·  Abstract 1 of 68Pediatrics Digest

·  Abstract 2 of 68Pediatrics Perspective

·  Abstract 3 of 68Article

Six Developmental Trajectories Characterize Children With Autism

OBJECTIVE: The goal of this study was to describe the typical longitudinal developmental trajectories of social and communication functioning in children with autism and to determine the correlates of these trajectories.

METHODS: Children with autism who were born in California from 1992 through 2001 and enrolled with the California Department of Developmental Services were identified. Subjects with <4 evaluations present in the database were excluded, resulting in a sample of 6975 children aged 2 to 14 years. Score sequences were constructed based on 9 evaluative items for social, communication, and repetitive behavior functioning. Typical trajectories were identified by using group-based latent trajectory modeling, and multinomial logistic regression models were used to determine the odds of classification within each trajectory varied by individual and family-level factors.

RESULTS: Six typical patterns of social, communication, and repetitive behavior functioning were identified. These trajectories displayed significant heterogeneity in developmental pathways, and children whose symptoms were least severe at first diagnosis tended to improve more rapidly than those severely affected. One group of ∼10% of children experienced rapid gains, moving from severely affected to high functioning. Socioeconomic factors were correlated with trajectory outcomes; children with non-Hispanic, white, well-educated mothers were more likely to be high functioning, and minority children with less-educated mothers or intellectual disabilities were very unlikely to experience rapid gains.

CONCLUSIONS: Children with autism have heterogeneous developmental pathways. One group of children evidenced remarkable developmental change over time. Understanding what drives these outcomes is thus critical.

KEY WORDS

• autistic disorder
• longitudinal outcomes
• trajectory models

• Accepted January 4, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 4 of 68Article

Maternal Metabolic Conditions and Risk for Autism and Other Neurodevelopmental Disorders

OBJECTIVE: We examined whether metabolic conditions (MCs) during pregnancy (diabetes, hypertension, and obesity) are associated with autism spectrum disorder (ASD), developmental delays (DD), or impairments in specific domains of development in the offspring.

METHODS: Children aged 2 to 5 years (517 ASD, 172 DD, and 315 controls) were enrolled in the CHARGE (Childhood Autism Risks from Genetics and the Environment) study, a population-based, case-control investigation between January 2003 and June 2010. Eligible children were born in California, had parents who spoke English or Spanish, and were living with a biological parent in selected regions of California. Children’s diagnoses were confirmed by using standardized assessments. Information regarding maternal conditions was ascertained from medical records or structured interview with the mother.

RESULTS: All MCs were more prevalent among case mothers compared with controls. Collectively, these conditions were associated with a higher likelihood of ASD and DD relative to controls (odds ratio: 1.61 [95% confidence interval: 1.10–2.37; odds ratio: 2.35 [95% confidence interval: 1.43–3.88], respectively). Among ASD cases, children of women with diabetes had Mullen Scales of Early Learning (MSEL) expressive language scores 0.4 SD lower than children of mothers without MCs (P < .01). Among children without ASD, those exposed to any MC scored lower on all MSEL and Vineland Adaptive Behavior Scales (VABS) subscales and composites by at least 0.4 SD (P < .01 for each subscale/composite).

CONCLUSIONS: Maternal MCs may be broadly associated with neurodevelopmental problems in children. With obesity rising steadily, these results appear to raise serious public health concerns.

KEY WORDS

• autism
• developmental delay
• diabetes
• epidemiology
• hypertension
• obesity

• Accepted December 19, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 5 of 68Article

Level of NICU Quality of Developmental Care and Neurobehavioral Performance in Very Preterm Infants

OBJECTIVE: To examine the relation between the neurobehavior of very preterm infants and the level of NICU quality of developmental care.

METHODS: The neurobehavior of 178 very preterm infants (gestational age ≤29 weeks and/or birth weight ≤1500 g) from 25 NICUs participating in a large multicenter, longitudinal study (Neonatal Adequate Care for Quality of Life, NEO-ACQUA) was examined with a standardized neurobehavioral assessment, the NICU Network Neurobehavioral Scale (NNNS). A questionnaire, the NEO-ACQUA Quality of Care Checklist was used to evaluate the level of developmental care in each of the NICUs. A factor analyses applied to NEO-ACQUA Quality of Care Checklist produced 2 main factors: (1) the infant-centered care (ICC) index, which measures parents’ involvement in the care of their infant and other developmentally oriented care interventions, and (2) the infant pain management (IPM) index, which measures the NICU approach to and the procedures used for reducing infant pain. The relations between NNNS neurobehavioral scores and the 2 indexes were evaluated.

RESULTS: Infants from NICUs with high scores on the ICC evidenced higher attention and regulation, less excitability and hypotonicity, and lower stress/abstinence NNNS scores than infants from low-care units. Infants from NICUs with high scores on the IPM evidenced higher attention and arousal, lower lethargy and nonoptimal reflexes NNNS scores than preterm infants from low-scoring NICUs.

CONCLUSIONS: Very preterm infant neurobehavior was associated with higher levels of developmental care both in ICC and in IPM, suggesting that these practices support better neurobehavioral stability.

KEY WORDS

• preterm infant
• very low birth weight
• developmental care
• pain management
• neurobehavioral examination
• NNNS

• Accepted January 5, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 6 of 68Article

Qualitative Brain MRI at Term and Cognitive Outcomes at 9 Years After Very Preterm Birth

OBJECTIVE: A prospective study was performed to assess the relationship between the appearance of cerebral MRI at term and the cognitive functioning at 9 years old in very preterm born infants.

METHODS: Seventy-six very preterm born infants (birth weight <1500 g or gestational age ≤32 weeks) obtained cerebral MRI at term-equivalent period, which was assessed by using established composite scores for the white and gray matter; cognitive outcomes at 9 years old were assessed in 60 subjects by using Wechsler Intelligence Scale for Children, Third Edition.

RESULTS: Mildly low scores on the different IQ indices (<85) were observed in 23.3% (verbal IQ), 41.7% (performance IQ), and 30.0% (full-scale IQ) of the cohort, whereas moderately low scores (<70) were noted in 3.3% (verbal IQ), 11.7% (performance IQ), and 11.7% (full-scale IQ); cerebral palsy was diagnosed in 10.0%, whereas special assistance at school was required in 56.7%. Abnormal white matter appearances predicted mildly low verbal, performance, and full-scale IQs; moderately low performance and full-scale IQs; cerebral palsy; and the requirement for special assistance at school. Abnormal white matter appearances predicted mild cognitive impairment even after the adjustment for known clinical risk factors. In contrast, abnormal gray matter appearances did not predict any of the outcome measures.

CONCLUSIONS: In a cohort of very preterm born infants, abnormal white matter appearance on term MRI showed consistent associations with cognitive impairments at 9 years old, further supporting the benefit of obtaining term MRI for very preterm born infants.

KEY WORDS

• preterm infants
• MRI
• cognitive impairments
• white matter injury
• gray matter injury

• Accepted January 5, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 7 of 68Article

Complementary and Alternative Medicine Use and Adherence With Pediatric Asthma Treatment

BACKGROUND AND OBJECTIVE: Complementary and alternative medicine (CAM) use for pediatric asthma is increasing. The authors of previous studies linked CAM use with decreased adherence to conventional asthma medicines; however, these studies were limited by cross-sectional design. Our objective was to assess the effect of starting CAM on pediatric adherence with daily asthma medications.

METHODS: We used a retrospective cohort study design. Telephone surveys were administered to caregivers of patients with asthma annually from 2004 to 2007. Dependent variables were percent missed doses per week and a previously validated “Medication Adherence Scale score.” Independent variables included demographic factors, caregiver perception of asthma control, and initiation of CAM for asthma. We used multivariate linear regression to assess the relationship between medication adherence and previous initiation of CAM.

RESULTS: From our longitudinal data set of 1322 patients, we focused on 187 children prescribed daily medications for all 3 years of our study. Patients had high rates of adherence. The mean percent missed asthma daily controller medication doses per week was 7.7% (SD = 14.2%). Medication Adherence Scale scores (range: 4–20, with lower scores reflecting higher adherence) had an overall mean of 7.5 (SD = 2.9). In multivariate analyses, controlling for demographic factors and asthma severity, initiation of CAM use was not associated with subsequent adherence (P > .05).

CONCLUSIONS: The data from this study suggest that CAM use is not necessarily “competitive” with conventional asthma therapies; families may incorporate different health belief systems simultaneously in their asthma management. As CAM use becomes more prevalent, it is important for physicians to ask about CAM use in a nonjudgmental fashion.

KEY WORDS

• alternative medicine
• adherence
• asthma

• Accepted December 22, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 8 of 68Article

Randomized Trial of Probiotics and Calcium on Diarrhea and Respiratory Tract Infections in Indonesian Children

OBJECTIVE: To investigate the effects of calcium and probiotics on the incidence and duration of acute diarrhea and acute respiratory tract infections (ARTIs) in low-socioeconomic communities of Jakarta, Indonesia.

METHODS: We conducted a 6-month, double-blind, placebo-controlled study in 494 healthy children aged 1 to 6 years who received low-lactose milk with low calcium content (LC; ∼50 mg/day; n = 124), regular calcium content (RC; ∼440 mg/day; n = 126), RC with 5.10⁸ colony-forming units per day of Lactobacillus casei CRL431 (casei; n = 120), or RC with 5.10⁸ colony-forming units per day of Lactobacillus reuteri DSM17938 (reuteri; n = 124). Number and duration of diarrhea and ARTIs episodes were primary and secondary outcomes, respectively.

RESULTS: Incidence of World Health Organization–defined diarrhea (≥3 loose/liquid stools in 24 hours) was not significantly different between RC and LC (relative risk [RR]: 0.99 [95% confidence interval (CI): 0.62–1.58]), between casei and RC (RR: 1.21 [95% CI: 0.76–1.92]), or between reuteri and RC (RR: 0.76 [95% CI: 0.46–1.25]) groups. Incidence of all reported diarrhea (≥2 loose/liquid stools in 24 hours) was significantly lower in the reuteri versus RC group (RR: 0.68 [95% CI: 0.46–0.99]). Irrespective of the definition used, reuteri significantly reduced diarrhea incidence in children with lower nutritional status (below-median height-and-weight-for-age z score). None of the interventions affected ARTIs.

CONCLUSIONS: RC milk, alone or with L casei, did not reduce diarrhea or ARTIs in Indonesian children. L reuteri may prevent diarrhea, especially in children with lower nutritional status.

KEY WORDS

• acute diarrhea
• calcium
• children
• developing country
• probiotics
• Indonesia
• Lactobacillus casei CRL431
• Lactobacillus reuteri DSM17938

• Accepted January 5, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 9 of 68Article

Reference Ranges for Lymphocyte Counts of Neonates: Associations Between Abnormal Counts and Outcomes

BACKGROUND AND OBJECTIVE: Both high and low lymphocyte counts at birth have been associated with adverse outcomes. However, the validity of defining a lymphocyte count as “abnormal” depends on having an accurate reference range. We established a reference range for neonatal lymphocyte counts by using multihospital data and used this to assess previously reported relationships between abnormal counts and early onset sepsis (EOS), intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP), periventricular leukomalacia, and birth asphyxia.

METHODS: We first created a data set that excluded counts from neonates with diagnoses previously associated with abnormal lymphocyte counts. Then the complete data (counts excluded plus included in the reference range) were used to test associations between abnormal counts and EOS, IVH, ROP, periventricular leukomalacia, and outcomes after birth asphyxia.

RESULTS: Lymphocyte counts were retrieved from 40 487 neonates, 10 860 of which were excluded from the reference range. A count >95th percentile was associated with EOS (2.07; 95% confidence interval [CI]: 1.80–2.38) and IVH ≥grade 3 (2.93; 95% CI: 1.83–4.71). A count <5th percentile was associated with EOS (odds ratio:1.24; 95% CI: 1.04–1.48), IVH ≥grade 3 (3.23; 95% CI: 1.95–5.36), and ROP ≥stage 3 (4.80: 95% CI: 2.38–9.66). Among 120 meeting criteria for birth asphyxia, those with a low count and a high nucleated red cell count had higher mortality (37% vs 11%, P = .001), more transfusions (P = .000), and more neurology referrals (P < .01).

CONCLUSIONS: A reference range for lymphocytes can identify neonates with abnormal counts, which can be useful because these neonates are at higher risk for certain adverse outcomes.

KEY WORDS

• reference range
• lymphocyte
• diagnosis
• outcome

• Accepted January 6, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 10 of 68Article

Cumulative Social Risk and Obesity in Early Childhood

OBJECTIVES: The goal of this study was to examine the relationship between cumulative social adversity and childhood obesity among preschool-aged children (N = 1605) in the Fragile Families and Child Wellbeing Study.

METHODS: Maternal reports of intimate partner violence, food insecurity, housing insecurity, maternal depressive symptoms, maternal substance use, and father’s incarceration were obtained when the child was 1 and 3 years of age. Two cumulative social risk scores were created by summing the 6 factors assessed at ages 1 and 3 years. Child height and weight were measured at 5 years of age. Logistic regression models stratified according to gender were used to estimate the association between cumulative social risk and obesity, adjusting for sociodemographic factors.

RESULTS: Seventeen percent of children were obese at age 5 years, and 57% had at least 1 social risk factor. Adjusting for sociodemographic factors, girls experiencing high cumulative social risk (≥2 factors) at age 1 year only (odds ratio [OR]: 2.1 [95% confidence interval [CI]: 1.1–4.1]) or at 3 years only (OR: 2.2 [95% CI: 1.2–4.2]) were at increased odds of being obese compared with girls with no risk factors at either time point. Those experiencing high cumulative risk at age 1 and 3 years were not at statistically significant odds of being obese (OR: 1.9 [95% CI: 0.9–4.0]). No significant associations were noted among boys.

CONCLUSIONS: There seems to be gender differences in the effects of cumulative social risk factors on the prevalence of obesity at 5 years of age. Understanding the social context of families could make for more effective preventive efforts to combat childhood obesity.

KEY WORDS

• cumulative risk
• food insecurity
• housing insecurity
• obesity
• social risk factors
• social stress
• violence

• Accepted December 16, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 11 of 68Article

Obese Mexican American Children Have Elevated MCP-1, TNF-α, Monocyte Concentration, and Dyslipidemia

BACKGROUND AND OBJECTIVE: Obesity is an independent risk factor for chronic disease. The prevalence of obesity is especially high among Mexican American children. Peripheral blood monocytes are altered with obesity contributing to elevated systemic inflammation and increased risk of chronic disease. In addition, obesity alters the circulating levels of cytokines/chemokines that influence monocyte behavior. The study objective was to investigate alterations in blood monocytes and plasma cytokines/chemokine levels among healthy weight (standardized BMI [zBMI] ≤85th percentile; n = 66), overweight (zBMI 85th–95th percentile; n = 23), and obese (zBMI ≥95th percentile; n = 39) Mexican American children.

METHODS: Blood samples were analyzed for total and subset monocyte concentration via flow cytometry. Serum monocyte chemoattractant protein-1 (MCP-1), fractalkine, interleukin-8, and tumor necrosis factor α (TNF-α) were measured by using a Milliplex MagPix assay. Serum cholesterol, high-density lipoproteins, triglycerides, and glucose were measured by using an enzymatic assay.

RESULTS: Total monocyte concentration (P = .012), classic monocyte concentration (P = .045), MCP-1 (P = .015), and TNF-α (P = .002) were significantly greater in obese children compared with healthy weight children. Also, overweight and obese children had elevated triglycerides (P = .001) and reduced high-density lipoproteins (P = .033) compared with healthy weight children.

CONCLUSIONS: Childhood obesity alters monocytes and circulating chemokines, putting children at a greater risk of developing obesity-related chronic diseases in adulthood. Further characterization of early immune alterations in childhood obesity may provide additional clinical insight into the assessment of obesity-related disease risk.

KEY WORDS

• childhood obesity
• cardiovascular disease
• type 2 diabetes mellitus
• systemic inflammation
• inflammation and disease

• Accepted December 16, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 12 of 68Article

Parental Separation and Pediatric Cancer: A Danish Cohort Study

OBJECTIVE: The purpose of this study was to determine the risk for separation (ending cohabitation) of the parents of a child with a diagnosis of cancer.

METHODS: In a nationwide cohort, we compared the risk for ending cohabitation of the parents of 2450 children (aged 0–20 years) given a diagnosis of cancer with the risk of parents of 44 853 randomly selected, gender- and age-matched cancer-free children. We adjusted for socioeconomic position and demographic factors. Rate ratios and 95% confidence intervals for separation were estimated in a Cox proportional hazards model.

RESULTS: The parents of children with cancer did not have a higher risk for separation than the general population (rate ratio: 1.00 [95% confidence interval: 0.91–1.10]). Separate analyses according to type of cancer and survival of the child similarly yielded null results.

CONCLUSIONS: Experiencing cancer in a child does not seem to be a risk factor for separation. Our study will allow clinicians to reassure parents and to support them in facing the trauma of cancer in their child.

KEY WORDS

• childhood cancer
• cohabitation
• divorce
• parents

• Accepted December 21, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 13 of 68Article

Intakes of Alcohol and Folate During Adolescence and Risk of Proliferative Benign Breast Disease

OBJECTIVES: To examine the combined effect of alcohol and folate intake during adolescence on the risk of proliferative benign breast disease (BBD).

METHODS: We used data from 29 117 women in the Nurses’ Health Study II who completed both adolescent alcohol consumption questions in 1989 and an adolescent diet questionnaire in 1998. A total of 659 women with proliferative BBD diagnosed between 1991 and 2001 were confirmed by central pathology review. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CIs), adjusted for established risk factors of breast cancer.

RESULTS: Adolescent alcohol consumption was dose-dependently associated with an increased risk of proliferative BBD (hazard ratio = 1.15 per 10 g/day consumption; 95% CI, 1.03–1.28). There was no significant association between adolescent folate intake and the risk of proliferative BBD. Stratified analyses showed that each 10-g/day alcohol intake during adolescence was associated with a 21% (95% CI, 1.01–1.45) increase in the risk of proliferative BBD among women with low folate intake during adolescence, which was not significantly different from the alcohol-associated risk among women with moderate and high folate intake during adolescence (P for interaction = 0.18).

CONCLUSIONS: Adolescent alcohol consumption is associated with increased risk of proliferative BBD, which may not be reduced by increased folate intake during adolescence.

KEY WORDS

• alcohol
• folate
• adolescence
• benign breast disease
• premalignant breast lesions

• Accepted January 10, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 14 of 68Article

High Blood Pressure in 2.5-Year-Old Children Born Extremely Preterm

OBJECTIVE: Adolescents and young adults born preterm have elevated blood pressure (BP). The objective of this study was to investigate if BP is elevated at 2.5 years of age after an extremely preterm birth (EXPT).

METHODS: In a regional subset of the national population-based cohort Extremely Preterm Infants in Sweden Study, BP at 2.5 years of age was studied in 68 survivors of EXPT (gestational age: 23.6–26.9 weeks; mean ± SD birth weight: 810 ± 164 g), and 65 matched controls born at term.

RESULTS: At follow-up at 2.5 years of corrected age, EXPT children had significantly higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) z scores than controls born at term, according to pediatric BP nomograms by age, gender, and height. The proportion of SBP ≥90th percentile was 44% (30 of 68) in EXPT children and 23% (15 of 65) in controls (P = .01). In logistic regression analyses stratified according to gender, EXPT was associated with an odds ratio for a SBP ≥90th percentile of 3.32 (95% confidence interval: 1.25–8.81) among boys. The corresponding odds ratio among EXPT girls was 2.18 (95% confidence interval: 0.62–7.61). In EXPT children, SBP and DBP z scores were inversely correlated to catch-up growth from 36 weeks’ postmenstrual age to follow-up at 2.5 years of age.

CONCLUSIONS: Children born extremely preterm have elevated office SBP and DBP at a corrected age of 2.5 years. This finding might have implications for their cardiovascular health later in life.

KEY WORDS

• blood pressure
• extremely preterm birth
• pediatrics
• risk factors

• Accepted December 29, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 15 of 68Article

Comparison of Mercury and Aneroid Blood Pressure Measurements in Youth

OBJECTIVE: Because of concerns about the safety and environmental impact of mercury, aneroid sphygmomanometers have replaced mercury-filled devices for blood pressure (BP) measurements. Despite this change, few studies have compared BP measurements between the 2 devices.

METHODS: The SEARCH for Diabetes in Youth Study conducted a comparison of aneroid and mercury devices among 193 youth with diabetes (48% boys, aged 12.9 ± 3.7 years; 89% type 1). Statistical analyses included estimating Pearson correlation coefficients, Bland-Altman plots, paired t tests, and fitting regression models, both overall and stratified by age (<10 vs ≥10–18 years).

RESULTS: Mean mercury and aneroid systolic and diastolic BPs were highly correlated. For the entire group, there was no significant difference in mean systolic BP using the aneroid device, but there was a −1.53 ± 5.06 mm Hg difference in mean diastolic BP. When stratified by age, a lower diastolic BP (−1.78 ± 5.2 mm Hg) was seen in those ≥10 to 18 years using the aneroid device. No differences in systolic BP were observed, and there were no differences in BP by device in individuals <10 years. Regression analyses did not identify any explanatory variables.

CONCLUSIONS: Although a small discrepancy between diastolic BP measurements from aneroid versus mercury devices exists, this variation is unlikely to be clinically significant, suggesting that either device could be used in research or clinical settings.

KEY WORDS

• pediatrics
• blood pressure

• Accepted January 12, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 16 of 68Article

Evaluation of a Clinical Dehydration Scale in Children Requiring Intravenous Rehydration

OBJECTIVES: To evaluate the reliability and validity of a previously derived clinical dehydration scale (CDS) in a cohort of children with gastroenteritis and evidence of dehydration.

METHODS: Participants were 226 children older than 3 months who presented to a tertiary care emergency department and required intravenous rehydration. Reliability was assessed at treatment initiation, by comparing the scores assigned independently by a trained research nurse and a physician. Validity was assessed by using parameters reflective of disease severity: weight gain, baseline laboratory results, willingness of the physician to discharge the patient, hospitalization, and length of stay.

RESULTS: Interobserver reliability was moderate, with a weighted κ of 0.52 (95% confidence interval [CI] 0.41, 0.63). There was no correlation between CDS score and percent weight gain, a proxy measure of fluid deficit (Spearman correlation coefficient = −0.03; 95% CI −0.18, 0.12). There were, however, modest and statistically significant correlations between CDS score and several other parameters, including serum bicarbonate (Pearson correlation coefficient = −0.35; 95% CI −0.46, −0.22) and length of stay (Pearson correlation coefficient = 0.24; 95% CI 0.11, 0.36). The scale’s discriminative ability was assessed for the outcome of hospitalization, yielding an area under the receiver operating characteristic curve of 0.65 (95% CI 0.57, 0.73).

CONCLUSIONS: In children administered intravenous rehydration, the CDS was characterized by moderate interobserver reliability and weak associations with objective measures of disease severity. These data do not support its use as a tool to dictate the need for intravenous rehydration or to predict clinical course.

KEY WORDS

• dehydration
• gastroenteritis
• clinical score
• severity of illness
• emergencies

• Accepted January 12, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 17 of 68Article

Risk Factors for Hospitalization With Lower Respiratory Tract Infections in Children in Rural Alaska

OBJECTIVE: Lower respiratory tract infections (LRTIs) are a major cause of morbidity for children worldwide and particularly for children from developing and indigenous populations. In this study, we evaluated risk factors for hospitalization with LRTI in a region in southwest Alaska.

METHODS: The study was conducted from October 1, 2006, to September 30, 2007, in the Yukon Kuskokwim Delta region of Alaska. Cases were recruited from children <3 years of age hospitalized with LRTI. Controls were recruited during visits to the surrounding communities in the region and matched posthoc to cases on the basis of subregion, season, and age. Parents were interviewed for potential risk factors, and medical records were reviewed. Participants had a nasopharyngeal swab sample taken for polymerase chain reaction (PCR) testing for a panel of respiratory viruses. Samples positive for respiratory syncytial virus, human metapneumovirus, or parainfluenza type 3 were quantitated by reverse transcriptase real-time quantitative PCR.

RESULTS: One hundred twenty-eight cases were matched to 186 controls. In a multivariable conditional logistic regression model, significantly (P < .05) increased risk of hospitalization was associated with medically high-risk status, having a woodstove in the house, being bottle fed, and vomiting after feeding; living in a house that had 2 or more rooms with sinks was a protective factor. Viral loads in hospitalized cases were significantly higher than those in controls, but a strict cutoff level was not observed.

CONCLUSIONS: Several risk factors for LRTI hospitalization were identified in this high risk population. Some factors are amenable to environmental and behavioral interventions.

• pneumonia
• respiratory infectious diseases
• case-control study
• risk factors
• Alaska Native

• Accepted January 6, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 18 of 68Article

Comparison of Adolescent, Young Adult, and Adult Women’s Maternity Experiences and Practices

BACKGROUND AND OBJECTIVE: Pregnant adolescents face unique challenges. Understanding the experiences, knowledge, and behaviors of adolescents during the pregnancy and postpartum periods may contribute to improvement of their maternity care. The purpose of this study was to compare the maternity experiences, knowledge, and behaviors of adolescent, young adult, and adult women by using a nationally representative sample.

METHODS: This study used data from the Canadian Maternity Experiences Survey (N = 6421). The weighted proportions of each variable were calculated by using survey sample weights. Logistic regression was used to estimate odds ratios. Bootstrapping techniques were used to calculate variance estimates for prevalence and 95% confidence intervals.

RESULTS: Adolescents and young adults were more likely to experience physical abuse in the previous 2 years, initiate prenatal care late, not take folic acid before or during pregnancy, have poor prenatal health behaviors, have a lower cesarean delivery rate, have lower breastfeeding initiation and duration rates, experience more stressful life events, experience postpartum depression symptoms, and rate their infant’s health as suboptimal than adult women. Adolescents were more likely to rate their own health as suboptimal.

CONCLUSIONS: Adolescents have unique needs during pregnancy and postpartum. Health care professionals should seek to provide care in a manner that acknowledges these needs.

KEY WORDS

• abuse
• adolescent
• Canada
• Maternity Experiences Survey
• perinatal care
• postpartum
• pregnancy

• Accepted January 5, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 19 of 68Article

Birth Asphyxia: A Major Cause of Early Neonatal Mortality in a Tanzanian Rural Hospital

OBJECTIVE: Early neonatal mortality within the first 24 hours contributes substantially to overall neonatal mortality rates. The definition of birth asphyxia (BA) is imprecise, and reliable cause-specific mortality data are limited; thus the estimated proportion of BA-related deaths globally remains questionable. The objective was to determine the presumed causes of neonatal death within the first 24 hours in a rural hospital in Northern Tanzania.

METHODS: This is a prospective descriptive observational study conducted in the delivery room and adjacent neonatal area. Research assistants were trained to observe and record events related to labor, neonatal resuscitation, and 24-hour postnatal course. BA was defined as failure to initiate spontaneous respirations and/or 5-minute Apgar score <7, prematurity as gestational age <36 weeks, and low birth weight (LBW) as birth weight <3rd centile for gestational age. Data were analyzed with χ² and Student’s t tests.

RESULTS: Over 1 year, 4720 infants were born and evaluated. Of these, 256 were admitted to the neonatal area. Forty-nine infants died secondary to BA (61%), prematurity (18%), LBW (8%), infection (2%), congenital abnormalities (8%), and unclear reason (2%). The 5-minute Apgar score was ≥7 in 50% of the infants who died secondary to BA.

CONCLUSIONS: Most cases of early neonatal mortality were related to BA, and prematurity and LBW are additional important considerations. Reducing perinatal mortality requires a multifaceted approach with attention to issues related to BA, potential complications of prematurity, and LBW. The 5-minute Apgar score is a poor surrogate of BA.

KEY WORDS

• millennium developmental goal 4
• neonatal mortality
• low-resource settings
• causes of neonatal deaths

• Accepted January 5, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 20 of 68Article

Barriers to Medication Adherence in HIV-Infected Children and Youth Based on Self- and Caregiver Report

OBJECTIVE: Nonadherence to antiretroviral therapy among children/youth with HIV often is associated with disease progression. This study examined the agreement between child and caregiver perceptions of barriers to adherence and factors associated with these barriers.

METHODS: Children/youth with perinatally acquired HIV and their parents/caregivers (n = 120 dyads) completed a questionnaire about 19 potential barriers to adherence to the child’s antiretroviral therapy regimen. Agreement between the 2 reports was measured via the kappa statistic. Factors associated with the barriers were assessed by using multiple logistic regression.

RESULTS: Of the 120 children, 55% were African American, 54% were boys, and the average age was 12.8 years. The most frequently reported barrier by either the caregiver or youth was “forgot.” There were varying degrees of agreement between child and caregiver on the following barriers: “forgot,” “taste,” “child was away from home,” “child refused,” and “child felt good.” Children who knew their HIV status were more likely to report logistical barriers, such as scheduling issues. Children with a biological parent as their caregiver were more likely to report regimen or fear of disclosure as a barrier.

CONCLUSIONS: Lack of agreement was observed for more than half of the studied barriers, indicating discrepancies between children’s and caregivers’ perceptions of factors that influence medication-taking. The findings suggest a need for interventions that involve both child and caregiver in the tasks of remembering when to administer the child’s medications, sustaining adherence, and appropriately transitioning medication responsibility to the youth.

KEY WORDS

• children
• HIV
• adherence
• adolescents
• pediatric

• Accepted January 12, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 21 of 68Article

Relationship Between Maternal and Neonatal Staphylococcus aureus Colonization

OBJECTIVE: The study aimed to assess whether maternal colonization with Staphylococcus aureus during pregnancy or at delivery was associated with infant staphylococcal colonization.

METHODS: For this prospective cohort study, women were enrolled at 34 to 37 weeks of gestation between 2007 and 2009. Nasal and vaginal swabs for culture were obtained at enrollment; nasal swabs were obtained from women and their infants at delivery and 2- and 4-month postbirth visits. Logistic regression was used to determine whether maternal colonization affected infant colonization.

RESULTS: Overall, 476 and 471 mother-infant dyads had complete data for analysis at enrollment and delivery, respectively. Maternal methicillin-resistant S aureus (MRSA) colonization occurred in 10% to 17% of mothers, with the highest prevalence at enrollment. Infant MRSA colonization peaked at 2 months of age, with 20.9% of infants colonized. Maternal staphylococcal colonization at enrollment increased the odds of infant staphylococcal colonization at birth (odds ratio; 95% confidence interval: 4.8; 2.4–9.5), hospital discharge (2.6; 1.3–5.0), at 2 months of life (2.7; 1.6–4.3), and at 4 months of life (2.0; 1.1–3.5). Similar results were observed for maternal staphylococcal colonization at delivery. Fifty maternal-infant dyads had concurrent MRSA colonization: 76% shared isolates of the same pulsed-field type, and 30% shared USA300 isolates. Only 2 infants developed staphylococcal disease.

CONCLUSIONS: S aureus colonization (including MRSA) was extremely common in this cohort of maternal-infant pairs. Infants born to mothers with staphylococcal colonization were more likely to be colonized, and early postnatal acquisition appeared to be the primary mechanism.

KEY WORDS

• Staphylococcus aureus
• child
• colonization
• epidemiology
• pregnancy

• Accepted December 15, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 22 of 68Article

Early or Delayed Enteral Feeding for Preterm Growth-Restricted Infants: A Randomized Trial

BACKGROUND: Growth-restricted preterm infants are at increased risk of developing necrotizing enterocolitis (NEC) and initiation of enteral feeding is frequently delayed. There is no evidence that this delay is beneficial and it might further compromise nutrition and growth.

METHODS: Infants with gestation below 35 weeks, birth weight below the 10th centile, and abnormal antenatal umbilical artery Doppler waveforms were randomly allocated to commence enteral feeds “early,” on day 2 after birth, or “late,” on day 6. Gradual increase in feeds was guided by a “feeding prescription” with rate of increase the same for both groups. Primary outcomes were time to achieve full enteral feeding sustained for 72 hours and NEC.

RESULTS: Four hundred four infants were randomly assigned from 54 hospitals in the United Kingdom and Ireland (202 to each group). Median gestation was 31 weeks. Full, sustained, enteral feeding was achieved at an earlier age in the early group: median age was 18 days compared with 21 days (hazard ratio: 1.36 [95% confidence interval: 1.11–1.67]). There was no evidence of a difference in the incidence of NEC: 18% in the early group and 15% in the late group (relative risk: 1.2 [95% confidence interval: 0.77–1.87]). Early feeding resulted in shorter duration of parenteral nutrition and high-dependency care, lower incidence of cholestatic jaundice, and improved SD score for weight at discharge.

CONCLUSIONS: Early introduction of enteral feeds in growth-restricted preterm infants results in earlier achievement of full enteral feeding and does not appear to increase the risk of NEC.

KEY WORDS

• infant premature
• infant very low birth weight
• enterocolitis
• necrotizing
• enteral nutrition
• Doppler ultrasound imaging
• blood flow velocity

• Accepted December 22, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 23 of 68Article

Supplemental Written Information Improves Prenatal Counseling: A Randomized Trial

OBJECTIVE: To determine if maternal knowledge of prematurity is improved when verbal gestational age-specific counseling is supplemented with written gestational age-specific information.

METHODS: Prospective, randomized study of 60 pregnant participants assessed to be at risk for premature delivery between 23 and 34 weeks’ gestation. Counseling in the control group consisted of gestational age–specific verbal information, and counseling in the intervention group consisted of written gestational age–specific information 1 hour before the verbal gestational age–specific information. Both groups completed a Prematurity Knowledge Questionnaire after counseling and the State-Trait Anxiety Inventory before and after counseling. The Prematurity Knowledge Questionnaire consisted of questions regarding short-term problems (immature lungs, intraventricular hemorrhage, retinopathy, feeding problems, infection, apnea, and jaundice), long-term problems (chronic lung disease, postdischarge respiratory infections, visual impairment, hearing impairment, brain damage, and learning and behavior problems), and numerical outcome data (probabilities of survival, survival without significant morbidity, severe intraventricular hemorrhage, severe retinopathy, and chronic lung disease).

RESULTS: Knowledge of short-term problems was not statistically different between the intervention (82%) and control groups (67%). Knowledge of long-term problems was better in the intervention (71%) than the control group (45%). Knowledge of numerical data was better in the intervention (48%) than the control group (29%). State-Trait Anxiety Inventory scores decreased after counseling in the intervention group.

CONCLUSIONS: Supplementation of face-to-face verbal counseling with written information improved knowledge of long-term problems and knowledge of numerical outcome data, and it also decreased anxiety in women expecting a premature delivery.

KEY WORDS

• counseling
• communication
• parent
• premature infant
• physician

• Accepted January 5, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 24 of 68Article

Automated Primary Care Screening in Pediatric Waiting Rooms

BACKGROUND AND OBJECTIVE: Implementing US Preventive Services Task Force and American Academy of Pediatrics preventive service guidelines within the short duration of a visit is difficult because identifying which of a large number of guidelines apply to a particular patient is impractical. Clinical decision support system integrated with electronic medical records offer a good strategy for implementing screening in waiting rooms. Our objective was to determine rates of positive risk screens during typical well-care visits among children and adolescents in a primary care setting.

METHODS: Child Health Improvement through Computer Automation (CHICA) is a pediatric clinical decision support system developed by our research group. CHICA encodes clinical guidelines as medical logic modules to generate scanable paper forms: the patient screening form to collect structured data from patient families in the waiting room and the physician worksheet to provide physician assessments at each visit. By using visit as a unit of analysis from CHICA’s database, we have determined positive risk screen rates in our population.

RESULTS: From a cohort of 16 963 patients, 408 601 questions were asked in 31 843 visits. Of the questions asked, 362 363 (89%) had a response. Of those, 39 176 (11%) identified positive risk screens in both the younger children and the adolescent age groups.

CONCLUSIONS: By automating the process of screening and alerting the physician to those who screened positive, we have significantly decreased the burden of identifying relevant guidelines and screening of patient families in our clinics.

KEY WORDS

• preventive services guidelines
• CHICA
• screening

• Accepted January 6, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 25 of 68Article

Antenatal Glucocorticoid Exposure and Long-Term Alterations in Aortic Function and Glucose Metabolism

OBJECTIVE: Animal studies have demonstrated long-term effects of in utero glucocortcoid exposure on vascular development and glucose metabolism. We hypothesized that there would be a similar impact in humans.

METHODS: One hundred and two young adults born preterm aged 23 to 28 years, with prospective data collection from birth, and 95 adults born term after uncomplicated pregnancies underwent cardiovascular MRI. We compared cardiac and aortic structure and function, as well as cardiovascular risk profile, in a nested case-control study of 16 participants exposed to antenatal steroids and 32 who were not, but with otherwise similar perinatal care. Outcomes were compared with normal ranges in those born term.

RESULTS: Adults whose mothers had received antenatal steroids had decreased ascending aortic distensibility (9.88 ± 3.21 vs 13.62 ± 3.88 mm Hg⁻¹ × 10³, P = .002) and increased aortic arch pulse wave velocity (5.45 ± 1.41 vs 4.47 ± 0.91 m/s, P = .006). The increase in stiffness was equivalent to that of term adults a decade older. Those who had in utero exposure to antenatal steroids also had significant differences in homeostatic model assessments for β-cell function (P = .010), but in multiple regression analysis this did not explain the impact of steroids on aortic function.

CONCLUSIONS: Antenatal glucocorticoid exposure in preterm infants is associated with increased aortic arch stiffness and altered glucose metabolism in early adulthood.

KEY WORDS

• antenatal glucocorticoids
• preterm infants
• aortic stiffness
• programming
• cardiac function

• Accepted December 23, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 26 of 68Article

Clinical Research Involving Children: Registration, Completeness, and Publication

BACKGROUND AND OBJECTIVE: Effective health care for children must be based on thorough analyses of the best research evidence. The objective of this study was to examine registration, completeness, and publication of studies involving children.

METHODS: We searched the ClinicalTrials.gov registry to identify all closed studies involving children and examined them for completeness and availability of results. We examined publication in peer-reviewed journals for 160 randomly selected National Institutes of Health (NIH)–funded studies from 2000 through 2010 and for 758 randomly selected completed studies.

RESULTS: Of 3428 closed studies involving children identified in ClinicalTrials.gov, 2385 (70%) were completed, 28 (0.8%) suspended, 152 (4.4%) terminated, and 38 (1.1%) withdrawn. The proportion of non-completed studies (terminated and suspended) increased linearly by 186% between 2001 and 2009, from 1.9% to 8.4%. Of the 152 terminated studies, 48 did not report reasons for termination, 21 cited safety concerns, and 83 cited poor recruitment or other administrative reasons. Only 29% of completed studies were published. Publication that did occur was an average of 2 years after study completion. Completed interventional studies were published more often than observational studies. Completed industry-funded studies were published less often than studies funded by the NIH. Registered NIH-funded trials were published more often than unregistered.

CONCLUSIONS: Results are unavailable for more than half of the studies involving children, revealing a substantial publication bias. Registration and posting of results on ClinicalTrials.gov should be mandatory for all studies involving children.

KEY WORDS

• clinical research involving children
• databases as topic
• human experimentation/standards
• publication bias
• child advocacy
• bioethics

• Accepted December 14, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 27 of 68Article

Pharmacologic Treatment of Repetitive Behaviors in Autism Spectrum Disorders: Evidence of Publication Bias

OBJECTIVE: The goal of this study was to examine the efficacy of serotonin receptor inhibitors (SRIs) for the treatment of repetitive behaviors in autism spectrum disorders (ASD).

METHODS: Two reviewers searched PubMed and Clinicaltrials.gov for randomized, double-blind, placebo-controlled trials evaluating the efficacy of SRIs for repetitive behaviors in ASD. Our primary outcome was mean improvement in ratings scales of repetitive behavior. Publication bias was assessed by using a funnel plot, the Egger’s test, and a meta-regression of sample size and effect size.

RESULTS: Our search identified 5 published and 5 unpublished but completed trials eligible for meta-analysis. Meta-analysis of 5 published and 1 unpublished trial (which provided data) demonstrated a small but significant effect of SRI for the treatment of repetitive behaviors in ASD (standardized mean difference: 0.22 [95% confidence interval: 0.07–0.37], z score = 2.87, P < .005). There was significant evidence of publication bias in all analyses. When Duval and Tweedie's trim and fill method was used to adjust for the effect of publication bias, there was no longer a significant benefit of SRI for the treatment of repetitive behaviors in ASD (standardized mean difference: 0.12 [95% confidence interval: –0.02 to 0.27]). Secondary analyses demonstrated no significant effect of type of medication, patient age, method of analysis, trial design, or trial duration on reported SRI efficacy.

CONCLUSIONS: Meta-analysis of the published literature suggests a small but significant effect of SRI in the treatment of repetitive behaviors in ASD. This effect may be attributable to selective publication of trial results. Without timely, transparent, and complete disclosure of trial results, it remains difficult to determine the efficacy of available medications.

KEY WORDS

• antidepressive agents
• autism
• meta-analysis
• pervasive child development disorders
• publication bias

• Accepted February 29, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 28 of 68Article

Measles-Containing Vaccines and Febrile Seizures in Children Age 4 to 6 Years

BACKGROUND: In the United States, children receive 2 doses of measles-mumps-rubella vaccine (MMR) and varicella vaccine (V), the first between ages 1 to 2 years and the second between ages 4 to 6 years. Among 1- to 2-year-olds, the risk of febrile seizures 7 to 10 days after MMRV is double that after separate MMR + V. Whether MMRV or MMR + V affects risk for febrile seizure risk among 4- to 6-year-olds has not been reported.

METHODS: Among 4- to 6-year-old Vaccine Safety Datalink members, we identified seizures in the emergency department and hospital from 2000 to 2008 and outpatient visits for fever from 2006 to 2008 during days 7 to 10 and 0 to 42 after MMRV and MMR + V. Incorporating medical record reviews, we assessed seizure risk after MMRV and MMR + V.

RESULTS: From 2006 through 2008, 86 750 children received MMRV; from 2000 through 2008, 67 438 received same-day MMR + V. Seizures were rare throughout days 0 to 42 without peaking during days 7 to 10. There was 1 febrile seizure 7 to 10 days after MMRV and 0 after MMR + V. Febrile seizure risk was 1 per 86 750 MMRV doses (95% confidence interval, 1 per 3 426 441, 1 per 15 570) and 0 per 67 438 MMR + V doses (1 per 18 282).

CONCLUSIONS: This study provides reassurance that MMRV and MMR + V were not associated with increased risk of febrile seizures among 4- to 6-year-olds. We can rule out with 95% confidence a risk greater than 1 febrile seizure per 15 500 MMRV doses and 1 per 18 000 MMR + V doses.

KEY WORDS

• measles
• varicella
• seizures
• vaccine
• fever

• Accepted January 10, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 29 of 68Article

Effective Analgesia Using Physical Interventions for Infant Immunizations

BACKGROUND: To measure the analgesic effectiveness of the 5 S’s (swaddling, side/stomach position, shushing, swinging, and sucking) alone and combined with sucrose, during routine immunizations at 2 and 4 months.

METHODS: We conducted a prospective, randomized, placebo-controlled trial with 2- and 4-month-old infants during well-child visits. Patients were assigned into 4 groups (2 × 2) receiving either 2 mL of water or 2 mL of 24% oral sucrose and then either standard-of-care comfort measures by parents or intervention with the 5 S’s immediately postvaccination. The Modified Riley Pain Score was used to score the infants’ pain at 15-second intervals for 2 minutes, then every 30 seconds up to 5 minutes postvaccination. Repeated-measures analysis of variance examined between group differences and within-subject variability of treatment effect on overall pain scores and length of crying.

RESULTS: Two hundred thirty infants were enrolled. Results revealed significantly different mean pain scores between study groups with the exception of the 5S’s and 5S’s with sucrose groups. These 2 groups had lower similar mean scores over time, followed by sucrose alone, then control. The same trend was found with the proportion of children crying as with the mean pain score outcome measure.

CONCLUSIONS: Physical intervention of the 5 S’s (swaddling, side/stomach position, shushing, swinging, and sucking) provided decreased pain scores on a validated pain scale and decreased crying time among 2- and 4-month-old infants during routine vaccinations. The use of 5S’s did not differ from 5S’s and sucrose.

KEY WORDS

• immunizations
• vaccines
• pain management
• infant
• analgesia

• Accepted January 11, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 30 of 68Article

Decreasing Prevalence of Obesity Among Young Children in Massachusetts From 2004 to 2008

OBJECTIVE: To examine whether the obesity prevalence is increasing, level, or decreasing among young US children (aged <6 years) in the past decade; and to compare regional data to those of 2 national databases.

METHODS: We analyzed data from 108 762 well-child visits (36 827 children) at a multisite pediatric practice in eastern Massachusetts during 1999–2008. By using the Centers for Disease Control and Prevention 2000 gender-specific growth charts, we defined obesity as weight-for-length ≥95th percentile for children aged <24 months and BMI ≥95th percentile for children aged 24 to <72 months. By using multivariable logistic regression, we estimated gender-specific obesity trends in 2 separate periods, 1999–2003 and 2004–2008, adjusting for age group, race/ethnicity, health insurance, and practice site.

RESULTS: From 1999 to 2003, the obesity prevalence was fairly stable among both boys and girls. From 2004 to 2008, the obesity prevalence substantially decreased among both boys and girls. The decline in obesity prevalence during 2004–2008 was more pronounced among children insured by non-Medicaid health plans than among those insured by Medicaid.

CONCLUSIONS: Among children aged <6 years at this multisite pediatric practice, obesity prevalence decreased during 2004–2008, which is in line with national data showing no increase in prevalence during this time period. The smaller decrease among Medicaid-insured children may portend widening of socioeconomic disparities in childhood obesity.

KEY WORDS

• obesity
• BMI
• child
• infant
• prevalence
• trends
• epidemiology

• Accepted October 28, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 31 of 68Article

Race and Unequal Burden of Perioperative Pain and Opioid Related Adverse Effects in Children

BACKGROUND: Interindividual variability in pain perception and analgesic response is a major problem in perioperative practice. Adult studies suggest pain management is influenced by patient’s race. The objective of this study is to evaluate the influence of race on perioperative pain treatment in children.

METHODS: Prospective observational study evaluating effect of race on analgesia and opioid related adverse effects after tonsillectomy in African American and Caucasian children. A sample of 194 healthy children between 6 and 15 years of age were included. Race was self-identified by parents. All participants received standard perioperative care with a standard anesthetic and an intraoperative dose of morphine. Analgesia outcomes included maximum postoperative pain scores, postoperative opioid requirement, and analgesic interventions. Safety outcomes included incidences of opioid related adverse effects.

RESULTS: African American children experienced significantly more postoperative pain than Caucasian children as measured by postoperative opioid requirement (P = .0011), maximum postoperative pain scores (P < .0001), and analgesic interventions (P < .0001) in the recovery room. Although Caucasian children received relatively less opioids perioperatively, they had significantly higher opioid related adverse effects (P = .039). African American children with obstructive sleep apnea were more likely to have prolonged post anesthesia recovery unit stay due to inadequate pain control.

CONCLUSIONS: After similar uses of intraoperative morphine for tonsillectomy, there was an unequal burden of increased pain in African American children and increased opioid adverse effects in Caucasian children in the recovery room. Though Caucasian children received relatively less opioids perioperatively, they had higher incidences of opioid related adverse effects than African American children.

KEY WORDS

• pain management
• pain response
• pain sensitivity
• race
• safety

• Accepted January 9, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 32 of 68Article

Child and Adult Outcomes of Chronic Child Maltreatment

OBJECTIVE: To describe how child maltreatment chronicity is related to negative outcomes in later childhood and early adulthood.

METHODS: The study included 5994 low-income children from St Louis, including 3521 with child maltreatment reports, who were followed from 1993–1994 through 2009. Children were 1.5 to 11 years of age at sampling. Data include administrative and treatment records indicating substance abuse, mental health treatment, brain injury, sexually transmitted disease, suicide attempts, and violent delinquency before age 18 and child maltreatment perpetration, mental health treatment, or substance abuse in adulthood. Multivariate analysis controlled for potential confounders.

RESULTS: Child maltreatment chronicity predicted negative childhood outcomes in a linear fashion (eg, percentage with at least 1 negative outcome: no maltreatment = 29.7%, 1 report = 39.5%, 4 reports = 67.1%). Suicide attempts before age 18 showed the largest proportionate increase with repeated maltreatment (no report versus 4+ reports = +625%, P < .0001). The dose-response relationship was reduced once controls for other adverse child outcomes were added in multivariate models of child maltreatment perpetration and mental health issues. The relationship between adult substance abuse and maltreatment report history disappeared after controlling for adverse child outcomes.

CONCLUSIONS: Child maltreatment chronicity as measured by official reports is a robust indicator of future negative outcomes across a range of systems, but this relationship may desist for certain adult outcomes once childhood adverse events are controlled. Although primary and secondary prevention remain important approaches, this study suggests that enhanced tertiary prevention may pay high dividends across a range of medical and behavioral domains.

KEY WORDS

• child abuse
• child neglect
• child maltreatment

• Accepted January 13, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 33 of 68Article

Health Risks of Oregon Eighth-Grade Participants in the “Choking Game”: Results From a Population-Based Survey

OBJECTIVE: To examine the risk behaviors associated with participation in the “choking game” by eighth-graders in Oregon.

METHODS: We obtained data from the 2009 Oregon Healthy Teens survey, a cross-sectional weighted survey of 5348 eighth-graders that questioned lifetime prevalence and frequency of choking game participation. The survey also included questions about physical and mental health, gambling, sexual activity, nutrition, physical activity/body image, exposure to violence, and substance use.

RESULTS: Lifetime prevalence of choking game participation was 6.1% for Oregon eighth-graders, with no differences between males and females. Of the eighth-grade choking game participants, 64% had engaged in the activity more than once and 26.6% >5 times. Among males, black youth were more likely to participate than white youth. Among both females and males, Pacific Islander youth were much more likely to participate than white youth. Multivariate logistic regression revealed that sexual activity and substance use were significantly associated with choking game participation for both males and females.

CONCLUSIONS: At >6%, the prevalence of choking game participation among Oregon youth is consistent with previous findings. However, we found that most of those who participate will put themselves at risk more than once. Participants also have other associated health risk behaviors. The comprehensive adolescent well visit, as recommended by the American Academy of Pediatrics, is a good opportunity for providers to conduct a health behavior risk assessment and, if appropriate, discuss the dangers of engaging in this activity.

KEY WORDS

• adolescent medicine
• adolescents
• injury prevention and control
• preventive health care visits
• risk assessment

• Accepted January 10, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 34 of 68Article

Magnesium Use in Asthma Pharmacotherapy: A Pediatric Emergency Research Canada Study

OBJECTIVES: To examine the use of intravenous magnesium in Canadian pediatric emergency departments (EDs) in children requiring hospitalization for acute asthma and association of administration of frequent albuterol/ipratropium and timely corticosteroids with hospitalization.

METHODS: Retrospective medical record review at 6 EDs of otherwise healthy children 2 to 17 years of age with acute asthma. Data were extracted on history, disease severity, and timing of ED stabilization treatments with inhaled albuterol, ipratropium, corticosteroids, and magnesium. Primary outcome was the proportion of hospitalized children given magnesium in the ED. Secondary outcome was the ED use of “intensive therapy” in hospitalized children, defined as 3 albuterol inhalations with ipratropium and corticosteroids within 1 hour of triage.

RESULTS: A total of 19 (12.3%) of 154 hospitalized children received magnesium (95% confidence interval 7.1, 17.5) versus 2 of 962 discharged patients. Children given magnesium were more likely to have been previously admitted to ICU (odds ratio [OR] 11.2), hospitalized within the past year (OR 3.8), received corticosteroids before arrival (OR 4.0), presented with severe exacerbation (OR 6.1), and to have been treated at 1 particular center (OR 14.9). Forty-two (53%) of 90 hospitalized children were not given “intensive therapy.” Children receiving “intensive therapy” were more likely to present with severe disease to EDs by using asthma guidelines (ORs 8.9, 3.0). Differences in the frequencies of all stabilization treatments were significant across centers.

CONCLUSIONS: Magnesium is used infrequently in Canadian pediatric EDs in acute asthma requiring hospitalization. Many of these children also do not receive frequent albuterol and ipratropium, or early corticosteroids. Significant variability in the use of these interventions was detected.

KEY WORDS

• acute asthma
• emergency medicine
• emergency department
• children
• intravenous magnesium

• Accepted January 13, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 35 of 68Article

Maternal Caffeine Consumption and Infant Nighttime Waking: Prospective Cohort Study

OBJECTIVE: Coffee and other caffeinated beverages are commonly consumed in pregnancy. In adults, caffeine may interfere with sleep onset and have a dose-response effect similar to those seen during insomnia. In infancy, nighttime waking is a common event. With this study, we aimed to investigate if maternal caffeine consumption during pregnancy and lactation leads to frequent nocturnal awakening among infants at 3 months of age.

METHODS: All children born in the city of Pelotas, Brazil, during 2004 were enrolled on a cohort study. Mothers were interviewed at delivery and after 3 months to obtain information on caffeine drinking consumption, sociodemographic, reproductive, and behavioral characteristics. Infant sleeping pattern in the previous 15 days was obtained from a subsample. Night waking was defined as an episode of infant arousal that woke the parents during nighttime. Multivariable analysis was performed by using Poisson regression.

RESULTS: The subsample included 885 of the 4231 infants born in 2004. All but 1 mother consumed caffeine in pregnancy. Nearly 20% were heavy consumers (≥300 mg/day) during pregnancy and 14.3% at 3 months postpartum. Prevalence of frequent nighttime awakeners (>3 episodes per night) was 13.8% (95% confidence interval: 11.5%–16.0%). The highest prevalence ratio was observed among breastfed infants from mothers consuming ≥300 mg/day during the whole pregnancy and in the postpartum period (1.65; 95% confidence interval: 0.86–3.17) but at a nonsignificant level.

CONCLUSIONS: Caffeine consumption during pregnancy and by nursing mothers seems not to have consequences on sleep of infants at the age of 3 months.

KEY WORDS

• sleep
• sleep duration
• infant sleeping
• night waking
• infant
• caffeine
• coffee

• Accepted December 22, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 36 of 68Article

Inpatient Hospital Care of Children With Trisomy 13 and Trisomy 18 in the United States

BACKGROUND AND OBJECTIVE: Trisomy 13 and trisomy 18 are generally considered fatal anomalies, with a majority of infants dying in the first year after birth. The inpatient hospital care that these patients receive has not been adequately described. This study characterized inpatient hospitalizations of children with trisomy 13 and trisomy 18 in the United States, including number and types of procedures performed.

METHODS: Retrospective repeated cross-sectional assessment of hospitalization data from the nationally representative US Kids’ Inpatient Database, for the years 1997, 2000, 2003, 2006, and 2009. Included hospitalizations were of patients aged 0 to 20 years with a diagnosis of trisomy 13 or trisomy 18.

RESULTS: The number of hospitalizations for each trisomy type ranged from 846 to 907 per year for trisomy 13 (P = .77 for temporal trend) and 1036 to 1616 per year for trisomy 18 (P < .001 for temporal trend). Over one-third (36%) of the hospitalizations were of patients older than 1 year of age. Patients underwent a total of 2765 major therapeutic procedures, including creation of esophageal sphincter (6% of hospitalizations; mean age 23 months), repair of atrial and ventricular septal defects (4%; mean age 9 months), and procedures on tendons (4%; mean age 8 years).

CONCLUSIONS: Children with trisomy 13 and trisomy 18 receive significant inpatient hospital care. Despite the conventional understanding of these syndromes as lethal, a substantial number of children are living longer than 1 year and undergoing medical and surgical procedures as part of their treatment.

KEY WORDS

• child health services
• chronic conditions
• cohort studies
• congenital abnormalities/anomalies
• delivery of care

• Accepted December 22, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 37 of 68Article

Diagnostic Imaging and Negative Appendectomy Rates in Children: Effects of Age and Gender

BACKGROUND AND OBJECTIVES: Diagnostic imaging is often used in the evaluation of children with possible appendicitis. The utility of imaging may vary according to a patient’s age and gender. The objectives of this study were (1) to examine the use of computed tomography (CT) and ultrasound for age and gender subgroups of children undergoing an appendectomy; and (2) to study the association between imaging and negative appendectomy rates (NARs) among these subgroups.

METHODS: Retrospective review of children presenting to 40 US pediatric emergency departments from 2005 to 2009 (Pediatric Health Information Systems database). Children undergoing an appendectomy were stratified by age and gender for measuring the association between ultrasound and CT use and the outcome of negative appendectomy.

RESULTS: A total of 8 959 155 visits at 40 pediatric emergency departments were investigated; 55 227 children had appendicitis. The NAR was 3.6%. NARs were highest for children younger than 5 years (boys 16.8%, girls 14.6%) and girls older than 10 years (4.8%). At the institutional level, increased rates of diagnostic imaging (ultrasound and/or CT) were associated with lower NARs for all age and gender subgroups other than children younger than 5 years, The NAR was 1.2% for boys older than 5 years without any diagnostic imaging.

CONCLUSIONS: The impact of diagnostic imaging on negative appendectomy rate varies by age and gender. Diagnostic imaging for boys older than 5 years with suspected appendicitis has no meaningful impact on NAR. Diagnostic strategies for possible appendicitis should incorporate the risk of negative appendectomy by age and gender.

• appendicitis
• computed tomography
• ultrasound
• radiation
• pediatric
• diagnostic studies
• abdominal pain
• health services research
• male
• adolescent

• Accepted January 9, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 38 of 68Article

Association of Malodorous Urine With Urinary Tract Infection in Children Aged 1 to 36 Months

OBJECTIVE: To determine whether parental reporting of malodorous urine is associated with urinary tract infection (UTI) in children.

METHODS: We conducted a prospective consecutive cohort study in the emergency department of a pediatric hospital from July 31, 2009 to April 30, 2011. All children aged between 1 and 36 months for whom a urine culture was prescribed for suspected UTI (ie, unexplained fever, irritability, or vomiting) were assessed for eligibility. A standardized questionnaire was administered to the parents by a research assistant. The primary outcome measure was a UTI.

RESULTS: Three hundred ninety-six children were initially enrolled, but 65 were excluded a posteriori either because a urine culture, although prescribed, was not done (11), was collected by bag (39), and/or showed gross contamination (25). Therefore, 331 children were included in the final analysis. Their median age was 12 months (range, 1–36). Criteria for UTI were fulfilled in 51 (15%). A malodorous urine was reported by parents in 57% of children with UTI and in 32% of children without UTI. On logistic regression, malodorous urine was associated with UTI (odds ratio 2.83, 95% confidence interval: 1.54–5.20). This association remained statistically significant when adjusted for gender and the presence of vesicoureteral reflux (odds ratio 2.73, 95% confidence interval: 1.46–5.08).

CONCLUSIONS: Parental reporting of malodorous urine increases the probability of UTI among young children being evaluated for suspected UTI. However, this association is not strong enough to definitely rule in or out a diagnosis of UTI.

KEY WORDS

• urinary tract infection
• child
• odor
• urine

• Accepted January 18, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 39 of 68Article

Effects of Description of Options on Parental Perinatal Decision-Making

OBJECTIVE: To examine whether parents’ delivery room management decisions for extremely preterm infants are influenced by (1) the degree of detail with which options (comfort care [CC] or intensive care [IC]) are presented or (2) their order of presentation.

METHODS: A total of 309 volunteers, 18 to 55 years old, were each randomized to 1 of 4 groups: (1) detailed descriptions, CC presented first; (2) detailed descriptions, IC presented first; (3) brief descriptions, CC presented first; or (4) brief descriptions, IC presented first. Each received the description of a hypothetical delivery of a 23-week gestation infant and chose either IC or CC. Open-ended and structured questions elicited reasoning. Data were analyzed by χ² and logistic regression analysis.

RESULTS: Neither degree of detail, comparing groups 1+2 with 3+4 (37% vs 41%, odds ratio = 0.85, 95% confidence interval = 0.54–1.34, P = .48), nor order, comparing groups 1+3 with 2+4 (40% vs 37%, odds ratio = 0.88, 95% confidence interval = 0.56–1.39; P = .59), influenced the likelihood of choosing IC. Participants choosing IC were more likely to invoke sanctity of life and religiosity as personal values. Additional reasons for choosing IC were experiences with infants born at later gestational ages, giving the infant a chance, not watching their infant die, and equating CC with euthanasia. Some choosing CC wanted to avoid infant suffering.

CONCLUSIONS: The degree of detail and order of presentation had no effect on treatment decisions, suggesting that individuals bring well-articulated preexisting preferences to such decisions. Understanding beliefs and attitudes motivating these preferences can assist physicians in helping parents make informed decisions consistent with their values.

• decision-making
• extreme prematurity
• counseling
• palliative care
• intensive care

• Accepted December 22, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 40 of 68Article

Factors Related to Voluntary Parental Decision-Making in Pediatric Oncology

OBJECTIVE: The aim of the current study was to examine demographic and contextual correlates of voluntariness in parents making research or treatment decisions for their children with cancer.

METHODS: Participants included 184 parents of children with cancer who made a decision about enrolling the child in a research or treatment protocol within the previous 10 days. Parents completed questionnaires that assessed voluntariness, external influence by others, concern that the child’s care would be negatively affected if the parent did not agree, time pressure, information adequacy, and demographics.

RESULTS: Lower perceived voluntariness was associated with lower education, male gender, minority status, and not having previous experience with a similar decision. Parents who reported lower voluntariness also perceived more external influence and time pressure, had more concern about the child’s care being negatively affected if they declined, and perceived that they had either too much or not enough information about the decision. In a multivariate regression, education, minority status, gender, external influence, and too little information remained significantly associated with voluntariness.

CONCLUSIONS: Several groups of parents appear to be at risk for decreased voluntariness when making research or treatment decisions for their seriously ill children, including fathers, nonwhite parents, and those with less education. Parental voluntariness may be enhanced by helping parents to mitigate the effects of unhelpful or unwanted influences by others and ensuring that their information needs are met.

• informed consent
• parental permission
• decision-making
• pediatrics
• oncology
• ethics

• Accepted January 12, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 41 of 68Article

The Dance Between Attending Physicians and Senior Residents as Teachers and Supervisors

OBJECTIVE: To examine how attending physicians and senior residents negotiated shared responsibilities for teaching and supervising on clinical work rounds.

METHODS: As part of a larger ethnographic field study, we observed clinical work rounds on a General Pediatrics ward over 8 months, and interviewed 14 of 18 attending physicians and 9 of 11 senior residents whom we observed. Struck by the frequency of 2 codes in that data set (“stand back” and “step up”), we used the metaphor of a dance as an analytic strategy for understanding the dynamic relationship between attending physicians and senior residents.

RESULTS: Like a traditional dance with a priori choreography, and consistent with the traditional premise in graduate medical education, attending physicians frequently “stood back” and senior residents, accordingly, “stepped up” and took on teaching and supervising responsibilities. Less often, both attending physicians and senior residents assumed the lead, or attending physicians stepped up rather than entrust senior residents. The complex clinical context sometimes changed the choreography. Attending physicians and senior residents understood their mutual responsibilities but were not bound by them; they improvised to maintain high-quality patient care.

CONCLUSIONS: The metaphor of a dance enabled us to better understand not only how attending physicians and senior residents negotiate shared responsibilities for teaching and supervision on clinical work rounds, but also how the clinical context impacts this negotiation. A better understanding of this negotiated relationship may help to clarify assumptions and set realistic expectations for what it might take for senior residents to assume progressive responsibility for these responsibilities in today’s clinical context.

• clinical education/teaching
• resident education/training
• pediatric residents
• competency-based education

• Accepted December 22, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 42 of 68Article

Tenfold Medication Errors: 5 Years’ Experience at a University-Affiliated Pediatric Hospital

BACKGROUND AND OBJECTIVES: Tenfold medication errors are a significant source of risk to pediatric patients. This may be because of wide variations in age, weight, dosing ranges, and off-label practices, but few studies exclusively devoted to examining pediatric 10-fold error have identified the circumstances and mechanisms that lead to such errors. We examined all 10-fold medication errors reported within an academic, university-affiliated pediatric hospital to make recommendations for future initiatives that could improve medication safety in pediatric practice.

METHODS: We retrospectively evaluated all medication-related incident reports submitted to a voluntary safety-reporting database over a 5-year period for reports describing 10-fold medication error. Main outcome measures comprised severity of error, drugs and drug classes involved, 10-fold medication error enablers, mechanisms, and contributing causes.

RESULTS: From 6643 medication-related safety reports, 252 10-fold medication errors were identified at a mean reporting rate of 0.062 per 100 total patient days. Morphine was the most frequently reported medication, and opioids were the most frequently reported drug class. Twenty-two reports described patient harm. Intravenous formulations, paper ordering, and drug-delivery pumps were frequent error enablers. Errors of dose calculation, documentation of decimal points, and confusion with zeroes were frequent contributing causes to 10-fold medication error.

CONCLUSIONS: This study exclusively and comprehensively examined 10-fold medication errors over a prolonged time in pediatric inpatients. We discuss recommendations of vigilance for specific drugs and standardized order sets for opioids and antibiotics, and identify the administering phase of the medication process as a high-risk practice that can result in pediatric 10-fold medication error.

• drug error
• 10-fold medication error
• pediatrics
• patient safety

• Accepted January 5, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 43 of 68Review Article

The Effect of the School Environment on the Emotional Health of Adolescents: A Systematic Review

BACKGROUND AND OBJECTIVES: The evidence base for the importance of the school environment for adolescent emotional health has never been systematically reviewed. We aimed to synthesize the evidence for the effect on adolescent emotional health of (1) interventions targeting the school environment and (2) the school environment in cohort studies.

METHODS: Searches of Medline, Embase, PsychINFO, CINAHL, ERIC, the Social Citation Index, and the gray literature were conducted. Criteria for inclusion were (1) cohort or controlled trial designs, (2) participants aged 11 to 18 years, (3) emotional health outcomes, and (4) school environment exposure or intervention. Relevant studies were retrieved and data extracted by 2 independent reviewers.

RESULTS: Nine papers reporting 5 controlled trials were reviewed, along with 30 cohort papers reporting 23 studies. Two nonrandomized trials found some evidence that a supportive school environment improved student emotional health, but 3 randomized controlled trials did not. Six (20%) cohort papers examined school-level factors but found no effect. There was some evidence that individual perceptions of school connectedness and teacher support predict future emotional health. Multilevel studies showed school effects were smaller than individual-level effects. Methodological shortcomings were common.

CONCLUSIONS: There is limited evidence that the school environment has a major influence on adolescent mental health, although student perceptions of teacher support and school connectedness are associated with better emotional health. More studies measuring school-level factors are needed. Randomized controlled trials evaluating 1 or 2 environmental components may have more success in establishing effective and feasible interventions compared with complex whole-school programs.

• adolescence
• school environment
• emotional health
• depression
• mental health

• Accepted December 22, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 44 of 68State-of-the-Art Review Article

The Human Microbiome and Its Potential Importance to Pediatrics

The human body is home to more than 1 trillion microbes, with the gastrointestinal tract alone harboring a diverse array of commensal microbes that are believed to contribute to host nutrition, developmental regulation of intestinal angiogenesis, protection from pathogens, and development of the immune response. Recent advances in genome sequencing technologies and metagenomic analysis are providing a broader understanding of these resident microbes and highlighting differences between healthy and disease states. The aim of this review is to provide a detailed summary of current pediatric microbiome studies in the literature, in addition to highlighting recent findings and advancements in studies of the adult microbiome. This review also seeks to elucidate the development of, and factors that could lead to changes in, the composition and function of the human microbiome.

KEY WORDS

• human microbiome
• metagenome
• microbiota
• pediatric diseases
• dysbiosis
• probiotic

• Accepted January 4, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 45 of 68Special Article

2011 Joseph W. St Geme Jr Lecture: Five Things I'd Like to See Changed in American Pediatrics, Five Lessons I've Learned

OBJECTIVE: In response to limitations in access to subspecialty care, I present personal observations and suggestions related to education of future pediatricians regarding development of critical thinking skills, care of complex and chronically ill patients, development of empathy, and restoration of responsibility that may help ameliorate this serious problem. Toward this end, I also offer 1 approach, a 24/7 telephone consultation network, for enriching interaction of primary care providers (PCPs) and subspecialists who can potentially provide rapid access to needed advice, reduce demand for subspecialty appointments, bolster decision-making and expertise, and realign resources with need.

METHODS: Data were obtained from 579 requests by PCPs for telephone consultation by subspecialists in 8 areas (including child psychiatry).

RESULTS: Of calls, 27% took <5 minutes and 79% took 5 to 15 minutes. Of calls, 28% resulted in a clinic visit; 8% prompted hospital transfer, hospital admission, or referral to an emergency department; and the remaining 64% resulted in continued management by PCP with reinforcement of the plan. Assuming most inquiries would have resulted in referral to a subspecialist were there no telephone consultation, we estimated that 70% (8+64%) of consultations realigned resources with need, resulting in large saving of unnecessary clinic visits, travel, expense to families, lost days at work, or missed school.

CONCLUSIONS: Development of rapid telephone consultation networks could provide increased access to care for those children in greatest need, use limited resources more efficiently, foster collegial and productive relationships between medical providers, and increase expertise of PCPs and subspecialists.

KEY WORDS

• medical education
• access to health care
• chronic disease
• remote consultation
• decision support

• Accepted February 16, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 46 of 68Special Article

Developing the 2011 Integrated Pediatric Guidelines for Cardiovascular Risk Reduction

This article reviews aspects of development of the recently released “Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents” for pediatric care providers that remain in the area of human judgment. Discussed will be the context in which the guidelines were developed, the formal evidence review process, a consideration of how quality grades were established, key social/ethical issues that the panel confronted, and a critique of the final work with recommendations for future guideline development. Lessons learned are that both a formal evidence review process is essential to developing a credible document, and human judgment is critical to producing a meaningful result. Guideline development is a dynamic process that must be continuously self-critical as new evidence is acquired and sociopolitical and environmental contexts evolve.

KEY WORDS

• guidelines
• evidence-based medicine
• risk factors

• Accepted January 4, 2012.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 47 of 68Commentary

·  Abstract 48 of 68Commentary

·  Abstract 49 of 68Commentary

·  Abstract 50 of 68Commentary

·  Abstract 51 of 68Quality Report

Effectiveness of Antimicrobial Guidelines for Community-Acquired Pneumonia in Children

OBJECTIVE: To assess the effectiveness of guidelines and education on empirical therapy for community-acquired pneumonia.

METHODS: Administrative records for children with a primary diagnosis of pneumonia from January 2007 to September 2009 were reviewed. Antimicrobial use was measured monthly over 3 periods: (1) before creation of an antimicrobial stewardship task force (ASTF), (2) after ASTF formation but before release of guidelines for antimicrobial use, and (3) after guideline release. Antimicrobial use over time was assessed by using quasi-binomial logistic regression models that incorporated interrupted events, seasonality, and autocorrelation. Allowing calculation of immediate changes due to specific interventions and trends in use over each time period. The primary outcome was use of ampicillin as recommended in the guidelines versus ceftriaxone, the historical standard. Secondary outcomes included other antimicrobial use, length of stay, mortality, and readmission.

RESULTS: One thousand two hundred forty-six children met study criteria. Ampicillin use increased from 2% at baseline to 6% after ASTF formation and 44% after guideline release. Ceftriaxone use increased slightly (from 56% to 59%) after ASTF formation but decreased to 28% after guideline release. An immediate change in prescription occurred in the month after guideline publication and remained stable over the following year.

CONCLUSIONS: Guidelines and education can have an impact on antimicrobial use in the pediatric setting. Although the optimal strategies for pediatric antimicrobial stewardship programs still are being determined, we believe that our approach offers an inexpensive and low-risk step in the right direction.

KEY WORDS

• antibiotic use
• pneumonia

• Accepted November 16, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 52 of 68Quality Report

Long-term Reduction in Adverse Drug Events: An Evidence-Based Improvement Model

OBJECTIVES: To develop and test an evidence-based model for reducing medication errors and harm in hospitalized children.

METHODS: Prospective interrupted time series study evaluating the effectiveness of a multifaceted, staged intervention over 4 years in a major urban pediatric referral hospital. Guidelines for safe pediatric prescribing were implemented by using an evidence-based model. Key components included early clinician engagement and improved multidisciplinary communication, consensus development, interactive education, and timely data feedback by using iterative Plan-Do-Study-Act cycles. Impact on medication error and harm (adverse drug events, [ADEs]) was measured by using standard definitions and a multimethod approach. Prospective data from voluntary reports by nursing, medical, and pharmacy staff and intensive chart review were combined. All data were reviewed by a multidisciplinary panel, including causality assessments for ADEs.

RESULTS: Reviewed over 3 time periods were 1011 patients with 6651 medication orders. Total ADEs decreased by > 50% in the first year and this was maintained at 4 years. Greatest improvements were in potential ADEs, which decreased from 12.26 per 100 patients at baseline to 4.60 per 100 patients at 4 years (P < .05). Total medication errors decreased from 4.51 per 100 orders at baseline to 2.78 per 100 orders at 4 years (P < .05). Prescribing errors decreased by 65%, from 4.07 per 100 orders at baseline to 2.05 orders at 4 years (P < .05).

CONCLUSIONS: A multifaceted, evidence-based model for safe prescribing guideline implementation, engaging multidisciplinary clinicians, was effective in reducing medication error and harm in hospitalized children, resulting in sustained long-term improvement.

KEY WORDS

• medication errors
• drug toxicity
• health care outcome and process assessment
• evidence-based medicine
• practice guidelines as topic
• in-service training
• continuing medical education
• health services research
• translational research
• interdisciplinary communication

• Accepted November 28, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 53 of 68Case Report

More Codeine Fatalities After Tonsillectomy in North American Children

In 2009 we reported the fatal case of a toddler who had received codeine after adenotonsillectomy for obstructive sleep apnea syndrome. The child was an ultra-rapid metabolizer of cytochrome P4502D6 (CYP2D6). We now report 3 additional fatal or life-threatening cases from North America. In the 2 fatal cases, functional gene duplications encoding for CYP2D6 caused a significantly greater production of potent morphine from its parent drug, codeine. A severe case of respiratory depression in an extensive metabolizer is also noted. These cases demonstrate that analgesia with codeine or other opioids that use the CYP2D6 pathway after adenotonsillectomy may not be safe in young children with obstructive sleep apnea syndrome.

KEY WORDS

• codeine
• tonsillectomy
• sleep apnea

• Accepted December 6, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 54 of 68Case Report

Excessive Blinking and Ataxia in a Child With Occult Neuroblastoma and Voltage-Gated Potassium Channel Antibodies

A previously healthy 9-year-old girl presented with a 10-day history of slowly progressive unsteadiness, slurred speech, and behavior change. On examination there was cerebellar ataxia and dysarthria, excessive blinking, subtle perioral myoclonus, and labile mood. The finding of oligoclonal bands in the cerebrospinal fluid prompted paraneoplastic serological evaluation and search for an occult neural crest tumor. Antineuronal nuclear autoantibody type 1 (anti-Hu) and voltage-gated potassium channel complex antibodies were detected in serum. Metaiodobenzylguanidine scan and computed tomography scan of the abdomen showed a localized abdominal mass in the region of the porta hepatis. A diagnosis of occult neuroblastoma was made. Resection of the stage 1 neuroblastoma and treatment with pulsed corticosteroids resulted in resolution of all symptoms and signs. Excessive blinking has rarely been described with neuroblastoma, and, when it is not an isolated finding, it may be a useful clue to this paraneoplastic syndrome. Although voltage-gated potassium channel complex autoimmunity has not been described previously in the setting of neuroblastoma, it is associated with a spectrum of paraneoplastic neurologic manifestations in adults, including peripheral nerve hyperexcitability disorders.

KEY WORDS

• neuroblastoma
• autoimmune
• excessive blinking
• cerebellar ataxia
• VGKC antibody

• Accepted December 20, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 55 of 68Case Report

Neonatal Sweet Syndrome: A Potential Marker of Serious Systemic Illness

Sweet syndrome is an inflammatory disease characterized by fever and painful erythematous plaques with a dermal neutrophilic infiltrate. It is most common in adults, where it is often parainflammatory or paraneoplastic, but is rare in children. We describe 3 cases of neonatal Sweet syndrome, including 1 patient who had myelodysplastic syndrome and immunodeficiency, the first report of a premalignancy underlying infantile Sweet syndrome. We reviewed the literature on patients presenting with neutrophilic dermatosis in the first 6 months of life. Of 20 cases, 6 had a probable viral etiology, 4 primary immunodeficiencies, 3 neonatal lupus syndrome, 1 gastrointestinal involvement, 1 HIV, and 5 probable genetic cases. Three of these had chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome, caused by mutations in the PSMB8 gene. Most children who presented within the first 6 weeks of life had either a serious underlying condition, such as primary immunodeficiency, or a genetic Sweet syndrome, with 2 fatalities among this latter group. The outcome of postinfective cases was good. Extracutaneous involvement was unusual, whereas postinflammatory scarring and cutis laxa occurred in a minority of patients. In conclusion, Sweet syndrome in the neonatal period often heralds a serious underlying disorder and requires thorough investigation.

KEY WORDS

• Sweet syndrome
• neutrophilic dermatosis
• myelodysplastic syndrome
• neonatal
• primary immunodeficiency
• chronic granulomatous disease

• Accepted December 6, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 56 of 68Case Report

Severe Pulmonary Hypertension With Therapeutic l-Lysine Ibuprofen in 2 Preterm Neonates

Persistently patent ductus arteriosus (PDA), affecting approximately one-third of all very low birth weight infants, can lead to significant morbidity and mortality. Recently, ibuprofen has been recommended over indomethacin to close PDAs because of a reduction in risk of necrotizing enterocolitis. Pulmonary hypertension is a rare but potentially fatal complication of ibuprofen administration in preterm infants. We report 2 infants who developed this complication after receiving therapeutic l-lysine ibuprofen preparation for the PDA closure. The first infant, 1 of twins weighing 640 g, was born at 24 weeks’ gestation. The second infant, born at 26 weeks’ gestation, was small for gestational age, weighing 439 g. In both cases, ibuprofen was initiated after echocardiographic confirmation of a moderate-sized to large PDA and an otherwise normal intracardiac anatomy. Both infants had echocardiographic evidence of increased pulmonary vascular resistance but shunting across the PDA was left to right. The infants deteriorated within 48 to 72 hours, and repeat echocardiograms revealed evidence of severe pulmonary hypertension. Both infants died of refractory hypotension and hypoxemia. When considering the use of ibuprofen therapy for PDA closure, clinicians should keep in mind the potential serious complication of pulmonary hypertension, even if a shunt across the PDA is left to right.

KEY WORDS

• preterm infants
• patent ductus arteriosis
• ibuprofen
• indomethacin

• Accepted November 17, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 57 of 68Case Report

Postnatal Virilization Mimicking 21-Hydroxylase Deficiency in 3 Very Premature Infants

Premature infants are known to have elevated 17-hydroxyprogesterone and adrenal androgen concentrations immediately after birth, but the levels decrease rapidly. Virilization of normal premature female infants as a result of these high androgens has not been described. Three premature female infants born at 24 to 25 weeks’ gestation, with birth weights 550 to 880 g and significant neonatal complications were noted to develop clitoromegaly 2 weeks to 3 months after birth. All 3 had elevated 17-hydroxyprogesterone >100 nmol/L and testosterone >3 nmol/L concentrations. All were treated as simple virilizing 21-hydroxylase deficiency, but subsequent genetic analysis revealed no CYP21 mutations. Follow-up after discontinuation of treatment revealed no recurrent virilization and normal adrenal steroid levels. Postnatal virilization in sick premature girls may occur, and investigations may suggest 21-hydroxylase deficiency. Genetic analysis of CYP21 should be performed before the diagnosis is confirmed. Further studies are needed to better document the natural history and possible causes of postnatal adrenal androgen secretion in sick premature infants.

KEY WORDS

• postnatal virilization
• prematurity
• 17-hydroxyprogesterone
• adrenal androgens

• Accepted November 17, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 58 of 68Case Report

Profound Neonatal Hypoglycemia and Lactic Acidosis Caused by Pyridoxine-Dependent Epilepsy

Pyridoxine-dependent epilepsy (PDE) was first described in 1954. The ALDH7A1 gene mutations resulting in α-aminoadipic semialdehyde dehydrogenase deficiency as a cause of PDE was identified only in 2005. Neonatal epileptic encephalopathy is the presenting feature in >50% of patients with classic PDE. We report the case of a 13-month-old girl with profound neonatal hypoglycemia (0.6 mmol/L; reference range >2.4), lactic acidosis (11 mmol/L; reference range <2), and bilateral symmetrical temporal lobe hemorrhages and thalamic changes on cranial MRI. She developed multifocal and myoclonic seizures refractory to multiple antiepileptic drugs that responded to pyridoxine. The diagnosis of α-aminoadipic semialdehyde dehydrogenase deficiency was confirmed based on the elevated urinary α-aminoadipic semialdehyde excretion, compound heterozygosity for a known splice mutation c.834G>A (p.Val278Val), and a novel putative pathogenic missense mutation c.1192G>C (p.Gly398Arg) in the ALDH7A1 gene. She has been seizure-free since 1.5 months of age on treatment with pyridoxine alone. She has motor delay and central hypotonia but normal language and social development at the age of 13 months. This case is the first description of a patient with PDE due to mutations in the ALDH7A1 gene who presented with profound neonatal hypoglycemia and lactic acidosis masquerading as a neonatal-onset gluconeogenesis defect. PDE should be included in the differential diagnosis of hypoglycemia and lactic acidosis in addition to medically refractory neonatal seizures.

KEY WORDS

• pyridoxine-dependent epilepsy
• myoclonic epilepsy
• hypoxic ischemic encephalopathy
• neonatal hypoglycemia
• lactic acidosis
• ALDH7A1 deficiency

• Accepted December 22, 2011.

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 59 of 68Letter to the Editor

·  Abstract 60 of 68Letter to the Editor

·  Abstract 61 of 68Letter to the Editor

·  Abstract 62 of 68Letter to the Editor

·  Abstract 63 of 68Letter to the Editor

·  Abstract 64 of 68Letter to the Editor

·  Abstract 65 of 68Erratum

·  Abstract 66 of 68Erratum

·  Abstract 67 of 68From the American Academy of PediatricsClinical Report

Home Care of Children and Youth With Complex Health Care Needs and Technology Dependencies

Children and youth with complex medical issues, especially those with technology dependencies, experience frequent and often lengthy hospitalizations. Hospital discharges for these children can be a complicated process that requires a deliberate, multistep approach. In addition to successful discharges to home, it is essential that pediatric providers develop and implement an interdisciplinary and coordinated plan of care that addresses the child’s ongoing health care needs. The goal is to ensure that each child remains healthy, thrives, and obtains optimal medical home and developmental supports that promote ongoing care at home and minimize recurrent hospitalizations. This clinical report presents an approach to discharging the child with complex medical needs with technology dependencies from hospital to home and then continually addressing the needs of the child and family in the home environment.

• children and youth with special health care needs
• discharge planning
• habilitative services
• home care
• medical home
• technology dependency
• tube feedings

• Copyright © 2012 by the American Academy of Pediatrics

·  Abstract 68 of 68From the American Academy of PediatricsClinical Report

Management of Neonates With Suspected or Proven Early-Onset Bacterial Sepsis

With improved obstetrical management and evidence-based use of intrapartum antimicrobial therapy, early-onset neonatal sepsis is becoming less frequent. However, early-onset sepsis remains one of the most common causes of neonatal morbidity and mortality in the preterm population. The identification of neonates at risk for early-onset sepsis is frequently based on a constellation of perinatal risk factors that are neither sensitive nor specific. Furthermore, diagnostic tests for neonatal sepsis have a poor positive predictive accuracy. As a result, clinicians often treat well-appearing infants for extended periods of time, even when bacterial cultures are negative. The optimal treatment of infants with suspected early-onset sepsis is broad-spectrum antimicrobial agents (ampicillin and an aminoglycoside). Once a pathogen is identified, antimicrobial therapy should be narrowed (unless synergism is needed). Recent data suggest an association between prolonged empirical treatment of preterm infants (≥5 days) with broad-spectrum antibiotics and higher risks of late onset sepsis, necrotizing enterocolitis, and mortality. To reduce these risks, antimicrobial therapy should be discontinued at 48 hours in clinical situations in which the probability of sepsis is low. The purpose of this clinical report is to provide a practical and, when possible, evidence-based approach to the management of infants with suspected or proven early-onset sepsis.

• early-onset sepsis
• antimicrobial therapy
• group B streptococcus
• meningitis
• gastric aspirate
• tracheal aspirate
• chorioamnionitis
• sepsis screen
• blood culture
• lumbar puncture
• urine culture
• body surface cultures
• white blood count
• acute phase reactants
• prevention strategies

• Copyright © 2012 by the American Academy of Pediatrics