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Uteroplacental insufficiency (UPI) induced intrauterine growth restriction (IUGR) predisposes individuals to adult onset metabolic morbidities, including insulin resistance and cardiovascular disease. An underlying component of the development of these morbidities is adipose dysfunction; specifically a disproportionately abundant visceral adipose tissue. We hypothesize that IUGR will increase rats visceral adiposity and visceral expression of PPARgamma, a key regulator of adipogenesis. To test this hypothesis we employed a well described UPI induced IUGR rat model. Subcutaneous and visceral adipose levels were measured in adolescent control and IUGR rats using MRI. Expression of PPARgamma mRNA and protein, as well as PPARgamma target genes, was measured in neonatal, adolescent and adult rats. UPI induced IUGR increases the relative amount of visceral adipose tissue in male, but not female, adolescent rats in conjunction with an increase in PPARgamma2mRNA and protein in male visceral adipose. Importantly, these effects are seen prior to the onset of overt obesity. We conclude that increased PPARgamma2 expression in VAT of IUGR males is associated with increased visceral adiposity. We speculate that the increase in visceral adiposity may contribute to the metabolic morbidities experienced by this population. [ABSTRACT FROM AUTHOR]

Background: Premature birth is associated with increased adipose deposition after birth. Standard anthropometry (body weight, length, and head circumference) may not adequately assess fat deposition. Validated methods to assess adiposity are needed to optimize growth quality in preterm infants. The purpose of this study was to identify covariates of infant body fat., Methods: Air displacement plethysmography (ADP), standard anthropometry, and body circumferences were measured at hospital discharge in preterm (n = 28; 31-35 wk postmenstrual age (PMA)) and term (n = 28; 38-41 wks PMA) infants., Results: Body weight, length, and head circumference were lower for preterm infants (P < 0.05) at hospital discharge compared with that of term infants. Despite smaller body size and younger PMA, preterm infant percent body fat (%BF) by ADP was 12.33 ± 4.15% vs. 9.64 ± 4.01% in term infants (P = 0.01). Mid-arm circumference (MAC) is a covariate of %BF in both preterm and term infants (adjusted R(2) = 0.49; P < 0.001). In preterm infants alone, MAC accounted for 60.4% of the variability of percent body fat (%BF) by ADP (P < 0.01)., Conclusions: Preterm infants have increased body fat deposition as they approach term-corrected age, and MAC is a reliable, low-cost measure for monitoring infant body fat deposition in preterm and term infants.

Background: Preterm birth impairs the infant's stress response due to interruption of autonomic nervous system (ANS) development. Preterm infants demonstrate a prolonged and aberrant sympathetic response to stressors. ANS development may be promoted by massage therapy (MT), which has been shown to improve stress response in preterm infants., Aims: The aim of this study was to compare preterm infant ANS function and stress response during sleep and caregiving epochs, as measured by heart rate variability (HRV), after two weeks of twice-daily MT., Study Design: A subset of participants from a larger randomized, masked, controlled trial was used., Subjects: Twenty-one infants (8 males and 13 females) from a larger study of 37 medically stable preterm infants were studied. The infants were receiving full volume enteral feedings with a mean post-menstrual age of 31.4 (MT) and 30.9 (control) weeks., Outcome Measures: Low to high frequency (LF:HF) ratio of HRV was the outcome of interest., Results: There was a significant group×time×sex interaction effect (p<.05). Male control infants demonstrated a significant decline in LF:HF ratio from baseline to the second caregiving epoch, suggesting decreased mobilization of sympathetic nervous system response when exposed to stressors. Male MT infants demonstrated increased LF:HF ratio during caregiving and decreased LF:HF ratio during sleep epochs, suggesting improved ANS function, although this was not statistically significant. LF:HF ratio was similar in female MT and female control infants during caregiving and sleep., Conclusions: Control males had decreased HRV compared to MT males. There was no difference in HRV between MT and control females., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Preterm infants are exposed to numerous stressors during hospitalization and by term corrected gestational age they have lower body weight but a greater proportion of total body as well as abdominal visceral adipose tissue (VAT) accumulation. Greater abdominal VAT stores have a known association with metabolic syndrome. Mechanical-tactile stimulation (MTS) improves modulation of stress response in both humans and rodents. We hypothesize that MTS, administered during an established model of neonatal stress, would decrease stress-driven adiposity and prevent associated metabolic imbalances in adult rats. Neonatal stress, administered to rat pups from postnatal days 5 to P9, consisted of needle puncture and hypoxic/hyperoxic challenge during 60 min of maternal separation (STRESS; n=20). Mechanical-tactile stimulation (MTS; n=20) was administered to rat pups for 10 min during maternal separation in the stress protocol. Control animals received standard care (CTL; n=20). MRI measured adult (P120) abdominal total fat mass, subcutaneous (SAT) and visceral adipose tissue (VAT). Body weight and fasting serum adiponectin, leptin, glucose, insulin, and corticosterone were also measured. STRESS results in elevated VAT/SAT ratio compared to CTL but lower abdominal total fat mass and abdominal SAT. STRESS males experience hyperinsulinemia. Both STRESS and MTS had elevated leptin with lower adiponectin and corticosterone compared to CTL. In summary, neonatal stress promotes greater abdominal VAT accumulation and, in males, caused hyperinsulinemia and hypoadiponectinemia. Importantly, MTS normalized the VAT/SAT ratio and prevented hyperinsulinemia. We speculate that MTS ameliorates some of the negative metabolic consequences of early life perturbations due to neonatal stress exposure., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: Preterm infants are born with low bone mineral. Neonatal stress further impedes bone mineralization. Clinical evidence suggests that tactile and kinesthetic stimulation (TKS) improves bone phenotype and decreases stress response. Clinical and translational studies indicate the IGF-1 axis, responsible for postnatal growth and bone mineralization, is a key player. We hypothesized that TKS would attenuate the negative impact of neonatal stress on bone phenotype and the IGF-1 axis in weanling rats., Methods: Neonatal stress (STRESS) or TKS (STRESS + 10min TKS) was administered from D6 to D10. Control animals received standard care. Tissue was harvested on D21. Dual energy x-ray absorptiometry (DXA) and bone morphometry were performed and serum osteocalcin, type I procollagen N-terminal propeptide (PINP), tartrate-resistant acid phosphatase (TRAP), and bone and liver mRNA levels of IGF-1, IGF-1 receptor (IGF-1R), and growth hormone receptor (GHR) were measured., Results: Neonatal stress increased bone mineral content (BMC), area (BA), growth plate width, liver IGF-1 mRNA, and serum IGF-1. TKS maintained areal bone mineral density (aBMD) and bone specific IGF-1 and IGF-1R mRNA while STRESS decreased compared to controls., Conclusions: Neonatal stress results in apparent accelerated growth response. TKS differed from STRESS with improved tibia aBMD and increased bone specific IGF-1 mRNA.

Intrauterine growth restriction (IUGR) modifications to postnatal skeletal growth may increase adult fracture, especially in females who have greater risk of osteoporosis. Little is known about the effect of IUGR on the patterns of postnatal endochondral ossification and bone development. Here for the first time we reveal bone formation, mineralization, and strength in IUGR female rats during early postnatal life and adulthood. Endochondral ossification rate of the hypertrophic zone (HZ) and hypertrophic cell length (HCL) at distal femur and proximal tibia, and primary ossification center (POC) of the whole femur and tibia were quantified at birth to day 21. Bone area (BA), bone mineral content (BMC), and bone density by dual-energy X-ray absorptiometry and bone strength determined from three-point bending were measured at days 21 and 120. IUGR femur and tibia HZ, HCL, and POC were significantly diminished at birth to day 21. IUGR decreased BA and BMC as well as femur/tibia diameter, length, stiffness, and peak load values at days 21 and 120. Our findings demonstrate a negative long-term effect of IUGR on bone size, mineral content, and strength in weanling and adult female rats. We speculate that IUGR decreases endochondral ossification responsiveness, and in turn, postnatal linear skeletal growth, mineralization, and strength in female rats., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objectives: To assess the effect of massage on weight gain and body fat deposition in preterm infants., Study Design: Preterm infants (29-32 weeks) were randomized to the massage group (n = 22, 12 girls, 10 boys) or the control group (n = 22, 12 girls, 10 boys). Treatment was masked with massage or control care administered twice-daily by licensed massage therapists (6 d/wk for 4 weeks). Body weight, length, Ponderal Index (PI), body circumferences, and skinfold thickness (triceps, mid-thigh, and subscapular [SSF]) were measured. Circulating insulin-like growth factor I, leptin, and adiponectin levels were determined by enzyme-linked immunosorbent assay. Daily dietary intake was collected., Results: Energy and protein intake as well as increase in weight, length, and body circumferences were similar. Male infants in the massage group had smaller PI, triceps skinfold thickness, mid-thigh skinfold thickness, and SSF and increases over time compared with control male infants (P < .05). Female infants in the massage group had larger SSF increases than control female infants (P < .05). Circulating adiponectin increased over time in control group male infants (group × time × sex interaction, P < .01) and was correlated to PI (r = 0.39, P < .01)., Conclusions: Twice-daily massage did not promote greater weight gain in preterm infants. Massage did, however, limit body fat deposition in male preterm infants. Massage decreased circulating adiponectin over time in male infants with higher adiponectin concentrations associated with increased body fat. These findings suggest that massage may improve body fat deposition and, in turn, growth quality of preterm infants in a sex-specific manner., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: To test the hypothesis that massage would improve autonomic nervous system (ANS) function as measured by heart rate variability (HRV) in preterm infants., Study Design: Medically stable, 29- to 32-week preterm infants (17 massage, 20 control) were enrolled in a masked, randomized longitudinal study. Licensed massage therapists provided the massage or control condition twice a day for 4 weeks. Weekly HRV, a measure of ANS development and function, was analyzed using SPSS generalized estimating equations., Results: Infant characteristics were similar between groups. HRV improved in massaged infants but not in the control infants (P<0.05). Massaged males had a greater improvement in HRV than females (P<0.05). HRV in massaged infants was on a trajectory comparable to term-born infants by study completion., Conclusion: Massage-improved HRV in a homogeneous sample of hospitalized, medically stable, preterm male infants and may improve infant response to exogenous stressors. We speculate that massage improves ANS function in these infants.

Preterm delivery (<37 weeks post-menstrual age) is associated with suboptimal bone mass. We hypothesized that tactile/kinesthetic stimulation (TKS), a form of infant massage that incorporates kinesthetic movement, would increase bone strength and markers of bone accretion in preterm infants. Preterm, AGA infants (29-32 weeks) were randomly assigned to TKS (N=20) or Control (N=20). Twice daily TKS was provided 6 days per week for 2 weeks. Control infants received the same care without TKS treatment. Treatment was masked to parents, health care providers, and study personnel. Baseline and week two measures were collected for tibial speed of sound (tSOS, m/sec), a surrogate for bone strength, by quantitative ultrasound (Sunlight8000) and urine markers of bone metabolism, pyridinium crosslinks and osteocalcin (U-MidOC and unOC). Infant characteristics at birth and study entry as well as energy/nutrient intake were similar between TKS and Control. TKS intervention attenuated the decrease in tSOS observed in Control infants (p<0.05). Urinary pyridinium crosslinks decreased over time in both TKS and CTL (p<0.005). TKS infants experienced greater increases in urinary osteocalcin (U-MidOC, p<0.001 and unOC, p<0.05). We conclude that TKS improves bone strength in premature infants by attenuating the decrease that normally follows preterm birth. Further, biomarkers of bone metabolism suggest a modification in bone turnover in TKS infants in favor of bone accretion. Taken together, we speculate that TKS improves bone mineralization., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: Neonatal stress impairs postnatal bone mineralization. Evidence suggests that mechanical tactile stimulation (MTS) in early life decreases stress hormones and improves bone mineralization. Insulin-like growth factor (IGF1) is impacted by stress and essential to bone development. We hypothesized that MTS administered during neonatal stress would improve bone phenotype in later life. We also predicted an increase in bone specific mRNA expression of IGF1 related pathways., Methods: Neonatal stress (STRESS) and MTS (STRESS+10 min of MTS) were given from D6 to D10 of rat life and tissue was harvested on D60 of life. Dual energy x-ray absorptiometry (DXA), bone morphometry, serum osteocalcin, type I procollagen N-terminal propeptide (PINP), tartrate-resistant acid phosphatase (TRAP), and bone and liver mRNA levels of IGF1, IGF1 receptor (IGF1R), and growth hormone receptor (GHR) were measured., Results: Stress resulted in reduced bone area and bone mineral content (BMC) compared to naive control (CTL). MTS intervention increased BMC and tibial growth plate width compared to STRESS. MTS also resulted in higher osteocalcin, and, in males, lower TRAP (p<0.05). MTS resulted in three-fold, two-fold, and six-fold higher bone specific IGF1, IGF1R, and GHR, respectively (p ≤ 0.001) compared to STRESS., Conclusions: MTS in early postnatal life improves long-term bone mineralization. IGF1 and related pathways may explain improved BMC.

Objective: To validate use of chip-based immunoaffinity capillary electrophoresis on dried blood spot samples (DBSS) to measure obesity-related hormones., Methods: Chip-based immunoaffinity capillary electrophoresis was used to measure adiponectin, leptin and insulin in capillary serum and DBSS in pregnant women and infant heelstick at birth and six weeks. Concordance of measurements was determined with Pearson's correlation and Bland-Altman plots., Results: We report high concordance between results obtained from serum and DBSS., Conclusions: Ease of sample collection and storage makes DBSS an optimal method for use in studies involving neonates and young children, as well as studies conducted in areas where freezer storage is not available., (Copyright © 2011 Wiley-Liss, Inc.)

Stress in early life negatively influences growth quality through perturbations in body composition including increased fat mass. At term (40 weeks) preterm infants have greater fat mass and abdominal visceral adipose tissue than term-born infants. Mechanical-tactile stimulation (MTS) attenuates the stress response in preterm infants and rodents. We tested the hypothesis that MTS, administered during an established model of neonatal stress, would decrease stress-driven adiposity and prevent associated metabolic imbalances in rat pups. Pups received one of three treatments from postnatal days 5 to P9: Neonatal Stress (Stress; n=20) = painful stimulus and hypoxic/hyperoxic challenge during 60 min of maternal separation; MTS (n=20) = neonatal stress+10 min of MTS; or Control (n=20). Body weight, DXA whole body fat mass (g), MRI subcutaneous and visceral adipose tissue, and fasting adiponectin, leptin, glucose, insulin, and corticosterone were measured at weaning (P21). Stress and MTS weight gain (g/d) were accelerated following neonatal stress with greater fat mass, abdominal subcutaneous adipose tissue, serum adiponectin, leptin, and fasting glucose at weaning (P21). Male Stress and MTS pups had greater visceral adipose tissue depot. Male and female Stress pups were hyperinsulinemic. In summary, neonatal stress compromised body composition by increasing fat mass and abdominal subcutaneous adipose tissue depot, and in males, visceral adipose tissue depot. Importantly, MTS prevented hyperinsulinemia despite of stress-induced adiposity. We conclude that MTS during neonatal stress has the potential to minimize metabolic consequences associated with stress-driven perturbations in fat mass and abdominal adipose depots., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: The National Children's Study proposes to investigate biological, chemical, physical, and psychosocial environmental exposures and their role on health outcomes in pregnant women and children. One specific area of concern is contaminant exposure through the ingestion of solid foods. National food contaminant databases may miss dietary exposures unique to specific communities and sources of food., Objective: The purpose of this study was to evaluate the feasibility of community food item collection for the assessment of pesticide exposure in pregnant women and young children., Methods: A prospective observational design was used to test the food collection protocol in mothers (n=45) of children aged 15-24 months in Salt Lake City, Utah. Foods for collection were based on: 1) frequency of different foods consumed by the target population as determined by the National Health and Nutrition Examination Survey data; 2) child food frequency questionnaire; and 3) likelihood of pesticide contamination in the foods. Assessment measures included: demographics, environmental health survey, quality assurance checklist, and participant evaluation form., Results: An average of three food items were obtained from 44 households, yielding a collection rate of 97.8%. Overall, 100% of the food samples were rated as acceptable. Moreover, a vast majority of mothers reported that the study was not burdensome (95.5%) and that preparing the food sample was easy (93.2%)., Conclusions: This study suggests that the community food item collection methodology shows promise as a low-burden approach for capturing dietary exposures on a household level, and appears to be a feasible tool for large population studies to assess dietary exposures unique to specific communities., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Noninvasive measures of fetal and neonatal body composition may provide early identification of children at risk for obesity. Air displacement plethysmography provides a safe, precise measure of adiposity and has recently been validated in infants. Therefore, we explored relationships between term newborn percent body fat (%BF) measured by air displacement plethysmography to 2-dimensional ultrasound (2-D US) biometric measures of fetal growth and maternal and umbilical cord endocrine activity. A total of 47 mother/infant pairs were studied. Fetal biometrics by 2-D US and maternal blood samples were collected during late gestation (35 wk postmenstrual age); infants were measured within 72 h of birth. Fetal biometrics included biparietal diameter, femur length, head circumference, abdominal circumference (AC), and estimated fetal weight (EFW). Serum insulin, insulin-like growth factor (IGF) 1, IGF binding protein-3, and leptin concentrations were measured in umbilical cord and maternal serum. The mean %BF determined by plethysmography was 10.9 +/- 4.8%. EFW and fetal AC had the largest correlations with newborn %BF (R(2) = 0.14 and 0.10, respectively; P < 0.05); however, stepwise linear regression modeling did not identify any fetal biometric parameters as a significant predictor of newborn %BF. Newborn mid-thigh circumference (MTC; cm) and ponderal index (PI; weight, kg/length, cm(3)) explained 21.8 and 14.4% of the variability in %BF, respectively, and gave the best stepwise linear regression model (%BF = 0.446 MTC + 0.347 PI -29.692; P < 0.001). We conclude that fetal growth biometrics determined by 2-D US do not provide a reliable assessment of %BF in term infants.

Introduction: Few studies have evaluated the accuracy of parental perceptions of their child's weight status., Methods: A cross-sectional sample of children aged 5 to 12 years and their parents (n = 576 parent-child pairs) was enrolled from four schools. Child height and weight were measured. The parents classified their child on Likert scales ranging from "extremely overweight" to "extremely underweight." Parental perceptions were compared with their child's weight status according to body mass index (BMI) age-gender percentiles. Fisher-Halton-Freeman tests, chi(2), and logistic regression were used to compare demographic factors between parents who inaccurately estimated and those who accurately estimated child weight status., Results: Misclassification occurred 25% of the time (95% confidence interval: 21.4-28.5). All parents of children with a BMI greater than or equal to the 95th percentile classified their child in a category other than "extremely overweight," and 75% of children with a BMI from the 85th to less than the 95th percentile were misclassified as "about right" or "underweight." Boys were more likely to be misclassified than were girls (29% vs 21%, P = .03)., Conclusions: The majority of parents of obese and overweight children underestimate their child's weight status. Parents of boys are more likely to perceive their child's weight incorrectly.

Background: Altered nutrient intake and decreased exercise in response to cancer therapies and their side effects, particularly corticosteroids, may be key factors in the increased body weight and differences in physical fitness reported in survivors of childhood acute lymphoblastic leukemia (ALL)., Purpose: To assess (1) the effect of a home-based nutrition and exercise intervention program on cardiovascular fitness, strength, and flexibility in children with ALL during maintenance therapy and (2) the feasibility of conducting and evaluating a home-based exercise and nutrition program in this patient population., Design: Children ages 4 to 10 years with standard-risk ALL were randomized when starting maintenance therapy to a 12-month home-based exercise and nutrition program (n=6, 3 males/3 females) or control (n=7, 4 males/3 females) group. Assessment of anthropometrics, dietary intake, physical activity, and fitness was performed at baseline and 6 and 12 months of study., Results: Although age, body size, and nutrient intakes were similar between both subject groups at 0, 6, and 12 months, exercise and nutrition program children had greater improvement in physical activity and cardiovascular fitness between 6 and 12 months than control children., Conclusions: These results suggest that a home-based exercise intervention during maintenance therapy encouraged greater physical activity and improved cardiovascular fitness in children with standard-risk ALL. Further investigation involving larger populations of children with ALL is warranted.

Introduction: Lower leg bowing with tibial pseudarthrosis is associated with neurofibromatosis type 1 (NF1). The objective of the study is to determine if the geometry of the lower limb in individuals with neurofibromatosis type 1 (NF1) differs from controls, and to characterize the osseous components of the tibia in NF1., Methods: Peripheral quantitative computed tomography (pQCT) of the lower limb was performed (90 individuals with NF1 without tibial and/or fibular dysplasia: 474 healthy individuals without NF1). Subjects were 4-18 years of age. Individuals with NF1 were compared to controls using an analysis-of-covariance with a fixed set of covariates (age, weight, height, Tanner stage, and gender)., Results: Using pQCT, NF1 individuals without bowing of the lower leg have smaller periosteal circumferences (p<0.0001), smaller cortical area (p<0.0001), and decreased tibial cortical and trabecular bone mineral content (BMC) (p<0.0001) compared to controls., Discussion: Individuals with NF1 have a different geometry of the lower leg compared to healthy controls suggesting that NF1 haploinsufficiency impacts bone homeostasis although not resulting in overt anterolateral bowing of the lower leg.

Children and adolescents with poorly controlled type 1 diabetes mellitus (T1DM) are at risk for decreased bone mass. Growth hormone (GH) and its mediator, IGF-1, promote skeletal growth. Recent observations have suggested that children and adolescents with T1DM are at risk for decreased bone mineral acquisition. We examined the relationships between metabolic control, IGF-1 and its binding proteins (IGFBP-1, -3, -5), and bone mass in T1DM in adolescent girls 12-15 yr of age with T1DM (n = 11) and matched controls (n = 10). Subjects were admitted overnight and given a standardized diet. Periodic blood samples were obtained, and bone measurements were performed. Serum GH, IGFBP-1 and -5, glycosylated hemoglobin (HbA(1c)), glucose, and urine magnesium levels were higher and IGF-1 values were lower in T1DM compared with controls (p < 0.05). Whole body BMC/bone area (BA), femoral neck areal BMD (aBMD) and bone mineral apparent density (BMAD), and tibia cortical BMC were lower in T1DM (p < 0.05). Poor diabetes control predicted lower IGF-1 (r(2) = 0.21) and greater IGFBP-1 (r(2) = 0.39), IGFBP-5 (r(2) = 0.38), and bone-specific alkaline phosphatase (BALP; r(2) = 0.41, p < 0.05). Higher urine magnesium excretion predicted an overall shorter, lighter skeleton, and lower tibia cortical bone size, mineral, and density (r(2) = 0.44-0.75, p < 0.05). In the T1DM cohort, earlier age at diagnosis was predictive of lower IGF-1, higher urine magnesium excretion, and lighter, thinner cortical bone (r(2) >or=0.45, p < 0.01). We conclude that poor metabolic control alters the GH/IGF-1 axis, whereas greater urine magnesium excretion may reflect subtle changes in renal function and/or glucosuria leading to altered bone size and density in adolescent girls with T1DM.

Utah's Gold Medal Schools program supports the adoption of school policies that provide opportunities for nutritious food choices and regular physical activity. The effectiveness of Gold Medal Schools was evaluated via anthropometric measurements and dietary and physical activity surveys. The study population included first-, third-, and fifth-grade elementary school students and parents from four schools in Tooele County, UT. Two schools implemented Gold Medal Schools (intervention) and two did not (comparison). Data were collected at baseline (June 2005) and 1 year (May 2006). Body mass index (calculated as kg/m(2)) z scores increased significantly in the comparison group (0.53+/-0.38; P<0.05), but not in the intervention group (0.21+/-0.47; P=0.484), from baseline to 1 year. Children in the Gold Medal Schools cohort reported drinking fewer soft drinks per day (excluding diet drinks) at 1 year (P=0.008) and walking or biking to school more often at baseline and 1 year (P<0.001) than non-Gold Medal Schools children. While children in both groups increased the days per week they walked or biked to school, a substantial improvement was observed for the non-Gold Medal Schools students only (P<0.001). Overall, this pilot study suggests that Gold Medal Schools positively impacted body mass index z scores and health behaviors among elementary-aged students.

Objective: To determine if physical activity delivered by an infant's mother would be as effective in promoting bone mineral acquisition in preterm very low birth weight (VLBW) infants as the same intervention administered by a trained therapist., Patients and Methods: Preterm VLBW infants were randomized to receive daily physical activity administered by the infant's mother (MOM, n=11) or a trained therapist (OT, n=11), or control (n=11). Physical activity consisted of range of motion movements against passive resistance to all extremities for 5 to 10 min daily. All infants were fed mother's milk with fortification to 24 kcal oz(-1). Dual energy x-ray of the forearm bone area (BA, cm(2)), mineral content (BMC, g), and density (BMD, g/cm(2)) and measurement of bone formation (bone-specific alkaline phosphatase, BAP) and resorption (urine pyridinium crosslinks of collagen, Pyd) were obtained at study entry and at 2.0 kg of body weight., Result: Forearm BA and BMC gains were greater in MOM and OT infants compared to the control infants despite similar postnatal growth rate and nutrient intake. Serum BAP levels decreased in controls but remained unchanged in MOM and OT infants. Urine Pyd levels were similar at baseline to 2.0 kg for all groups. These findings suggest greater bone growth and mineral acquisition in MOM and OT infants than control infants., Conclusion: This study demonstrates that a physical activity program administered by the infant's own mother is as equally effective as therapist-administered physical activity in promoting greater bone growth and mineral acquisition in preterm VLBW infants.

Although neurofibromatosis type 1 (NF1) is a neurocutaneous disorder, skeletal abnormalities such as long-bone dysplasia, scoliosis, sphenoid wing dysplasia, and osteopenia are observed. To investigate the role of bone resorption as a mechanism for the bony abnormalities, we selected urinary pyridinium crosslinks (collagen degradation products excreted in urine) as a measure of bone resorption in NF1. Bone resorption was evaluated by quantitative assessment of the urinary excretion of pyridinium crosslinks [pyridinoline (Pyd) and deoxypyridinoline (Dpd)]. Total (free plus peptide-bound) pyridinium crosslinks from the first morning urines from 59 NF1 children (ages 5-19) were extracted and analyzed (17 children with a localized skeletal dysplasia, and 42 without). The data were compared with a healthy reference population without NF1 (n = 99). Multivariate analyses, controlling for age showed statistically significant increases for Dpd (p < 0.001) and the Dpd/Pyd ratio (p < 0.001) in NF1 individuals with and without a skeletal dysplasia. NF1 children have an increase in the urinary excretion of pyridinium crosslinks, reflecting increased bone resorption. The effects of NF1 haploinsufficiency likely contribute to abnormal bone remodeling, either directly or indirectly by aberrant Ras signaling, potentially predisposing NF1 individuals to localized skeletal defects.

Peripheral quantitative computed tomography (pQCT) has been used in a number of pediatric studies. Reference data for children are primarily limited to the radius. The purpose of this study was to establish normal reference ranges for pQCT measurements of the tibia for children. A cross-sectional sample of healthy, white, non-Hispanic children aged 5-18 years (n=416; 197 boys) was measured at the distal tibia metaphysis and diaphysis by pQCT to assess trabecular and cortical bone, respectively. Differences were determined between and within genders by height for bone geometry, density, and strength. Height-specific normal ranges were calculated, and gender-specific centile curves were generated. A positive, linear relationship was found between tibia cortical bone geometry and strength parameters and height (r2 >or=0.58, p<0.001), with mean values greater for boys than girls (p

Very low birth weight (VLBW; < or =1500 g), preterm infants have numerous physiological and developmental concerns, including growth and the provision of adequate nutrients to sustain growth. Growth is an important health care outcome measure for VLBW infants. Provision of energy and nutrients at levels to support growth and development is the goal of nutrition support for VLBW infants. Anthropometry and laboratory data are useful components of growth and nutrition assessment. The objectives of this paper are to describe: 1) the clinical application and interpretation of anthropometric measures of growth, and 2) the utilization and interpretation of laboratory tests of nutritional status in VLBW infants.

Objective: To characterize local bone geometry, density, and strength, using peripheral quantitative computed tomography (pQCT), compared with general bone characteristics as measured using dual x-ray absorptiometry (DXA), and to assess their relationship to disease-related factors in children with juvenile rheumatoid arthritis (JRA)., Methods: Forty-eight children ages 4-18 years with JRA (17 pauciarticular, 23 polyarticular, 8 systemic) were compared with age-matched healthy controls (n = 266). Measurements included cortical and trabecular bone geometry, density, and strength at the distal and midshaft tibia determined by pQCT, and whole-body, lumbar spine, and femoral neck measurements by DXA., Results: Methotrexate (MTX) was prescribed to 23 of 48 patients (47.9%) and glucocorticoids and MTX were prescribed to 15 of 48 patients (31.3%), with the greatest use in children with systemic JRA. All JRA patients had decreased tibia trabecular bone density, cortical bone size and strength, and muscle mass. Children with systemic JRA had lower femoral neck densities. Systemic JRA was associated with a shorter, less mineralized skeleton, while a narrower, less mineralized skeleton was observed in polyarticular JRA. The tibia diaphysis was narrower with decreased muscle mass, but normal, size-adjusted bone mineral in all subtypes indicated a localized effect of JRA on bone. Patients exposed to glucocorticoids and MTX or to glucocorticoids or MTX alone had greatly reduced trabecular density, cortical bone geometry properties, and bone mineral content, muscle mass, and bone strength., Conclusion: Children with JRA have decreased skeletal size, muscle mass, trabecular bone density, cortical bone geometry, and strength. Not surprisingly, these bone abnormalities are more pronounced in children with greater disease severity.

Objective: To assess whether children and adolescents with neurofibromatosis type 1 (NF1) have decreased bone mineral density (BMD)., Study Design: Bone densitometry of the whole body, hip, and lumbar spine was used in a case-to-control design (84 individuals with NF1: 293 healthy individuals without NF1). Subjects were 5 to 18 years old. Subjects with NF1 were compared with control subjects by using an analysis-of-covariance with a fixed set of covariates (age, weight, height, Tanner stage, and sex)., Results: Subjects with NF1 had decreased areal BMD (aBMD) of the hip (P <.0001), femoral neck (P <.0001), lumbar spine (P = .0025), and whole body subtotal (P <.0001). When subjects with NF1 were separated in groups with and without a skeletal abnormality, those who did not have a skeletal abnormality still had statistically significant decreases in aBMD compared with control subjects (P <.0001 for whole body subtotal aBMD), although they were less pronounced than in those with osseous abnormalities., Conclusions: These data suggest that individuals with NF1 have a unique generalized skeletal dysplasia, predisposing them to localized osseous defects. Dual energy x-ray absorptiometry may prove useful in identifying individuals with NF1 who are at risk for clinical osseous complications and monitoring therapeutic trials.

Skeletal anomalies are observed in neurofibromatosis type 1 (NF1), but the pathogenesis is unknown. Given that muscle mass is important in the development of the strength of bone, peripheral quantitative computed tomography (pQCT) was utilized to compare measurements of muscle compartments between NF1 individuals and controls. Forty individuals with NF1 (age 5-18 years) were evaluated. Cross-sectional measurements, at the 66% tibial site, were obtained using pQCT (XCT-2000, Stratec) and variables were compared to controls without NF1 ((age 5-18 years, N=380) using analysis-of-covariance controlling for age, height, Tanner stage, and gender. The NF1 cohort showed decreased total cross-sectional area [p<0.001], decreased muscle plus bone cross-sectional area [p<0.001], decreased muscle cross-sectional area [p<0.001], and decreased Stress Strain Index [p=0.010]. These data indicate that NF1 individuals have decreased muscle cross-sectional area and decreased bone strength than individuals without NF1.

Objective: To determine the nature and prevalence of dietary supplement use among chronically ill children., Design: This descriptive study used a self-report questionnaire., Subjects: A convenience sample of parents of 505 chronically ill children and adolescents seen in subspecialty medical clinics in Salt Lake City, UT. The medical conditions studied included asthma, cystic fibrosis, diabetes, cancer, liver and renal transplantations, seizures, and rheumatological and neurobehavioral disorders. Statistics Sample characteristics were described using frequencies, percentages, means, and standard deviations. chi 2 tests were used to compare sex, ethnicity, parental education level, and dietary supplement use variations among the various diagnostic categories. Analysis of variance with Bonferroni correction for multiple comparisons was used to determine differences among diagnosis groups for continuous variables, and the Kruskal-Wallis test was used to test categorical variables., Results: The population sampled was predominately white (88.5%), with a mean age of 9.9+/-5.3 years. Sixty-two percent of the population used dietary supplements, and 30% used nonprescribed supplements. Significant differences were noted among diagnosis groups, with the highest nonprescribed use reported in children with cancer (solid tumors=46%; leukemia=44%), cystic fibrosis (35%), neurobehavioral disorders (35%), and rheumatological disorders (34%). Only 20% of those using nonprescribed dietary supplements had discussed this use with the health care provider., Conclusions: Dietary supplement use is prevalent among chronically ill children, especially among those with a poor prognosis or for whom there are limited medical treatments. Few pediatric health care providers are aware of their patients' use of nonprescribed supplements. This is a concern because of the unknown effects of many supplements on growth and development and the potential for adverse drug interactions.

Objective: To track bone mineral acquisition in adolescents with type 1 diabetes (DM)., Study Design: Subjects were adolescents, ages 12 to 18 years, with DM (n=42) and a healthy regional reference (n=199). Measurements of tibia bone characteristics by peripheral quantitative computed tomography (pQCT) and spine and whole body (WB) by dual-energy x-ray absorptiometry (DEXA), anthropometrics, and lifestyle questionnaires were obtained during a 12-month period. Disease duration, insulin dose, renal function, and glycosylated hemoglobin (HbA1c) values for the previous 12 months were recorded., Results: Body size and maturation were similar between groups. DM had lower tibia, spine, and WB bone characteristics but greater muscle mass (LBM) and lower bone mineral content (BMC)/LBM at baseline and 12 months. Annual gains for tibia cortical bone and WB BMC/LBM were lower and inversely related to HbA1c levels (R=-0.36 to -0.51), whereas spine area and density and WBLBM were greater and were predicted by pubertal-driven growth. Overall, the DM cohort had 8.5% less WB BMC/LBM, suggesting that bone mineral deposition was not adequately adapted to muscle gains., Conclusions: Adolescents with type 1 diabetes continue to have smaller bone mass and bone size despite normal growth and maturation. Poor metabolic control appears to negatively influence bone mineral acquisition.

Objective: To determine whether bone characteristics in adolescents with type 1 diabetes mellitus (DM) are influenced by blood glucose regulation and disease duration. The subjects were adolescents with type 1 DM (n=55) recruited from the University of Utah's Primary Children's Pediatric Diabetes Treatment Center. A reference database consisting of 95 healthy adolescents from the same geographic area was used for comparison.Study design Measurements of the tibia by peripheral quantitative computed tomography were made to assess cortical and trabecular bone characteristics. Hip, spine, and whole body characteristics were measured by dual-energy x-ray absorptiometry. Height, weight, health histories, Tanner stage, disease duration, insulin regimen, and glycosylated hemoglobin values were recorded., Results: Age, maturation, and body size and composition values were similar between the subjects with type 1 DM and reference. Subjects with type 1 DM had lower tibia trabecular and femoral neck density and whole body mineral content and density. The mean glycosylated hemoglobin value was inversely related to tibia trabecular bone density (R(2)=-0.30) and whole body bone mineral content (R(2)=-0.25) and accounted for 3.0% to 8.9% of the variance., Conclusions: Altered bone mineral acquisition in adolescents with type 1 DM may limit peak bone mass acquisition and increase the risk of osteoporosis in later life.

Background: One in 5 American children is overweight, despite a decrease in total fat consumption. This has sparked an interest in the carbohydrate composition of diets, including the glycemic index (GI)., Objective: To investigate whether a low-GI meal replacement (LMR) produced similar metabolic, hormonal, and satiety responses in overweight adolescents as a low-GI whole-food meal (LWM) when compared with a moderately high-GI meal replacement (HMR)., Methods: Randomized, crossover study comparing LMR, HMR, and LWM in 16 (8 male/8 female) adolescents during 3 separate 24-hour admissions. The meal replacements consisted of a shake and a nutrition bar. Identical test meals were provided at breakfast and lunch. Metabolic and hormonal indices were assessed between meals. Measures of participants' perceived satiety included hunger scales and ad libitum food intake., Results: The incremental areas under the curve for glucose were 46% and 43% lower after the LMR and LWM, respectively, compared with the HMR. Insulin's incremental area under the curve was also significantly lower after both low GI test meals (LMR = 36%; LWM = 51%) compared with the HMR. Additional food was requested earlier after the HMR than the LMR (3.1 vs 3.9 hours, respectively), although voluntary energy intake did not differ., Conclusions: Differences in insulin response between the meal replacements occurred, and prolongation of satiety after the LMR, based on time to request additional food, was observed. We speculate that the prolonged satiety associated with low GI foods may prove an effective method for reducing caloric intake and achieving long-term weight control.

Background: Maximal bone acquisition in adolescent girls through dietary and lifestyle practices is advocated to prevent or minimize the development of osteoporosis and its associated complications in later life. Longitudinal investigations of bone acquisition in children and adolescents have utilized areal bone mineral density (BMD, mg/cm(2)) as a measure of bone mass and strength. Peripheral quantitative computed tomography (pQCT), which provides a three-dimensional display of data, separate analyses of bone compartments, and bone mass in terms of volumetric BMD (vBMD, mg/cm(3)), has recently been introduced for clinical use., Objective: To assess the impact of a 12-month daily calcium supplement on total and trabecular bone acquisition as measured by pQCT in preadolescent girls., Design: Early adolescent Caucasian girls (aged 12 years, Tanner Stage 2) were enrolled in a randomized trial of daily calcium supplement (TX, 800 mg calcium carbonate and 400 IU vitamin D) or placebo (C). Body weight, height, and distal tibia measurements by pQCT were obtained at enrollment, 6 and 12 months. Pubertal status and physical activity records were assessed at baseline and 12 months. Three-day food intake records were completed every three months., Results: Seventy-one girls completed the 12-month trial (TX=35, C=36). No differences were found for age, weight, height, body mass index, pubertal maturation, or reported physical activity at enrollment or during the study. Average intakes during the study were 1524 mg calcium and 496 IU vitamin D (TX) versus 865 mg calcium and 160 IU vitamin D (C) per day. Baseline total bone values were similar, however, trabecular values were greater in TX girls despite randomization. Percent changes were calculated to adjust for baseline differences. Because of the small cortical thickness at the 10% site (mean values < 1.6 mm), cortical mass and density were not analyzed. The percent changes for trabecular bone mineral content (BMC, mg) and vBMD were significantly greater in TX girls (+4.1% BMC and +1.0% vBMD TX versus -1.6% BMC and -2.0% vBMD C, p<0.006; ANCOVA) after 12 months of supplement. Trabecular bone area (BA, cm(2)) and total bone change, however, did not differ between groups., Conclusions: Daily calcium and vitamin D supplementation promotes greater trabecular BMC and vBMD acquisition in preadolescent girls. The single site selected for pQCT evaluation in this study did not allow evaluation of the cortical bone compartment. Future studies that utilize the pQCT technique need to incorporate multiple measurement sites to better assess total, cortical, and trabecular bone.

Objective: A study of daily physical activity was performed with 32 preterm infants to evaluate changes in body weight and bone mineralization., Study Design: Subjects were matched by birth weight and gestational age and randomly assigned to the physical activity (PA; n = 16) or to the control (C; n = 16) program. PA consisted of range of motion against passive resistance to all extremities for 5 to 10 minutes daily. Peripheral dual-energy x-ray of the right forearm (ulna and radius); biomarkers of bone formation (serum type I collagen C-terminal propeptide [PICP]) and resorption (urine pyridinoline cross-links of collagen [Pyd]); serum calcium, phosphate, alkaline phosphatase, parathyroid hormone (PTH), and 1, 25-(OH)(2) vitamin D; and urine levels of calcium, phosphate, and creatinine were obtained. All measurements were made at study entry and at 2.0 kg of body weight., Results: Despite a similar nutrient intake at advised levels for preterm infants, gains in body weight (g) and forearm bone length (cm), bone area (BA; cm(2)), bone mineral content (BMC; mg), and fat-free mass (g) were greater in PA infants. Forearm bone mineral density and fat mass gains did not differ between groups. Serum PICP levels remained constant in PA infants but decreased in C infants suggesting a slower rate of bone formation. Urine Pyd or bone resorption activity was similar between groups. A higher level of serum PTH was observed in PA infants at 2. 0 kg of body weight; however, the change from study entry to completion did not differ between groups. All other serum and urine values were similar and within normal limits., Conclusion: A daily PA program promotes greater gains in body weight, forearm length, BA, BMC, and fat-free mass in premature infants.

Objective: Infants with bronchopulmonary dysplasia (BPD) have been previously reported to have a decrease in growth velocity after stopping supplemental oxygen (SO). SO was stopped after a short-term recording (20-30 minutes) of pulse oxygen saturation (Sao2) of 92% or greater in room air. Other studies have documented that Sao2 decreases further during feedings and sleep in infants with BPD. Two questions were asked: (1) whether short-term, awake Sao2 studies would reliably predict prolonged sleep Sao2; and (2) how Sao2 sustained at 88% to 91% vs 92% or greater in room air would impact growth velocity in infants with BPD., Methodology: Short-term Sao2 studies were prospectively compared with prolonged sleep Sao2 (n = 63) and the growth velocity of infants who had SO discontinued after a prolonged sleep Sao2 recording of 88% to 91% (group 1; n = 14) versus 92% or greater (group 2; n = 34) in room air., Results: Failure to maintain Sao2 at predetermined levels occurred in 18 (29%) of 63 infants during their first prolonged sleep study. There was no correlation between short-term awake Sao2 and prolonged sleep Sao2 recordings (r = .02). Body weight, height, weight for height, and rate of weight gain were similar for all study infants before SO was stopped and remained constant for group 2 infants after SO was stopped. However, group 1 infants had a significant decrease in the rate of weight gain (17.3 +/- 13.1 vs 3.7 +/- 6.1 g/kg per day), and the mean z scores for weight gain and weight for height also decreased significantly for group 1 infants. Energy intake, incidence of acute infection, hematocrit values, and medication use did not differ before or after stopping SO in either group., Conclusions: This study indicated that short-term, awake Sao2 measurements do not predict prolonged sleep Sao2, and overall, infants with BPD continued a positive growth trend when Sao2, remained greater than 92% during prolonged sleep.

Infants fed a soy formula supplemented with selenite had plasma and erythrocyte selenium values lower than those of infants fed human milk. However, plasma and erythrocyte glutathione peroxidase activities were normal, indicating that the physiologic requirement for selenium was being met.

The selenium status of 46 orally fed vitamin E-sufficient preterm infants (birth weight less than 1700 gm) was studied longitudinally for 3 weeks to determine the efficacy of selenium supplementation. Infants were fed either human milk (n = 21; 24 ng selenium/ml), preterm formula (n = 13; 7.8 ng selenium/ml), or preterm formula supplemented with sodium selenite (n = 12; 34.8 ng selenium/ml). Plasma and erythrocyte selenium and glutathione peroxidase activity and urinary and dietary selenium content were evaluated on study day 1 (day enteral feeds reached 100 kcal/kg/day) and weekly for 3 weeks. Throughout the study, selenium intakes of infants fed preterm formula plus sodium selenite were greater than those of infants fed human milk, which were greater than those of infants fed preterm formula (p less than 0.001). After 3 weeks no differences were observed among groups for plasma or erythrocyte selenium or glutathione peroxidase. Plasma selenium and glutathione peroxidase values within all groups were low compared with those reported for term infants fed human milk. Whereas urinary selenium levels of infants fed preterm formula plus sodium selenite were greater than those of infants fed preterm formula at weeks 1 and 2 (p less than 0.01), infants fed human milk and preterm formula had lower levels at week 3 than on study day 1 (p less than 0.05). We conclude that blood selenium measurements typically used to monitor selenium status do not reflect dietary selenium intakes of orally fed preterm infants.