Environmental Phenols and Growth in Infancy: The Infant Feeding and Early Development Study.

CONTEXT: Higher mean and rapid increases in body mass index (BMI) during infancy are associated with subsequent obesity and may be influenced by exposure to endocrine-disrupting chemicals such as phenols. OBJECTIVE: In a prospective US-based cohort conducted 2010-2014, we investigated associations between environmental phenol exposures and BMI in 199 infants. METHODS: We measured seven urinary phenols at ages 6-8 and 12 weeks and assessed BMI z-score at up to 12 study visits between birth and 36 weeks. We examined individual and joint associations of averaged early infancy phenols with level of BMI z-score using mean differences (ß [95% confidence intervals (CI)]) and with BMI z-score trajectories using relative risk ratios (RR [95% CI]). RESULTS: Benzophenone-3, methyl and propyl paraben, and all phenols jointly were positively associated with higher mean BMI z-score (0.07 [-0.05, 0.18], 0.10 [-0.08, 0.27], 0.08 [-0.09, 0.25], 0.17 [-0.08, 0.43], respectively). Relative to a Stable trajectory, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, and all phenols jointly were positively associated with risk of a Rapid Increase trajectory (1.46 [0.89, 2.39], 1.33 [0.88, 2.01], 1.66 [1.03, 2.68], 1.41 [0.71, 2.84], respectively). CONCLUSION: Early phenol exposure was associated with a higher mean and rapid increase in BMI z-score across infancy, signaling potential long-term cardiometabolic consequences of exposure.

IMPROVE-BMT: A Pilot Randomized Controlled Trial of Prehabilitation Exercise for Adult Hematopoietic Stem Cell Transplant Recipients.

Background: There is limited evidence on the effects of aerobic and resistance training exercise interventions to improve physical function and patient-reported outcomes prior to autologous and allogeneic hematopoietic stem cell transplant (HSCT). IMPROVE-BMT was a single-site, pilot randomized controlled trial investigating the feasibility, acceptability, and safety of a pragmatic resistance training exercise program prior to HSCT compared to usual HSCT care. Secondary aims included differences in physical function between the exercise group (EX) and usual care control group (UC). Methods: Outcome measurements were assessed: prior to HSCT, on/around day of HSCT admission, +30 days post-HSCT, and +100 days post-HSCT. The exercise intervention was a home-based exercise program that incorporated resistance-band and bodyweight exercises. Results: Acceptability among participants was 83%; exercise adherence averaged at 92%; and there were zero exercise-related adverse or serious adverse events. The average pre-transplant exercise phase was 6.28 weeks (2.71-18.29 weeks). EX (n = 36) demonstrated larger increases in the six-minute walk test distance, short physical performance battery scores, and 30-s chair stands compared to UC (n = 38) and demonstrated significant within-group improvements for the six-minute walk test, the short physical performance battery, the 30-s chair stands, and the timed up-and-go test. Conclusions: IMPROVE-BMT demonstrates that pragmatic exercise is highly feasible for HSCT recipients and can potentially lead to enhanced recovery that may not be achievable in non-exercisers.

GWAS-informed data integration and non-coding CRISPRi screen illuminate genetic etiology of bone mineral density.

Over 1,100 independent signals have been identified with genome-wide association studies (GWAS) for bone mineral density (BMD), a key risk factor for mortality-increasing fragility fractures; however, the effector gene(s) for most remain unknown. Informed by a variant-to-gene mapping strategy implicating 89 non-coding elements predicted to regulate osteoblast gene expression at BMD GWAS loci, we executed a single-cell CRISPRi screen in human fetal osteoblast 1.19 cells (hFOBs). The BMD relevance of hFOBs was supported by heritability enrichment from cross-cell type stratified LD-score regression involving 98 cell types grouped into 15 tissues. 24 genes showed perturbation in the screen, with four (ARID5B, CC2D1B, EIF4G2, and NCOA3) exhibiting consistent effects upon siRNA knockdown on three measures of osteoblast maturation and mineralization. Lastly, additional heritability enrichments, genetic correlations, and multi-trait fine-mapping revealed that many BMD GWAS signals are pleiotropic and likely mediate their effects via non-bone tissues that warrant attention in future screens.

Relative leg-to-arm skeletal strength proportions in orangutans by species and sex.

Among extant great apes, orangutans climb most frequently. However, Bornean orangutans (Pongo pygmaeus) exhibit higher frequencies of terrestrial locomotion than do Sumatran orangutans (Pongo abelii). Variation in long bone cross-sectional geometry is known to reflect differential loading of the limbs. Thus, Bornean orangutans should show greater relative leg-to-arm strength than their Sumatran counterparts. Using skeletal specimens from museum collections, we measured two cross-sectional geometric measures of bone strength: the polar section modulus (Zpol) and the ratio of maximum to minimum area moments of inertia (Imax/Imin), at the midshaft of long bones in Bornean (n = 19) and Sumatran adult orangutans (n = 12) using medical CT and peripheral quantitative CT scans, and compared results to published data of other great apes. Relative leg-to-arm strength was quantified using ratios of femur and tibia over humerus, radius, and ulna, respectively. Differences between orangutan species and between sexes in median ratios were assessed using Wilcoxon rank sum tests. The tibia of Bornean orangutans was stronger relative to the humerus and the ulna than in Sumatran orangutans (p = 0.008 and 0.025, respectively), consistent with behavioral studies that indicate higher frequencies of terrestrial locomotion in the former. In three Zpol ratios, adult female orangutans showed greater leg-to-arm bone strength compared to flanged males, which may relate to females using their legs more during arboreal locomotion than in adult flanged males. A greater amount of habitat discontinuity on Borneo compared to Sumatra has been posited as a possible explanation for observed interspecific differences in locomotor behaviors, but recent camera trap studies has called this into question. Alternatively, greater frequencies of terrestriality in Pongo pygmaeus may be due to the absence of tigers on Borneo. The results of this study are consistent with the latter explanation given that habitat continuity was greater a century ago when our study sample was collected.

Bile salt hydrolase catalyses formation of amine-conjugated bile acids.

Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes1-6; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine N-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of bsh and mutants in Escherichia coli and bsh knockout and complementation in Bacteroides fragilis to demonstrate that BSH generates BBAAs. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of bsh-expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network.

Paediatric dominant and non-dominant handgrip reference curves and the association with body composition.

BACKGROUND: Lack of paediatric reference data limits the utility of handgrip strength as a measure of fitness and well-being. AIM: To develop paediatric handgrip reference curves and evaluate associations with body size and composition and race/ethnicity group. SUBJECTS AND METHODS: Handgrip, body size and composition data were obtained from National Health and Nutrition Examination Survey 2011-2014 participants aged 6-20 years. Densitometry-derived fat and appendicular lean soft tissue mass index Z-scores (FMIZ, ALSTMIZ) were generated in participants >8 years. Dominant and non-dominant handgrip reference curves were created using the LMS method. Analyses included sample weights to produce nationally representative estimates. RESULTS: Differences in handgrip strength according to hand dominance increased with age. Handgrip strength was associated with height and arm length Z-scores (R = 0.42 to 0.47) and ALSTMIZ (R = 0.54). Handgrip strength was higher in the non-Hispanic Black group and lower in the Mexican American compared to non-Hispanic White group. Group differences were attenuated when adjusted for height, arm length or ALSTMIZ. CONCLUSION: Paediatric handgrip reference curves were generated from which individual Z-scores can be calculated separately for dominant versus non-dominant hand and adjusted for body size. Association with ALSTMIZ suggests handgrip Z-score may be used as a measure of functional body composition.

3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity.

The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts. Integrating childhood obesity GWAS summary statistics with our existing 3D genomic datasets for 57 human cell types, consisting of high-resolution promoter-focused Capture-C/Hi-C, ATAC-seq, and RNA-seq, we applied stratified LD score regression and calculated the proportion of genome-wide SNP heritability attributable to cell type-specific features, revealing pancreatic alpha cell enrichment as the most statistically significant. Subsequent chromatin contact-based fine-mapping was carried out for genome-wide significant childhood obesity loci and their linkage disequilibrium proxies to implicate effector genes, yielded the most abundant number of candidate variants and target genes at the BDNF, ADCY3, TMEM18 and FTO loci in skeletal muscle myotubes and the pancreatic beta-cell line, EndoC-BH1. One novel implicated effector gene, ALKAL2 - an inflammation-responsive gene in nerve nociceptors - was observed at the key TMEM18 locus across multiple immune cell types. Interestingly, this observation was also supported through colocalization analysis using expression quantitative trait loci (eQTL) derived from the Genotype-Tissue Expression (GTEx) dataset, supporting an inflammatory and neurologic component to the pathogenesis of childhood obesity. Our comprehensive appraisal of 3D genomic datasets generated in a myriad of different cell types provides genomic insights into pediatric obesity pathogenesis.

Bone health in children with recurrent and chronic pancreatitis: A multi-center cross sectional analysis.

BACKGROUND/OBJECTIVES: Bone health of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) is not well studied. METHODS: This retrospective study was performed at three sites and included data from INSPPIRE-2. RESULTS: Of the 87 children in the study: 46 had ARP (53%), 41 had CP (47%). Mean age was 13.6 ± 3.9 years at last DXA scan. The prevalence of low height-for-age (Z-score < -2) (13%, 10/78) and low bone mineral density (BMD) adjusted for height (Z-score < -2) (6.4%, 5/78) were higher than a healthy reference sample (2.5%, p < 0.0001 and p = 0.03, respectively). CONCLUSION: Children with ARP or CP have lower height and BMD than healthy peers. Attention to deficits in growth and bone mineral accrual in children with pancreatic disease is warranted.

Reference ranges for body composition indices by dual energy X-ray absorptiometry from the Bone Mineral Density in Childhood Study Cohort.

BACKGROUND: Body composition assessment aids evaluation of energy stores and the impact of diseases and interventions on child growth. Current United States pediatric reference ranges from the National Health and Nutrition Examination Survey (NHANES) include 20% of children with obesity, body mass index of ≥95th percentile. OBJECTIVES: This study aimed to develop dual energy X-ray absorptiometry (DXA) based reference ranges in a diverse cohort with low-obesity prevalence from the Bone Mineral Density in Childhood Study (BMDCS). METHODS: This is a secondary analysis of a longitudinal, prospective, observational cohort. Healthy children (height and BMI within 3rd to 97th percentiles, ages 5-19 y at enrollment), from 5 United States centers were measured annually for ≤7 visits. Whole body scans were acquired using Hologic scanners. A subsample underwent repeat measurements to determine precision. We generated reference ranges for appendicular and total lean soft tissue mass index (LSTM Index), fat mass index (FMI), and other body composition measures. Resulting curves were compared to NHANES and across subgroups. Sex and age-specific equations were developed to adjust body composition Z-scores for height Z score. RESULTS: We obtained 9846 scans of 2011 participants (51% female, 22% Black, 17% Hispanic, 48% White, 7% Asian/Pacific Islander, and 6% with obesity). Precision (percent coefficient of variation) ranged from 0.7% to 1.96%. Median and-2 standard deviation curves for BMDCS and NHANES were similar, but NHANES +2 standard deviation LSTM Index and FMI curves were distinctly greater than the respective BMDCS curves. Subgroup differences were more extreme for appendicular LSTM Index-Z (mean ± SD: Asian -0.52 ± 0.93 compared with Black 0.77 ± 0.87) than for FMI-Z (Hispanic 0.29 ± 0.98 compared with Black -0.14 ± 1.1) and were smaller for Z-scores adjusted for height Z-score. CONCLUSIONS: These reference ranges add to sparse normative data regarding body composition in children and adolescents and are based on a cohort with an obesity prevalence similar to current BMI charts. Awareness of subgroup differences aids in interpreting results.

The neighborhood environment and sleep health in adolescents.

OBJECTIVE: Neighborhood-level factors, including education, health and environment, and socioeconomic exposures, are important contextual determinants of child health. We explored whether these factors, measured via the Childhood Opportunity Index 2.0, were associated with sleep health in adolescents. METHODS: Actigraphy was used to assess sleep duration, timing, and efficiency among 110 adolescents in eighth (13.9 (0.4)) and ninth (14.9 (0.4)) grade. Home addresses were geocoded and linked to Childhood Opportunity Index 2.0 scores (including 3 subtype scores and the 29 individual factor Z-scores). Mixed-effects linear regression was used to determine associations between the Childhood Opportunity Index 2.0 scores and the sleep outcomes, adjusting for sex, race, parent education, household income, school grade and weeknight status. Interactions were also tested by school grade, weeknight status, sex, and race. RESULTS: No associations were observed between overall or subtype scores with sleep outcomes in adolescents. However, we detected associations between select individual Childhood Opportunity Index 2.0 Z-scores, spanning health & environment and education domains, and sleep outcomes. For example, greater fine particulate matter was associated with later timing of sleep onset and offset; ozone concentration was associated with earlier sleep onset and offset; greater exposure to extreme temperature was associated with later sleep onset and offset and increased odds of optimal sleep efficiency. CONCLUSIONS: Specific neighborhood factors indexed by the Childhood Opportunity Index 2.0 were associated with sleep health among adolescents. In particular, neighborhood air quality measures were associated with sleep timing and efficiency, warranting further investigation.

From growth charts to growth status: how concepts of optimal growth and tempo influence the interpretation of growth measurements.

Growth measurements are largely uninterpretable without comparison to a growth chart. Consequently, the characteristics of a growth chart become an integral component of the interpretation of growth measurements. The concepts of optimal growth and tempo are well recognised by auxologists, yet their implications for interpretation of growth measurements remain problematic. This narrative review discusses the concept of optimal growth and how it serves as a guiding principle in the development and use of growth charts. The challenges of operationalising tempo for growth assessment are also discussed. Illustrative examples highlight the importance of these two central concepts in the use and interpretation of growth measurements.

Physical Activity in Youth with Down Syndrome and Its Relationship with Adiposity.

PURPOSE: The aims of this study are to (1) compare physical activity (PA) and sedentary activity (SA) in youth with and without Down syndrome (DS and non-DS) and examine the relationships of PA and SA with their traditional risk factors (age, sex, race, and body mass index Z score [BMI-Z]) and (2) explore the relationship of PA with visceral fat (VFAT) in both groups. METHODS: SenseWear accelerometry data from at least 2 weekdays and 1 weekend day were collected from youth with DS (N = 77) and non-DS (N = 57) youth. VFAT was measured by dual x-ray absorptiometry. RESULTS: In age-, sex-, race-, and BMI-Z-adjusted models, those with DS engaged in more minutes of light PA (LPA) ( p < 0.0001) and less SA ( p = 0.003) and trended toward fewer minutes of moderate-to-vigorous PA (MVPA) ( p = 0.08) than non-DS youth. No race or sex differences in MVPA were detected in those with DS, unlike non-DS. After additional adjustment for pubertal status, the relationship between MVPA and VFAT approached significance ( p = 0.06), whereas the relationships of LPA and SA with VFAT were maintained ( p ≤ 0.0001 for both). CONCLUSION: Youth with DS engage in more LPA compared with non-DS, which, in typically developing populations, can confer a more favorable weight status. Increasing the opportunity for youth with DS to engage in LPA as part of their activities of daily living may offer a viable strategy for achieving healthy weight when barriers restrict pursuit of more vigorous PA.

Beyond Dimorphism: Body Size Variation Among Adult Orangutans Is Not Dichotomous by Sex.

Among extant great apes, orangutans are considered the most sexually dimorphic in body size. However, the expression of sexual dimorphism in orangutans is more complex than simply males being larger than females. At sexual maturity, some male orangutans develop cheek pads (flanges), while other males remain unflanged even after becoming reproductively capable. Sometimes flange development is delayed in otherwise sexually mature males for a few years. In other cases, flange development is delayed for many years or decades, with some males even spending their entire lifespan as unflanged adults. Thus, unflanged males of various chronological ages can be mistakenly identified as "subadults." Unflanged adult males are typically described as "female-sized," but this may simply reflect the fact that unflanged male body size has only ever been measured in peri-pubescent individuals. In this study, we measured the skeletons of 111 wild adult orangutans (Pongo spp.), including 20 unflanged males, 45 flanged males, and 46 females, resulting in the largest skeletal sample of unflanged males yet studied. We assessed long bone lengths (as a proxy for stature) for all 111 individuals and recorded weights-at-death, femoral head diameters, bi-iliac breadths, and long bone cross-sectional areas (CSA) (as proxies for mass) for 27 of these individuals, including seven flanged males, three adult confirmed-unflanged males, and three young adult likely-unflanged males. ANOVA and Kruskal-Wallis tests with Tukey and Dunn post-hoc pairwise comparisons, respectively, showed that body sizes for young adult unflanged males are similar to those of the adult females in the sample (all P ≥ 0.09 except bi-iliac breadth), whereas body sizes for adult unflanged males ranged between those of adult flanged males and adult females for several measurements (all P < 0.001). Thus, sexually mature male orangutans exhibit body sizes that range from the female end of the spectrum to the flanged male end of the spectrum. These results exemplify that the term "sexual dimorphism" fails to capture the full range of variation in adult orangutan body size. By including adult unflanged males in analyses of body size and other aspects of morphology, not as aberrations but as an expected part of orangutan variation, we may begin to shift the way that we think about features typically considered dichotomous according to biological sex.

African American mothers' perceptions of infant body size are prospectively associated with infant growth and BMI.

OBJECTIVES: The effect of mothers' perceptions of infant body size on infant growth and later BMI is poorly understood. We aimed to assess whether maternal perceptions were associated with infant BMI and weight gain and to identify factors that may influence maternal perceptions. METHODS: We analyzed data from a prospective, longitudinal study of pregnant African American women living with healthy weight (BMI < 25 kg/m2 ) or obesity (BMI ≥ 30 kg/m2 ). We collected sociodemographic, feeding mode, perceived stress, depression, and food insecurity information. The African American Infant Body Habitus Scale assessed maternal perceptions of infant body size at age 6 months. A "maternal satisfaction with infant body size" score was derived. Infant BMI z-scores (BMIZ) were calculated at 6 and 24 months. RESULTS: Maternal perception and satisfaction scores did not differ between obese (n = 148) and healthy weight (n = 132) groups. Perception of infant size at 6 months was positively associated with infant BMIZ at 6 and 24 months. A positive association of maternal satisfaction scores with change in infant BMIZ from 6 to 24 months indicated that BMIZ changed less for infants whose mothers preferred them to be smaller at 6 months. Perception and satisfaction scores were not associated with feeding variables, maternal stress, depression, socioeconomic status, or food security status. CONCLUSION: Mothers' perceptions of and satisfaction with infant size correlated with current and later infant BMI. However, mother's perceptions were not associated with maternal weight status or other factors explored for their potential to impact maternal perceptions. Further work is needed to elucidate factors linking maternal perception/satisfaction and infant growth.

IMPROVE-BMT: a protocol for a pilot randomised controlled trial of prehabilitation exercise for adult haematopoietic stem cell transplant recipients.

INTRODUCTION: Haematopoietic stem cell transplant (HSCT) in adults is an intensive medical procedure for a variety of haematological malignancies. Although there is a large body of evidence demonstrating the negative effects of HSCT on physical function and psychosocial parameters, there is limited evidence on the impact of HSCT on body composition and bone health. Further, aerobic and resistance-training exercise interventions aimed at improving physical function and patient-reported outcomes largely take place during the peritransplant and post-transplant period. Prehabilitative exercise, or exercise prior to medical treatment, has been successfully deployed in presurgical candidates and other tumour sites, yet there is a paucity of evidence on the effect of prehabilitation in HSCT patients. The aim of this study is to investigate the feasibility, acceptability and safety of a resistance training exercise programme in patients with haematological malignancies prior to HSCT. METHODS AND ANALYSIS: IMpact of PRehabilitation in Oncology Via Exercise-Bone Marrow Transplant is a single-site, pilot randomised controlled trial of an exercise intervention compared with usual care. The primary aim is to assess the feasibility, acceptability and safety of the resistance-training exercise intervention prior to HSCT. Secondary aims include evaluating the differences in physical function, body composition, bone mineral density and patient-reported outcomes between the exercise group and usual care control group. Outcome measurements will be assessed: prior to HSCT, on/around day of HSCT admission, +30 days post-HSCT and +100 days post-HSCT. The exercise intervention is a home-based resistance training exercise programme that incorporates resistance band and body weight exercises. The primary outcomes will be reported as percentages and/or mean values. The secondary outcomes will be analysed using appropriate statistical methods to portray within-group and between-group differences. ETHICS AND DISSEMINATION: The study has Penn State College of Medicine approval. Results will be disseminated through scientific publication and presentation at exercise-related and oncology-related scientific meetings. TRIAL REGISTRATION NUMBER: NCT03886909.

Assessment of fluid removal using ultrasound, bioimpedance and anthropometry in pediatric dialysis: a pilot study.

BACKGROUND: Fluid overload is associated with morbidity and mortality in children receiving dialysis. Accurate clinical assessment is difficult, and using deuterium oxide (D2O) to measure total body water (TBW) is impractical. We investigated the use of ultrasound (US), bioimpedance spectroscopy (BIS), and anthropometry to assess fluid removal in children receiving maintenance hemodialysis (HD). METHODS: Participants completed US, BIS, and anthropometry immediately before and 1-2 h after HD for up to five sessions. US measured inferior vena cava (IVC) diameter, lung B-lines, muscle elastography, and dermal thickness. BIS measured the volume of extracellular (ECF) and intracellular (ICF) fluid. Anthropometry included mid-upper arm, calf and ankle circumferences, and triceps skinfold thickness. D2O was performed once pre-HD. We assessed the change in study measures pre- versus post-HD, and the correlation of change in study measures with percent change in body weight (%∆BW). We also assessed the agreement between TBW measured by BIS and D2O. RESULTS: Eight participants aged 3.4-18.5 years were enrolled. Comparison of pre- and post-HD measures showed significant decrease in IVC diameters, lung B-lines, dermal thickness, BIS %ECF, mid-upper arm circumference, ankle, and calf circumference. Repeated measures correlation showed significant relationships between %∆BW and changes in BIS ECF (rrm =0.51, 95% CI 0.04, 0.80) and calf circumference (rrm=0.80, 95% CI 0.51, 0.92). BIS TBW correlated with D2O TBW but overestimated TBW by 2.2 L (95% LOA, -4.75 to 0.42). CONCLUSION: BIS and calf circumference may be helpful to assess changes in fluid status in children receiving maintenance HD. IVC diameter, lung B-lines and dermal thickness are potential candidates for future studies.

Promoting Sleep Duration in the Pediatric Setting Using a Mobile Health Platform: A Randomized Optimization Trial.

Objective: Determine the optimal combination of digital health intervention component settings that increase average sleep duration by ≥30 minutes per weeknight. Methods: Optimization trial using a 25 factorial design. The trial included 2 week run-in, 7 week intervention, and 2 week follow-up periods. Typically developing children aged 9-12y, with weeknight sleep duration <8.5 hours were enrolled (N=97). All received sleep monitoring and performance feedback. The five candidate intervention components (with their settings to which participants were randomized) were: 1) sleep goal (guideline-based or personalized); 2) screen time reduction messaging (inactive or active); 3) daily routine establishing messaging (inactive or active); 4) child-directed loss-framed financial incentive (inactive or active); and 5) caregiver-directed loss-framed financial incentive (inactive or active). The primary outcome was weeknight sleep duration (hours per night). The optimization criterion was: ≥30 minutes average increase in sleep duration on weeknights. Results: Average baseline sleep duration was 7.7 hours per night. The highest ranked combination included the core intervention plus the following intervention components: sleep goal (either setting was effective), caregiver-directed loss-framed incentive, messaging to reduce screen time, and messaging to establish daily routines. This combination increased weeknight sleep duration by an average of 39.6 (95% CI: 36.0, 43.1) minutes during the intervention period and by 33.2 (95% CI: 28.9, 37.4) minutes during the follow-up period. Conclusions: Optimal combinations of digital health intervention component settings were identified that effectively increased weeknight sleep duration. This could be a valuable remote patient monitoring approach to treat insufficient sleep in the pediatric setting.

Diet Quality and Cardiometabolic Risk Factors in Adolescents with Down Syndrome.

BACKGROUND: Youth with Down syndrome (DS) have a high prevalence of obesity and dyslipidemia. Diet quality may influence cardiometabolic risk (CMR) in youth. OBJECTIVE: The aim of this secondary analysis was to investigate the relationship between diet quality (Healthy Eating Index [HEI-2015]) with CMR factors in youth with DS compared with age, sex, race, ethnicity, and body mass index percentile matched, typically developing controls. DESIGN: Adolescents (aged 10 to 20 years) with DS and controls of comparable age, sex, race, ethnicity, and body mass index percentile were recruited from 2012 to 2017 for a cross-sectional study from two large children's hospitals (Children's Hospital of Philadelphia and the Children's National Health System in Washington, DC). PARTICIPANTS AND SETTING: CMRs in 143 adolescents with DS were compared with 100 controls. Exclusion criteria consisted of major organ-system illnesses. MAIN OUTCOME MEASURES: The average of three 24-hour dietary recalls was used to calculate the HEI-2015. Anthropometrics, blood pressure, and fasting labs were collected. STATISTICAL ANALYSES PERFORMED: Group differences were tested using Wilcoxon rank-sum tests. Relationships of CMR factors with HEI-2015 score within DS and controls were tested using linear regression models adjusted for sex, age, race, and body mass index z score. RESULTS: Compared with controls (n = 100, median age = 14.8 years [interquartile range = 12.2 to 17.3 years]; 41% male; 24% African American; 65% with body mass index ≥85th percentile), adolescents with DS (n = 143, median age = 14.7 years [interquartile range = 11.4 to 17.4 years]; 44% male; 18% African American; 62% with body mass index ≥85th percentile) had higher scores (more aligned with dietary recommendations) for total HEI-2015 (DS: 52.7 [interquartile range = 46.8 to 58.6] vs controls: 45.1 [interquartile range = 39.5 to 55.0]; P < 0.0001). Youth with DS also had higher HEI-2015 component scores for fruits, greens/beans, dairy, refined grains, and saturated fats, but lower whole grains and sodium scores. Within the group with DS, total HEI-2015 was not significantly associated with CMR measures. Whereas HEI-2015 in the DS group was negatively associated with fasting glucose levels, the difference did not meet the set level of statistical significance (-0.14, 95% CI -0.29 to 0.00; P = 0.053). CONCLUSIONS: Adolescents in both the control and DS groups reported low-quality diets, although the DS group had HEI-2015 scores more closely aligned with recommendations. In the DS group, diet quality was not significantly associated with CMR factors. Although further research is needed, these results suggest that dyslipidemia in youth with DS may not be related to dietary intake.