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Obesity as a major risk factor for childhood hypertension necessitates careful blood pressure (BP) monitoring of those affected. This study aimed to compare BP classification in a cohort of children affected by obesity using tables versus digital calculations in two sets of guidelines.This study was a secondary analysis of data collected from a randomised clinical trial of a multidisciplinary life-style assessment and intervention program. Baseline data from 237 children with a body mass index99th percentile or91st percentile with weight-related comorbidities and available BP measurements were analysed. We assessed agreement between tables and algorithms in classification of elevated BP/pre-hypertension and hypertension based on the American Academy of Paediatrics (AAP) clinical practice guidelines (CPG) and the older Fourth Report using Cohen's weighted kappa. The prevalence of hypertensive diagnoses was also compared between the two guidelines.Agreement between BP tables and algorithmic calculation of percentiles was discordant, though improved in the AAP CPG compared to the Fourth Report (Cohen's kappa = 0.70 vs. 0.57, respectively). None (0%) were missed diagnoses, and 59 (24.9%) were false positives for the Fourth Report, and 0 (0%) were missed diagnoses, and 49 (20.9%) were false positives for the AAP CPG. Under the recent guidelines, there was an increase in prevalence of 6.0% (95% confidence interval (CI) 2.5-9.4%; P = 0.0001) for BP ≥90th percentile, and of 3.0% (95% CI 0.4-5.6%; p = 0.016) for hypertension (BP ≥ 95th percentile) in the cohort (18.0% and 6.8%, respectively, increased from 12.0% and 3.8%).Digital calculators over tables in clinical practice are recommended where possible to improve the accuracy of paediatric BP classification. Substantial rates of elevated BP/Hypertension were found in this cohort of children and adolescents with overweight and obesity.

Robinow syndrome (RS) is a genetically heterogeneous skeletal dysplasia with recent reports suggesting an osteosclerotic form of the disease. We endeavored to investigate the full spectrum of skeletal anomalies in a genetically diverse cohort of RS patients with a focus on the bone micro-architecture. Seven individuals with molecularly confirmed RS, including four with DVL1 variants and single individuals with variants in WNT5A, ROR2, and GPC4 underwent a musculoskeletal focused physical examination, dual-energy X-ray absorptiometry (DEXA) scan, and high-resolution peripheral quantitative computed tomography (HR-pQCT). Skeletal examination revealed variability in limb shortening anomalies consistent with recent reports. DEXA scan measures revealed increased total body bone mineral density (BMD) (3/7), cranial BMD (5/7), and non-cranial BMD (1/7). Cranial osteosclerosis was only observed in DVL1-RS (4/4) and GPC4-RS (1/1) subjects and in one case was complicated by choanal atresia, bilateral conductive hearing loss, and cranial nerve III, VI, and VII palsy. HR-pQCT revealed a unique pattern of low cortical BMD, increased trabecular BMD, decreased number of trabeculations, and increased thickness of the trabeculations for the DVL1-RS subjects. The spectrum of skeletal anomalies including the micro-architecture of the bones observed in RS has considerable variability with some osteosclerosis genotype-phenotype correlations more frequent with DVL1 variants.

Background: Long-term outcomes of preterm infants fed an exclusive human milk-based (EHM) diet using a donor human milk-based fortifier are not well defined. Materials and Methods: Infants ≤1,250 g birth weight (BW) were studied prospectively at two outpatient visits: 12–15 and 18–22 months corrected age (CA). Dual-energy X-ray absorptiometry and Bayley Scales of Infant and Toddler Development III (BSID-III) were performed at 18–22 months CA. Results: In this pilot study, 51 preterm infants (gestational age 27.8 ± 2.6 weeks and BW 893 ± 204 g) were evaluated. While anthropometric z-scores were significantly lower at discharge compared with birth, z-scores returned to birth levels by 12–15 months CA (length and head circumference [HC]) and 18–22 months CA (weight). Body composition at 2 years of age was similar to term-matched controls. Inpatient growth was significantly correlated with bone density, lean mass (LM), and fat-free mass at 18–22 months CA. Increased mother's own milk (MOM) was significantly correlated with decreased fat mass indices. BSID-III showed that 0% of cognitive composite scores were

New generation, multicomponent parenteral lipid emulsions provide key fatty acids for brain growth and development, such as docosahexaenoic acid (DHA) and arachidonic acid (AA), yet the content may be suboptimal for preterm infants. Our aim was to test whether DHA and AA-enriched lipid emulsions would increase activity, growth, and neurodevelopment in preterm piglets and limit brain inflammation. Cesarean-delivered preterm pigs were given three weeks of either enteral preterm infant formula (ENT) or TPN with one of three parenteral lipid emulsions: Intralipid (IL), SMOFlipid (SMOF) or an experimental emulsion (EXP). Activity was continuously monitored and weekly blood sampling and behavioral field testing performed. At termination of the study, whole body and tissue metrics were collected. Neuronal density was assessed in sections of hippocampus (HC), thalamus, and cortex. Frontal cortex (FC) and HC tissue were assayed for fatty acid profiles and expression of genes of neuronal growth and inflammation. After 3 weeks of treatment, brain DHA content in SMOF, EXP and ENT pigs was higher (P < 0.01) in FC but not HC vs. IL pigs. There were no differences in brain weight or neuron density among treatment groups. Inflammatory cytokine TNFα and IL-1β expression in brain regions were increased in IL pigs (P < 0.05) compared to other groups. Overall growth velocity was similar among groups, but IL pigs had higher percent body fat and increased insulin resistance compared to other treatments (P

The objective of this study is to compare changes in body composition, lifestyle factors, and metabolic responses occurring in living kidney transplant recipient patients after transplantation.The study was a single-site, prospective, observational study. To identify metabolic responses during the initial years after transplantation, we obtained state-of-the-art, high-resolution measurements of body composition from a 4-compartment model using dual-energy X-ray absorptiometry, air displacement plethysmography, and total body potassium and nitrogen counters. We also assessed dietary recalls and actigraphy before transplantation and 3- and 12-month after transplantation. The study was conducted at a quaternary care hospital outpatient transplant center and a United States Department of Agriculture Agricultural Research Service center. Thirty-one adults receiving a living donor kidney allograft were studied. The main outcome measures were change in body composition at 3 months and 1 year after transplantation, and this was correlated with the occurrence of insulin resistance.In patients receiving a successful kidney transplant from living donors treated with standard immunosuppression, significant increases in body weight were detected at 3 and 12 months after transplantation (2.2 kg, P = .03 and 6.6 kg, P .0001, respectively). Weight gain was principally due to adipose tissue accumulation in the truncal region. There was no increase in muscle mass or fluid accumulation. Weight gain was not associated with changes in resting energy expenditure or physical activity. Notably, increases in visceral and subcutaneous adipose tissue were positively correlated with insulin resistance.Successful transplantation was associated with increased insulin resistance and weight gain without increases in muscle or fluid. This metabolic pattern suggests potential interventions that could prevent or mitigate the consequences of adipose tissue accumulation in transplant recipients.

Peer reviewed: True, Acknowledgements: We thank John Reilly for his advice on data sources and data access; Cara L Eckhardt, Josephine Avila, Igor Y Kon, and Jinzhong Wang from the Eckhardt et al study23; and all staff involved in recruitment and data collection from the included studies. Data gathered from South Africa was supported by South Africa Medical Research Council and National Research Foundation., Objective To evaluate the performance of a UK based prediction model for estimating fat-free mass (and indirectly fat mass) in children and adolescents in non-UK settings. Design Individual participant data meta-analysis. Setting 19 countries. Participants 5693 children and adolescents (49.7% boys) aged 4 to 15 years with complete data on the predictors included in the UK based model (weight, height, age, sex, and ethnicity) and on the independently assessed outcome measure (fat-free mass determined by deuterium dilution assessment). Main outcome measures The outcome of the UK based prediction model was natural log transformed fat-free mass (lnFFM). Predictive performance statistics of R2 , calibration slope, calibration-in-the-large, and root mean square error were assessed in each of the 19 countries and then pooled through random effects meta-analysis. Calibration plots were also derived for each country, including flexible calibration curves. Results The model showed good predictive ability in non-UK populations of children and adolescents, providing R2 values of >75% in all countries and >90% in 11 of the 19 countries, and with good calibration (ie, agreement) of observed and predicted values. Root mean square error values (on fat-free mass scale) were

Background Our aim was to investigate if moderate to vigorous physical activity (MVPA), calcium intake interacts with bone mineral density (BMD)-related single nucleotide polymorphisms (SNPs) to influence BMD in 750 Hispanic children (4-19y) of the cross-sectional Viva La Familia Study. Methods Physical activity and dietary intake were measured by accelerometers and multiple-pass 24 h dietary recalls, respectively. Total body and lumbar spine BMD were measured by dual energy X-ray absorptiometry. A polygenic risk score (PRS) was computed based on SNPs identified in published literature. Regression analysis was conducted with PRSs, MVPA and calcium intake with total body and lumbar spine BMD. Results We found evidence of statistically significant interaction effects between the PRS and MVPA on total body BMD and lumbar spine BMD (p p = 1.1 × 10− 5) and lumbar spine BMD (β = − 0.042 ± 0.013, p = 0.0016) in low MVPA group, as compared to high MVPA group (β = − 0.015 ± 0.006, p = 0.02; β = 0.008 ± 0.01, p = 0.4, respectively). Discussion The study indicated that calcium intake does not modify the relationship between genetic variants and BMD, while it implied physical activity interacts with genetic variants to affect BMD in Hispanic children. Due to limited sample size of our study, future research on gene by environment interaction on bone health and functional studies to provide biological insights are needed. Conclusions Bone health in Hispanic children with high genetic risk for low BMD is benefitted more by MVPA than children with low genetic risk. Our results may be useful to predict disease risk and tailor dietary and physical activity advice delivery to people, especially children.

Obesity appears to have a negative impact on pediatric bone health, and insulin resistance may mediate this relationship. It is unclear if cardiorespiratory fitness (CRF) has a protective effect on bone in obese children. We tested the hypothesis that CRF attenuates the negative effect of obesity and insulin resistance on skeletal health in a large cohort of Hispanic youth. We studied 413 (193 males and 220 females) children and adolescents from the Viva la Familia Study. They were all pubertal; mean age (SD) 13.4 ± 2.3 years; 27% were normal weight (NW), 19% overweight (OW) and 54% obese (OB). They underwent measurement of body composition, total body bone mineral content (BMC) and density (BMD) by DXA scan; VO2peak using the ramp protocol on a treadmill for CRF; fasting glucose and insulin. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. BMC increased from NW to OW to OB (mean 1.35 ± 0.4, 1.41 ± 0.4, and 1.49 ± 0.4 kg, respectively, p=.005). Peak VO2 decreased from NW to OW to OB (41.3 ± 9.7, 35.5 ± 7.7, 28.9. ± 5.5 mL/kg per min, respectively, p In conclusion, lean body mass is the major determinant of BMC and BMD in Hispanic youth. Adiposity associated insulin resistance has a negative effect on BMC and BMD. CRF contributes positively to the variance in BMC and BMD. This suggests that CRF and higher lean mass attenuate the adverse effects of insulin resistance on bone health in children.

Background: The extent to which breastfeeding is protective against later-life obesity is controversial. Little is known about differences in infant body composition between breastfed and formula-fed infants, which may reflect future obesity risk.Objective: We aimed to assess associations of infant feeding with trajectories of growth and body composition from birth to 7 mo in healthy infants.Design: We studied 276 participants from a previous study of maternal vitamin D supplementation during lactation. Mothers used monthly feeding diaries to report the extent of breastfeeding. We measured infants' anthropometrics and used dual-energy X-ray absorptiometry to assess body composition at 1, 4, and 7 mo. We compared changes in infant size (z scores for weight, length, and body mass index [BMI (in kg/m2)]) and body composition (fat and lean mass, body fat percentage) between predominantly breastfed and formula-fed infants, adjusting in linear regression for sex, gestational age, race/ethnicity, maternal BMI, study site, and socioeconomic status.Results: In this study, 214 infants (78%) were predominantly breastfed (median duration: 7 mo) and 62 were exclusively formula fed. Formula-fed infants had lower birth-weight z scores than breastfed infants (-0.22 ± 0.86 and 0.16 ± 0.88, respectively; P < 0.01) but gained more in weight and BMI through 7 mo of age (weight z score difference: 0.37; 95% CI: 0.04, 0.71; BMI z score difference: 0.35; 95% CI: 0, 0.69), with no difference in linear growth (z score difference: 0.05; 95% CI: -0.24, 0.34). Formula-fed infants gained more lean mass (difference: 303 g; 95% CI: 137, 469 g) than breastfed infants, but not fat mass (difference: -42 g; 95% CI: -299, 215 g).Conclusions: Formula-fed infants gained weight more rapidly and out of proportion to linear growth than did predominantly breastfed infants. These differences were attributable to greater accretion of lean mass, rather than fat mass. Any later obesity risk associated with infant feeding does not appear to be explained by differential adiposity gains in infancy.

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by poikiloderma, small stature, sparse hair, skeletal abnormalities, increased risk of osteosarcoma, and decreased bone mass. To date, there has not been a comprehensive evaluation of the prevalence and extent of metabolic bone disease in RTS. Furthermore, the mechanisms that result in this phenotype are largely unknown. In this report, we provide a detailed evaluation of 29 individuals with RTS with respect to their metabolic bone status including bone mineral density, calcium kinetics studies, and markers of bone remodeling. We show that individuals with RTS have decreased areal bone mineral density. Additionally, we demonstrate that the presence of pathogenic variants in RECQL4 and low bone mineral density correlate with the history of increased risk of fractures. Using a RECQL4-deficient mouse model that recapitulates skeletal abnormalities seen in individuals with RTS, we demonstrate that generalized skeletal involvement is likely due to decreased osteogenesis. Our findings are clinically relevant as they may help in the risk stratification of patients with RTS and also in the identification of individuals who may benefit from additional surveillance and management of metabolic bone disease.

Background Fat-free mass index (FFMI) and fat mass index (FMI) are superior to BMI and fat percentage in evaluating nutritional status. However, existing references fail to account for racial/ethnic differences in body composition among children. Objectives Our goal was to produce age-based normative references for FFMI and FMI in children for specific racial/ethnic groups. Methods Body composition, weight, and height were measured in 1122 normal healthy children aged 2-21 y. Bone mineral content measured by DXA, total body water by deuterium dilution, and total body potassium by whole-body γ counting were combined to calculate fat-free mass (FFM) and fat mass (FM) using equations based on the Reference Child and Adolescent models. FFMI and FMI were calculated by dividing FFM and FM by height squared, respectively. After outlier removal, the LMS (Lambda-Mu-Sigma) function within R's GAMLSS package was used to produce age-based FFMI and FMI growth curves for black (B), white (W), and Hispanic (H) children for each sex. Combined models were produced in cases where outcomes did not differ by race/ethnicity. Resulting models were compared with previously published FFMI and FMI models. Results FFMI and FMI models based on 1079 children, aged 2-21 y, were created for both sexes. FFMI models for B children showed higher values throughout. W and H children were combined to produce FFMI models for each sex. H boys were modeled individually for FMI, whereas W and B boys were combined. FMI models for girls were created for each race/ethnicity. Models agreed well with those based on children from the United Kingdom of comparable race/ethnicity. Conclusions Race/ethnicity-specific references for FFMI and FMI will increase the accuracy of health and nutrition status assessment in children over race/ethnicity-generic references. The models allow the calculation of SD scores to assess health and nutrition status in children.

Background Although the impact of gestational weight gain (GWG) on birth weight in twin pregnancies has been demonstrated, the specific components of GWG have not been delineated for twin gestations. Fetal body composition has been shown to be modifiable in singleton gestations based on nutritional intervention strategies and may prove to have similar modifications in twin gestations. Objective We aimed to determine the relation of maternal body composition changes to birth weight, birth length, and neonatal fat mass (FM) in dichorionic-diamniotic twin pregnancies. Design This is a prospective study of 20 women with twin gestations. Comparisons were made between body composition variables during each trimester and for the entire pregnancy and compared with the outcomes of birth weight, neonatal fat percentage, and birth length. Results GWG within or above compared with below the IOM recommendations was associated with higher birth weights (P = 0.03, P = 0.04, respectively), but also with higher postpartum weight retention (P = 0.001). Total maternal protein gain over the pregnancy was positively associated with birth weight (P = 0.03). Changes in maternal fat-free mass (FFM), total body water (TBW), and FM from the first to the third trimester were not associated with either birth weight or neonatal FM percentage. However, maternal FM change from the second to the third trimester was significantly correlated to neonatal FM percentage (P = 0.02). Third trimester GWG and total protein gain were positively correlated with neonatal birth length (P = 0.02 and 0.03, respectively). Maternal FFM over all 3 trimesters showed a positive relation with neonatal birth length (P = 0.01). Conclusions Significant increases in maternal protein are associated with greater birth weight and neonatal birth length. Protein accretion, in contrast to TBW and FM gains, may be the most critical component of maternal GWG in dichorionic twin gestations.

Background Estimated energy requirement (EER) has not been defined for twin pregnancy. This study was designed to determine the EER of healthy women with dichorionic-diamniotic (DCDA) twin pregnancies. Objectives We aimed to estimate energy deposition from changes in maternal body protein and fat; to measure resting energy expenditure (REE), physical activity level (PAL), and total energy expenditure (TEE) throughout pregnancy and postpartum; and to define the EER based on the sum of TEE and energy deposition for twin gestation. Design This is a prospective study of 20 women with DCDA twin gestations. Maternal EER, energy deposition, REE, TEE, and PAL were obtained during the first, second, and third trimesters of pregnancy and immediately postpartum. A mixed-effects linear regression model for repeated measures with random intercept was used to test for the effects of BMI groups and time. Results Gains in total body protein (mean ± SD: 2.1 ± 0.7 kg) and fat mass (5.9 ± 2.8 kg) resulted in total energy deposition of 67,042 ± 25,586 kcal between 0 and 30-32 weeks of gestation. REE increased 26% from 1392 ± 162 to 1752 ± 172 kcal/d across the 3 trimesters, whereas TEE increased 17% from 2141 ± 283 to 2515 ± 337 kcal/d. Physical activity decreased steadily throughout pregnancy. Reductions in physical activity did not compensate for the rise in REE and energy deposition, thus requiring an increase in dietary energy intake as pregnancy progressed. EER increased 29% from 2257 ± 325 kcal/d in the first trimester to 2941 ± 407 kcal/d in the second trimester, and stayed consistent at 2906 ± 350 kcal/d in the third trimester. Conclusion Increased energy intake, on average ∼700 kcal/d in the second and third trimesters when compared with the first trimester, is required to support gestational weight gain and the rise in energy expenditure of DCDA twin pregnancies.

Source output stability is important for accurate measurement in prompt gamma neutron activation. This is especially true when measuring low-concentration elements such as in vivo nitrogen (~2.5 % of body weight). We evaluated the stability of the compact DT neutron generator within an in vivo nitrogen measurement system. Review of gamma event/time patterns and data from an auxiliary detector showed significant variations among repeated phantom runs. Neutron generator instability had a significant effect on measurement precision. The neutron generator used in our system must be monitored for output consistency. Adjustments must be made to measurement results to correct for generator instability.

Objective Maternal adiposity is associated with poor offspring cardiometabolic health. We aimed to evaluate the relationship of maternal pre-pregnancy body mass index (BMI) on the BMI, body composition and cardiometabolic characteristics of the offspring. Methods Forty offspring of overweight/obese mothers (O-OW) and 28 offspring of normal weight mothers (O-NW) underwent evaluation of body composition, abdominal fat distribution, blood pressure measurement, fasting lipids and an oral glucose tolerance test. The anthropometric and cardiometabolic characteristics of O-OW were compared with those of O-NW, and the relationship to maternal BMI was evaluated. Results Subjects (mean age: 12.6 ± 0.4, female: 52.9%) had similar gestational age, birth weight, age, gender, and Tanner stage. However, O-OW had a significantly higher BMI (24.4 ± 1.2 vs. 19.7 ± 0.8 kg/m2, p = 0.001), % body fat (31.7 ± 1.6 vs. 24.6 ± 1.1%, p

Objective Energetic adaptations induced by bariatric surgery have not been studied in adolescents or for extended periods postsurgery. Energetic, metabolic, and neuroendocrine responses to Roux-en-Y gastric bypass (RYGB) surgery were investigated in extremely obese adolescents. Methods At baseline and at 1.5, 6, and 12 months post-baseline, 24-h room calorimetry, body composition, and fasting blood biochemistries were measured in 11 obese adolescents relative to five matched controls. Results In the RYGB group, mean weight loss was 44 ± 19 kg at 12 months. Total energy expenditure (TEE), activity EE, basal metabolic rate (BMR), sleep EE, and walking EE significantly declined by 1.5 months (P = 0.001) and remained suppressed at 6 and 12 months. Adjusted for age, sex, fat-free mass, and fat mass, EE was still lower than baseline (P = 0.001). Decreases in serum insulin, leptin, and triiodothyronine (T3), gut hormones, and urinary norepinephrine (NE) paralleled the decline in EE. Adjusted changes in TEE, BMR, and/or sleep EE were associated with decreases in insulin, homeostatic model assessment, leptin, thyroid stimulating hormone, total T3, peptide YY3-36, glucagon-like peptide-2, and urinary NE and epinephrine (P = 0.001-0.05). Conclusions Energetic adaptations in response to RYGB-induced weight loss are associated with changes in insulin, adipokines, thyroid hormones, gut hormones, and sympathetic nervous system activity and persists 12 months postsurgery.

Objective: The purpose of this study was to assess the effect of soy isoflavone supplementation on quality of life in postmenopausal women. Methods: A multicenter, randomized, double-blind, placebo-controlled 24-month trial was conducted to assess the effect of 80 or 120 mg of daily aglycone hypocotyl soy isoflavone supplementation on quality of life in 403 postmenopausal women using a validated Menopause-Specific Quality of Life questionnaire. Results: Menopause-Specific Quality of Life domain scores at 1 year and 2 years were similar to baseline. There were no differences in domain scores among treatment groups. Conclusions: Soy isoflavone supplementation offers no benefit to quality of life in postmenopausal women.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with skeletal involvement. It is caused by mutations in fibrillin1 (FBN1) gene resulting in activation of TGF-β, which developmentally regulates bone mass and matrix properties. There is no consensus regarding bone mineralization in children with MFS. Using dual-energy X-ray absorptiometry (DXA), we evaluated bone mineralization in 20 children with MFS unselected for bone problems. z-Scores were calculated based on age, gender, height, and ethnicity matched controls. Mean whole body bone mineral content (BMC) z-score was 0.26 ± 1.42 (P = 0.41). Mean bone mineral density (BMD) z-score for whole body was −0.34 ± 1.4 (P = 0.29) and lumbar spine was reduced at −0.55 ± 1.34 (P = 0.017). On further adjusting for stature, which is usually higher in MFS, mean BMC z-score was reduced at −0.677 ± 1.37 (P = 0.04), mean BMD z-score for whole body was −0.82 ± 1.55 (P = 0.002) and for lumbar spine was −0.83 ± 1.32 (P = 0.001). An increased risk of osteoporosis in MFS is controversial. DXA has limitations in large skeletons because it tends to overestimate BMD and BMC. By adjusting results for height, age, gender, and ethnicity, we found that MFS patients have significantly lower BMC and BMD in whole body and lumbar spine. Evaluation of diet, exercise, vitamin D status, and bone turnover markers will help gain insight into pathogenesis of the reduced bone mass. Further, larger longitudinal studies are required to evaluate the natural history, incidence of fractures, and effects of pharmacological therapy. © 2012 Wiley Periodicals, Inc.

Background: Soy isoflavones are naturally occurring phytochemicals with weak estrogenic cellular effects. Despite numerous clinical trials of short-term isoflavone supplementation, there is a paucity of data regarding longer-term outcomes and safety. Objective: Our aim was to evaluate the clinical outcomes of soy hypocotyl isoflavone supplementation in healthy menopausal women as a secondary outcome of a trial on bone health. Design: A multicenter, randomized, double-blind, placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg aglycone equivalent soy hypocotyl isoflavones plus calcium and vitamin D on the health of 403 postmenopausal women. At baseline and after 1 and 2 y, clinical blood chemistry values were measured and a well-woman examination was conducted, which included a mammogram and a Papanicolaou test. A cohort also underwent transvaginal ultrasound measurements to assess endometrial thickness and fibroids. Results: The baseline characteristics of the groups were similar. After 2 y of daily isoflavone exposure, all clinical chemistry values remained within the normal range. The only variable that changed significantly was blood urea nitrogen, which increased significantly after 2 y (P = 0.048) but not after 1 y (P = 0.343) in the supplementation groups. Isoflavone supplementation did not affect blood lymphocyte or serum free thyroxine concentrations. No significant differences in endometrial thickness or fibroids were observed between the groups. Two serious adverse events were detected (one case of breast cancer and one case of estrogen receptor–negative endometrial cancer), which was less than the expected population rate for these cancers. Conclusion: Daily supplementation for 2 y with 80–120 mg soy hypocotyl isoflavones has minimal risk in healthy menopausal women. This trial was registered at clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT00665860","term_id":"NCT00665860"}}NCT00665860

Objectives To assess the validity of body mass index (BMI) and age- and sex-standardized BMI z-score (BMIZ) as surrogates for adiposity (body fat percentage [BF%], fat mass, and fat mass index [kg/m2]) at 3 time points in infancy (1, 4, and 7 months) and to assess the extent to which the change in BMIZ represents change in adiposity. Study design We performed a secondary analysis of 447 full-term infants in a previous trial of maternal vitamin D supplementation during lactation. Study staff measured infant anthropometrics and assessed body composition with dual-energy x-ray absorptiometry at 1, 4, and 7 months of age. We calculated Spearman correlations (rs) among BMI, BMIZ, and adiposity at each time point, and between change in BMIZ and change in adiposity between time points. Results Infants (N = 447) were 52% male, 38% white, 31% black, and 29% Hispanic. The BMIZ was moderately correlated with BF% (rs = 0.43, 0.55, 0.48 at 1, 4, and 7 months of age, respectively). BMIZ correlated more strongly with fat mass and fat mass index, particularly at 4 and 7 months of age (fat mass rs = 0.72-0.76; fat mass index rs = 0.75-0.79). Changes in BMIZ were moderately correlated with adiposity changes from 1 to 4 months of age (rs = 0.44 with BF% change; rs = 0.53 with fat mass change), but only weakly correlated from 4 to 7 months of age (rs = 0.21 with BF% change; rs = 0.27 with fat mass change). Conclusions BMIZ is moderately correlated with adiposity in infancy. Changes in BMIZ are a poor indicator of adiposity changes in later infancy. BMI and BMIZ are limited as surrogates for adiposity and especially adiposity changes in infancy. Trial Registration ClinicalTrials.gov : NCT00412074 .

The efficacy of daily porcine growth hormone (GH) injections versus plasmid-driven porcine GH-releasing hormone (pGHRH) production to promote growth was assessed. Ten-day-old piglets were injected intramuscularly with 0.1, 1, or 3 mg pGHRH, or a control plasmid followed by electroporation. Plasmid constructs were driven by a synthetic muscle-specific promoter. A fifth group received daily injections of GH [0.15 mg/(kg·day)]. Control and pGHRH-treated pigs were pair-fed to GH-treated pigs. Body composition was assessed by dual-energy X-ray absorptiometry (DXA). Weight gains of GH- and pGHRH-treated pigs were greater than of controls (P < 0.001) due to greater lean mass accretion; fat accretion was similar across all treatments. Weight gain of pGHRH- and GH-treated pigs was similar for 6 weeks, but over the final 10 days, only pigs administered the highest plasmid dose maintained higher growth rates. Serum insulin-like growth factor-I (IGF-I) levels were two- to threefold higher in GH- and pGHRH-treated pigs than in controls after 4 weeks (P = 0.05), but subsequently decreased to control levels in the pGHRH-treated group. Organ weights were greater in GH- than pGHRH-treated and control piglets (P < 0.02). These results demonstrate that pGHRH transfer is effective for promoting growth and avoids the need for the frequent injections necessitated with peptide hormone use.

Many body composition measurement systems are calibrated against a single-sized reference phantom. Prompt-gamma neutron activation (PGNA) provides the only direct measure of total body nitrogen (TBN), an index of the body’s lean tissue mass. In PGNA systems, body size influences neutron flux attenuation, induced gamma signal distribution, and counting efficiency. Thus, calibration based on a single-sized phantom could result in inaccurate TBN values. We used Monte Carlo simulations (MCNP-5; Los Alamos National Laboratory) in order to map a system’s response to the range of body weights (65–160 kg) and body fat distributions (25–60%) in obese humans. Calibration curves were constructed to derive body-size correction factors relative to a standard reference phantom, providing customized adjustments to account for differences in body habitus of obese adults. The use of MCNP-generated calibration curves should allow for a better estimate of the true changes in lean tissue mass that many occur during intervention programs focused only on weight loss.

Objective: Dual-energy X-ray absorptiometry (DXA) is often cited as a criterion method for body composition measurements. We have previously shown that a new DXA software version (Hologic Discovery V12.1) will affect whole-body bone mineral results for subjects weighing

Objective: The aim of this study is to analyze the body composition of patients receiving emergent dialysis and compare their body cell mass (BCM) and fat-free mass (FFM) with those of normal subjects. The care of patients receiving sporadic, emergent dialysis treatment is a growing public health concern and the magnitude of muscle wasting that occurs in this population is not known. Design and Methods: We used a cross-sectional design with matching to determine differences in total body potassium - an indicator of both BCM and FFM - between emergent dialysis patients and healthy normal subjects. We studied 22 subjects using a 40K counter that measures BCM and FFM and compared them to controls after matching with sex, height and weight. Results: In the matched comparison, BCM and FFM were significantly lower in subjects with end-stage renal disease (ESRD). Unadjusted BCM was 4.7 kg lower and FFM was 8.8 kg lower for those with ESRD compared to those without ESRD (p < 0.001, p < 0.001, respectively). Comparison with unmatched controls who underwent 40K analysis also revealed significantly lower BCM (4.1 kg) and FFM (7.7 kg) in the ESRD subjects (p = 0.004). After adjusting for age, height, weight and gender, BCM and FFM were lower by 4.2 and 7.8 kg, respectively (p < 0.001). Repeated observations were available for a subset of ESRD subjects, and the rate of FFM loss over time was significant, with the ESRD subjects demonstrating 2.2 kg per year decline (p = 0.01). Conclusion: We conclude that among other consequences, muscle wasting indicated by decline in BCM and FFM is a significant concern in the growing emergent dialysis population.

Changes in the relative proportions of bone, muscle, water, visceral tissues, and body fat occur during growth. In the 1980s, reference models of body composition for children and adolescents were constructed by adjusting data on total body water (TBW), total body potassium (TBK), and regional bone mineral (BMC) data from several different Caucasian populations. In our study, we measured TBW, TBK, and total body BMC in 856 healthy European-American, African-American, and Mexican-American children. When we reconstructed the reference models using our contemporary data, we found that the body's bone, protein, and fat compartments are slightly but significantly different from the earlier models. Our study provides the range of normal body composition of healthy children, aged 5-18 years, and accounts for differences related to gender and ethnicity.

The newest version of whole body dual-energy X-ray absorptiometry (DXA) analysis software from Hologic (Discovery 12.1) is designed to enhance bone detection in smaller subjects. We re-analyzed 1127 pediatric scans (ages 1.8–18.5 yr) previously analyzed using software version 11.2. Regression analysis compared new and original results for bone area (BA), bone mineral content (BMC), bone mineral density (BMD), and DXA-derived body weight. Changes in total and regional bone results were compared with age, weight, and height. New results were highly correlated with original analyses (R 2 ≥ 0.9), but there were large differences at the individual subject level. The BA and BMC values increased in subjects less than 40 kg weight, resulting in a lower BMD. Original and new results were equivalent by about age 14 yr in both genders. Regional bone data showed the greatest changes in the legs. The newest software produces significant changes in bone values in subjects weighing less than 40 kg, compared with earlier versions. This effect increases with decreasing body weight. This will impact interpretation of longitudinal pediatric DXA studies, as well as existing pediatric whole body bone reference databases. Investigators must recognize which DXA software version they are using, and which version produced any reference database they may use for comparison.

The prompt- and delayed-gamma neutron activation techniques have been used for the non-invasive measurement of human body composition. In recent years, neutron irradiators have used only transuranic isotopic sources (238PuBe, 241AmBe, 252Cf). However, in today’s security-minded environment, the use of alternate neutron sources may provide some advantages. We have examined several designs for an irradiator that would use a high-output, miniature D-T neutron generator (MF Physics). The use of this type of neutron source will lessen the storage, security, and transport issues associated with continuous-output isotopic neutron sources. To determine the scientific impact of this decision, we have performed Monte Carlo simulations (MCNP-4B2; Los Alamos National Laboratory) to aid in the design of the irradiator system, evaluating shielding materials, collimation, and source-to-subject distance, for the measurement of total body nitrogen (TBN). Based on internal flux distributions within the simulated body region of a subject, several design options were identified. The final design will be selected based on the optimization of precision, dose, and exposure time.

Few studies of the VDR polymorphisms have looked at calcium metabolism or long-term effects. We measured bone mineralization and calcium metabolic parameters longitudinally in a group of 99 adoles- cents. We found a significant relationship between calcium absorption and skeletal calcium accretion and the Fok1, but not other VDR or related, genetic polymorphisms. It seems that the Fok1 polymorphism directly affects bone mineralization during pubertal growth through an effect on calcium absorption. Introduction: There are few data regarding the relationship between genetic markers for low bone mass and changes in calcium metabolism in childhood or adolescence. We sought to identify the effects of polymor- phisms of the vitamin D receptor (VDR) on calcium and bone mineral metabolism in a longitudinal study of pubertal adolescents. Materials and Methods: Adolescents (n 99) received comprehensive stable isotope studies of calcium absorption, bone calcium kinetics, and bone mineralization. Studies were repeated 12 months later. Polymor- phisms of putative genetic markers were determined and related to bone mineralization and calcium metabolic finding. Results were analyzed by ANOVA in which changes over time were determined using the initial value as a covariate. Results: Polymorphisms of the Fok1 gene of the VDR were significantly related to calcium absorption (p 0.008) and whole body BMC (p 0.03) and BMD (p 0.006). The Fok1 effect on whole body BMD was significant for those with Ca intake >800 mg/day (p < 0.001), whereas for those with Ca intake 800 mg/day, the Fok1 genotype did not have a significant effect on whole body BMD (p 0.40). The Fok1 genotype was significantly related to the changes during the year in whole body calcium accretion, with the ff genotype having a 63 ± 20 mg/day deficit compared with the FF genotype (p 0.008). Conclusions: The Fok1 polymorphism of the VDR receptor seems to directly affect bone mineral accretion during pubertal growth through an effect on calcium absorption. The relationship between different genetic polymorphisms and bone mineral metabolism may vary by life stage as well as diet. J Bone Miner Res 2005;20:945-953. Published online on January 31, 2005; doi: 10.1359/JBMR.050114

Background: Bioelectrical impedance spectroscopy (BIS) may provide a noninvasive, rapid method for the assessment of total body water (TBW), extracellular water (ECW), and intracellular water (ICW). Few studies, however, have examined the accuracy of BIS in pediatric populations. Objective: Our objective was to evaluate the accuracy ol BIS for the measurement of TBW, ECW, and ICW in healthy children. Design: Dual-energy X-ray absorptiometry (DXA), total body potassium (TBK), and BIS measurements were performed in 347 children (202 males and 145 females aged 4-18 y). The reference values for TBW, ECW, and ICW were defined by using a DXA+TBK model. BIS values were evaluated by using the method of Bland and Altman. A randomly selected calibration group (n = 231) was used to derive new BIS constants that were tested in the remaining group (n = 116). Results: BIS values were highly correlated with the reference values (r 2 = 0.94-0.97, P < 0.0001), but differences between the BIS and DXA+TBK models for individuals were significant (P < 0.001). Use of new BIS constants reduced the mean differences between the BIS and DXA+TBK models; the SDs of the mean differences were improved (1.8 L for TBW, 1.4 L for ICW and 1.0 L for ECW) for the total population. Conclusions: On a population basis, BIS can be calibrated to replace the DXA+TBK model for the assessment of TBW, ECW and ICW in healthy children. The accuracy of the BIS measure ment in individual children may be refined further by using age-and sex-specific adjustments for the BIS calibration constants.

Backgruund: Accuratc assessment of body composition in in­ rants ami chi Idren is fundamental to understanding normal growth and development. Validation of methods applicable to pediatric populations is needed. In the absence of a gold stan­ dard, thi, study was conducted 10 compare methods using total body water. total body potassium, total body electrical conduc­ tivity. ami dual energy x-ray absorptiometry measurements for thc estimation or body rat mass in infants and toddlers. Methods: Repeated body composition measurements were per­ formed on 7b healthy term infants at 0.5, 3. 6, 9, 12, 18. and 24 months of age. Total body water was determined by deuterium dililtion and convcrted to fat-free mass. Total body electrical conductivity was used 10 measure fat mass. Total body potas­ sillm was estimated by whole-body counting and converted to l'at-1'I'

Total body chlorine (TBC1) provides an estimate of extracellular water. We have examined the feasibility of measuring TBC1 using the 5.6, 6.1, and 8.6 MeV C1 peaks produced during in vivo prompt-gamma neutron activation (dose

The feasibility of measuring total body carbon (TBC) based on prompt-gamma activation analysis (PGAA) of the human body was examined. Preliminary analyzes for 33 healthy pre-menopausal women indicated a range of TBC values (7.1±4.4 kg) which translated to 17.1±6.5 kg body fat (27.9%±7.9% of body weight). An advantage of the PGAA measurement is that fat mass can be obtained simultaneous with that of total body protein mass, both indices serving as useful body composition markers of the nutritional status.

Dual-energy X-ray absorptiometry (DXA) requires phantoms for quality control and cross-calibration. No commercially available phantoms are designed specifically for whole-body scanning of infants.We fabricated a phantom closely matching a 7-kg human infant in body habitus using polyvinyl chloride (PVC), nylon mix, and polyethylene for bone, lean tissue, and fat, respectively, for evaluating the comparability of instruments used in studies on infant body composition. We scanned the phantom multiple times for short- and long-term repeatability and then shipped it to six other sites for comparison scans. All instruments were Hologic Delphi or Discovery models. Scan analyses were in-house procedures (Hologic V12.1).Short- and long-term results were not significantly different. Nylon mix underrepresented expected lean mass values by 5%, PVC underrepresented bone by 12%, and polyethylene overrepresented fat by 30%. Precision values were as follows: lean mass ≈ 3%; bone ≈ 3.5%; and fat = 5.5-7.5%. Instruments differed significantly for bone mineral content and density results in most instances. Three instruments differed in fat and lean mass. The two Hologic models differed significantly in all compartments except bone density.The phantom design came close to emulating bone, lean tissue, and fat and showed good reproducibility. Significant differences among various DXA instruments highlight the necessity of cross-calibration for any multicenter studies.

Total body neutron activation analysis (NAA) was used to examine the elemental composition of 22 piglets in the weight range 0.7 kg to 3.4 kg. The accuracy of the NAA technique, compared to direct chemical carcass analysis, established it as an equivalent chemical criterion (reference) method. The body composition of 14 human infant cadavers was also examined by NAA and by dual-energy x-ray absorptiometry (DXA). The DXA-derived lean, fat, and bone compartments were compared with an NAA chemical model of composition. Each of the three compartments was significantly correlated (r=0.85–0.95,p

In an earlier report, we showed that a 2-week, residential summer camp (Kamp K'aana) led to improved body weight, body mass index, body mass index z score, and self-esteem among obese children. To assess whether improvements in body weight and self-esteem translate into improvement in body fat and weight-related quality of life, we measured the changes in body fat by bioimpedance and quality of life by Impact of Weight on Quality of Life instrument on 42 multiethnic obese children who took part in our Kamp K'aana program. Significant reduction in body fat was detected with significant improvements in the weight-related quality of life scores.

Total body nitrogen (TBN) can be used to estimate total body protein, an important body composition component at the molecular level. A system using the associated particle technique in conjunction with prompt gamma neutron activation analysis has been developed for the measurement of TBN in vivo. The system uses a compact D, T neutron generator (~107 n/s) coupled to an internal alpha-particle detector, and a counting system with six bismuth germinate detectors. 14 Subjects were scanned from shoulders to hips (20 min scan time

The accuracy of body-composition measurements by dual-energy x-ray absorptiometry (DXA) was assessed by comparison with total carcass chemical analysis in 16 pigs with a weight range of 5-35 kg. Two software versions for body-composition analyses with the DXA instrument were evaluated. Although both software versions accurately predicted body weight, there were significant differences in the partitioning between bone mineral content (BMC), nonbone lean tissue, and body-fat compartments. All estimates of body composition were highly correlated (r2 > or = 0.98) with the results of the direct chemical reference method. SEEs were 226-271 g for body weight, 387-429 g for fat, 3.5-4.3 kg for fat-free mass, and 35.4-36.5 g for BMC. For bone, both software versions produced BMC values that were approximately 25% below the total carcass ash content. For the absolute mass of body fat, one DXA analysis provided underestimates that averaged 19.5% below the reference chemical method, whereas the alternate software version resulted in over-estimates, averaging 15.5%. Conversely, the average fat-free compartment was initially overestimated by 968 g, then underestimated by 892 g. The impact of these differences in the body-composition analyses by DXA were examined in a group of 18 young boys 4-12 y of age.

The body composition of 23 infants was examined at postmortem. All infants were live births and lived from 1 to 192 days. Their body weights at birth ranged from 480 to 3280 g; gestational ages ranged from 24 to 42 weeks. Total body composition was determined using the nondestructive in-situ procedures of 40K counting and neutron activation analysis. The absolute amounts of K, Ca, P, Na, and Cl were measured. Although body Cl was in general agreement with estimates for the reference fetus model, body K and Na values were lower. Body Ca content was higher than the reference fetus at body weights above 2 kg, yet body P levels agreed with the reference fetus. Furthermore, those infants whose survival was brief had reduced body K, an index of body cell mass. All elements except body Cl were linearly related to fat-free mass (FFM). The correlations with gestational age were non-significant when the variation in elemental content was accounted for by FFM or body weight. The two preterm infants who survived for more than 10 weeks had significantly reduced bone growth as shown by their Ca and P deficiences.

During construction of the whole body counter (WBC) at the Children's Nutrition Research Center (CNRC), efficiency calibration was needed to translate acquired counts of (40)K to actual grams of potassium for measurement of total body potassium (TBK) in a diverse subject population. The MCNP Monte Carlo n-particle simulation program was used to describe the WBC (54 detectors plus shielding), test individual detector counting response, and create a series of virtual anthropomorphic phantoms based on national reference anthropometric data. Each phantom included an outer layer of adipose tissue and an inner core of lean tissue. Phantoms were designed for both genders representing ages 3.5 to 18.5 years with body sizes from the 5th to the 95th percentile based on body weight. In addition, a spherical surface source surrounding the WBC was modeled in order to measure the effects of subject mass on room background interference. Individual detector measurements showed good agreement with the MCNP model. The background source model came close to agreement with empirical measurements, but showed a trend deviating from unity with increasing subject size. Results from the MCNP simulation of the CNRC WBC agreed well with empirical measurements using BOMAB phantoms. Individual detector efficiency corrections were used to improve the accuracy of the model. Nonlinear multiple regression efficiency calibration equations were derived for each gender. Room background correction is critical in improving the accuracy of the WBC calibration.

Few data exist on the elemental composition of the human body during infancy. The scarcity of the data is due, in part, to the destructive nature of total body analyses normally required for the classical chemical approach. To help determine such data for infants, we have developed a neutron activation facility for nondestructive postmortem analyses. The system consists of a multisource241AmBe irradiator and a multidetector NaI(T1) whole body counter. The total body contents of K, Ca, P, Na and Cl are determined. Postmortem examinations have been performed in twelve infant cadavers. These results are compared with those of the reference fetus.

The total body elemental content of seventeen neonates at postmortem was examined; deaths had occurred within 10 days of birth. Body weights ranged from 510 to 4,050 g at examination; gestational ages at birth ranged from 24 to 42 weeks. Nondestructive in situ procedures were used: 40 K counting and delayed-gamma neutron activation analysis. The total body content of K, Ca, P, Na, and Cl was measured and compared with estimates for the reference fetus model. Body elemental contents were significantly correlated with body weight (r = 0.92-0.98, P < 0.001). These data will be useful in determining postnatal nutritional needs. © 1993 Wiley-Liss, Inc.

Neutron activation analysis provides an accurate elemental assessment of body compositional compartments; the analytical technique identifies skeletal, muscle, protein, and fat masses. Our irradiator system uses 56241AmBe sources (4.4·107 n/s each) which can be arranged in four basic geometries to examine body sizes from a preterm infant (500 g, 30 cm) to a very large adult (120 kg, 2m). Both in vivo and human cadaver studies have been performed. Precisions of 1 to 2% for total body Ca, P, Na, and Cl have been obtained.

We have examined several whole body counting geometries for exclusive use in total body potassium (TBK) measurements in preterm infants. This paper describes two counters, one for very-low-birth-weight (VLBW) infants with body weights under 2000 g, and a second counter for larger preterm infants. Both systems use large-volume NaI(Tl) detectors (10.2 cm × 10.2 cm × 45.7 cm) and are operated in a low background room. The standard error for a TBK measurement decreases from 5% at 1 kg body weight to 2% at 4.5 kg weight.

Characteristic gamma-rays are emitted promptly by elements during exposure to neutrons. These emissions enable a radioanalytical analysis of the body's composition of protein (nitrogen), water (hydrogen), and fat (carbon). We have used this method in vivo to determine the body composition of obese and lean pigs (10 to 20 kg body wt) fed an altered cholesterol diet.