The Journal of Pediatrics

2013-06-01

Masthead

2013-06-01

Information for Readers

2013-06-01

Media and adolescents: a complex relationship

Thomas R. Welch — 2013-06-01

There has been a lot of attention paid in the lay media and professional literature to the impact of media on such outcomes as pediatric obesity and violence. Despite this attention, the primary research literature devoted to these topics is not extensive. The literature that does exist is complicated and does not lend itself to simple “sound bites.”

More support for diagnosis and treatment of HIV infection in early infancy

Sarah S. Long — 2013-06-01

In a trial comparing two treatment regimens of antiretroviral therapy (ART) with 48 months of follow-up in young children infected with HIV in South Africa, Shiau et al evaluated specific growth outcomes stratified by the age at initiation of ART. Data show that the trajectory of weight and height growth is more acute in those whose therapy was initiated before 6 months of age. In infants with early initiation of therapy, weight recovery neared population norms within 12 months, and height growth improved over 12-24 months and remained an average 1.0 score below population norms at 48 months of therapy. By 48 months of ART, growth outcomes were similar for groups of treated children regardless of age at commencement.

Generalists' role in vaccine safety reporting

Thomas R. Welch — 2013-06-01

Every pediatrician involved in the day-to-day process of administering vaccines is aware of how fraught with complexity it has become. On one hand, many pediatricians have seen in their professional lifetimes the virtual disappearance of once-feared childhood disorders. On the other hand, unwarranted concerns about vaccine safety are leaving more and more children unprotected.

Interventions and outcomes of preterms

Alan H. Jobe — 2013-06-01

The neurodevelopmental outcomes of preterm infants degrade as birth weight and gestational age decrease, and the best indicator for improved outcomes is the socioeconomic status of the family. In this issue of The Journal, Van Hus et al report that a 6-month behavioral assessment intervention program after hospital discharge had sustained beneficial effects for the children at 5.5 years of age—a remarkable outcome. Perhaps this package of interventions for at-risk infants and their families is contributing some of what is provided by higher socioeconomic status of families. The study demonstrates that the early discharge period is a vulnerable time for the very preterm infant.

Physical activity, sedentarism, and adiposity

Stephen R. Daniels — 2013-06-01

Although energy balance is clearly important in the process of obesity development, the relative contributions of sedentary time and moderate-to-vigorous physical activity have been questioned. In this issue of The Journal, Kwon et al address this question using data from the Iowa Bone Development Cohort Study, which is a longitudinal study of children followed from 8 to 13-15 years of age. The authors found that higher moderate-to-vigorous physical activity was associated with lower fat mass. Sedentary time and frequency of breaks in sedentary time were not associated with fat mass. These results do not mean that sedentary time is not important. It is clear that sedentary time can displace time for physical activity. These results emphasize the fact that sedentary time should be replaced with time devoted to moderate-to-vigorous physical activity to prevent increasing fat mass and obesity in children and adolescents.

More work to do in order to prevent dog bite injuries

Sarah S. Long — 2013-06-01

In a well done study by investigators at the Centers for Disease Control and Prevention of inpatient and outpatient care of American Indian and Native Alaska children given at Indian Health Service and tribal health facilities during 2001-2008, disproportionate rates of injuries were shown in these populations compared with the general US population. Outpatient visits peaked in Alaska Native boys 5-9 years old who had the alarming rate of visits for dog bite injury of 1% per year.

“Pharmaco-epidemiology”

Thomas R. Welch — 2013-06-01

Regular readers of The Journal will have noted an increasing number of published studies over the past few years based upon the mining of “administrative databases.” These are data that are generated for nonresearch purposes (eg, billing), but also contain information that can be employed for targeted clinical studies. The disadvantages of such an approach are many, not the least of which is that the data are very limited and not designed for clinical investigation. The powerful advantage of the approach is that it permits the analysis of huge amounts of data over a wide geographic and temporal range.

Pediatric Oncology in Developing Countries: Challenges and Solutions

Yasmine White, Valerie P. Castle, Andrew Haig — 2013-06-01

In developed countries, pediatric cancers are one of the leading causes of death in children. As the under-5-year mortality rate in developing countries drops because of improved sanitation, immunization, and access to basic medical care, pediatric cancers become increasingly important, rising to a position of the third or fourth most common cause of childhood death. It is estimated that 80%-85% of pediatric cancer cases occur in the developing world, where the 5-year survival can be less than 10% (in contrast to the US and western European countries, where it is approximately 70%). Individual physicians and institutions have developed several programs that model how pediatric cancers can be effectively treated in a resource-poor setting. International partnerships involving twinning, the development of supportive services, and telecare have all proven to be effective in improving pediatric cancer outcomes in developing countries.

Genetics and Pediatric Unconjugated Hyperbilirubinemia

Jon F. Watchko — 2013-03-01

Clinical studies of healthy adults suggest that ∼50% of total serum bilirubin variance can be explained by genetic factors. Hepatic bilirubin uridine diphosphate glucuronosyltransferase isoenzyme 1A1 (UGT1A1) (OMIM*191740) gene polymorphisms account for most of this variance. Solute carrier organic anion transporter 1B1 (SLCO1B1) (OMIM*604843) polymorphisms make a far less, but still significant, contribution. Even in newborns where nongenetic factors, incomplete penetrance of allelic variants, and developmental modulation of UGT1A1 and SLCO1B1 expression partially mask genetic contributors, a growing literature suggests a modulatory role of bilirubin metabolism gene variants on neonatal hyperbilirubinemia risk.

Changing the Paradigm in Pediatric Acute Kidney Injury

Patrick D. Brophy — 2013-03-04

In this issue of The Journal, Misurac et al provide a single-center tertiary care retrospective analysis of nonsteroidal anti-inflammatory drug (NSAID)-associated acute kidney injury (AKI), formerly known as acute renal failure, in a large pediatric cohort. During a 10-year period, they found that 2.7% of patients developed NSAID-associated AKI as diagnosed by The International Classification of Diseases, Ninth Revision, codes and stratified by the Pediatric Risk, Injury, Failure, Loss, End Stage (pRIFLE) criteria. These numbers may have been greater. However, the authors rightfully censured their data by excluding patients with multifactorial etiologies of AKI beyond NSAID use. What was surprising was the finding that the majority of these patients developed AKI despite receiving NSAID dosing determined on the basis of recommended guidelines.

Newborns and Other Children: In Defense of Differential Attitudes and Treatment

Lainie Friedman Ross, Joel E. Frader — 2013-02-18

In this issue of The Journal, Fontana et al provide data that infants in one large Montreal women’s and children’s hospital die differently than older children in the same institution. Their data reinforce findings from many studies in Europe, Canada, and the US: most pediatric deaths occur in intensive care units and involve some limitation of treatment, frequently the withdrawal of mechanical ventilation. Fontana et al also found that in their hospital, patients in the pediatric intensive care unit (PICU) were more likely to be physically unstable at the time of death, whereas death of patients in the neonatal intensive care unit (NICU) is more elective and the infants might have survived, albeit with uncertainty about any individual’s outcome. The authors suggest that this is evidence that we undervalue infants and that NICU babies deserve a decision-making process similar to that used for older children. They conclude by claiming, “If we can recognize the biases we have and the true reasoning behind our decision-making processes, only then can we be empowered to respond appropriately and consistently to the needs of sick children and their families.”

Ligation of the Patent Ductus Arteriosus in Preterm Infants: Understanding the Physiology

Afif F. El-Khuffash, Amish Jain, Patrick J. McNamara — 2013-02-13

The diagnosis and management of preterm neonates with a patent ductus arteriosus (PDA) that fails to close after medical management poses a major challenge. The association of prolonged ductal patency with morbidities including feeding intolerance, necrotizing enterocolitis (NEC), severe intraventricular hemorrhage (IVH), metabolic acidosis, renal failure, increased ventilator dependence, bronchopulmonary dysplasia (BPD), and pulmonary hemorrhage are well recognized. In addition, a PDA failing medical treatment is associated with a 4- to 7-fold increase in mortality. This association remains significant after adjustment for gestation, birth weight, disease severity, and other comorbidities, including IVH, NEC, and sepsis.

Modes of Death in Pediatrics: Differences in the Ethical Approach in Neonatal and Pediatric Patients

2013-01-14

Objective: To compare end-of-life decisions for neonatal and pediatric patients.Study design: This study involved a chart review of all pediatric deaths occurring over a 2-year period at a large maternal-child university hospital. Modes of death were compared.Results: Of the 220 deaths analyzed, 145 occurred in intensive care units (ICUs), including 77 in the neonatal ICU (NICU) and 68 in the pediatric ICU (PICU). Only 6% of deaths were preceded by cardiopulmonary resuscitation. Dying while on the respirator was the most common mode of death in the PICU (51%) and the least common in the NICU (5%; P < .05). Unstable physiology at time of death was much more common in the PICU (82% vs 47%; P < .05). Withdrawal of life-sustaining interventions (LSI) in stable patients for quality of life reasons was the most common cause of death in the NICU (53% vs 16%; P < .05). Seventy-five children died outside of an ICU because LSI were withheld; neonates died mainly of extreme prematurity, and older children died mainly from terminal illness.Conclusion: The majority of pediatric deaths occur in ICUs. Modes of death in the NICU and the PICU are strikingly different. A greater proportion of deaths in the NICU occur in infants with stable physiology who might not have died had LSI not been withdrawn. Most deaths outside of ICUs are attributable to withholding of LSI. A significant proportion of neonates in whom LSI are withheld have a possibility of intact survival, unlike older patients.

Sustained Developmental Effects of the Infant Behavioral Assessment and Intervention Program in Very Low Birth Weight Infants at 5.5 Years Corrected Age

2013-01-14

Objective: To evaluate the effect of the Infant Behavioral Assessment and Intervention Program (IBAIP) in very low birth weight (VLBW) infants on cognitive, neuromotor, and behavioral development at 5.5 years corrected age (CA).Study design: In a randomized controlled trial, 86 VLBW infants received post discharge IBAIP intervention until 6 months CA, and 90 VLBW infants received standard care. At 5.5 years CA, cognitive and motor development, and visual-motor integration were assessed with the Wechsler Preschool and Primary Scale of Intelligence, third Dutch version, the Movement Assessment Battery for Children, second edition, and the Developmental Test of Visual Motor Integration. Neurologic conditions were assessed with the neurologic examination according to Touwen, and behavior with the Strengths and Difficulties Questionnaire.Results: At 5.5 years CA, 69 children in the intervention and 67 children in the control group participated (response rate 77.3%). Verbal and performance IQ-scores <85 occurred significantly less often in the intervention than in the control group (17.9% vs 33.3%, P = .041, and 7.5% vs 21.2%, P = .023, respectively). However, after adjustment for differences, only the OR for performance IQ was significant: 0.24, 95% CI: 0.06-0.95. Adjusted mean scores on Wechsler Preschool and Primary Scale of Intelligence, third version subtasks block design and vocabulary, the Movement Assessment Battery for Children, second edition component aiming and catching, and the Developmental Test of Visual Motor Integration were significantly better in the intervention group. No intervention effect was found on the Strengths and Difficulties Questionnaire.Conclusion: The IBAIP leads, 5 years after the early neurobehavioral intervention, to improvements on performance IQ, ball skills, and visual-motor integration at 5.5 years CA.

50 Years Ago in The Journal of Pediatrics: Neonatal Fibrous Dysplasia

Melissa S. Putman, Catherine M. Gordon — 2013-06-01

Turner AF, Mikity VG, Meyers HI. J Pediatr 1963;62:936-7 Fifty years ago, Turner et al reported the first case of fibrous dysplasia (FD) occurring during infancy in The Journal. Shortly after birth, the patient was diagnosed with a cyst-like lesion involving the distal portion of her left fibula. The lesion was biopsied, confirming FD. A tibial graft was later performed because of progressive bony deformity, which was complicated by nonunion of the distal portion. Although the etiology of FD was unknown at the time of this report, the authors postulated that it may be a congenital disorder given the early presentation of this patient.

Late-Onset Sepsis in Very Low Birth Weight Infants from Singleton and Multiple-Gestation Births

2013-01-15

Objectives: To describe and compare the incidence of late-onset sepsis (LOS) and demographic and clinical characteristics associated with LOS in very low birth weight (VLBW) infants from singleton and multiple births, and to examine the heritability of susceptibility to LOS among VLBW twins by comparing same-sex and unlike-sex twin pairs.Study design: The study group comprised infants with birth weight 401-1500 g seen at clinical centers of the Eunice Kennedy Shriver National Institute of Child and Human Development Neonatal Research Network between 2002 and 2008. Only the first episode of LOS was included in our analysis. Stepwise logistic regression models were fitted separately for singleton and multiple pregnancies to examine the maternal and neonatal factors associated with LOS. LOS due solely to gram-negative bacteria in singleton and multiple pregnancies was also examined in separate models. The heritability of LOS was estimated by examining the concordance of LOS in twins from same-sex and unlike-sex pairs.Results: LOS occurred in 25.0% (3797 of 15 178) of singleton and 22.6% (1196 of 5294) of multiple-birth VLBW infants. Coagulase-negative staphylococci were the most common infecting organisms, accounting for 53.2% of all LOS episodes in singletons and 49.2% in multiples. Escherichia coli and Klebsiella species were the most commonly isolated gram-negative organisms, and Candida albicans was the most commonly isolated fungus. Concordance of LOS did not differ significantly between same-sex and unlike-sex twin pairs.Conclusion: LOS remains a common problem in VLBW infants. The incidence of LOS is similar for singleton and multiple-birth infants. The similar concordance of LOS in same-sex and unlike-sex twin pairs provides no evidence that susceptibility to LOS among VLBW infants is genetically determined.

Cause-Specific Mortality of Very Preterm Infants and Antenatal Events

2013-01-21

Objective: To assess the relationship between antenatal factors and cause-specific risk of death in a large area-based cohort of very preterm infants.Study design: The ACTION (Accesso alle Cure e Terapie Intensive Ostetriche e Neonatali) study recruited during an 18-month period all infants 22-31 weeks' gestational age admitted to neonatal care in 6 Italian regions (n = 3040). We analyzed the data of 2974 babies without lethal or acutely life-threatening malformations. Cause-specific risks of death adjusted for competing causes were calculated, and region-stratified multiple Cox regression analyses were used to study the association between cause-specific mortality and infants' characteristics, pregnancy complications, antenatal steroids, and place of birth.Results: Deaths attributable to respiratory problems and intraventricular hemorrhage prevailed in the first 2 weeks of life, and those attributable to infections and gastrointestinal diseases afterwards. Antepartum hemorrhage was associated with respiratory deaths (hazard ratio [HR] 1.6, 95% CI 1.1-2.4), and maternal infection with deaths attributable to asphyxia (HR 32.5, 95% CI 4.1-259.4) and to respiratory problems (HR 2.8, 95% CI 1.6-5.2). Preterm premature rupture of membranes increased the likelihood of deaths due to neonatal infection (HR 1.8, 95% CI 1.0-3.1), and preterm labor/contractions of those due to respiratory (HR 1.5, 95% CI 1.1-2.0) and gastrointestinal diseases (HR 5.8, 95% CI 2.1-16.3). In addition, a birth weight z-score <−1 was associated with increasing hazards of death resulting from asphyxia, late infections, respiratory, and gastrointestinal diseases.Conclusions: Different complications of pregnancy lead to different cause-specific mortality patterns in very preterm infants.

Positioning Effects on Lung Function and Breathing Pattern in Premature Newborns

2013-01-14

Objective: To compare breathing patterns and lung function in the supine, lateral, and prone positions in oxygen-dependent preterm infants.Study design: Respiratory function in preterm infants receiving nasal continous positive airway pressure therapy for mild respiratory failure was evaluated by respiratory inductive plethysmography. Infants were randomized to supine, left lateral, and prone positions for 3 hours. A nest provided a semiflexed posture for the infants placed in the left lateral position, similar to the in utero position. Tidal volume (Vt), phase angle between abdominal and thoracic movements, rib cage contribution to Vt, and dynamic elevation of end-expiratory lung volume were measured.Results: Fraction of inspired O2 was similar in the 3 positions for 19 infants (mean gestational age, 27 ± 2 weeks; mean birth weight, 950 ± 150 g; mean postnatal age, 17 ± 5 days). However, arterial O2 saturation and Vt were higher in the left lateral and prone positions than in the supine position (P < .05). The phase angle between abdominal and thoracic movements was lower and rib cage contribution to Vt was higher in the left lateral and prone positions than in the supine position (P < .05). Dynamic elevation of end-expiratory lung volume was greater in the supine position than in the left lateral and prone positions (P < .05).Conclusion: In oxygen-dependent preterm infants, both the left lateral and prone positions improve lung function by optimizing breathing strategy. In the neonatal intensive care unit, the left lateral position can be used as an alternative to the prone position for mild respiratory failure.

Initiation of Antiretroviral Therapy Before 6 Months of Age is Associated with Faster Growth Recovery in South African Children Perinatally Infected with Human Immunodeficiency Virus

2013-01-14

Objective: To describe the effects of age at antiretroviral therapy (ART) initiation on growth outcomes among children infected with HIV followed for 48 months after treatment initiation.Study design: This secondary analysis describes anthropometric changes in children infected with HIV in Johannesburg, South Africa who initiated ritonavir-boosted lopinavir-based ART before 24 months of age and were randomized to continue ritonavir-boosted lopinavir or to receive nevirapine after achieving and maintaining virologic suppression. Weight, height, and head circumference were measured at visits over 48 months post-ART initiation. Growth patterns including weight-for-age z-scores (WAZs), height-for-age z-scores, body mass index-for-age z-scores, and head circumference for age z-score were compared between children initiating ART <6 months, 6-12 months, and 12-24 months of age.Results: A total of 195 children (mean ± SD age 10.7 ± 5.9 months), including 54 (27.7%) <6 months, 69 (35.4%) 6-12 months, and 72 (36.9%) 12-24 months of age at ART initiation, were evaluated. In the first 12 months on treatment, children <6 months of age at ART initiation experienced more rapid improvement in WAZ (1.98 vs 1.44, P = .084) and head circumference for age z-score (1.24 vs 0.45, P = .004) than children who initiated ART between 12-24 months of age. By 48 months on ART, growth outcomes were similar, regardless of age at ART initiation. WAZ approached population norms by 12 months on ART. Although improving, height-for-age z-scores remained on average 1.0 z-score below population norms at 48 months of therapy.Conclusions: Initiation of ART before 6 months of age results in more rapid growth recovery in children infected with HIV. These data provide further evidence for the importance of prompt diagnosis and early initiation of ART for infants infected with HIV.

UGT1A1 Genetic Analysis as a Diagnostic Aid for Individuals with Unconjugated Hyperbilirubinemia

2013-01-07

Objective: To assess the clinical utility of UGT1A1 genetic testing and describe the spectrum and prevalence of UGT1A1 variations identified in pediatric unconjugated hyperbilirubinemia (UCH), and to characterize specific genotype-phenotype relationships in suspected Gilbert and Crigler–Najjar syndromes.Study design: A retrospective study was conducted to review clinical information and UGT1A1 genotyping data from 181 pediatric patients referred for UCH. In silico analyses were performed to aid in the assessment of novel UGT1A1 variants.Results: Overall, 146/181 pediatric patients had at least one heterozygous UGT1A1 functional variant. Identified UGT1A1 variants included 17 novel variants, 7 rare star alleles, and 1 rare variant. There were 129 individuals who possessed the TA7 (*28) promoter repeat and 15 individuals who possessed the *6 (c.211G > A) variation. Out of the 104 individuals with accompanying bilirubin levels, 41 individuals did not have identifiable UGT1A1 variants that explained their UCH, although glucose-6-phosphate dehydrogenase deficiency and other causes of UCH could not be ruled out.Conclusion: Much of the observed UCH could be attributed to variation at the UGT1A1 locus, and UGT1A1 testing helped to substantiate a genetic diagnosis, thereby aiding in individual and family disease management. Although UGT1A1 variation plays a large role in UCH, genetic assessment of UGT1A1 alone may not be comprehensive. Assessment of additional genes may also be useful to evaluate genetic causes for UCH.

Nonsteroidal Anti-Inflammatory Drugs Are an Important Cause of Acute Kidney Injury in Children

2013-01-28

Objective: To characterize nonsteroidal anti-inflammatory drug (NSAID)-associated acute kidney injury (AKI) in children.Study design: We conducted a retrospective chart review of children diagnosed with AKI through the use of International Classification of Diseases, Ninth Revision diagnosis code 584.5 or 584.9 from January 1999 to June 2010. Medical records were reviewed to confirm the diagnosis of AKI and to quantify NSAID administration. Pediatric RIFLE criteria were used to codify AKI. Patients were not classified as having NSAID-associated AKI if they had a diagnosis explaining AKI or comorbid clinical conditions predisposing to AKI development.Results: Patients (N = 1015) were identified through International Classification of Diseases, Ninth Revision screening. Twenty-one children had clinical, laboratory, and radiographic studies suggesting NSAID-associated acute tubular necrosis and 6 had findings suggesting NSAID-associated acute interstitial nephritis, representing 2.7% (27 of 1015) of the total cohort with AKI and 6.6% when excluding complex patients with multifactorial AKI. Children with NSAID-associated AKI had a median (range) age of 14.7 years (0.5-17.7 years); 4 patients (15%) were <5 years old. Fifteen of 20 children (75%) for whom dosing data were available received NSAIDs within recommended dosing limits. Patients <5 years old were more likely to require dialysis (100% vs 0%, P < .001), intensive care unit admission (75% vs 9%, P = .013), and a longer length of stay (median 10 vs 7 days, P = .037).Conclusions: NSAID-associated AKI accounted for 2.7% of AKI in this pediatric population. AKI typically occurred after the administration of correctly dosed NSAIDs. Young children with NSAID-associated AKI may have increased disease severity.

Alterations in Ventricular Structure and Function in Obese Adolescents with Nonalcoholic Fatty Liver Disease

2012-12-20

Objective: To determine the association among nonalcoholic fatty liver disease (NAFLD), metabolic function, and cardiac function in obese adolescents.Study design: Intrahepatic triglyceride (IHTG) content (magnetic resonance spectroscopy), insulin sensitivity and β-cell function (5-hour oral glucose tolerance test with mathematical modeling), and left ventricular function (speckle tracking echocardiography) were determined in 3 groups of age, sex, and Tanner matched adolescents: (1) lean (n = 14, body mass index [BMI] = 20 ± 2 kg/m2); (2) obese with normal (2.5%) IHTG content (n = 15, BMI = 35 ± 3 kg/m2); and (3) obese with increased (8.7%) IHTG content (n = 15, BMI = 37 ± 6 kg/m2).Results: The disposition index (β-cell function) and insulin sensitivity index were ∼45% and ∼70% lower, respectively, and whole body insulin resistance, calculated by homeostasis model of assessment-insulin resistance (HOMA-IR), was ∼60% greater, in obese than in lean subjects, and ∼30% and ∼50% lower and ∼150% greater, respectively, in obese subjects with NAFLD than those without NAFLD (P < .05 for all). Left ventricular global longitudinal systolic strain and early diastolic strain rates were significantly decreased in obese than in lean subjects, and in obese subjects with NAFLD than those without NAFLD (P < .05 for all), and were independently associated with HOMA-IR (β = 0.634). IHTG content was the only significant independent determinant of insulin sensitivity index (β = −0.770), disposition index (β = −0.651), and HOMA-IR (β = 0.738).Conclusions: These findings demonstrate that the presence of NAFLD in otherwise asymptomatic obese adolescents is an early marker of cardiac dysfunction.

50 Years Ago in The Journal of Pediatrics: The Vectorcardiographic Significance of Upright T Waves in V1 and V2 during the First Months of Life

Samuel S. Gidding — 2013-06-01

Castellanos A Jr, Lemberg L, Catellanos A. J Pediatr 1963;62:827-37 Fifty years ago, the diagnosis of congenital heart disease relied on integrating clinical information from physical examination, radiography, and electrocardiography. Right ventricular hypertrophy detected on electrocardiography after day 4-7 of life was one of the most important of these criteria, with the absence of the transition from the upright T wave seen in the first few days of life to an inverted T wave in the right chest leads seen during childhood defined right ventricular hypertrophy. Castellanos et al present typical electrocardiograms and vectorcardiograms of infants with persistent upright T waves secondary to congenital heart disease and uncommon transient alterations in the electrocardiogram secondary to metabolic disturbance. Notably absent from the article is an analysis of the sensitivity and specificity of persistent upright T waves for diagnosing congenital heart disease.

Which Contributes More to Childhood Adiposity-High Levels of Sedentarism or Low Levels of Moderate-through-Vigorous Physical Activity? The Iowa Bone Development Study

Soyang Kwon, Trudy L. Burns, Steven M. Levy, Kathleen F. Janz — 2013-01-10

Objective: To examine the relative importance of sedentarism and moderate-to-vigorous physical activity for adiposity development in children and adolescents.Study design: A total of 277 boys and 277 girls (95% white; two-thirds of parents with college graduation or higher education) from the Iowa Bone Development Cohort Study completed body fat and accelerometry measurement at examinations of 8, 11, 13, and/or 15 years of age (during 2000-2009). The main exposure was accelerometry-measured sedentary time, frequency of breaks in sedentary time, and moderate- to vigorous-intensity physical activity time. The outcome was dual energy x-ray absorptiometry-measured body fat mass.Results: Adjusted for age, height, physical maturity, and sedentary time, growth models showed that high moderate-to-vigorous physical activity time was associated with low body fat mass in both boys (coefficient β = −0.10 ± 0.02) and girls (β = −0.05 ± 0.01; P < .01). However, sedentary time and frequency of breaks in sedentary time were not associated with body fat mass.Conclusions: This study does not support an independent effect of sedentarism on adiposity. The preventive effect of moderate- to vigorous-intensity physical activity on adiposity in children and adolescents remained strong after adjusting for the effect of sedentarism.

Reality Television Predicts Both Positive and Negative Outcomes for Adolescent Girls

Christopher J. Ferguson, Kimberlee Salmond, Kamla Modi — 2013-01-07

Objective: To assess the influence of media, specifically reality television, on adolescent behavior.Study design: A total of 1141 preteen and adolescent girls (age range 11-17) answered questions related to their reality television viewing, personality, self-esteem, relational aggression, appearance focus, and desire for fame.Results: Our results indicated that the influence of reality television on adolescent behavior is complex and potentially related to the adolescents' intended uses and gratifications for using reality television. Reality television viewing was positively related to increased self-esteem and expectations of respect in dating relationships. However, watching reality television also was related to an increased focus on appearance and willingness to compromise other values for fame. Reality television viewing did not predict relational aggression.Conclusion: The potential influences of reality television use on adolescent girls are both positive and negative, defying easy categorization.

50 Years Ago in The Journal of Pediatrics: Pleural Effusion in the Neonatal Period

Farouk H. Sadiq — 2013-06-01

Perry RE, Hodgman J, Cass AB. J Pediatr 1963;62:838-43 Perry et al presented a single case of a term newborn infant with chylous pleural effusion, and reviewed eleven other cases that had been reported in the literature. Many of these required repeated thoracentesis before resolution. Three patients died from malnutrition (protein loss) and secondary infection. The etiology of pleural effusion in most of these cases was thought to be due to defects in the thoracic duct.

Wireless Motility Capsule Test in Children with Upper Gastrointestinal Symptoms

2013-01-07

Objective: To compare scintigraphic gastric emptying and antroduodenal manometry (ADM) studies with the wireless motility capsule test in symptomatic pediatric patients.Study design: Patients aged 8-17 years with severe upper gastrointestinal symptoms (ie, nausea, vomiting, retching, abdominal pain) referred for ADM were recruited. A standardized protocol for ADM was used. On a different day, participants were given a standardized meal and then swallowed the wireless motility capsule. A wireless receiver unit worn during the study recorded transmitted data. If not performed previously, a 2-hour scintigraphic gastric emptying study was completed at the time of ADM testing.Results: A total of 22 patients were recruited, of whom 21 had complete scintigraphic gastric emptying study data and 20 had complete ADM data. The wireless motility capsule test had 100% sensitivity and 50% specificity in detecting gastroparesis compared with the 2-hour scintigraphic gastric emptying study. The wireless motility capsule test detected motor abnormalities in 17 patients, compared with 10 detected by ADM. Dichotomous comparison yielded a diagnostic difference between ADM and the wireless motility capsule test (P < .01). Migrating motor complexes were recognized in all patients by both ADM and the wireless motility capsule test. The wireless motility capsule test was well tolerated in all patients, and there were no side effects.Conclusion: In symptomatic pediatric patients, the wireless motility capsule test is highly sensitive compared with scintigraphic gastric emptying studies in detecting gastroparesis, and seems to be more sensitive than ADM in detecting motor abnormalities.

50 Years Ago in The Journal of Pediatrics: A Note on Studies of Salt Excretion in Sweat: Relationships between Rate, Conductivity, and Electrolyte Composition of Sweat from Patients with Cystic Fibrosis and from Control Subjects

Tanja Gonska — 2013-06-01

Gibson, LE, di Sant’Agnese, PA. J Pediatr 1963;62:855-67 The sweat test is inseparably linked to cystic fibrosis (CF). In fact, early observations of high salt losses in the sweat of patients with CF not only led to the development of the sweat chloride test in 1959, but also attracted researchers to work on sweat glands to search for the primary disease defect. Using a highly innovative approach, Gibson and Sant’Agnese built a device to demonstrate in vivo a linear relation between sweat secretion and salt excretion. Knowing that sweat glands consist of a coil secreting a precursor fluid and a tubule system to reabsorb salt, the authors concluded that the precursor fluid (and not tubular fluid re-absorption) is different and, thus, defective in CF. Today, we know that defective re-absorption of salt in the sweat tubule system is responsible for elevated sweat sodium and chloride concentrations in patients with CF. The precursor fluid, the primary fluid secreted in the coil of sweat glands, is isotonic and unaltered in CF.

Stool Consistency, but Not Frequency, Correlates with Total Gastrointestinal Transit Time in Children

2013-01-14

Objectives: To evaluate the correlation between stool characteristics (consistency and frequency) and gut transit time in children and to determine whether the Bristol Stool Form Scale is a reliable method of assessing intestinal transit rate in children.Study design: From March 2011 to March 2012, 44 children (25 boys and 19 girls, mean age 7.8 years) with a diagnosis of functional constipation and 36 healthy, nonconstipated children (17 boys and 19 girls, mean age 7.6 years) were enrolled. All participants maintained a 1-week stool diary, recording the time and date of every bowel movement and stool form, and then completed a validated questionnaire on functional constipation according to Rome III criteria. Whole gut transit time (WGTT) was then assessed using the radiopaque markers test.Results: There was a significant correlation between stool form and WGTT in both constipated and nonconstipated children (correlation coefficient −0.84, P < .001). By contrast, there was no correlation between either stool frequency and WGTT or stool frequency and stool form. Multivariate logistic regression analysis, using WGTT as a dependent variable, showed that the sole variable significantly associated with WGTT was stool form (regression coefficient 2.9, OR 18.4, 95% CI 5.4-62.5, P < .001).Conclusion: In this prospective, observational, case-control study, we show that stool form, as measured by the Bristol Stool Form Scale, rather than stool frequency, correlates with WGTT in both constipated and nonconstipated children.

Cardiac Function in Congenital Adrenal Hyperplasia: A Pattern of Reversible Cardiomyopathy

2013-01-21

Objective: To evaluate cardiac function in infants with congenital adrenal hyperplasia (CAH) before and after corticosteroid replacement therapy.Study design: This prospective, case-control study included 9 infants with CAH. Cardiac function was assessed by echocardiography at presentation and after corticosteroid replacement therapy. Six term infants underwent 2 echocardiograms each and served as the control group. Data on fractional shortening (FS), rate-corrected velocity of circumferential fiber shortening (Vcf), wall stress, tissue Doppler indices, myocardial performance index, left ventricular mass, and Vcf/wall stress were obtained.Results: The infants with CAH exhibited myocardial dysfunction at baseline and lower systolic blood pressure (SBP) compared with the control group. FS, a measure of systolic contractility, differed significantly from before to after corticosteroid treatment (mean, 32.3% ± 4.7% pretreatment, 39.9% ± 5.0% posttreatment). Vcf, a preload-independent measure of cardiac contractility, also differed significantly before and after treatment (mean, 1.23 ± 0.16 circumferences/second pretreatment, 1.45 ± 0.22 circumferences/second posttreatment). SBP was also lower (mean, 84 ± 9.3 mmHg) and improved with treatment (mean, 95 ± 4.8 mmHg). The control group demonstrated no statistically significant changes in FS, Vcf, or SBP. There was a change in left ventricular mass in the control group between the 2 studies.Conclusion: Newborns with CAH have evidence for cardiac dysfunction at baseline that reverses with corticosteroid replacement therapy. These data suggest that corticosteroids play a direct role in modulating cardiac function in the newborn.

Low Total, Low-Density Lipoprotein, High-Density Lipoprotein, and Non–High-Density Lipoprotein Cholesterol Levels in Patients with Complex Congenital Heart Disease after Fontan Palliation

Wendy Whiteside, Meng Tan, Sunkyung Yu, Albert Rocchini — 2013-01-14

Objective: To test the hypothesis that patients with complex congenital heart disease who have undergone Fontan palliation have low total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels.Study design: We retrospectively reviewed the random serum lipid profiles obtained at cardiology clinic visits between May 2010 and November 2011 in patients who had undergone the Fontan procedure. We compared these serum lipid levels against age- and sex-matched established normal data from the Third National Health and Nutrition Examination Survey.Results: Eighty-eight patients who had undergone the Fontan procedure also had laboratory test data obtained during their visits. Median total cholesterol level in the Fontan group was 127 mg/dL (IQR, 116-144 mg/dL), median HDL-C was 40 mg/dL (IQR, 33-45 mg/dL), median non–HDL-C was 86 mg/dL (IQR, 76-109 mg/dL), and median LDL-C was 66 mg/dL (IQR, 57-83 mg/dL). Total cholesterol, LDL-C, non–HDL-C, and HDL-C levels were significantly lower in patients who had undergone a Fontan procedure compared with age- and sex-matched normal individuals (mean z-score, −1.4, −1.2, −1.0, and −1.0 respectively; all P < .0001). Cholesterol levels were below the 25th percentile for age and sex for total cholesterol in 82% of patients, for LDL-C in 76%, for non–HDL-C in 67%, and for HDL-C in 57%.Conclusion: Patients who have undergone the Fontan procedure have significantly lower serum total cholesterol, LDL-C, HDL-C and non-HDL-C levels than age- and sex-matched normal individuals. Although the implications of this finding are unknown, it raises the possibility of abnormalities in cholesterol absorption, synthesis, or catabolism in this patient population.

N-Terminal Pro-Brain Natriuretic Peptide and Risk of Coronary Artery Lesions and Resistance to Intravenous Immunoglobulin in Kawasaki Disease

2013-01-07

Objective: To determine whether the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) can be a useful marker not only to identify the patients with Kawasaki disease (KD) who are at a higher risk of developing coronary artery lesions (CAL), and predict resistance to intravenous immunoglobulin (IVIG).Study design: We enrolled 80 patients with the acute phase of KD at a single center. The demographic, clinical, and laboratory data were prospectively collected.Results: Nineteen of the 80 patients developed CAL, despite IVIG administration. They had a significantly higher serum NT-proBNP level in comparison with the patients without CAL. The NT-proBNP cut-off value of 1300 pg/mL yielded a sensitivity of 95% and a specificity of 85% for predicting CAL. However, 17 of the 80 patients were IVIG non-responders. They also had a significantly higher serum NT-proBNP level in comparison with the IVIG responders. The NT-proBNP cut-off value of 800 pg/mL yielded a sensitivity of 71% and a specificity of 62% for predicting IVIG non-responders.Conclusions: The serum NT-proBNP level is increased in children with KD with CAL and IVIG resistance. It may be useful to predict CAL and IVIG resistance in KD.

Relationship of Sleep to Pulmonary Function in Mucopolysaccharidosis II

William I. Wooten, Joseph Muenzer, Bradley V. Vaughn, Marianne S. Muhlebach — 2013-01-10

Objective: To study the sleep characteristics, pulmonary function, and their relationships in an enzyme naive population of patients with mucopolysaccharidoses (MPS) II (Hunter syndrome).Study design: The analyzed subjects (30 patients with MPS II with a median age of 9 years) had been enrolled in an MPS II natural history study and a phase I/II enzyme replacement clinical study in which they underwent standard polysomnography including spirometry and plethysmography, if cooperative. Descriptive statistics and nonparametric correlation were performed for demographic, sleep, and pulmonary function variables.Results: Median apnea-hypopnea index was 6.4, with obstructive sleep apnea observed in 27/30 subjects. Sleep architecture was characterized by diminished rapid-eye movement sleep duration (median 13%), and decline in sleep efficiency and slow-wave sleep duration in older individuals. Oxygen desaturation below 90% occurred in 26/30 subjects, and hypoventilation above 50 Torr occurred in 11/23 subjects with accurate end-tidal carbon dioxide recordings. Of 15 subjects with reliable spirometry, median forced expiratory volume in 1 second was below 80% predicted in 12/15 subjects. Forced expiratory volume in 1 second in percent-predicted was inversely related to apnea-hypopnea index and increase from baseline end-tidal carbon dioxide (P = .023, rs= −0.58), (P < .001, rs = −0.82).Conclusion: Sleep in MPS II is characterized by obstructive sleep apnea, altered sleep architecture, and impaired gas exchange. Sleep disruption is related to daytime pulmonary function, thus both systems should be evaluated when sleep abnormalities are suspected.

A Prospective Randomized Trial on Preventative Methods for Positional Head Deformity: Physiotherapy versus a Positioning Pillow

2013-01-14

Objective: To evaluate the impact of stretching exercises versus available bedding pillows on positional head deformities.Study design: Fifty children aged 5 months or younger with positional head deformity were included in this prospective clinical trial (n = 20 plagiocephaly, n = 10 brachycephaly, n = 20 combination). A random distribution was performed for treatment with the bedding pillow alone (n = 25) or with stretching exercises (n = 25) for 6 weeks. Anthropometric caliper measurements were done before and after that interval. Cranial vault asymmetry index (CVAI) and cranial index (CI) were calculated and analyzed using a descriptive statistical general linear model.Results: ΔCVAI in the stretching group was 2.09% for plagiocephaly and 2.34% for combined head deformities. Using the bedding pillow, ΔCVAI was 3.01% in plagiocephal children and 2.86% for combined head deformity. The ΔCI in the stretching group was 0.94% for isolated brachycephal children and 2.24% for combined head deformity. ΔCI in the pillow group was 3.63% for brachycephaly and 3.23% in children with combined head deformities, respectively.Conclusions: Bedding pillows and stretching exercises both resulted in improvements in positional cranial deformation. For children with combined plagiocephaly and brachycephaly, improvement in cranial asymmetry was slightly greater when using bedding pillows versus stretching.

Fluticasone Propionate Pharmacogenetics: CYP3A4*22 Polymorphism and Pediatric Asthma Control

2013-01-07

Objective: To determine the relationship between allelic variations in genes involved in fluticasone propionate (FP) metabolism and asthma control among children with asthma managed with inhaled FP.Study design: The relationship between variability in asthma control scores and genetic variation in drug metabolism was assessed by genotyping 9 single nucleotide polymorphisms in the CYP3A4, CYP3A5, and CYP3A7 genes. Genotype information was compared with asthma control scores (0 = well controlled to 15 = poorly controlled), determined using a questionnaire modified from the National Heart Lung and Blood Institute's Expert Panel 3 guidelines.Results: Our study cohort comprised 734 children with asthma (mean age, 8.8 ± 4.3 years) and was predominantly male (61%) and non-Hispanic white (53%). More than one-half of the children (56%; n = 413) were receiving an inhaled glucocorticoid daily, with FP the most frequently prescribed agent (65%). Among the children receiving daily FP, single nucleotide polymorphisms in CYP3A5 and CYP3A7 were not associated with asthma control scores. In contrast, asthma control scores were significantly improved in the 20 children (7%) with the CYP3A4*22 allele (median, 3; range, 0-6) compared with the 201 children without the CYP3A4*22 allele (median, 4; range, 0-15; P = .02). The presence of CYP3A4*22 was associated with improved asthma control scores by 2.1 points (95% CI, 0.5-3.8).Conclusion: The presence of CYP3A4*22, which is associated with decreased hepatic CYP3A4 expression and activity, was accompanied by improved asthma control in the FP-treated children. Decreased CYP3A4 activity may improve asthma control with inhaled FP.

Ammonia Control in Children Ages 2 Months through 5 Years with Urea Cycle Disorders: Comparison of Sodium Phenylbutyrate and Glycerol Phenylbutyrate

2013-01-15

Objectives: To examine ammonia levels, pharmacokinetics, and safety of glycerol phenylbutyrate (GPB; also referred to as HPN-100) and sodium phenylbutyrate (NaPBA) in young children with urea cycle disorders (UCDs).Study design: This open label switch-over study enrolled patients ages 29 days to under 6 years taking NaPBA. Patients underwent 24-hour blood and urine sampling on NaPBA and again on a phenylbutyric acid-equimolar dose of GPB and completed questionnaires regarding signs and symptoms associated with NaPBA and/or their UCD.Results: Fifteen patients (8 argininosuccinate lyase deficiency, 3 argininosuccinic acid synthetase deficiency, 3 ornithine transcarbamylase deficiency, 1 arginase deficiency) ages 2 months through 5 years enrolled in and completed the study. Daily ammonia exposure (24-hour area under the curve) was lower on GPB and met predefined noninferiority criteria (ratio of means 0.79; 95% CI 0.593-1.055; P = .03 Wilcoxon; 0.07 t test). Six patients experienced mild adverse events on GPB; there were no serious adverse events or significant laboratory changes. Liver tests and argininosuccinic acid levels among patients with argininosuccinate lyase deficiency were unchanged or improved on GPB. Eleven of 15 patients reported 35 symptoms on day 1; 23 of these 35 symptoms improved or resolved on GPB. Mean systemic exposure to phenylbutyric acid, phenylacetic acid, and phenylacetylglutamine (PAGN) were similar and phenylacetic acid exposure tended to be higher in the youngest children on both drugs. Urinary PAGN concentration was greater on morning voids and varied less over 24 hours on GPB versus NaPBA.Conclusions: GPB results in more evenly distributed urinary output of PAGN over 24 hours were associated with fewer symptoms and offers ammonia control comparable with that observed with NaPBA in young children with UCDs.

Endocrine Evaluation of Children with and without Shwachman-Bodian-Diamond Syndrome Gene Mutations and Shwachman-Diamond Syndrome

2013-01-10

Objective: To characterize the endocrine phenotype of patients with Shwachman-Diamond syndrome (SDS).Study design: Clinically indicated endocrine screening data from 43 patients with SDS or SDS-like presentation were analyzed according to sex, age, and genetic testing. In addition to 25 patients with biallelic Shwachman-Bodian-Diamond syndrome (SBDS) gene mutations, we evaluated 18 patients with cytopenias who were receiving pancreatic enzyme replacement but were without SBDS mutation. We performed a retrospective review of growth records and clinically indicated endocrine evaluations.Results: Of patients with SBDS mutations, 2 had low stimulated growth hormone levels, 2 had mildly elevated thyrotropin levels, 5 had abnormal glucose levels, and 1 had an elevated follicle-stimulating hormone level (post transplantation). In contrast, 1 patient without SBDS mutations had postprandial hyperglycemia and 3 had mildly low free thyroxine levels without short stature. Endocrine abnormalities were identified in 19% of short patients and 26% of the whole group. Of patients with SBDS mutations, 56% had a height expressed in SD units from the mean for age and sex of <−1.8, in contrast to only 12% of patients without SBDS mutations (38% of the whole group). Body mass index z score was significantly greater in the group with SBDS mutations (P < .001).Conclusion: Although short stature was more common in patients with SBDS mutations, no consistent endocrine phenotype was observed in patients with SDS regardless of genetic testing.

Use of Clinical Practice Guidelines on Long-term Prophylaxis in Severe Hemophilia in France: A Retrospective Audit

2013-01-21

Objectives: To evaluate the impact of the 2002 guidelines on the current status of prophylaxis in French children with severe hemophilia A or B.Study design: Clinical information was captured, in a prospective way, using FranceCoag Network. We retrospectively studied 291 patients with severe (<1 IU/dL) hemophilia A and B, with no history of inhibitors.Results: Our results demonstrate that the availability of national medical guidelines has improved clinical practice in France. In the past decade, the proportion of children with severe hemophilia undergoing prophylaxis has shown a significant 2- to 3-fold increase: ∼80% of these children >3 years of age are now receiving prophylaxis. In severe hemophilia A and B, the age at which prophylaxis commences has significantly decreased: 4.0 and 6.1 years for the period 1996-1999 as opposed to 1.8 and 1.4 years for the period 2004-2007 (P = .0001).Conclusions: Long-term clinical and physical evaluations of patients will be necessary to establish the benefits of this increase in prophylactic treatment on the prevention of hemophilic arthropathy.

Differentiating Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis from Other Forms of Hemophagocytic Lymphohistiocytosis

2013-01-21

Objectives: To identify measures distinguishing macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis (sJIA) from familial hemophagocytic lymphohistiocytosis (FHL) and virus-associated hemophagocytic lymphohistiocytosis (VA-HLH) and to define appropriate cutoff values. To evaluate suggested dynamic measures differentiating MAS in patients with sJIA from sJIA flares.Study design: In a cohort of patients referred for evaluation of hemophagocytic lymphohistiocytosis, we identified 27 patients with sJIA and MAS (MAS/sJIA) fulfilling the criteria of the proposed preliminary diagnostic guideline for the diagnosis of MAS in sJIA. Ten measures at diagnosis were compared between the MAS/sJIA group and 90 patients with FHL and 42 patients with VA-HLH, and cutoff values were determined. In addition, 5 measures were analyzed for significant change from before MAS until MAS diagnosis.Results: Neutrophil count and C-reactive protein were significantly higher in patients with MAS/sJIA compared with patients with FHL and patients with VA-HLH, with 1.8 × 109/L neutrophils (sensitivity 85%, specificity 83%) and 90 mg/L C-reactive protein (74%, 89%) as cutoff values. Soluble CD25 <7900 U/L (79%, 76%) indicated MAS/sJIA rather than FHL/VA-HLH. Platelet (−59%) and white blood cell count (−46%) displayed a significant decrease, and neutrophil count (−35%) and fibrinogen (−28%) showed a trend during the development of MAS. However, a substantial portion of patients had values at diagnosis of MAS within or above the normal range for white blood cells (84%), neutrophils (77%), platelets (26%), and fibrinogen (71%).Conclusion: Readily available measures can rapidly differentiate between MAS/sJIA and FHL/VA-HLH. The findings substantiate that a decline of measures may facilitate the distinction of MAS from flares of sJIA.

Leveraging Administrative Data to Monitor Rituximab Use in 2875 Patients at 42 Freestanding Children's Hospitals across the United States

2012-12-26

Objective: To describe the pharmacoepidemiology of rituximab use in children and to estimate the frequency of infectious events within a 1-year period after rituximab exposure.Study design: This is a retrospective cohort study of patients who received rituximab at 1 of 42 children's hospitals contributing data to the Pediatric Health Information System between January 1999 and June 2011. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) discharge diagnosis codes were analyzed to categorize underlying diseases (hematologic malignancies, primary immunodeficiencies, autoimmune diseases, and transplant recipients) and to estimate inpatient infectious complication rates within each category.Results: A total of 2875 patients with 4639 rituximab admissions were identified. The median age at index admission was 11 years (IQR, 5-15 years). The rate of rituximab admissions increased from 3 to 185 per 100 000 admissions per year over the study interval. During the 1-year follow-up period, 463 patients (16%) died. Infectious events were assessed in 2246 of the rituximab-exposed patients; 6.1% were diagnosed with sepsis and 2.0% with septic shock. The frequency of sepsis ranged from 2.4% in patients with autoimmune diseases to 12.2% in those with primary immunodeficiencies. Three patients were assigned an ICD-9-CM discharge diagnosis code for Pneumocystis joroveci pneumonia, 1 patient was assigned an ICD-9-CM discharge diagnosis code for hepatitis B, and 1 patient was assigned an ICD-9-CM discharge diagnosis code for progressive multifocal leukoencephalopathy.Conclusion: The use of rituximab has increased significantly in children with a variety of underlying diseases. Based on ICD-9-CM code data, the rates of sepsis and other life-threatening infections after rituximab exposure vary depending on the underlying condition. Based on surveillance of infection using ICD-9-CM diagnosis codes, the rates of opportunistic infections appear to be low.

Lymph-Node-First Presentation of Kawasaki Disease Compared with Bacterial Cervical Adenitis and Typical Kawasaki Disease

2013-01-09

Objective: To identify characteristics differentiating the node-first presentation of Kawasaki disease (NFKD) from bacterial cervical lymphadenitis (BCL) and typical Kawasaki disease (KD).Study design: From our prospectively collected database, we compared clinical, laboratory, and imaging characteristics of NFKD and BCL cohorts and performed multivariable logistic regression to identify variables that distinguish NFKD from BCL. We then compared outcomes of patients with NFKD and patients with typical KD treated during the same period.Results: Over 7 years, 57 patients were hospitalized for NFKD, 78 for BCL, and 287 for typical KD. Patients with NFKD were older and had more medical encounters and longer duration of illness before the correct diagnosis was made than did patients with BCL. Of patients with NFKD, 33% had an admission diagnosis of bacterial adenitis or abscess. Compared with patients with BCL, patients with NFKD had lower leukocyte (white blood cell), hemoglobin, and platelet counts and higher absolute band counts (ABCs), C-reactive protein (CRP), alanine transaminase and γ-glutamyl transpeptidase levels, and erythrocyte sedimentation rates. In the multivariable analysis, smaller nodes, lower white blood cell count, and higher ABC and CRP were independently associated with NFKD. Patients with NFKD had multiple enlarged solid nodes and comparable rates of retropharyngeal edema. Compared with patients with typical KD, patients with NFKD were older, had more severe inflammation, and had similar rates of coronary artery abnormalities and resistance to intravenous immune globulin.Conclusions: High ABC and CRP values and multiple enlarged solid nodes in febrile patients with cervical adenopathy should prompt consideration of NFKD to prevent delayed diagnosis of KD. Retropharyngeal edema on radiography should not dissuade from the diagnosis of NFKD.

Comparison between Liquid and Tablet Formulations of Levothyroxine in the Initial Treatment of Congenital Hypothyroidism

2013-01-14

Objective: To evaluate the effects of liquid (drops) and tablet formulations of levothyroxine in homogeneous groups of infants with congenital hypothyroidism (CH) as diagnosed through neonatal screening.Study design: Forty-two consecutive infants with CH were subdivided into 2 groups consisting of infants with the severe or the moderate/mild form. For each form, the infants with CH were randomly assigned to receive liquid (group 1) or tablet (group 2) formulation. In all patients, thyroid function tests were performed before the beginning of therapy and at 15 and 30 days and at 3 and 6 months after the beginning of therapy.Results: In the severe form, after 15 days of treatment, serum thyrotropin (TSH) levels became normal in 8 of 9 patients in group 1 and in 5 of 9 patients in group 2; serum free triiodothyronine (fT3) levels were significantly higher in group 1 than in group 2; and serum fT4 levels were higher than the upper limit of the normal range in all patients in both groups. During the follow-up, there were significantly more patients with suppressed TSH concentrations in group 1 than in group 2. In the moderate/mild form, the patients of group 1 and group 2 showed median values of TSH, fT3, and fT4 that were not significantly different. No clinical or electrocardiographic signs of heart disease were found. There were no significant differences in the developmental quotient between group 1 and group 2 patients with severe and moderate/mild CH.Conclusions: Our data seem to indicate that there is not complete bioequivalence between drops and tablets, especially in infants with severe CH.

Dog Bite Injuries among American Indian and Alaska Native Children

2013-01-17

Objective: To examine dog bites among American Indian (AI) and Alaska Native (AN) children visiting Indian Health Service and tribal health facilities.Study design: We retrospectively analyzed hospitalizations and outpatient visits with a diagnosis of dog bite between 2001 and 2008 in AI/AN children aged <20 years. Rates of dog bite hospitalizations and outpatient visits were estimated by age group, sex, region, and number and location of open wounds using Indian Health Service data. Analyses of hospitalizations for the general US population aged <20 years used the Nationwide Inpatient Sample.Results: The average annual dog bite hospitalization rate was higher among AI/AN children in Alaska (6.1/100 000 population) and the Southwest region (5.3/100 000) compared with the general US child population (3.1/100 000; 95% CI, 2.9-3.3/100 000). The average annual outpatient visit rate in AI/AN children was highest in the Alaska (596.4/100 000), Southwest (540.0/100 000), and Northern Plains West (537.6/100 000) regions. The hospitalization rate was highest in both AI/AN and US males aged <5 years, and outpatient visit rates were highest in AI/AN males aged 5-9 years. Open wounds diagnoses were most commonly seen on the head, neck, and face in hospitalized children (45.5% of open wounds in AI/AN children, 59.3% in US children; SE, 1.0%) and on the leg in AI/AN outpatients (35.6%).Conclusion: Dog bites represent a significant public health threat in AI/AN children in the Alaska, the Southwest, and Northern Plains West regions of the US. Enhanced animal control and education efforts should reduce dog bite injuries and associated problems with pets and stray dogs, such as emerging infectious diseases.

Comprehensive Assessment of Serious Adverse Events Following Immunization by Health Care Providers

2013-02-28

Many events occurring after vaccination have been attributed to vaccines, when in fact the association was often due to chance. However, as with any medical intervention, there are times when adverse events are caused by immunizations. Distinguishing which events are causally related to vaccine, rather than coincidental events, is a challenge for the pediatrician and a major focus of vaccine safety science. Consider a child who presents with aseptic meningitis after immunization. Because of the temporal relationship, one may suspect the immunizations as the cause, yet subsequent isolation of enterovirus from cerebrospinal fluid implicates the enteroviral infection instead. The term adverse event following immunization (AEFI) is defined as any untoward event that occurs after immunization, regardless of causal association. AEFI is the preferred notation to describe such clinical events because the term is free from implications regarding causal relationship and favors an open mind about the role of immunizations. AEFIs are a common part of routine clinical practice. The Clinical Immunization Safety Assessment (CISA) network has reviewed many individual cases of AEFIs and found that when a comprehensive investigation for alternative etiologies of the AEFI is completed, other causes for the event can often be identified. Yet, such comprehensive evaluations are rarely performed. We describe a stepwise approach to the comprehensive assessment of serious AEFIs by health care providers. The main objective is to highlight the important role that health care providers play in this effort by actively evaluating for the most likely causes of serious events when they occur after immunization.

Rapid-Antigen Detection Tests for Group A Streptococcal Pharyngitis: Revisiting False-Positive Results Using Polymerase Chain Reaction Testing

2013-03-04

We investigated mechanisms of the false-positive test results on rapid-antigen detection test (RADT) for group A Streptococcal (GAS) pharyngitis. Most RADT false-positives (76%) were associated with polymerase chain reaction-positive GAS results, suggesting that RADT specificity could be considered close to 100%. Finding that 61% of GAS culture-negative but RADT-positive cases were positive on both GAS polymerase chain reaction and Staphylococcus aureus testing, we posit bacterial inhibition as causative.

Aggressive Transformation of Juvenile Myelomonocytic Leukemia Associated with Duplication of Oncogenic KRAS due to Acquired Uniparental Disomy

2013-02-11

A small fraction of cases of juvenile myelomonocytic leukemia (JMML) develop massive disease activation. Through genomic analysis of JMML, which developed in an individual with mosaicism for oncogenic KRAS mutation with rapid progression, we identified acquired uniparental disomy at 12p. We demonstrated that duplication of oncogenic KRAS is associated with rapid JMML progression.

Dysphagia Lusoria in an Infant

2013-02-18

A 12-month-old girl presented with worsening symptoms of dysphagia to solids. She had a longstanding history of gastroesophageal reflux manifested as spitting up and irritability treated with a proton pump inhibitor. With the addition of baby foods, the reflux symptoms improved; with the addition of table foods, she developed difficulty swallowing and food refusal. She had no history of stridor, coughing, gagging, or choking with feeds. Her examination was normal with weight and length at the 75th percentile for age. During the visit, she was noted to take juice without difficulty, but she could not be coaxed into eating solids. An esophagram showed a filling defect within the upper esophagus, suggestive of an aberrant vessel (; available at www.jpeds.com). Computed tomography with 3-dimensional reconstruction confirmed an aberrant right subclavian artery (ARSA) compressing the posterior aspect of the esophagus (). Because ARSA is usually asymptomatic, an endoscopy was performed to assess for esophagitis. At endoscopy, the esophageal mucosa was normal in appearance; biopsy examinations confirmed normal mucosa. The aberrant vessel was seen as a transverse compression of the upper esophagus ().

Bilateral External Ophthalmoplegia in Biotin-Responsive Basal Ganglia Disease

Brahim Tabarki, Fahad Al-Sheikh, Saad Al-Shahwan, Guilio Zuccoli — 2013-01-28

A 10-year-old girl with a 4-month history of abnormal gait and dysarthria was admitted to the hospital with altered mental status that had progressed over the previous 3 days in the context of febrile illness. The patient's family reported that she did not use drugs, and the family history is remarkable only for consanguinity. On physical examination, she was confused, having generalized dystonia and bilateral external ophthalmoplegia, and she was anarthric.

Blotchy Baby: A Case of Phakomatosis Pigmentovascularis

Paul Brittain, Erica J. Walsh, Aimee C. Smidt — 2013-02-04

A Native American female infant was born at 34 weeks' gestation with extensive, gray-blue, symmetric patches involving the trunk and extremities, representing dermal melanocytosis ( and ; available at www.jpeds.com). She also had facial reticulated vascular patches, consistent with capillary malformation (port-wine stain; ), and unilateral corneal clouding. Ophthalmologic examination confirmed infantile glaucoma. Dermal melanocytosis in combination with capillary malformation and glaucoma is indicative of phakomatosis pigmentovascularis (PPV) type IIb.

The Water Lily Sign

2013-02-04

A 14-year-old Ethiopian girl presented to her local doctor with a 3-day history of vomiting and epigastric pain. She had immigrated to Australia 2 years earlier after living on a sheep farm in Ethiopia. Clinical examination was unremarkable. Apart from peripheral blood eosinophilia (0.72 × 109/L), laboratory investigations, including urea and electrolyte levels and liver function tests, were normal. An abdominal computed tomography scan showed a fluid-filled structure in the right lobe of her liver with the “water lily sign” of germinal layer detachment from the cyst wall found in hydatid cysts (; available at www.jpeds.com). Serology for Echinococcus granulosus was positive, confirming the diagnosis. She was treated with albendazole 7.5 mg/kg twice daily for 12 weeks before and 2 weeks after cyst removal (), the definitive management for single large hydatid cysts.

Giant Varicocele Inducing Chronic Pelvic Pain in a Girl

2013-01-21

A 15-year-old girl presented with a 2-year history of recurrent abdominal pain, stipsis, and pelvic pain. She was operated at birth for a correction of type 1 persistent truncus arteriosus using a “Hancock's conduct” replaced 3 years after with an aortic homograft. She underwent several cardiac catheterizations. At admission, her vital signs were normal, and laboratory studies and urinalysis were unremarkable. An ultrasound showed the presence of a pelvic varicocele. The angio-computed tomography showed a giant pelvic varicocele () with an inferior vena cava obstruction/atresia (). Chronic pelvic pain is a common problem and is defined as continuous or intermittent pain for ≥6 months. Common causes of chronic pelvic pain include endometriosis, pelvic adhesions, atypical menstrual pain, and inflammatory bowel disease. Pelvic varicocele is found in approximately one half of the women with chronic pelvic pain affecting only premenopausal women. Pelvic varicocele as a cause of chronic pelvic pain has never been described in pediatric/adolescent girls. Cardiac surgery and related catheterizations would be considered in the etiology of chronic pelvic pain attributable to pelvic varicocele in adolescent girls leading to a close follow-up based on serial ultrasound evaluations. In this case, embolotherapy is not recommended. Ovarian veins are the only way to ensure that the blood returns because the vena cava is completely atretic and occluded. For this reason, we achieved pain control with analgesic drugs, planning surgical treatment based on the prosthetic substitution of the vena cava at 20 years of age.

Transient Aquagenic Palmar Hyperwrinkling

José M. Martín, Zaira M. Pellicer, Rebeca Bella, Esperanza Jordá — 2013-01-17

A healthy 3-year-old boy was referred to us for evaluation of a 1-year history of a whitish discoloration and wrinkling of the palms after brief immersion in water. Before exposure to water, physical examination showed normal palmar skin (). Three minutes after water immersion at 20°C, multiple translucent white papules appeared on his palms, and wrinkling of the palmar surface was clearly evident (). After drying, the skin normalized within 10 minutes. There was no involvement of other cutaneous areas. No other family members were similarly affected.

A Wart in the Esophagus

Maria Chiara Pellegrin, Sara Dal Bo, Stefano Martelossi, Alessandro Ventura — 2013-01-14

A 17-year-old male patient who smokes and has been affected by Crohn's disease since age 11 years was evaluated after methotrexate suspension. Methotrexate was stopped 4 months earlier because of nausea and the feeling of a foreign body in his throat. These symptoms developed after 4 years of therapy and disappeared soon after the suspension.

Correction

2013-06-01

In the Supplement article, “Growth Curves: How to Best Measure Growth of the Preterm Infant,” by Bhatia, J Pediatr 2013;162:S2-6, the author inadvertently provided the incorrect version of Figure 3, which “pulled” down the non-shaded curves when the two curves were superimposed. Below is the correct version of .

Erratum

2013-06-01

The Editor’s Perspective published in the April 2013 issue of The Journal (J Pediatr 2013;162:661), which referred to the article, “Exercise-Induced Bronchoconstriction in School-Aged Children Who Had Chronic Lung Disease in Infancy,” by Joshi et al, J Pediatr 2013;162:813-8, was published in error. The correct Editor's Perspective is below:

The Journal of Pediatrics

Table of Contents

Masthead

Information for Readers

Media and adolescents: a complex relationship

More support for diagnosis and treatment of HIV infection in early infancy

Generalists' role in vaccine safety reporting

Interventions and outcomes of preterms

Physical activity, sedentarism, and adiposity

More work to do in order to prevent dog bite injuries

“Pharmaco-epidemiology”

Pediatric Oncology in Developing Countries: Challenges and Solutions

Genetics and Pediatric Unconjugated Hyperbilirubinemia

Changing the Paradigm in Pediatric Acute Kidney Injury

Newborns and Other Children: In Defense of Differential Attitudes and Treatment

Ligation of the Patent Ductus Arteriosus in Preterm Infants: Understanding the Physiology

Modes of Death in Pediatrics: Differences in the Ethical Approach in Neonatal and Pediatric Patients

Sustained Developmental Effects of the Infant Behavioral Assessment and Intervention Program in Very Low Birth Weight Infants at 5.5 Years Corrected Age

50 Years Ago in The Journal of Pediatrics: Neonatal Fibrous Dysplasia

Late-Onset Sepsis in Very Low Birth Weight Infants from Singleton and Multiple-Gestation Births

Cause-Specific Mortality of Very Preterm Infants and Antenatal Events

Positioning Effects on Lung Function and Breathing Pattern in Premature Newborns

Initiation of Antiretroviral Therapy Before 6 Months of Age is Associated with Faster Growth Recovery in South African Children Perinatally Infected with Human Immunodeficiency Virus

UGT1A1 Genetic Analysis as a Diagnostic Aid for Individuals with Unconjugated Hyperbilirubinemia

Nonsteroidal Anti-Inflammatory Drugs Are an Important Cause of Acute Kidney Injury in Children

Alterations in Ventricular Structure and Function in Obese Adolescents with Nonalcoholic Fatty Liver Disease

50 Years Ago in The Journal of Pediatrics: The Vectorcardiographic Significance of Upright T Waves in V1 and V2 during the First Months of Life

Which Contributes More to Childhood Adiposity-High Levels of Sedentarism or Low Levels of Moderate-through-Vigorous Physical Activity? The Iowa Bone Development Study

Reality Television Predicts Both Positive and Negative Outcomes for Adolescent Girls

50 Years Ago in The Journal of Pediatrics: Pleural Effusion in the Neonatal Period

Wireless Motility Capsule Test in Children with Upper Gastrointestinal Symptoms

50 Years Ago in The Journal of Pediatrics: A Note on Studies of Salt Excretion in Sweat: Relationships between Rate, Conductivity, and Electrolyte Composition of Sweat from Patients with Cystic Fibrosis and from Control Subjects

Stool Consistency, but Not Frequency, Correlates with Total Gastrointestinal Transit Time in Children

Cardiac Function in Congenital Adrenal Hyperplasia: A Pattern of Reversible Cardiomyopathy

Low Total, Low-Density Lipoprotein, High-Density Lipoprotein, and Non–High-Density Lipoprotein Cholesterol Levels in Patients with Complex Congenital Heart Disease after Fontan Palliation

N-Terminal Pro-Brain Natriuretic Peptide and Risk of Coronary Artery Lesions and Resistance to Intravenous Immunoglobulin in Kawasaki Disease

Relationship of Sleep to Pulmonary Function in Mucopolysaccharidosis II

A Prospective Randomized Trial on Preventative Methods for Positional Head Deformity: Physiotherapy versus a Positioning Pillow

Fluticasone Propionate Pharmacogenetics: CYP3A4*22 Polymorphism and Pediatric Asthma Control

Ammonia Control in Children Ages 2 Months through 5 Years with Urea Cycle Disorders: Comparison of Sodium Phenylbutyrate and Glycerol Phenylbutyrate

Endocrine Evaluation of Children with and without Shwachman-Bodian-Diamond Syndrome Gene Mutations and Shwachman-Diamond Syndrome

Use of Clinical Practice Guidelines on Long-term Prophylaxis in Severe Hemophilia in France: A Retrospective Audit

Differentiating Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis from Other Forms of Hemophagocytic Lymphohistiocytosis

Leveraging Administrative Data to Monitor Rituximab Use in 2875 Patients at 42 Freestanding Children's Hospitals across the United States

Lymph-Node-First Presentation of Kawasaki Disease Compared with Bacterial Cervical Adenitis and Typical Kawasaki Disease

Comparison between Liquid and Tablet Formulations of Levothyroxine in the Initial Treatment of Congenital Hypothyroidism

Dog Bite Injuries among American Indian and Alaska Native Children

Comprehensive Assessment of Serious Adverse Events Following Immunization by Health Care Providers

Rapid-Antigen Detection Tests for Group A Streptococcal Pharyngitis: Revisiting False-Positive Results Using Polymerase Chain Reaction Testing

Aggressive Transformation of Juvenile Myelomonocytic Leukemia Associated with Duplication of Oncogenic KRAS due to Acquired Uniparental Disomy

Dysphagia Lusoria in an Infant

Bilateral External Ophthalmoplegia in Biotin-Responsive Basal Ganglia Disease

Blotchy Baby: A Case of Phakomatosis Pigmentovascularis

The Water Lily Sign

Giant Varicocele Inducing Chronic Pelvic Pain in a Girl

Transient Aquagenic Palmar Hyperwrinkling

A Wart in the Esophagus

Correction

Erratum