The Journal of Pediatrics - Articles in Press

Newborn Screening Results in Children with Central Hypothyroidism - Corrected Proof

Todd D. Nebesio, Michael P. McKenna, Zeina M. Nabhan, Erica A. Eugster — 2010-03-11

Objective: To investigate newborn screening results in children with congenital hypopituitarism, including central hypothyroidism, and to determine whether there were differences between children who had abnormal results and children with normal newborn screening results.Study design: Medical records of children with central hypothyroidism observed in our pediatric endocrinology clinics from 1990 to 2006 were reviewed.Results: Forty-two subjects (22 boys) were identified. Eight children (19%) had a low total thyroxine level (<5.0 mcg/dL) on the newborn screening test. The average total thyroxine level in the remaining 34 subjects was 9.8 ± 3.4 mcg/dL. Thyrotropin levels were within the reference range in all children. No differences were found in the 2 groups for birth history, jaundice (53% overall), hypoglycemia (36% overall), or micropenis (43% of boys). Fifty-seven percent of children had septo-optic dysplasia, and 98% had multiple pituitary hormone deficiencies. Children with an abnormal newborn screening results were initially examined by a pediatric endocrinologist at an average age of 4.6 ± 5.0 months, and children with normal newborn screening results were initially examined at an average age of 16.9 ± 26.7 months (P = .037).Conclusions: Most children with congenital central hypothyroidism have normal thyroid function at birth. Normal newborn screening results can be falsely reassuring and may contribute to a delay in diagnosis of hypopituitarism despite classic clinical features.

Benefits of Care Coordination for Children with Complex Disease: A Pilot Medical Home Project in a Resident Teaching Clinic - Corrected Proof

Thomas S. Klitzner, Leslie A. Rabbitt, Ruey-Kang R. Chang — 2010-03-11

Objective: To study the integration of comprehensive care coordination for children with complex disease in our resident education clinic at University of California Los Angeles by analyzing alterations in medical resource use.Study design: The Pediatric Medical Home Project at University of California Los Angeles was designed to include 4 basic elements: 1) 60-minute intake appointment; 2) follow-up appointments twice the length of a standard visit; 3) access to a “family liaison”; and 4) a family notebook (“All about Me” binder). From the initial cohort of 43 patients, encounter data on 30 were analyzed to determine use of outpatient, urgent, emergency department (ED), and inpatient services. Encounters for each patient were compared for a period of 1 year before and 1 year after enrollment.Results: The average number of ED visits per patient decreased from 1.1 ± 1.7 before enrollment to 0.5 ± 0.9 after medical home enrollment (P = .02). However, no significant change was found in use of any of the other health care resources studied.Conclusions: Incorporating a program of care coordination according to the principles of the medical home into an outpatient pediatric residency teaching clinic may not only serve as a training vehicle for pediatric residents, but also create favorable alterations in medical resource use.

Language and Motor Skills Are Impaired in Infants with Biliary Atresia Before Transplantation - Corrected Proof

Susan E. Caudle, Jennifer M. Katzenstein, Saul J. Karpen, Valérie A. McLin — 2010-03-11

Objective: To test the hypothesis that in very young patients with biliary atresia, cognitive deficits are apparent before transplantation.Study design: With the Mullen Scales of Early Learning (Mullen), we examined 15 infants (mean age, 7.8 months) with biliary atresia, correlating Mullen scores with standard clinical and biochemical parameters.Results: Overall, participants displayed significant delays in gross motor and language skills, and fine motor and visual reasoning skills were relatively preserved. The international normalized ratio correlated inversely with gross (P < .01) and fine (P < .05) motor skills. Growth parameters correlated positively with expressive language ability, but length of hospitalization and mode of feeding did not. Age at performance of the Kasai procedure was found to correlate with receptive language performance (P < .05).Conclusions: Very young children with biliary atresia display a characteristic profile of early developmental deficits before transplantation. These findings suggest that early intervention and aggressive nutritional management should be the standard of care to minimize neurocognitive effects.

Palivizumab Utilization and Compliance: Trends in Respiratory Syncytial Virus Prophylaxis in Florida - Corrected Proof

Christian Hampp, Arwa Saidi, Almut G. Winterstein — 2010-03-11

Objectives: To analyze adherence to guidelines to prevent respiratory syncytial virus hospitalization and to a monthly immunoprophylaxis schedule in the absence of prior authorization requirements.Study design: Among Florida Medicaid fee-for-service recipients 0 to 2 years of age from the 1998/1999 season through the 2004/2005 season with available birth certificates, we identified indications for palivizumab prophylaxis based on claims data. At least 4 doses of palivizumab in the 5 core season-months were considered full season coverage.Results: Of 302 101 children-seasons, 6089 were associated with 24 469 doses of palivizumab. In the 2004/2005 season, 73.6% of children with chronic lung disease received immunoprophylaxis: 67.6% children with gestational age <32 weeks, 37% with congenital heart disease, 26.4% with cystic fibrosis, and 19.4% with severe immunodeficiency. Multiple indications increased the likelihood for prophylaxis from 34.9% to 80.4%. Full season coverage was consistent across indications at approximately 70%. From the 1998/1999 season through the 2004/2005 season, 8038 doses were administered during 2051 children-seasons without any indication; mostly (69.6%) where premature children had exceeded the recommended age range for prophylaxis.Conclusions: High utilization rates were found in children with multiple indications, and compliance with a monthly schedule was consistently high. One third of doses were administered outside of guidelines, suggesting suboptimal utilization of resources in the absence of prior authorization.

Overweight Is Highly Prevalent In Children with Type 1 Diabetes And Associates with Cardiometabolic Risk - Corrected Proof

2010-03-11

Objectives: To determine the prevalence of traditional cardiometabolic risk factors and to assess the effect of overweight/obesity on the occurrence of these risk factors in a cohort of children with type 1 diabetes mellitus (T1DM).Study design: Two hundred eighty-three consecutive patients (3 to 18 years of age) attending an outpatient clinic for T1DM care were included. The prevalence of cardiometabolic risk factors, the metabolic syndrome, and high alanine aminotransferase, were assessed before and after stratification for weight status.Results: Of all children (median age, 12.8 years; interquartile range, 9.9 to 16.0; median diabetes duration, 5.3 years; interquartile range, 2.9 to 8.6), 38.5% were overweight/obese (Z-body mass index ≥1.1). Overall, median HbA1c levels were 8.2% (interquartile range, 7.4 to 9.8), and HbA1c ≥7.5% was present in 73.9%. Microalbuminuria was found in 17.7%, high triglycerides (>1.7 mmol/L) in 17.3%, high LDL-cholesterol (>2.6 mmol/L) in 28.6%, low HDL-cholesterol (<1.1 mmol/L) in 21.2%, and hypertension in 13.1% of patients. In the overweight/obese children with T1DM, versus normal-weight children, a higher prevalence of hypertension (23.9% vs 5.7%), the metabolic syndrome (25.7% vs 6.3%), and alanine aminotransferase >30 IU/L (15.6% vs 4.5%) was found (all P < .05).Conclusions: Overweight/obesity and cardiometabolic risk factors were highly prevalent in a pediatric cohort with T1DM. Hypertension, the metabolic syndrome, and high alanine aminotransferase were significantly more prevalent in overweight/obese compared with normal-weight children with T1DM.

Individual and Combined Effects of ApoE and MTHFR 677C/T Polymorphisms on Cognitive Performance in Spanish Adolescents: The AVENA Study - Corrected Proof

2010-03-11

Objective: To examine the individual and combined associations of ApoE and MTHFR 677C/T polymorphisms with cognitive performance in adolescents.Study design: The study comprised 412 Spanish adolescents (13 to 18.5 years of age). Cognitive performance (verbal, numeric and reasoning abilities, and an overall score) was measured by the Spanish-version of the SRA-Test of Educational-Ability.Results: We observed no differences in the cognitive performance study variables in adolescents carrying or not carrying the ApoE ε4 variant. Adolescents without the MTHFR 677TT genotype had significantly better cognitive performance than their TT peers. The analysis of the combined effect of these polymorphisms revealed that those individuals carrying both the ApoE ε4 variant and the MTHFR 677TT genotype had significantly worse cognitive performance than their peers with other genotype combinations. These findings were independent of sex, age pubertal status, socioeconomic status, physical activity, and skipping breakfast.Conclusions: The results of the present study suggest that the ApoE ε4 alone is not associated with cognitive performance in adolescents. Individuals with the MTHFR 677TT genotype had slightly impaired cognitive performance, whereas we observed a combined effect of both the ApoE ε4 variant and the MTHFR 677TT genotype on cognitive performance. More research is needed in larger population samples to corroborate our findings.

Time for Initial Response to Steroids Is a Major Prognostic Factor in Idiopathic Nephrotic Syndrome - Corrected Proof

2010-03-11

Objective: To identify early prognostic factors for idiopathic nephrotic syndrome (INS) in childhood.Study design: A retrospective analysis of 103 patients with INS at onset, all treated in a single center with the same induction protocol, was conducted. Minimum length of follow-up was 2 years; median length of follow-up was 43 months. Survival data were assessed with Cox-Mantel analysis. Predictive values were estimated with receiver operating characteristic curves.Results: The median time of response to steroid therapy was 7 days. A significant association was found between the interval from onset of steroid therapy to remission and the risk of relapsing within 3 months after steroid therapy discontinuation (P < .0001). A similar association was found between the time to achieve remission and the risk of developing frequent relapsing or steroid-dependent nephrotic syndrome (P < .0001), the prescription of maintenance steroid therapy (P < .003), and the prescription of all other non-steroid drugs (P < .0001) during follow-up. Patients with non-relapsing and infrequent relapsing nephrotic syndrome had a median time to achieve remission <7 days; in patients with frequent relapsing and steroid-dependent nephrotic syndrome, this median was >7 days.Conclusion: The interval from onset of steroid therapy to remission is an accurate early prognostic factor in INS.

Effects of Cushing Disease on Bone Mineral Density in a Pediatric Population - Corrected Proof

2010-03-11

Objective: To evaluate bone mineral density (BMD) in children with Cushing disease before and after transphenoidal surgery (TSS).Study design: Hologic dual-energy x-ray absorptiometry (DXA) scans of 35 children with Cushing disease were analyzed retrospectively. Sixteen of the 35 patients had follow-up DXA scans performed 13 to 18 months after TSS. BMD and bone mineral apparent density (BMAD) for lumbar spine (LS) L1 to L4 and femoral neck (FN) were calculated.Results: Preoperatively, 38% and 23% of patients had osteopenia of the LS and FN, respectively. Both BMD and BMAD Z-scores of the LS were worse than those for the FN (–1.60 ± 1.37 versus –1.04 ± 1.19, P = .003), and (–1.90 ± 1.49 versus –0.06 ± 1.90, P < .001); postoperative improvement in BMD and BMAD were more pronounced in LS than in the FN (0.84 ± 0.88 versus 0.15 ± 0.62, P<.001; and 0.73 ± 1.13 versus –0.26 ± 1.21, P = .015). Pubertal stage, cortisol levels, and length of disease had no effect on BMD.Conclusions: In children with Cushing disease, vertebral BMD was more severely affected than femoral BMD and this effect was independent of degree or duration of hypercortisolism. BMD for the LS improved significantly after TSS; osteopenia in this group may be reversible.

Elevated Ambulatory Blood Pressure in a Multi-Ethnic Population of Obese Children and Adolescents - Corrected Proof

Alexandra Aguilar, Vlady Ostrow, Francesco De Luca, Elizabeth Suarez — 2010-03-11

Objectives: To evaluate the relationship among ambulatory blood pressure (ABP), body mass index (BMI), and homeostasis model assessment (HOMA) in a multi-ethnic population of obese children with clinic blood pressure in the reference range.Study design: A total of 43 obese normotensive children (7-17 years old) were recruited. ABP monitoring, oral glucose tolerance test, lipid levels, and urine microalbumin levels were obtained.Results: Fourteen percent of the subjects had elevated 24-hour systolic blood pressure (SBP), 9.3% had elevated daytime SBP, and 32.6 % elevated nighttime SBP. For diastolic blood pressure, 4.7% of the sample had an elevated mean nighttime value. Children with more severe obesity (BMI SD score >2.5) had higher 24-hour and nighttime SBP than children with less severe obesity (BMI SD score ≤2.5). Children with HOMA values in the highest quartile had larger waist circumference and higher clinic blood pressure than children with HOMA values in the lowest quartile, and no difference in the mean ABP values was found in the 2 groups . Multiple linear regression analysis showed that 24-hour and nighttime SBP were significantly correlated with BMI SD score.Conclusion: Obese children with normal clinic blood pressure often exhibit elevated ABP. The risk for ambulatory hypertension appears to be correlated with the degree of obesity.

Children with Chronic Illness Return to Their Baseline Functional Status after Organ Dysfunction on the First Day of Admission in the Pediatric Intensive Care Unit - Corrected Proof

Katri V. Typpo, Nancy J. Petersen, Laura A. Petersen, M. Michele Mariscalco — 2010-03-11

Objective: To determine chronic illness outcomes after admission with multiple organ dysfunction syndrome (MODS) for patients in the pediatric intensive care unit (PICU).Study design: We evaluated consecutive PICU admissions from 35 US children's hospitals from January 2004–December 2005 in the virtual PICU Performance System database. We excluded hospitals with >10% missing values for MODS variables and patients < 1 month or > 18 years of age. MODS was identified by laboratory and vital sign values from day of admission with International Pediatric Sepsis Consensus Conference criteria. Chronic illness was identified by secondary diagnoses, classified by modified Delphi method. We evaluated functional outcomes with pediatric overall performance category and pediatric cerebral performance category scores from PICU admission and discharge.Results: Of 44 693 admissions, 52.1% had a chronic diagnosis. Chronic diagnoses increased MODS at PICU admission (24.6% vs 12.0%, P < .001) and mortality rates (3.7% vs 1.9%, P < .001). Patients with a chronic diagnosis had similar changes in pediatric overall performance category and pediatric cerebral performance category scores from PICU admission to discharge as previously healthy children. However, outcome in different chronic diagnosis categories was variable.Conclusions: Chronic illness increased MODS incidence at PICU admission and impacted all-cause PICU mortality rates. Although, in aggregate, children who survive return to baseline functional status, this varies by chronic illness category.

Urinary Cytokines and Renal Doppler Study in Kawasaki Disease - Corrected Proof

2010-02-22

Objective: To investigate whether renal vasculitis is the sole cause or merely a contributing cause of renal inflammation in Kawasaki disease (KD).Study design: This prospective study in a university medical center in Taiwan enrolled 24 children with KD between June 2004 and November 2005. All patients underwent a technetium-99 m dimercaptosuccinic acid scintigraphy single-photon emission computed tomography scan, the results of which were used to group the patients with KD as with or without renal involvement. Urine samples underwent a cytokine analysis. Renal Doppler ultrasonography was used to evaluate renal vasculitis by measuring the pulsatility index (PI) and resistance index (RI).Results: Ten of the 24 patients (42%) with renal inflammatory foci were the study group; the remainder composed the control group. Urinary interleukin (IL)-6 levels were significantly higher in the study group (496.7 ± 310.9 vs 115.0 ± 65.9 ng/g urinary creatinine; P < .01), as were PI values (1.85 ± 0.70 vs 1.44 ± 0.53; P < .05). Urinary IL-6 levels and PI values were significantly (P < .05) correlated.Conclusions: Increased urinary IL-6 and elevated renal Doppler measures suggest that immune-mediated vasculitis is one of the mechanisms causing renal inflammation in KD.

Five-Year Outcome of Children With “Growing Pains”: Correlations With Pain Threshold - Corrected Proof

Yosef Uziel, Gil Chapnick, Lutfi Jaber, Dan Nemet, Philip J. Hashkes — 2010-02-22

Objective: To examine the 5-year outcome in a cohort of children with “growing pains” and the association with changes in pain threshold.Study design: Subjects were 44 children with growing pains studied previously, and controls were 38 pain-free children matched by sex and age. Current status of growing pains and other pain syndromes were assessed by parental questionnaires. Pain threshold was measured with a Fisher-type dolorimeter. Outcomes were correlated with the pain threshold.Results: We examined 35/44 patients (80%) after 5 years. Eighteen patients (51%) experienced resolution of growing pains. In 14 of the 17 patients with persistent growing pains (83%), episodes were less frequent and milder. The prevalence of accompanying pain syndromes decreased from 20% to 14%. No patient developed fibromyalgia. Pain thresholds were similar in the entire growing pains cohort and healthy controls, but those with continued growing pains had significantly lower thresholds than controls (P <.05) and patients with resolved growing pains (P <.02).Conclusions: We confirm that growing pains has a benign prognosis and probably represents a pain amplification syndrome of early childhood.

A Randomized Intervention of Montelukast for Post-Bronchiolitis: Effect on Eosinophil Degranulation - Corrected Proof

2010-02-22

Objective: To investigate the effect of montelukast on eosinophil degranulation and recurrent wheezing episodes in post-respiratory syncytial virus (RSV) bronchiolitis.Study design: Two hundred infants (age, 6-24 months) who were hospitalized with their first episode of acute RSV bronchiolitis were randomized in a double-blind, placebo-controlled, parallel comparison of 4-mg montelukast granules (RSV-MONT group) or matching placebo (RSV-PLC group) administered for 3 months. Serum eosinophil-derived neurotoxin (EDN) levels were measured (primary outcome), and recurrent wheezing was documented (secondary outcome) for 12 months. Comparisons were made with control subjects (control group, n = 50).Results: At the end of the 3-month treatment period, the RSV-PLC group (n = 71) exhibited significantly elevated EDN levels (P < .0001), and the RSV-MONT group (n = 79) showed significantly decreased EDN levels (P < .01) when compared with the initial levels. As a result, EDN levels in the 2 RSV groups significantly differed at this point (P < .0001) and remained different for the entire 12-month follow-up period. Cumulative recurrent wheezing episodes at 12 months were significantly lower in the RSV-MONT group (P = .039).Conclusion: Montelukast treatment reduces eosinophil degranulation and is associated with a decrease in recurrent wheezing episodes in post-RSV bronchiolitis.

Psychological Effects of False-Positive Results in Cystic Fibrosis Newborn Screening: A Two-Year Follow-up - Corrected Proof

2010-02-22

Objective: To evaluate parental stress after a false-positive result at the time of the cystic fibrosis (CF) newborn screening (NBS), attributable to heterozygotism or persistent hypertrypsinemia.Study design: A prospective study was conducted in 86 French families at 3, 12, and 24 months after NBS. A psychologist conducted interviews with a questionnaire, the Perceived Stress Scale, and the Vulnerable Child Scale.Results: Overall, 96.5% of parents said they had been anxious at the time of the sweat test. However, 86% felt entirely reassured 3 months after the test. The mean Perceived Stress Scale score did not differ from that observed in the French population. Mean Vulnerable Child Scale scores were high, associated with a low Parental Perception of Child Vulnerability. These results did not differ significantly at 1 and 2 years. In total, 86% to 100% of families no longer worried about CF. All parents stated that they would have the test performed again for another child.Conclusions: CF NBS can lead to false-positive results, causing parental anxiety, which quickly decreases after a sweat test performed soon after the phone call.

From Regulatory Problems in Infancy to Attention-Deficit/Hyperactivity Disorder in Childhood: A Moderating Role for the Dopamine D4 Receptor Gene? - Corrected Proof

2010-02-22

Objective: To examine whether the dopamine receptor D4 gene (DRD4) exon III VNTR moderates the risk of infants with regulatory disorders for developing attention-deficit/hyperactivity disorder (ADHD) later in childhood.Study design: In a prospective longitudinal study of children at risk for later psychopathology, 300 participants were assessed for regulatory problems in infancy, DRD4 genotype, and ADHD symptoms and diagnoses from childhood to adolescence. To examine a potential moderating effect on ADHD measures, linear and logistic regressions were computed. Models were fit for the main effects of the DRD4 genotype (presence or absence of the 7r allele) and regulatory problems (presence or absence), with the addition of the interaction term. All models were controlled for sex, family adversity, and obstetric risk status.Results: In children without the DRD4-7r allele, a history of regulatory problems in infancy was unrelated to later ADHD. But in children with regulatory problems in infancy, the additional presence of the DRD4-7r allele increased the risk for ADHD in childhood.Conclusions: The DRD4 genotype seems to moderate the association between regulatory problems in infancy and later ADHD. A replication study is needed before further conclusions can be drawn, however.

Distinct Abnormalities in the Innate Immune System of Children with Down Syndrome - Corrected Proof

Beatrijs L.P. Bloemers, Grada M. van Bleek, Jan L.L. Kimpen, Louis Bont — 2010-02-22

Objective: To analyze the frequency and phenotype of cells of the innate immune system in the peripheral blood of children with Down syndrome (DS).Study design: Flow cytometric analysis of expression of cell surface markers was performed in children with DS (n = 41) and healthy age-matched controls (n = 41).Results: Compared with controls, children with DS had significantly lower absolute total leukocyte counts, lymphocytes, monocytes, and granulocytes, but 1.5-times higher absolute numbers of CD14dimCD16+ monocytes (147 × 106/L vs 93 × 106/L; P = .02). This difference is fully explained by a higher percentage of CD14dimCD16+ monocytes within the monocyte compartment (28.7% vs 13.4%; P <.001). The absolute numbers of myeloid dendritic cells were lower in DS (13.8 × 106/L vs 22.7 × 106/L; P <.001). The numbers of plasmacytoid dendritic cells and natural killer cells were normal. Absolute numbers of invariant natural killer T cells were very low overall, but significantly lower in children with DS than in controls (1.2 × 106/L vs 3.7 × 106/L; P = .01).Conclusions: Children with DS exhibited distinct abnormalities in cells of the innate immune system. Most strikingly, they had a high number of proinflammatory CD14dimCD16+ monocytes. This elevated level of CD14dimCD16+ monocytes may play an important role in the onset and maintenance of chronic inflammatory disease in DS.

Elevated Serum IL-8 Levels in Ataxia Telangiectasia - Corrected Proof

2010-02-22

Serum interleukin (IL)-8 levels were measured in 50 patients with ataxia telangiectasia (A-T) and 22 without A-T. In a cross-sectional study, the geometric mean of IL-8 level was significantly higher in the patients with A-T (P <.0001). Elevated serum IL-8 levels in patients with A-T suggest that systemic inflammation may contribute to the disease phenotype.

The Rate of Bloodstream Infection Is High in Infants with Short Bowel Syndrome: Relationship with Small Bowel Bacterial Overgrowth, Enteral Feeding, and Inflammatory and Immune Responses - Corrected Proof

2010-02-22

Objective: This pilot study in parenteral nutrition–dependent infants with short bowel syndrome (SBS) evaluated the impact of feeding route and intestinal permeability on bloodstream infection (BSI), small bowel bacterial overgrowth (SBBO), and systemic immune responses, as well as fecal calprotectin as a biomarker for SBBO.Study design: Ten infants (ages 4.2-15.4 months) with SBS caused by necrotizing enterocolitis were evaluated. Nutritional assessment, breath hydrogen testing, intestinal permeability, fecal calprotectin, serum flagellin- and lipopolysaccharide-specific antibody titers, and proinflammatory cytokine concentrations (tumor necrosis factor–α [TNF-α], interleukin-1 β, -6, and -8) were performed at baseline and at 60 and 120 days. Healthy, age-matched control subjects (n = 5) were recruited.Results: BSI incidence was high (80%), and SBBO was common (50%). SBBO increased the odds for BSI (>7-fold; P = .009). Calprotectin levels were higher in children with SBS and SBBO versus those without SBBO and healthy control subjects (P < .05). Serum TNF-α, was elevated at baseline versus controls. Serum TNF-α and interleukin-1 β, -6, and -8 levels diminished with increased enteral nutrition. Anti-flagellin and anti-lipopolysaccharide immunoglobulin G levels in children with SBS were lower versus control subjects and rose over time.Conclusion: In children with SBS, SBBO increases the risk for BSI, and systemic proinflammatory response decreases with increasing enteral feeding and weaning parenteral nutrition.

Suspected foreign body inhalation in children: What are the indications for bronchoscopy? - Corrected Proof

John Massie, Michelle Fink — 2010-02-22

To the Editor: Cohen et al should be congratulated on presenting such a clear approach to inhaled foreign bodies in children. Their study systematizes what has been our clinical approach over many years, emphasizing the importance of the initial history of aspiration and the presence of ongoing cough (or sudden onset of cough in the absence of a witnessed aspiration event), particularly in the toddler. Physical examination of the chest and chest radiography are important too but are less likely to be positive. Their article, however, gives no detail about the chest radiograph requested. The traditional teaching was for an inspiratory and expiratory chest film to look for differential emptying of the lung on expiration created by a ball-valve effect on the affected side. Capturing the correct respiratory phase is nearly impossible from most toddlers, rendering the test unhelpful unless there is significant atelectasis (more often after prolonged aspiration) or a radiopaque foreign body (rare). Our practice is to request lateral decubitus films, which guarantees good emptying of the lungs on the dependent side to emphasize gas trapping. Can the authors clarify the chest radiography technique used in their study?

Association Between Peanut Allergy and Asthma Morbidity - Corrected Proof

Alyson B. Simpson, Ejaz Yousef, Jobayer Hossain — 2010-02-15

Objective: To evaluate the relationship between peanut allergy and asthma morbidity in school-age children.Study design: The study involved a medical chart review to assess the association of peanut allergy with asthma morbidity in children beyond age 3 years. Peanut allergy was assessed by specific and validated criteria. A Poisson regression model was used to compare the frequency of systemic steroid use and of hospitalization for asthma beyond age 3 years in children with asthma with and without peanut allergy.Results: Children with peanut allergy had a 2.32-times greater rate of hospitalization (P = .03) and a 1.59-times greater rate of systemic steroid use (P <.001) after controlling for covariates.Conclusions: Peanut allergy serves as an early marker for asthma morbidity. Early prevention and intervention can improve quality of care.

Antithrombotic Treatment in Neonatal Cerebral Sinovenous Thrombosis: Results of the International Pediatric Stroke Study - Corrected Proof

2010-02-11

Objective: To identify predictors of antithrombotic treatment in neonates with cerebral sinovenous thrombosis (CSVT) in a large multinational study.Study design: Neonates with CSVT from 10 countries were enrolled in the International Pediatric Stroke Study from 2003 through 2007. Term neonates with CSVT who presented with neurologic symptoms or signs of systemic illness and neuroimaging evidence of thrombus or flow interruption within cerebral venous system were included.Results: Of 341 neonates enrolled, 84 had isolated CSVT. Neuroimaging findings, available in 67/84 neonates, included venous ischemic infarction in 5, hemorrhagic infarction or other intracranial hemorrhage in 13, both infarction and hemorrhage in 26, and no parenchymal lesions in 23. Treatment data, available in 81/84 neonates, included antithrombotic medications in 52% (n = 43), comprising heparin (n = 14), low molecular weight heparin (n = 34), warfarin (n = 1), and aspirin (n = 2). By univariate logistic regression analysis, deep venous system thrombosis (P = .05) and location in the United States (P = .001) predicted nontreatment. Presence of infarction, hemorrhage, dehydration, systemic illness, and age did not predict treatment or nontreatment. In multivariate analysis only geographic location remained significant.Conclusions: In neonatal CSVT, regional antithrombotic treatment practices demonstrate considerable variability and uncertainty about indications for antithrombotic therapy. Additional studies are warranted.

Herpes Simplex Virus Testing and Hospital Length of Stay in Neonates and Young Infants - Corrected Proof

Samir S. Shah, Jessica Volk, Zeinab Mohamad, Richard L. Hodinka, Joseph J. Zorc — 2010-02-11

Objective: To examine whether ordering testing of cerebrospinal fluid (CSF) for herpes simplex virus (HSV) by polymerase chain reaction (PCR) in neonates and young infants is associated with increased hospital length of stay (LOS) or increased hospital charges.Study design: This retrospective cohort study enrolled infants age ≤56 days who underwent lumbar puncture in the emergency department in 2005-2006. The primary “exposure” was CSF HSV PCR, and the primary outcomes were LOS and hospital charges.Results: CSF HSV PCR was performed in 282 of 889 eligible infants (31.7%). The median test turnaround time was 22 hours. The median LOS was 2 days, and median hospital charge was $10 166. In multivariate analysis, CSF HSV PCR testing was associated with a LOS increase of 28% for infants age ≤28 days and 39% for infants age 29-56 days. LOS increased by 22% for every 12-hour increase in test turnaround time. CSF HSV PCR testing was associated with a 41% increase in hospital charges.Conclusions: In infants evaluated by lumbar puncture in the emergency department, CSF HSV PCR testing was associated with a significantly longer LOS and higher hospital charges.

Long-term Behavioral Consequences of Infant Feeding: The Limits of Observational Studies - Corrected Proof

Michael S. Kramer — 2010-02-11

Many studies have reported positive effects of breastfeeding (perhaps more appropriately denoted as negative effects of formula feeding) on cognitive ability. However, relatively few studies have examined the association between infant feeding and long-term child or adolescent behavior, and the results have been mixed. In this issue of The Journal, Oddy et al report the results of a large pregnancy/birth cohort study of this association, with follow-up of the offspring to age 14 years. This is clearly 1 of the best studies carried out in this area. Its strengths include a large sample size, high follow-up rates, prospective ascertainment of both exposure (infant feeding) and outcome (child behavior), repeated measures of a well-validated outcome measure (the Child Behavior Checklist), extensive measurement and control for a large number of potentially confounding variables, and statistical methods that account for the repeated measurements over time within the same cohort of children.

Two-Year Neurodevelopmental Outcomes of Ventilated Preterm Infants Treated with Inhaled Nitric Oxide - Corrected Proof

2010-02-08

Objective: In a randomized multi-center trial, we demonstrated that inhaled nitric oxide begun between 7 and 21 days and given for 24 days significantly increased survival without bronchopulmonary dysplasia (BPD) in ventilated premature infants weighing <1250 g. Because some preventative BPD treatments are associated with neurodevelopmental impairment, we designed a follow-up study to assess the safety of nitric oxide.Study design: Our hypothesis was that inhaled nitric oxide would not increase neurodevelopmental impairment compared with placebo. We prospectively evaluated neurodevelopmental and growth outcomes at 24 months postmenstrual age in 477 of 535 surviving infants (89%) enrolled in the trial.Results: In the treated group, 109 of 243 children (45%) had neurodevelopmental impairment (moderate or severe cerebral palsy, bilateral blindness, bilateral hearing loss, or score <70 on the Bayley Scales II), compared with 114 of 234 (49%) in the placebo group (relative risk, 0.92; 95% CI, 0.75-1.12; P = .39). No differences on any subcomponent of neurodevelopmental impairment or growth variables were found between inhaled nitric oxide or placebo.Conclusions: Inhaled nitric oxide improved survival free of BPD, with no adverse neurodevelopmental effects at 2 years of age.

A Follow-up Study of Preterm Infants Given Budesonide Using Surfactant as a Vehicle to Prevent Chronic Lung Disease in Preterm Infants - Corrected Proof

Huang T. Kuo, Hong C. Lin, Chang H. Tsai, I.C. Chouc, Tsu F. Yeh — 2010-02-08

Objective: Our study of early intratracheal instillation of budesonide using surfactant as vehicle showed a significant decrease in death or chronic lung disease (CLD) in preterm infants with severe respiratory distress syndrome (RDS). We now report the long-term outcome at about 2 to 3 years of age.Study design: Of the 75 potential survivors, 67 (90%) were studied (35 budesonide-treated, 32 control). All infants had birth weight <1500 g and had severe RDS requiring intermittent mechanical ventilation shortly after birth. The treated group received a mixture of budesonide and surfactant every 8 hours. The control group received only surfactant.Results: The physical growth and the neurological examinations were comparable between the groups at follow-up. Infants in the group treated with budesonide tended to have higher PDI and MDI scores than infants in the control group (79 ± 20 vs 74 ± 18 and 80 ± 19 vs 75 ± 20), but these differences were not statistically significant. The incidence of neurodevelopmental impairment was 11 (31%) in the treated group and 13 (40%) in the control group (P = .367).Conclusions: Early intratracheal instillation of budesonide using surfactant as a vehicle significantly improved pulmonary outcome without causing long-term adverse effects.

Dietary and Physical Activity Patterns in Children with Obstructive Sleep Apnea - Corrected Proof

2010-02-08

Objective: To assess dietary and physical activity patterns and morning circulating blood levels of the orexigenic hormones ghrelin and visfatin in children with either obesity, obstructive sleep apnea (OSA), or both conditions.Study design: In this cross-sectional design, 5- to 9-year-old participants (n = 245) from the community were identified. After overnight polysomnography, caregivers filled out a food and physical activity questionnaire, and the child underwent a fasting blood draw for ghrelin and visfatin plasma levels.Results: Compared with control subjects, obese children with OSA ate 2.2-times more fast food, ate less healthy food such as fruits and vegetables, and were 4.2-times less frequently involved in organized sports. OSA was positively correlated with plasma ghrelin levels (R2, 0.73; P < .0001), but not visfatin levels, particularly when obesity was present.Conclusion: OSA and obesity in children may adversely impact dietary preferences and may be particularly detrimental to daily physical activity patterns. Furthermore, increased ghrelin levels support the presence of increased appetite and caloric intake in obese patients with OSA, which in turn may further promote the severity of the underlying conditions.

Bacterial Enteritis as a Risk Factor for Childhood Intussusception: A Retrospective Cohort Study - Corrected Proof

Cade M. Nylund, Lee A. Denson, James M. Noel — 2010-02-08

Objective: To assess the relationship between bacterial enteritis and intussusception.Study design: The Patient Administration Systems and Biostatistics Activity database from January 2002 to December 2005 was examined for clinic visits or hospital admission to a Department of Defense medical facility for children age 0-5 years. The study included the International Statistical Classification of Diseases and Related Health Problems diagnosis-related group (DRG) codes for infections with Yersinia enterocolitica, Escherichia coli, Shigella species, Salmonella species, and Campylobacter. Identified patients were then assessed for the intussusception DRG code for 0-180 days postinfection. The total number of children enrolled in military treatment facilities in the same age group (denominator) was obtained.Results: Bacterial enteritis significantly increased the relative risk of intussusception. An increased risk was found following infection with Salmonella, E coli, Shigella, and Campylobacter. The relative risk for intussusception following any bacterial enteritis was 40.6 (95% confidence interval = 28.6-57.5; P < .0001).Conclusions: Bacterial enteritis is a significant risk factor for the subsequent development of intussusception in children.

MEALTRAIN: What Do Inpatient Hospitalized Children Choose to Eat? - Corrected Proof

2010-02-08

Data from the menu ordering system was used to calculate servings/child/day of food groups ordered by pediatric inpatients. The children ordered a mean of 5.0 ± 0.56 servings of fruits and vegetables/day, which decreased to 3.5 ± 0.27 servings when juice was removed. “Foods-to-limit” were ordered 3.8 ± 0.31 times/day. Interventions to improve healthier choices are warranted.

Muscular dystrophy revealed by incidentally discovered elevated aminotransferase levels - Corrected Proof

Pietro Vajro, Ennio Del Giudice, Claudio Veropalumbo — 2010-02-08

To the Editor: We read with interest the report by Ciafaloni et al and the related editorial by Kaufmann on the persisting delay (approximately 2.5 years) between the onset of symptoms and time of definitive diagnosis of Duchenne/Becker Muscular Dystrophy (DBMD), because of the frequent misdiagnosis with motor or global developmental delay. We call the attention to another possible confounding factor not mentioned by the authors.

Randomized trial of adenotonsillectomy versus expectant treatment in PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome: Is the impasse over? - Corrected Proof

Bhavneet Bharti, Sahul Bharti — 2010-02-08

To the Editor: The results of an interesting study by Garavello et al comparing adenotonsillectomy in children who have PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome with expectant treatment can be aptly described as an absolute risk reduction of 58% (95% CI, 29%-76%) in PFAPA episodes on 18-month follow-up and a number needed to treat of 2 (95% CI, 1-3). This very large effect size, however, needs to be triangulated in the light of some perspectives on the study. First, a surgical failure rate of 37% (95% CI, 19%-59%; 7 of 19 had PFAPA recurrences) in the first year may not be clinically acceptable for a benign disorder characterized by self-resolving episodes responding strikingly to single dose of oral corticosteroid, no short- and long-term physical consequences, and also, the propensity to outgrow the problem by the age of 10 years. Second, because the primary outcome was resolution or recurrence of episodes on follow-up, the choice of control group patients with only expectant treatment (ie, oral corticosteroid) seems methodologically less efficient. A more active control group with the use of a prophylactic drug like cimetidine (with 29% event resolution) was warranted because the use of episode-ameliorating corticosteroid can escalate recurrences in some patients. Third, the duration of the episode-free period was compared with the t test, completely ignoring the skewed nature of such time-related data and presence of right censoring when patients had complete resolution. Ideally, this important outcome should have been compared more reliably by using Kaplan Meier survival analysis. Finally, the study fails to address the superiority of combined adenotonsillectomy compared with tonsillectomy alone (64%-100% efficacy), appropriate age of surgical intervention, and incremental cost-effectiveness in terms of costs per episode averted. To conclude, potentially modest benefits of adenotonsillectomy in PFAPA need to be weighed against the benign nature and heterogeneity of episode recurrence, comparative cost-effectiveness with medical therapy, and risk of surgery in centers with less experience.

Array Comparative Genomic Hybridization as a Diagnostic Tool for Syndromic Heart Defects - Corrected Proof

2010-02-08

Objectives: To investigate different aspects of the introduction of array comparative genomic hybridization (aCGH) in clinical practice.Study design: A total 150 patients with a syndromic congenital heart defect (CHD) of unknown cause were analyzed with aCGH at 1-Mb resolution. Twenty-nine of these patients, with normal results on 1Mb aCGH, underwent re-analysis with 244-K oligo-microarray. With a logistic regression model, we assessed the predictive value of patient characteristics for causal imbalance detection. On the basis of our earlier experience and the literature, we constructed an algorithm to evaluate the causality of copy number variants.Results: With 1-Mb aCGH, we detected 43 structural variants not listed as clinically neutral polymorphisms, 26 of which were considered to be causal. A systematic comparison of the clinical features of these 26 patients to the remaining 124 patients revealed dysmorphism as the only feature with a significant predictive value for reaching a diagnosis with 1-Mb aCGH. With higher resolution analysis in 29 patients, 75 variants not listed as clinically neutral polymorphisms were detected, 2 of which were considered to be causal.Conclusions: Molecular karyotyping yields an etiological diagnosis in at least 18% of patients with a syndromic CHD. Higher resolution evaluation results in an increasing number of variants of unknown significance.

Perspectives and Preferences among the General Public Regarding Physician Selection and Board Certification - Corrected Proof

2010-02-08

Objectives: To characterize parental attitudes regarding board certification and other factors that influence selection of physicians to care for children.Study design: A web-based survey administered in 2008 to a random sample of 3621 adults ≥18 years of age stratified by parents and non-parents. Proportion of respondents who view board certification and other measures of quality as important factors in selecting a physician to care for children.Results: Survey completion rate was 62%. Almost all (95%) believe it is important or very important for doctors who care for children to be assessed on their quality of care, receive high ratings from patients (91%), and pass a written test at regular intervals (88%). Most reported that recommendations from friends or family (84%) and board certification (82%) were important or very important factors in choosing a physician for their child. Seventy-seven percent of parents stated that they would be likely to change their child's physician if he/she did not maintain board certificationConclusion: Parents report a preference for board-certified physicians and expect them to participate in Maintenance of Certification. Greater understanding of quality measures and the board certification process would empower consumers to make more informed decisions in selecting a physician for their children.

Reply - Corrected Proof

Werner Garavello, Renato Maria Gaini — 2010-02-08

To the Editor: We thank Bharti et al for their interest in our article, and we completely share the sentiment of the provocative title of their Letter to the Editor. The impasse is not over yet!

Traumatic Delivery, Diaphragmatic Paresis, and “Dextrocardia” - Corrected Proof

Nicholas M. Allen, Tom Clarke, Stephanie P. Ryan, Ireti Farombi-Oghuvbu — 2010-02-08

A term male infant weighing 4170 g was delivered vaginally, by forceps extraction. Apgar scores and cord blood pHs were normal. He was noted to have a left-sided Erb's palsy, tachypnea, and mild chest recession. Oxygen saturations were 87% in room air, and the initial chest radiograph showed an elevated left hemi-diaphragm with mediastinal shift to the right (). Fluoroscopy screening of the diaphragm demonstrated paradoxical movement of the left hemi-diaphragm consistent with left diaphragmatic paresis. He improved clinically and was discharged home after 9 days. Both the diaphragmatic paresis and the Erb's palsy had resolved by 3 months of age.

Long-Term Treatment of Cystinosis in Children with Twice-Daily Cysteamine - Corrected Proof

2010-02-08

Objective: Cystinosis causes renal and other organ failure. Treatment with 6-hourly cysteamine bitartrate (Cystagon, Mylan, Morgantown, West Virginia) reduces intracellular cystine and the rate of organ deterioration. A recent study showed that an enteric-release cysteamine required less frequent daily dosing. This report describes the long-term use of enteric-coated (EC) cysteamine bitartrate (Cystagon) in children with cystinosis.Study design: After a pharmacokinetic and pharmacodynamic study of EC-cysteamine in children with cystinosis, 5 patients remained on twice-daily treatment. White blood cell cystine levels were measured 12 hours after ingestion every 4 to 8 weeks. These levels were then compared with the patient's previous 6-h post-dose levels taken while on regular cysteamine bitartrate before entering the study. Blood chemistry was also measured.Results: Five children with cystinosis (mean age, 9 years; range, 8 to 17 years) who previously took cysteamine bitartrate (mean dose, 47 mg/kg body wt), received EC-cysteamine for 10 to 27 months (mean dose, 25 mg/kg body wt) and had mean white blood cell cystine levels of 0.77 and 0.71 nmol half-cystine/mg protein, respectively. During the study period, patients maintained adequate growth and there was no significant deterioration in renal or thyroid function. Two children were required to restart acid suppression after 6 months on EC-cysteamine therapy.Conclusions: Long-term, twice-daily EC-cysteamine, given at approximately 60% of the previous daily dose of cysteamine bitartrate, was effective at maintaining white blood cell cystine levels within a satisfactory range. There was no significant deterioration in renal or thyroid function.

Prevalence of Congenital Heart Disease at Live Birth in Taiwan - Corrected Proof

2010-02-08

Objectives: To investigate the prevalence at live birth of congenital heart disease (CHD) in Taiwan.Study design: Patients with CHD born from 2000 to 2006 were identified from National Health Insurance databases.Results: CHD prevalence was 13.08 per 1000 live births: 12.05 (simple, 10.53; severe, 1.51) in male infants and 14.21 (simple, 12.90; severe, 1.32) in female infants. Ventricular septal defect (VSD; 4.0) was the most common defect, followed by secundum atrial septal defect (ASDII; 3.2), patent ductus arteriosus (PDA; 2.0), pulmonary stenosis (PS; 1.2), tetralogy of Fallot (TOF; 0.63), coarctation of aorta (CoA; 0.25), transposition of great arteries (TGA; 0.21), endocardial cushion defect (ECD; 0.20), double outlet of right ventricle (DORV; 0.15), total anomalous pulmonary venous return (TAPVR; 0.11), aortic stenosis (0.09), hypoplastic left heart syndrome (HLHS; 0.062), Ebstein anomaly (0.047), and tricuspid atresia (0.046). Female predominance was observed in VSD, ASDII, PDA, and ECD; and male predominance was observed in TGA and TOF. Ratios of western prevalence to our Asian prevalence were high for HLHS (3.68-4.5), CoA (1.13-1.96), TGA (1.09-1.83), and tricuspid atresia (1.09-2.57), but low for PS (0.15-0.99), TOF (0.41-0.92), and possibly ASDII.Conclusions: In this Asian population, the prevalence of CHD was at the high end of the reported range, with more PS and TOF, but fewer left-sided obstructions, TGA, and tricuspid atresia.

Susceptibility-Weighted Imaging in Neurodegeneration in Langerhans Cell Histiocytosis - Corrected Proof

Gulhan Ertan, Thierry A.G.M. Huisman — 2010-02-08

A 15-year-old boy with confirmed Langerhans cell histiocytosis (LCH) was referred for magnetic resonance imaging (MRI). Conventional MRI, using T1- and T2-weighted sequences, detected bilateral T2-hyperintense and T1-hypointense, non-contrast-enhancing signal alterations within the pons, dentate nuclei, and adjacent cerebellar white matter (). In addition, discrete T1-hyperintense calcifications were noted in the globus pallidus. These lesions represent the classical pattern of neurodegeneration in LCH (ND-LCH).

Risk Factors for Short- and Long-Term Morbidity in Children with Esophageal Atresia - Corrected Proof

Julie Castilloux, Angela J. Noble, Christophe Faure — 2010-02-02

Objective: To describe short- (first year of age) and long-term (after 1 year of age) outcome in patients with esophageal atresia and identify early predictive factors of morbidity in the first month of life.Study design: Charts of children with esophageal atresia born January 1990 to May 2005 were reviewed. A complicated evolution was defined as the occurrence of at least 1 complication: severe gastroesophageal reflux, esophageal stricture requiring dilatations, recurrent fistula needing surgery, need for gavage feeding for ≥3 months, severe tracheomalacia, chronic respiratory disease, and death.Results: A total of 134 patients were included. Forty-nine percent of patients had a complicated evolution before 1 year of age, and 54% had a complicated evolution after 1 year. With bivariate analysis, predictive variables of a complicated evolution were demonstrated, including twin birth, preoperative tracheal intubation, birth weight <2500 g, long gap atresia, anastomotic leak, postoperative tracheal intubation ≥5 days, and inability to be fed orally by the end of the first month. After 1 year of age, the complicated evolution was only associated with long gap atresia and inability to be fed orally in the first month. A hospital stay ≥30 days was associated with a risk of a complicated evolution at 1 year and after 1 year of age (odds ratio, 9.3 [95% CI, 4.1-20.8] and 3.5 [95% CI, 1.6-7.6], respectively).Conclusion: Early factors are predictive of morbidity in children with esophageal atresia.

Health-Related Quality of Life Across Pediatric Chronic Conditions - Corrected Proof

2010-02-01

Objective: To compare health-related quality of life (HRQOL) across 8 pediatric chronic conditions, including 5 understudied populations, and examine convergence between youth self-report and parent-proxy report.Study design: Secondary data from 589 patients and their caregivers were collected across the following conditions: obesity, eosinophilic gastrointestinal disorder, inflammatory bowel disease, epilepsy, type 1 diabetes, sickle cell disease, post–renal transplantation, and cystic fibrosis. Youth and caregivers completed age-appropriate self-report and/or parent-proxy report generic HRQOL measures.Results: Youth diagnosed with eosinophilic gastrointestinal disorder and obesity had lower HRQOL than other pediatric conditions by parent report. Caregivers reported lower HRQOL by proxy report than youth self-reported across most subscales.Conclusions: Use of brief, easily administered, and reliable assessments of psychosocial functioning, such as HRQOL, may provide clinicians additional opportunities for intervention or services targeting improved HRQOL relative to the needs of each population.

Birth Weight, Family History of Diabetes, and Metabolic Syndrome in Children and Adolescents - Corrected Proof

2010-01-28

Objective: To evaluate whether a coupled family history of diabetes (FHD) and low birth weight (LBW) or high birth weight (HBW) is associated with metabolic syndrome (MetS) in children and adolescents.Study design: A total of 1262 children and adolescents age 7-15 years were randomly selected to enroll in this cross-sectional, community-based study.Results: In the overall population, HBW (odds ratio [OR] = 1.4; 95% confidence interval [CI] = 1.2-10.9), but not LBW (OR = 0.97; 95% CI = 0.6-2.1), was significantly associated with MetS. In the group without FHD, HBW (OR = 1.730; 95% CI = 1.1-2.7), but not LBW (OR = 1.139; 95% CI = 0.7-23), was associated with MetS. In the group with FHD, both LBW (OR = 2.690; 95% CI = 1.4-15.1) and HBW (OR = 3.289; 95% CI = 1.3-30.6) were associated with MetS. Both LBW (OR = 4.710; 95% CI = 1.4-39.7) and HBW (OR = 3.127; 95% CI = 1.3-45.1) were associated with MetS in children and adolescents with FHD in the maternal branch but not in the paternal branch.Conclusions: HBW or LBW, in combination with positive FHD in the maternal branch, are determinants of MetS.

Renal, Pancreatic, Splenic, Mesenteric, and Portal Venous Gas as a Sign of Intestinal Necrosis - Corrected Proof

Dan Arbell, Ram Elazary, Benjamin Z. Koplewitz — 2010-01-27

A 14-year-old boy presented with acute abdominal distention causing a severe restrictive respiratory distress that necessitated endotracheal intubation, diffuse peritoneal irritation, and profound metabolic acidosis. The boy had Waardenburg syndrome, a rare autosomal dominant inherited disorder, with severe hypopigmentation, hearing loss, limb abnormalities, and mental retardation, but without previously identified gastrointestinal involvement.

Thrombocytopenic Purpura after Measles-Mumps-Rubella Vaccination: A Systematic Review of the Literature and Guidance for Management - Corrected Proof

Elpis Mantadakis, Evangelia Farmaki, George R. Buchanan — 2010-01-25

Objective: To determine the incidence of immune thrombocytopenic purpura (ITP) after measles-mumps-rubella (MMR) immunization compared with natural measles and rubella, its clinical course and outcome, and the risk of recurrence after repeat MMR vaccination.Study design: We performed a systematic review of the Ovid MEDLINE (1950 to present) bibliographic database. We selected studies that reported cases of thrombocytopenia in a known number of children who were immunized with MMR vaccine before development of ITP. We also extracted data from the same and other studies regarding bleeding manifestations and the resolution of MMR-associated thrombocytopenia or thrombocytopenic purpura within 6 months. Finally, we studied the risk of ITP recurrence after MMR immunization or reimmunization.Results: On the basis of 12 studies, the incidence of MMR-associated ITP ranged from 0.087 to 4 (median 2.6) cases per 100 000 vaccine doses. Severe bleeding manifestations were rare, and MMR-associated thrombocytopenia resolved within 6 months from diagnosis in 93% of the children. MMR vaccination of unimmunized patients with ITP and revaccination of patients with prior ITP did not lead to recurrence of thrombocytopenia.Conclusions: MMR-associated ITP is rare, self-limited, and non-life threatening, and susceptible children with ITP should be immunized with MMR at the recommended ages.

Predicting Liver Failure in Parenteral Nutrition-Dependent Short Bowel Syndrome of Infancy - Corrected Proof

2010-01-25

Objectives: To test the hypothesis that early trends in common blood tests may delineate risks of liver failure (LF) in infants with parenteral nutrition-associated liver disease (PNALD) from short bowel syndrome and suggest criteria for transplant referral.Study design: Total levels of bilirubin, gamma-glutamyl transferase, albumin, alanine aminotransferase, platelet count, and absolute neutrophil count were recorded every 3 months for 61 infants with PNALD who were being considered for intestinal transplant starting at age 3 months until death without transplant (n = 12), LF with transplant (n = 35), or liver recovery without transplant (n = 14). Probabilities of LF were determined with logistic regression.Results: Independent predictors of LF were, in descending order, total bilirubin level (odds ratio [OR] = 1.195), platelet count (OR = 0.992), and albumin level (OR = 0.248). Predicted probabilities of eventual LF varied from 36% to 38% at ages 3 to 6 months when the total bilirubin level was 6.0 mg/dL, platelet count was 220 x 103/μL, and albumin level was 3.5 g/dL to 83% to 84% when the total bilirubin level was 11.7 mg/dL, platelet count was 168 x 103/μL, and albumin level was 3.0 g/dL.Conclusions: Transplant referral for a total bilirubin level of 6 mg/dL between 3 to 6 months of age is appropriate, because the probability of LF is at least 36%.

Small Volumes of Feed Can Trigger Transient Lower Esophageal Sphincter Relaxation and Gastroesophageal Reflux in the Right Lateral Position in Infants - Corrected Proof

2010-01-25

Objective: To investigate the threshold amount of constantly infused feed needed to trigger lower esophageal sphincter relaxation (TLESR) in the right lateral position (RLP) and left lateral position (LLP).Study design: Eight healthy infants (3 male; gestational age: 32.9 ± 2.4 weeks; corrected age: 36.1 ± 1.3 weeks) were studied using an esophageal impedance-manometry catheter incorporating an intragastric infusion port. After tube placement, infants were randomly positioned in RLP or LLP. They were then tube-fed their normal feed (62.5 [40 to 75] mL) at an infusion rate of 160 mL/h. Recordings were made during the feed and 15 minutes thereafter. The study was repeated with the infant in the opposite position.Results: More TLESRs were triggered in the RLP compared with LLP (4.0 [3.0 to 6.0] vs 2.5 [1.0 to 3.0], P = .027). First TLESR occurred at a significantly lower infused volume in RLP compared with LLP (10.6 ± 9.4 vs 21.0 ± 4.9 mL, P = .006). The percentage of feed infused at time of first TLESR was significantly lower in RLP compared with LLP (17.6% ± 15.5% vs 35.4% ± 8.02%, P = .005).Conclusions: In the RLP, TLESRs and gastroesophageal reflux are triggered at volumes unlikely to induce gastric distension.

Four-Year Prospective Clinical Trial of Agalsidase Alfa in Children with Fabry Disease - Corrected Proof

2010-01-25

Objectives: To investigate a 4-year prospective clinical trial of agalsidase alfa in children with Fabry disease, an X-linked metabolic disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A.Study design: Seventeen (16 boys, 1 girl; age range, 7.3 to 18.4 years) of the 24 children who completed a 6-month, open-label agalsidase alfa study enrolled in a 3.5-year extension study that investigated the safety and potential efficacy of long-term treatment. All 17 patients completed the initial 6-month study, and 10 patients (9 boys) completed the extension study.Results: Agalsidase alfa was well tolerated. In treated boys, there were sustained, statistically-significant improvements in the clinical features of Fabry disease, including reduced plasma globotriaosylceramide levels, reduced pain severity assessed by the Brief Pain Index, and improved heart rate variability. Mean urine globotriaosylceramide levels were reduced to normal range (P < .05 compared with baseline during 1.5 to 4 years). Kidney function and left ventricular mass indexed to height remained stable throughout.Conclusions: This clinical trial demonstrates that treatment with agalsidase alfa was well tolerated and associated with improvement of Fabry disease–related features.

Prevalence of Increased Arterial Stiffness in Children with Type 1 Diabetes Mellitus Differs by Measurement Site and Sex: The SEARCH for Diabetes in Youth Study - Corrected Proof

2010-01-25

Objective: To discuss vascular stiffness commonly encountered in children with type 1 diabetes mellitus (T1DM).Study design: We examined 535 subjects with T1DM (14.6 years; 53% male, 88% non-Hispanic white) and 241 healthy control subjects (17.8 years; 42% male, 39% non-Hispanic white). Abnormalities in brachial distensibility (BrachD), pulse wave velocity, and augmentation index corrected to a HR of 75 (AIx-75) were examined.Results: Subjects with T1DM had higher body mass index, LDL-cholesterol, fasting glucose, and blood pressure than control subjects. Diabetic subjects had lower BrachD and higher AIx-75 indicating increased stiffness. Age-adjusted pulse wave velocity–trunk (aorto-femoral) was higher in cases (all P ≤ < .05). Increased peripheral stiffness was more common than central stiffness in subjects with T1DM (low BrachD in 33% vs high PWV-trunk in 9.9%). Male subjects with type 1 diabetes had a higher prevalence of VS abnormalities than females. Presence of T1DM, male sex, and increased mean arterial pressure were the most consistent independent determinants of vascular stiffness.Conclusions: Increased vascular stiffness is present in youth with T1DM with peripheral abnormalities predominating especially in males. Traditional risk factors are important correlates. Identifying early vascular abnormalities in youth with T1DM will allow for implementation of more aggressive risk factor management.

Low Aerobic Fitness and Obesity Are Associated with Lower Standardized Test Scores in Children - Corrected Proof

Christian K. Roberts, Benjamin Freed, William J. McCarthy — 2010-01-25

Objective: To investigate whether aerobic fitness and obesity in school children are associated with standardized test performance.Study design: Ethnically diverse (n = 1989) 5th, 7th, and 9th graders attending California schools comprised the sample. Aerobic fitness was determined by a 1-mile run/walk test; body mass index (BMI) was obtained from state-mandated measurements. California standardized test scores were obtained from the school district.Results: Students whose mile run/walk times exceeded California Fitnessgram standards or whose BMI exceeded Centers for Disease Control sex- and age-specific body weight standards scored lower on California standardized math, reading, and language tests than students with desirable BMI status or fitness level, even after controlling for parent education among other covariates. Ethnic differences in standardized test scores were consistent with ethnic differences in obesity status and aerobic fitness. BMI-for-age was no longer a significant multivariate predictor when covariates included fitness level.Conclusions: Low aerobic fitness is common among youth and varies among ethnic groups, and aerobic fitness level predicts performance on standardized tests across ethnic groups. More research is needed to uncover the physiological mechanisms by which aerobic fitness may contribute to performance on standardized academic tests.

A Severe Form of Kawasaki Disease Presenting with Only Fever and Cervical Lymphadenopathy at Admission - Corrected Proof

2010-01-25

Objective: To examine the characteristics of patients with Kawasaki disease (KD) presenting with only fever and cervical lymphadenopathy at admission.Study design: The laboratory and clinical findings of patients with definite KD presenting with only fever and cervical lymphadenopathy at admission (KDiL) were compared with those of all other patients with KD.Results: Sixteen patients with KDiL (8.6%) and 171 patients without KDiL were examined. The patients with KDiL were significantly older (KDiL/non-KDiL: 4.9±2.5/2.2±1.9 years) and admitted earlier (3.0±1.2/3.9±1.3 days of illness) than the patients without KDiL. They also showed significantly elevated white blood cell counts and C-reactive protein levels. Patients with KDiL were treated with the same dose of intravenous immunoglobulin as the patients without KDiL but were treated slightly later and had significantly higher frequency of additional intravenous immunoglobulin treatment (38%/10%) and coronary artery abnormalities (25%/5%). After adjustment for age, white blood cell count, and day of illness at admission or first intravenous immunoglobulin administration, the presence of KDiL significantly increased the risk of being a nonresponder to IVIG treatment or development of a coronary artery abnormality.Conclusions: KDiL indicates a severe form of KD associated with increased risks of additional intravenous immunoglobulin treatment and coronary artery abnormalities. Patients with KDiL may require heightened surveillance and more aggressive treatment.

Early Emerging Nicotine-Dependence Symptoms: A Signal of Propensity for Chronic Smoking Behavior in Adolescents - Corrected Proof

Lisa Dierker, Robin Mermelstein — 2010-01-25

Objective: To evaluate the predictive validity of nicotine-dependence symptoms in 9th- and 10th-grade adolescents.Study design: A total of 594 adolescents who had not smoked more than 100 cigarettes in their lifetime and 152 adolescents who had smoked more than 100 cigarettes in their lifetime were included in the analysis. The predictive validity of 10 nicotine-dependence items administered at baseline was evaluated at the 24-month follow-up assessment.Results: For those who smoked fewer than 100 cigarettes, higher levels of experienced nicotine-dependence symptoms at baseline, as well as individual symptoms, predicted current and daily smoking behavior at the 24-month follow-up, over and above baseline smoking. For adolescents who had smoked more than 100 cigarettes at baseline, the level of nicotine dependence and individual symptom endorsement did not predict smoking behavior at the 24-month follow-up.Conclusions: Our findings demonstrate that early emerging dependence symptoms reported at low levels of smoking exposure signal a greater propensity for continued smoking behavior not accounted for by current or past smoking exposure. Screening for these early emerging symptoms among novice adolescent smokers represents an important and unused tool in tobacco control efforts aimed at preventing the development of chronic smoking patterns.

Common Variants Near Melanocortin 4 Receptor Are Associated with General and Visceral Adiposity in European- and African-American Youth - Corrected Proof

2010-01-13

Objective: Recent genome-wide association studies found common variants near the melanocortin 4 receptor gene associated with obesity. This study aimed to assess the influence of the identified single nucleotide polymorphisms rs17782313 and rs17700633 on general and visceral adiposity in European- and African-American youth.Study design: In 1890 youth (49.1% European-American, 45.6% male, mean age 16.7 years), we examined the associations of the rs17782313 and rs17700633 with anthropometry, percent body fat, visceral adipose tissue, and subcutaneous abdominal adipose tissue. Interaction of the single nucleotide polymorphisms with ethnicity or sex was investigated and haplotype analyses conducted.Results: Rs17782313 was significantly associated with weight (P = .02) and waist circumference (P = .03) in all subjects and with body mass index (P = .002) in females. In females rs17700633 was significantly associated with percent body fat (P = .001), visceral adipose tissue (P < .001), and subcutaneous abdominal adipose tissue (P < .001). Rs17700633 was significantly associated with fasting insulin and homeostasis model assessment, but the significance attenuated after adjustment for percent body fat. These findings were confirmed by haplotype analysis. No significant interactions of the variants with ethnicity were found for any of these phenotypes.Conclusions: The relatively large effect of these common variants near melanocortin 4 receptor on general and visceral adiposity in childhood, especially in girls, could prove helpful in elucidating the molecular mechanisms underlying the development of obesity in early life.