Cord blood telomere length in Latino infants: relation with maternal education and infant sex.

OBJECTIVE: Telomere length (TL) has important consequences for early disease and lifelong health. However, few studies have examined determinants of TL at birth. STUDY DESIGN: Here we test associations between cord blood TL and parental and birth factors associated with exposure to stress and indicative of healthy intrauterine life in Latino infants. We tested associations that were significant in bivariate analysis in a multivariate regression model to identify independent predictors for shorter TL at birth. RESULT: Two novel and independent predictors emerged in our analysis of 54 infants. Female gender was associated with longer TL by ~350 base pairs (adjusted ß-coefficient for male gender=-369.57, (95% confidence interval, -718.21 to (-)20.92), P=0.02); rho=-0.26, P=0.057). Increased maternal high-school education, as indicated by a high-school diploma or additional education beyond high school, was also associated with longer TL, by ~500 base pairs (adjusted ß-coefficient for high-school diploma or greater=505.68 (95% confidence interval, 151.69 to 859.68), P<0.01); rho=0.36, P<0.01). Increasing head circumference trended towards statistical significance in association with longer TL (adjusted ß-coefficient = 7.33; 95% confidence interval -0.52 to 15.18; P=0.07). When we removed all infants who had been exposed to high oxidative stress in pregnancy including those exposed to maternal hypertension, preeclampsia, gestational diabetes, and those who were low birth weight or preterm birth (n=7), increasing birth weight percentile was associated with longer TL (adjusted ß-coefficient=8.04 (95% confidence interval 0.07 to 16.00), P=0.048). CONCLUSION: Shorter TL at birth is associated with being male, low maternal education (less than a high school degree), and a trend towards lower birth weight and head circumference. Given the critical role of long TL in predicting health and disease, these findings contribute to the growing literature attempting to understand determinants of TL.

Telomere length is associated with oppositional defiant behavior and maternal clinical depression in Latino preschool children.

Exposure to psychological stress and depression are associated with shorter white blood cell telomere length (TL) in adults, possibly via associated lifelong oxidative stressors. Exposure to maternal depression increases risk for future depression and behavior problems in children, and Latino youth are at high risk. Few studies have evaluated the role of exposure to maternal depression or child behavior in relation to TL in children. We assessed early-childhood exposures to maternal depression from birth to the age of 5 years and child behavior from ages 3-5 years in a cohort of Latino children in relation to child leukocyte TL at ages 4 and 5 years. Children who had oppositional defiant behavior at 3, 4 or 5 years had shorter TL than those without by ~450 base pairs (P < 0.01). In multivariate analyses, independent predictors for shorter TL at 4 and 5 years of age included oppositional defiant disorder at 3, 4 or 5 years (ß = -359.25, 95% CI -633.84 to 84.66; P = 0.01), exposure to maternal clinical depression at 3 years of age (ß = -363.99, 95% CI -651.24 to 764.74; P = 0.01), shorter maternal TL (ß = 502.92, 95% CI 189.21-816.63) and younger paternal age at the child's birth (ß = 24.63, 95% CI 1.14-48.12). Thus, exposure to maternal clinical depression (versus depressive symptoms) in early childhood was associated with deleterious consequences on child cellular health as indicated by shorter TL at 4 and 5 years of age. Similarly, children with oppositional defiant behavior also had shorter TL, possibly related to early exposures to maternal clinical depression. Our study is the first to link maternal clinical depression and oppositional defiant behavior with shorter TL in the preschool years in a relatively homogenous population of low-income Latino children.

No association between childcare and obesity at age 4 in low-income Latino children.

BACKGROUND: Previous studies have found an association between early entry to childcare and risk for overweight and obesity at 3 years of age. These studies, however, have been conducted primarily with higher income White populations or have found increased risk in the children of educated mothers. OBJECTIVE: To assess the relationship between timing of entry to childcare and duration of childcare and pediatric overweight and obesity in a high risk population. METHODS: Using data from a longitudinal cohort of low-income Latino children in San Francisco, we evaluated the association between time of entry to childcare, hours in childcare, and risk for overweight and obesity at age 4. Similarly, we evaluated the relationship between these same childcare parameters and body mass index Z score and risk of having a waist circumference (WC) percentile ≥90th at 4 years of age. RESULTS: In contrast with previous studies, we found no association between being in childcare at 4 years of age or number of hours per week in childcare and risk for childhood overweight, obesity or WC ≥90th percentile at age 4. Additionally, we found no association between age of entry to childcare (≤6 months or ≤12 months of age) with risk for overweight or obesity at age 4. Future studies need to further evaluate the differential impact of childcare on early childhood obesity in relation to race/ethnicity and lower socioeconomic status. CONCLUSION: Low-income children may not be at increased risk for obesity in relation to early childcare exposure.

Maternal BMI and migration status as predictors of childhood obesity in Mexico.

OBJECTIVE: To assess the association of maternal migration to Baja California, body mass index (BMI) status, children's perceived food insecurity, and childhood lifestyle behaviors with overweight (BMI > 85% ile), obesity (BMI > 95% ile) and abdominal obesity (Waist Circumference > 90% ile). METHODS: Convenience sampling methods were used to recruit a cross-sectional sample of 4th, 5th and 6th grade children and their parents at Tijuana and Tecate Public Schools. Children's and parents' weights and heights were measured. Children were considered to have migrant parents if parents were not born in Baja California. RESULTS: One hundred and twenty-two children and their parents were recruited. The mean age of the children was 10.1 ± 1.0 years. Forty nine per cent of children were overweight or obese. Children with obese parents (BMI > 30) had greater odds of being obese, Odds Ratio (OR) 4.9 (95% Confidence Interval (CI), 1.2-19, p = 0.03). Children with migrant parents had greater odds of being obese, OR= 3.7 (95% CI, 1.6-8.3), p = 0.01) and of having abdominal obesity, OR = 3.2 (95% CI, 1.4-7.1, p = 0.01). Children from migrant parents have greater risk of higher consumption of potato chips, OR = 8.0 (95% CI, 2.1-29.1, p = 0.01). Children from non-migrant parents had greater odds of being at risk of hunger. CONCLUSIONS: Parental obesity and migration are associated with increased risk of obesity among Mexican children. Children whose parents were born in Baja California have greater odds of being at risk of hunger. Further studies should evaluate the role of migration on risk for childhood obesity.

Risk factors for macrosomia in infants born to Latina women.

OBJECTIVE: To assess risk factors for macrosomic infant birth among Latina women. STUDY DESIGN: Prospective study of Latina women recruited during pregnancy from prenatal clinic at San Francisco General Hospital. Information was obtained through a structured interview and review of medical records. RESULT: A total of 11% of women delivered macrosomic infants (birth weight >4000 g). In unadjusted analyses, significant risk factors for macrosomia included older maternal age, increasing gravidity, previous history of macrosomic birth and pre-pregnancy overweight. After adjusting for confounders using multivariate analyses, older mothers (10-year increments) had an elevated risk of macrosomia (odds ratio (OR) 2.59; 95% confidence interval (CI) 1.28 to 5.24). CONCLUSION: Efforts to reduce macrosomia in Latina women should focus on older mothers.

Effects of intravenous secretin on language and behavior of children with autism and gastrointestinal symptoms: a single-blinded, open-label pilot study.

BACKGROUND: Autism is a severe developmental disorder with poorly understood etiology. A recently published case series describes 3 autistic children with gastrointestinal symptoms who underwent endoscopy and intravenous administration of secretin and were subsequently noted by their parents to demonstrate improved language skills over a 5-week period. This report sparked tremendous public interest, and investigators at several sites moved quickly to design controlled trials to test the efficacy of secretin as a therapy for autistic children. However, this is the first effort specifically designed to replicate the initial reported findings in terms of patient age, presenting symptoms, and drug administration. OBJECTIVE: To rigorously apply the scientific method by assessing the reproducibility of the reported effects of intravenous secretin on the language of young children with autism and gastrointestinal symptoms. METHODS: We performed a single-blinded, prospective, open-label trial by conducting formal language testing and blinded behavioral rating both before and repeatedly after a standardized infusion of secretin. We selected autistic children who were similar in age and profile to those described in the published retrospective case review. Inclusion criteria for study participation included age (3-6 years), confirmed diagnosis of autism, and reported gastrointestinal symptoms (16 had chronic diarrhea, 2 had gastroesophageal reflux, and 2 had chronic constipation). Twenty children (18 male) were admitted to the Pediatric Clinical Research Center at the University of California, San Francisco after administration of the Preschool Language Scale-3 (PLS-3). A 3 CU/kg dose of secretin (Secretin-Ferring) was administered intravenously (upper endoscopy was not performed). Behavioral ratings were derived using the Autism Observation Scale applied to a 30-minute time sample of the child's behavior consisting of a videotape of the PLS-3 (structured setting) and a second free play session with a standard set of developmentally appropriate toys. Participants then returned for follow-up evaluations, with readministrations of the PLS-3 at 1, 2, 3, and 5 weeks' postinfusion, and videotaping of each session for later blinded review by 2 independent observers using the Autism Observation Scale, uninformed about week of posttreatment. We also surveyed parents of our study children about their impressions of the effects of secretin using a 5-point Likert scale for parents to rate changes seen in their child. RESULTS: With a total study completion rate across all participants of 96%, repeated measures analyses of variance revealed no significant increases in children's language skills from baseline across all 5 study time periods after a single infusion of secretin. Similarly, neither significant decreases in atypical behaviors nor increases in prosocial behaviors and developmentally appropriate play skills emerged. Furthermore, no relationship was found between parental reports of change and observable improvement in the sample. Despite the objective lack of drug effect, 70% of parents in our study reported moderate to high change in their child's language and behavior. Furthermore, 85% of parents reported that they felt that their child would obtain at least some additional benefits from another infusion of secretin. CONCLUSIONS: The results of our pilot study indicate that intravenous secretin had no effects in a 5-week period on the language and behavior of 20 children with autism and gastrointestinal symptoms. The open-label, prospective design of our study with blinded reviews of patients both before and after secretin administration follows the scientific method by seeking to reproduce an observed phenomenon using validating and reliable outcome measures. Pilot studies remain a mandatory step for the design of future randomized, clinical trials investigating potential treatments for children with autism.

Orthotopic liver transplantation for autoimmune hepatitis and cryptogenic chronic hepatitis in children.

BACKGROUND: Autoimmune hepatitis (AIH) and cryptogenic chronic hepatitis (CCH) are important causes of liver failure in children, frequently necessitating orthotopic liver transplantation (OLT). The aim of this study is to review disease progression and potential differences between subgroups of children with AIH and CCH. METHODS: The medical records of 65 children diagnosed with AIH or CCH between 1980 and 1998 were evaluated. RESULTS: The median age at presentation was 9 years, 8 months (range 4 months-19 years), and the median follow-up period was 8 years (range 3 months-18 years, 10 months). Forty-one patients (63%) were female. Twenty-eight patients were Hispanic, 28 were Caucasian, 8 were African-American, and 1 was Asian. Forty-three patients (66%) were diagnosed with type 1 AIH, 8 (12%) with type 2 AIH, and 14 (22%) with CCH. Forty patients (62%) underwent OLT (51% of those with type 1 AIH, 75% of those with type 2 AIH, and 86% of those with CCH). Thirteen (33%) of the transplanted patients experienced disease recurrence. African-American patients experienced a significantly higher rate of disease recurrence post-OLT than did Hispanic patients. Seven patients (11%) died, two without OLT, and five posttransplantation. CONCLUSIONS: AIH and CCH frequently necessitate OLT in children. CCH is a more aggressive disease than Type 1 AIH among children with these disorders. Ethnicity influences the rate of disease recurrence after liver transplantation.

Does liver transplantation affect growth pattern in Alagille syndrome?

Alagille syndrome (AGS) is frequently associated with growth failure, which has been attributed to concurrent congenital anomalies, cholestasis, and malabsorption and/or malnutrition. However, the underlying cause of the growth failure is not well understood. Our objective is to analyze the growth pattern in 26 patients with AGS and the possible effect that orthotopic liver transplantation (OLT) may have on this pattern. The standardized height, weight, and growth velocity of 26 pair-matched patients with AGS were compared. Thirteen patients underwent OLT. Repeated-measure ANOVA methods were used for the statistical analysis. The overall mean standardized height (z score) was -2.92 in the OLT group versus -1.88 in the non-OLT group (P =.03). The overall mean standardized weight was -1. 21 in the non-OLT group and -1.67 in the OLT group (P =.23). In 15 patients, birth weight was 2.82 +/- 0.4 kg, for a mean standardized weight of -0.95, and weight at diagnosis was 4.53 +/- 2.12 kg, for a mean standardized weight of -1.56. Bone age was delayed in the 9 patients who underwent bone-age analysis. Growth hormone therapy administered to 2 patients did not improve growth. Patients with AGS had growth failure secondary to other factors in addition to liver disease. Growth failure beginning in the prenatal period supports a genetic basis for this feature. Growth improvement up to normal levels should not be expected as a benefit of OLT in these patients. Growth failure as a primary indication for OLT should be cautiously examined in patients with AGS.

Micronutrient shortfalls in young children's diets: common, and owing to inadequate intakes both at home and at child care centers.

Numerous studies documented low intakes of iron, zinc, calcium, and other micronutrients in young children. A recent report suggests that intakes are low in both home food and food provided at day care centers. Most of the young children in that study could not have obtained adequate intakes of key micronutrients without major dietary changes. Is it time to recommend routine multivitamin/mineral supplementation for all young children?

Variable morbidity in alagille syndrome: a review of 43 cases.

BACKGROUND: Alagille syndrome is one of the most common inherited disorders that cause chronic liver disease in children. Early reports suggested a benign course in these patients. Subsequent reports showed significant morbidity and mortality. This study was designed to analyze the long-term clinical course in Alagille syndrome. METHODS: The records of children with Alagille syndrome seen during a 20-year period were reviewed. RESULTS: Forty-three patients were identified. Liver disease was diagnosed before 12 months of age in 95%. The frequencies of renal anomalies (50%) and intracranial hemorrhage (12%) were significant. The high incidence of chronic otitis media (35%) has not been reported previously. One patient had a renal transplant. Vascular compromise as a pathologic mechanism for some characteristics of the syndrome is also suggested by the presence of small bowel stenosis and atresia, tracheal and bronchial stenosis, renal artery stenosis, middle aortic syndrome, and avascular necrosis of the humeral and femoral heads. Twenty (47%) patients underwent liver transplantation. Five of six who underwent Kasai procedure required liver transplantation. Twelve died (28%), five after liver transplantation. One patient died of intracranial bleeding. Sixteen (37%) without liver transplantation and 15 (35%) who underwent liver transplantation are alive. CONCLUSIONS: Some patients with early-onset and more severe liver disease can benefit from liver transplantation. Careful and complete assessment should be made of infants with a cholestatic syndrome, to avoid misdiagnosis and unnecessary Kasai procedures. Our observation of vascular compromise in various organ systems suggests that notch signaling pathway defects affect angiogenesis in Alagille syndrome.

Effects of red blood cell transfusion on resting energy expenditure in adolescents with sickle cell anemia.

BACKGROUND: Previous studies indicate that resting energy expenditure is elevated in children with sickle cell anemia, possibly caused in part by hemolysis and increased erythropoietic activity. The purpose of the present investigation was to determine whether erythrocyte transfusion normalizes resting energy expenditure in sickle cell anemia. METHODS: Five adolescents with sickle cell anemia (12-16 years old; 4 boys, 1 girl) were studied before and 1 week after erythrocyte transfusion before elective surgery or at the initial transfusion for growth failure. Resting energy expenditure was measured by indirect calorimetry, and laboratory measures were determined by routine, validated methods. Data comparisons were by nonparametric analysis. RESULTS: After erythrocyte transfusion, total hemoglobin levels increased (difference (D) = 15 g/l; p < 0.05), whereas hemoglobin S (D = -0.36; p < 0.05) and reticulocyte count (D = -0.12; p < 0.05) decreased. Mean pretransfusion resting energy expenditure was elevated to 124% above predicted levels (p < 0.05) and increased further to 134% above prediction (p < 0.05 vs. pretransfusion levels). Plasma triiodothyronine (T3) levels increased (D = 0.17 nmol/l; p < 0.05), reverse T3 (rT3) levels tended to decline (D = -0.04 nmol/l; p = 0.14), and rT3/T3 decreased (D = -0.03; p < 0.05). Plasma insulin-like growth factor-I (IGF-I) levels were low-normal before transfusion and did not change, despite the change in resting energy expenditure. CONCLUSIONS: The results confirm that resting energy expenditure is elevated in patients with sickle cell anemia. However, resting energy expenditure further increased after transfusion, despite decreased erythropoietic activity. A posttransfusion decrease in rT3/T3 may contribute to the increased resting energy expenditure. That there was no change in IGF-I implies that the growth hormone-IGF system is not involved in posttransfusion regulation of resting energy expenditure. Therefore, our data are not consistent with the hypothesis that increased resting energy expenditure in sickle cell anemia is directly related to erythropoietic activity. The mechanisms by which resting energy expenditure increases after transfusion in sickle cell anemia require additional investigation.

Elevated resting energy expenditure in adolescents with sickle cell anemia.

OBJECTIVE: To assess the reliability of standard prediction equations in estimating resting energy expenditure (REE) values in adolescents with sickle cell anemia. SUBJECTS/DESIGN: Body composition and metabolic measurements were performed in 8 adolescents, aged 11 to 18 years, with homozygous sickle cell anemia. REE was measured by indirect calorimetry under standard conditions, and measurements were compared with 4 prediction formulas (Harris-Benedict, Schofield, Mayo Clinic, and Food and Agriculture Organization/World Health Organization/United Nations University). Fat-free mass was measured to assess REE per unit of actively metabolizing tissue. Fat-free mass was expressed as a mean of values obtained by densitometry, deuterium dilution, 40K-counting, and total body electrical conductivity. STATISTICAL ANALYSES: Repeated measures analysis of variance was performed to determine whether measured REE values and predicted values differed. The Fischer test was used to identify which predicted values differed significantly from the measured REE. RESULTS: All 4 prediction formulas significantly underestimated REE. Group mean values for the prediction formulas ranged from 83% to 89% of the measured value. REE averaged 47.7 +/- 10.0 kcal/kg fat-free mass per day, which is 30% to 50% higher than reported values in healthy adolescent populations. CONCLUSIONS: These data suggest that REE is elevated in adolescents with sickle cell anemia. Standard equations used to predict REE are unreliable in these patients. APPLICATIONS: REE in patients with sickle cell anemia is best determined by indirect or direct measurement of energy expenditure. Clinically useful formulas to estimate REE should be developed for patients with conditions, including sickle cell anemia, where the metabolic rate may be altered.