Pippa Simpson

The Association of Child and Household Food Insecurity With Childhood Overweight Status

CONTEXT. The prevalence of childhood overweight status is increasing. Some have suggested that childhood overweight is associated with food insecurity, defined as limited or uncertain access to enough nutritious food. OBJECTIVES. The purpose of this work was to assess the association of household and child food insecurity with childhood overweight status. METHODS. The National Health and Nutrition Examination Survey 1999–2002 uses a stratified multistaged probability sample and collects a broad array of data from a nationally representative sample of US citizens. All children 3 to 17 years old in this sample are included in these analyses. We measured BMI categorized as at risk for overweight or greater (≥85%) or overweight (≥95%) and household and child food security/insecurity using the US Food Security Scale. RESULTS. When compared with children from food-secure households, children from food-insecure households were more likely to demonstrate significant associations with being at risk for overweight or greater in the following demographic categories: 12 to 17 years, girls, white, and in households with income <100% and >4 times the federal poverty level. Household food insecurity is associated with child overweight status in children aged 12 to 17, girls, and children who live in households with incomes >4 times the federal poverty level. Child food insecurity demonstrated the same associations with being at risk for overweight or greater, as did household food insecurity, but associations were also seen in 3- to 5-year-old children, boys, and Mexican American children. Child food insecurity is significantly associated with child overweight status for children aged 12 to 17, girls, white children, and children in families with income ≤100% poverty level. Controlling for ethnicity, gender, age, and family poverty index level, childhood food insecurity is associated with a child being at risk for overweight status or greater, but not overweight status. CONCLUSIONS. Household and child food insecurity are associated with being at risk for overweight and overweight status among many demographic categories of children. Child food insecurity is independently associated with being at risk for overweight status or greater while controlling for important demographic variables. Future longitudinal research is required to determine whether food insecurity is causally related to child overweight status.

Human hepatic flavin-containing monooxygenases 1 (FMO1) and 3 (FMO3) developmental expression

The flavin-containing monooxygenases (FMOs) are important for the metabolism of numerous therapeutics and toxicants. Six mammalian FMO genes (FMO1–6) have been identified, each exhibiting developmental and tissue- and species-specific expression patterns. Previous studies demonstrated that human hepatic FMO1 is restricted to the fetus whereas FMO3 is the major adult isoform. These studies failed to describe temporal expression patterns, the precise timing of the FMO1/FMO3 switch, or potential control mechanisms. To address these questions, FMO1 and FMO3 were quantified in microsomal fractions from 240 human liver samples representing ages from 8 wk gestation to 18 y using Western blotting. FMO1 expression was highest in the embryo (8–15 wk gestation; 7.8 ± 5.3 pmol/mg protein). Low levels of FMO3 expression also were detectable in the embryo, but not in the fetus. FMO1 suppression occurred within 3 d postpartum in a process tightly coupled to birth, but not gestational age. The onset of FMO3 expression was highly variable, with most individuals failing to express this isoform during the neonatal period. FMO3 was detectable in most individuals by 1-2 y of age and was expressed at intermediate levels until 11 y (12.7 ± 8.0 pmol/mg protein). These data suggest that birth is necessary, but not sufficient for the onset of FMO3 expression. A gender-independent increase in FMO3 expression was observed from 11 to 18 y of age (26.9 ± 8.6 pmol/mg protein). Finally, 2- to 20-fold interindividual variation in FMO1 and FMO3 protein levels were observed, depending on the age bracket.

A Central Role for Induced Regulatory T Cells in Tolerance Induction in Experimental Colitis

In addition to thymus-derived or natural T regulatory (nTreg) cells, a second subset of induced T regulatory (iTreg) cells arises de novo from conventional CD4+ T cells in the periphery. The function of iTreg cells in tolerance was examined in a CD45RBhighCD4+ T cell transfer model of colitis. In situ-generated iTreg cells were similar to nTreg cells in their capacity to suppress T cell proliferation in vitro and their absence in vivo accelerated bowel disease. Treatment with nTreg cells resolved the colitis, but only when iTreg cells were also present. Although iTreg cells required Foxp3 for suppressive activity and phenotypic stability, their gene expression profile was distinct from the established nTreg “genetic signature,” indicative of developmental and possibly mechanistic differences. These results identified a functional role for iTreg cells in vivo and demonstrated that both iTreg and nTreg cells can act in concert to maintain tolerance.

Muscle inflammatory response and insulin resistance: synergistic interaction between macrophages and fatty acids leads to impaired insulin action

Obesity is characterized by adipose tissue expansion as well as macrophage infiltration of adipose tissue. This results in an increase in circulating inflammatory cytokines and nonesterified fatty acids, factors that cause skeletal muscle insulin resistance. Whether obesity also results in skeletal muscle inflammation is not known. In this study, we quantified macrophages immunohistochemically in vastus lateralis biopsies from eight obese and eight lean subjects. Our study demonstrates that macrophages infiltrate skeletal muscle in obesity, and we developed an in vitro system to study this mechanistically. Myoblasts were isolated from vastus lateralis biopsies and differentiated in culture. Coculture of differentiated human myotubes with macrophages in the presence of palmitic acid, to mimic an obese environment, revealed that macrophages in the presence of palmitic acid synergistically augment cytokine and chemokine expression in myotubes, decrease IkappaB-alpha protein expression, increase phosphorylated JNK, decrease phosphorylated Akt, and increase markers of muscle atrophy. These results suggest that macrophages alter the inflammatory state of muscle cells in an obese milieu, inhibiting insulin signaling. Thus in obesity both adipose tissue and skeletal muscle inflammation may contribute to insulin resistance.

Volume-outcome relationships in pediatric intensive care units.

Context. Pediatric intensive care units (PICUs) have expanded nationally, yet few studies have examined the potential impact of regionalization and no study has demonstrated whether a relationship between patient volume and outcome exists in these units. Documentation of an inverse relationship between volume and outcome has important implications for regionalization of care. Objectives. This study examines relationships between the volume of patients and other unit characteristics on patient outcomes in PICUs. Specifically, we investigate whether an increase in patient volume improves mortality risk and reduces length of stay. Design and Setting. A prospective multicenter cohort design was used with 16 PICUs. All of the units participated in the Pediatric Critical Care Study Group. Participants. Data were collected on 11 106 consecutive admissions to the 16 units over a 12-month period beginning in January 1993. Main Outcome Measures. Risk-adjusted mortality and length of stay were examined in multivariate analyses. The multivariate models used the Pediatric Risk of Mortality score and other clinical measures as independent variables to risk-adjust for illness severity and case-mix differences. Results. The average patient volume across the 16 PICUs was 863 with a standard deviation of 341. We found significant effects of patient volume on both risk-adjusted mortality and patient length of stay. A 100-patient increase in PICU volume decreased risk-adjusted mortality (adjusted odds ratio: .95; 95% confidence interval: .91–.99), and reduced length of stay (incident rate ratio: .98; 95% confidence interval: .975–.985). Other PICU characteristics, such as fellowship training program, university hospital affiliation, number of PICU beds, and childrens hospital affiliation, had no effect on risk-adjusted mortality or patient length of stay. Conclusions. The volume of patients in PICUs is inversely related to risk-adjusted mortality and patient length of stay. A further understanding of this relationship is needed to develop effective regionalization and referral policies for critically ill children.

The accumulation of whole body skeletal mass in third- and fourth-grade children: Effects of age, gender, ethnicity, and body composition

The purpose of this longitudinal study is to describe bone mass and body composition, and the annual changes in these measurements, among third grade students recruited from a suburban school district. Whole body bone mineral content (WBBMC), bone mineral density (WBBMD), fat, and lean mass were measured by dual-energy X-ray absorptiometry. Bone mass in the lumbar spine (LBMC) region of the whole body scan was also utilized. 773 students (38% white, 57% black, 5% other) had baseline visits; 561 had a second measurement a year later. At baseline, black children have significantly higher WBBMC, WBBMD, height, and lean mass than whites. Black males, but not black females, have a greater LBMC. There are no significant gender differences in body size, WBBMC, or WBBMD, although girls have a greater LBMC and fat mass, and boys have a higher lean mass. Most of these differences persist in visit 2. The annual change in bone and lean mass is greater in blacks. Stepwise linear regression analyses of bone mass on body size, gender, and ethnicity and their interactions indicate that log-transformed weight explains most of the variance in both WBBMC and WBBMD (multiple r2 = 0.90 and 0.64, respectively). There are significant black/white differences in intercepts and slopes. Other variables explain only another 1%-2% of the variance. The strongest Pearson correlations are between changes in bone mass and changes in lean mass and log-transformed weight (r ranging from 0.62 to 0.84, p = 0.0001). We conclude that there is a significant black/white, but not male/female difference in whole body bone mass and bone density before puberty. Ethnic and gender differences in bone and body composition suggest that the lean component may contribute to a greater peak bone mass in blacks vs. whites, and perhaps in males vs. females.

Interactions of inflammatory pain and morphine in infant rats: Long-term behavioral effects

Neonatal rat pups exposed to repetitive acute pain show decreases in pain threshold and altered behavior during adulthood. A model using prolonged inflammatory pain in neonatal rats may have greater clinical relevance for investigating the long-term behavioral effects of neonatal pain in ex-preterm neonates. Neonatal rat pups were exposed to repeated formalin injections on postnatal (P) days 1-7 (P1-P7), with or without morphine pretreatment, and were compared with untreated controls. Behavioral testing during adulthood assessed pain thresholds using hot-plate (HP) and tail-flick (TF) tests, alcohol preference, and locomotor activity (baseline and postamphetamine). Adult rats exposed to neonatal inflammatory pain exhibited longer HP latencies than controls and male rats had longer HP thresholds compared to females. Male rats exposed to neonatal morphine alone exhibited longer TF latencies than controls. Both neonatal morphine treatment and neonatal inflammatory pain decreased ethanol preference, but their effects were not additive. During adulthood, male rats exposed to neonatal inflammatory pain exhibited less locomotor activity than untreated controls. We conclude that neonatal formalin and morphine treatment have specific patterns of long-term behavioral effects in adulthood, some of which are attenuated when the two treatments are combined.

Bradycardia during anesthesia in infants. An epidemiologic study.

Background:The frequency and morbidity of bradycardia during anesthesia in infants are not well documented. This study sought to determine the frequency of bradycardia during anesthesia in infants (0 to 1 yr) compared to that in older children, describe causes and morbidity, and identify factors that influence its frequency. Methods:Computerized information abstracted from 7,979 anesthetic records of patients ages 0–4 yr undergoing non-cardiac surgery were examined for the presence or absence of intraoperative bradycardia. To study bradycardia in infants, 4,645 anesthetics in patients aged 0–1 yr were considered. Those with bradycardia to heart rates less than 100 beats/min were examined for causes, morbidity, and treatment of the bradycardia. For analysis of influencing factors, the frequency of bradycardia in infants was related to age, sex, race, ASA physical status, surgical site (body cavity), complexity (major or minor) and duration, type of primary anesthetist, type of supervising anesthesiologist, and anesthetic agents. Logistic regression was used to estimate the significance (P < 0.05) and odds ratios for each. Results:The frequency of bradycardia was 1.27% In the 1st yr of life, but only 0.65% in the third and 0.16% in the 4th yr, a significant difference. Causes of bradycardia in infants included disease or surgery in 35%, the dose of inhalation agent in 35%, and hypoxemia in 22%. Morbidity included hypotension in 30%, asystole or ventricular fibrillation in 10%, and death in 8%. Treatment involved epinephrine in 30% and chest compression in 25%. Associated factors included an ASA physical status of 3–5 (vs. 1 or 2) and longer (vw. shorter) surgery. Bradycardia was less than half as likely when the supervising anesthesiologist was a member of the Pediatric Anesthesia Service as with other anesthesiologists (P < 0.001). Conclusions:Bradycardia is more frequent in infants undergoing anesthesia compared to older children and is associated with substantial morbidity. It is more likely in sicker infants undergoing prolonged surgery and less likely when a pediatric anesthesiologist is present.

Dexamethasone for the prevention of postextubation airway obstruction: a prospective, randomized, double-blind, placebo-controlled trial.

OBJECTIVE To determine whether dexamethasone prevents postextubation airway obstruction in young children. DESIGN Prospective, randomized, double-blind, placebo-controlled study. SETTING Pediatric intensive care unit of a university teaching hospital. PATIENTS Sixty-six children, < 5 yrs of age, intubated and mechanically ventilated for > 48 hrs. INTERVENTIONS Patients were randomized to receive intravenous dexamethasone (0.5 mg/kg, maximum dose 10 mg) or saline, every 6 hrs for six doses, beginning 6 to 12 hrs before elective extubation. MEASUREMENTS AND MAIN RESULTS Dependent variables included the presence of stridor, Croup Score, and pulsus paradoxus at 10 mins, 6, 12, and 24 hrs after extubation; need for aerosolized racemic epinephrine and reintubation. The dexamethasone and placebo groups were similar in age (median 3 months [range 1 to 57] vs. 4 months [range 1 to 59], p = .6), frequency of underlying airway anomalies (3/33 vs. 3/33, p = 1.0), and duration of mechanical ventilation (median 3.3 days [range 2.1 to 39] vs. 3.5 days [range 2.1 to 15], p = .7). The dexamethasone group had a lower frequency of stridor, Croup Score, and pulsus paradoxus measurement at 10 mins and at 6 and 12 hrs after extubation. Fewer dexamethasone-treated patients required epinephrine aerosol (4/31 vs. 22/32, p < .0001) and reintubation (0/31 vs. 7/32, p < .01). Three patients exited the study early-one patient in the dexamethasone group had occult gastrointestinal hemorrhage and one patient in each group had hypertension. CONCLUSION Pretreatment with dexamethasone decreases the frequency of postextubation airway obstruction in children.

Fontan Palliation in the Modern Era: Factors Impacting Mortality and Morbidity

BACKGROUND Advances in management of the Fontan patient include interval superior cavopulmonary shunt, total cavopulmonary connection, either lateral tunnel or extracardiac conduit, and the use of a fenestration. Coincident with these improvements, Fontan palliation has been applied to a wider ranger of anatomic subgroups. METHODS A cross-sectional analysis of 256 consecutive patients undergoing a total cavopulmonary connection Fontan after superior cavopulmonary shunt between January 1, 1994, and June 30, 2007 were studied. Fenestration was used selectively. Fontan failure was defined as death, transplant, or takedown. Event-free survival was defined as freedom from death, transplant, Fontan takedown, functional class III to IV, pacemaker, antiarrhythmic medication, protein-losing enteropathy, stroke, or thrombus. RESULTS Survival was 97% +/- 1%, 96% +/- 1%, and 94% +/- 2%, respectively, at 1, 5, and 10 years. Event-free survival was 96% +/- 1%, 87% +/- 3%, and 64% +/- 6%, respectively, at 1, 5, and 10 years. Factors predicting worse event-free survival included longer cross-clamp time (p = 0.003), fenestration (p = 0.014), and longer hospital length of stay (p = 0.016). Ventricular morphology did not predict outcome. Left ventricle (n = 113, 44%) versus right ventricle (n = 142, 56%) failure-free survival (death, transplant, or Fontan takedown) at 10 years was 92% +/- 4% versus 91% +/- 3%, respectively (p = 0.19). Left ventricle versus right ventricle event-free survival at 10 years was 75% +/- 7% versus 67% +/- 9%, respectively (p > 0.1). CONCLUSIONS Survival for patients undergoing a completion Fontan in the current era is excellent, but patients remain at risk for morbid events. In the intermediate follow-up period, we could not identify a difference in outcome between dominant left and right ventricle morphology.