Obesity at Age 6 Months Is Associated with Shorter Preschool Leukocyte Telomere Length Independent of Parental Telomere Length.

OBJECTIVE: To assess whether early modifiable dietary factors and obesity measures are associated with leukocyte telomere length at 3-5 years of age after controlling for the heritability of leukocyte telomere length in a prospective cohort of low-income Latina mothers and their children in San Francisco. STUDY DESIGN: We analyzed data from the Latinx, Eating and Diabetes cohort, a prospective study of 97 woman-infant dyads. We used linear regression models to evaluate associations between early dietary factors and obesity measures and child leukocyte telomere length at 3-5 years of age. Multivariable models included child age at the time of telomere collection, breastfeeding at 6 months (yes/no), obesity at 6 months, maternal education, child sex, and maternal and paternal leukocyte telomere length. RESULTS: Data for 73 of the 97 children at 3-5 years of age were analyzed. Any breastfeeding at 6 months was positively associated (ß = 0.14; P = .02) and obesity at 6 months was negatively associated (ß = -0.21; P < .001) with leukocyte telomere length in bivariate analyses. In multivariable models including parental leukocyte telomere length, obesity at 6 months was associated with a shorter leukocyte telomere length at 3-5 years of age (ß = -0.15; P = .02). Analyses of dietary factors showed high flavored milk consumption at 3 years of age was associated with shorter leukocyte telomere length after adjustment for possible confounders. CONCLUSIONS: In a low-income Latinx population, obesity at 6 months of age is negatively associated with cellular health at 3-5 years of age after controlling for genetic factors (parental leukocyte telomere length) associated with leukocyte telomere length. Early life obesity may be more deleterious for cellular health than obesity later in childhood.

Early-Onset Acute Recurrent and Chronic Pancreatitis Is Associated with PRSS1 or CTRC Gene Mutations.

OBJECTIVES: To assess whether the age of onset was associated with unique features or disease course in pediatric acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). STUDY DESIGN: Demographic and clinical information on children with ARP or CP was collected at INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE) centers. The Cochran-Armitage trend test and Jonckheere-Terpstra test were used to examine for differences between pediatric age groups (<6, 6-11, and ≥12 years). RESULTS: Between September 2012 and March 2016, 342 children with ARP or CP were enrolled; 129 (38%) were <6 years of age at the time of first diagnosis of acute pancreatitis, 111 (32%) were 6-11 years of age, and 102 (30%) were ≥12 years of age. Early-onset disease was associated with mutations in cationic trypsinogen (PRSS1) (P < .01), chymotrypsin C (CTRC) (P = .01), family history of acute pancreatitis (P = .02), family history of CP (P < .01), biliary cysts (P = .04), or chronic renal failure (P = .02). Later-onset disease was more commonly present with hypertriglyceridemia (P = .04), ulcerative colitis (P = .02), autoimmune diseases (P < .0001), or medication use (P < .01). Children with later-onset disease also were more likely to visit the emergency department (P < .05) or have diabetes (P < .01). CONCLUSIONS: Early-onset pancreatitis is associated strongly with PRSS1 or CTRC mutations and family history of pancreatitis. Children with later-onset disease are more likely to have nongenetic risk factors. Future studies are needed to investigate whether the disease course, response to therapy, or clinical outcomes differ relative to the timing of disease onset.

Complications of Endoscopic Retrograde Cholangiopancreatography in Pediatric Patients; A Systematic Literature Review and Meta-Analysis.

OBJECTIVES: To systematically review risks and summarize reported complication rates associated with the performance of endoscopic retrograde cholangiopancreatography (ERCP) in children during the past 2 decades. STUDY DESIGN: A systematic literature search of MEDLINE, Embase, and Web of Science from January 1995 to January 2016 was conducted for observational studies published in English. Studies reporting ERCP complications in patients <21 years without history of liver transplant or cholecystectomy were included. A summary estimate of the proportion of children who experienced complications following ERCP was derived via a random effects meta-analysis. RESULTS: Thirty-two studies involving 2612 children and 3566 procedures were included. Subjects' ages ranged from 3 days to 21 years. Procedures were performed for biliary (54%), pancreatic (38%), and other (8%) indications; 56% of ERCPs were interventional. The pooled complication rate was 6% (95% CI 4%- 8%). Procedural complications included post-ERCP pancreatitis (166, 4.7%), bleeding (22, 0.6%), and infections (27, 0.8%). The pooled estimate of post-ERCP pancreatitis was 3% (95% CI 0.02-0.05), and other complications were 1% (95% CI 0.02-0.05). In the subgroup with neonatal cholestasis, the pooled complication rate was 3% (95% CI 0.01-0.07). Adult and pediatric gastroenterologists and surgeons performed the ERCPs. Available data limited the ability to report differences between pediatric-trained and other endoscopists. CONCLUSIONS: Complications associated with pediatric ERCP range widely in severity and are reported inconsistently. Our review suggests 6% of pediatric ERCPs have complications. Further studies that use systematic and standardized methodologies are needed to determine the frequency and risk factors for ERCP-related complications.

A Risk Score for Childhood Obesity in an Urban Latino Cohort.

OBJECTIVE: To assess whether individual obesity risk factors, present during gestation, and the first 6 months of life, can be combined into a simple prognostic model that has the ability to accurately predict childhood obesity at age 5 years in a high-risk cohort. STUDY DESIGN: A total of 201 Latina women were recruited during pregnancy, and their infants followed longitudinally. Ten risk factors for childhood obesity were included in an initial logistic model; a second reduced model was created via stepwise deletion (confirmed with nonparametric conditional random forest classifier), after which 5 risk factors remained. From each model, an obesity risk equation was derived, and an obesity risk score was generated for each patient. Derived algorithms were assessed using discrimination, calibration, and via predictive statistics. RESULTS: Of the 166 children followed through age 5 years, 56 (32%) met criteria for childhood obesity. Discrimination accuracy for both derivation models was excellent, and after optimism-corrected bootstrapping, both models showed meaningful clinical performance. Both models were adequately calibrated, showed strong sensitivity and negative predictive value at conservatively set obesity risk thresholds, and displayed excellent specificity among those classified as highest risk. Birth weight z-score and change in weight-for-age z-score between birth and 6 months were the risk factors with the strongest contribution to the obesity risk score. CONCLUSIONS: Obesity risk algorithms are reliable in their prediction of childhood obesity and have the potential to be integrated into the electronic medical record. These models could provide a filter for directing early prevention resources to children with high obesity risk but should be evaluated in a larger external dataset.

Pediatric chronic pancreatitis is associated with genetic risk factors and substantial disease burden.

OBJECTIVE: To determine the clinical presentation, diagnostic variables, risk factors, and disease burden in children with chronic pancreatitis. STUDY DESIGN: We performed a cross-sectional study of data from the International Study Group of Pediatric Pancreatitis: In Search for a Cure, a registry of children with acute recurrent pancreatitis and chronic pancreatitis. Between-group differences were compared using Wilcoxon rank-sum test. RESULTS: Among 170 subjects in the registry, 76 (45%) had chronic pancreatitis; 57% were female, 80% were white; median age at diagnosis was 9.9 years. Pancreatitis-predisposing genetic mutations were identified in 51 (67%) and obstructive risk factors in 25 (33%). Toxic/metabolic and autoimmune factors were uncommon. Imaging demonstrated ductal abnormalities and pancreatic atrophy more commonly than calcifications. Fifty-nine (77%) reported abdominal pain within the past year; pain was reported as constant and receiving narcotics in 28%. Children with chronic pancreatitis reported a median of 3 emergency department visits and 2 hospitalizations in the last year. Forty-seven subjects (70%) missed 1 day of school in the past month as the result of chronic pancreatitis; 26 (34%) missed 3 or more days. Children reporting constant pain were more likely to miss school (P = .002), visit the emergency department (P = .01), and experience hospitalizations (P = .03) compared with children with episodic pain. Thirty-three children (43%) underwent therapeutic endoscopic retrograde pancreatography; one or more pancreatic surgeries were performed in 30 (39%). CONCLUSIONS: Chronic pancreatitis occurs at a young age with distinct clinical features. Genetic and obstructive risk factors are common, and disease burden is substantial.

Bimodal distribution of risk for childhood obesity in urban Baja California, Mexico.

In Mexico, higher socioeconomic status (SES) has been found to be associated with increased risk for obesity in children. Within developed urban areas, however, there may be increased risk among lower SES children. Students in grades 4-6 from five public schools in Tijuana and Tecate, Mexico, were interviewed and weight, height and waist circumference (WC) measurements were taken. Interviews consisted of questions on food frequency, food insecurity, acculturation, physical activity and lifestyle practices. Multivariate logistic models were used to assess risk factors for obesity (having a body mass index [BMI] ≥95th percentile) and abdominal obesity (a WC >90th percentile) using Stata 11.0. Five hundred and ninety students were enrolled; 43.7% were overweight or obese, and 24.3% were obese and 20.2% had abdominal obesity. Independent risk factors for obesity included watching TV in English (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.06-2.41) and perceived child food insecurity (OR 1.57, 95% CI 1.05-2.36). Decreased risk for obesity was associated with female sex (OR 0.64, 95% CI 0.43-0.96), as was regular multivitamin use (OR 0.63, 95% CI 0.42-0.94). Risk obesity was also decreased with increased taco consumption (≥1×/week; OR 0.64, 95% CI 0.43-0.96). Independent risk factors for abdominal obesity included playing video games ≥1×/week (OR 1.18, 95% CI 1.11-2.96) and older age group (10-11 years, OR 2.47, 95% CI 1.29-4.73 and ≥12 years, OR 2.21, 95% CI 1.09-4.49). Increased consumption of tacos was also associated with decreased risk for abdominal obesity (≥1×/week; OR 0.56, 95% CI 0.40-1.00). We found a bimodal distribution for risk of obesity and abdominal obesity in school aged children on the Mexican border with the United States. Increased risk for obesity and abdominal obesity were associated with factors indicative of lower and higher SES including watching TV in English, increased video game playing and perceived food insecurity. Increased consumption of tacos (≥1×/week) was associated with decreased risk, possibly suggesting an association with children from middle income families. Regular multivitamin use was protective and future studies may focus on micronutrient supplementation as a means to prevent obesity in children or further investigate factors associated with vitamin use. Additionally, future studies need to examine the processes of acculturation on both sides of the US-Mexican border that contribute to increased risk for obesity in children in relation to SES.

Acculturation, dietary practices and risk for childhood obesity in an ethnically heterogeneous population of Latino school children in the San Francisco bay area.

Previous studies have found increased acculturation to the US lifestyle increases risk for obesity in Latinos. However, methodologies differ, and results in children are inconsistent. Moreover, previous studies have not evaluated risk factors within the heterogeneous US population. We recruited 144 self-identified Latino school children and their mother or father in grades 4-6 in San Francisco parochial schools and South San Francisco public schools using an information letter distributed to all students. Children and parents had weights, heights, demographic information, dietary patterns and lifestyle variables collected in English or Spanish through an interview format. A high percentage of our children were overweight [≥85th percentile body mass index (BMI)] (62.5%) and obese (≥95th percentile BMI) (45.2%). Correspondingly parents also had a high percentage of overweight (BMI ≥ 25 & <30) (40.8%) and obesity (BMI ≥ 30) (45.3%). Mexico was the country of origin for 62.2% of parents, and 26.6% were from Central or South America. In multivariate logistic analysis, speaking Spanish at home was an independent risk factor for obesity [odds ratio (OR) 2.97, 95% confidence interval (CI) 1.28-6.86]. Eating breakfast daily (OR 0.34, 95% CI 0.15-0.78) and consumption of tortas (a Mexican fast food sandwich) (OR 0.45, 95% CI 0.21-1.00) were associated with decreased risk. In stratified analysis, significant differences in risk factors existed between Mexican origin versus Central/South American Latino children. The processes of acculturation likely impact eating and lifestyle practices differentially among Latino groups. Interventions should focus on ensuring that all children eat a nutritious breakfast and take into consideration ethnicity when working with Latino populations.

Growth hormone treatment for growth failure in pediatric patients with Crohn's disease.

OBJECTIVE: To investigate the effect of human growth hormone (GH) injections on growth velocity in growth-impaired children with Crohn's disease (CD). STUDY DESIGN: Ten children and adolescents (mean age, 12.6 +/- 4.5 years; 6 males) with CD and poor height growth were treated with open-label recombinant GH, 0.043 mg/kg/day administered via subcutaneous injection, for 1 year. Patients were retrospectively matched with untreated patients (3 comparisons per case) by race, age, sex, and baseline height. Primary endpoint was height velocity; secondary endpoints were disease activity, body composition, and bone density determined by dual-energy x-ray absorptiometry scan. RESULTS: Mean height velocity increased by 5.33 +/- 3.40 (mean +/- standard deviation) cm/year in the GH-treated patients during the year of GH treatment, compared with 0.96 +/- 3.52 cm/year in the comparison group (P = .03). Height z-score increased by 0.76 +/- 0.38 in the treated group, compared with 0.16 +/- 0.40 in the comparison group (P < .01), and weight z-score increased by 0.81 +/- 0.89 in the treated group, compared with 0.00 +/- 0.57 in the comparison group (P < .01). Bone density revealed an increase of 0.31 +/- 0.33 in the lumbar spine z-score (P = .03 vs baseline). CONCLUSIONS: GH treatment increases height velocity and may enhance bone mineralization in children with CD. A randomized controlled trial in a large cohort of children is needed to evaluate the ultimate impact of GH treatment.

Children with early-onset inflammatory bowel disease (IBD): analysis of a pediatric IBD consortium registry.

OBJECTIVE: To determine the characteristics of inflammatory bowel disease (IBD) in young patients. STUDY DESIGN: Uniform data were collected from a cohort of patients with IBD who were enrolled from January 2000 to November 2002 at six pediatric centers (Pediatric IBD Consortium). RESULTS: Of 1370 children in the registry, the mean age at IBD diagnosis was 10.3 +/- 4.4 years; 54% were male, and 86% were white. Diagnosis was confirmed in 87 (6.1%) under 3 years of age, 211 (15.4%) before 6 years, 654 (47.7%) at 6 to 12 years, and 505 (36.9%) at 13 to 17 years. More than 63% of children younger than 8 years of age had isolated colonic disease, whether Crohn disease, ulcerative colitis (UC), or indeterminate colitis. Conversely, only 35% of those 8 years of age or older had isolated colonic disease ( P < .0001). Overall, 29% had one or more family members with IBD. The subgroup of children younger than 3 years of age with UC had the highest prevalence of first-degree relatives with IBD (44%). CONCLUSIONS: This demographically diverse pediatric IBD cohort revealed age-related variation in the distribution of IBD phenotype, with a high prevalence of isolated colonic disease in young children. Positive family history was especially common in young patients with UC.

Economic and psychologic costs for maternal caregivers of gastrostomy-dependent children.

OBJECTIVE: To examine the economic and psychologic costs of care provided by maternal caregivers to children with gastrostomy tube (GT) feedings. STUDY DESIGN: We conducted a 3-site study of primary maternal caregivers of 101 chronically ill children, with (n = 50) and without (n = 51) enteral nutrition support by GT to determine the time spent providing technical care, nontechnical care, and health care management and to assess depressive mood and quality of life. Associated costs were determined. RESULTS: Caregivers spent 339.7 +/- 34.1 (SEM) min/d to provide all care. Children with a GT required more than twice as much care time as children without a GT: 484.5 +/- 54.6 versus 197.8 +/- 30.6 min/d ( P < .0001). The mean annual total value of home care by the primary caregiver for a child with a GT was 37,232 dollars, compared with 15,004 dollars for the child without a GT. Caregivers of children with GT were no more depressed or less satisfied with their lives than caregivers of children without GT. CONCLUSIONS: Use of a GT for enteral nutrition support is associated with significant increased care time by the primary caregiver but not at additional psychologic cost compared with caring for chronically ill children.

Pathophysiologic basis for growth failure in children with ichthyosis: an evaluation of cutaneous ultrastructure, epidermal permeability barrier function, and energy expenditure.

OBJECTIVE: Because an impaired epidermal permeability barrier is present in many of the ichthyoses, we examined the contribution of barrier failure to caloric requirements in children with ichthyosis and growth failure. STUDY DESIGN: Transepidermal water loss (TEWL) and ultrastructural parameters of the permeability barrier were evaluated in 10 hospitalized children with ichthyosis and growth failure. Nutritional intake, resting energy expenditure, and calories lost as heat of evaporation were determined. RESULTS: Mean basal TEWL rates were markedly elevated in all study patients in comparison to the expected upper limit of normal (39.6+/-20.6 vs 8.7 mL/m(2) per hour). The severity of abnormalities in the ultrastructure of permeability barrier-related structures, assessed semiquantitatively, correlated significantly to mean basal TEWL rates (P <.001). Total body daily TEWL was elevated (746 +/- 468 vs 209 mL/d), resulting in a caloric drain of 433 +/- 272 kcal/d (21 +/- 9.8 kcal/kg per day) through heat of evaporation. Nutrient intake exceeded requirements in all, but resting energy expenditure exceeded predicted in 5 of 6 patients and correlated significantly with mean basal TEWL rates (P <.005). CONCLUSIONS: A defective permeability barrier in children with ichthyosis can result in ample chronic losses of water and calories to impair growth.