Comparison of percentile tables and algorithm-based calculators for classification of blood pressures in children and adolescents with obesity: A secondary analysis of a clinical trial.

AIM: 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. METHODS: 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 index >99th percentile or >91st 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. RESULTS: 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%). CONCLUSIONS: 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.

External validation of a prediction model for estimating fat mass in children and adolescents in 19 countries: individual participant data meta-analysis.

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 <4 kg in 17 of the 19 settings. Pooled values (95% confidence intervals) of R2, calibration slope, and calibration-in-the-large were 88.7% (85.9% to 91.4%), 0.98 (0.97 to 1.00), and 0.01 (-0.02 to 0.04), respectively. Heterogeneity was evident in the R2 and calibration-in-the-large values across settings, but not in the calibration slope. Model performance did not vary markedly between boys and girls, age, ethnicity, and national income groups. To further improve the accuracy of the predictions, the model equation was recalibrated for the intercept in each setting so that country specific equations are available for future use. CONCLUSION: The UK based prediction model, which is based on readily available measures, provides predictions of childhood fat-free mass, and hence fat mass, in a range of non-UK settings that explain a large proportion of the variability in observed fat-free mass, and exhibit good calibration performance, especially after recalibration of the intercept for each population. The model demonstrates good generalisability in both low-middle income and high income populations of healthy children and adolescents aged 4-15 years.

Adiposity, Insulin Resistance, Cardiorespiratory Fitness, and Bone Health in Hispanic Children.

CONTEXT: Childhood obesity disproportionately affects Hispanic youth. The skeletal system appears to be a target organ of the adverse effects of obesity. Yet, the relationship between adiposity and bone health in youth and the modulating factors are not well understood. OBJECTIVE: This work aims to examine the relationship between adiposity, insulin resistance (IR), cardiorespiratory fitness (CRF), and bone mass in Hispanic youth. METHODS: A total of 951 Hispanic youth (50% male), aged 4 to 19 years, participated in this cross-sectional design study from the Viva La Familia Study at Children's Nutrition Research Center. Bone mineral content (BMC) and density (BMD), lean mass (LM), total body fat mass (FM), truncal FM were obtained using dual-energy x-ray absorptiometry. Fasting glucose and insulin were obtained and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. CRF was measured using a treadmill ramp protocol. We applied linear regression models and mediation analyses. RESULTS: Adiposity measures were negatively related to BMC and BMD after accounting for LM and sex. IR negatively contributed whereas CRF positively contributed to the variance in BMC and BMD, more notably in the pubertal age group. In mediation analysis, HOMA-IR partially mediated the negative relationship of adiposity to BMC (standardized indirect effect [IE] = -0.0382; 95% CI, -0.0515 to -0.0264) whereas the sequential IE of HOMA-IR and CRF partially attenuated (IE = -0.0026; 95% CI, -0.0053 to -0.0005) this relationship. Similar findings were seen with BMD as the primary outcome. CONCLUSION: IR mediates the negative relationship between adiposity and bone mass whereas CRF may partially attenuate it.

Targeting TGF-ß for treatment of osteogenesis imperfecta.

BACKGROUNDCurrently, there is no disease-specific therapy for osteogenesis imperfecta (OI). Preclinical studies demonstrate that excessive TGF-ß signaling is a pathogenic mechanism in OI. Here, we evaluated TGF-ß signaling in children with OI and conducted a phase I clinical trial of TGF-ß inhibition in adults with OI.METHODSHistology and RNA-Seq were performed on bones obtained from children. Gene Ontology (GO) enrichment assay, gene set enrichment analysis (GSEA), and Ingenuity Pathway Analysis (IPA) were used to identify dysregulated pathways. Reverse-phase protein array, Western blot, and IHC were performed to evaluate protein expression. A phase I study of fresolimumab, a TGF-ß neutralizing antibody, was conducted in 8 adults with OI. Safety and effects on bone remodeling markers and lumbar spine areal bone mineral density (LS aBMD) were assessed.RESULTSOI bone demonstrated woven structure, increased osteocytes, high turnover, and reduced maturation. SMAD phosphorylation was the most significantly upregulated GO molecular event. GSEA identified the TGF-ß pathway as the top activated signaling pathway, and IPA showed that TGF-ß1 was the most significant activated upstream regulator mediating the global changes identified in OI bone. Treatment with fresolimumab was well-tolerated and associated with increases in LS aBMD in participants with OI type IV, whereas participants with OI type III and VIII had unchanged or decreased LS aBMD.CONCLUSIONIncreased TGF-ß signaling is a driver pathogenic mechanism in OI. Anti-TGF-ß therapy could be a potential disease-specific therapy, with dose-dependent effects on bone mass and turnover.TRIAL REGISTRATIONClinicalTrials.gov NCT03064074.FUNDINGBrittle Bone Disorders Consortium (U54AR068069), Clinical Translational Core of Baylor College of Medicine Intellectual and Developmental Disabilities Research Center (P50HD103555) from National Institute of Child Health and Human Development, USDA/ARS (cooperative agreement 58-6250-6-001), and Sanofi Genzyme.

Genetic variants and physical activity interact to affect bone density in Hispanic children.

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 < 0.05). Higher PRS was associated with a lower total body BMD (ß = - 0.040 ± 0.009, p = 1.1 × 10- 5) and lumbar spine BMD (ß = - 0.042 ± 0.013, p = 0.0016) in low MVPA group, as compared to high MVPA group (ß = - 0.015 ± 0.006, p = 0.02; ß = 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.

Characterization of the Robinow syndrome skeletal phenotype, bone micro-architecture, and genotype-phenotype correlations with the osteosclerotic form.

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.

Fat and fat-free mass index references in children and young adults: assessments along racial and ethnic lines.

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.

Growth, Body Composition, and Neurodevelopmental Outcomes at 2 Years Among Preterm Infants Fed an Exclusive Human Milk Diet in the Neonatal Intensive Care Unit: A Pilot Study.

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 <70. Conclusions: In addition to returning to BW, length, and HC z-scores by 2 years of age, body composition analysis revealed that increase in body size was appropriate as reflected by LM and bone density similar to matched term controls without an increase in fat mass. No child had severe cognitive developmental delay using a cutoff score of 70. Inpatient growth and increased receipt of MOM correlated with favorable growth and body composition outcomes. Positive outcomes as shown in this study to confirm postdischarge safety of an EHM diet during hospitalization.

Genetic variants affecting bone mineral density and bone mineral content at multiple skeletal sites in Hispanic children.

CONTEXT: Osteoporosis is a major public health burden with significant economic costs. However, the correlates of bone health in Hispanic children are understudied. OBJECTIVE: We aimed to identify genetic variants associated with bone mineral density (BMD) and bone mineral content (BMC) at multiple skeletal sites in Hispanic children. METHODS: We conducted a cross-sectional genome-wide linkage analysis, genome-wide and exome-wide association analysis of BMD and BMC. The Viva La Familia Study is a family-based cohort with a total of 1030 Hispanic children (4-19 years old at baseline) conducted in Houston, TX. BMD and BMC were measured by Dual-energy X-ray absorptiometry. RESULTS: Significant heritability were observed for BMC and BMD at multiple skeletal sites ranging between 44 and 68% (P < 2.8 × 10-9). Significant evidence for linkage was found for BMD of pelvis and left leg on chromosome 7p14, lumbar spine on 20q13 and left rib on 6p21, and BMC of pelvis on chromosome 20q12 and total body on 14q22-23 (logarithm of odds score > 3). We found genome-wide significant association between BMC of right arm and rs762920 at PVALB (P = 4.6 × 10-8), and between pelvis BMD and rs7000615 at PTK2B (P = 7.4 × 10-8). Exome-wide association analysis revealed novel association of variants at MEGF10 and ABRAXAS2 with left arm and lumber spine BMC, respectively (P < 9 × 10-7). CONCLUSIONS: We identified novel loci associated with BMC and BMD in Hispanic children, with strongest evidence for PTK2B. These findings provide better understanding of bone genetics and shed light on biological mechanisms underlying BMD and BMC variation.

New generation lipid emulsions increase brain DHA and improve body composition, but not short-term neurodevelopment in parenterally-fed preterm piglets.

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-1ß 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 < 0.05). ENT pigs spent more time in higher physical activity levels compared to all TPN groups, but there were no differences in exploratory behavior among groups. We conclude that a soybean oil emulsion increased select brain inflammatory cytokines and multicomponent lipid emulsions enriched with DHA and AA in parenteral lipids results in increased cortical DHA and improved body composition without affecting short term neurodevelopmental outcomes.

Successful Kidney Transplantation Is Associated With Weight Gain From Truncal Obesity and Insulin Resistance.

OBJECTIVE: 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. DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Impact of changes in maternal body composition on birth weight and neonatal fat mass in dichorionic twin pregnancies.

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.

Estimated energy requirements increase across pregnancy in healthy women with dichorionic twins.

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.

Validity of Body Mass Index as a Measure of Adiposity in Infancy.

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.

Associations of infant feeding with trajectories of body composition and growth.

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.

Generalized metabolic bone disease and fracture risk in Rothmund-Thomson syndrome.

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.

Adverse Effects of Sporadic Dialysis on Body Composition.

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.

Mother's pre-pregnancy BMI is an important determinant of adverse cardiometabolic risk in childhood.

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/m(2) , p = 0.001), % body fat (31.7 ± 1.6 vs. 24.6 ± 1.1%, p < 0.001), visceral fat (41.9 ± 4.7 vs. 26.1 ± 3.9 cm(2) , p = 0.012) with no difference in lean body mass compared with O-NW. O-OW had lower whole body insulin sensitivity index (WBISI) with an adverse cardiovascular disease risk profile [higher blood pressure (BP), triglycerides to high-density lipoprotein (HDL) ratio, hs-C-reactive protein (CRP) and lower HDL]. In addition to offspring's %body fat (ß = -0.60, p < 0.001), maternal pre-pregnancy BMI (ß = -0.19, p = 0.046) contributed significantly and independently to the offspring's WBISI (R(2) =0.55, p < 0.001). CONCLUSIONS: High pre-pregnancy BMI is an important contributor to excess adiposity, insulin resistance, and cardiometabolic disease risk in the offspring during childhood.

Energetic adaptations persist after bariatric surgery in severely obese adolescents.

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.