Expansion and mechanistic insights into de novo DEAF1 variants in DEAF1-associated neurodevelopmental disorders.

De novo deleterious and heritable biallelic mutations in the DNA binding domain (DBD) of the transcription factor deformed epidermal autoregulatory factor 1 (DEAF1) result in a phenotypic spectrum of disorders termed DEAF1-associated neurodevelopmental disorders (DAND). RNA-sequencing using hippocampal RNA from mice with conditional deletion of Deaf1 in the central nervous system indicate that loss of Deaf1 activity results in the altered expression of genes involved in neuronal function, dendritic spine maintenance, development, and activity, with reduced dendritic spines in hippocampal regions. Since DEAF1 is not a dosage-sensitive gene, we assessed the dominant negative activity of previously identified de novo variants and a heritable recessive DEAF1 variant on selected DEAF1-regulated genes in 2 different cell models. While no altered gene expression was observed in cells over-expressing the recessive heritable variant, the gene expression profiles of cells over-expressing de novo variants resulted in similar gene expression changes as observed in CRISPR-Cas9-mediated DEAF1-deleted cells. Altered expression of DEAF1-regulated genes was rescued by exogenous expression of WT-DEAF1 but not by de novo variants in cells lacking endogenous DEAF1. De novo heterozygous variants within the DBD of DEAF1 were identified in 10 individuals with a phenotypic spectrum including autism spectrum disorder, developmental delays, sleep disturbance, high pain tolerance, and mild dysmorphic features. Functional assays demonstrate these variants alter DEAF1 transcriptional activity. Taken together, this study expands the clinical phenotypic spectrum of individuals with DAND, furthers our understanding of potential roles of DEAF1 on neuronal function, and demonstrates dominant negative activity of identified de novo variants.

Relationships between food-related behaviors, obesity, and medication use in individuals with Smith-Magenis syndrome.

BACKGROUND: Smith-Magenis syndrome (SMS) is a complex neurodevelopmental disorder that includes obesity and food-seeking/satiety-related behaviors. AIMS: This study examined associations between food-related/hyperphagic behaviors, weight, and medication use in individuals with SMS. METHODS/PROCEDURES: Caregivers of individuals with SMS in the Parents and Researchers Interested in SMS (PRISMS) Patient Registry completed a demographic/medication questionnaire, the Hyperphagia Questionnaire for Clinical Trials, and the Food Related Problems Questionnaire. OUTCOMES/RESULTS: Among 49 participants (Mage = 16.41 ± 12.73 years, range = 4-69 years, 55% girls/women), individuals with SMS with overweight/obesity (n = 22) had worse overall food-related problems including greater impaired satiety (p < 0.05), maladaptive eating behaviors (p < 0.05), inappropriate response (p < 0.01), and hyperphagia (p < 0.01) compared to individuals of normal/underweight (n = 27). Those taking anti-depressants/anxiolytics (n = 16) had greater maladaptive eating behaviors (p < 0.05), hyperphagic behaviors (p < 0.05), and hyperphagic severity (p < 0.05) than those not taking anti-depressants/anxiolytics (n = 33). Boys/men with SMS had greater maladaptive eating behaviors (p < 0.05), inappropriate response (p < 0.05), and hyperphagic drive (p < 0.01) than girls/women with SMS. CONCLUSIONS/IMPLICATIONS: Maladaptive food-related behaviors were higher in individuals with SMS with overweight/obesity, taking anti-depressants/anxiolytics, or who were male. Medications in this population should be chosen with weight-related side effects in mind.

Detection of low-level parental somatic mosaicism for clinically relevant SNVs and indels identified in a large exome sequencing dataset.

BACKGROUND: Due to the limitations of the current routine diagnostic methods, low-level somatic mosaicism with variant allele fraction (VAF) < 10% is often undetected in clinical settings. To date, only a few studies have attempted to analyze tissue distribution of low-level parental mosaicism in a large clinical exome sequencing (ES) cohort. METHODS: Using a customized bioinformatics pipeline, we analyzed apparent de novo single-nucleotide variants or indels identified in the affected probands in ES trio data at Baylor Genetics clinical laboratories. Clinically relevant variants with VAFs between 30 and 70% in probands and lower than 10% in one parent were studied. DNA samples extracted from saliva, buccal cells, redrawn peripheral blood, urine, hair follicles, and nail, representing all three germ layers, were tested using PCR amplicon next-generation sequencing (amplicon NGS) and droplet digital PCR (ddPCR). RESULTS: In a cohort of 592 clinical ES trios, we found 61 trios, each with one parent suspected of low-level mosaicism. In 21 parents, the variants were validated using amplicon NGS and seven of them by ddPCR in peripheral blood DNA samples. The parental VAFs in blood samples varied between 0.08 and 9%. The distribution of VAFs in additional tissues ranged from 0.03% in hair follicles to 9% in re-drawn peripheral blood. CONCLUSIONS: Our study illustrates the importance of analyzing ES data using sensitive computational and molecular methods for low-level parental somatic mosaicism for clinically relevant variants previously diagnosed in routine clinical diagnostics as apparent de novo.

Low-level parental somatic mosaic SNVs in exomes from a large cohort of trios with diverse suspected Mendelian conditions.

PURPOSE: The goal of this study was to assess the scale of low-level parental mosaicism in exome sequencing (ES) databases. METHODS: We analyzed approximately 2000 family trio ES data sets from the Baylor-Hopkins Center for Mendelian Genomics (BHCMG) and Baylor Genetics (BG). Among apparent de novo single-nucleotide variants identified in the affected probands, we selected rare unique variants with variant allele fraction (VAF) between 30% and 70% in the probands and lower than 10% in one of the parents. RESULTS: Of 102 candidate mosaic variants validated using amplicon-based next-generation sequencing, droplet digital polymerase chain reaction, or blocker displacement amplification, 27 (26.4%) were confirmed to be low- (VAF between 1% and 10%) or very low (VAF <1%) level mosaic. Detection precision in parental samples with two or more alternate reads was 63.6% (BHCMG) and 43.6% (BG). In nine investigated individuals, we observed variability of mosaic ratios among blood, saliva, fibroblast, buccal, hair, and urine samples. CONCLUSION: Our computational pipeline enables robust discrimination between true and false positive candidate mosaic variants and efficient detection of low-level mosaicism in ES samples. We confirm that the presence of two or more alternate reads in the parental sample is a reliable predictor of low-level parental somatic mosaicism.

Parental somatic mosaicism for CNV deletions - A need for more sensitive and precise detection methods in clinical diagnostics settings.

To further assess the scale and level of parental somatic mosaicism, we queried the CMA database at Baylor Genetics. We selected 50 unrelated families where clinically relevant apparent de novo CNV-deletions were found in the affected probands. Parental blood samples screening using deletion junction-specific PCR revealed four parents with somatic mosaicism. Droplet digital PCR (ddPCR), qPCR, and amplicon-based next-generation sequencing (NGS) were applied to validate these findings. Using ddPCR levels of mosaicism ranged from undetectable to 18.5%. Amplicon-based NGS and qPCR for the father with undetectable mosaicism was able to detect mosaicism at 0.39%. In one mother, ddPCR analysis revealed 15.6%, 10.6%, 8.2%, and undetectable levels of mosaicism in her blood, buccal cells, saliva, and urine samples, respectively. Our data suggest that more sensitive and precise methods, e.g. CNV junction-specific LR-PCR, ddPCR, or qPCR may allow for a more refined assessment of the potential disease recurrence risk for an identified variant.

Behavior Modification of Diet and Parent Feeding Practices in a Community- Vs Primary Care-Centered Intervention for Childhood Obesity.

OBJECTIVE: To evaluate behavior modification of diet and parent feeding practices in childhood obesity interventions. DESIGN: Secondary analysis of randomized, controlled trial comparing Mind, Exercise, Nutrition … Do It! (MEND2-5 and MEND/Coordinated Approach to Child Health [CATCH6-12]) vs Next Steps at baseline and 3 and 12 months. SETTING: Austin and Houston, TX. PARTICIPANTS: A total of 549 Hispanic and black children randomized to programs by age groups (2-5, 6-8, and 9-12 years) INTERVENTIONS: Twelve-month MEND2-5 and MEND/CATCH6-12 vs Next Steps. MAIN OUTCOME MEASURE(S): Diet (MEND-friendly/unfriendly food groups and Healthy Eating Index-2010) and parent feeding practices (parental overt control, discipline, limit setting, monitoring, reinforcement, modeling, and covert control; and food neophobia). ANALYSIS: Mixed-effects linear regression. RESULTS: Changes in diet quality, consumption of MEND-unfriendly foods, and parent feeding practices did not differ between programs. In both interventions, MEND-unfriendly vegetables, grains, dairy and protein, added fat and desserts/sugar-sweetened beverages declined in 2-5- and 6-8-year-olds (P < .001). Healthy Eating Index-2010 improved in 2-5- (treatment; P = .002) and 6-8-year-olds (P = .001). Parental overt control decreased and limit setting, discipline, monitoring, reinforcement, and covert control increased with both interventions in 2-5- and 6-8-year-olds (P < 0.01-0.001). CONCLUSIONS: Diet quality, consumption of MEND-unfriendly foods, and parent feeding practices were altered constructively in 2 pediatric obesity interventions, especially in 2-5- and 6-8-year-olds.

Efficacy of a Community- Versus Primary Care-Centered Program for Childhood Obesity: TX CORD RCT.

OBJECTIVE: This randomized controlled trial was conducted to determine comparative efficacy of a 12-month community-centered weight management program (MEND2-5 for ages 2-5 or MEND/CATCH6-12 for ages 6-12) against a primary care-centered program (Next Steps) in low-income children. METHODS: Five hundred forty-nine Hispanic and black children (BMI ≥ 85th percentile), stratified by age groups (2-5, 6-8, and 9-12 years), were randomly assigned to MEND2-5 (27 contact hours)/MEND/CATCH6-12 (121.5 contact hours) or Next Steps (8 contact hours). Primary (BMI value at the 95th percentile [%BMIp95 ]) and secondary outcomes were measured at baseline, 3 months (Intensive Phase), and 12 months (Transition Phase). RESULTS: For age group 6-8, MEND/CATCH6-12 resulted in greater improvement in %BMIp95 than Next Steps during the Intensive Phase. Effect size (95% CI) was -1.94 (-3.88, -0.01) percentage points (P = 0.05). For age group 9-12, effect size was -1.38 (-2.87, 0.16) percentage points for %BMIp95 (P = 0.07). MEND2-5 did not differentially affect %BMIp95 . Attendance averaged 52% and 22% during the Intensive and Transition Phases. Intervention compliance was inversely correlated to change in %BMIp95 during the Intensive Phase (P < 0.05). In the Transition Phase, %BMIp95 was maintained or rebounded in both programs (P < 0.05). CONCLUSIONS: MEND/CATCH6-12 was more efficacious for BMI reduction at 3 months but not 12 months compared to Next Steps in underserved children. Intervention compliance influenced outcomes, emphasizing the need for research in sustaining family engagement in low-income populations.

Energy Cost of Activities in Preschool-Aged Children.

BACKGROUND: The absolute energy cost of activities in children increase with age due to greater muscle mass and physical capability associated with growth and developmental maturation; however, there is a paucity of data in preschool-aged children. Study aims were 1) to describe absolute and relative energy cost of common activities of preschool-aged children in terms of VO2, energy expenditure (kilocalories per minute) and child-specific metabolic equivalents (METs) measured by room calorimetry for use in the Youth Compendium of Physical Activity, and 2) to predict METs from age, sex and heart rate (HR). METHODS: Energy expenditure (EE), oxygen consumption (VO2), HR, and child-METs of 13 structured activities were measured by room respiration calorimetry in 119 healthy children, ages 3 to 5 years. RESULTS: EE, VO2, HR, and child-METs are presented for 13 structured activities ranging from sleeping, sedentary, low-, moderate- to high-active. A significant curvilinear relationship was observed between child-METs and HR (r2 = .85; P = .001). CONCLUSION: Age-specific child METs for 13 structured activities in preschool-aged children will be useful to extend the Youth Compendium of Physical Activity for research purposes and practical applications. HR may serve as an objective measure of MET intensity in preschool-aged children.

Role of physical activity and sleep duration in growth and body composition of preschool-aged children.

OBJECTIVE: The impact of physical activity patterns and sleep duration on growth and body composition of preschool-aged children remains unresolved. Aims were (1) to delineate cross-sectional associations among physical activity components, sleep, total energy expenditure (TEE), and body size and composition; and (2) to determine whether physical activity components, sleep, and TEE predict 1-year changes in body size and composition in healthy preschool-aged children. METHODS: Anthropometry, body composition, accelerometry, and TEE by doubly labeled water were measured at baseline; anthropometry and body composition were repeated 1 year later (n = 111). RESULTS: Cross-sectionally, positive associations between sedentary activity and weight and fat-free mass (FFM) (P = 0.009-0.047), and a negative association between moderate-vigorous physical activity (MVPA) and percent fat mass (FM) (P = 0.015) were observed. TEE and activity energy expenditure (AEE) were positively associated with weight, body mass index (BMI), FFM, and FM (P = 0.0001-0.046). Prospectively, TEE, AEE, physical activity level, and MVPA, but not sedentary activity, were positively associated with changes in BMI (P = 0.0001-0.051) and FFM (P = 0.0001-0.037), but not percent FM. Sleep duration inversely predicted changes in FM (P = 0.005) and percent FM (P = 0.006). CONCLUSIONS: Prospectively, MVPA, TEE, AEE, and physical activity level promote normal growth and accretion of FFM, whereas sleep duration inversely predicts changes in adiposity in preschool-aged children.

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.

Revision of Dietary Reference Intakes for energy in preschool-age children.

BACKGROUND: Dietary Reference Intakes (DRI) for energy aim to balance energy expenditure at a level of physical activity consistent with health and support adequate growth in children. DRIs were derived from total energy expenditure (TEE) measured by using the doubly labeled water (DLW) method; however, the database was limited in the 3-5-y-old range. OBJECTIVE: We reexamined the DRI for energy for preschool-age children. DESIGN: Ninety-seven healthy, normal-weight, preschool-age children (mean ± SD age: 4.5 ± 0.9 y) completed a 7-d DLW protocol while wearing accelerometer and heart rate-monitoring devices. RESULTS: Mean TEE and physical activity level (PAL) averaged 1159 ± 171 kcal/d and 1.34 ± 0.14, respectively. TEE predicted by DRI equations agreed with observed TEE (+34 kcal/d or 3%) if the sedentary PAL category was assumed but was overestimated by using the low active (+219 kcal/d or 19%), active (398 kcal/d or 34%), and very active (593 kcal/d or 51%) PAL categories. PAL categories were redefined on the basis of the narrower PAL range observed in preschoolers (range: 1.05-1.70) compared with older children and adults (range: 1.0-2.5). Sex-specific nonlinear regression models were newly developed to predict TEE from age, weight, height, and new PAL categories. The mean absolute error of TEE prediction equations was 0.00 ± 35 kcal/d or 0.1 ± 3%. Ancillary measures, such as total accelerometer counts and total daily steps, that were significantly correlated (P = 0.01-0.05) with TEE (r = 0.26-0.38), TEE per kilogram (r = 0.31-0.41), and PAL (r = 0.36-0.48) may assist in the classification of preschoolers into PAL categories. CONCLUSIONS: Current DRIs for energy overestimate energy requirements of preschool-age children because of the erroneous classification of children into PAL categories. New TEE prediction equations that are based on DLW and appropriate PAL categories are recommended for preschool-age children. This trial was registered at clinicaltrials.gov as H12067.

A residential summer camp can reduce body fat and improve health-related quality of life in obese children.

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.

Physical activity and nutrition attitudes in obese Hispanic children with non-alcoholic steatohepatitis.

AIM: To assess nutrition, physical activity and healthful knowledge in obese children with biopsy-proven non-alcoholic steatohepatitis (NASH or NA) compared to children without liver disease. METHODS: Children with biopsy-proven NASH comprised the NASH group. Age, sex and ethnicity matched control groups consisted of obese (OB) and lean (CO) children with no liver disease. Subjects were administered the School Physical Activity and Nutrition Survey and one blood draw was obtained. RESULTS: Fifty-seven patients were enrolled with a mean age of 12.1 ± 2.1 years, and all were Hispanic. Even though the OB and NA had a similar increased body mass index (%), 35% of the NA group always read nutrition labels compared to none in the OB (P < 0.05), and more NA children felt their diet is "less healthy". NA consumed the least amount of fruits with only 25% having ≥ 1 fruit/d vs 45% in OB and 64.7% in CO (P < 0.05 NA vs CO). Only 15% of NA subjects performed light exercise vs 35% and 59% of OB and CO groups, respectively (P = 0.02). The mean physical activity score was lowest in the NA group (P < 0.05). Amongst the subjects with NASH, we found that 100% of patients with grade 2 or 3 fibrosis had a sedentary score > 2 compared to only 63.6% of those with grade 1 or no fibrosis (P < 0.05). CONCLUSION: Children with NASH had increased se-dentary behavior, decreased activity, and fruit intake. Larger studies may determine the benefit of changing these behaviors as treatment for NASH.

An innovative summer camp program improves weight and self-esteem in obese children.

To determine the potential benefits of a residential summer camp to treat childhood obesity, 21 obese, multiethnic children (aged 11.4+/-1.4 years; body mass index [BMI] percentile 98.5+/-1.4; BMI z score 2.30+/-0.33) from a diverse socioeconomic background were enrolled in a 2-week summer camp program. Significant improvements (P<0.04) were observed in self-esteem (+0.27+/-0.33 point), body weight (-3.7+/-1.2 kg), BMI (-1.60+/-0.48 kg/m), BMI z score (-0.12+/-0.06), number of curl ups (+10.9+/-21.5), systolic and diastolic blood pressure (-10.8+/-13.4 and -9.4+/-5.5 mmHg, respectively), and heart rate (-8.2+/-12.7 bpm).

Nutrient adequacy and diet quality in non-overweight and overweight Hispanic children of low socioeconomic status: the Viva la Familia Study.

OBJECTIVE: The role of diet quality and nutrient adequacy in the etiology of childhood obesity is poorly understood. The specific aims of these analyses were to assess overall diet quality and nutrient adequacy, and test for association between weight status and diet in children from low socioeconomic status (SES) Hispanic families at high risk for obesity. DESIGN: A cross-sectional study design was used to assess dietary intake in low-SES Hispanic children with and without overweight who were enrolled in the Viva la Familia Study. Multiple-pass 24-hour dietary recalls were recorded on two random, weekday occasions. Diet quality was evaluated according to the Dietary Guidelines for Americans. Nutrient adequacy was assessed using z scores based on estimated average requirement or adequate intake. SUBJECTS/SETTING: The study included 1,030 Hispanic children and adolescents, aged 4 to 19 years, in Houston, TX, who participated between November 2000 and August 2004. STATISTICAL ANALYSIS: STATA software (version 9.1, 2006, STATA Corp, College Station, TX) was used for generalized estimating equations and random effects regression. RESULTS: Diet quality did not adhere to the Dietary Guidelines for Americans for fat, cholesterol, saturated fatty acids, fiber, added sugar, and sodium. Although energy intake was significantly higher in children with overweight, food sources, diet quality, macro- and micronutrient composition were similar between non-overweight and overweight children. Relative to estimated average requirements or adequate intake levels, mean nutrient intakes were adequate (70% to 98% probability) in the children without and with overweight, except for vitamins D and E, pantothenic acid, calcium, and potassium, for which z scores cannot be interpreted given the uncertainty of their adequate intake levels. CONCLUSIONS: Whereas the diets of low-SES Hispanic children with and without overweight were adequate in most essential nutrients, other components of a healthful diet, which promote long-term health, were suboptimal. Knowledge of the diets of high-risk Hispanic children will inform nutritional interventions and policy.

Overestimation of infant and toddler energy intake by 24-h recall compared with weighed food records.

BACKGROUND: Twenty-four-hour dietary recalls have been used in large surveys of infant and toddler energy intake, but the accuracy of the method for young children is not well documented. OBJECTIVE: We aimed to determine the accuracy of infant and toddler energy intakes by a single, telephone-administered, multiple-pass 24-h recall as compared with 3-d weighed food records. DESIGN: A within-subjects design was used in which a 24-h recall and 3-d weighed food records were completed within 2 wk by 157 mothers (56 non-Hispanic white, 51 non-Hispanic black, and 50 Hispanic) of 7-11-mo-old infants or 12-24-mo-old toddlers. Child and caregiver anthropometrics, child eating patterns, and caregiver demographics and social desirability were evaluated as correlates of reporting bias. RESULTS: Intakes based on 3-d weighed food records were within 5% of estimated energy requirements. Compared with the 3-d weighed food records, the 24-h recall overestimated energy intake by 13% among infants (740 +/- 154 and 833 +/- 255 kcal, respectively) and by 29% among toddlers (885 +/- 197 and 1140 +/- 299 kcal, respectively). Eating patterns (ie, frequency and location) did not differ appreciably between methods. Macronutrient and micronutrient intakes were higher by 24-h recall than by 3-d weighed food record. Dairy and grains contributed the most energy to the diet and accounted for 74% and 54% of the overestimation seen in infants and toddlers, respectively. Greater overestimation was associated with a greater number of food items reported by the caregiver and lower child weight-for-length z scores. CONCLUSIONS: The use of a single, telephone-administered, multiple-pass 24-h recall may significantly overestimate infant or toddler energy and nutrient intakes because of portion size estimation errors.

Metabolic and behavioral predictors of weight gain in Hispanic children: the Viva la Familia Study.

BACKGROUND: Despite the high prevalence of overweight among Hispanic children in the United States, definitive predictors of weight gain have not been identified in this population. OBJECTIVE: The study objective was to test sociodemographic, metabolic, and behavioral predictors of 1-y weight gains in a large cohort of Hispanic children studied longitudinally. DESIGN: Subjects (n = 879) were siblings from 319 Hispanic families enrolled in the Viva la Familia Study. Families were required to have at least one overweight child aged 4-19 y. One-year changes in weight and body composition by dual-energy X-ray absorptiometry were measured. Data were from parental interviews, birth certificates, multiple-pass 24-h dietary recalls, 3-d accelerometry, 24-h respiration calorimetry, measurements of eating in the absence of hunger, and measurement of fasting blood biochemistry indexes by radioimmunoassay. Generalized estimating equations and principal component analysis were applied. RESULTS: Weight gain increased with age (P = 0.001), peaking at approximately 10 y of age in girls and approximately 11 y of age in boys. Mean (+/-SD) weight gain was significantly higher in overweight (7.5 +/- 3.7 kg/y) than in nonoverweight (4.4 +/- 2.4 kg/y) children and in boys than in girls. When adjusted for age, age squared, sex, and Tanner stage, the final model indicated a child's body mass index (BMI; kg/m2) status, maternal BMI, energy expenditure (total energy expenditure, basal metabolic rate, and sleeping metabolic rate), and fasting blood biochemistry indexes (total triiodothyronine, insulin, leptin, and ghrelin) as independent, positive predictors of weight gain (P = 0.01-0.001). CONCLUSION: Knowledge of the metabolic and behavioral predictors of weight gain in Hispanic children will inform prevention and treatment efforts to address this serious public health problem in the United States.