The Journal of Pediatrics - Articles in Press

Insurance Status and the Care of Children in the Emergency Department - Corrected Proof

Rebekah Mannix, Vincent Chiang, Anne M. Stack — 2012-05-14

Objectives: To determine whether insurance status is associated with the use of diagnostic testing or intervention in the emergency department (ED) care of children.Study design: Retrospective cross-sectional analysis of ED visits using data from the National Hospital Ambulatory Medical Care Survey (1999-2008). Children <19 years old were categorized as having private insurance, public insurance, or no insurance. The main outcome measure was the adjusted odds of testing (laboratory or radiologic) or intervention (medication or procedure), controlling for demographic, clinical, and hospital specific factors. Illness severity was controlled for using triage and admission status.Results: Forty-five percent (95% CI; 44, 47) of visits were characterized as having private insurance compared with 43% with public insurance (95% CI; 42, 44) and 12% without insurance (95% CI; 11, 13). Children with public insurance and no insurance received less testing compared with those with private insurance (adjusted OR 0.78, 95% CI; 0.73, 0.84 and adjusted OR 0.78, 95% CI; 0.72, 0.84, respectively). Similar patterns were seen in the use of medications and performance of procedures.Conclusions: Non-private insurance status is associated with decreased utilization of diagnostic testing and intervention in children visiting the ED. It is unclear whether these patterns represent appropriate utilization, overutilization in patients with private insurance, or underutilization in patients without private insurance. Further studies are needed to evaluate whether these disparate care patterns impact health outcomes and could have important implications for the allocation of healthcare resources within the ED as well as the primary care setting.

Treatment, Survival, and Thromboembolic Outcomes of Thrombotic Storm in Children - Corrected Proof

2012-05-14

Objective: To describe the course and management of thrombotic storm in 8 children.Study design: Clinical data were collected and analyzed for consecutive children diagnosed with thrombotic storm, aged 6 months to 21 years inclusive, in the context of a single-institution prospective inception cohort study. Thrombotic storm was defined as newly diagnosed multisite venous thromboembolism (VTE) with acute thrombus progression despite conventional or higher than conventional dosing of heparin or low molecular weight heparin. All evaluations and therapies were ordered by the treating physicians in the context of clinical decision making.Results: Eight of the 178 children with VTE enrolled in the cohort between March 2006 and November 2009 were diagnosed with thrombotic storm. Antiphospholipid antibodies were acutely positive in 6 children, of whom heparin-induced thrombocytopenia was confirmed by serotonin release assay in 2 and atypical in 1. One child died. Five children received a direct thrombin inhibitor, titrated to achieve normalization of markedly elevated D-dimer levels. All children were transitioned to fondaparinux or enoxaparin before receiving extended anticoagulation with warfarin. Immunomodulatory therapy was instituted in all children. During follow-up (median duration, 3 years; range, 2-6 years), 3 of the 7 surviving children experienced recurrent VTE, and 4 children had clinically significant postthrombotic syndrome.Conclusion: Thrombotic storm is an infrequent but potentially fatal presentation of VTE in children. Administration of direct thrombin inhibitors and immune modulation can achieve quiescence, although long-term adverse outcomes are common.

Premature Subclinical Atherosclerosis in Pediatric Inflammatory Bowel Disease - Corrected Proof

2012-05-14

Objectives: To investigate the risk for developing an early endothelial dysfunction based on increased intima media thickness (IMT) and reduced flow-mediated dilation (FMD) in children with inflammatory bowel disease (IBD), and to evaluate the role of traditional and nontraditional risk factors in determining premature atherosclerosis.Study design: We studied 27 patients with Crohn's disease (CD) and 25 patients with ulcerative colitis (UC) (mean age, 15.2 years; mean duration of disease, 48.05 months); 31 subjects served as controls. Demographic data (age, sex, family history of diabetes, cardiovascular disease, hypertension, hypercholesterolemia), traditional risk factors for atherosclerosis (blood pressure, body mass index, active and passive smoking, dyslipidemia), and UC and CD activity indexes (Pediatric Ulcerative Colitis Activity Index and Pediatric Crohn's Disease Activity Index, respectively) were collected. The IMT of the carotid arteries was measured by high-resolution B-mode ultrasound, and endothelial function was evaluated by FMD in the brachial artery in response to reactive hyperemia.Results: Compared with controls, patients with CD had significantly greater exposure to passive smoking and had lower body mass index and high-density lipoprotein cholesterol values. IMT was significantly higher in patients than controls (P < .0001), and the percentage of FMD was significantly lower in both patients with CD (P < .0001) and patients with UC (P < .01) versus controls. In multivariate analysis, diagnosis of IBD was an independent risk factor for atherosclerosis.Conclusion: Premature endothelial dysfunction occurs in pediatric IBD. This represents a new challenge in the management of pediatric IBD, leading to prevention strategies of cardiovascular disease.

Early Developmental Outcomes following Major Noncardiac and Cardiac Surgery in Term Infants: A Population-Based Study - Corrected Proof

2012-05-14

Objective: To ascertain developmental differences between term infants after major noncardiac surgery and cardiac surgery compared with healthy control infants in New South Wales, Australia.Study design: This prospective population-based cohort study enrolled infants between August 1, 2006, and December 31, 2008, who required major noncardiac surgery within the first 90 days of life. Developmental outcomes were compared in these children, cohorts of term infants requiring cardiac surgery, and healthy controls. Infants were assessed at 1 year of age using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III).Results: Of the 784 infants enrolled, 688 (90.2%) of infants alive at 1 year were assessed. Of these, 539 infants were term and were included in the present analysis. Compared with controls, the infants who underwent cardiac surgery had significantly lower (P < .001) mean scores in all 5 BSID-III subscales, and the infants who underwent noncardiac surgery had significantly lower (P < .05) mean scores in 4 of the 5 BSID-III subscales. The greatest difference was in the incidence of gross motor delay in both the cardiac surgery group (OR, 0.25; 95% CI, 0.16-0.41) and the noncardiac surgery group (OR, 0.41; 95% CI, 0.26-0.63).Conclusion: This unique population-based prospective study compared the developmental outcomes of infants who underwent major noncardiac surgery and cardiac surgery. Major surgery in infants was found to be significantly associated with developmental delay at 1 year of age compared with control infants. These data have important implications for interventions and clinical review in the first year of life.

Healthcare Utilization and Comorbidity Burden among Children and Young Adults in the United States with Systemic Lupus Erythematosus or Inflammatory Bowel Disease - Corrected Proof

2012-05-14

Objective: We sought to assess the feasibility of using a health insurance claims database to estimate the prevalence and health care utilization and costs among children diagnosed with systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD).Study design: This was a retrospective analysis of the LifeLink insurance claims database for the years 2000-2006. Children (0-15 years) and young adults (16-25 years) with ≥2 diagnosis claims for SLE or IBD were selected as the 2 cohorts of interest. For each member of the SLE and IBD cohorts, 2 individuals were randomly selected for a matched comparison group. All the analyses were descriptive in nature, CI for differences between means and 2 proportions for measures including health care utilization, comorbidity burden were based on t tests and 2-group tests of proportions.Results: We identified 278 patients with SLE (prevalence estimate: 7.9 per/100 000 population) and 1174 patients with IBD (33.2 per/100 000 population). The mean annual total medical costs was substantially higher for the SLE (difference: $22 223; 95% CI: $14 961-$29 485) and IBD (difference: $16 238; 95% CI: $14 395-$18 082) cohorts compared with those of the comparator cohort. We observed higher comorbidity burdens in the SLE and IBD cohorts than we saw in the comparator cohort.Conclusions: Administrative claims data can be a useful tool for assessing the comparative prevalence and associated resource utilization of rare conditions such as SLE and IBD.

Risk Factors for Mortality in Children with Abusive Head Trauma - Corrected Proof

2012-05-14

Objective: We sought to identify risk factors for mortality in a large clinical cohort of children with abusive head trauma.Study design: Bivariate analysis and multivariable logistic regression models identified demographic, physical examination, and radiologic findings associated with in-hospital mortality of children with abusive head trauma at 4 pediatric centers. An initial Glasgow Coma Scale (GCS) ≤8 defined severe abusive head trauma. Data are shown as OR (95% CI).Results: Analysis included 386 children with abusive head trauma. Multivariable analysis showed children with initial GCS either 3 or 4-5 had increased mortality vs children with GCS 12-15 (OR = 57.8; 95% CI, 12.1-277.6 and OR = 15.6; 95% CI, 2.6-95.1, respectively, P < .001). Additionally, retinal hemorrhage (RH), intraparenchymal hemorrhage, and cerebral edema were independently associated with mortality. In the subgroup with severe abusive head trauma and RH (n = 117), cerebral edema and initial GCS of 3 or 4-5 were independently associated with mortality. Chronic subdural hematoma was independently associated with survival.Conclusions: Low initial GCS score, RH, intraparenchymal hemorrhage, and cerebral edema are independently associated with mortality in abusive head trauma. Knowledge of these risk factors may enable researchers and clinicians to improve the care of these vulnerable children.

Does Preterm Birth Influence Cardiovascular Risk in Early Adulthood? - Corrected Proof

2012-05-14

Objective: To investigate the effect of preterm birth on risk factors for cardiovascular disease (CVD), independent of birth size.Study design: Observational study using data of 406 healthy participants aged 18-24 years, from the PROgramming factors for Growth And Metabolism and Prematurity and Small for Gestational Age studies. Associations between gestational age (GA), systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), blood pressure variability, heart rate (HR), pulse wave velocity, and carotid intima media thickness (cIMT) were studied. To study the differential effects of preterm birth and small birth size for gestational age, these parameters were also analyzed in subgroups born either preterm or term: young adults born small for gestational age with short or normal adult stature, and young adults born appropriate for gestational age with normal adult stature.Results: Subjects born preterm (GA <36 weeks) had higher unadjusted SBP, PP, SBP and DBP variability, and HR, but a lower DBP than subjects born term. GA was inversely associated with SBP, PP, blood pressure variability, and HR, and positively associated with DBP, also after adjustment for confounders. There was no effect of GA on pulse wave velocity and cIMT, a marker of atherosclerosis. Of all the CVD risk factors measured, higher PP affected cIMT the most.Conclusions: Young adults born preterm might have a higher risk for CVD than those born term.

Umbilical Cord Milking Stabilizes Cerebral Oxygenation and Perfusion in Infants Born before 29 Weeks of Gestation - Corrected Proof

2012-05-14

Objective: To investigate the effects of umbilical cord milking at birth on cerebral perfusion and systemic perfusion in very low birth weight (VLBW) infants.Study design: Cerebral tissue oxygenation index and cerebral fractional tissue oxygen extraction were monitored in 50 stable VLBW infants (gestational age <29 weeks, birth weight <1250 g), with 26 allocated to the milked group and 24 to the control group. We used near-infrared spectroscopy 3-6, 12, 18, 24, 36, 48, and 72 hours after birth. Left ventricular end-diastolic dimension, left ventricular ejection fraction, left ventricle (LV) Tei index (measurement of left ventricular systolic and diastolic function), left ventricular cardiac output, and superior vena cava flow were measured concurrently using echocardiography.Results: There were no significant differences in gestational age and birth weight between the 2 groups. Hematocrit, left ventricular end-diastolic dimension, left ventricular cardiac output, and superior vena cava flow were higher in the milked group than in the control group, with improvement in the LV Tei index despite the absence of left ventricular ejection fraction changes within 24 hours after birth. Tissue oxygenation index increased and cerebral fractional tissue oxygen extraction decreased in the milked group within 24 hours after birth.Conclusion: Umbilical cord milking stabilized cerebral oxygenation and perfusion in VLBW infants by improving LV diastolic function by increasing LV preload.

Functional Defecation Disorders in Children: Comparing the Rome II with the Rome III Criteria - Corrected Proof

2012-05-14

Objectives: To evaluate the prevalence of pediatric functional defecation disorders (FDD) using the Rome III criteria and to compare these data with those obtained using Rome II criteria.Study design: A chart review was performed in patients referred to a tertiary outpatient clinic with symptoms of constipation and/or fecal incontinence. All patients received a standardized bowel questionnaire and physical examination, including rectal examination. The prevalence of pediatric FDD according to both Rome criteria sets was assessed.Results: Patients with FDD (n = 336; 61% boys, mean age 6.3 ± 3.5 SD) were studied: 39% had a defecation frequency ≤2/wk, 75% had fecal incontinence, 75% displayed retentive posturing, 60% had pain during defecation, 49% passed large diameter stools, and 49% had a palpable rectal fecal mass. According to the Rome III criteria, 87% had functional constipation (FC) compared with only 34% fulfilling criteria for either FC or functional fecal retention based on the Rome II definitions (P < .001). Of the patients with a rectal fecal mass, 95% would also have been correctly identified as having FC without a rectal examination. Twenty-nine patients (11%) fulfilled the criteria for functional nonretentive fecal incontinence according to both the Rome II and Rome III criteria.Conclusion: The pediatric Rome III criteria for FC are less restrictive than the Rome II criteria. The Rome III criteria are an important step forward in the definition and recognition of FDD in children.

The Increasing Onset of Type 1 Diabetes in Children - Corrected Proof

2012-05-14

Objective: To identify trends in the recent onset of type 1 diabetes (T1D) in Colorado youth seen at the Barbara Davis Center (BDC) and compare these changes over time.Study design: A retrospective chart review was performed of patients ages 0-20 years at diagnosis of T1D and type 2 diabetes who were seen at the BDC, were living within Colorado at diagnosis, and were seen within 1 month of diagnosis between 1996 and 2010. The review included age of onset, sex, month and season of onset, islet autoantibodies, diabetes type, hemoglobin A1c level, and body mass index.Results: Newly diagnosed youth with diabetes (n = 2841) were seen at the BDC between 1996 and 2010. Of these, 2686 (94.4%) had T1D. The number of newly diagnosed youth increased over the 15 years by 5.71% per year when adjusted for population (P < .0001). When analyzed in 5-year periods, the average number of new onset T1D cases, age-adjusted to the population, increased by 9.46% per year from 1996-2000 to 2001-2005. The increase was only 4.86% per year from 2001-2005 to 2006-2010. Islet autoimmune markers appeared to correlate with changes in T1D new onset cases.Conclusion: T1D in youth increased significantly from the late 1990s-2005 and has increased at a lesser rate more recently. Data suggests that even though T1D has increased in all age groups, the greatest increase was in the 5-9 year age category.

Natural History of Pediatric Intestinal Failure: Initial Report from the Pediatric Intestinal Failure Consortium - Corrected Proof

2012-05-14

Objective: To characterize the natural history of intestinal failure (IF) among 14 pediatric centers during the intestinal transplantation era.Study design: The Pediatric Intestinal Failure Consortium performed a retrospective analysis of clinical and outcome data for a multicenter cohort of infants with IF. Entry criteria included infants <12 months receiving parenteral nutrition (PN) for >60 continuous days. Enteral autonomy was defined as discontinuation of PN for >3 consecutive months. Values are presented as median (25th, 75th percentiles) or as number (%).Results: 272 infants with a gestational age of 34 weeks (30, 36) and birth weight of 2.1 kg (1.2, 2.7) were followed for 25.7 months (11.2, 40.9). Residual small bowel length in 144 patients was 41 cm (25.0, 65.5). Diagnoses were necrotizing enterocolitis (71, 26%), gastroschisis (44, 16%), atresia (27, 10%), volvulus (24, 9%), combinations of these diagnoses (46, 17%), aganglionosis (11, 4%), and other single or multiple diagnoses (48, 18%). Prescribed medications included oral antibiotics (207, 76%), H2 blockers (187, 69%), and proton pump inhibitors (156, 57%). Enteral feeding approaches varied among centers; 19% of the cohort received human milk. The cohort experienced 8.9 new catheter-related blood stream infections per 1000 catheter days. The cumulative incidences for enteral autonomy, death, and intestinal transplantation were 47%, 27%, and 26%, respectively. Enteral autonomy continued into the fifth year after study entry.Conclusions: Children with IF endure significant mortality and morbidity. Enteral autonomy may require years to achieve. Improved medical, nutritional, and surgical management may reduce time on PN, mortality, and need for transplantation.

Screening for Glucose-6-Phosphate Dehydrogenase Deficiency in Newborns—Practical Considerations - Corrected Proof

Jon F. Watchko — 2012-05-14

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked enzymopathy and noteworthy cause of severe neonatal hyperbilirubinemia and kernicterus worldwide. X-linkage of the G6PD gene results in hemizygous deficient males, homozygous deficient females, and a subset of affected heterozygous females via X-chromosome inactivation. This issue of The Journal features 2 reports on screening newborns for G6PD deficiency during their birth hospitalization. These are timely studies given the evolving debate over the need for, and potential utility of, point-of-care birth hospitalization screening for G6PD deficiency in the United States (A Planning Conference: Utility of Screening for G6PD Deficiency to Prevent Severe Neonatal Hyperbilirubinemia; May 11-12, 2007, Bethesda, MD; and A Stake-Holders Conference to Determine the Feasibility of G6PD Deficiency Identification for Prevention of Severe Neonatal Hyperbilirubinemia; July 28-29, 2009, Bethesda, Maryland) and elsewhere. These 2 reports: (1) demonstrate the clinical feasibility of point of care birth hospitalization G6PD enzyme activity assessment; (2) highlight the challenge of identifying G6PD deficiency in female heterozygotes; and (3) represent the 2 alternative screening strategies, universal and targeted for this condition. Each of these points merits further comment.

Delayed Onset Lactogenesis II Predicts the Cessation of Any or Exclusive Breastfeeding - Corrected Proof

Elizabeth Brownell, Cynthia R. Howard, Ruth A. Lawrence, Ann M. Dozier — 2012-05-11

Objective: To evaluate the association between delayed lactogenesis II (>3 days postpartum; delayed onset lactogenesis II [DLII]) and the cessation of any and exclusive breastfeeding at 4-weeks postpartum.Study design: We constructed multivariable logistic regression models using data from 2491 mothers enrolled in the prospective Infant Feeding Practice Study II cohort. Models included DLII, known risk factors for breastfeeding cessation (age, education, race, parity/previous breastfeeding, and exclusive breastfeeding plan), and potential confounders identified in bivariate analyses (P ≤ .1). Backward selection processes (P ≤ .1) determined risk factor retention in the final model.Results: DLII was associated with cessation of any and exclusive breastfeeding at 4-weeks postpartum (OR 1.62; CI 1.14-2.31; OR 1.62; CI 1.18-2.22, respectively); numerous independent risk factors qualified for inclusion in the multivariable model(s) and were associated with the outcome(s) of interest (eg, supplemental nutrition program for women, infants, and children enrollment, onset of prenatal care, feeding on-demand, time initiated first breastfeed, hospital rooming-in, obstetric provider preference for exclusive breastfeeding, and maternal tobacco use).Conclusions: Women experiencing DLII may be less able to sustain any and/or exclusive breastfeeding in the early postpartum period. Routine assessment of DLII in postpartum breastfeeding follow-up is warranted. Women with DLII may benefit from additional early postpartum interventions to support favorable breastfeeding outcomes.

Predictive Value of Serum Uric Acid Levels for the Diagnosis of Metabolic Syndrome in Adolescents - Corrected Proof

Jen-Yu Wang, Yen-Lin Chen, Chun-Hsien Hsu, Sai-Hung Tang, Chung-Ze Wu, Dee Pei — 2012-05-11

Objective: To evaluate the cause-effect relationships between serum levels of uric acid (UA) and metabolic syndrome (MetS) in an adolescent-male cohort that was followed for 2.7 years.Study design: We enrolled male adolescents aged between 10 and 15 years at the baseline. A total of 613 subjects were divided into quartiles according to their UA levels, from UA-1 (the lowest) to UA-4 (the highest).Results: After the mean follow-up period of 2.7 ± 0.97 years, 19 (3.1%) subjects developed MetS. Waist circumference (WC), systolic blood pressure, high density lipoprotein cholesterol (HDL-C), and log triglyceride levels were significantly related to baseline UA levels. Compared with the UA-1 group, subjects in the UA-4 group had significantly higher OR for abnormal WC, blood pressure, and HDL-C at the end of follow-up and had a 6.39-fold higher OR (95% CI 1.41-29.08; P < .05) for having MetS. Subjects with UA >7.6 mg/dL had a 4.32 (95% CI 1.57-11.93) higher risk of developing MetS.Conclusions: In this longitudinal study, we found that serum UA is correlated with future WC, systolic blood pressure, triglyceride, and HDL-C and is a risk factor for developing MetS. UA might be valuable in predicting adolescent MetS.

Physical Activity and Psychiatric Problems in Children - Corrected Proof

2012-05-11

We studied whether physical activity, measured by wrist-worn accelerometers, is associated with mother- and teacher-rated psychiatric problems in 8-year-old children (n = 199). Higher overall physical activity and more time spent in more intense physical activity were associated with lower odds for psychiatric problems in emotional, social, and behavioral domains.

Diagnosis of Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency Using High-Resolution Melting Analysis and a Clinical Scoring System - Corrected Proof

2012-05-11

Objective: To assess the diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) by using high-resolution melting (HRM) analysis and a clinical scoring system.Study design: Genetic variations in the 18 coding exons were prescreened using HRM analysis and then confirmed by direct sequencing. To establish a scoring system, clinical features of 20 patients with NICCD diagnosed in Taiwan between the years 2000 and 2008 were compared with those of 47 patients with biliary atresia and 35 with infantile cholestasis.Results: Eight types of mutations/polymorphisms were identified in patients with NICCD, including 5 mutations in the coding region or splice site (c.851del4, c.1638ins23, R553Q, IVS6+5G > A, IVS11+1G > A), and 3 single-nucleotide polymorphisms (IVS11+17C > G, IVS4+6A > G/rs6957975, and c.1194A > G/rs2301629). The 3 hotspot mutations (c.851del4, c.1638ins23, and IVS6+5G > A) comprised 33/35 (94.3%) mutated alleles. The patients with NICCD had a higher frequency of the rs6957975 polymorphism compared with 103 healthy controls (P < .0001). A 6-point scoring system was proposed according to clinical parameters. The patients with NICCD tended to score ≥4 points, whereas biliary atresia and other infantile cholestasis tended to score <4 points (P < .0001).Conclusions: HRM analysis was efficient and effective in detecting mutations. Three common mutations comprised the majority of mutations found in our patients. The IVS4+6A > G polymorphism was associated with NICCD. A scoring system may help to differentiate patients with NICCD from those with biliary atresia.

Systemic hyalinosis: new terminology, severity grading system, and surgical approach - Corrected Proof

Rafael Denadai, Debora Romeo Bertola, Cassio Eduardo Raposo-Amaral — 2012-05-11

We read with interest the study by Spiliopoulos et al. Although the nomenclature (systemic hyalinosis) used in their study indicates that infantile systemic hyalinosis and juvenile hyaline fibromatosis represent a single disease of varying severity, the term “systemic” excludes several patients with localized forms, including the boy reported by the authors. Thus, the adoption of another single term—hyaline fibromatosis syndrome (HFS)—seems to make the clinicopathological correlation in a clearer and simpler way for diagnosis. In addition, patients with HFS can be divided into mild, moderate, severe, and lethal subtypes (eg, the boy reported by Spiliopoulos et al could be classified as moderate) according to the modified severity grading system recently proposed by our group.

Spermatogenesis in a Prepubertal Boy - Corrected Proof

2012-05-11

A 7.5-year-old boy was evaluated for sparse unilateral right scrotal hair. No somatic growth spurt, acne, voice changes, body odor, or enlargement of penis was observed. Testicular volumes were 4 mL on the right and 2 mL on the left. Bone age was 6 years. Basal and stimulated gonadotropins and serum testosterone were in the prepubertal range. Adrenal androgens, 17-hydroxyprogesterone, and urinary steroid profile were normal. A diagnosis of isolated premature pubarche was made. At review 6 months later, no pubertal progression or acceleration in growth velocity was seen. Repeat ultrasound revealed a 2 × 3 × 3 mm hypoechoic mass. He underwent excision and histopathology confirmed the presence of a Leydig cell tumor with evidence of spermatocyte maturation ().

Hair-on-End Skull in an Infant without Anemia - Corrected Proof

Tai-Heng Chen, San-Nan Yang — 2012-05-11

A 10-month-old female presented 2 months after a minor head trauma with a history of persistent periorbital bruising, temporal bulging, and proptosis. Laboratory data reported thrombocytopenia without anemia. Skull radiograph revealed diffuse widening of sutures and sunburst periosteal reaction involving the bilateral facial and frontotemporal bones (, A). Cranial computed tomography showed a characteristic “hair-on-end” appearance of the skull (, B). Calvarial metastases were suspected; abdominal magnetic resonance imaging and excisional biopsy confirmed a primary left adrenal neuroblastoma.

Pulmonary Innate Immunity in Children with Protracted Bacterial Bronchitis - Corrected Proof

2012-05-11

Objective: To determine bronchoalveolar lavage (BAL) levels of 3 innate immunity components (human β-defensin-2 [hBD2], mannose-binding lectin [MBL], and surfactant protein-A [SP-A]), the relationship with airway neutrophilia and infection, and cytokine production of stimulated BAL cells in children with current protracted bacterial bronchitis (PBB), children with resolved PBB (PBB well), and controls.Study design: BAL of 102 children (mean age 2.8 years) fulfilling predefined criteria of current PBB (n = 61), PBB well (n = 20), and controls (n = 21) was cultured (quantitative bacteriology) and viruses examined by polymerase chain reaction. hBD2, MBL, and SP-A were measured, and cytokine production by lipopolysaccharide-stimulated BAL cells was determined.Results: Median hBD2 and MBL levels were significantly higher in the current PBB group (hBD2 = 164.4, IQR 0-435.5 pg/mL; MBL = 1.7, 0.4-4 ng/mL) than in the PBB well group (hBD2 = 0, IQR 0-85.2; MBL = 0.6, IQR 0.03-2.9) and controls (hBD2 = 3.6, IQR 0-126; MBL = 0.4, IQR 0.02-79). hBD2 was significantly higher in children with airway infection (n = 54; median 76.9, IQR 0-397.3) compared with those without (n = 48; 0, IQR 0-236.3), P = .04. SP-A levels and cytokine production of stimulated BAL cells were similar between groups.Conclusion: In children’s airways, hBD2, but not MBL and SP-A, relates to inflammation and infection. In children with PBB, mechanisms involving airway hBD2 and MBL are augmented. These pulmonary innate immunity components and the ability of BAL cells to respond to stimuli are unlikely to be deficient.

Cerebrospinal Fluid Reference Ranges in Term and Preterm Infants in the Neonatal Intensive Care Unit - Corrected Proof

2012-05-11

Objective: To determine reference ranges of cerebrospinal fluid (CSF) laboratory findings in term and preterm infants in the neonatal intensive care unit.Study design: Data were collected prospectively as part of a multisite study of infants aged <6 months undergoing lumbar puncture for evaluation of suspected sepsis. Infants with a red blood cell count >500 cells/μL or a known cause of CSF pleocytosis were excluded from the analysis.Results: A total of 318 infants met the inclusion criteria. Of these, 148 infants (47%) were preterm, and 229 (72%) received antibiotics before undergoing lumbar puncture. The upper reference limit of the CSF white blood cell (WBC) count was 12 cells/μL in preterm infants and 14 cells/μL in term infants. CSF protein levels were significantly higher in preterm infants (upper reference limit, 209 mg/dL vs 159 mg/dL in term infants; P < .001), and declined with advancing postnatal age in both groups (preterm, P = .008; term, P < .001). CSF glucose levels did not differ in term and preterm infants. Antibiotic exposure did not significantly affect CSF WBC, protein, or glucose values.Conclusions: CSF WBC counts are not significantly different in preterm and term infants. CSF protein levels are higher and decline more slowly with postnatal age in preterm infants compared with term infants. This study provides CSF reference ranges for hospitalized preterm and term infants, particularly in the first month of life.

The EPICure Study: Association between Hemodynamics and Lung Function at 11 Years after Extremely Preterm Birth - Corrected Proof

2012-05-11

Objective: To investigate the relationship between disturbed lung function and large-artery hemodynamics in school-age children born extremely preterm (EP) (at 25 completed weeks of gestation or less).Study design: This was a cross-sectional study of participants from the EPICure study, now aged 11 years (n = 66), and 86 age- and sex-matched term-born classmates. Spirometry parameters (including forced expiratory volume in 1 second), blood pressure, and augmentation index (AIx, a composite of arterial stiffness and global wave reflections) were measured.Results: Compared with their classmates, the EP children had significantly impaired lung function, particularly those with neonatal bronchopulmonary dysplasia. Peripheral blood pressure did not differ significantly between the 2 groups, but AIx values were on average 5% higher (95% CI, 2%-8%) in the preterm infants, remaining significant after adjustment for potential confounders. Neonatal bronchopulmonary dysplasia status was not related to AIx. Lung function and maternal smoking were independently associated with AIx; AIx increased by 2.7% per z-score reduction in baseline forced expiratory volume in 1 second and by 4.9% in those whose mothers smoked during pregnancy.Conclusion: The independent association between impaired lung function and cardiovascular physiology in early adolescence implies higher cardiovascular risk for children born EP, and suggests that prevention of chronic neonatal lung disease may be a priority in reducing later cardiovascular risk in preterm infants.

Late Onset Necrotizing Enterocolitis in Infants following Use of a Xanthan Gum-Containing Thickening Agent - Corrected Proof

Jennifer Beal, Benson Silverman, Jodeanne Bellant, Thomas E. Young, Karl Klontz — 2012-05-11

Adverse event reports submitted to the US Food and Drug Administration suggested a possible association between necrotizing enterocolitis and ingestion of a commercial feed thickener by premature infants. Review in 2011 of 22 cases with exposure revealed a distinct illness pattern.

Breastfeeding and oxycodone - Corrected Proof

Colleen M. Rivers, Dean Olsen, Lewis S. Nelson — 2012-05-11

We read with interest the retrospective study by Lam et al, in which the authors set out to quantify the central nervous system depression observed in neonates breastfed by mothers taking oxycodone, codeine, or acetaminophen. Given the multiple reports of infant death in the setting of being breastfed by mothers taking codeine, the increased potency of oxycodone compared with codeine at the mu opioid receptor, and fact that oxycodone is transferred into breast milk, the question posed by this group deserves serious attention. We commend their efforts but respectfully identify concerns in their methodology that question the validity of their conclusion that maternal oxycodone consumption is associated with infant central nervous system depression.

Eczema Herpeticum in Children: Clinical Features and Factors Predictive of Hospitalization - Corrected Proof

Nadia Jennifer Chiara Luca, Irene Lara-Corrales, Elena Pope — 2012-05-11

Objective: To describe the clinical characteristics of pediatric patients with eczema herpeticum and to determine the predictors of hospitalization, and recurrence and repeat episodes.Study design: A retrospective cohort study of patients 0-18 years of age diagnosed with eczema herpeticum between May 2000 and April 2009 was carried out at a tertiary pediatric care center in Canada. Seventy-nine patients were included. The primary outcome was hospitalization; secondary outcomes were recurrent and repeat episodes of eczema herpeticum.Results: At presentation, 76% of 79 patients with eczema herpeticum had a generalized eruption, 56% had fever, 37% had systemic symptoms, and 10% had eye involvement (keratoconjunctivitis). Forty-five patients (57%) were hospitalized. Predictors for hospitalization included male sex (OR = 3.09; 95% CI, 1.20-7.95, P = .017), fever (OR = 5.75; 95% CI, 2.17-15.26, P < .001), systemic symptoms (OR = 2.84; 95% CI, 1.06-7.62, P = .035), and age <1 year (OR = 7.17; 95% CI, 2.17-23.72, P = .001). Recurrence rate (<1 month) was 8.9% and rate of repeat episodes (>1 month) was 16%. Hospitalized patients were more likely to have a repeat episode (OR = 8.25; 95% CI, 0.99-68.69, P = .05). Patients with a previous history of eczema herpeticum had increased likelihood of early recurrence (OR = 6.80; 95% CI, 0.99-46.62, P = .05) and repeat episodes (OR = 9.43; 95% CI, 1.52-55.9, P = .01).Conclusions: Predictors of hospitalization in this cohort included male sex, age <1 year, fever, and systemic symptoms at presentation. Hospitalized patients may be at risk for repeat episodes of eczema herpeticum.

Reply - Corrected Proof

Jessica Lam, Parvaz Madadi, Gideon Koren — 2012-05-11

We would like to thank Rivers et al for their interest in our work. In our study, we compared the maternal reports of central nervous system (CNS) depression in breastfed infants exposed to oxycodone with those exposed to codeine or acetaminophen alone. Rivers et al raise a concern about the potential for recall bias in this study and suggested the need for quantitative data, such as “detection of infant urine oxycodone metabolite or determining the number of hours slept per day.” A closer examination of our study will reveal that we did indeed collect and report the number of hours that breastfed infants slept (Table VI). Furthermore, recall bias was controlled in our study design by the use of a non–opioid-exposure group—the acetaminophen cohort. Given that acetaminophen is not expected to result in neonatal CNS depression from a pharmacological standpoint, reports of CNS depression from mothers whose breastfed infants were exposed to only acetaminophen represent the baseline rates of CNS depression based on maternal report. This rate was determined to be 0.5%.

Attention Deficit Hyperactivity Disorder and Cognitive Function in Duchenne Muscular Dystrophy: Phenotype-Genotype Correlation - Corrected Proof

2012-05-07

Objectives: To assess attention deficit hyperactivity disorder (ADHD) in boys affected by Duchenne muscular dystrophy (DMD) and to explore the relationship with cognitive abilities and genetic findings.Study design: Boys with DMD (n = 103; 4-17 years of age, mean: 12.6) were assessed using a cognitive test (Wechsler scales). Assessment of ADHD was based on the Diagnostic Statistical Manual, Fourth Edition, Text Revision criteria and on the long version of the Conners Parents and Teachers Rating Scales.Results: ADHD was found in 33 of the 103 boys with DMD. Attention problems together with hyperactivity (17/33) or in isolation (15/33) were more frequent than hyperactivity alone, which was found in 1 patient. Intellectual disability (ID) was found in 27/103 (24.6%). Sixty-two of the 103 boys had no ID and no ADHD, 9 had ID but no ADHD, 14 had ADHD but no ID, and 18 had both. ADHD occurred more frequently in association with mutations predicted to affect Dp140 expression (exon 45-55) and in those with mutations predicted to affect all dystrophin product, including Dp71 (ie, those that have promoter region and specific first exon between exons 62 and 63 but were also relatively frequent).Conclusions: Our results suggest that ADHD is a frequent feature in DMD. The risk of ADHD appears to be higher in patients carrying mutations predicted to affect dystrophin isoforms expressed in the brain and are known to be associated with higher risk of cognitive impairment.

Transient Defect in Nitric Oxide Generation after Rupture of Fetal Membranes and Responsiveness to Inhaled Nitric Oxide in Very Preterm Infants with Hypoxic Respiratory Failure - Corrected Proof

Outi Aikio, Juhani Metsola, Reetta Vuolteenaho, Marja Perhomaa, Mikko Hallman — 2012-05-03

Objective: To study antenatal risk factors and inflammatory responses during hypoxic respiratory failure (HRF) in infants of very low gestational age (VLGA, ≤32.0 weeks).Study design: Of a cohort of 765 VLGA infants, 144 required mechanical ventilation. Airway specimens from these patients were prospectively studied. Infants who developed HRF (oxygenation index >25) with echocardiographic diagnosis of pulmonary hypertension were treated with inhaled nitric oxide (iNO). Three gestation comparison groups were formed on the basis of specific antenatal complications: prolonged preterm rupture of membranes (PPROM), spontaneous preterm birth, and preeclampsia. Chest radiographs were studied and airway specimens were analyzed for concentrations of tumor necrosis factor-α, interleukin (IL)-6, IL-8, IL-10, IL-12p70, IL-1β, and nitrite + nitrate over 4 days.Results: Seventeen (2.2% of all VLGA infants) developed HRF. In all 17 cases, PPROM complicated the antenatal course; these infants responded to iNO, regardless of infection or PPROM. The chest radiographs of HRF and non-HRF PPROM infants were similar. Airway proinflammatory cytokines and nitrite + nitrate levels were low in infants with HRF, but they increased during iNO treatment and remained elevated after discontinuation of iNO. Each of the 3 comparison groups had different and characteristic patterns of airway cytokines and nitrite + nitrate levels.Conclusions: Seven percent of VLGA infants with preterm rupture of membranes and 15% of those with PPROM developed HRF, characterized by pulmonary hypertension that acutely responds to iNO. These infants may have a transient deficiency in the inflammatory response, including a defect in nitric oxide generation in airspaces.

Hemodynamic Effects of Fluid Restriction in Preterm Infants with Significant Patent Ductus Arteriosus - Corrected Proof

2012-04-26

Objective: To determine the hemodynamic impact of fluid restriction in preterm newborns with significant patent ductus arteriosus.Study design: Newborns ≥24 and <32 weeks’ gestational age with significant patent ductus arteriosus were eligible for this prospective multicenter observational study. We recorded hemodynamic and Doppler echocardiographic variables before and 24 hours after fluid restriction.Results: Eighteen newborns were included (gestational age 24.8 ± 1.1 weeks, birth weight 850 ± 180 g). Fluid intake was decreased from 145 ± 15 to 108 ± 10 mL/kg/d. Respiratory variables, fraction of inspired oxygen, blood gas values, ductus arteriosus diameter, blood flow-velocities in ductus arteriosus, in the left pulmonary artery and in the ascending aorta, and the left atrial/aortic root ratio were unchanged after fluid restriction. Although systemic blood pressure did not change, blood flow in the superior vena cava decreased from 105 ± 40 to 61 ± 25 mL/kg/min (P < .001). The mean blood flow-velocity in the superior mesenteric artery was lower 24 hours after starting fluid restriction.Conclusions: Our results do not support the hypothesis that fluid restriction has beneficial effects on pulmonary or systemic hemodynamics in preterm newborns.

Obesity Care Strategies in Primary Care Practices - Corrected Proof

2012-04-26

We evaluated pediatric obesity clinics for internal referrals developed at 5 primary care offices. Clinics developed site-specific strategies: 1 group approach and 4 clinics providing individualized care only. Clinicians reported patient/family motivation as an important referral consideration and compliance as the greatest challenge and perceive clinics to have provided some help.

Preterm Infants of Lower Gestational Age at Birth Have Greater Waist Circumference-Length Ratio and Ponderal Index at Term Age than Preterm Infants of Higher Gestational Ages - Corrected Proof

2012-04-26

Objective: To assess anthropometric changes from birth to hospital discharge in infants born preterm and compare with a reference birth cohort of infants born full-term.Study design: Retrospective chart review was conducted of 501 preterm and 1423 full-term infants. We evaluated birth and hospital discharge weight, length, and waist circumference (WC). WC/length ratio (WLR), ponderal index, and body mass index (BMI) were calculated. Preterm infants were categorized into quartiles (Q1-4) based on birth weight (BW).Results: At birth mean length, WC, WLR, BMI, and ponderal index were all significantly less for preterm infants in the lowest BW quartile (Q1) than preterm infants in higher BW quartiles or full-term infants. Although their weight, length, and BMI remained significantly less at discharge, preterm infants in Q1 had a disproportionate increase in WLR and ponderal index such that at discharge their WLR and ponderal index were greater than infants in Q2-3 and comparable with infants in Q4 and full-term infants. Discharge WLR and ponderal index in Q1 were significantly higher with decreasing postmenstrual age at birth.Conclusions: Preterm infants of a lower birth postmenstrual age have disproportionate increases in WLR and ponderal index that are suggestive of increased visceral and total adiposity.

Predictive Value of Adenosine 5'-Monophosphate Challenge in Preschool Children for the Diagnosis of Asthma 5 Years Later - Corrected Proof

2012-04-26

We evaluated the predictive values of preschool bronchial challenge with nebulized adenosine 5'-monophosphate (AMP) using the auscultation method for having asthma 5 years later. Preschool AMP challenge had a high negative (90%) and a moderate positive (67%) predictive value for asthma 5 years later. Positive predictive value increased with the age at which the challenge was performed. The degree of preschool response to AMP was associated with the severity of asthma at school age.

Increased Inspired Oxygen in the First Hours of Life is Associated with Adverse Outcome in Newborns Treated for Perinatal Asphyxia with Therapeutic Hypothermia - Corrected Proof

Hemmen Sabir, Sally Jary, James Tooley, Xun Liu, Marianne Thoresen — 2012-04-20

Objective: To assess whether increased inspired oxygen and/or hypocarbia during the first 6 hours of life are associated with adverse outcome at 18 months in term neonates treated with therapeutic hypothermia.Study design: Blood gas values and ventilatory settings were monitored hourly in 61 newborns for 6 hours after birth. We investigated if there was an association between increased inspired oxygen and/or hypocarbia and adverse outcome (death or disability by Bayley Scales of Newborn Development II examination at 18-20 months).Results: Hypothermia was started from 3 hours 45 minutes (10 minutes-10 hours) and median lowest Pco2 level within the first 6 hours of life was 30 mm Hg (16.5-96 mm Hg). The median highest fraction of inspiratory oxygen within the first hour of life was 0.43 (0.21-1.00). The area under the curve fraction of inspiratory oxygen and Pao2 for hours 1-6 of life was 0.23 (0.21-1.0) and 86 mm Hg (22-197 mm Hg), respectively. We did not find any association between any measures of hypocapnia and adverse outcome (P > .05), but increased inspired oxygen correlated with adverse outcome, even when excluding newborns with initial oxygenation failure (P < .05).Conclusion: Increased fraction of inspired oxygen within the first 6 hours of life was significantly associated with adverse outcome in newborns treated with therapeutic hypothermia following hypoxic ischemic encephalopathy.

Youth Violence across Multiple Dimensions: A Study of Violence, Absenteeism, and Suspensions among Middle School Children - Corrected Proof

2012-04-20

Objective: To determine how multidimensional measures of violence correlate with school absenteeism and suspensions among middle school youth.Study design: A cross-sectional survey was conducted in 2004 with 28 882 sixth graders from an urban school district. Data were collected on role (witness, victim, perpetrator) and mode (verbal, physical, weapons) of past-year violence exposures, and absences and suspensions over 1 academic year. Associations between violence and absenteeism and suspension were estimated using generalized linear models.Results: ORs for suspension increased from witnessing to victimization to perpetration and then victimization-perpetration. Among those exposed to weapons, victims (ORboys = 1.45; ORgirls = 1.38) had similar or slightly higher ORs for absenteeism than perpetrators (ORboys = 1.39; ORgirls = 1.17). Boy victims and witnesses of physical violence had similar absenteeism patterns as those unexposed to physical violence. Of all exposed girls, victim-perpetrators had the highest ORs for absenteeism (OR = 1.76).Conclusion: Exposure to violence correlated with absenteeism and suspension. The strength of these relationships depended on mode and role in exposure. Our cross-sectional data limits our ability to establish causality. Findings have implications for prevention.

Sleep Problems, Fatigue, and Cognitive Performance in Chinese Kindergarten Children - Corrected Proof

2012-04-20

Objective: To examine sleep problems and fatigue and their associations with cognitive performance in Chinese kindergarten children.Study design: A cross-sectional analysis of baseline data from Jintan Child Cohort Study was conducted, which includes a cohort of 1656 kindergarten children in Jintan City, Jiangsu Province, China. The sample used in the current study consisted of 1385 children (44.8% girls, mean age 5.72 [SD = 0.42] years) for whom data on sleep problems or cognitive performance were available. Child Behavior Checklist was used to measure child sleep problems and fatigue, and Wechsler Preschool and Primary Scale of Intelligence–Revised was used to assess child IQ.Results: Sleep problems were prevalent, ranging from 8.9% for difficulty maintaining sleep to 70.5% for unwilling to sleep alone. Other reported sleep problems were difficulty initiating sleep (39.4%), nightmares (31.6%), sleep talking (28%), sleeping less (24.7%), and sleep resistance (23.4%). Fatigue was also prevalent, with 29.6% of children reported to be overtired and 12.6% lack of energy. Children with difficulty maintaining sleep, sleep talking, sleep resistance, or nightmares scored 2-3 points lower in full IQ than children without sleep problems. Children reported to have fatigue scored 3-6 points lower in full IQ than those children without fatigue.Conclusions: Sleep problems and fatigue are prevalent in Chinese kindergarten children. Furthermore, sleep problems and fatigue are associated with poor cognitive performance.

Cow’s Milk Challenge Increases Weakly Acidic Reflux in Children with Cow’s Milk Allergy and Gastroesophageal Reflux Disease - Corrected Proof

2012-04-19

Objective: To assess and compare the pattern of reflux in a selected population of infants with cow’s milk (CM) allergy (CMA) and suspected gastroesophageal reflux disease (GERD) while on dietary exclusion and following challenge with CM.Study design: Seventeen children (median age: 14 months) with a proven diagnosis of CMA and suspected GERD underwent 48-hour multichannel intraluminal impedance-pH monitoring. For the first 24 hours, the infants were kept on amino acid–based formula, and for the subsequent 24 hours, they were challenged with CM.Results: The total reflux episodes and the number of weakly acidic episodes were higher during CM challenge compared with the amino acid–based formula period [total reflux episodes: 105 (58-127.5) vs 65 (39-87.5), P < .001; weakly acidic episodes: 53 (38.5-60.5) vs 19 (13-26.5), P < .001; median (25th-75th)]. No differences were found for either acid or weakly alkaline episodes (not significant). The number of weakly acidic episodes reaching the proximal, mid, and distal esophagus was higher during CM challenge (P < .001). No differences were found in either acid exposure time or number of long-lasting episodes (not significant).Conclusions: In children with CMA and suspected GERD, CM exposure increases the number of weakly acidic reflux episodes. CM challenge during 48-hour multichannel intraluminal impedance-pH monitoring identifies a subgroup of patients with allergen-induced reflux, and in selected cases of children with CMA in whom GERD is suspected, its use could be considered as part of diagnostic work-up.

Thrombotic Complications and Thromboprophylaxis Across All Three Stages of Single Ventricle Heart Palliation - Corrected Proof

2012-04-19

Objectives: To describe the incidence of thrombotic complications across all 3 stages of single ventricle palliation and the association between thromboprophylaxis use and thrombotic risk.Study design: Two separate cross-sectional studies were performed that included 195 patients born between 2003-2008 and 162 patients who underwent Fontan after 2000.Results: The incidence of thrombotic complications was 40% and 28% after initial palliation and superior cavopulmonary connection (SCPC), respectively; 5-year freedom from thrombotic complications after Fontan was 79%. Thromboprophylaxis was initiated for 70%, 46%, and 94% of patients after initial palliation, SCPC, and Fontan, respectively. Thromboprophylaxis with enoxaparin (vs no thromboprophylaxis) was associated with a reduction in risk of thrombotic complications after initial palliation (hazard ratio [HR] 0.5, P = .05) and SCPC (HR 0.2, P = .04). Thromboprophylaxis with warfarin was associated with a reduction in thrombotic complications after Fontan (HR 0.27, P = .05 vs acetylsalicylic acid; HR 0.18, P = .02 vs no thromboprophylaxis). Thrombotic complications were associated with increased mortality after initial palliation (HR 5.5, P < .001) and SCPC (HR 12.5, P < .001). Three patients experienced major bleeding complications without permanent sequelae (2 enoxaparin, 1 warfarin).Conclusions: Given the negative impact of thrombotic complications on survival, the low risk of serious bleeding complications, and the association between thromboprophylaxis and lowered thrombotic complication risk across all 3 palliative stages, routine use of thromboprophylaxis from the initial palliation to the early post-Fontan period in this population may be indicated.

A Potential New Method to Estimate Tissue Cystine Content in Nephropathic Cystinosis - Corrected Proof

Ranjan Dohil, Alison Carrigg, Robert Newbury — 2012-04-19

Objectives: To evaluate intestinal mucosal cystine crystal (CC) load as a way to estimate tissue cystine content in children with cystinosis.Study design: Intestinal mucosal biopsies were obtained endoscopically from children (ages 2-18 years) with cystinosis. Using a special processing technique, CC within histiocytes were easily visible and enumerable in the mucosal tissue. Mean CC counts, calculated from stomach and duodenum combined (CC-GD), were correlated with duration of cysteamine treatment, estimated glomerular filtration rate (eGFR), and mean white blood cells (WBC) cystine levels.Results: Seventeen subjects (6 male) were enrolled in 2 studies from 2001 and 2003. The CC-GD count (mean 12.5 ± 1.41 crystals/histiocyte) was lower than the colonic crystal count (mean 23.6 ± 3.38, P = .0031). Nine of 17 subjects underwent repeated endoscopy 2 years later and the trend for CC-GD was to decrease over time (P = .065). Biopsies, however, were never completely depleted of CC. In subjects who were diagnosed before age 18 months, the percent change from baseline of both eGFR and CC-GD were inversely correlated (P = .026). Mean WBC cystine levels were positively correlated with CC-GD (P = .023).Conclusions: CC are easily visible in the intestinal mucosa. CC-GD counts appear to correlate with eGFR and may help monitor response to treatment. Even when mean WBC cystine levels are low, the mucosal CC are not depleted suggesting that tissue cysteamine levels may not achieve therapeutic efficacy.

Growth of Preterm and Full-Term Children Aged 0-4 Years: Integrating Median Growth and Variability in Growth Charts - Corrected Proof

2012-04-19

Objectives: To assess the distribution of height, weight, and head circumference (HC) in preterm infants for ages 0-4 years, by gestational age (GA) and sex, and to construct growth reference charts for preterm-born children, again by GA and sex, for monitoring growth in clinical practice.Study design: The community-based cohort study covered a quarter of the Netherlands. 1690 preterm infants (GA, 25-35+6 weeks) and a random sample of 634 full-term control infants (GA 38-41+6), who were followed from birth to 4 years of age. Height, weight, and HC were regularly assessed during routine well-child visits and data were retrospectively collected.Results: At all ages, the median height and weight of preterm children were lower compared with full-term children. Growth depended on the child's GA. Increase in HC showed an early catch-up and was similar to full-term children by the age of 1. Height, weight, and HC were more variable in boys, particularly in the very preterm children.Conclusions: At 0 to 4 years, the growth of preterm children differed from that of full-term children and depended on their GA. The greater variability of growth in boys suggests that they are more vulnerable to the complications of preterm birth that influence growth. These growth charts are the most precise tools currently available for monitoring growth in preterm children.

Obesity and Neglect: It's about the Child - Corrected Proof

David B. Allen, Norman Fost — 2012-04-16

Recently, controversy has arisen when a proposal for (and subsequent report of) state intervention to protect a child from life-threatening consequences of obesity was countered by assertions that removal of a child from his or her home was never justified by obesity alone. The predominantly negative reaction to considering such an intervention reflects a failure to address two issues: (1) persistent misunderstanding of the purpose of, and the criteria needed for, state action related to child neglect of any cause; and (2) doubt that consequences of obesity alone could ever meet this threshold. In this discussion, we apply principles that guide determination of child medical neglect in general to life-threatening childhood obesity, and specify the required conditions for state intervention that preserve both the possibility for and rarity of its necessity. The key concept is that extreme obesity alone does not constitute imminent harm, but in rare cases its health consequences do. In these rare cases, pediatricians are obligated, as in any situation of child abuse or neglect, to take necessary actions to protect the child.

Candida Virulence Properties and Adverse Clinical Outcomes in Neonatal Candidiasis - Corrected Proof

2012-04-16

Objective: To determine whether premature infants with invasive Candida infection caused by strains with increased virulence properties have worse clinical outcomes than those infected with less virulent strains.Study design: Clinical isolates were studied from 2 populations of premature infants, those colonized with Candida spp (commensal; n = 27) and those with invasive candidiasis (n = 81). Individual isolates of C albicans and C parapsilosis were tested for virulence in 3 assays: phenotypic switching, adhesion, and cytotoxicity. Invasive isolates were considered to have enhanced virulence if detected at a level >1 SD above the mean for the commensal isolates in at least one assay. Outcomes of patients with invasive isolates with enhanced virulence were compared with those with invasive isolates lacking enhanced virulence characteristics.Results: Enhanced virulence was detected in 61% of invasive isolates of C albicans and 42% of invasive isolates of C parapsilosis. All C albicans cerebrospinal fluid isolates (n = 6) and 90% of urine isolates (n = 10) had enhanced virulence, compared with 48% of blood isolates (n = 40). Infants with more virulent isolates were younger at the time of positive culture and had higher serum creatinine levels.Conclusion: Individual isolates of Candida species vary in their virulence properties. Strains with higher virulence are associated with certain clinical outcomes.

Health-Related Quality of Life and Behavior of Triplets at Adolescent Age - Corrected Proof

2012-04-16

Objectives: To assess health-related quality of life (HRQoL) and behavior of triplets compared with matched singletons at adolescent age and to identify medical and sociodemographic predictors of outcome.Study design: Fifty-four triplets (19 sets, mean [SD] gestational age 32.0 [2.4] weeks, birth weight 1580 [450] g) and 51 gestational age-, birth weight-, and sex-matched singleton controls self-rated their HRQoL at age 14.5 (0.3) years. Proxy reports about HRQoL and behavior were obtained by parents and teachers. HRQoL was measured with the Kidscreen-52 questionnaire child and parent form, and behavior with the Achenbach Child Behavior Checklist.Results: Self- and parent-reported HRQoL values was similar in both groups except for the dimensions “mood and emotions” and “autonomy,” which were better (P = .001, P = .03) in triplets. Parents reported significantly less behavioral problems in triplets compared with controls. Compared with community norms, both HRQoL and behavior measures in triplets were in the normal range. Parent-reported HRQoL was predicted by dichorionicity.Conclusions: HRQoL and behavioral outcome in adolescent triplets was good in our study and was, in some aspects, better than in matched singleton controls. Dichorionicity is an important outcome determinant.

Neonatal Benzodiazepines Exposure during Breastfeeding - Corrected Proof

Lauren E. Kelly, Shirley Poon, Parvaz Madadi, Gideon Koren — 2012-04-16

Objective: To assess central nervous system depression and other adverse effects in infants exposed to benzodiazepines through breast milk.Study design: A prospectively recruited, retrospectively assessed cohort study of mothers who contacted the Motherisk program regarding the safety of benzodiazepines and were invited to participate in a follow-up program regarding the effects of these medications on their infants during lactation.Results: A total of 124 consenting women participated. Adverse outcomes, specifically sedation, was identified in only 1.6% (2 of 124) of infants and was not associated with benzodiazepine dose, number of hours breastfed, or any demographic trait. Mothers reporting adverse outcomes in themselves (26% [32 of 124]) were more likely to be taking concomitantly a greater number of central nervous system depressants.Conclusions: This study supports the continued recommendation to initiate breastfeeding while taking benzodiazepines postpartum.

Bed sharing and sudden infant death syndrome - Corrected Proof

Roger W. Byard — 2012-04-16

In a meta-analysis by Vennemann et al regarding bed sharing and the risk of sudden infant death syndrome (SIDS), the authors concluded that “bed sharing is a risk factor for SIDS.” Although many infant deaths occur in shared sleeping situations, is it correct to attribute these deaths solely to SIDS and to not acknowledge other possibilities, such as suffocation? Infant deaths in shared sleeping situations on sofas are an excellent example of a dangerous sleeping environment—a short, sloping, and soft sleeping surface with a distinct possibility of infant wedging or overlaying—and yet the authors state that there is “an excess of SIDS bed sharing deaths on sofas.” Of note, they also comment that “emerging evidence suggests that there is also a significant interaction between bed sharing and parental use of drugs and alcohol.” Would not sedative substances in a parent's system be more likely to reduce parental rather than infant arousal, with potentially dire consequences for the infant? The recent finding of a difference in sex ratio between infants who die while sharing a sleeping surface with adults (M:F = 1:1) compared with those who die sleeping alone (M:F = 2:1) also suggests that the 2 groups may be different. It is recognized that the authors derived their data from previously published material. However, can such deaths be so confidently accepted as being due to SIDS in the face of risk factors for asphyxiation? In addition, it is not clear whether the studies that were analyzed had full death-scene examinations, which has been a standard requirement for the diagnosis of SIDS since 1991. In terms of understanding these deaths and recognizing the potential shortcomings of some of the data, it would seem appropriate to at least acknowledge the possibility of a potentially significant alternative diagnosis.

Blunt Head Trauma in Children in a Community Health Care Setting: Outcomes and Variables Associated with the Use of Computed Tomography - Corrected Proof

2012-04-16

Objective: To evaluate the incidence of clinically important traumatic brain injury (ciTBI) in children presenting to a community hospital setting and identified factors associated with computed tomography (CT) use.Study design: Retrospective cohort study of consecutive children presenting with blunt head trauma to a community emergency department or clinic over 12 months. Logistic regression models were used to compare differences in characteristics between patients who received and did not receive CT scans.Results: Of 1007 patients, 62% male, age 14 days-18 years (270 <2 years, 737 ≥2 years), 189 (18%) had CT scans, 2 (0.2%) showed evidence of ciTBI on CT, 13 (1.3%) hospitalized, and none required neurosurgical intervention or died. Factors associated with CT use in patients ≥2 years: history of vomiting (OR 4.08, 95% CI 2.08-7.99, P < .001), change in behavior (OR 2.83, 95% CI 1.63-4.91, P < .001), headache (OR 3.4, 95% CI 1.87-6.16, P < .001), loss of consciousness (OR 2.83, 95% CI 1.38-5.8, P = .004), and abnormal neurologic examination (OR 26.18, 95% CI 2.26-303.05, P = .009). Patients were more likely to receive CT scans in community emergency departments than clinics (OR 7.04, 95% CI 2.40-20.65, P = .002).Conclusion: Patients in our community hospital setting are at low risk of ciTBI. The clinical indicators used to determine the need for CT in patients with more significant mechanisms of injury to pediatric or academic centers may not apply to this group. Future studies are required to determine which clinical indications are significant in this setting.

Fifty Years of Surgery for Single Ventricle: Now What? - Corrected Proof

William T. Mahle, William L. Border — 2012-04-16

Although congenital heart defects that can be considered single ventricle lesions are relatively uncommon, they have been a major focus of pediatric cardiac research over the past 20 years. The fascination and struggle surrounding these patients with this condition relates to the unsatisfactory long-term outcomes that many practicing clinicians are observing. As a higher proportion of these patients survive to adolescence and adulthood, we are in the midst of a new wave of important cross-sectional data that demands a critical reappraisal of our conventional management strategies and may require a novel paradigm to translate the early surgical successes into a more sustainable success.

Reply - Corrected Proof

Ursula Kiechl-Kohlendorfer, Mechtild M. Vennemann — 2012-04-16

Clear selection criteria were set before reviewing the reports on bed sharing and sudden infant death syndrome (SIDS). Only studies in which an adequate definition for SIDS was given and in which autopsies were performed in >95% of cases were included in the meta-analysis. A comprehensive death scene investigation as a standard requirement for the diagnosis of SIDS was not explicitly mentioned in all of the included papers. Therefore, suffocation in a few cases cannot be ruled out.

The Two-Thumb Technique Using an Elevated Surface is Preferable for Teaching Infant Cardiopulmonary Resuscitation - Corrected Proof

Trang K. Huynh, Rae Jean Hemway, Jeffrey M. Perlman — 2012-04-16

Objectives: To determine whether the two-thumb technique is superior to the two-finger technique for administering chest compressions using the floor surface and the preferred location for performing infant cardiopulmonary resuscitation (CPR) (ie, floor, table, or radiant warmer).Study design: Twenty Neonatal Resuscitation Program trained medical personnel performed CPR on a neonatal manikin utilizing the two-thumb vs two-finger technique, a compression to ventilation ratio of 30:2 for 2 minutes in random order on the floor, table, and radiant warmer.Results: Compression depth favored the two-thumb over two-finger technique on the floor (27 ± 8 mm vs 23 ± 7), table (26 ± 7 mm vs 22 ± 7), and radiant warmer (29 ± 4 mm vs 23 ± 4) (all P < .05). Per individual subject, the compression depth varied widely using both techniques and at all surfaces. More variability between compressions was observed with the two-finger vs two-thumb technique on all surfaces (P < .05). Decay in compression over time occurred and was greater with the two-finger vs two-thumb technique on the floor (−5 ± 7 vs −1 ± 6 mm; P < .05) and radiant warmer (−3 ± 6 vs −0.3 ± 2 mm; P < .05), compared with the table (−3 ± 9 vs −4 ± 5 mm). Providers favored the table over radiant warmer, with the floor least preferred and most tiring.Conclusions: The two-thumb technique is superior to the two-finger technique, achieving greater depth, less variability, and less decay over time. The table was considered most comfortable and less tiring. The two-thumb technique should be the preferred method for teaching lay persons infant CPR preferably using an elevated firm surface.

Early Skin-to-Skin Care in Extremely Preterm Infants: Thermal Balance and Care Environment - Corrected Proof

2012-04-13

Objective: To evaluate infant thermal balance and the physical environment in extremely preterm infants during skin-to-skin care (SSC).Study design: Measurements were performed in 26 extremely preterm infants (gestational age 22-26 weeks; postnatal age, 2-9 days) during pretest (in incubator), test (during SSC), and posttest (in incubator) periods. Infants' skin temperature and body temperature, ambient temperature, and relative humidity were measured. Evaporimetry was used to determine transepidermal water loss, and insensible water loss through the skin was calculated.Results: The infants maintained a normal body temperature during SSC. Transfer to and from SSC was associated with a drop in skin temperature, which increased during SSC. Ambient humidity and temperature were lower during SSC than during incubator care. Insensible water loss through the skin was higher during SSC.Conclusion: SSC can be safely used in extremely preterm infants. SSC can be initiated during the first week of life and is feasible in infants requiring neonatal intensive care, including ventilator treatment. During SSC, the conduction of heat from parent to infant is sufficiently high to compensate for the increase in evaporative and convective heat loss. The increased water loss through the skin during SSC is small and should not affect the infant's fluid balance.

RICH (Rapidly Involuting Congenital Hemangioma): Not Only a Definition of Wealth - Corrected Proof

2012-04-13

We describe the case of a newborn female infant, born at term with a birth weight of 3750 g via uncomplicated vaginal delivery. On physical examination, a 5- × 4-cm, round, firm violaceous lesion surrounded by a pale halo was present on the left shoulder (, A). This lesion had not been detected by prenatal ultrasound. Ultrasonographic examination at birth showed a superficial mass, mostly confined to the subcutaneous tissue, uniformly hypoechoic, with a hyperechoic edge. The lesion was diffusely vascular, characterized by multiple vessels (, B), compatible with a rapidly involuting congenital hemangioma (RICH).