The Journal of Pediatrics - Articles in Press

Hypoglycemia is Associated with Increased Risk for Brain Injury and Adverse Neurodevelopmental Outcome in Neonates at Risk for Encephalopathy - Corrected Proof

2012-02-10

Objective: To investigate the contribution of hypoglycemia in the first 24 hours after birth to brain injury in term newborns at risk for neonatal encephalopathy.Study design: A prospective cohort of 94 term neonates born between 1994 and 2010 with early postnatal brain magnetic resonance imaging studies were analyzed for regions of brain injury. Neurodevelopmental outcome was assessed at 1 year of age.Results: Hypoglycemia (glucose <46 mg/dL) in the first 24 hours after birth was detected in 16% of the cohort. Adjusting for potential confounders of early perinatal distress and need for resuscitation, neonatal hypoglycemia was associated with a 3.72-fold increased odds of corticospinal tract injury (P=.047). Hypoglycemia was also associated with 4.82-fold increased odds of 1-point worsened neuromotor score (P=.038) and a 15-point lower cognitive and language score on the Bayley Scales of Infant Development (P=.015).Conclusion: Neonatal hypoglycemia is associated with additional risks in the setting of neonatal encephalopathy with increased corticospinal tract injury and adverse motor and cognitive outcomes.

Zinc Protoporphyrin–to–Heme Ratios in High-Risk and Preterm Infants - Corrected Proof

Carissa F. Cheng, Joan C. Zerzan, Donna B. Johnson, Sandra E. Juul — 2012-02-10

Objectives: To refine the reference range for the zinc protoporphyrin–to–heme ratio (ZnPP/H) of preterm infants, we assessed the impact of maternal risk factors on ZnPP/H and evaluated the impact of changes in iron supplementation on iron status.Study design: The reference range for neonatal ZnPP/H was refined using prospective data from 31 reference infants ≤35 weeks’ postmenstrual age (PMA) plus retrospective data from 51 infants <30 weeks’ PMA, and 59 infants 30-40 weeks’ PMA. Cord blood and first week of life values were compared when both were available. The impact of maternal risk factors was assessed by examining prospectively collected ZnPP/H from 48 high-risk infants. The effect of changing iron supplementation guidelines was evaluated by retrospective chart review of serial ZnPP/H from 194 infants.Results: Cord ZnPP/H was lower at 30-35 weeks’ gestation than at 24-26 weeks’ gestation (P = .01). Cord ZnPP/H values from insulin-dependent diabetic mothers were elevated compared with reference values. Changing the iron supplementation protocol was not associated with improved ZnPP/H measurements.Conclusions: Cord blood and postnatal reference ranges for ZnPP/H are defined. Iron balance depends on a complex interaction of prenatal and postnatal factors.

Lack of an Effect of Lactobacillus reuteri DSM 17938 in Preventing Nosocomial Diarrhea in Children: A Randomized, Double-Blind, Placebo-Controlled Trial - Corrected Proof

Monika Wanke, Hania Szajewska — 2012-02-10

Objective: To evaluate the efficacy of administering Lactobacillus reuteri DSM 17938 for the prevention of nosocomial diarrhea.Study design: Children (n = 106; aged 1-48 months) admitted to the hospital for reasons other than diarrhea were enrolled in a randomized, double-blind, placebo-controlled trial. They received L reuteri DSM 17938 at a dose of 108 colony-forming units (n = 54) or a placebo (n = 52) orally, once daily, for the duration of the hospital stay.Results: Data from all children were included in the final analysis. L reuteri DSM 17938 did not significantly affect the risk of developing nosocomial diarrhea, defined as 3 loose or watery stools per day in a 24-hour period that occurred >72 hours after admission (risk ratio 1.06, 95% CI 0.7-1.5) or rotavirus infection (1.04, 0.6-1.6). There was also no difference between the probiotic and placebo groups for any of the other secondary outcomes (ie, incidence of rotavirus infection, incidence of diarrhea, duration of diarrhea, incidence of recurrent diarrhea, incidence of chronic diarrhea, length of hospital stay in days, and frequency of need for rehydration). No adverse events were reported.Conclusion: In hospitalized children, the administration of L reuteri DSM 17938 compared with placebo had no effect on the overall incidence of nosocomial diarrhea, including rotavirus infection.

Oral Disposition Index in Obese Youth from Normal to Prediabetes to Diabetes: Relationship to Clamp Disposition Index - Corrected Proof

2012-02-10

Objective: We sought to assess the glucose disposition index using an oral glucose tolerance test (OGTT; oDI) compared with the glucose disposition index measured from the combination of the euglycemic-hyperinsulinemic and hyperglycemic clamps (cDI) in obese pediatric subjects spanning the range of glucose tolerance.Study design: Overweight/obese adolescents (n = 185) with varying glucose tolerance (87 normal, 54 impaired, 31 with type 2 diabetes, and 13 with type 1 diabetes) completed an OGTT and both a hyperinsulinemic-euglycemic and a hyperglycemic clamp study. Indices of insulin sensitivity and β-cell function were calculated, and 4 different oDI estimates were calculated as the products of insulin and C-peptide-based sensitivity and secretion indices.Results: Mirroring the differences across groups by cDI, the oDI estimates were greatest in normal glucose tolerance adolescents and lowest in type 2 diabetes mellitus and obese with type 1 diabetes mellitus adolescents. The insulin-based oDI estimates correlated with cDI overall (r ≥ 0.74, P < .001) and within each glucose tolerance group (r ≥ 0.40, P < .001). Also, oDI and cDI predicted 2-hour OGTT glucose similarly.Conclusions: The oDI is a simple surrogate estimate of β-cell function relative to insulin sensitivity that can be applied to obese adolescents with varying glucose tolerance in large-scale epidemiological studies where the applicability of clamp studies is limited due to feasibility, cost, and labor intensiveness.

Which Neuroprotective Agents are Ready for Bench to Bedside Translation in the Newborn Infant? - Corrected Proof

2012-02-10

Neonatal encephalopathy caused by perinatal hypoxia-ischemia in term newborn infants occurs in 1 to 3 per 1000 births and leads to high mortality and morbidity rates with life-long chronic disabilities. Although therapeutic hypothermia is a significant advance in the developed world and improves outcome, hypothermia offers just 11% reduction in risk of death or disability, from 58% to 47%. Therefore, there still is an urgent need for other treatment options. Further, there are currently no clinically established interventions that can be given antenatally to ameliorate brain injury after fetal distress.

Pediatric Sedation with Propofol—Continuing Evolution of Procedural Sedation Practice - Corrected Proof

Joseph P. Cravero — 2012-02-10

Propofol is a highly effective yet politically charged sedative-hypnotic. Disagreement over where it may be administered and by whom continues to generate attention, whether in a celebrity bedroom or in the magnetic resonance image scanner. The rapid onset and recovery kinetics of propofol, together with the absence of nausea or other emergence phenomena, create a highly desirable pharmacologic profile. On the other hand, the potency of propofol has lead to safety concerns over which specialists should be granted sedation privileges for its use. In this issue of The Journal of Pediatrics, Srinivasan et al describe the adverse events and interventions recorded during propofol procedural sedation delivered by pediatric hospitalists over almost 4 years. The authors should be complimented for reporting the outcomes of their practice and adding to the collected literature on propofol sedation. The data from this study are worth comment and discussion, both as an example of difficulties encountered with most pediatric sedation studies and as a reflection of the current status of propofol sedation administered by providers other than anesthesiologists.

Plasma Follistatin-Like Protein 1 is Elevated in Kawasaki Disease and May Predict Coronary Artery Aneurysm Formation - Corrected Proof

2012-02-10

Objective: To determine whether plasma levels of follistatin-like protein 1 (FSTL-1), a pro-inflammatory protein produced by mesenchymal tissue, including cardiac myocytes, correlate with the development of Kawasaki disease (KD) and coronary artery aneurysms (CAA).Study design: FSTL-1 plasma levels were measured serially with enzyme-linked immunosorbent assay in 48 patients with KD at time of diagnosis and, when available, 2 weeks, 6 weeks, and 6 months after onset of disease. These were compared with FSTL-1 plasma levels in 23 control subjects. Data were analyzed with generalized estimating equations.Results: Plasma FSTL-1 levels were elevated in patients with acute KD compared with control subjects (P = .0086). FSTL-1 levels remained significantly elevated at 2 weeks after disease onset, but returned to control levels by 6 months. Seven patients with CAA had significantly higher FSTL-1 levels at the time of diagnosis than patients in whom aneurysms did not develop (P = .0018). Sensitivity and specificity rates for CAA at a specific FSTL-1 cutoff point (178 ng/mL) were 85% and 71%.Conclusions: Plasma levels of FSTL-1 are elevated in acute KD and may predict cardiac morbidity in this disease. These results suggest a possible role for FSTL-1 in the formation of CAAs.

Reply - Corrected Proof

Rosemary D. Higgins, Tonse N.K. Raju, A. David Edwards — 2012-02-10

The National Institute of Child Health and Human Development Workshop summary reviewed the evidence for implementing hypothermia therapy for neonatal encephalopathy (NE) in low- and middle-income settings (although we said “countries,” we meant “settings”) for reasons noted in the report and supported with citations.

Parvovirus B19 and necrotizing enterocolitis in neonates - Corrected Proof

Orsolya Genzel-Boroviczény, Gundula Jäger, Hermann M. Schätzl — 2012-02-10

We read with interest the report by Blau et al regarding transfusion-related acute gut injury: A possible additional unexplored cause could be infection with parvovirus B through red blood cell transfusions. During an epidemic of necrotizing enterocolitis (NEC) lasting 8 weeks, we detected parvovirus B19 in blood and stool samples of 8 of 12 cases, whereas only 2 of the 32 healthy controls had a positive stool and none had a positive blood sample. The gestational age ranged from 27 to 32 weeks, with postnatal age from 4 days to 6 weeks. Six of the eight infants developed NEC within 1 week. Before the onset of symptoms, all infants had tolerated their enteral feedings well; one infant had never been fed. Stool and blood cultures were negative for other enteric pathogens and rotavirus. Subsequently, all blood transfusions were screened for parvovirus B19 DNA with polymerase chain reaction. Three of 36 transfusions were found to be positive for parvovirus B19. Blood transfusions from these 3 positive donors were given to 5 infants. One infant died of massive NEC 3 days after the transfusion; the other 4 infants did not develop any symptoms. We believe that there is evidence that parvovirus B19 infection can cause NEC in neonates and the virus can be transmitted via infected transfusions.

Breastfeeding Protects against Current Asthma up to 6 Years of Age - Corrected Proof

2012-01-30

Objective: To investigate the effects of breastfeeding on wheezing and current asthma in children 2 to 6 years of age.Study design: Infants (n=1105) were enrolled in a prospective birth cohort in New Zealand. Detailed information about infant feeding was collected using questionnaires administered at birth and at 3, 6, and 15 months. From this, durations of exclusive and any breastfeeding were calculated. Information about wheezing and current asthma was collected at 2, 3, 4, 5, and 6 years. Logistic regression was used to model associations between breastfeeding and outcomes with and without adjustment for confounders.Results: After adjustment for confounders, each month of exclusive breastfeeding was associated with significant reductions in current asthma from 2 to 6 years (all, P<.03). Current asthma at 2, 3, and 4 years was also reduced by each month of any breastfeeding (all, P<.005). In atopic children, exclusive breastfeeding for ≥3 months reduced current asthma at ages 4, 5, and 6 by 62%, 55%, and 59%, respectively.Conclusion: Breastfeeding, particularly exclusive breastfeeding, protects against current asthma up to 6 years. Although exclusive breastfeeding reduced risk of current asthma in all children to age 6, the degree of protection beyond 3 years was more pronounced in atopic children.

Vitamin A Supplementation Improves Retinal Function in Infants at Risk of Retinopathy of Prematurity - Corrected Proof

2012-01-30

Objective: Preterm infants show reduced retinal sensitivity at term corrected age compared with newborn term infants. We tested the hypothesis that retinal sensitivity in preterm infants is improved by early, high-dose vitamin A.Study design: We report a double-blind, randomized controlled trial of infants <32 weeks’ gestation and/or <1501 g birth weight. Supplemented infants received additional intramuscular vitamin A 10 000 IU 3 times weekly from day 2 for a minimum of 2 weeks or until establishment of oral feeding. Hepatic stores were assessed by relative dose response (RDR). The primary outcome measure was cone-corrected dark-adapted retinal rod sensitivity measured by electroretinogram at 36 weeks’ postmenstrual age (PMA).Results: Eighty-nine infants (42 supplemented and 47 controls) were recruited. Plasma retinol was higher in supplemented infants at 7 and 28 days (median, 1.0 vs 0.5 μmol/L and 0.7 vs 0.6 μmol/L; P < .001 and .03, respectively). Neither plasma retinol nor RDR differed between groups at 36 weeks’ PMA. Retinal sensitivity was greater in supplemented infants (−0.81 vs −0.61 log cd • s • m−2; P < .03) and was not related to RDR.Conclusions: Early high-dose intramuscular vitamin A supplementation for infants at risk of retinopathy of prematurity improves retinal function at 36 weeks’ PMA.

Windows of Lead Exposure Sensitivity, Attained Height, and Body Mass Index at 48 Months - Corrected Proof

2012-01-30

Objective: To examine longitudinal associations of prenatal, infancy, and early childhood lead exposure during sensitive periods with height and body mass index (BMI).Study design: A total of 773 participants were recruited between 1994 and 2005 in Mexico City. Lead exposure history categories were constructed for the prenatal period (maternal patellar lead concentration) and for infancy and childhood (mean child blood lead concentration at birth to 24 months and 30-48 months, respectively). Linear regression models were used to study lead exposure history with height and BMI at 48 months.Results: Mean height at age 48 months was significantly lower in children with a blood lead level exceeding the median during infancy (−0.84 cm; 95% CI, −1.42 to −0.25) than in children with a level below the median. Prenatal lead exposure was not associated with height at 48 months. Results for attained BMI generally trended in the same direction as for height.Conclusion: Our findings suggest an effect of lead exposure early in life on height attainment at 48 months, with the exposure window of greatest sensitivity in infancy.

Hepcidin Concentrations in Serum and Urine Correlate with Iron Homeostasis in Preterm Infants - Corrected Proof

2012-01-30

Objectives: To evaluate whether hepcidin concentrations in serum (Hep(S)) and urine (Hep(U)) correlate with iron metabolism, erythropoiesis, and inflammation in preterm infants.Study design: Thirty-one preterm infants (23-32 weeks gestational age) were included. The concentration of the mature, 25 amino-acid form of hepcidin was determined by enzyme-linked immunosorbent assay in serum, urine, blood counts, reticulocytes, and iron measurements.Results: Median (IQR) Hep(S) was 52.4 (27.9-91.9) ng/mL. The highest values were measured in patients with systemic inflammation. Hep(S) and Hep(U) correlated strongly (P = .0007). Hep(S) and Hep(U) also correlated positively with ferritin (P = .005 and P = .0002) and with reticulocyte hemoglobin content (P = .015 and P = .015). Hep(S) and Hep(U) correlated negatively with soluble transferrin receptor/ferritin-ratio (P = .005 and P = .003). Infants with lower hemoglobin concentrations and higher reticulocyte counts had lower Hep(S) (P = .0016 and P = .0089).Conclusion: In sick preterm infants, iron status, erythropoiesis, anemia, and inflammation correlated with the mature 25 amino-acid form of hepcidin. Further evaluation of Hep(U) for non-invasive monitoring of iron status in preterm infants appears justified.

Timing of Patent Ductus Arteriosus Treatment and Respiratory Outcome in Premature Infants: A Double-Blind Randomized Controlled Trial - Corrected Proof

Ilene R.S. Sosenko, M. Florencia Fajardo, Nelson Claure, Eduardo Bancalari — 2012-01-30

Objective: To determine whether “early” ibuprofen treatment, at the onset of subtle patent ductus arteriosus (PDA) symptoms, would improve respiratory outcome in premature infants compared with “expectant” management, with ibuprofen treatment only when the PDA becomes hemodynamically significant (HS).Study design: We conducted a randomized double-blind controlled trial of infants with gestational ages 23 to 32 weeks and birth weights 500 to 1250 g who had echocardiography for subtle PDA symptoms (metabolic acidosis, murmur, bounding pulses). Infants were then randomized to “early” treatment (blinded ibuprofen; n = 54) or “expectant management” (blinded placebo, n = 51). If the PDA became HS (pulmonary hemorrhage, hypotension, respiratory deterioration), infants received open label ibuprofen. Infants with HS PDA at enrollment were excluded from the study. Respiratory outcomes and mortality and major morbidities were determined.Results: “Early” treatment infants received ibuprofen at median age of 3 days; infants in the “expectant group” in whom HS symptoms developed (20%) received ibuprofen at median of 11 days. A total of 49% of “expectant” infants never required ibuprofen or ligation. No significant differences were found in the primary outcome (days on oxygen [O2] during the first 28 days), death, O2 at 36 weeks, death or O2 at 36 weeks, intestinal perforation, surgical necrotizing enterocolitis, grades III and IV intracranial hemorrhage, periventricular leukomalacia, sepsis or retinopathy of prematurity.Conclusion: Infants with mild signs of PDA do not benefit from early PDA treatment compared with delayed treatment.

Incidence of Febrile Urinary Tract Infections in Children after Successful Endoscopic Treatment of Vesicoureteral Reflux: A Long-Term Follow-Up - Corrected Proof

Manuela Hunziker, Nochiparambil Mohanan, Federica D’Asta, Prem Puri — 2012-01-30

Objective: To evaluate the incidence of febrile urinary tract infection (UTI) after successful endoscopic correction of intermediate and high-grade vesicoureteral reflux (VUR).Study design: Medical records of 1271 consecutive children (male, 411; female, 903) who underwent successful endoscopic correction of VUR were reviewed. Factors potentially influencing postoperative UTIs, such as history of presentation, age, sex, grade of VUR, renal scarring, and agent used for the endoscopic injection, were analyzed.Results: Febrile UTI developed in 73 children (5.7%) after successful endoscopic correction of VUR. Thirty-nine children had a single episode of UTI, and 34 children had two or more episodes at 1 month to 5.9 years (median, 1 year) after correction of VUR. With multivariate analysis, female sex (P < .001), history of preoperative bladder/bowel dysfunction (BBD; P = .005), and BBD after endoscopic correction (P = .001) were revealed to be the most important independent risk factors for a febrile UTI after successful correction of VUR.Conclusions: The incidence of febrile UTIs after successful correction of intermediate and high grade VUR is low. Female sex and BBD were the most important risk factors in the development of febrile UTI. Our data supports the importance of assessing bladder and bowel habits in older children with febrile UTIs after endoscopic correction of VUR.

Effects of Sleep Patterns and Obesity on Increases in Blood Pressure in a 5-Year Period: Report from the Tucson Children's Assessment of Sleep Apnea Study - Corrected Proof

Kristen Hedger Archbold, Monica M. Vasquez, James L. Goodwin, Stuart F. Quan — 2012-01-30

Objectives: To determine associations between body mass index and sleep on blood pressure in a 5-year period from childhood to adolescence.Study design: Study consisted of a longitudinal, community-based sample of 334 children recruited at ages 6 through 11 years. Each participant underwent in-home polysomnography initially and then 5 years later. Individual systolic blood pressure (SBP) and diastolic blood pressure (DBP) were calculated at both points during wake periods and classified as hypertensive when SBP or DBP was ≥95th standardized percentiles for height and weight.Results: Hypertension was present in 3.6% of the sample at time one and increased to 4.2% 5 years later. Obesity prevalence increased from 15.0% to 19.5%. Normal changes in sleep architecture were observed in the sample. With random effects modeling, which controlled for age, sex, and ethnicity, change in obesity status and decrease in total sleep time were indicated to be associated with increases in SBP. Change in obesity status was also associated with increases in DBP in the 5-year period. A trend for sleep-disordered breathing to increase SBP was noted.Conclusions: Increases in SBP and DBP were associated with increasing body mass index and decreased total sleep time in a 5-year period from childhood to adolescence.

Pulmonary Involvement in Pediatric-Onset Multisystem Langerhans Cell Histiocytosis: Effect on Course and Outcome - Corrected Proof

2012-01-30

Objectives: To assess the effect of pulmonary involvement on the course and outcome of multisystem Langerhans cell histiocytosis (MS-LCH) in children.Study design: We conducted a retrospective analysis of 420 consecutive patients with MS-LCH. In this analysis, the term “risk organs” is defined as involvement of the liver, spleen, and/or hematopoietic system. The effect of pulmonary involvement on survival was assessed with multivariate Cox regression with adjustment for risk organs involvement and age.Results: Pulmonary involvement in MS-LCH was present at diagnosis in 102 patients (24%). Of the 318 patients without pulmonary involvement at diagnosis, it developed in 28 within a median of 10 months (range, 1 month-5.5 years). The 5-year overall survival rate in patients without risk organ involvement at diagnosis was 96% in patients without pulmonary involvement and 94% in those with pulmonary involvement. In patients with risk organ involvement at diagnosis, the 5-year overall survival rate was 73% in patients without pulmonary involvement and 65% in patients with pulmonary involvement. In multivariate analysis, pulmonary involvement at diagnosis had no significant impact on survival rats (P = .109, hazard ratio = 1.5).Conclusions: In multivariate analysis, pulmonary involvement was not an independent prognostic variable and should therefore be excluded from the definition of risk organ involvement in MS-LCH.

Impact of Prenatal Diagnosis on Neurocognitive Outcomes in Children with Transposition of the Great Arteries - Corrected Proof

2012-01-30

Objectives: To assess the effect of prenatal diagnosis of congenital heart disease on neurocognitive outcomes in children with d-transposition of the great arteries (TGA) after surgical correction.Study design: A prospective study of children born with a TGA between 2003 and 2005 and aged 4 to 6 years was conducted. General intelligence, language, executive functions, and social cognition scores and preoperative, intraoperative, and postoperative factors were evaluated according to time of TGA diagnosis. Neurocognitive data were also compared with a control group.Results: Forty-five eligible patients (67% male) were examined; 29 had a prenatal diagnosis of TGA and 16 did not. All children were comparable in age, sex, and demographic variables. Diagnostic groups did not differ in preoperative, intraoperative, and postoperative variables. Preoperative acidosis was more frequent in the postnatal group (18% versus 3%). All patients had normal IQ scores, language, and verbal working memory. However, neurocognitive deficits were more prevalent and more severe in children with a postnatal-TGA. Prenatal diagnosis was associated with better outcomes in executive functions.Conclusions: Prenatal diagnosis of TGA is associated with better neurocognitive outcomes. Time of diagnosis may influence the development of early complex cognitive skills such as executive functions.

Follow-Up of Children Diagnosed with Familial Hypercholesterolemia in a National Genetic Screening Program - Corrected Proof

2012-01-30

Objective: To assess the follow-up of children diagnosed as having familial hypercholesterolemia (FH) in the nationwide DNA-based cascade screening program (the Netherlands).Study design: Questionnaires covering topics such as demographics, family history, physician consultation, and treatment were sent to parents of patients with FH (age 0-18 years), 18 months after diagnosis.Results: We retrieved 207 questionnaires of patients aged 10.9 ± 4.2 years (mean ± SD) at diagnosis; 48% were boys, and the mean low-density lipoprotein cholesterol (LDL-C) level at diagnosis was 167 ± 51 mg/dL. Of these patients, 164 (79%) consulted a physician: a general practitioner (35%), lipid-clinic specialist (27%), pediatrician (21%), internist (11%), or another physician (6%). LDL-C level at diagnosis and a positive family history for cardiovascular disease were independent predictors for physician consultation. Of the patients who visited a physician, 62% reported to have received lifestyle advice, and 43 (26%) were prescribed statin treatment. Independent predictors for medication use were age, LDL-C level, and educational level of parents.Conclusion: The follow-up of children with FH after diagnosis established through cascade screening is inadequate. Better education of patients, parents, and physicians, with a structured follow-up after screening, should improve control of LDL-C levels and hence cardiovascular risk in children with FH.

Hypothermia for neonatal encephalopathy in resource-poor environments - Corrected Proof

2012-01-30

The executive summary of the workshop on hypothermia for neonatal encephalopathy suggested research priorities, including the urgent need for trials for therapeutic hypothermia in low-moderate income countries such as India. Reasons stated as to why the results of completed trials cannot be extrapolated to low-income countries include differences in patient profile, increased infection, lack of facilities, and potential loss of neuroprotection with low-tech cooling devices.

Declining School Performance as a Harbinger of a Treatable Neurodegenerative Condition - Corrected Proof

Pankaj Prasun, Vinod K. Misra — 2012-01-30

On starting a new school year, an 11-year-old honors student began having difficulty focusing. His grades in mathematics declined, soon followed by a decline in other subjects. He began having visual difficulty, although the results of an ophthalmologic evaluation were normal. Attention-deficit/hyperactivity disorder initially was diagnosed because of the boy’s associated symptoms of forgetfulness and short attention span. Psychostimulant medications were prescribed, but his symptoms continued to worsen. Because of his progression, cerebral magnetic resonance imaging was obtained, the results of which showed extensive white matter changes suggesting a neurodegenerative condition (). Results of blood testing subsequently revealed abnormally high levels of saturated very long chain fatty acids. The boy was then found to have a pathogenic mutation in the ABCD1 gene, confirming the diagnosis of X-linked adrenoleukodystrophy 6 months after the onset of symptoms. Immediately after the diagnosis was made, the boy was evaluated for bone marrow transplantation as a curative treatment, but by then his neurological disease was too advanced for him to be a candidate.

Primary Care Providers Can Help Prevent Cardiovascular Disease in Children—And Their Parents - Corrected Proof

Reginald L. Washington — 2012-01-30

Post-mortem studies of children, adolescents, and young adults demonstrate that early atherosclerotic lesions of fatty streaks and fibrous plaques are significantly related to elevations in levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (HDL) cholesterol, lower levels of HDL-cholesterol, and the presence and intensity of risk factors. The extent of atherosclerosis in the aorta and coronary arteries was correlated with the presence of abnormal lipid levels, obesity, a measure of hypertension, and evidence of cigarette smoking in the Pathobiological Determinants of Atherosclerosis in Youth study.

Use of Paralysis in Silo-Assisted Closure of Gastroschisis - Corrected Proof

2012-01-30

Objective: To examine the association between pre-closure neuromuscular paralysis and time to final surgical closure for infants with gastroschisis undergoing silo reduction.Study design: This study was an exploratory review of observational variables obtained from the Canadian Pediatric Surgery Network database. The focus was on the subset of infants with gastroschisis undergoing silo reduction between May 2005 and March 2009. Of the 186 infants, paralysis use could be ascertained for 167 infants (79 received pre-closure paralysis and 88 received none). Groups were compared by using statistical tests, with relationships explored using regression analysis.Results: Infants receiving paralysis took longer to achieve closure by an average of 3 days (8 versus 5 days; P < .001) and had greater mean number of ventilation days (12 versus 7 days; P < .001). The relationship between paralysis and days to closure remained after adjusting for other variables.Conclusions: In infants with gastroschisis undergoing silo reduction, use of paralysis was associated with longer time to closure. Pre-closure paralysis should be carefully weighed in this population.

Maternal Self-Efficacy Reduces the Impact of Prenatal Stress on Infant’s Crying Behavior - Corrected Proof

Margarete I. Bolten, Nadine S. Fink, Christina Stadler — 2012-01-30

Objective: To determine whether prenatal stress is associated with behavioral and emotional regulation problems (crying/fussing) in infants, after controlling for confounding factors. Furthermore, the study investigated the stress-buffering effect of maternal self-efficacy.Study design: Data were collected in 120 pregnant women (29±3.2 weeks gestation) and their infants at 6 weeks of age. Expecting mothers completed a structured interview and self-report questionnaires on prenatal stress and self-efficacy. Crying/fussing data were obtained with a validated parental diary.Results: After controlling for confounding variables, multiple regression analyses show that prenatal stress and self-efficacy accounted for 20% of the variance of infant’s fussing and crying behavior. Results suggest a mediating role of self-efficacy. Babies of mothers reporting high levels of prenatal stress cried less when their mother had high levels of self-efficacy compared with mothers with low self-efficacy. In addition, mothers of infants with excessive crying reported more symptoms of stress, depression, and anxiety in pregnancy.Conclusion: To foster the development of well-adapted parent-infant relationships and potentially to reduce infant crying in the early postpartum phase, health care professionals need special education about the effects of prenatal stress and interventions that promote self-efficacy.

Effect of Ethnicity and Race on Cognitive and Language Testing at Age 18-22 Months in Extremely Preterm Infants - Corrected Proof

2012-01-24

Objective: To evaluate the relationship of race/ethnicity to Cognitive and Language scores on the Bayley Scales of Infant and Toddler Development, Third Edition in extremely preterm toddlers (<28 + 0 weeks’ estimated gestational age).Study design: This cohort study included extremely preterm toddlers seen at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers evaluated at 18-22 months adjusted age from 3 race/ethnic groups (white, black, and Hispanic white). Multivariate regression modeling was used to identify race/ethnic differences, after adjusting for medical and psychosocial factors.Results: The study population comprised 369 whites, 352 blacks, and 144 Hispanic whites. Cognitive scores differed among the 3 groups on unadjusted analysis (P ≤ .001), but not after adjusting for medical and psychosocial factors (P = .13). Language scores differed on adjusted and unadjusted analyses. Whites scored higher than blacks and Hispanic whites, and blacks scored higher than Hispanic whites.Conclusions: A combination of medical variables and primary caretaker education accounted for differences in Bayley Scales of Infant and Toddler Development, Third Edition Cognitive scores among the 3 groups. Black and Hispanic white toddlers had lower Language scores than whites, even after adjustment. Early intervention should be targeted to these identified risk factors. Assessment of early language development in minority children may be warranted.

Increased Albuminuria in 4-Year-Old Preterm-Born Children with Normal Height - Corrected Proof

Rachel Vieux, Jean-Michel Hascoët, Patricia Franck, F. Guillemin — 2012-01-19

Objective: To determine risk factors for high blood pressure (BP), increased markers of glomerulosclerosis, and tubular dysfunction in 4-year-old preterm-born children.Study design: The study group was a longitudinal cohort of 119 children with BP, albuminuria, and β2 microglobulin measurements obtained during the neonatal period and at age 4 years.Results: Systolic BP was >95th percentile in 15 (12.6%) of the children at age 4 years and lower in those born small for gestational age compared with those born appropriate for gestational age. Preterm-born 4-year-olds with height <−1 SD had lower systolic and diastolic BP, and 14.4% of the 4-year-olds had albuminuria. Albuminuria was less prevalent in the 4-year-olds with height <−1 SD than in those with height ≥−1 SD (6.8% vs 19.3%; P=.04). Mean albuminuria level was 1.0±0.7 mg/mmol in 4-year-olds with height <−1 SD and 1.4±1.3 mg/mmol in those with height ≥−1 SD. In multivariate analysis, albuminuria level was increased by 0.4±0.2 mg/mmol in preterm-born children with normal height at age 4, and by 0.5±0.2 mg/mmol in females, after adjustment for gestational age, sex, neonatal morbidity, and intrauterine growth restriction. These results were unchanged after adjustment for body mass index.Conclusion: Normal height at age 4 years may be associated with an increased risk for glomerulosclerosis in preterm-born children.

Clinical Sepsis in Neonates and Young Infants, United States, 1988-2006 - Corrected Proof

Susan L. Lukacs, Stephanie J. Schrag — 2012-01-19

Objective: To describe the burden and characteristics of clinical neonatal sepsis in the United States and evaluate incidence rates after the issuance of intrapartum antibiotic prophylaxis (IAP) guidelines.Study design: This is a cross-sectional study of hospitalizations of infants aged <3 months diagnosed with sepsis from the 1988-2006 National Hospital Discharge Survey. The National Hospital Discharge Survey collects data annually on inpatient discharges from a national probability sample of approximately 500 short-stay hospitals. We examined sepsis hospitalizations, defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes, and compared sepsis hospitalization rates for 2 time periods after the issuance of IAP guidelines (1996-2001 and 2002-2006) with 1988-1995 using national natality data as the population denominator. We used Joinpoint (Surveillance Research Program, National Cancer Institute, Bethesda, Maryland) regression to assess the average annual percent change (AAPC) in rates.Results: Between 1988 and 2006, there were more than 2.5 million sepsis-related hospitalizations in infants aged <3 months (112 000-146 000 annually). In 2006, the sepsis hospitalization rate was 30.8/1000 births. The rate was more than 3 times higher in preterm infants compared with term infants (85.4/1000 preterm births vs 23.1/1000 term births). The AAPC in sepsis hospitalization rate was -3.6% (95% CI, -2.1% to 5.1%) for term infants during 1996-2002 and did not change significantly after issuance of the revised 2002 guidelines. For preterm infants, the AAPC was -1.2% (95% CI, -2.2% to 0.1%) annually from 1988 to 2006.Conclusion: Clinical neonatal sepsis declined in the post-IAP era, mirroring trends observed in group B streptococcal early-onset neonatal sepsis surveillance. Preterm infants were affected disproportionately and exhibited a modest but steady decline in sepsis hospitalization rate.

Abatacept and Sodium Thiosulfate for Treatment of Recalcitrant Juvenile Dermatomyositis Complicated by Ulceration and Calcinosis - Corrected Proof

Bita Arabshahi, Robert A. Silverman, Olcay Y. Jones, Lisa G. Rider — 2012-01-16

We report the successful use of abatacept and sodium thiosulfate in a patient with severe recalcitrant juvenile dermatomyositis complicated by ulcerative skin disease and progressive calcinosis. This combination therapy resulted in significant reductions in muscle and skin inflammation, decreased corticosteroid dependence, and halted the progression of calcinosis.

Use of Technology with Health Care Providers: Perspectives from Urban Youth - Corrected Proof

2012-01-16

Objective: To evaluate urban youths’ use of and access to technology and solicit their opinions about using technology with healthcare providers.Study design: Urban youth (aged 14-24 years) were invited to participate in focus groups in which a trained focus group facilitator used a survey and a structured guide to elicit responses regarding the foregoing objective. All sessions were audiotaped and transcribed. Emergent themes were determined with the assistance of Atlas TI. Survey data were analyzed in SPSS (SPSS Inc, Chicago, Illinois).Results: Eight focus groups including 82 primarily low-income urban African-American adolescents and young adults (mean age, 18.5 years) were completed. The participants reported fairly high access to and use of technology. However, they expressed some concerns regarding the use of technology with healthcare providers. Many worried about the confidentiality of conversations conducted using technology. Face-to-face meetings with a healthcare provider were preferred by most participants, who felt that the information provided would be better tailored to their individual needs and more credible.Conclusion: Although urban youth were high users of technology, they expressed reservations about using technology with health care providers. When developing new technology communication and information dissemination strategies, it is critical to understand and address these concerns while involving young people in the research and development process.

The Child as Proband for Future Parental Cardiometabolic Disease: The 26-Year Prospective Princeton Lipid Research Clinics Follow-Up Study - Corrected Proof

John A. Morrison, Charles J. Glueck, Ping Wang — 2012-01-16

Objective: To evaluate children’s cardiovascular disease (CVD) risk factors as predictors of parents’ subsequent CVD, type 2 diabetes mellitus (T2DM), and high blood pressure (HBP).Study design: We conducted a 26-year prospective follow-up of 852 5- to 19-year-old black and white schoolchildren (mean age, 12 years; Lipid Research Clinics, 1973-8), and parents (mean age, 40 years) from 519 families in Princeton Schools, Cincinnati, Ohio. Schoolchildren were reassessed in the Princeton Follow-up study 1999-2003 at mean age 39 years; CVD, T2DM, and HBP history of their 1038 parents were reassessed by mean age 66 years. We assessed relationships of childhood risk factors with parental CVD, T2DM, and HBP. Child-probands identified with triglyceride (TG) levels, blood pressure, low-density lipoprotein cholesterol levels, body mass index (BMI), and glucose level greater than and high-density lipoprotein cholesterol levels less than established cutoff points.Results: Pediatric HBP (P=.006) and low high-density lipoprotein cholesterol (P=.018) were predictive of parental CVD at age ≤50 years. Pediatric HBP (P=.02) and high TG (P=.03) were predictive of parental CVD at age ≤60 years. Pediatric high TG (P=.009) and high low-density lipoprotein cholesterol (P=.04) were predictive of parental CVD by age 66 years. Pediatric high BMI (P=.0006) were predictive of parental T2DM. Pediatric high BMI (P=.003) and black race (P=.004) were predictive of parental HBP.Conclusions: Pediatric risk factors identify families with parents at increased risk for CVD, T2DM, and HBP, emphasizing the usefulness of the child as proband.

Cancer in Children with Nonchromosomal Birth Defects - Corrected Proof

2012-01-13

Objective: To examine whether the incidence of childhood cancer is elevated in children with birth defects but no chromosomal anomalies.Study design: We examined cancer risk in a population-based cohort of children with and without major birth defects born between 1988 and 2004, by linking data from the California Birth Defects Monitoring Program, the California Cancer Registry, and birth certificates. Cox proportional hazards models generated hazard ratios (HRs) and 95% CIs based on person-years at risk. We compared the risk of childhood cancer in infants born with and without specific types of birth defects, excluding infants with chromosomal anomalies.Results: Of the 4869 children in the birth cohort with cancer, 222 had a major birth defect. Although the expected elevation in cancer risk was observed in children with chromosomal birth defects (HR, 12.44; 95% CI, 10.10-15.32), especially for the leukemias (HR, 28.99; 95% CI, 23.07-36.42), children with nonchromosomal birth defects also had an increased risk of cancer (HR, 1.58; 95% CI, 1.33-1.87), but instead for brain tumors, lymphomas, neuroblastoma, and germ cell tumors.Conclusion: Children with nonchromosomal birth defects are at increased risk for solid tumors, but not leukemias. Dysregulation of early human development likely plays an important role in the etiology of childhood cancer.

Growth in Children and Adolescents with Type 1 Diabetes - Corrected Proof

2012-01-13

Objective: To investigate the effect of type 1 diabetes on growth and adult height.Study design: Data from 22 651 children (10 494 females) with type 1 diabetes documented at onset of the disease from specialized centers in Germany and Austria were analyzed. Patients of non-German and non-Austrian origin and patients with celiac disease were excluded from the analysis. Near-adult height data were available in 1685 patients.Results: At the time of diagnosis of type 1 diabetes, the mean age of the 22 651 children was 8.8 ± 4.2 years, with a mean height SDS of 0.22 ± 1.0. The 1685 patients with diabetes onset before age 11 years reached a mean adult height of −0.16 ± 1.0 SDS. Mean adult height was was 167.1 ± 6.2 cm (−0.16 ± 0.97 SDS) in females (n = 846) and 179.6 ± 7.1 cm (−0.17 ± 1.0 SDS) in males (n = 839). Mean duration of diabetes was 9.1 ± 2.6 years, and mean Hemoglobin A1c concentration was 7.9% ± 1.2% (63 ± 10 mmol/mol). In a multivariate regression model, adult height was positively correlated with height at onset of diabetes (P < .0001) and negatively with mean Hemoglobin A1c (P < .0001) and duration of diabetes (P = .0015).Conclusion: Height at the time of diagnosis of type 1 diabetes is above average. Even with intensive insulin therapy, growth and adult height remain indicators of metabolic diabetes control in the 21st century.

Transitional Changes in Cardiac and Cerebral Hemodynamics in Term Neonates at Birth - Corrected Proof

2012-01-13

Objective: To describe cardiac function, cerebral regional oxygen saturation (rSO2), and cerebral blood flow (CBF) that correspond to changes in arterial oxygen saturation (SaO2) in normal term neonates immediately after birth and after the transition.Study design: In this prospective observational study, cardiac function and cerebral hemodynamics were assessed by echocardiography and Doppler ultrasonography 3 times during the first 20 minutes after vaginal delivery, then again at 24-48 hours after delivery. Cerebral rSO2 (by near-infrared spectroscopy) and preductal SaO2 (by pulse oximetry) were assessed continuously.Results: In 20 neonates, SaO2 increased progressively from 65% at 1 minute after birth to 97% at 17 minutes after birth. Cerebral rSO2 increased from 47% at 1 minute to 83% at 8 minutes, then decreased progressively to 73% at 20 minutes. Middle cerebral artery mean velocity decreased from 34 cm/s at 7 minutes to 25 cm/s at 14 minutes. The patent ductus arteriosus (PDA) shunt was balanced at 5 minutes but became increasingly left to right. Left ventricular stroke volume was increased. Middle cerebral artery mean velocity demonstrated an inverse relationship with the PDA shunt. Further hemodynamic changes were noted on the posttransitional assessment.Conclusion: After birth, ductal shunting rapidly changes from balanced to left to right, with a responsive increase in left ventricular stroke volume. Cerebral rSO2 increases as SaO2 rises during the first 8 minutes, subsequently, it decreases due to a drop in CBF and despite a further increase in SaO2. The reduction in CBF is likely due to an increase in arterial O2 content, PDA shunting, or both.

Iron Deficiency in Infancy is Associated with Altered Neural Correlates of Recognition Memory at 10 Years - Corrected Proof

2012-01-13

Objective: To determine the long-term effects of iron deficiency on the neural correlates of recognition memory.Study design: Non-anemic control participants (n=93) and 116 otherwise healthy formerly iron-deficient anemic Chilean children were selected from a larger longitudinal study. Participants were identified at 6, 12, or 18 months as iron-deficient anemic or non-anemic and subsequently received oral iron treatment. This follow-up was conducted when participants were 10 years old. Behavioral measures and event-related potentials from 28 scalp electrodes were measured during an new/old word recognition memory task.Results: The new/old effect of the FN400 amplitude, in which new words are associated with greater amplitude than old words, was present within the control group only. The control group also showed faster FN400 latency than the formerly iron-deficient anemic group and larger mean amplitude for the P300 component.Conclusions: Although overall behavioral accuracy is comparable in groups, the results show that group differences in cognitive function have not been resolved 10 years after iron treatment. Long-lasting changes in myelination and energy metabolism, perhaps especially in the hippocampus, may account for these long-term effects on an important aspect of human cognitive development.

Improving Detection by Pediatric Residents of Endotracheal Tube Dislodgement with Capnography: A Randomized Controlled Trial - Corrected Proof

Melissa L. Langhan, Marc Auerbach, Alla N. Smith, Lei Chen — 2012-01-13

Objective: The authors sought to determine if capnography could improve time to correction of a simulated endotracheal tube (ETT) dislodgement by pediatric residents.Study design: Pediatric residents attended a didactic session that included interpretation of capnography. A randomized controlled study was then performed using patient simulators. Residents were randomized to standard monitoring (control group) or standard monitoring plus capnography (intervention group). The primary outcome was time to correction of ETT dislodgement. Correction of dislodgement prior to decline in pulse oximetry was our secondary outcome.Results: Twenty-seven subjects completed the simulation. Subjects in the intervention group corrected the ETT dislodgement faster than those in the control group (2.38 minutes vs 3.92 minutes, P = .02). There were no differences in time to correction based on postgraduate year, clinical experiences, or comfort with capnography. Two subjects corrected the dislodgement prior to changes in pulse oximetry, both from the intervention group. Fifty-nine percent of subjects had seen capnography used in the past and 82% felt very or somewhat comfortable with capnography.Conclusion: Capnography decreased time to correction of ETT dislodgement by pediatric residents. Capnography should be considered as an essential monitoring device for intubated patients to enhance patient safety.

Rapid and Progressive Pulmonary Fibrosis in 2 Families with DNA Repair Deficiencies of Undetermined Etiology - Corrected Proof

2012-01-12

Known genetic causes of pediatric interstitial lung disease include disorders of surfactant metabolism, telomerase, and DNA repair. We report 4 children from 2 families with rapidly progressive and fatal pulmonary fibrosis. A novel DNA repair defect unrelated to the ataxia-telangiectasia mutated gene was found in 1 child from each family.

β-cell Dysfunction in Adolescents and Adults with Newly Diagnosed Type 2 Diabetes Mellitus - Corrected Proof

2012-01-12

Objective: To compare β-cell function in adolescents and adults with newly diagnosed type 2 diabetes (T2DM).Study design: Thirty-nine adolescents with T2DM, 38 age- and weight-matched control subjects, and 19 adults with T2DM were studied. The adolescent subjects with diabetes were divided on the basis of whether they needed insulin to control their initial hyperglycemia. The primary outcome variable was the disposition index, computed from the acute insulin response to glucose corrected for insulin sensitivity (1/Homeostatic model assessment of insulin resistance).Results: The disposition index was significantly reduced in all 3 diabetic groups (control n=3360, adolescents with T2DM without insulin n=630, adolescents with T2DM with insulin n=120, adults with T2DM n=200; P<.001), and the adolescents with more severe hyperglycemia at diagnosis had lower disposition index than those with a more modest presentation (P<.05).Conclusion: At the time of diagnosis, adolescents with T2DM have significant β-cell dysfunction, comparable with adults newly diagnosed with T2DM. Thus, severe β-cell impairment can develop within the first two decades of life and is likely to play a central role in the pathogenesis of T2DM in adolescents.

An Evidence-Based Catheter Bundle Alters Central Venous Catheter Strategy in Newborn Infants - Corrected Proof

Meggan Butler-O’Hara, Carl T. D’Angio, Hyacinth Hoey, Timothy P. Stevens — 2012-01-12

Objective: To assess whether introduction of an evidence-based percutaneously inserted central catheter (PICC) care bundle reduced the risk of central line-associated bloodstream infection (CLABSI), thus altering the comparative risk of CLABSI in infants.Study design: This retrospective cohort study included all infants for whom an umbilical venous catheter (UVC) was placed as part of routine care between Jan 1, 2006, and Dec 31, 2009, a period during which standardized PICC insertion and care bundles were introduced. Duration of UVC use was divided in ≤7 days and >7 days.Results: Infants in the ≤7 days UVC group had 1.0 CLABSI/1000 catheter days, and infants in the >7 days UVC group had 4.0 CLABSI/1000 catheter days (P < .001). Controlling for birth weight, gestational age, and antibiotic use, the >7 days UVC group had a greater risk of CLABSI (OR, 5.48) than the ≤7 days UVC group. CLABSI rate increased more rapidly in UVC than PICC with increasing duration of catheter rose.Conclusions: Replacement of a UVC with a PICC when central venous access is needed after 7 days of age may reduce CLABSI.

Pulmonary Tumor Thrombotic Microangiopathy with Cor Pulmonale due to Desmoplastic Small Round Cell Tumor - Corrected Proof

Evita T. Sadimin, Adrienne G. Collier, Joseph W. Gaffney, Billie Fyfe — 2012-01-12

A 12-year-old boy presented acutely after an episode of syncope with perioral cyanosis. He died 19 hours after admission due to cor pulmonale as a complication of metastatic desmoplastic small round cell tumor in the lungs with associated tumor thrombotic microangiopathy.

Executive Summary of the Workshop “Nutritional Challenges in the High Risk Infant” - Corrected Proof

2012-01-12

Pediatricians caring for preterm infants at the beginning of the 20th century faced the daunting challenge of providing nutritional support for their patients, who were surviving at increasing numbers because of the introduction of neonatal incubators. In a few decades, several key innovations followed. These included tube feeding, human milk banking systems, infant formulas, and, in the late 1970s through the 1980s, continuous intravenous nutrition.

Gastrointestinal Bleeding in Infantile Hemangioma: A Complication of Segmental, Rather than Multifocal, Infantile Hemangiomas - Corrected Proof

2012-01-12

Objective: To highlight an association of facial segmental hemangiomas with gastrointestinal bleeding in infants with infantile hemangiomas.Study design: We conducted a multicenter retrospective case series study.Results: Ten female patients met study inclusion criteria; 8 were Caucasian, 9 had a facial segmental hemangioma, and 9 cases met the diagnostic criteria for definitive posterior fossa malformations, hemangioma, arterial lesions, cardiac anomalies/coarctation of the aorta and eye abnormalities syndrome with abnormalities of the aorta and cerebral arteriopathy. Severe gastrointestinal bleeding requiring blood transfusion occurred in 9 cases, with age at presentation of gastrointestinal bleeding ranging from 8 days to 6 months. When detected, the location of the hemangioma in the small intestine was in the distribution of the superior mesenteric artery. More than one agent was required to control the gastrointestinal bleeding, including oral or intravenous steroids, vincristine, oral propranolol, interferon, and resection of the small intestine. All cases needed ongoing support care with red blood cell transfusions.Conclusions: Gastrointestinal bleeding is a rare complication of true infantile hemangioma. The segmental pattern of the cutaneous hemangioma associated with gastrointestinal bleeding should suggest a segmental infantile hemangioma of the lower gastrointestinal tract.

Implementation of Clinical Practice Guidelines for Pediatric Weight Management - Corrected Proof

2012-01-12

Objective: To evaluate the effect of computer-assisted decision tools that standardize pediatric weight management in a large, integrated health care system for the diagnosis and management of child and adolescent obesity.Study design: This was a large scale implementation study to document the impact of the Kaiser Permanente Southern California Pediatric Weight Management Initiative. An average of 739 816 outpatient visits per year in children and adolescents from 2007 to 2010 were analyzed. Height, weight, evidence of exercise and nutrition counseling, and diagnoses of overweight and obesity were extracted from electronic medical records.Results: Before the initiative, 66% of all children and adolescents had height and weight measured. This increased to 94% in 2010 after 3 years of the initiative (P < .001). In children and adolescents who were overweight or obese, diagnosis of overweight or obesity increased significantly from 12% in 2007 to 61% in 2010 (P < .001), and documented counseling rates for exercise and nutrition increased significantly from 1% in 2007 to 50% in 2010 (P < .001).Conclusions: Computer-assisted decision tools to standardize pediatric weight management with concurrent education of pediatricians can substantially improve the identification, diagnosis, and counseling for overweight or obese children and adolescents.

Diagnostic Accuracy of a Specific Cytokine Pattern in Hemophagocytic Lymphohistiocytosis in Children - Corrected Proof

2012-01-09

Objective: The study goal was to determine the diagnostic accuracy of a specific cytokine pattern including interferon-gamma (IFN-γ), interleukin (IL)-10, and IL-6 for hemophagocytic lymphohistiocytosis (HLH) in febrile children.Study design: In this prospective study, 756 patients with fever admitted to a hematology-oncology unit were enrolled. The causes of fever were documented and the serum cytokines, including IFN-γ, tumor necrosis factor-alpha (TNF-α), IL-10, IL-6, IL-4, and IL-2, were determined using cytometric bead array techniques.Results: Of 1474 episodes of fever that were analyzed, 71 episodes of HLH manifested a specific cytokine pattern of highly increased levels of IFN-γ (median level: 1088.5 pg/mL) and IL-10 (623.5 pg/mL) but a moderately increased level of IL-6 (51.1 pg/mL). IL-6 was predominantly increased to varied extents in patients in the sepsis group (244.6 pg/mL) and the nonsepsis infection group (34.7 pg/mL). The diagnostic accuracy of IFN-γ and IL-10 for HLH was 99.5% and 92.8%, respectively. By applying the cutoff point of 100 pg/mL, IFN-γ had a sensitivity of 94.4% and a specificity of 97.2% for HLH. When using the criteria of IFN-γ >75 pg/mL and IL-10 >60 pg/mL, the specificity reached 98.9% and the sensitivity was 93.0%.Conclusions: The specific cytokine pattern of markedly elevated levels of IFN-γ and IL-10 with only modestly elevated IL-6 levels has high diagnostic accuracy for HLH and may be a useful approach to differentiate HLH from infection.

Free-Running Disorder in a Sighted Adolescent - Corrected Proof

Andres Santiago Endara-Bravo, Supat Thammasitboon, David Thomas — 2012-01-09

An 11-year-old girl presented with sleepiness/insomnia of 2 years’ duration. On some days she slept from 3 p.m. to the next morning, whereas on other days she could not fall asleep until 3 a.m. but had to get up at 6 a.m. for school. On weekends she usually slept until noon. On some other days, she slept from 10 p.m. to 6 a.m. This irregular pattern repeated every few weeks.

Cerebral Autoregulation in Neonates with a Hemodynamically Significant Patent Ductus Arteriosus - Corrected Proof

Valerie Y. Chock, Chandra Ramamoorthy, Krisa P. Van Meurs — 2012-01-09

Objective: Very low birth weight (VLBW) preterm infants are at risk for impaired cerebral autoregulation with pressure passive blood flow. Fluctuations in cerebral perfusion may occur in infants with a hemodynamically significant patent ductus arteriosus (hsPDA), especially during ductal closure. Our goal was to compare cerebral autoregulation using near-infrared spectroscopy in VLBW infants treated for an hsPDA.Study design: This prospective observational study enrolled 28 VLBW infants with an hsPDA diagnosed by echocardiography and 12 control VLBW infants without an hsPDA. Near-infrared spectroscopy cerebral monitoring was applied during conservative treatment, indomethacin treatment, or surgical ligation. A cerebral pressure passivity index (PPI) was calculated, and PPI differences were compared using a mixed-effects regression model. Cranial ultrasound and magnetic resonance imaging data were also assessed.Results: Infants with surgically ligated hsPDAs were more likely to have had a greater PPI within 2 hours following ligation than were those treated with conservative management (P=.04) or indomethacin (P=.0007). These differences resolved by 6 hours after treatment.Conclusions: Cerebral autoregulation was better preserved after indomethacin treatment of an hsPDA compared with surgical ligation. Infants requiring surgical hsPDA ligation may be at increased risk for cerebral pressure passivity in the 6 hours following surgery.

Crossed-Fused Testicular Ectopia: A Case for the Use of Laparoscopy to Evaluate Nonpalpable Testicles - Corrected Proof

Jack M. Zuckerman, Jyoti Upadhyay — 2012-01-09

A 1-year-old male was referred for evaluation of a nonpalpable right testicle. In children with nonpalpable testicles, it our practice to proceed with diagnostic laparoscopy in an attempt to identify an intra-abdominal testicle or blind-ending spermatic vessels regardless of ultrasound findings. In the operating room, we performed diagnostic laparoscopy through the umbilical stump. We identified a vas deferens passing from the right side to the left side, and what appeared to be a testicle in the area of the left internal inguinal ring ( and ). In the left groin, we found both testicles fused together with a common blood supply, but a separate vas deferens. We placed the right testicle transseptally into the right hemiscrotum.

Additional information regarding “Dravet syndrome: Inroads into understanding epileptic encephalopathies” - Corrected Proof

Katsuhiro Kobayashi, Yoko Ohtsuka, Iori Ohmori — 2012-01-09

Morse wrote a comprehensive review on Dravet syndrome, a type of epileptic encephalopathy with a genetic background of, in most cases, mutations of the SCN1A gene that encodes the neuronal voltage-gated sodium channel NaV1.1. As Morse indicated, the incidence of this disorder probably is underestimated, because it is often mistaken for complex febrile seizures during infancy. However, early diagnosis and accompanying aggressive treatment starting in infancy, focusing on prevention of the occurrence of status epilepticus in particular, is important for affected children, given that a favorable seizure prognosis appears to be related to the experience of a small number of episodes of status epilepticus.

Health-Related Quality of Life in Adolescents with or at Risk for Type 2 Diabetes Mellitus - Corrected Proof

2012-01-05

Objective: To evaluate how adolescents with or at risk for type 2 diabetes mellitus (T2DM) and their parent/guardians (parents) perceive adolescents’ health-related quality of life.Study design: We interviewed overweight/obese, 12- to 18-year-old youth with T2DM, prediabetes, or insulin resistance and one parent from 5 US sites. Assessments included Pediatric Quality of Life Inventory (PedsQL), Health Utilities Index, family conflict, and diabetes burden.Results: In 108 adolescents, diagnoses included 40.7% with T2DM, 25.0% with prediabetes, and 34.3% with insulin resistance. PedsQL summary score (SS) was higher in adolescents than parents (P=.02). Parents rated physical functioning lower than adolescents (P<.0001), but there were no differences in psychosocial health. Adolescent PedsQL SS did not differ with diagnosis, but was inversely associated with adolescent body mass index z-score (P=.0004) and family conflict (P<.0001) and associated with race/ethnicity (P<.0001). Number of adolescent co-morbidities (P=.007) and burden of diabetes care (P<.05) were inversely associated with parent PedsQL SS. There were no differences in the Health Utilities Index-Mark 3 multi-attribute utility score.Conclusions: Parents perceive their adolescents’ physical functioning as more impaired than adolescents themselves. Contextual factors including severity of obesity, race/ethnicity, family conflict, and burden of diabetes care influence health-related quality of life. Family-based approaches to treatment and prevention of T2DM may benefit from increased attention to the biopsychosocial context.

Influence of Race and Socioeconomic Status on the Diagnosis of Child Abuse: A Randomized Study - Corrected Proof

2012-01-05

Objectives: To measure empirically the influence of race and socioeconomic status (SES) on the diagnosis of child abuse and willingness to report to child protection services.Study design: A total of 5000 pediatricians randomly selected from the American Medical Association’s Masterfile received 1 of 4 randomly assigned versions of a fictional clinical presentation of a child (black/white + high SES/low SES) that described an unwitnessed event in a mobile 18-month-old child resulting in an oblique femur fracture. Outcome measures included ranking the degree to which the injury was accidental versus abuse and agreement with reporting the injury to child protection services.Results: A total of 2109 of 4423 physicians responded (47.7%). Patient’s race did not have an effect on a diagnosis of abuse (black, 45% versus white, 46%). Abuse was more likely to be diagnosed in patients with low SES (48% versus 43%, overall P = .02).Conclusion: This study supports earlier work demonstrating physicians’ greater willingness to consider abuse as a potential cause of injury in low SES children. It failed to demonstrate the finding of retrospective, real world studies of an increased likelihood to consider abuse in black patients. Future work should try to understand why there remains a differential approach to evaluating minority children for abuse in real world settings.

Reply - Corrected Proof

Anne Tsampalieros, Anne Griffiths, Nick Barrowman, David R. Mack — 2012-01-05

We hope that the fewest number of children possible who undergo endoscopy are found to have normal macroscopic and microscopic findings. At the same time, we hope that children with inflammatory bowel disease (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), are selected to undergo endoscopy and are not overlooked, leading to delayed diagnosis. Blood tests remain the simplest form of testing to guide this decision making, based on availability and cost, and thus warrant careful evaluation. We found that 4 standard blood tests—complete blood count (CBC) with hemoglobin and platelet counts, albumin, and erythrocyte sedimentation rate (ESR)—were normal in 9% of all children with CD and in 19% of all children with UC, which is problematic.