wt.% Ca versus 3.95 [0.71]wt.% Ca, p<0.001) compared to controls. There was no between-group difference in CaPEAK (21.12 [0.97]wt.% Ca for type 2 diabetes versus 20.44 [1.30]wt.% Ca for controls, p=0.121). CONCLUSION: The combination of elevated mean calcium concentration in bone and lower mineralization heterogeneity in adults with type 2 diabetes may have deleterious effects on the biomechanical properties of bone. These microscopic alterations in bone mineralization, which may be mediated by suppressed bone remodeling, further elucidate higher fracture risk in adults with type 2 diabetes.

Bone Health in Childhood: Usefulness of Biochemical Biomarkers.

Development of the human skeleton begins in early embryonic life and continues through childhood into early adulthood. The acquisition of peak bone mass during these vulnerable periods may impact on skeletal fragility in later adult years. Once the skeleton has reached maturity, bone remodelling continues with periodic replacement of old bone with new at the same location. Bone biomarkers are specifically derived biomarkers that reflect both formation by osteoblasts and resorption by osteoclasts. Children have significantly higher concentrations of bone biomarkers than adults due to both skeletal growth and rapid bone turnover during childhood and adolescence. Biochemical assessment of markers of bone turnover may be important in the diagnosis, prognosis and management of metabolic bone disease. This review will discuss the various serum bone markers used for assessing bone health and the factors that influence their utility.

Alendronate for steroid-induced osteopenia in children with acute lymphoblastic leukaemia or non-Hodgkin's lymphoma: results of a pilot study.

BACKGROUND/OBJECTIVES: Osteopenia is a significant morbidity in children undergoing therapy for acute lymphoblastic leukaemia (ALL) or non-Hodgkin's lymphoma (NHL). We conducted a pilot study to assess the impact of alendronate on whole body bone mineral content (WB-BMC), lumbar spine bone mineral density (LS-BMD), biochemical measures of bone mineral metabolism, as well as gross motor function and health-related quality of life (HRQL) in children undergoing therapy for ALL or NHL. METHODS: Ten children (nine boys) between the ages of 3.6 and 14.6 years, on identical maintenance chemotherapy for ALL or NHL were treated with oral alendronate once weekly, and daily calcium supplementation, for a period of six months. Outcome measures were WB-BMC and LS-BMD; biochemical measures of bone mineral metabolism including plasma osteocalcin, C-terminal telopeptide of type I collagen (CTx), serum calcium, 25-hydroxy-vitamin D (25-OHD), and parathyroid hormone (PTH); as well as assessments of motor function and HRQL. RESULTS: A gain in Z score was observed in 7/9 evaluable patients for WB-BMC (mean increase of 0.49) and LS-BMD (0.51). Plasma osteocalcin and CTx showed a change in bone turnover favouring formation over resorption. Serum calcium and 25-OHD remained normal throughout treatment. After an initial spike, serum PTH returned to baseline values at week 4. Measures of motor function showed some improvement and there were modest gains in HRQL. CONCLUSIONS: Alendronate therapy was tolerated well. Further study in a larger sample of children with ALL or NHL is warranted, in the context of a randomized clinical trial.

Long-term valproate and lamotrigine treatment may be a marker for reduced growth and bone mass in children with epilepsy.

PURPOSE: To determine whether long-term treatment with valproate (VPA) and/or lamotrigine (LTG) in children with epilepsy is associated with altered growth and/or bone metabolism. METHODS: Twenty-seven boys and 26 girls, aged 3 to 17 years (9.2 +/- 3.9, mean +/- SD), with epilepsy treated with VPA and/or LTG for > or =2 years were evaluated for growth, nutrient intakes, physical activity, bone mineral density (BMD), and blood biochemical indices of mineral and bone metabolism. RESULTS: Twenty-three (43.4%) of the children had a body height below the 10th percentile. Z-scores for BMD below -1.5 occurred in 24.4% of the children. When patients were divided into two groups according to daily activity score, a significantly lower Z-score for total body BMD (p = 0.007), percentile for body height (p = 0.05), and plasma parathyroid hormone (PTH; p = 0.04), osteocalcin (p = 0.04) and 25-hydroxyvitamin D (25OHD) (p = 0.01) were found in the inactive compared with the active group. Z-score for total body BMD was correlated with daily activity score (r = 0.43, p = 0.008). Plasma intact osteocalcin and intact PTH values correlated significantly (r = 0.36, p = 0.02). Plasma 1,25-dihydroxyvitamin D was within normal range for all subjects. When patients were divided into LTG-alone, VPA-alone, and LTG-plus-VPA treatment groups, significantly lower (p < 0.05) plasma osteocalcin and percentile for body height were found in the VPA-plus-LTG treatment group. CONCLUSIONS: Long-term VPA and LTG therapy, particularly when combined, is associated with short stature, low BMD, and reduced bone formation. These alterations may be mediated primarily through reduced physical activity rather than through a direct link to the VPA and/or LTG therapy.

Elevated intact parathyroid hormone is associated with reduced biochemical markers of bone formation and resorption measured in blood in infant piglets receiving oral dexamethasone for 15 days.

Seven-day-old male Yorkshire piglets were randomized to receive either dexamethasone (DEX) 0.5 mg/kg/day or placebo (water) for 15 days (n = 8/group). Body weight and length, plasma intact parathyroid hormone (PTH), N-Mid osteocalcin and C-terminal telopeptide of type I collagen (CTx) were measured at baseline and end of the study. The indices of bone metabolism did not differ between DEX and placebo groups at baseline. At the end of the study, plasma intact PTH was increased (p < 0.01) and N-Mid osteocalcin (p < 0.01) and CTx (p < 0.01) were decreased from baseline value in the DEX group but not in the placebo group. The reduction (Z-score) in N-Mid osteocalcin was greater than that in CTx (p < 0.05). We conclude that exogenous DEX in young piglets stimulates a rise in circulating intact PTH. Both circulating CTx and osteocalcin are reduced with the decline in osteocalcin greater than that in CTx.

Randomized trial of breastfeeding support in very low-birth-weight infants.

OBJECTIVE: To determine if supplementary structured breastfeeding counseling (SSBC) for both parents compared with conventional hospital breastfeeding support (CHBS) improves the duration of breastfeeding in very low-birth-weight infants up to 1 year old. DESIGN: Randomized trial with longitudinal follow-up of infants at term, and ages 1, 3, 6, and 12 months (infant ages corrected for prematurity). SETTING: A tertiary-level neonatal intensive care unit (NICU) and geographically defined region in central-west Ontario, Canada. PARTICIPANTS: Parents of infants with a birth weight less than 1500 g, who planned to breastfeed. INTERVENTIONS: The SSBC consisted of viewing a video on breastfeeding for preterm infants; individual counseling by the research lactation consultant; weekly personal contact in the hospital; and frequent postdischarge contact through the infants' first year or until breastfeeding was discontinued. The CHBS group had standard breastfeeding support from regular staff members confined to the period of hospitalization in the NICU. MAIN OUTCOME MEASURE: Duration of breastfeeding. RESULTS: At study entry, there were no statistically significant differences in major demographic characteristics between groups. The mean duration of breastfeeding was 26.1 weeks (SD = 20.8; median, 17.4) in the SSBC group and 24.0 weeks (SD = 20.5; median, 17.4) in the CHBS group (not statistically significant). CONCLUSIONS: Long-term breastfeeding counseling of parents of very low-birth-weight infants in this study did not demonstrate a significant difference in duration of breastfeeding. These results may be explained by the high motivation to breastfeed in both groups, a relatively advantaged population, and the availability of community breastfeeding resources, which may have diminished any significant differences that could have resulted from a breastfeeding intervention. The results of this study, compared with previous studies of very low-birth-weight infants, indicate a new trend to longer duration of breastfeeding in preterm infants.

Magnesium absorption using stable isotope tracers in healthy children and children treated for leukemia.

Intestinal magnesium (Mg) absorption was measured in six healthy children (control) and in four children treated for acute lymphoblastic leukemia with the single-isotope fecal recovery technique (SIFRT). The objective of this study was to determine Mg absorption in young children with acute lymphoblastic leukemia using stable isotope tracers. Fractional and absolute absorption levels determined by SIFRT were not significantly different between children with acute lymphoblastic leukemia (fractional absorption: 58.3 +/- 10.6% [mean +/- SEM], absolute absorption: 3.66 +/- 0.71 mg x kg(-1) x d(-1), [0.15 +/- 0.03 mmol x kg(-1) x d(-1)]) and control children (fractional absorption: 61.4 +/- 7.5%, absolute absorption: 5.69 +/- 0.85 mg x kg(-1) x d(-1), [0.23 +/- 0.03 mmol x kg(-1) x d(-1)]). Average Mg absorption in young children (aged 3--8 y) was 60.2 +/- 5.8%. This study describes the first application of the SIFRT to assess Mg absorption in young children and illustrates the feasibility of the SIFRT in this age group to obtain more accurate information on Mg absorption.

Special nutritional needs of infants for prevention of and recovery from bronchopulmonary dysplasia.

Extremely low birth weight infants who develop severe respiratory disease may have special nutrient requirements imposed by a combination of enhanced utilization of nutrients or the need for epithelial cell repair resulting from the disease process, as well as to support catch-up growth. Inositol, free fatty acids, vitamin E and vitamin A are proposed as nutrients for which infants at risk of chronic pulmonary insufficiency may have special requirements. Of these nutrients, only for vitamin A does suggestive evidence exist that high doses when given intramuscularly may reduce the incidence of death or chronic lung disease. Exogenous steroid therapy (dexamethasone), which is often used to improve pulmonary compliance in ventilated premature infants, may compromise vitamin A status and induce restricted somatic and bone mineral growth. Supplemental nutrition by means of enriched infant formulas has provided benefits in growth and bone mass accretion to infants recovering from bronchopulmonary dysplasia up to 3-mo corrected age. This growth advantage was not sustained over the subsequent 9 mo, suggesting that prolonged nutritional support is required until catch-up growth is complete. Further studies are required to delineate the needs for specific nutrients such as antioxidant vitamins and minerals or vitamin A that may play a role in preventing severe chronic lung disease in premature infants. As well, the role of supplemental nutrition (beyond the requirements of term infants) to support catch-up growth and maintenance during the critical stages of early development requires further investigation before evidence-based nutrient recommendations can be developed for this special population of infants.

Calcium competes with zinc for a channel mechanism on the brush border membrane of piglet intestine.

Interactions between Ca(+2) and Zn(+2) at the intestinal brush border membrane occur via unclear mechanisms. We hypothesized that Zn(+2) and Ca(+2) are transported across the brush border membrane via a multidivalent metal channel. Using brush border membrane vesicles (BBMV) prepared from intestines of 8 sow-fed piglets, we sought to determine whether Ca(+2) competes with Zn(+2) for uptake. Extravesicular Zn(+2) was removed with ethylenediamine-tetraacetic acid. Time curves of Zn(+2) and Ca(+2) uptake by BBMV were conducted with increasing concentrations of Ca(+2) and Zn(+2), respectively. Saturation curves compared kinetic parameters of Zn(+2) uptake with and without Ca(+2). In addition, Zn(+2) uptake was measured in the presence of various classical Ca(+2) channel modulators. Over 20 min, a 0.4x concentration of Zn(+2) lowered Ca(+2) uptake by vesicles, whereas a 30x concentration of Ca(+2) was necessary to lower Zn(+2) uptake. These data suggest that Ca(+2) has lower affinity than Zn(+2) for a brush border membrane transport protein. Kinetic parameters showed higher K(m) values with 4 or 15 mM Ca(+2) but unchanged J(max), suggesting competitive inhibition. The Ca(+2) channel blocking agents, La(+3), Ba(+2), verapamil, and diltiazem, inhibited Zn(+2) uptake, whereas calcitriol, trans 1,2 cyclohexanediol, cis/trans 1,3 cyclohexanediol, and the L-type Ca(+2) channel agonist, Bay K8644, induced Zn(+2) uptake. These data were consistent with competition for a common transport mechanism on the brush border membrane, possibly a novel multimetal channel. Copyright 2001 Elsevier Science Inc.

Divalent metals inhibit and lactose stimulates zinc transport across brush border membrane vesicles from piglets.

Interactions between metals of similar coordination chemistry are of relevance to infant nutrition due to the highly variable metal:metal ratios found in formulas. Using ratios similar to those found in infant formulas, our objectives were to determine the effects of metals and of lactose and other saccharides on Zn(+2) transport across intestinal brush border membranes. Brush border membrane vesicles prepared from intestines of 5 preweaned piglets were used to determine whether Ca(+2), Mg(+2), Fe(+2), Cu(+2), Cd(+2), or Mn(+2) would antagonize Zn(+2) uptake. (65)Zn(+2) uptake by brush border membrane vesicles was measured over 20 min with metal concentrations constant, and at 1 min with increasing metal concentrations. Zn(+2) bound to the external surface of vesicles was removed with ethylenediamine-tetraacetic acid. Lactose induced Zn(+2) uptake to a greater extent than glucose polymer, whereas maltose, galactose, or galactose/glucose had no effect. Over 20 min, a 10:1 concentration of Fe(+2), Cd(+2), Cu(+2), and Mn(+2) lowered Zn(+2) uptake significantly (P < 0.05). Higher concentrations of divalent cation significantly lowered Zn(+2) (0.2 or 0.1 mM) uptake for all metals tested (P < 0.05), except for Mn(+2) (0.1 mM Zn(+2)). Inhibition constant determination quantified relative competitive potential with Mg(+2) < Ca(+2) << Mn(+2) < Fe(+2) < Zn(+2) << Cu(+2). Relative amounts of Ca(+2), Mg(+2), and Fe(+2) similar to those found in infant formulas reduced Zn(+2) uptake by at least 40%. Our data demonstrate that dietary minerals compete during brush border membrane transport, and may help explain antagonistic mineral interactions observed in vivo. Divalent metal concentrations and lactose content of milk affect zinc absorption in neonates and must be carefully considered in formula design.

Factors influencing body composition of premature infants at term-adjusted age.

We investigated the influence of body size at birth, feeding of mother's milk versus formula, or standard-term formula versus energy- or nutrient-enriched formula on the growth and whole body bone mineral content (BMC), lean and fat mass (using dual-energy X-ray absorptiometry) of low-birth-weight (LBW) infants to term-adjusted age. LBW infants who were appropriate for gestational age were lighter and shorter than term-born infants (n = 46) but had a higher percent fat mass (19-28% vs. 15 +/- 7%). For LBW infants fed standard formula or mother's milk after hospital discharge, the mean BMC expressed either as a function of weight (17 +/- 2, 19 +/- 2 vs. 20 +/- 2 g/kg) or length (1.1 +/- 0.2, 1.1 +/- 0.2 vs. 1.5 +/- 0.2 g/cm) was more than 1 SD below term infant values. However, infants fed a nutrient-enriched formula from hospital discharge had BMC within 1 SD below term infants. Infants who were born small, compared to appropriate for gestational age, compared to infants of similar birth weight had lower percent body fat (16 +/- 6 vs. 19 +/- 5) and lower BMC (47 +/- 3 vs. 62 +/- 5 g) at term age. Both size at birth and diet influence patterns of growth and body composition in early life in very-low-birth-weight (VLBW) infants. The long-term significance of these variable growth patterns in VLBW infants in early life requires further investigation.

Human milk feeding of the micropremie.

There is increasing evidence that mother's milk is an appropriate feeding even for LBW and VLBW infants. During early neonatal life, supplements in the form of human milk fortifiers or single nutrients may be necessary to maintain an adequate biochemical status especially for sodium, phosphorus, and protein. The ideal amount and balance of supplemental nutrients to add to mother's milk for small premature infants remain unknown. From research to date, it is clear that growth responses to fortified mother's milk fed in early life may not be the most important outcomes in relation to long-term growth and development. Infants who receive human milk in early life may be at reduced risk for developing infections and allergy as well as osteopenia and growth failure. Further studies are needed to provide a better understanding of the role of human milk as the sole source of nutrition in premature infants, especially the micropremie.