Rice protein-based infant formula: current status and future development.

Rice is the world's leading staple cereal food and is the major source of protein for many parts of the world. Rice is among the first solid foods fed to infants in many cultures, in part because of its hypoallergenicity from lack of gluten. Nutritional quality of rice protein compares favorably with other cereal proteins including wheat, oat and barley. It is rich in methionine and cystine, although as is the case for other cereals, it is an incomplete protein source for human infants with lysine and threonine being the primary limiting amino acids. Fortification of rice proteins with these two limiting amino acids improves its protein quality. Rice protein-based infant formulas (RPF) were initially based on high protein rice flours, but more recently are based on rice protein concentrates, isolates or hydrolysates, fortified with lysine and threonine. Hypoallergenicity efficacy, particularly for hydrolyzed rice protein-based formulas, has been reported, and limited data indicated that rice protein based infant formula may provide potentially adequate alternative if standard milk- or soy protein-based formulas are not tolerated. Unlike the rice-protein based infant formula, rice beverage formulas made from rice flour are nutritionally inadequate for infants. Reports have indicated stunted growth in infants/children fed rice beverage formulas. Future development for the RPF include those based on genetically improved rice with high lysine and threonine content, supplementation with appropriate mineral and fat blend, and long-term clinical studies in infants to confirm its efficacy and safety.

Regional bone mass measurement from whole-body dual energy X-ray absorptiometry scan.

There are no data on the relative accuracy and precision of regional bone mass measurement from whole-body dual energy X-ray absorptiometry (DXA) scans in small young subjects. Twelve domestic swine piglets (2550-17,660 g) were scanned on a single-beam and on a fan beam densitometer using each humerus and femur as the region of interest to determine the validity of five different scan modes: two infant whole body (IWB), two spine, and one rat whole body (RWB) scan mode in the determination of regional bone mass measurements. DXA bone mineral content (BMC( measurements from RWB and IWB fan beam and IWB single-beam scans were highly predictive of ash weight (adjusted r2 = 0.98, 0.94, 0.94, respectively). Correlation between left and right limbs was highly significant (p < 0.001 for all comparisons) for ash weight (r = 0.99) and for DXA measurements of BMC (r = 0.92-0.99), area (r = 0.92-0.99), and bone mineral density (r = 0.87-0.99) for all modes of DXA scan. Repeatability (as standard deviation of differences of repeated scans) varied with scan mode and DXA parameters and ranged from 1.5 to 7.6%and from 1.8 to 14.7% for intra-and interoperator, respectively. We conclude that regional DXA measurements from IWB and RWB scans can be assessed accurately and with adequate precision for clinical use in subjects with low bone mass comparable with infants and young children. The RWB scan is useful for research studies. However, appropriate training and documentation of precision errors is needed to minimize repeatability errors.

Disproportionate alterations in body composition of large for gestational age neonates.

OBJECTIVE: The objective was to compare dual-energy x-ray absorptiometry-measured body composition between large (LGA) and appropriate (AGA) birth weight for gestational age neonates. STUDY DESIGN: LGA term infants (n = 47) with birth weights > or =4000 g were compared with 47 gestational age-matched AGA infants; 11 LGA infants were born to mothers with gestational (9) or pregestational diabetes (2). Dual-energy x-ray absorptiometry scans were performed at 1.8 +/- 1.0 days after birth. RESULTS: Body weight and length were the dominant predictors of body composition in LGA and AGA neonates. However, LGA neonates had significantly (P <.001, all comparisons) higher absolute amounts of total body fat, lean body mass, and bone mineral content and had significantly (P <.001, all comparisons) higher proportions of total body fat and bone mineral content but lower lean body mass as a percent of body weight. The changes for total body fat and lean body mass as a percent of body weight were greatest (P <.001) in LGA infants whose mothers had impaired glucose tolerance. CONCLUSION: LGA neonates have higher body fat and lower lean body mass than AGA infants. Impaired maternal glucose tolerance exaggerated these body composition changes.

Prediction of bone strength in growing animals using noninvasive bone mass measurements.

This study aims to test the hypothesis that noninvasive bone mass measurements can be used to predict bone strength in a piglet model. Dual energy X-ray absorptiometry measurements of bone mineral content (BMC), bone mineral density (BMD), and bone area (BA) were obtained from four sets of bones (left and right humeri and femora) of 12 piglets (6-68 days and 2250-17660 g). Bone strength, defined by the energy to bone failure, fracture moment, and flexural rigidity, was determined from three point bending tests using an Instron material testing system. Results show that bone mass between left and right extremities was highly correlated (r = 0.96 to 0.99, P < or 0.001 all comparisons) and was similar for bone strength (r = 0.85 to 0.98, P < 0.01 all comparisons). However, based on the standard deviation of the difference between measurements from left and right extremities, the agreement sides was better for bone mass than for bone strength measurements (r = 0.68-0.99, P < = 0.05-< or = 0.001). The predictive ability of bone mass on bone strength varied (adjusted r2 = 0.41-0.97) depending on the bone tested and the measurement parameter used, although remained statistically significant in all instances (P < 0.05-< or = 0.001). We conclude that the developing organisms, noninvasive bone mass measurements are correlated with and predictive of bone strength, although bones from the same side and same anatomical site should be used for comparison purposes.

Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta.

Preclinical models have shown that transplantation of marrow mesenchymal cells has the potential to correct inherited disorders of bone, cartilage, and muscle. The report describes clinical responses of the first children to undergo allogeneic bone marrow transplantation (BMT) for severe osteogenesis imperfecta (OI), a genetic disorder characterized by defective type I collagen, osteopenia, bone fragility, severe bony deformities, and growth retardation. Five children with severe OI were enrolled in a study of BMT from human leukocyte antigen (HLA)-compatible sibling donors. Linear growth, bone mineralization, and fracture rate were taken as measures of treatment response. The 3 children with documented donor osteoblast engraftment had a median 7.5-cm increase in body length (range, 6.5-8.0 cm) 6 months after transplantation compared with 1.25 cm (range, 1.0-1.5 cm) for age-matched control patients. These patients gained 21.0 to 65.3 g total body bone mineral content by 3 months after treatment or 45% to 77% of their baseline values. With extended follow-up, the patients' growth rates either slowed or reached a plateau phase. Bone mineral content continued to increase at a rate similar to that for weight-matched healthy children, even as growth rates declined. These results suggest that BMT from HLA-compatible donors may benefit children with severe OI. Further studies are needed to determine the full potential of this strategy.

Do sweat calcium losses affect bone mass during firefighter training?

Although participation in vigorous exercise is associated with increased bone mass, recent evidence suggests that loss of calcium in sweat may result in a negative calcium balance and, ultimately, a decrease in bone mass. Anthropometric characteristics, habitual physical activity levels, dietary calcium intake, bone mineral content, and bone turnover markers were measured in 42 male recruits before and after 4 months of firefighter training. During two strenuous mid-training sessions, sweat calcium concentrations were measured; they averaged 1.1 mM. Whole body and total hip bone mineral content increased significantly, as did one marker of bone formation, and were not associated with sweat calcium concentration. This study demonstrates that intense physical training sessions that produce high sweat rates do not have an adverse effect on the bone mineral content of healthy young men.

Physiologic predictors of lumbar spine bone mass in neonates.

Dual energy x-ray absorptiometry (DXA) of the lumbar spine (LS) was measured in 201 singleton infants with birth weights from 1152 to 3970 g and gestational ages from 27 to 42 wk. All infants were well and studied at a mean (+/-SD) of 2.1 (+/-1.6) days after birth. There were 75 Caucasian (46 males, 29 females) and 126 African American infants (58 males, 68 females). Scan acquisition of the first to fourth lumbar vertebrae was performed with a single beam whole body scanner (Hologic QDR 1000/W densitometer, Hologic Inc, Waltham, MA, U.S.A.) using the infant spine mode. Scan analysis was performed with software version 4.57Q and consistent region of interest. The SD of difference for duplicate LS scans is <1.4% at a mean bone mineral content (BMC) of 2.14 g. Results show that LS BMC, area, bone mineral density (BMD) increased by approximately 550%, 280% and 180%, respectively, between 27 and 42 wk gestational age. Body mass accounted for about 70% and 55% of the variance in BMC and BMD respectively. In contrast, the infant's length appears to be the best determinant of LS area and accounts for about 75% of the variance in LS area. Race, gender or season has little or no effect on LS bone mass. There was progressive increase in BMC and area from first to fourth lumbar vertebra but BMD was significantly higher only at the fourth lumbar vertebra. We conclude that DXA LS can be performed even in small preterm infants. Its excellent precision, low radiation exposure and rapid scan acquisition offers promise as a useful tool for widespread use in pediatrics. Our data may be used as a basis for further studies in physiologic and pathologic situations that may affect bone mineralization in infants.

Body composition in human infants at birth and postnatally.

The predictive values of anthropometric measurements, race, gender, gestational and postnatal ages, and season at birth and at study for the total body dual energy X-ray absorptiometry (DXA)-derived lean mass (LM), fat mass (FM) and fat mass as a percentage of body weight (%FM) were determined in 214 singleton appropriate birth weight for gestational age infants [101 Caucasian (60 boys, 41 girls) and 113 African American (55 boys, 58 girls)]. Gestational ages were 27-42 wk and the infants were studied between birth and 391 d, weighing between 851 and 13446 g. In addition, predictive value of body weight, LM and FM for DXA bone measurements was also determined. Scan acquisition used Hologic QDR 1000/W densitometer and infant platform and scans without significant movement artifacts were analyzed using software 5.64p. Body weight, length, gender and postnatal age were significant predictors of LM (adjusted R:(2) >0. 94) and FM (adjusted R:(2) >0.85). Physiologic variables had little predictive value for %FM except in the newborns (adjusted R:(2) 0. 69). Body weight was the dominant predictor of LM and FM, although length had similar predictive value for LM with increasing postnatal age. Female infants had less LM and more FM throughout infancy (P: < 0.01). LM or FM offered no advantage over body weight in the prediction of bone mass measurements. DXA is a useful means with which to determine body composition, and our data are important in the design and assessment of nutritional intervention studies.

Body composition measurements during infancy.

Infancy is the period of most rapid postnatal growth and is accompanied by major changes in body composition (BC). There are many challenges to successfully measuring BC of infants in vivo, which include the inherent limitations in the underlying assumptions for each technique. The small body mass and rapid nonuniform changes in body parts, that is, the components of BC during infancy, can strain the technical limits of all methods. Many techniques for in vivo BC measurement used in older people have been applied to infants. However, the vast majority of them either are difficult to adapt for widespread use in infants, or the roles and limitations for using them during infancy are ill-defined because of limited or no critical validation and cross-calibration studies. Based on validation data from animals, well-defined methodological issues in data acquisition and analyses, availability of normative data, and pertinent accuracy and precision of the technique to allow us to determinate clinically relevant changes in BC within a reasonable time interval, three techniques appear to be most suitable for in vivo BC measurement in infants. Anthropometric measurements can be used in field studies or for group comparisons, and total body electrical conductivity (TOBEC) and selected dual-energy X-ray absorptiometry (DXA) measurements can be used to compare BC in individual infants. DXA has the advantages of being able to measure bone mass and the potential to be adaptable to the widely available existing instruments. However, regardless of the techniques used in measuring BC in infants, meticulous attention to details in data acquisition and data analysis, and a knowledge of the limitations of the particular technique are the prerequisites for generating valid data.

Maternal calcium supplementation and fetal bone mineralization.

OBJECTIVE: To determine the effect of maternal calcium supplementation during pregnancy on fetal bone mineralization. METHODS: Healthy mothers with early ultrasound confirmation of dates and singleton pregnancies were enrolled in a double-masked study and randomized before 22 weeks' gestation to 2 g/day of elemental calcium or placebo until delivery. Maternal dietary intake at randomization and at 32-33 weeks' gestation was recorded with 24-hour dietary recalls. Dual-energy x-ray absorptiometry measurements of the whole body and lumbar spine of the neonates were performed before hospital discharge. RESULTS: The infants of 256 women (128 per group) had dual-energy x-ray absorptiometry measurements during the first week of life. There were no significant differences between treatment groups in gestational age, birth weight, or length of the infants, or in the total-body or lumbar spine bone mineral content. However, when bone mineral content was analyzed by treatment group within quintiles of maternal dietary calcium intake, total body bone mineral content (mean +/- standard error of the mean) was significantly greater in infants born to calcium-supplemented mothers (64.1+/-3.2 versus 55.7+/-2.7 g in the placebo group) in the lowest quintile of dietary calcium intake (less than 600 mg/day). The effect of calcium supplementation remained significant after adjustment for maternal age and maternal body mass index and after normalization for skeletal area and body length of the infant. CONCLUSION: Maternal calcium supplementation of up to 2 g/day during the second and third trimesters can increase fetal bone mineralization in women with low dietary calcium intake. However, calcium supplementation in pregnant women with adequate dietary calcium intake is unlikely to result in major improvement in fetal bone mineralization.

Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta.

In principle, transplantation of mesenchymal progenitor cells would attenuate or possibly correct genetic disorders of bone, cartilage and muscle, but clinical support for this concept is lacking. Here we describe the initial results of allogeneic bone marrow transplantation in three children with osteogenesis imperfecta, a genetic disorder in which osteoblasts produce defective type I collagen, leading to osteopenia, multiple fractures, severe bony deformities and considerably shortened stature. Three months after osteoblast engraftment (1.5-2.0% donor cells), representative specimens of trabecular bone showed histologic changes indicative of new dense bone formation. All patients had increases in total body bone mineral content ranging from 21 to 29 grams (median, 28), compared with predicted values of 0 to 4 grams (median, 0) for healthy children with similar changes in weight. These improvements were associated with increases in growth velocity and reduced frequencies of bone fracture. Thus, allogeneic bone marrow transplantation can lead to engraftment of functional mesenchymal progenitor cells, indicating the feasibility of this strategy in the treatment of osteogenesis imperfecta and perhaps other mesenchymal stem cell disorders as well.

Postnatal development of bone mineral status during infancy.

OBJECTIVE: To determine postnatal development in bone mineral status and its relationship to anthropometric measurements and other physiologic variables during the first year. METHODS: Cross-section observational study of total body bone mineral content (TB BMC) and density (TB BMD) of 130 healthy infants (71 male and 59 female with 63 white and 67 African American) between 1 and 391 days. Whole body dual energy X ray absorptiometry (DXA) scans were performed on unsedated infants using a bone densitometer with pediatric platform. Scan analyses were performed with software version V5.64P. The ability of study independent variables to explain variance in bone mineral status was determined by multiple linear regression analysis. RESULTS: During infancy, average TB BMC increased by 389% and TB BMD increased by 157%. The best determinant of bone mineral status is body weight which accounted for 97% of TB BMC, 98% of TB area and 86% of TB BMD variation. Postnatal age and body length jointly added only 1%, < 1% and 2.5%, respectively, to the explained variation of these DXA measurements; race, gender and season all failed to reach statistical significance. CONCLUSION: In healthy infants, body weight is the dominant predictor of bone mineral status. The percent increase in TB BMC differs from increase in TB BMD. Normative data generated from this study would be useful in the identification of abnormal bone mineral status in infants.

Effect of hand dominance on bone mass measurement in sedentary individuals.

The aim of this study was to determine in healthy sedentary subjects the effect of hand dominance on side-to-side difference in bone area and bone mass for upper and lower extremities. Dual-energy X-ray absorptiometry (DXA) measurements of both forearms and hips were performed on 193 right-handed and 20 left-handed subjects as determined by self-report. Scan acquisition and scan analyses were performed by one investigator, but all scan pairs were independently assessed for symmetry of positioning and movement artifacts by three investigators. Results show that DXA measurements between sides may be highly correlated regardless of the symmetry of the scan pair. However, asymmetric DXA scan pairs may have more than twice the side-to-side difference found in symmetric DXA scan pairs at the hip. Side-to-side differences between subregions were greater than the differences between measurements at the total radius, ulna, or hip. For symmetric pairs of DXA scans, the dominant forearm has significantly higher bone area and bone mineral content (BMC). Bone mineral density (BMD) was significantly higher only in the ulna of the dominant forearm. However, the nondominant forearm has higher values than dominant forearm in at least one DXA measurement in >24% of the subjects. There were no significant differences in any DXA measurements between hips, and higher DXA measurements did not occur significantly more frequently at the hip corresponding to the dominant hand. We conclude that healthy sedentary subjects tend to have proportionally higher bone area and BMC in the dominant forearm that results in similar BMD between dominant and nondominant forearms. This relationship does not appear to be applicable to measurements at the hip. In addition, there is a significant proportion of subjects with higher bone area and BMC in the nondominant extremities. Thus, in sedentary subjects, the consistency in the use of same extremity and the consistency in scan acquisition techniques and scan analyses is of greater importance than the selection of an extremity based on hand dominance in DXA studies.

Laboratory assessment of nutritional metabolic bone disease in infants.

OBJECTIVES: There are numerous laboratory investigations available for the assessment of an infant with suspected metabolic bone disease (MBD); thus, comprehensive laboratory investigations on every aspect of MBD would impose unnecessary stress to the infant and the costs involved would be prohibitive. An overview of the assessment of an infant with suspected MBD, in particular, nutrition-related bone disease, is presented. Our objectives include an understanding of: 1. the importance of appropriate information from history and physical examination to guide the laboratory investigations; 2. relevance and limitations of specific laboratory investigations: a. radiologic studies include diagnostic radiographs and quantitative bone mass determination by dual energy x-ray absorptiometry, b. biochemical measurements to determine mineral homeostasis and bone turnover, c. vitamin (vitamin D metabolites) and hormonal (parathyroid hormone and calcitonin) measurements; with respect to diagnosis and monitoring of the natural progress or response to therapy. CONCLUSION: Relevant information from clinical history and physical examination, and an understanding of the role and limitations of various laboratory investigations, would allow the optimal utilization of laboratory tests in the assessment of an infant with MBD.

Dual-energy X-ray absorptiometry studies of bone mineral status in newborn infants.

We studied bone mineral status using dual-energy X-ray absorptiometry (DXA) on 150 singleton newborn infants with birth weights 1002-3990 g and gestational ages (GA) 27-42 weeks. Eighty-five infants were preterm (< 38 weeks), and 79 infants were low birth weight (< or = 2500 g). In addition, we aimed to determined the predictive value of anthropometric measurements, race, and gender on variability in bone mineral status. Data were acquired using a whole body DXA scanner with a pediatric platform. Scan analyses were performed with software version V5.64P. Results showed a highly significant (p < 0.001 for all comparisons) correlation among the continuous independent variables, gestational age, birth weight, study weight, study bare weight, and study length, and between independent and each of the dependent variables, total body bone mineral content (TB BMC), TB area, and TB bone mineral density (TB BMD). The best single determinant of bone mineral status is body weight, accounting for 95% of TB BMC and TB area and for 86% of TB BMD variation. Body length was the only additional significant predictor of TB area. Inclusion of postnatal age (during the first week after birth), race, gender, or season, either individually or in combination, failed to improve bone mineral status explanation. By term (GA 38-42 weeks, birth weight 2700-3990 g), the mean TB BMC was 68.2 g, TB area 307.6 cm2, and TB BMD 0.221 g/cm2. We conclude that DXA can be performed even in small preterm infants during the newborn period. Our results can be used as a basis for further studies in physiologic and pathologic situations that might affect bone mineralization in infants.

Visual acuity and fatty acid status of term infants fed human milk and formulas with and without docosahexaenoate and arachidonate from egg yolk lecithin.

Preterm infants fed formulas with docosahexaenoic acid (DHA, 22:6n-3) during the interval equivalent to the last intrauterine trimester and beyond have higher circulating DHA and transiently higher visual acuity compared with infants fed formulas containing linolenic acid. In term infants several nonrandomized studies of infants receiving DHA from human milk suggest a relationship between DHA status and acuity, but the evidence for a cause-and-effect relationship is mixed. In the present study, term infants were randomly assigned to a standard term formula (n = 20) or the same formula with egg yolk lecithin to provide DHA (0.1%) and arachidonic acid (AA, 20:4n-6, 0.43%) (n = 19) at levels reported in milk of American women. A third group of infants was breast fed for > or = 3 mo (n = 19). Grating visual acuity (Teller Acuity Card procedure) and plasma and red blood cell (RBC) phosphatidylcholine (PC) and phosphatidylethanolamine (PE) DHA and AA were determined at corrected ages of 2, 4, 6, 9 (acuity only), and 12 mo past term = 40 wk postmenstrual age (PMA). At 2 mo breast-fed infants and infants fed the supplemented formula had higher grating acuity than term infants fed standard formula. As in preterm infants, the increase was transient. Plasma PC DHA and AA and RBC PE AA increased by 2 mo in supplemented infants, but RBC PE DHA in supplemented infants was not higher than in controls until 4 mo and beyond. Despite normal intrauterine accumulation of DHA and AA, infants fed formula with 2% linolenic acid and 0.1% DHA had better 2-mo visual acuity than infants fed formula with 2% linolenic acid.

Technical considerations of dual-energy X-ray absorptiometry-based bone mineral measurements for pediatric studies.

Dual X-ray absorptiometry (DXA) measurements have been shown to provide useful information on bone mineral status in young pediatric subjects. The purpose of this study was to challenge this system under various conditions to determine the clinical and experimental parameters that may be encountered which could interfere with DXA-based bone mineral content (BMC) and bone mineral density (BMD) measurements. Variations in data acquisition, including the covering of step phantom (external calibration standard) with a cotton blanket or partial exclusion of step phantom in the scan field, tissue freezing, or the presence of small nonmetallic objects, did not significantly alter DXA BMC or BMD measurements. By contrast, the presence of movement artifact, radiographic contrast media, and nonmetallic orthopedic casts significantly interfered with DXA BMC and BMC measurements. Variability in operator-dependent analysis of DXA scans occurred with regional analysis of whole body scans for DXA BMC and BMD measurements (average coefficient of variation was 2.9% and 1%, respectively, depending on the region analyzed) but did not affect the total (whole body) result. A minor adjustment in the manual delineation of the step phantom during data analysis may result in almost a 30% difference in DXA BMC and BMD. We conclude that movement artifact, radiographic contrast media, nonmetallic or orthopedic cast, and variations in operator-dependent data analysis may interfere with DXA BMC and BMD measurement in young pediatric subjects. Therefore, appropriate care should be taken to reduce or eliminate such interference.

Effect of different vitamin A intakes on very-low-birth-weight infants.

Formula-fed infants with birth weights < or = 1500 g (n = 61) were stratified by 250-g birth-weight ranges and randomly assigned to receive one of three preterm infant formulas (vitamin A contents of 820 IU, 1640 IU, or 2900 IU/MJ; 1 RE = 3.3 IU vitamin A activity) when subjects tolerated 0.314 MJ.kg-1.d-1. Experimental formula feedings were continued until infants weighed approximately 2 kg or until hospital discharge. Vitamin A status as indicated by serum retinol and retinol-binding protein (RBP) concentrations significantly decreased during experimental formula feeding at the lowest vitamin A intake. All subjects fed the formula providing the lowest vitamin A intake had hyporetinolemia (< 0.70 mumol/L, or < 20 micrograms/dL), which occurred less frequently (P < 0.05) with the intermediate (6 of 20) and the high (6 of 21) vitamin A intakes. Other outcome measures, including increases in weight, length, and head circumference, and ventilatory support and oxygen therapy, were not different among groups. After the end of the experimental formula-feeding period, all infants were fed standard infant formulas with a vitamin A content of 715 IU/MJ. In a subset of 19 of these infants, subsequent vitamin A status was monitored at ages 6-12 mo and was found to be comparable with that of older children and adults, regardless of the vitamin A content of the formula fed during hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)