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Polar bear at Lincoln Park Zoo, July 2009 [About the Cover]

About This Journal [About This Journal]

This Month in Archives of Pediatrics & Adolescent Medicine [This Month in Archives of Pediatrics & Adolescent Medicine]

Safety and Transparency of Pediatric Drug Trials [Article]

Objectives To quantify the frequency and type of new safety information arising from studies performed under the auspices of the Pediatric Exclusivity Program, to describe the dissemination of these findings in the peer-reviewed literature and compare this with the US Food and Drug Administration (FDA) review, and to describe their effect on pediatric labeling. Design Cohort study of the 365 trials performed for 153 drugs. Setting The Pediatric Exclusivity incentive from December 1997 through September 2007. Participants Food and Drug Administration publicly available records and peer-reviewed literature retrievable by MEDLINE search. Main Exposures New safety findings obtained from the trials completed for exclusivity. Outcome Measures Concordance of the information highlighted in the peer-reviewed article abstracts with the information in the FDA labeling and drug reviews. Results There were 137 labeling changes; we evaluated 129 of these (the 8 selective serotonin reuptake inhibitors were excluded from review). Thirty-three products (26%) had pediatric safety information added to the labeling. Of these, 12 products had neuropsychiatric safety findings and 21 had other important safety findings. Only 16 of 33 of these trials (48%) were reported in the peer-reviewed literature; however, 7 of 16 focused on findings substantively different from those highlighted in the FDA reviews and labeling changes. Conclusions Medication adverse events in children often differ from those in adults, particularly those that are neuropsychiatric in nature. Labeling changes for pediatric use demonstrate that pediatric drug studies provide valuable and unique safety data that can guide the use of these drugs in children. Unfortunately, most of these articles are not published, and almost half of the published articles focus their attention away from the crucial safety data.

Influence of Changes in Supply on the Distribution of Pediatric Subspecialty Care [Article]

Objectives To examine whether recently certified pediatric subspecialists enter markets that previously lacked subspecialists and to determine whether changes in overall supply are associated with changes in geographic availability of care. Design Multiple cross-sectional analyses. Setting United States. Participants Physician data for 2003 and 2006 from the American Board of Pediatrics. Main Exposure New entrants, defined as subspecialists who first obtained certification after 2003. Main Outcome Measures We examined the following: (1) whether new entrants were more likely to practice in locations lacking certified subspecialists; (2) changes in the percentage of hospital referral regions (HRRs) with at least 1 subspecialist; and (3) changes in the number of subspecialists per HRR. Results Ten pediatric subspecialties experienced increases in supply and 5 experienced decreases. For 8 of the 15 pediatric subspecialties studied, new entrants were more likely than previously certified physicians to locate in an HRR that lacked a subspecialist in 2003. The percentage of HRRs with a subspecialist increased significantly for 3 of the 10 pediatric subspecialties with increases in supply. Among HRRs with a subspecialist in 2003, the average number of subspecialists per HRR increased between 2003 and 2006 for 6 of the 10 pediatric subspecialties with total supply increases and decreased for 4 of the 5 subspecialties with decreases in supply. Conclusions Increases in the number of pediatric subspecialists generally did not lead to improvements in distribution and may actually reinforce the existing distribution for certain pediatric subspecialties. However, because newly certified subspecialists are more likely to enter an HRR that previously lacked a subspecialist, long-term increases in supply may lead to improvements in distribution.

Improving Health Outcomes for Youth Living With the Human Immunodeficiency Virus: A Multisite Randomized Trial of a Motivational Intervention Targeting Multiple Risk Behaviors [Article]

Objective To determine if Healthy Choices, a motivational interviewing intervention targeting multiple risk behaviors, improved human immunodeficiency virus (HIV) viral load. Design A randomized, 2-group repeated measures design with analysis of data from baseline and 6- and 9-month follow-up collected from 2005 to 2007. Setting Five US adolescent medicine HIV clinics. Participants A convenience sample with at least 1 of 3 risk behaviors (nonadherence to HIV medications, substance abuse, and unprotected sex) was enrolled. The sample was aged 16 to 24 years and primarily African American. Of the 205 enrolled, 19 did not complete baseline data collections, for a final sample size of 186. Young people living with HIV were randomized to the intervention plus specialty care (n = 94) or specialty care alone (n = 92). The 3- and 6-month follow-up rates, respectively, were 86% and 82% for the intervention group and 81% and 73% for controls. Intervention Healthy Choices was a 4-session individual clinic-based motivational interviewing intervention delivered during a 10-week period. Motivational interviewing is a method of communication designed to elicit and reinforce intrinsic motivation for change. Outcome Measure Plasma viral load. Results Youth randomized to Healthy Choices showed a significant decline in viral load at 6 months postintervention compared with youth in the control condition (β = –0.36, t = –2.15, P = .03), with those prescribed antiretroviral medications showing the lowest viral loads. Differences were no longer significant at 9 months. Conclusion A motivational interviewing intervention targeting multiple risk behaviors resulted in short-term improvements in viral load for youth living with HIV. Trial Registration clinicaltrials.gov Identifier: NCT00103532

Predictors of Suboptimal Virologic Response to Highly Active Antiretroviral Therapy Among Human Immunodeficiency Virus-Infected Adolescents: Analyses of the Reaching for Excellence in Adolescent Care and Health (REACH) Project [Article]

Objective To examine the prevalence and biopsychosocial predictors of suboptimal virologic response to highly active antiretroviral therapy (HAART) among human immunodeficiency virus–infected adolescents. Design Population-based cohort study. Setting Sixteen academic medical centers across 13 cities in the United States. Participants One hundred fifty-four human immunodeficiency virus–infected adolescents who presented for at least 2 consecutive visits after initiation of HAART. Main Outcome Measures Viral load (plasma concentration of human immunodeficiency virus RNA) and CD4+ lymphocyte count. Results Of the 154 adolescents enrolled in the study, 50 (32.5%) demonstrated early and sustained virologic suppression while receiving HAART. The remaining 104 adolescents (67.5%) had a poor virologic response. Adequate adherence (>50%)—reported by 70.8% of respondents—was associated with 60% reduced odds of suboptimal virologic suppression in a multivariable logistic regression model (adjusted odds ratio = 0.4; 95% confidence interval, 0.2-1.0). Exposure to suboptimal antiretroviral therapy prior to HAART, on the other hand, was associated with more than 2-fold increased odds of suboptimal virologic response (adjusted odds ratio = 2.6; 95% confidence interval, 1.1-5.7). Conclusions Fully two-thirds of human immunodeficiency virus–infected adolescents in the current study demonstrated a suboptimal virologic response to HAART. Nonadherence and prior single or dual antiretroviral therapy were associated with subsequent poor virologic responses to HAART. These predictors of HAART failure echo findings in pediatric and adult populations. Given the unique developmental stage of adolescence, age-specific interventions are indicated to address high rates of nonadherence and therapeutic failure.

Time From First Intercourse to First Sexually Transmitted Infection Diagnosis Among Adolescent Women [Article]

Objective To determine the time between first intercourse and first sexually transmitted infection (STI) with Chlamydia trachomatis, Neisseria gonorrhoeae, or Trichomonas vaginalis and time between repeated infections. Design Observational study. Setting Three adolescent medicine clinics. Participants A cohort of 386 urban young women aged 14 to 17 years at enrollment. Main Outcome Measures Age at first intercourse; organism-specific interval between first intercourse and first STI diagnosis; interval between repeated infections; and age at first STI test prior to study participation. Results Participants had first intercourse at a young age (first, second, and third quartiles were 13, 14, and 15 years of age, respectively). By age 15 years, 25% of the women acquired their first STI, most often C trachomatis. Median interval between first intercourse and first STI diagnosis was 2 years. Within 1 year of first intercourse, 25% had their first C trachomatis infection. Repeated infections were common; within 3.6, 6, and 4.8 months, 25% of the women with prior C trachomatis, N gonorrhoeae, and T vaginalis infection were reinfected with the respective organisms. Considerable delay in STI testing was found for those who began sex at a younger age. The median interval between first sex and first test were 4.9, 3.5, 2.1, 1.8, and 1.2 years for those who had first sex at ages 10, 11, 12, 13, and 14 years, respectively. Conclusions Timely screening and treatment are important for prevention of STI sequelae. For urban adolescent women, STI screening (especially for C trachomatis) should begin within a year after first intercourse and infected individuals should be retested every 3 to 4 months.

Efficacy of Sexually Transmitted Disease/Human Immunodeficiency Virus Sexual Risk-Reduction Intervention for African American Adolescent Females Seeking Sexual Health Services: A Randomized Controlled Trial [Article]

Objectives To evaluate the efficacy of an intervention to reduce incident sexually transmitted disease (STD) and enhance STD/human immunodeficiency virus (HIV)–preventive behaviors and psychosocial mediators. Design A randomized controlled trial of an HIV prevention program. Setting Clinic-based sample in Atlanta, Georgia. Participants African American adolescent females (N = 715), aged 15 to 21 years, seeking sexual health services. Participants completed an audio computer-assisted self-interview and provided self-collected vaginal specimens for STD testing. Intervention Intervention participants received two 4-hour group sessions and 4 telephone contacts over a 12-month period, targeting personal, relational, sociocultural, and structural factors associated with adolescents' STD/HIV risk, and were given vouchers facilitating male partners' STD testing/treatment. Main Outcome Measure Incident chlamydial infections. Results Over the 12-month follow-up, fewer adolescents in the intervention had a chlamydial infection (42 vs 67; risk ratio [RR], 0.65; 95% confidence interval [CI], 0.42 to 0.98; P = .04) or recurrent chlamydial infection (4 vs 14; RR, 0.25; 95% CI, 0.08 to 0.83; P = .02). Adolescents in the intervention also reported a higher proportion of condom-protected sex acts in the 60 days preceding follow-up assessments (mean difference, 10.84; 95% CI, 5.27 to 16.42; P < .001) and less frequent douching (mean difference, –0.76; 95% CI, –1.15 to –0.37; P = .001). Adolescents in the intervention were also more likely to report consistent condom use in the 60 days preceding follow-up assessments (RR, 1. 41; 95% CI, 1.09 to 1.80; P = .01) and condom use at last intercourse (RR, 1.30; 95% CI, 1.09 to 1.54; P = .005). Intervention effects were observed for psychosocial mediators of STD/HIV–preventive behaviors. Conclusion Interventions for African American adolescent females can reduce chlamydial infections and enhance STD/HIV–preventive behaviors and psychosocial mediators of STD/HIV–preventive behaviors. Trial Registration clinicaltrials.gov Identifier: NCT00633906

Trends and Factors Associated With Infant Sleeping Position: The National Infant Sleep Position Study, 1993-2007 [Article]

Objective To determine trends and factors associated with choice of infant sleeping position. Design Annual nationally representative telephone surveys from 1993 through 2007. Setting Forty-eight contiguous states of the United States. Participants Nighttime caregivers of infants born within the last 7 months; approximately 1000 interviews were given each year. Main Outcome Measure Whether infant is usually placed supine to sleep. Results For the 15-year period, supine sleep increased (P < .001) and prone sleep decreased (P < .001) for all infants, with no significant difference in trend by race. Since 2001, a plateau has been reached for all races. Factors associated with increased supine sleep between 1993 and 2007 included time, maternal race other than African American, higher maternal educational level, not living in Southern states, first-born infant, and full-term infant. The effect of these variables was reduced when variables related to maternal concerns about infant comfort, choking, and advice from physicians were taken into account. Between 2003 and 2007, there was no significant yearly increase in supine sleep. Choice of sleep position could be explained almost entirely by caregiver concern about comfort, choking, and advice. Race no longer was a significant predictor. Conclusions Since 2001, supine sleep has reached a plateau, and there continue to be racial disparities. There have been changes in factors associated with sleep position, and maternal attitudes about issues such as comfort and choking may account for much of the racial disparity in practice. To decrease sudden infant death syndrome rates, we must ensure that public health measures reach the populations at risk and include messages that address concerns about infant comfort and choking.

Effects of Local Institutional Review Board Review on Participation in National Practice-Based Research Network Studies [Article]

Objective To describe the process and outcomes of local institutional review board (IRB) review for 2 Pediatric Research in Office Settings (PROS) studies. Design Pediatric Research in Office Settings conducted 2 national studies concerning sensitive topics: (1) Child Abuse Recognition Experience Study (CARES), an observational study of physician decision making, and (2) Safety Check, a violence prevention intervention trial. Institutional review board approval was secured by investigators' sites, the American Academy of Pediatrics, and practices with local IRBs. Practices were queried about IRB rules at PROS enrollment and study recruitment. Setting Pediatric Research in Office Settings practices in 29 states. Participants Eighty-eight PROS practices (75 IRBs). Main Exposure Local IRB presence. Main Outcome Measures Local IRB presence, level of PROS assistance, IRB process, study participation, data collection completion, and minority enrollment. Results Practices requiring additional local IRB approval agreed to participate less than those that did not (CARES: 33% vs 52%; Safety Check: 41% vs 56%). Of the 88 practices requiring local IRB approval, 55 received approval, with nearly 50% needing active PROS help, many requiring consent changes (eg, contact name additions, local IRB approval stamps), and 87% beginning data collection. Median days to obtain approval were 81 (CARES) and 109 (Safety Check). Practices requiring local IRB approval were less likely to complete data collection but more likely to enroll minority patients. Conclusions Local IRB review was associated with lower participation rates, substantial effort navigating the process (with approval universally granted without substantive changes), and data collection delays. When considering future reforms, the national human subject protections system should consider the potential redundancy and effect on generalizability, particularly regarding enrollment of poor urban children, related to local IRB review.

Adverse Childhood Experiences and Adult Risk Factors for Age-Related Disease: Depression, Inflammation, and Clustering of Metabolic Risk Markers [Article]

Objective To understand why children exposed to adverse psychosocial experiences are at elevated risk for age-related disease, such as cardiovascular disease, by testing whether adverse childhood experiences predict enduring abnormalities in stress-sensitive biological systems, namely, the nervous, immune, and endocrine/metabolic systems. Design A 32-year prospective longitudinal study of a representative birth cohort. Setting New Zealand. Participants A total of 1037 members of the Dunedin Multidisciplinary Health and Development Study. Main Exposures During their first decade of life, study members were assessed for exposure to 3 adverse psychosocial experiences: socioeconomic disadvantage, maltreatment, and social isolation. Main Outcome Measures At age 32 years, study members were assessed for the presence of 3 age-related-disease risks: major depression, high inflammation levels (high-sensitivity C-reactive protein level >3 mg/L), and the clustering of metabolic risk biomarkers (overweight, high blood pressure, high total cholesterol, low high-density lipoprotein cholesterol, high glycated hemoglobin, and low maximum oxygen consumption levels. Results Children exposed to adverse psychosocial experiences were at elevated risk of depression, high inflammation levels, and clustering of metabolic risk markers. Children who had experienced socioeconomic disadvantage (incidence rate ratio, 1.89; 95% confidence interval, 1.36-2.62), maltreatment (1.81; 1.38-2.38), or social isolation (1.87; 1.38-2.51) had elevated age-related-disease risks in adulthood. The effects of adverse childhood experiences on age-related-disease risks in adulthood were nonredundant, cumulative, and independent of the influence of established developmental and concurrent risk factors. Conclusions Children exposed to adverse psychosocial experiences have enduring emotional, immune, and metabolic abnormalities that contribute to explaining their elevated risk for age-related disease. The promotion of healthy psychosocial experiences for children is a necessary and potentially cost-effective target for the prevention of age-related disease.

Error in Table in: Selective Serotonin Reuptake Inhibitor Exposure In Utero and Pregnancy Outcomes [Correction]

A National Survey of Obesity Prevention Practices in Head Start [Article]

Objective To describe obesity prevention practices and environments in Head Start, the largest federally funded early childhood education program in the United States. Design Self-administered survey as part of the Study of Healthy Activity and Eating Practices and Environments in Head Start (SHAPES). Setting Head Start, 2008. Participants Directors of all 1810 Head Start programs, excluding those in US territories. Outcome Measures Descriptive measures of reported practices and environments related to healthy eating and gross motor activity. Results The 1583 (87%) programs responding to the survey enrolled 828 707 preschool children. Of these programs, 70% reported serving only nonfat or 1% fat milk. Ninety-four percent of programs reported that each day they served children some fruit other than 100% fruit juice; 97% reported serving some vegetable other than fried potatoes; and 91% reported both of these daily practices. Sixty-six percent of programs said they celebrated special events with healthy foods or nonfood treats, and 54% did not allow vending machines for staff. Having an on-site outdoor play area at every center was reported by 89% of programs. Seventy-four percent of programs reported that children were given structured (adult-led or -guided) gross motor activity for at least 30 minutes each day; 73% reported that children were given unstructured gross motor activity for at least 30 minutes each day, and 56% reported both of these daily practices. Conclusion Most Head Start programs report doing more to support healthy eating and gross motor activity than required by federal performance standards in these areas.

Formal Production Features of Infant and Toddler DVDs [Article]

Objective To describe how DVDs designed for very young children are constructed, focusing on the formal production features used to present the program content. Design Descriptive study of the concentrations of perceptually salient, nonsalient, and reflective formal features. Participants Fifty-nine DVDs designed for children younger than 3 years. Main Exposure The presence and absence of specific formal features. Outcome Measures Concentrations of reflective (singing, rhyming, camera zooms, and moderate character action), perceptually salient (rapid pacing, fast action, camera cuts, sound effects, character vocalizations, and visual special effects), and nonsalient (low-action sequences, narration, and dialogue by men, women, or children) formal features. Results Programs were composed of high concentrations of perceptually salient features, such as rapid pace and camera cuts, which are difficult even for older children to understand. Reflective features, which provide opportunities to rehearse content, were relatively rare. Character action was typically nonsalient. The DVDs used speech only 24% of the time and failed to selectively use speakers, such as choosing a child over an adult for dialogue and narration, which garners slightly older children's visual attention. Conclusions Producers who claim that their programs are educational should pay more attention to how they transmit content. Most programs directed at infants and toddlers rely on perceptually salient features like rapid pacing and camera cuts, which may elicit attention and interest but are most likely very difficult for a young audience to understand.

Picture of the Month--Quiz Case [Special Feature]

Picture of the Month--Diagnosis [Special Feature]

Adequacy of the Supply of Pediatric Subspecialists: So Near, Yet So Far [Editorial]

Adolescent Human Immunodeficiency Virus Prevention: What We Have Accomplished and What Still Needs to Be Done [Editorial]

It Is Time to Professionalize Institutional Review Boards [Editorial]

Infant Sleep Position: Back to Sleep [Advice for Patients]

Two Japanese infants with congenital generalized lipodystrophy due to BSCL2 mutations

Neonatal MRI in preterm infants with periventricular leukomalacia and mild disability

Changes in pulmonary arterial pressure in term-infants with hypoxicischemic encephalopathy

Association between serum adipocytokine and cholesterol levels in cord blood

The significance of measurement of serum unbound bilirubin concentrations in high-risk infants

Relationship between free T4 levels and postnatal steroid therapy in preterm infants

Reduced oxygen protocol decreases the incidence of threshold retinopathy of prematurity in infants of 33 weeks gestation

The relation of arterial stiffness with intrauterine growth retardation

Breastfeeding reduces the severity of respiratory syncytial virus infection among young infants: A multi-center prospective study

Feeding on one side or both sides in a breast-feeding session

Influence of smoking on human milk tumor necrosis factor-, interleukin-1, and soluble vascular cell adhesion molecule-1 levels at postpartum seventh day

Psychopathology in thalassemia major

Bilateral basal ganglia infarction after mild head trauma

HajduCheney syndrome: Infantile onset of hydrocephalus and serpentine fibulae

Congenital systemic juvenile xanthogranuloma with placental lesion

Acute renal failure caused by fungus balls in renal pelvises

Successful bone marrow transplantation in chronic granulomatous disease

Diagnostic and therapeutic value of naloxone after intoxication with tramadol in a young girl

Oral megadose methylphenidate ingestion for suicide attempt

Fatal degeneration of specialized cardiac muscle associated with chronic active EpsteinBarr virus infection

Congenital upper thoracic spondyloptosis with multiple other associated anomalies

Erratum

Announcements

Complementary, Holistic, and Integrative Medicine: Sensory Integration

Car Safety

Respiratory Failure

Index of Suspicion

Clarification

Visual Diagnosis: A Small Bowel Obstruction

Addison Disease

Adolescent Nutrition

Long-term Corticosteroid Use

Antibiotic Susceptibility

Cumulative Index Ends

CME Clarification

Thank You!

Association of Tobacco and Lead Exposures With Attention-Deficit/Hyperactivity Disorder

OBJECTIVE: The study objective was to determine the independent and joint associations of prenatal tobacco and childhood lead exposures with attention-deficit/hyperactivity disorder (ADHD), as defined by current diagnostic criteria, in a national sample of US children. METHODS: Data are from the 2001–2004 National Health and Nutrition Examination Survey, a cross-sectional, nationally representative sample of the US population. Participants were 8 to 15 years of age (N = 2588). Prenatal tobacco exposure was measured by report of maternal cigarette use during pregnancy. Lead exposure was assessed by using current blood lead levels. The Diagnostic Interview Schedule for Children was used to ascertain the presence of ADHD in the past year, on the basis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. RESULTS: A total of 8.7% (95% confidence interval [CI]: 7.3%–10.1%) of children met criteria for ADHD. Prenatal tobacco exposure (adjusted odds ratio [aOR]: 2.4 [95% CI: 1.5–3.7]) and higher current blood lead concentrations (aOR for third versus first tertile: 2.3 [95% CI: 1.5–3.8]) were independently associated with ADHD. Compared with children with neither exposure, children with both exposures (prenatal tobacco exposure and third-tertile lead levels) had an even greater risk of ADHD (aOR: 8.1 [95% CI: 3.5–18.7]) than would be expected if the independent risks were multiplied (tobacco-lead exposure interaction term, P < .001). CONCLUSIONS: Prenatal tobacco and childhood lead exposures are associated with ADHD in US children, especially among those with both exposures. Reduction of these common toxicant exposures may be an important avenue for ADHD prevention.

Intellectual Outcome from Preschool Traumatic Brain Injury: A 5-Year Prospective, Longitudinal Study

INTRODUCTION: Traumatic brain injury (TBI) is a common, acquired disability that may be used as a model to understand the impact of early brain injury on brain structure and function. To date, few studies have followed very young children over time after insult. OBJECTIVE: To plot recovery and outcome of intellectual ability after early TBI over the 5 years after injury, and to identify predictors of outcome including injury, sociodemographic and preinjury characteristics, and acute functional recovery. DESIGN: Children aged between 2 and 7 years who were diagnosed with TBI (N = 54) were consecutively recruited on admission to the Royal Children's Hospital, Victoria, Australia, to participate in a prospective, longitudinal study. Our study had a between-factor design that used injury severity as the independent variable. The participants were categorized into groups according to injury severity (mild, moderate, or severe), and were compared with healthy control participants (n = 16) at the acute time point, and at 12 months, 30 months, and 5 years after injury. Intellectual measures, including verbal and nonverbal skills, attention, and processing speed, were administered. RESULTS: Children with severe injuries demonstrated slower recovery and poorer cognitive outcomes up to 5 years after injury than did those who were observed for less severe injuries. Recovery trajectories were associated with injury severity over the first 30 months after injury, with the greatest deterioration in function observed for more severe injuries. From 30 months to 5 years after injury, progress was stable. Only injury severity (as determined by the Glasgow Coma Scale score) and acute cognitive performance were strong predictors of 5-year outcomes. CONCLUSIONS: This study has confirmed the high risk of persisting and global deficits associated with severe brain insult in early childhood. Contrary to previous speculation about "growing into deficits," children with severe brain insults have more protracted recovery periods but do not continue to lose ground compared with their peers. By 30 months after insult, recovery seems to stabilize and children begin to make appropriate developmental gains.

Relative Impact of Influenza and Respiratory Syncytial Virus in Young Children

OBJECTIVE: We measured the relative impact of influenza and respiratory syncytial virus (RSV) infections in young children in terms of emergency department (ED) visits, clinical care requirements, and overall resource use. METHODS: Patients who were aged ≤7 years and treated in the ED of a tertiary care pediatric hospital for an acute respiratory infection were enrolled during 2 winter seasons between 2003 and 2005. We quantified health care resource use for children with influenza or RSV infections, and extrapolated results to estimate the national resource use associated with influenza and RSV infections. RESULTS: Nationally, an estimated 10.2 ED visits per 1000 children were attributable to influenza and 21.5 visits per 1000 to RSV. Children who were aged 0 to 23 months and infected with RSV had the highest rate of ED visits with 64.4 visits per 1000 children. Significantly more children required hospitalization as a result of an RSV infection compared with influenza, with national hospitalization rates of 8.5 and 1.4 per 1000 children, respectively. The total number of workdays missed yearly by caregivers of children who required ED care was 246965 days for influenza infections and 716404 days for RSV infections. CONCLUSION: For young children, RSV is associated with higher rates of ED visits, hospitalization, and caregiver resource use than is influenza. Our results provide data on the large number of children who receive outpatient care for influenza and RSV illnesses and serve to inform analyses of prevention programs and treatments for both influenza and RSV disease.

Pediatric Hospital Adherence to the Standard of Care for Acute Gastroenteritis

BACKGROUND: Adherence to published care guidelines for the management of acute gastroenteritis (AGE) is unknown. OBJECTIVES: To evaluate the association of AGE guideline adherence with outcomes and resource use at pediatric hospitals. DESIGN/METHODS: We studied children aged 6 months to 6 years with an International Classification of Diseases, Ninth Edition (ICD-9) discharge code indicative of AGE and without comorbid conditions in the emergency department, observation setting, or hospital. Laboratory studies, antiemetic use, and antibiotic use were evaluated, and the length of stay, mean adjusted total charges, and readmission proportion were documented. Multiple analysis of variance determined if the variance of adjusted charges, length of stay, and diagnostic studies were hospital-related. A regression analysis determined the association between guideline adherence and outcomes. RESULTS: There were a total of 188873 patients; 174594 (92.4%) were not admitted, and 14279 (7.6%) were admitted. There was substantial variation in resource use among hospitals. The mean adjusted total charge for all patients was $863 (SD: 1336). The mean adjusted total charge for nonadmitted patients was $591 (SD: 636). Individual hospitals contributed to the variance of mean length of stay, total adjusted charges, and use of diagnostic studies after controlling for covariates (P < .001). Guideline adherence was associated with a mean decrease in the average adjusted cost ($591) for nonadmitted patients of $296 (95% confidence interval: –399 to –193). CONCLUSIONS: Guideline-adherent hospitals demonstrated 50% lower charges for emergency department or observation patients with uncomplicated AGE without adversely affecting outcomes. Use of resources not routinely recommended by published AGE guidelines remains common in pediatric hospitals.

Recurrent Abdominal Pain in Childhood Urolithiasis

OBJECTIVE: Our goal was to establish the clinical presentation and features of pain attacks in children with recurrent abdominal pain (RAP) and urolithiasis. METHODS: We compared the rate of previous appendectomy among 100 consecutive patients with that of 270 control subjects. We also compared the frequency of pain attacks with that reported by children with functional or organic gastrointestinal RAP. RESULTS: Fifty-three patients had no history of dysuria or gross hematuria, and only 35 had hematuria at the first visit; 41 patients were evaluated for urolithiasis only because of a family history of kidney stones associated with RAP. Twenty-nine patients had been previously hospitalized for abdominal symptoms. Sixteen patients and 4 control subjects (1.5%) had undergone a previous appendectomy (P < .0001). Two to 28 months before the diagnosis of urolithiasis, 37 patients underwent abdominal ultrasonography, which did not show urinary stones. Sixty-nine percent of subjects younger than 8 years of age had central/diffuse abdominal pain. The mean frequency of pain attacks was 4 to 9 times lower than in patients with functional or organic gastrointestinal RAP. CONCLUSIONS: Because of the inconstant occurrence of dysuria and hematuria, the location of pain in areas other than the flank, and the lack of calculi shown on imaging studies performed after pain attacks, the urologic origin of pain may be overlooked and ineffective procedures performed. The possibility of urolithiasis should be considered in children with RAP who have a family history of urolithiasis and/or infrequent pain attacks, even when dysuria and hematuria are lacking, and in younger children even when pain is not lateral.

Severe Thrombocytopenia in the NICU

OBJECTIVE: Severe thrombocytopenia (platelets ≤ 50000/µL) in a NICU patient can have significant consequences; however, previous reports have not focused exclusively on NICU patients with counts this low. METHODS: We identified all patients with severe thrombocytopenia who were cared for in the Intermountain Healthcare level III NICUs from 2003–2007. RESULTS: Among 11281 NICU admissions, severe thrombocytopenia was identified in 273 (2.4%). Just over 30% of these presented in the first three days of life. Half presented by day 10, 75% by day 27, and 95% by day 100. The prevalence was inversely related to birth weight. Cutaneous bleeding was more common in patients with platelet counts of <20000/µL; however, no statistically significant correlation was found between platelet counts and pulmonary, gastrointestinal, or intraventricular bleeding. The most common explanations for severe thrombocytopenia were acquired varieties of consumptive thrombocytopenia. Platelet transfusions (median 5, range 0–76) were administered to 86% of the patients. No deaths were ascribed to exsanguinations. The mortality rate did not correlate with the lowest platelet count but was proportionate to the number of platelet transfusions. CONCLUSION: The prevalence of severe thrombocytopenia in the NICU is inversely proportional to birth weight and most cases are acquired consumptive thrombocytopenias. We speculate that very low platelet counts are a causal factor in cutaneous bleeding, but pulmonary, gastrointestinal, and intraventricular bleeding are less influenced by the platelet count and occur primarily from causes other than severe thrombocytopenia. The lowest platelet count does not predict the mortality rate but the number of platelet transfusions received does.

Skin-to-Skin Contact and/or Oral 25% Dextrose for Procedural Pain Relief for Term Newborn Infants

OBJECTIVE: The goal was to compare the efficacy of oral 25% dextrose treatment and/or skin-to-skin contact for analgesia in term newborns during intramuscular injection of a hepatitis B vaccine. METHODS: A prospective, randomized, partially blinded, clinical trial was performed with 640 healthy term newborns. Infants at 12 to 72 hours of life were assigned randomly to receive an intramuscular injection of hepatitis B vaccine in the right thigh according to 4 analgesia groups, that is, no analgesia (routine); oral 25% dextrose treatment, given 2 minutes before the injection; skin-to-skin contact, initiated 2 minutes before the injection and persisting throughout the procedure; and a combination of the oral dextrose treatment and skin-to-skin contact strategies. For all groups, Neonatal Facial Coding System and Neonatal Infant Pain Scale scores were evaluated before the procedure, during thigh cleansing, during the injection, and 2 minutes after the injection. Premature Infant Pain Profile scores also were assessed for all infants. Pain scores were compared among the 4 groups. RESULTS: The use of oral 25% dextrose treatment reduced the duration of procedural pain in the studied population. Skin-to-skin contact decreased injection pain and duration. The combination of the 2 analgesic measures was more effective than either measure separately for term newborns. CONCLUSIONS: Nonpharmacologic analgesic measures were effective for the treatment of procedural pain in term infants. The combination of oral 25% dextrose treatment and skin-to-skin contact acted synergistically to decrease acute pain in healthy neonates.

Rectal Fecal Impaction Treatment in Childhood Constipation: Enemas Versus High Doses Oral PEG

OBJECTIVE: We hypothesized that enemas and polyethylene glycol (PEG) would be equally effective in treating rectal fecal impaction (RFI) but enemas would be less well tolerated and colonic transit time (CTT) would improve during disimpaction. METHODS: Children (4–16 years) with functional constipation and RFI participated. One week before disimpaction, a rectal examination was performed, symptoms of constipation were recorded, and the first CTT measurement was started. If RFI was determined, then patients were assigned randomly to receive enemas once daily or PEG (1.5 g/kg per day) for 6 consecutive days. During this period, the second CTT measurement was started and a child's behavior questionnaire was administered. Successful rectal disimpaction, defecation and fecal incontinence frequencies, occurrence of abdominal pain and watery stools, CTTs (before and after disimpaction), and behavior scores were assessed. RESULTS: Ninety-five patients were eligible, of whom 90 participated (male, n = 60; mean age: 7.5 ± 2.8 years). Forty-six patients received enemas and 44 PEG, with 5 dropouts in each group. Successful disimpaction was achieved with enemas (80%) and PEG (68%; P = .28). Fecal incontinence and watery stools were reported more frequently with PEG (P < .01), but defecation frequency (P = .64), abdominal pain (P = .33), and behavior scores were comparable between groups. CTT normalized equally (P = .85) in the 2 groups. CONCLUSION: Enemas and PEG were equally effective in treating RFI in children. Compared with enemas, PEG caused more fecal incontinence, with comparable behavior scores. The treatments should be considered equally as first-line therapy for RFI.

Pompe Disease in Infants: Improving the Prognosis by Newborn Screening and Early Treatment

OBJECTIVE: Pompe disease causes progressive, debilitating, and often life-threatening musculoskeletal, respiratory, and cardiac symptoms. Favorable outcomes with early intravenous enzyme-replacement therapy and alglucosidase alfa have been reported, but early clinical diagnosis before the development of severe symptoms has rarely been possible in infants. METHODS: We recently conducted a newborn screening pilot program in Taiwan to improve the early detection of Pompe disease. Six of 206088 newborns screened tested positive and were treated for Pompe disease. Five had the rapidly progressive form of Pompe disease, characterized by cardiac and motor involvement, and were treated soon after diagnosis. The sixth patient was started on treatment at 14 months of age because of progressive muscle weakness. Outcomes were compared with treated patients whose disease was diagnosed clinically and with untreated historical control subjects. RESULTS: At the time of this report, patients had been treated for 14 to 32 months. The 5 infants who had early cardiac involvement demonstrated normalization of cardiac size and muscle pathology with normal physical growth and age-appropriate gains in motor development. The infant without cardiac involvement also achieved normal motor development with treatment. Survival in patients who had newborn screening was significantly improved compared with those in the untreated reference cohort (P = .001). Survival in the treated clinical comparators was reduced but not statistically different from that in the newborn screening group (P = .48). CONCLUSIONS: Results from this study indicate that early treatment can benefit infants with Pompe disease and highlight the advantages of early diagnosis, which can be achieved by newborn screening.

Risk Factors Associated With Deformational Plagiocephaly

OBJECTIVE: This study was designed to statistically evaluate the independent and interacting effects of biological and environmental risk factors that influence lateralization of deformational plagiocephaly (DP) in an attempt to provide future guidance for clinical treatment. METHODS: A database of >20000 children treated for DP was examined by using 2- and 3-way factor analyses for categorical frequency data, representing the largest statistical analysis of DP to date. Data on parity, zygosity, intrauterine presentation, birth number and weight, sleep position, lateralization, and sex were collected from parents of children with DP who were treated at Cranial Technologies, Inc, from 1990 to 2007. RESULTS: As with most DP studies, male patients were significantly overrepresented. Nonetheless, after statistically accounting for sex in our analyses, DP is significantly correlated with primiparity, fewer vertex but more breech and transverse intrauterine presentations, twinning (specifically, dizygosity), and, finally, right-sided lateralization. Additional analyses revealed that several factors correlated with DP, such as intrauterine presentation, sleep position, and lateralization, are not easily explained by an underlying biological factor. Instead, sleep position was the single greatest predictor of lateralization. CONCLUSION: Although previous studies have argued for both environmental and underlying biological factors associated with DP, we found that lateralization in children with DP could be largely explained by environmental factors such as sleep position.

Transition to Adult Care for Youths With Diabetes Mellitus: Findings From a Universal Health Care System

OBJECTIVES: The goals were (1) to describe rates of diabetes mellitus (DM)-related hospitalizations and retinopathy screening before and after transition to adult care and (2) to test whether different methods of transfer of care were associated with improved outcomes. METHODS: In a retrospective cohort study, we included 1507 young adults with DM of ≥5-year duration and tracked these patients until 20 years of age. RESULTS: DM-related hospitalization rates increased from 7.6 to 9.5 cases per 100 patient-years in the 2 years after transition to adult care (P = .03). Previous DM-related hospitalizations, lower income, female gender, and living in areas with low physician supply were associated with higher admission rates. With controlling for all other factors, individuals who were transferred to a new allied health care team with no change in physician were 77% less likely (relative risk: 0.23 [95% confidence interval: 0.05–0.79]) to be hospitalized after the transition than were those transferred to a new physician with either a new or no allied health care team. The rates of eye examinations were stable across the transition to adult care (72% vs 70%; P = .06). Female patients, patients with higher income, and patients with previous eye care were more likely to have an eye care visit after transfer. CONCLUSIONS: During the transition to adult health care, there is increased risk of DM-related hospitalizations, although this may be attenuated in youths for whom there is physician continuity. Eye care visits were not related to transition; however, rates were below evidence-based guideline recommendations.

Attitudes of Adolescent Cancer Survivors Toward End-of-Life Decisions for Minors

OBJECTIVES: The present study aimed to investigate the attitudes of adolescent cancer survivors toward end-of-life decisions with life-shortening effects, including nontreatment decisions (NTDs), intensified alleviation of pain and symptoms (APS), and euthanasia, and the influence of illness experience on these attitudes. METHODS: Adolescent cancer survivors were interviewed with a structured questionnaire using hypothetical case descriptions. The results were compared with a study of 1769 adolescents without experience of chronic illness. RESULTS: Eighty-three adolescents, 11 to 18 years of age, were interviewed. In terminal situations, 70% to 90% found requests for NTDs acceptable, 84% requests for APS, and 57% to 64% requests for euthanasia. Requests for end-of-life decisions were less acceptable in nonterminal situations, where 28% found requests for NTDs acceptable, 39% to 47% requests for APS, and 11% to 21% requests for euthanasia. Frequently cited reasons for holding back physicians from administering a lethal drug to a child were the child not being well informed about his or her condition (92%) and the parents' opinion not being asked (92%). Compared with adolescents without experience with chronic illness, cancer survivors were more accepting toward requests for NTDs and APS in terminal situations. CONCLUSIONS: Adolescent cancer survivors, like other adolescents, want to be involved in medical decision-making at the end of life. They value autonomous decision-making, without excluding parents from the process. The experience of living through a life-threatening illness can alter adolescents' attitudes toward requests for NTDs and APS.

Energy Expenditure for Breastfeeding and Bottle-Feeding Preterm Infants

OBJECTIVE: We hypothesized that resting energy expenditure (REE) would be higher after breastfeeding than after bottle-feeding. METHODS: Nineteen preterm infants (gestational age: 32 weeks) in stable condition who were nourished entirely with their mothers' breast milk were assigned randomly to feeding either by bottle or at the breast. Each infant served as his or her own control subject. REE was measured for 20 minutes after feeding. Breast milk quantity was evaluated with prefeeding and postfeeding weighing. REE values for bottle-feeding and breastfeeding were compared with paired t tests. RESULTS: Contrary to our null hypothesis, the group's mean REE values after bottle-feeding and breastfeeding were very similar (284.7 ± 26.8 kJ/kg per day [68.3 ± 6.4 kcal/kg per day] vs 282.6 ± 28.5 kJ/kg per day [67.5 ± 6.8 kcal/kg per day]; not significant). The duration of feeding was significantly longer for breastfeeding than for bottle-feeding (20.1 ± 7.9 vs 7.8 ± 2.9 minutes; P < .0001). CONCLUSION: There was no significant difference in REE when infants were breastfed versus bottle-fed. Longer feeding times at the breast did not increase REE. We speculate that it is safe to recommend feeding at the breast for infants born at >32 weeks when they can tolerate oral feeding.

Neurodevelopmental Outcome of Infants With Unilateral or Bilateral Periventricular Hemorrhagic Infarction

OBJECTIVE: Periventricular hemorrhagic infarction (PVHI) is a major contributing factor to poor neurodevelopmental outcomes in preterm infants. We hypothesized that surviving infants with unilateral PVHI would have more favorable outcomes than those with bilateral PVHI. METHODS: This was a multicenter, retrospective study of infants who were admitted to 3 NICUs in North Carolina from 1998 to 2004. The clinical course and late neuroimaging studies and neurodevelopmental outcomes of 69 infants who weighed <1500 g and had confirmed PVHI on early cranial ultrasonography were reviewed. A predictive model for Bayley Scales of Infant Development, Second Edition, Mental Developmental Index (MDI) <70 was constructed by using radiologic and clinical variables. RESULTS: Infants with unilateral PVHI had higher median MDI (82 vs 49) and Psychomotor Developmental Index (53 vs 49) than infants with bilateral PVHI. Infants with unilateral PVHI were less likely to have severe cerebral palsy (adjusted odds ratio: 0.15 [95% confidence interval (CI): 0.05–0.45]) than infants with bilateral PVHI. Infants who had unilateral PVHI and developed periventricular leukomalacia and retinopathy of prematurity that required surgery had an increased probability of having MDI <70 compared with those without these complications (probability of MDI <70: 89% [95% CI: 0.64–1.00] vs 11% [95% CI: 0.01–0.28]). CONCLUSIONS: Infants with unilateral PVHI had better motor and cognitive outcomes than infants with bilateral PVHI. By combining laterality of PVHI, periventricular leukomalacia, and retinopathy of prematurity it is possible to estimate the probability of having an MDI <70, which will assist clinicians when counseling families.

Decreased Regional Brain Volume and Cognitive Impairment in Preterm Children at Low Risk

OBJECTIVE: To investigate whether preterm children with low risk for neurodevelopmental deficits show long-term changes in gray matter (GM) and white matter (WM) volumes compared with term children and to relate these changes to cognitive outcome. METHODS: MRI was used to evaluate 20 preterm children who were determined to be at low risk for neurodevelopmental deficits and were born between 30 and 34 weeks’ gestational age without major neonatal morbidity or cerebral pathology in the neonatal period and 22 matched, term control subjects. Volumetric images were analyzed by means of voxel-based morphometry to identify regional cerebral alterations. Children also underwent cognitive and behavioral/emotional assessments. RESULTS: Preterm children showed global and regional GM volume reductions in several brain areas, including temporal and parietal lobes and concomitant WM volume reductions in the same areas, although only the left temporal regions achieved statistical significance. Global intellectual performance in the preterm group was significantly decreased compared with control subjects. Neither behavioral nor emotional problems were found in the preterm group. In the whole sample, we found a positive correlation between GM volume bilaterally in the middle temporal and in the postcentral gyri with IQ. Positive correlations were observed between GM and gestational age at birth in parietal and temporal cerebral regions and with WM in parietal regions. CONCLUSION: Preterm birth has an important impact on the neurodevelopmental and cognitive outcome of children at 9 years of age, being a risk factor for decreased regional cortical GM and WM even in preterm children with low risk for neurodevelopmental deficits.

Association Between Adherence and Glycemic Control in Pediatric Type 1 Diabetes: A Meta-analysis

CONTEXT: Although adherence has been identified in practice guidelines for youth with type 1 diabetes to promote optimal glycemic control, there has been no systematic integration of studies investigating the adherence-glycemic control link. This recommendation partly stemmed from the Diabetes Control and Complications Trial (DCCT); however, this trial did not comprehensively measure adherence and had only 195 adolescents. OBJECTIVE: Our goal was to determine the magnitude of the adherence-glycemic control link in pediatric type 1 diabetes and evaluate its correlates. METHODS: Our data sources were PubMed (1950–2008), Scopus (1950–2008), and references from reviews in pediatric type 1 diabetes. Studies that included youth under age 19 with type 1 diabetes and a reported association between adherence and glycemic control were eligible for inclusion. Articles were not included if they contained youth with type 2 diabetes, had study samples that overlapped with other studies, or the results came from intervention studies. Of the eligible 26 studies, 21 had sufficient statistical data. Two authors independently extracted information by using a standardized protocol. Agreement between coders was high. RESULTS: The mean effect size across 21 studies, including 2492 youth with type 1 diabetes, was –0.28 (95% confidence interval: –0.32 to –0.24). As adherence increases, A1c values decrease. No sample or disease characteristics were correlates of the adherence-glycemic control link. Pre-DCCT studies had a mean effect size of –0.32 (8 studies; 1169 participants) compared with –0.25 in post-DCCT studies (13 studies; 1323 participants). CONCLUSIONS: This meta-analysis supports the adherence-glycemic control link in pediatric type 1 diabetes. The weaker post-DCCT association suggests that the approach to intensive diabetes management has shortcomings. We conclude that this is because of a mismatch between what scientists and clinicians know is the best way to manage pediatric type 1 diabetes and the capabilities of youth and their families.

HIV Risk Reduction Among Detained Adolescents: A Randomized, Controlled Trial

OBJECTIVES: Criminally involved adolescents engage in high levels of alcohol-related risky sex. A theory-based sexual and alcohol risk-reduction intervention was designed, implemented, and evaluated in juvenile detention facilities. Participants and Methods. In a randomized, controlled trial, 484 detained adolescents received 1 of 3 group-based interventions: combined sexual and alcohol risk reduction (group psychosocial intervention [GPI] + group motivational enhancement therapy [GMET]); sexual risk reduction only (GPI); or HIV/sexually transmitted disease prevention information only (group information-only intervention [GINFO]). Follow-up data were obtained 3, 6, 9, and 12 months after the intervention. Behavioral outcomes were condom-use behavior, frequency of intercourse while drinking, and alcohol-related problems. RESULTS: Condom-use behavior measured as frequency of condom use during sex (ranging from never to always) decreased over time, although the GPI and GPI + GMET interventions mitigated this tendency at the 3-, 6-, and 9-month follow-up assessments. Although both active interventions were significantly more successful than the GINFO condition and the pattern of effects favored the GPI + GMET, there were no statistically significant differences between the GPI and GPI + GMET interventions. CONCLUSIONS: Findings support the feasibility of integrating alcohol-specific sexual risk content into a theory-based sexual risk-reduction intervention and provide additional evidence that theory-based interventions are effective at reducing risky sex in this population. There was limited evidence of intervention effects on alcohol-use outcomes. Future research should focus on strengthening the GPI + GMET to most effectively target risky sexual behavior among at-risk adolescents.

Antiretroviral Exposure and Lymphocyte mtDNA Content Among Uninfected Infants of HIV-1-Infected Women

OBJECTIVE: Concern for potential adverse effects of antiretroviral (ARV) chemotherapy used to prevent mother-to-child HIV transmission has led the US Public Health Service to recommend long-term follow-up of ARV-exposed children. Nucleoside reverse transcriptase inhibitor ARV agents can inhibit DNA polymerase , impairing mitochondrial DNA (mtDNA) synthesis and resulting in depletion or dysfunction. METHODS: We measured the mtDNA content of stored peripheral blood mononuclear cells (PBMCs) of 411 healthy children who were born to HIV-uninfected women and 213 uninfected infants who were born to HIV-infected women with or without in utero and neonatal ARV exposure. Cryopreserved PBMC mtDNA was quantified by using the Primagen Retina Mitox assay. RESULTS: Geometric mean PBMC mtDNA levels were lower at birth in infants who were born to HIV-infected women. Among HIV-exposed children, mtDNA levels were lowest in those who were not exposed to ARVs, higher in those with exposure to zidovudine alone, and higher still in those with combination nucleoside reverse transcriptase inhibitor exposure. A similar pattern was observed in the corresponding women. Levels of mtDNA increased during the first 5 years of life in all HIV-exposed children but achieved normal levels only in those with ARV exposure. CONCLUSIONS: Levels of mtDNA are lower than normal in HIV-exposed children. Contrary to expectation, PBMC mtDNA levels are significantly higher in ARV-exposed, HIV-uninfected infants and their infected mothers compared with ARV-unexposed infants and women. By 5 years, levels of PBMC mtDNA rise to normal concentrations in ARV-exposed children but remain depressed in ARV-unexposed children.

Natural History of Spinal Anomalies and Scoliosis Associated With Esophageal Atresia

OBJECTIVE: Clinical characteristics of spinal deformities that commonly occur in patients with esophageal atresia (EA) are unclear. The objective of this study was to assess the incidence and natural history of spinal anomalies and scoliosis in patients with EA. METHODS: A population-based cohort of 100 adults who had an operation for EA in our hospital were examined clinically and radiographically for spinal deformities. The results were compared with data obtained from normal population-based controls. RESULTS: Vertebral anomalies were observed in 45 patients, predominating in the cervical spine in 38 patients. Any additional anomaly was the most significant risk factor (odds ratio [OR]: 27 [95% confidence interval (CI): 8–100]) for the occurrence of vertebral anomalies. Scoliosis of >10° was observed in 56 patients, >20° in 11 patients, and >45° in 1 patient. The risk for scoliosis of >10° was 13-fold (OR: 13 [95% CI: 8.3–21]), and the risk for scoliosis of >20° was 38-fold (OR: 38 [95% CI: 14–106]) compared with those in the normal population. Thoracotomy-induced rib fusions (OR: 3.6 [95% CI: 0.7–19]) and other associated anomalies (OR: 2.1 [95% CI: 0.9–2.9]) were the strongest predictive factors for scoliosis. The general clinical course of spinal deformities was mild, and none of the patients had undergone spinal surgery. CONCLUSIONS: The risk of scoliosis is 13-fold after repair of EA in relation to general population. Nearly half of the patients have vertebral anomalies predominating in the cervical spine. Most of these deformities were not diagnosed primarily or during growth. Spinal surgery is rarely indicated.

Continuous Monitoring of Cerebrovascular Pressure Reactivity After Traumatic Brain Injury in Children

OBJECTIVE: We hypothesized that pressure reactivity index (PRx) values indicating preserved cerebrovascular pressure autoregulation would be associated with survival in children with traumatic brain injury (TBI). This hypothesis was tested in a prospective, blinded, observational, pilot study. METHODS: Twenty-one children admitted between May 2006 and September 2008 with severe TBI necessitating invasive intracranial pressure monitoring were enrolled in this study. The PRx was continuously monitored as a moving, linear correlation coefficient between low-frequency waves of intracranial and arterial blood pressures. Positive values of PRx approaching 1 indicate impaired cerebrovascular pressure reactivity, whereas negative PRx values or values close to 0 indicate preserved cerebrovascular pressure reactivity. Survival was the primary outcome and was compared with the average PRx value obtained during the intracranial pressure-monitoring period. RESULTS: PRx was associated with survival in this cohort; survivors (N = 15) had a mean PRx ± SD of 0.08 ± 0.19, and nonsurvivors (N = 6) had a mean PRx of 0.69 ± 0.21 (P = .0009). In this sample, continuous PRx monitoring suggested impaired cerebrovascular pressure reactivity at low levels of cerebral perfusion pressure (CPP) and intact cerebrovascular pressure reactivity at higher levels of CPP. CONCLUSIONS: Intact cerebrovascular pressure reactivity quantified with the PRx is associated with survival after severe head trauma in children. The PRx is CPP dependent in children. The PRx may be useful for defining age-specific and possibly patient-specific optimal targets for CPP after TBI.

Prenatal Di(2-ethylhexyl)Phthalate Exposure and Length of Gestation Among an Inner-City Cohort

OBJECTIVE: Our objective was to assess the relationship between di(2-ethylhexyl)phthalate (DEHP) exposure during pregnancy and gestational age at delivery among 311 African American or Dominican women from New York City. METHODS: Forty-eight-hour personal air and/or spot urine samples were collected during the third trimester. DEHP levels were measured in air samples and 4 DEHP metabolite levels were measured in urine. Specific gravity was used to adjust for urinary dilution. Gestational age was abstracted from newborn medical records (n = 289) or calculated from the expected date of delivery (n = 42). Multivariate linear regression models controlled for potential confounders. RESULTS: DEHP was detected in 100% of personal air samples (geometric mean: 0.20 µg/m3 [95% confidence interval [CI]: 0.18–0.21 µg/m3]); natural logarithms of air concentrations were inversely but not significantly associated with gestational age. Two or more of the DEHP metabolites were detected in 100% of urine samples (geometric mean: 4.8–38.9 ng/mL [95% CI: 4.1–44.3 ng/mL]). Controlling for potential confounders, gestational age was shorter by 1.1 days (95% CI: 0.2–1.8 days) for each 1-logarithmic unit increase in specific gravity-adjusted mono(2-ethylhexyl)phthalate concentrations (P = .01) and averaged 5.0 days (95% CI: 2.1–8.0 days) less among subjects with the highest versus lowest quartile concentrations (P = .001). Results were similar and statistically significant for the other DEHP metabolites. CONCLUSIONS: Prenatal DEHP exposure was associated with shorter gestation but, given inconsistencies with previous findings for other study populations, results should be interpreted with caution, and additional research is warranted.

Variants in the UGT1A1 Gene and the Risk of Pediatric Nonalcoholic Fatty Liver Disease

OBJECTIVE: Oxidative stress is increased in nonalcoholic fatty liver disease (NAFLD). Variants in the UGT1A1 gene contribute to increased bilirubin levels, and bilirubin can act as an antioxidant. We hypothesize that variant UGT1A1 genotypes reduce the risk for NAFLD development. METHODS: Two hundred thirty-four obese children 6 to 13 years of age were recruited. NAFLD was determined through liver ultrasonography. The UGT1A1 genotypes UGT1A1*6 and UGT1A1*28 were detected. We assessed the effects of UGT1A1 genotypes on pediatric NAFLD. RESULTS: In total, 12% of the obese children had NAFLD. The subjects with NAFLD had lower serum total bilirubin levels (0.25 ± 0.30 mg/dL) than did those without NAFLD (0.36 ± 0.38 mg/dL; P = .021). With conditioning on the effects of age- and gender-adjusted BMI, waist/hip ratio, and adiponectin levels, variant UGT1A1*6 genotypes were a protecting factor for NAFLD, with an estimated adjusted odds ratio of 0.31 (95% confidence interval: 0.11–0.91; P = .033), but variant UGT1A1*28 genotypes were not significantly associated with the occurrence of NAFLD. CONCLUSIONS: Variant UGT1A1*6 genotypes are associated with a lower risk of NAFLD in obese Taiwanese children. The UGT1A1 genotype is a new risk factor for pediatric NAFLD.

Multidisciplinary Management of Hunter Syndrome

Antioxidant Effect of Bilirubin and Pediatric Nonalcoholic Fatty Liver Disease

Prevalence of Sexually Transmitted Infections Among Female Adolescents Aged 14 to 19 in the United States

OBJECTIVE: Most young women initiate sexual activity during adolescence; risk for sexually transmitted infections (STIs) accompanies this initiation. In this study we estimated the prevalence of the most common STIs among a representative sample of female adolescents in the United States. METHODS: Data were analyzed from 838 females who were aged 14 to 19 and participating in the nationally representative National Health and Nutrition Examination Survey 2003–2004. After interview and examination, survey participants provided biological specimens for laboratory testing. The main outcome was weighted prevalence of at least 1 of 5 STIs: Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, herpes simplex virus type 2, and human papillomavirus (HPV) (any of 23 high-risk types or type 6 or 11). RESULTS: Prevalence of any of the 5 STIs was 24.1% among all and 37.7% among sexually experienced female adolescents. HPV (23 high-risk types or type 6 or 11) was the most common STI among all female adolescents (prevalence: 18.3%), followed by C trachomatis infection (prevalence: 3.9%). Prevalence of any of the STIs was 25.6% among those whose age was the same or 1 year greater than their age at sexual initiation and 19.7% among those who reported only 1 lifetime sex partner. CONCLUSIONS: The prevalence of STIs among female adolescents is substantial, and STIs begin to be acquired soon after sexual initiation and with few sex partners. These findings support early and comprehensive sex education, routine HPV vaccination at the age of 11 to 12 years, and C trachomatis screening of sexually active female adolescents.

Adherence Feedback to Improve Asthma Outcomes Among Inner-City Children: A Randomized Trial

OBJECTIVE: We evaluated the longitudinal effects of home-based asthma education combined with medication adherence feedback (adherence monitoring with feedback [AMF]) and asthma education alone (asthma basic care [ABC]) on asthma outcomes, relative to a usual-care (UC) control group. METHODS: A total of 250 inner-city children with asthma (mean age: 7 years; 62% male; 98% black) were recruited from a pediatric emergency department (ED). Health-outcome measures included caregiver-frequency of asthma symptoms, ED visits, hospitalizations, and courses of oral corticosteroids at baseline and 6-, 12-, and 18-month assessments. Adherence measures included caregiver-reported adherence to inhaled corticosteroid (ICS) therapy and pharmacy records of ICS refills. Multilevel modeling was used to examine the differential effects of AMF and ABC compared with UC. RESULTS: ED visits decreased more rapidly for the AMF group than for the UC group, but no difference was found between the ABC and UC groups. The AMF intervention led to short-term improvements in ICS adherence during the active-intervention phase relative to UC, but this improvement decreased over time. Asthma symptoms and courses of corticosteroids decreased more rapidly for the ABC group than for the UC group. Hospitalization rates did not differ between either intervention group and the UC group. No differences were found between the ABC and AMF groups on any outcome. CONCLUSIONS: Asthma education led to improved adherence and decreased morbidity compared with UC. Home-based educational interventions may lead to modest short-term improvements in asthma outcomes among inner-city children. Adherence feedback did not improve outcomes over education alone.

Improving Asthma Outcomes in Minority Children: A Randomized, Controlled Trial of Parent Mentors

OBJECTIVE: Because asthma disproportionately affects minorities, we evaluated the effects of parent mentors (PMs) on asthma outcomes in minority children. METHODS: This randomized, controlled trial allocated minority asthmatic children to the PM intervention or traditional asthma care. Intervention families were assigned PMs (experienced parents of asthmatic children who received specialized training). PMs met monthly with children and families at community sites, phoned parents monthly, and made home visits. Ten asthma outcomes and costs were monitored for 1 year. Outcomes were examined by using both intention-to-treat analyses and stratified analyses for high participants (attending ≥25% of community meetings and completing ≥50% of PM phone interactions). RESULTS: Patients were randomly assigned to PMs (n = 112) or the control group (n = 108). In intention-to-treat analyses, intervention but not control children experienced significantly reduced rapid-breathing episodes, asthma exacerbations, and emergency department (ED) visits. High participants (but not controls or low participants) experienced significantly reduced wheezing, asthma exacerbations, and ED visits and improved parental efficacy in knowing when breathing problems are controllable at home. Mean reductions in missed parental work days were greater for high participants than controls. The average monthly cost per patient for the PM program was $60.42, and net savings of $46.16 for high participants. CONCLUSIONS: For asthmatic minority children, PMs can reduce wheezing, asthma exacerbations, ED visits, and missed parental work days while improving parental self-efficacy. These outcomes are achieved at a reasonable cost and with net cost savings for high participants. PMs may be a promising, cost-effective means for reducing childhood asthma disparities.

Aripiprazole in the Treatment of Irritability in Children and Adolescents With Autistic Disorder

OBJECTIVE: The objective of this study was to evaluate short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder who were manifesting behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these. METHODS: This 8-week, double-blind, randomized, placebo-controlled, parallel-group study was conducted of children and adolescents (aged 6–17 years) with autistic disorder. Patients were randomly assigned (1:1) to flexibly dosed aripiprazole (target dosage: 5, 10, or 15 mg/day) or placebo. Efficacy outcome measures included the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression–Improvement score (CGI-I). Safety and tolerability were also assessed. RESULTS: Ninety-eight patients were randomly assigned to receive placebo (n = 51) or aripiprazole (n = 47). Mean improvement in Aberrant Behavior Checklist irritability subscale score was significantly greater with aripiprazole than with placebo from week 1 through week 8. Aripiprazole demonstrated significantly greater global improvements than placebo, as assessed by the mean CGI-I score from week 1 through week 8; however, clinically significant residual symptoms may still persist for some patients. Discontinuation rates as a result of adverse events (AEs) were 10.6% for aripiprazole and 5.9% for placebo. Extrapyramidal symptom-related AE rates were 14.9% for aripiprazole and 8.0% for placebo. No serious AEs were reported. Mean weight gain was 2.0 kg on aripiprazole and 0.8 kg on placebo at week 8. CONCLUSIONS: Aripiprazole was efficacious in children and adolescents with irritability associated with autistic disorder and was generally safe and well tolerated.

Cardiopulmonary Resuscitation for Bradycardia With Poor Perfusion Versus Pulseless Cardiac Arrest

OBJECTIVE: The objective of this study was to assess whether pediatric inpatients who receive cardiopulmonary resuscitation (CPR) for bradycardia with poor perfusion are more likely to survive to hospital discharge than pediatric inpatients who receive CPR for pulseless arrest (asystole/pulseless electrical activity [PEA]), after controlling for confounding characteristics. METHODS: A prospective cohort from the National Registry of Cardiopulmonary Resuscitation was enrolled between January 4, 2000, and February 23, 2008. Patients who were younger than 18 years and had an in-hospital event that required chest compressions for >2 minutes were eligible. Patients were divided into 2 groups on the basis of initial rhythm and pulse state: bradycardia/poor perfusion and asystole/PEA. Patient characteristics, event characteristics, and clinical characteristics were analyzed as possible confounders. Univariate analysis between bradycardia and asystole/PEA patient groups was performed. Multivariable logistic regression was used to determine whether an initial state of bradycardia/poor perfusion was independently associated with survival to discharge. RESULTS: A total of 6288 patients who were younger than 18 years were reported; 3342 met all inclusion criteria. A total of 1853 (55%) patients received chest compressions for bradycardia/poor perfusion compared with 1489 (45%) for asystole/PEA. Overall, 755 (40.7%) of 1353 patients with bradycardia survived to hospital discharge, compared with 365 (24.5%) of 1489 patients with asystole/PEA. After controlling for known confounders, CPR for bradycardia with poor perfusion was associated with increased survival to hospital discharge. CONCLUSIONS: Pediatric inpatients with chest compressions initiated for bradycardia and poor perfusion before onset of pulselessness were more likely to survive to discharge than pediatric inpatients with chest compressions initiated for asystole or PEA.

Food Allergy Among Children in the United States

OBJECTIVES: The goals were to estimate the prevalence of food allergy and to describe trends in food allergy prevalence and health care use among US children. METHODS: A cross-sectional survey of data on food allergy among children <18 years of age, as reported in the 1997–2007 National Health Interview Survey, 2005–2006 National Health and Nutrition Examination Survey, 1993–2006 National Hospital Ambulatory Medical Care Survey and National Ambulatory Medical Care Survey, and 1998–2006 National Hospital Discharge Survey, was performed. Reported food allergies, serum immunoglobulin E antibody levels for specific foods, ambulatory care visits, and hospitalizations were assessed. RESULTS: In 2007, 3.9% of US children <18 years of age had reported food allergy. The prevalence of reported food allergy increased 18% (z = 3.4; P < .01) from 1997 through 2007. In 2005–2006, serum immunoglobulin E antibodies to peanut were detectable for an estimated 9% of US children. Ambulatory care visits tripled between 1993 and 2006 (P < .01). From 2003 through 2006, an estimated average of 317000 food allergy-related, ambulatory care visits per year (95% confidence interval: 195000–438000 visits per year) to emergency and outpatient departments and physician's offices were reported. Hospitalizations with any recorded diagnoses related to food allergy also increased between 1998–2000 and 2004–2006, from an average of 2600 discharges per year to 9500 discharges per year (z = 3.4; P < .01), possibly because of increased use of food allergy V codes. CONCLUSION: Several national health surveys indicate that food allergy prevalence and/or awareness has increased among US children in recent years.

Radiation Exposure in 212 Very Low and Extremely Low Birth Weight Infants

OBJECTIVE: We determined the frequency and estimated effective radiation dose (E) from conventional diagnostic radiographs for infants who had birth weight of ≤1500 g (very low birth weight [VLBW] infants) and were treated in a NICU. METHODS: Entrance skin doses were experimentally measured for all standard weight-dependent exposure settings. For each radiograph in the radiologic file, the exposed area on the film was measured manually. Together with clinical data obtained from the Vermont Oxford Network, medical charts, and radiologic files, we estimated E. E values per radiograph and per child were compared with recommended reference values and annual natural background radiation (NBR). We used reference data to estimate the risk for radiation-induced cancers. RESULTS: Of 212 VLBW infants, 194 required at least 1 conventional radiograph. Measured entrance skin dose varied between 11.8 and 15.0 µGy. Calculated E received was 16 microsievert (µSv; median) per radiograph and 71.5 µSv (median) per infant for the whole stay. Infants with birth weight ≤750 g, length of stay ≥16 weeks, congenital malformations, or oxygen dependence for ≥36 weeks were at risk for high numbers of radiographs and high radiation dose. Compared with the annual NBR, the median of 4 radiographs per infant contributes 12 days of NBR. We estimated that only 1 of 60000 NICU-treated VLBW infants will develop a fatal malignancy up to 15 years of age. CONCLUSIONS: We found that NICU-treated VLBW infants had low radiation exposure compared with the annual NBR.

Prevalence of Down Syndrome Among Children and Adolescents in 10 Regions of the United States

OBJECTIVE: We aimed to estimate the prevalence of Down syndrome (DS) among children and adolescents aged 0 to 19 years in 10 regions of the United States. METHODS: This study was a cross-sectional analysis of live-born infants with DS during 1979–2003 from 10 population-based birth defects registries in the United States. We estimated the prevalence of DS at birth and among children aged 0 to 19 years in each region and in all regions pooled. The prevalence of DS among children and adolescents was calculated overall and according to age group, race/ethnicity, infant gender, and presence of a major heart defect. RESULTS: From 1979 through 2003, the prevalence of DS at birth increased by 31.1%, from 9.0 to 11.8 per 10000 live births in 10 US regions. In 2002, the prevalence among children and adolescents (0–19 years old) was 10.3 per 10000. The prevalence of DS among children in a given age group consistently increased over time but decreased with age within a given birth cohort. The pooled prevalence of DS among children and adolescents was lower among non-Hispanic black individuals and other racial/ethnic groups compared with non-Hispanic white individuals; it was also lower among females than males. CONCLUSIONS: This study provides prevalence estimates of DS among children and adolescents from 10 US regions. These estimates varied according to region, race/ethnicity, and gender, suggesting possible variation in prevalence at birth or in survival rates on the basis of these characteristics.

The Changing Face of Childhood Celiac Disease in North America: Impact of Serological Testing

OBJECTIVE: The goal was to evaluate the impact of immunoglobulin A endomysial antibody testing on the incidence and clinical presentation of childhood celiac disease. METHODS: The incidence and clinical presentation of celiac disease in patients <18 years of age in 1990–1996 (pretesting group) versus 2000–2006 (testing group) were compared. RESULTS: The median age at diagnosis was 2 years (95% confidence interval: 2–4 years) in the pretesting group (N = 36), compared with 9 years (95% confidence interval: 8–10 years) in the testing group (N = 199; P < .001); the female/male ratios (1.6:1) were similar (P = .982). The incidence of celiac disease increased from 2.0 cases per 100000 children (pretesting group) to 7.3 cases per 100000 children (testing group; P = .0256). The frequency of classic celiac disease presentations decreased from 67% (pretesting group) to 19% (testing group; P < .001), but the incidence of classic celiac disease did not differ (0.8 vs 1.6 cases per 100000; P = .154). In the testing group, 13 previously unrecognized clinical presentations were observed in 98 children, including 35 with family history, 18 with abdominal pain, and 14 with type 1 diabetes mellitus. The frequency of Marsh IIIc lesions decreased from 64% (pretesting group) to 44% (testing group; P = .0403). In the testing group, classic celiac disease remained predominant (67%) in young children (<3 years), whereas atypical gastrointestinal and silent presentations predominated in older children. CONCLUSIONS: Antibody testing for celiac disease tripled the incidence of celiac disease and quadrupled the median age at diagnosis.

Spatial Accessibility to Providers and Vaccination Compliance Among Children With Medicaid

OBJECTIVE: We examined the relationship between spatial accessibility to pediatric immunization providers and vaccination compliance in a low-income, urban population of children. METHODS: In 2007, we accessed the Washington, DC, Immunization Information System (IIS) to collect data on the immunization statuses and residential addresses of children who were aged 19 to 35 months and had Medicaid insurance. In addition, we calculated each child's spatial accessibility to pediatric vaccination providers by assessing the provider-to-population ratio at each residential address. Spatial accessibility was divided into tertiles (low, medium, and high) of access. The relationship between spatial accessibility to providers and vaccination compliance was examined by using logistic regression analysis adjusting for age, type of vaccination provider, and enrollment in child care status. RESULTS: Overall for our cohort of 4195 children, 80.5% of the children were up-to-date with vaccinations. Vaccination coverage ranged from 61.6% to 100% (median: 79.2%) among different neighborhoods. Having the highest level of access to pediatric vaccination providers was associated with 36% higher odds of being up-to-date as compared with having the lowest level of access. The middle tertile of access was associated with 25% higher odds of being up-to-date. CONCLUSIONS: Within our low-income, urban population, children with higher spatial accessibility to pediatric vaccination providers were more likely to be up-to-date with vaccinations. This association may guide future studies and efforts to ensure adequate immunization coverage for children regardless of where they live.

Nonaccidental Head Injury Is the Most Common Cause of Subdural Bleeding in Infants <1 Year of Age

OBJECTIVE: Subdural bleeding (SDB) in infants is considered an essential symptom of nonaccidental head injury (NAHI). Recently, this view has been challenged by the "unified hypothesis," which claims that SDB in infants is related to hypoxia and brain swelling rather than to traumatic shearing of bridging veins. We analyzed a large series of infants' autopsies for the presence and causes of SDB, which should be a common event according to the unified hypothesis. METHODS: Autopsy, clinical, and legal information for infants <1 year of age from a single institution over 50 years were analyzed regarding cause of death, presence, morphology, and cause of SDB, and brain weight. RESULTS: From a total of 16 661 autopsies during the study period, 715 (4.3%) involved infants <1 year of age. Fifty (7.0%) of those had SDB. NAHI was identified in 17 patients. The most common cause of SDB was trauma (15 cases [30.0%]), with NAHI accounting for 14 cases. SDB was present in 82.4% of patients with NAHI but only 5.2% of infants with other causes of death. Four patients (8.0%) had unexplained SDB with no discernible cause of bleeding. Statistical analysis did not reveal any correlation between the presence of SDB and brain weight. CONCLUSIONS: In the study population, unexplained SDB in infants was an extreme rarity. Moreover, a correlation between brain swelling and the presence of SDB could not be drawn. Our data argue strongly against the unified hypothesis and strengthen the association between SDB and NAHI in infancy.

Screening for Occult Abdominal Trauma in Children With Suspected Physical Abuse

OBJECTIVES: The goals were (1) to determine the prevalence of occult abdominal trauma (OAT) in a sample of children with suspected physical abuse, (2) to assess the frequency of OAT screening, and (3) to assess factors associated with screening. METHODS: Charts of children evaluated for abusive injury were identified through a search of hospital discharge codes. Identified charts were reviewed to determine whether OAT screening occurred. Data on results of screening tests, abusive injuries identified, family demographic features, and characteristics of the emergency department visit were collected. RESULTS: Screening occurred for 51 (20%) of 244 eligible children. Positive results were identified for 41% of those screened and 9% of the total sample; 5% of children 12 to 23 months of age had OAT identified through imaging studies. Screening occurred more often in children presenting with probable abusive head trauma (odds ratio [OR]: 20.4 [95% confidence interval [CI]: 3.6–114.6]; P < .01), compared with those presenting with other injuries. Consultation with the child protection team (OR: 8.5 [95% CI: 3.5–20.7]; P < .01) and other subspecialists (OR: 24.3 [95% CI: 7.1–83.3]; P < .01) also increased the likelihood that OAT screening would occur. CONCLUSIONS: Our findings support OAT screening with liver and pancreatic enzyme measurements for physically abused children. This study also supports the importance of subspecialty input, especially that of a child protection team. Although many identified injuries may not require treatment, their role in confirming or demonstrating increased severity of maltreatment may be critical.

Association of Maternal Smoking Status With Breastfeeding Practices: Missouri, 2005

OBJECTIVE: We sought to determine the association of smoking status as a risk factor for reduced initiation and duration of breastfeeding. METHODS: The Missouri Pregnancy Related Assessment and Monitoring System collected a stratified sample of new mothers in 2005. Surveys were mailed, with telephone follow-up, and completed within 2 to 12 months after delivery. Respondents were classified as nonsmokers, smokers who quit during pregnancy, light smokers (≤10 cigarettes per day), or moderate/heavy smokers (>10 cigarettes per day). Multivariable binomial regression and Cox proportional hazards models were used to assess breastfeeding initiation and duration according to smoking status. RESULTS: Overall, 1789 women participated (weighted response rate: 61%). Approximately 74% of the women ever breastfed; 31% of the women ever smoked while pregnant. Compared with nonsmokers, the moderate/heavy smokers and light smokers were less likely to initiate breastfeeding, after controlling for sociodemographic characteristics, the presence of other smokers in the household, alcohol use, mode of delivery, and infant hospitalization. Compared with nonsmokers, the moderate/heavy smokers, light smokers, and smokers who quit during pregnancy were more likely to wean over time, controlling for the same covariates. There were no significant differences between nonsmokers and smokers regarding reasons for not initiating or ceasing breastfeeding. CONCLUSIONS: Mothers who smoked initiated breastfeeding less often and weaned earlier than nonsmoking mothers. Incorporating knowledge of the association between smoking and breastfeeding into existing smoking-cessation and breastfeeding programs could provide opportunities to reduce perinatal exposure to tobacco smoke, improve interest in breastfeeding, and address other barriers to breastfeeding that smoking mothers may face.

Depressive Symptoms in Nonresident African American Fathers and Involvement With Their Sons

OBJECTIVE: Our objective was to determine whether paternal depressive symptoms were associated with less father involvement among African American fathers not living with their children (ie, nonresident fathers). METHODS: We analyzed survey data for 345 fathers enrolled in a program for nonresident African American fathers and their preteen sons. Father involvement included measures of contact, closeness, monitoring, communication, and conflict. We used bivariate analyses and multivariate logistic regression analysis to examine associations between father involvement and depressive symptoms. RESULTS: Thirty-six percent of fathers reported moderate depressive symptoms, and 11% reported severe depressive symptoms. In bivariate analyses, depressive symptoms were associated with less contact, less closeness, low monitoring, and increased conflict. In multivariate analyses controlling for basic demographic features, fathers with moderate depressive symptoms were more likely to have less contact (adjusted odds ratio: 1.7 [95% confidence interval: 1.1–2.8]), less closeness (adjusted odds ratio: 2.1 [95% confidence interval: 1.3–3.5]), low monitoring (adjusted odds ratio: 2.7 [95% confidence interval: 1.4–5.2]), and high conflict (adjusted odds ratio: 2.1 [95% confidence interval: 1.2–3.6]). Fathers with severe depressive symptoms also were more likely to have less contact (adjusted odds ratio: 3.1 [95% confidence interval: 1.4–7.2]), less closeness (adjusted odds ratio: 2.6 [95% confidence interval: 1.2–5.7]), low monitoring (adjusted odds ratio: 2.8 [95% confidence interval: 1.1–7.1]), and high conflict (adjusted odds ratio: 2.6 [95% confidence interval: 1.1–5.9]). CONCLUSION: Paternal depressive symptoms may be an important, but modifiable, barrier for nonresident African American fathers willing to be more involved with their children.

Outcome of Term Infants Using Apgar Scores at 10 Minutes Following Hypoxic-Ischemic Encephalopathy

OBJECTIVE: The objective of this study was to determine whether Apgar scores at 10 minutes are associated with death or disability in early childhood after perinatal hypoxic-ischemic encephalopathy. METHODS: This was a secondary analysis of infants who were enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network hypothermia trial. Infants who were born at ≥36 weeks’ gestation and had clinical and/or biochemical abnormalities at birth and encephalopathy at <6 hours were studied. Logistic regression and classification and regression-tree analysis were used to determine associations between Apgar scores at 10 minutes and neurodevelopmental outcome, adjusting for covariates. Death or disability (moderate or severe) at 18 to 22 months of age was the measured outcome. RESULTS: Twenty of 208 infants were excluded (missing data). More than 90% of the infants had Apgar scores of 0 to 2 at 1 minute, and Apgar scores at 5 and 10 minutes shifted to progressively higher values; at 10 minutes, 27% of infants had Apgar scores of 0 to 2. After adjustment, each point decrease in Apgar score at 10 minutes was associated with a 45% increase in the odds of death or disability. Death or disability occurred in 76%, 82%, and 80% of infants with 10-minute Apgar scores of 0, 1, and 2, respectively. Classification and regression-tree analysis indicated that Apgar scores at 10 minutes were discriminators of outcome. CONCLUSIONS: Apgar scores at 10 minutes provide useful prognostic data before other evaluations are available for infants with hypoxic-ischemic encephalopathy. Death or moderate/severe disability is common but not uniform with Apgar scores of <3; caution is needed before adopting a specific time interval to guide duration of resuscitation.

Preschool-Aged Children's Television Viewing in Child Care Settings

OBJECTIVE: The goal was to quantify television viewing in day care settings and to investigate the characteristics of programs that predict viewing. METHODS: A telephone survey of licensed child care programs in Michigan, Washington, Florida, and Massachusetts was performed. The frequency and quantity of television viewing for infants, toddlers, and preschool-aged children were assessed. RESULTS: With the exception of infants, children in home-based child care programs were exposed to significantly more television on an average day than were children in center-based programs (infants: 0.2 vs 0 hours; toddlers: 1.6 vs 0.1 hours; preschool-aged children: 2.4 vs 0.4 hours). In a regression analysis of daily television time for preschool-aged children in child care, center-based programs were found to have an average of 1.84 fewer hours of television each day, controlling for the other covariates. Significant effect modification was found, in that the impact of home-based versus center-based child care programs differed somewhat depending on educational levels for staff members; having a 2- or 4-year college degree was associated with 1.41 fewer hours of television per day in home-based programs, but no impact of staff education on television use was observed in center-based programs. CONCLUSIONS: For many children, previous estimates of screen time significantly underestimated actual amounts. Pediatricians should council parents to minimize screen time in child care settings.

Booster Vaccinations: Can Immunologic Memory Outpace Disease Pathogenesis?

Almost all current vaccines work by the induction of antibodies in serum or on the mucosa to block adherence of pathogens to epithelial cells or interfere with microbial invasion of the bloodstream. However, antibody levels usually decline after vaccination to undetectable amounts if further vaccination does not occur. Persistence of vaccine-induced antibodies usually goes well beyond the time when they should have decayed to undetectable levels because of ongoing "natural" boosting or other immunologic mechanisms. The production of memory B and T cells is of clear importance, but the likelihood that a memory response will be fast enough in the absence of a protective circulating antibody level likely depends on the pace of pathogenesis of a specific organism. This concept is discussed with regard to Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis; hepatitis A and B; diphtheria, tetanus, and pertussis; polio, measles, mumps, rubella, and varicella; rotavirus; and human papilloma virus. With infectious diseases for which the pace of pathogenesis is less rapid, some individuals will contract infection before the memory response is fully activated and implemented. With infectious diseases for which the pace of pathogenesis is slow, immune memory should be sufficient to prevent disease.

Pediatric Robotic Surgery: Early Assessment

OBJECTIVES: This article reviews the evidence regarding the feasibility, safety, benefits, limitations, and costs of robotically assisted surgery in children, evaluates how the technology compares with other pediatric surgical techniques, and provides insights about the near and more-distant future of the technology. METHODS: The peer-reviewed medical pediatric literature was searched for studies that provided evidence of the feasibility and safety of robotic surgery in children and for studies that compared pediatric robotic surgery with conventional laparoscopic surgery or open surgery. RESULTS: A total of 8 case series and 5 studies comparing robotic surgery with open or conventional laparoscopic surgery met the selection criteria for review. A few small studies that focused on rare complex surgical procedures also were reviewed. All studies were designed to evaluate the feasibility and safety of robotic surgery in children. None of the studies was randomized, and some studies had a retrospective design. These studies demonstrated that a number of routine, robotically assisted, laparoscopic and thoracic procedures were feasible and safe when performed by surgeons experienced in the technique, although robotic surgery did not provide superior outcomes, compared with traditional laparoscopic and open surgery. The advantages of the robotic system were best seen in complex procedures that involved areas that were difficult to access and in procedures in which dissection of delicate, anatomic structures was required. CONCLUSIONS: Robotic surgery is feasible and safe for a number of pediatric surgical procedures, but evidence that it offers better clinical outcomes than conventional open or laparoscopic techniques is lacking.

Best-Practice Guidelines for Physical Activity at Child Care

Research has indicated that the child care center is a very strong predictor of preschool-aged children's physical activity levels, making this an important setting to help young children obtain physical activity that is appropriate for their health and development. However, some evidence suggests that organized child care may not adequately support children's physical activity needs. Although many organizations provide recommendations, guidelines, or standards for motor skill development and physical activity opportunities, no set of guidelines exist that directly target the overall physical activity environment at child care. Because of the lack of comprehensive recommendations, the Nutrition and Physical Activity Self-assessment for Child Care best-practice guidelines for healthy weight development were created on the basis of an extensive review of existing guidelines, research evidence, and expert review. The purpose of this article is to present these physical activity best-practice guidelines and provide data on how these guidelines compare to current practice in a large sample (N = 96) of child care centers in North Carolina. These best-practice guidelines include recommendations for 8 unique components of the child care environment, including active opportunities, fixed play environment, portable play environment, sedentary opportunities, sedentary environment, staff behavior, staff training/education, and physical activity policies. Our results showed that only a few of the best-practice guidelines were achieved by a majority of the 96 North Carolina child care centers that participated in this study. Establishing comprehensive guidelines for physical activity at child care could result in higher activity levels and healthier children, but more research is needed.

Promoting Early Literacy in Pediatric Practice: Twenty Years of Reach Out and Read

Reach Out and Read (ROR) is the first pediatric, evidence-based strategy to prevent problems of early childhood development and learning. With a start in a single clinic in Boston City Hospital in 1989, doctors working in >4000 clinics and practices gave ~5.7 million new books to >3.5 million children in all 50 states in 2008. ROR also has become a model for a different way of thinking about parent education during primary care encounters, based less on telling and more on creating real-time learning experiences. ROR flourished because of (1) the growth of pediatric interest in child development, (2) local leadership of pediatric champions as well as nonmedical supporters, coordinators, and volunteers, (3) evidence of effectiveness, and (4) public financial support attributable to strong bipartisan support in Congress, led by Senator Edward Kennedy. Since ROR started, an increasing amount of research confirms the importance of reading aloud for the development of language and other emergent literacy skills, which in turn helps children get ready for school and leads to later success in reading. Future goals include continued growth until all low-income children are reached with pediatric advice and books, a national campaign led by physicians encouraging all parents to read to their children every day, additional evidence-based, parent information to increase the effectiveness of parents reading to children, quality-improvement efforts to achieve the full potential, and global expansion.

The Role of Immunoprophylaxis in the Reduction of Disease Attributable to Respiratory Syncytial Virus

Pediatric Robotic-Assisted Surgery: Too Early an Assessment?

The 2009 COID Recommendations for RSV Prophylaxis: Issues of Efficacy, Cost, and Evidence-Based Medicine

Pediatrician-Family-Patient Relationships: Managing the Boundaries

All professionals are concerned about maintaining the appropriate limits in their relationships with those they serve. Pediatricians should be aware that, under normal circumstances, caring for one's own children presents significant ethical issues. Pediatricians also must strive to maintain appropriate professional boundaries in their relationships with the family members of their patients. Pediatricians should avoid behavior that patients and parents might misunderstand as having sexual or inappropriate social meaning. Romantic and sexual involvement between physicians and patients is unacceptable. The acceptance of gifts or nonmonetary compensation for medical services has the potential to affect the professional relationship adversely.

Physician Refusal to Provide Information or Treatment on the Basis of Claims of Conscience

Health care professionals may have moral objections to particular medical interventions. They may refuse to provide or cooperate in the provision of these interventions. Such objections are referred to as conscientious objections. Although it may be difficult to characterize or validate claims of conscience, respecting the individual physician's moral integrity is important. Conflicts arise when claims of conscience impede a patient's access to medical information or care. A physician's conscientious objection to certain interventions or treatments may be constrained in some situations. Physicians have a duty to disclose to prospective patients treatments they refuse to perform. As part of informed consent, physicians also have a duty to inform their patients of all relevant and legally available treatment options, including options to which they object. They have a moral obligation to refer patients to other health care professionals who are willing to provide those services when failing to do so would cause harm to the patient, and they have a duty to treat patients in emergencies when referral would significantly increase the probability of mortality or serious morbidity. Conversely, the health care system should make reasonable accommodations for physicians with conscientious objections.

Modified Recommendations for Use of Palivizumab for Prevention of Respiratory Syncytial Virus Infections

Palivizumab was licensed in June 1998 by the US Food and Drug Administration for prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients who are at increased risk of severe disease. Safety and efficacy have been established for infants born at or before 35 weeks' gestation with or without chronic lung disease of prematurity and for infants and children with hemodynamically significant heart disease. The American Academy of Pediatrics (AAP) published a policy statement on the use of palivizumab in November 1998 (American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics. 1998;102[5]:1211–1216) and revised it in December 2003 (American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics. 2003;112[6 pt 1]:1442–1446), and an AAP technical report on palivizumab was published in 2003 (Meissner HC, Long SS; American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics. 2003;112[6 pt 1]:1447–1452). On the basis of the availability of additional data regarding seasonality of RSV disease as well as the limitations in available data on risk factors for identifying children who are at increased risk of serious RSV lower respiratory tract disease, AAP recommendations for immunoprophylaxis have been updated in an effort to ensure optimal balance of benefit and cost from this expensive intervention. This statement updates and replaces the 2003 AAP statement and the 2006 Red Book and is consistent with the 2009 Red Book recommendations.

Supplemental Security Income (SSI) for Children and Youth With Disabilities

The Supplemental Security Income (SSI) program remains an important source of financial support for low-income families of children with special health care needs and disabling conditions. In most states, SSI eligibility also qualifies children for the state Medicaid program, providing access to health care services. The Social Security Administration (SSA), which administers the SSI program, considers a child disabled under SSI if there is a medically determinable physical or mental impairment or combination of impairments that results in marked and severe functional limitations. The impairment(s) must be expected to result in death or have lasted or be expected to last for a continuous period of at least 12 months. The income and assets of families of children with disabilities are also considered when determining financial eligibility. When an individual with a disability becomes an adult at 18 years of age, the SSA considers only the individual's income and assets. The SSA considers an adult to be disabled if there is a medically determinable impairment (or combination of impairments) that prevents substantial gainful activity for at least 12 continuous months. SSI benefits are important for youth with chronic conditions who are transitioning to adulthood. The purpose of this statement is to provide updated information about the SSI medical and financial eligibility criteria and the disability-determination process. This statement also discusses how pediatricians can help children and youth when they apply for SSI benefits.

ERRATUM

HIGH-RISK NEUROBLASTOMA: A Therapy in Evolution

ROLE OF CASPASE 8 AS A DETERMINANT IN TRAIL SENSITIVITY OF NEUROBLASTOMA CELL LINES

HYDROXYUREA-INDUCED HEMATOLOGICAL RESPONSE IN TRANSFUSION-INDEPENDENT BETA-THALASSEMIA INTERMEDIA: Case Series and Review of Literature

PERSISTENT ANTIBODY DEPLETION AFTER RITUXIMAB IN THREE CHILDREN WITH AUTOIMMUNE CYTOPENIAS

ASSOCIATION BETWEEN DEFB1 GENE HAPLOTYPE AND HERPES VIRUSES SEROPREVALENCE IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

HEPATOBLASTOMA METASTATIC TO THE RIGHT ATRIUM RESPONDING TO CHEMOTHERAPY ALONE

PERIPHERAL ARTERIAL TONOMETRY IN ASSESSING ENDOTHELIAL DYSFUNCTION IN PEDIATRIC SICKLE CELL DISEASE

SEVERE PURPURA FULMINANS DUE TO COEXISTENCE OF HOMOZYGOUS PROTEIN C DEFICIENCY AND HOMOZYGOUS METHYLENETETRAHYDROFOLATE REDUCTASE MUTATION

CLINICAL PROFILE AND HOME MANAGEMENT OF SICKLE CELL-RELATED PAIN: The Enugu (Nigeria) Experience

THE BENEFIT OF ATG IN IMMUNOSUPPRESSIVE THERAPY OF CHILDREN WITH MODERATE APLASTIC ANEMIA

RHABDOMYOSARCOMA OF THE EXTREMITIES: A Focus on Tumors Arising in the Hand and Foot

INCIDENCE OF PRIMARY CENTRAL NERVOUS SYSTEM TUMORS AMONG CHILDREN IN BELGRADE (SERBIA), 1991-2004

PANEL REACTIVE ANTIBODY IN THALASSEMIC SERUM INHIBITS PROLIFERATION AND DIFFERENTIATION OF CORD BLOOD CD34 + CELLS IN VITRO

ALLOGENEIC STEM CELL TRANSPLANTATION FOR MYELODYSPLASTIC SYNDROMES IN CHILDREN: A Report from the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON)

SEVERE HYPOCHROMIC MICROCYTIC ANEMIA IN A PATIENT WITH CONGENITAL ATRANSFERRINEMIA

EFFECT OF SOMATOSTATIN ANALOGUE OCTREOTIDE IN MEDULLOBLASTOMA IN XENOGRAFT AND CELL CULTURE STUDY

SUCCESSFUL TREATMENT OF KASABACH-MERRITT SYNDROME WITH VINCRISTINE AND DIAGNOSIS OF THE HEMANGIOMA USING THREE-DIMENSIONAL IMAGING

A NOVEL L218P MUTATION IN NADH-CYTOCHROME B5 REDUCTASE ASSOCIATED WITH TYPE I RECESSIVE CONGENITAL METHEMOGLOBINEMIA

PLASMA HEPARANASE AS A SIGNIFICANT MARKER OF TREATMENT RESPONSE IN CHILDREN WITH HODGKIN LYMPHOMA: Pilot Study

ALLOGENEIC CORD BLOOD TRANSPLANTATION IN CHILDREN WITH HEMATOLOGICAL MALIGNANCIES: A Long-Term Follow-Up Single-Center Study

EXTRA-OSSEOUS EWING SARCOMA

BONE MARROW TRANSPLANTATION OR HYDROXYUREA FOR SICKLE CELL ANEMIA: Long-Term Effects on Semen Variables and Hormone Profiles

ANTIBODY TITRATION AND IMMUNE RESPONSE OF IRANIAN β-THALASSEMIC PATIENTS TO HEPATITIS B VIRUSE VACCINE (BOOSTER EFFECT)

GROWTH STATUS IN CHILDREN AND ADOLESCENTS WITH SICKLE CELL DISEASE

CD10 AND CD34 EXPRESSION IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA IN MOROCCO: Clinical Relevance and Outcome

HEPATITIS G VIRUS INFECTION IN MULTITRANSFUSED EGYPTIAN CHILDREN

TRENDS IN SURVIVAL AFTER CHILDHOOD CANCER IN SLOVENIA BETWEEN 1957 AND 2007

SPERM CRYOPRESERVATION PRACTICES AMONG ADOLESCENT CANCER PATIENTS AT RISK FOR INFERTILITY

SPONTANEOUS THROMBOSIS OF HEPATIC ANEURYSMS IN AN INFANT WITH WISKOTT-ALDRICH SYNDROME

MULTIPLE CHROMOSOME ABNORMALITIES IN THE PLEURAL FLUID OF A PATIENT WITH RECURRENT EWING SARCOMA

THROMBOLYTICS FOR HYPERACUTE STROKE IN CHILDREN

HEMORHEOLOGICAL PARAMETERS IN CHILDREN WITH IRON-DEFICIENCY ANEMIA AND THE ALTERATIONS IN THESE PARAMETERS IN RESPONSE TO IRON REPLACEMENT

HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION IN CHILD HEMATOLOGIC MALIGNANCIES WITH G-CSF-MOBILIZED MARROW GRAFTS WITHOUT T-CELL DEPLETION: A Single-Center Report of 45 Cases

HYPEREOSINOPHILIC SYNDROME IN CHILDHOOD: Clinical and Molecular Features of Two Cases

THE CASE OF A 1-YEAR-OLD GIRL WITH HEREDITARY HYPERFERRITINEMIA CATARACT SYNDROME

ANAPLASTIC LARGE CELL LYMPHOMA WITH PRIMARY INVOLVEMENT OF SKELETAL MUSCLE: A Rare Case Report and Review of the Literature

POLAND SYNDROME WITH INTRACRANIAL GERM CELL TUMOR IN A CHILD

RHABDOMYOLYSIS DUE TO Escherichia coli SEPSIS IN THREE PEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

PARVOVIRUS B19-INDUCED PERSISTENT PURE RED CELL APLASIA IN A CHILD WITH T-CELL IMMUNODEFICIENCY

ALTERED IRON METABOLISM IN CHILDREN WITH HUMAN IMMUNODEFICIENCY VIRUS DISEASE

ACUTE LYMPHOBLASTIC LEUKEMIA SECONDARY TO CHEMORADIOTHERAPY FOR PERIVASCULAR EPITHELIOID CELL TUMOR OF UTERUS

CHOOSING THERAPY FOR ADOLESCENT FEMALES WITH CANCER: Fertility Should Matter

RELAPSE OF PRIMITIVE MEDIASTINAL LYMPHOMA AS A MYELOID MASS FOLLOWING BEAM AUTOLOGOUS TRANSPLANT AND SUBSEQUENT REFRACTORINESS TO MATCHED UNRELATED UMBILICAL CORD BLOOD ALLOGRAFT

TRANSFORMATION OF MYELODYSPLASTIC SYNDROME TO T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA IN A YOUNG ADULT

UNDULANT COURSE OF AFP: A Sign of Tumor Activation or Not?

EXPRESSION OF PTEN AND SHP1, INVESTIGATED FROM TISSUE MICROARRAYS IN PEDIATRIC ACUTE LYMPHOBLASTIC, LEUKEMIA

BONE FRACTURE: An Unusual Presentation of Acute Megakaryoblastic Leukemia

CERVICAL LYMPHADENOPATHY IN CHILDHOOD EPIDEMIOLOGY AND MANAGEMENT

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