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1.  Early Puberty, Negative Peer Influence, and Problem Behaviors in Adolescent Girls 
Pediatrics  2014;133(1):7-14.
OBJECTIVE:
To determine how early puberty and peer deviance relate to trajectories of aggressive and delinquent behavior in early adolescence and whether these relationships differ by race/ethnicity.
METHODS:
In this longitudinal study, 2607 girls from 3 metropolitan areas and their parents were interviewed at ages 11, 13, and 16 years. Girls reported on their age of onset of menarche, best friend’s deviant behavior, delinquency, and physical, relational, and nonphysical aggression. Parents provided information on family sociodemographic characteristics and girls’ race/ethnicity.
RESULTS:
Sixteen percent of girls were classified as early maturers (defined by onset of menarche before age 11 years). Overall, relational and nonphysical aggression increased from age 11 to age 16, whereas delinquency and physical aggression remained stable. Early puberty was associated with elevated delinquency and physical aggression at age 11. The relationship with early puberty diminished over time for physical aggression but not for delinquency. Best friend’s deviant behavior was linked with higher levels of all problem behaviors, but the effect lessened over time for most outcomes. Early puberty was associated with a stronger link between best friend’s deviance and delinquency, suggesting increased vulnerability to negative peer influences among early-maturing girls. A similar vulnerability was observed for relational and nonphysical aggression among girls in the “other” racial/ethnic minority group only.
CONCLUSIONS:
Early puberty and friends’ deviance may increase the risk of problem behavior in young adolescent girls. Although many of these associations dissipate over time, early-maturing girls are at risk of persistently higher delinquency and stronger negative peer influences.
doi:10.1542/peds.2013-0628
PMCID: PMC3876177  PMID: 24324002
puberty; peer influence; problem behavior; racial/ethnic differences
2.  Comorbidity Clusters in Autism Spectrum Disorders: An Electronic Health Record Time-Series Analysis 
Pediatrics  2014;133(1):e54-e63.
OBJECTIVE:
The distinct trajectories of patients with autism spectrum disorders (ASDs) have not been extensively studied, particularly regarding clinical manifestations beyond the neurobehavioral criteria from the Diagnostic and Statistical Manual of Mental Disorders. The objective of this study was to investigate the patterns of co-occurrence of medical comorbidities in ASDs.
METHODS:
International Classification of Diseases, Ninth Revision codes from patients aged at least 15 years and a diagnosis of ASD were obtained from electronic medical records. These codes were aggregated by using phenotype-wide association studies categories and processed into 1350-dimensional vectors describing the counts of the most common categories in 6-month blocks between the ages of 0 to 15. Hierarchical clustering was used to identify subgroups with distinct courses.
RESULTS:
Four subgroups were identified. The first was characterized by seizures (n = 120, subgroup prevalence 77.5%). The second (n = 197) was characterized by multisystem disorders including gastrointestinal disorders (prevalence 24.3%) and auditory disorders and infections (prevalence 87.8%), and the third was characterized by psychiatric disorders (n = 212, prevalence 33.0%). The last group (n = 4316) could not be further resolved. The prevalence of psychiatric disorders was uncorrelated with seizure activity (P = .17), but a significant correlation existed between gastrointestinal disorders and seizures (P < .001). The correlation results were replicated by using a second sample of 496 individuals from a different geographic region.
CONCLUSIONS:
Three distinct patterns of medical trajectories were identified by unsupervised clustering of electronic health record diagnoses. These may point to distinct etiologies with different genetic and environmental contributions. Additional clinical and molecular characterizations will be required to further delineate these subgroups.
doi:10.1542/peds.2013-0819
PMCID: PMC3876178  PMID: 24323995
autism; seizure; psychiatric disorders; comorbidity; clustering
3.  Addressing the Mental Health Needs of Pregnant and Parenting Adolescents 
Pediatrics  2014;133(1):114-122.
Adolescent parenthood is associated with a range of adverse outcomes for young mothers, including mental health problems such as depression, substance abuse, and posttraumatic stress disorder. Teen mothers are also more likely to be impoverished and reside in communities and families that are socially and economically disadvantaged. These circumstances can adversely affect maternal mental health, parenting, and behavior outcomes for their children. In this report, we provide an overview of the mental health challenges associated with teen parenthood, barriers that often prevent teen mothers from seeking mental health services, and interventions for this vulnerable population that can be integrated into primary care services. Pediatricians in the primary care setting are in a unique position to address the mental health needs of adolescent parents because teens often turn to them first for assistance with emotional and behavioral concerns. Consequently, pediatricians can play a pivotal role in facilitating and encouraging teen parents’ engagement in mental health treatment.
doi:10.1542/peds.2013-0927
PMCID: PMC3876179  PMID: 24298010
teen pregnancy; teen parenting; mental health; mental health interventions
4.  Screening for Behavioral Health Issues in Children Enrolled in Massachusetts Medicaid 
Pediatrics  2014;133(1):46-54.
OBJECTIVES:
To understand mandated behavioral health (BH) screening in Massachusetts Medicaid including characteristics of screened children, predictors of positive screens, and whether screening identifies children without a previous BH history.
METHODS:
Massachusetts mandated BH screening in particularly among underidentified groups. 2008. Providers used a billing code and modifier to indicate a completed screen and whether a BH need was identified. Using MassHealth claims data, children with ≥300 days of eligibility in fiscal year (FY) 2009 were identified and categorized into groups based on first use of the modifier, screening code, or claim. Bivariate analyses were conducted to determine differences among groups. BH history was examined by limiting the sample to those continuously enrolled in FY 2008 and 2009. Multivariate logistic regression was used to determine predictors of positive screens.
RESULTS:
Of 355 490 eligible children, 46% had evidence of screening. Of those with modifiers, 12% were positive. Among continuously enrolled children (FY 2008 and FY 2009) with evidence of screening, 43% with positive modifiers had no BH history. This “newly identified” group were more likely to be female, younger, minority, and from rural residences (P < .0001). Among children with modifiers; gender (male), age (5–7), being in foster care, recent BH history, and Hispanic ethnicity predicted having a positive modifier.
CONCLUSIONS:
The high rate of newly identified Medicaid children with a BH need suggests that screening is performing well, particularly among underidentified groups. To better assess screening value, future work on cost-effectiveness and the impact on subsequent mental health treatment is needed.
doi:10.1542/peds.2013-1180
PMCID: PMC3876180  PMID: 24298005
behavioral health; screening; primary care; medicaid
5.  Accuracy of Brief Screening Tools for Identifying Postpartum Depression Among Adolescent Mothers 
Pediatrics  2014;133(1):e45-e53.
OBJECTIVE:
To evaluate the accuracy of the Edinburgh Postnatal Depression Scale (EPDS) and 3 subscales for identifying postpartum depression among primiparous adolescent mothers.
METHODS:
Mothers enrolled in a randomized controlled trial to prevent postpartum depression completed a psychiatric diagnostic interview and the 10-item EPDS at 6 weeks, 3 months, and 6 months postpartum. Three subscales of the EPDS were assessed as brief screening tools: 3-item anxiety subscale (EPDS-3), 7-item depressive symptoms subscale (EPDS-7), and 2-item subscale (EPDS-2) that resemble the Patient Health Questionnaire-2. Receiver operating characteristic curves and the areas under the curves for each tool were compared to assess accuracy. The sensitivities and specificities of each screening tool were calculated in comparison with diagnostic criteria for a major depressive disorder. Repeated-measures longitudinal analytical techniques were used.
RESULTS:
A total of 106 women contributed 289 postpartum visits; 18% of the women met criteria for incident postpartum depression by psychiatric diagnostic interview. When used as continuous measures, the full EPDS, EPDS-7, and EPDS-2 performed equally well (area under the curve >0.9). Optimal cutoff scores for a positive depression screen for the EPDS and EPDS-7 were lower (≥9 and ≥7, respectively) than currently recommended cutoff scores (≥10). At optimal cutoff scores, the EPDS and EPDS-7 both had sensitivities of 90% and specificities of >85%.
CONCLUSIONS:
The EPDS, EPDS-7, and EPDS-2 are highly accurate at identifying postpartum depression among adolescent mothers. In primary care pediatric settings, the EPDS and its shorter subscales have potential for use as effective depression screening tools.
doi:10.1542/peds.2013-1628
PMCID: PMC3876181  PMID: 24344102
teenage; pregnancy; screening; postpartum depression; validity
6.  Validation of the Modified Checklist for Autism in Toddlers, Revised With Follow-up (M-CHAT-R/F) 
Pediatrics  2014;133(1):37-45.
OBJECTIVE:
This study validates the Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F), a screening tool for low-risk toddlers, and demonstrates improved utility compared with the original M-CHAT.
METHODS:
Toddlers (N = 16 071) were screened during 18- and 24-month well-child care visits in metropolitan Atlanta and Connecticut. Parents of toddlers at risk on M-CHAT-R completed follow-up; those who continued to show risk were evaluated.
RESULTS:
The reliability and validity of the M-CHAT-R/F were demonstrated, and optimal scoring was determined by using receiver operating characteristic curves. Children whose total score was ≥3 initially and ≥2 after follow-up had a 47.5% risk of being diagnosed with autism spectrum disorder (ASD; confidence interval [95% CI]: 0.41–0.54) and a 94.6% risk of any developmental delay or concern (95% CI: 0.92–0.98). Total score was more effective than alternative scores. An algorithm based on 3 risk levels is recommended to maximize clinical utility and to reduce age of diagnosis and onset of early intervention. The M-CHAT-R detects ASD at a higher rate compared with the M-CHAT while also reducing the number of children needing the follow-up. Children in the current study were diagnosed 2 years younger than the national median age of diagnosis.
CONCLUSIONS:
The M-CHAT-R/F detects many cases of ASD in toddlers; physicians using the 2-stage screener can be confident that most screen-positive cases warrant evaluation and referral for early intervention. Widespread implementation of universal screening can lower the age of ASD diagnosis by 2 years compared with recent surveillance findings, increasing time available for early intervention.
doi:10.1542/peds.2013-1813
PMCID: PMC3876182  PMID: 24366990
autism; screening; toddlers
7.  Characteristics of Youth Seeking Emergency Care for Assault Injuries 
Pediatrics  2014;133(1):e96-e105.
OBJECTIVE:
To characterize youth seeking care for assault injuries, the context of violence, and previous emergency department (ED) service utilization to inform ED-based injury prevention.
METHODS:
A consecutive sample of youth (14–24) presenting to an urban ED with an assault injury completed a survey of partner violence, gun/knife victimization, gang membership, and context of the fight.
RESULTS:
A total of 925 youth entered the ED with an assault injury; 718 completed the survey (15.4% refused); 730 comparison youth were sampled. The fights leading to the ED visit occurred at home (37.6%) or on streets (30.4%), and were commonly with a known person (68.3%). Fights were caused by issues of territory (23.3%) and retaliation (8.9%); 20.8% of youth reported substance use before the fight. The assault-injured group reported more peer/partner violence and more gun experiences. Assault-injured youth reported higher past ED utilization for assault (odds ratio [OR]: 2.16) or mental health reasons (OR: 7.98). Regression analysis found the assault-injured youth had more frequent weapon use (OR: 1.25) and substance misuse (OR: 1.41).
CONCLUSIONS:
Assault-injured youth seeking ED care report higher levels of previous violence, weapon experience, and substance use compared with a comparison group seeking care for other complaints. Almost 10% of assault-injured youth had another fight-related ED visit in the previous year, and ∼5% had an ED visit for mental health. Most fights were with people known to them and for well-defined reasons, and were therefore likely preventable. The ED is a critical time to interact with youth to prevent future morbidity.
doi:10.1542/peds.2013-1864
PMCID: PMC3876183  PMID: 24323994
youth; assault; injuries; alcohol; emergency department
8.  Association Between Pediatric Clinical Trials and Global Burden of Disease 
Pediatrics  2014;133(1):78-87.
BACKGROUND:
The allocation of research resources should favor conditions responsible for the greatest disease burden. This is particularly important in pediatric populations, which have been underrepresented in clinical research. Our aim was to measure the association between the focus of pediatric clinical trials and burden of disease and to identify neglected clinical domains.
METHODS:
We performed a cross-sectional study of clinical trials by using trial records in ClinicalTrials.gov. All trials started in 2006 or after and studying patient-level interventions in pediatric populations were included. Age-specific measures of disease burden were obtained for 21 separate conditions for high-, middle-, and low-income countries. We measured the correlation between number of pediatric clinical trials and disease burden for each condition.
RESULTS:
Neuropsychiatric conditions and infectious diseases were the most studied conditions globally in terms of number of trials (874 and 847 trials, respectively), while intentional injuries (5 trials) and maternal conditions (4 trials) were the least studied. Clinical trials were only moderately correlated with global disease burden (r = 0.58, P = .006). Correlations were also moderate within each of the country income levels, but lowest in low-income countries (r = .47, P = .03). Globally, the conditions most understudied relative to disease burden were injuries (–260 trials for unintentional injuries and –160 trials for intentional injuries), nutritional deficiencies (–175 trials), and respiratory infections (–171 trials).
CONCLUSIONS:
Pediatric clinical trial activity is only moderately associated with pediatric burden of disease, and least associated in low-income countries. The mismatch between clinical trials and disease burden identifies key clinical areas for focus and investment.
doi:10.1542/peds.2013-2567
PMCID: PMC3876184  PMID: 24344112
clinical trials; burden of disease; pediatric research
9.  Two-Year Impact of the Alternative Quality Contract on Pediatric Health Care Quality and Spending 
Pediatrics  2014;133(1):96-104.
OBJECTIVE:
To examine the 2-year effect of Blue Cross Blue Shield of Massachusetts’ global budget arrangement, the Alternative Quality Contract (AQC), on pediatric quality and spending for children with special health care needs (CSHCN) and non-CSHCN.
METHODS:
Using a difference-in-differences approach, we compared quality and spending trends for 126 975 unique 0- to 21-year-olds receiving care from AQC groups with 415 331 propensity-matched patients receiving care from non-AQC groups; 23% of enrollees were CSHCN. We compared quality and spending pre (2006–2008) and post (2009–2010) AQC implementation, adjusting analyses for age, gender, health risk score, and secular trends. Pediatric outcome measures included 4 preventive and 2 acute care measures tied to pay-for-performance (P4P), 3 asthma and 2 attention-deficit/hyperactivity disorder quality measures not tied to P4P, and average total annual medical spending.
RESULTS:
During the first 2 years of the AQC, pediatric care quality tied to P4P increased by +1.8% for CSHCN (P < .001) and +1.2% for non-CSHCN (P < .001) for AQC versus non-AQC groups; quality measures not tied to P4P showed no significant changes. Average total annual medical spending was ∼5 times greater for CSHCN than non-CSHCN; there was no significant impact of the AQC on spending trends for children.
CONCLUSIONS:
During the first 2 years of the contract, the AQC had a small but significant positive effect on pediatric preventive care quality tied to P4P; this effect was greater for CSHCN than non-CSHCN. However, it did not significantly influence (positively or negatively) CSHCN measures not tied to P4P or affect per capita spending for either group.
doi:10.1542/peds.2012-3440
PMCID: PMC4079291  PMID: 24366988
pay-for-performance; capitation; payment; pediatrics; children with special health care needs; preventive care; acute care quality; chronic disease care quality; asthma; ADHD
10.  Stratification of Risk of Early-Onset Sepsis in Newborns ≥34 Weeks’ Gestation 
Pediatrics  2014;133(1):30-36.
OBJECTIVE:
To define a quantitative stratification algorithm for the risk of early-onset sepsis (EOS) in newborns ≥34 weeks’ gestation.
METHODS:
We conducted a retrospective nested case-control study that used split validation. Data collected on each infant included sepsis risk at birth based on objective maternal factors, demographics, specific clinical milestones, and vital signs during the first 24 hours after birth. Using a combination of recursive partitioning and logistic regression, we developed a risk classification scheme for EOS on the derivation dataset. This scheme was then applied to the validation dataset.
RESULTS:
Using a base population of 608 014 live births ≥34 weeks’ gestation at 14 hospitals between 1993 and 2007, we identified all 350 EOS cases <72 hours of age and frequency matched them by hospital and year of birth to 1063 controls. Using maternal and neonatal data, we defined a risk stratification scheme that divided the neonatal population into 3 groups: treat empirically (4.1% of all live births, 60.8% of all EOS cases, sepsis incidence of 8.4/1000 live births), observe and evaluate (11.1% of births, 23.4% of cases, 1.2/1000), and continued observation (84.8% of births, 15.7% of cases, incidence 0.11/1000).
CONCLUSIONS:
It is possible to combine objective maternal data with evolving objective neonatal clinical findings to define more efficient strategies for the evaluation and treatment of EOS in term and late preterm infants. Judicious application of our scheme could result in decreased antibiotic treatment in 80 000 to 240 000 US newborns each year.
doi:10.1542/peds.2013-1689
PMCID: PMC4079292  PMID: 24366992
early-onset sepsis; late preterm infant; predictive modeling; term newborn
11.  Onset of Breast Development in a Longitudinal Cohort 
Pediatrics  2013;132(6):1019-1027.
BACKGROUND AND OBJECTIVES:
There is growing evidence of pubertal maturation occurring at earlier ages, with many studies based on cross-sectional observations. This study examined age at onset of breast development (thelarche), and the impact of BMI and race/ethnicity, in the 3 puberty study sites of the Breast Cancer and the Environment Research Program, a prospective cohort of >1200 girls.
METHODS:
Girls, 6 to 8 years at enrollment, were followed longitudinally at regular intervals from 2004 to 2011 in 3 geographic areas: the San Francisco Bay Area, Greater Cincinnati, and New York City. Sexual maturity assessment using Tanner staging was conducted by using standardized observation and palpation methods by trained and certified staff. Kaplan-Meier analyses were used to describe age at onset of breast maturation by covariates.
RESULTS:
The age at onset of breast stage 2 varied by race/ethnicity, BMI at baseline, and site. Median age at onset of breast stage 2 was 8.8, 9.3, 9.7, and 9.7 years for African American, Hispanic, white non-Hispanic, and Asian participants, respectively. Girls with greater BMI reached breast stage 2 at younger ages. Age-specific and standardized prevalence of breast maturation was contrasted to observations in 2 large cross-sectional studies conducted 10 to 20 years earlier (Pediatric Research in Office Settings and National Health and Nutrition Examination Survey III) and found to have occurred earlier among white, non-Hispanic, but not African American girls.
CONCLUSIONS:
We observed the onset of thelarche at younger ages than previously documented, with important differences associated with race/ethnicity and BMI, confirming and extending patterns seen previously. These findings are consistent with temporal changes in BMI.
doi:10.1542/peds.2012-3773
PMCID: PMC3838525  PMID: 24190685
puberty; girls; breast development; obesity
12.  Acetylcholinesterase Activity and Neurodevelopment in Boys and Girls 
Pediatrics  2013;132(6):e1649-e1658.
BACKGROUND:
Organophosphate exposures can affect children’s neurodevelopment, possibly due to neurotoxicity induced by acetylcholinesterase (AChE) inhibition, and may affect boys more than girls. We tested the hypothesis that lower AChE activity is associated with lower neurobehavioral development among children living in Ecuadorian floricultural communities.
METHODS:
In 2008, we examined 307 children (age: 4–9 years; 52% male) and quantified AChE activity and neurodevelopment in 5 domains: attention/executive functioning, language, memory/learning, visuospatial processing, and sensorimotor (NEPSY-II test). Associations were adjusted for demographic and socioeconomic characteristics and height-for-age, flower worker cohabitation, and hemoglobin concentration.
RESULTS:
Mean ± standard deviation AChE activity was 3.14 ± 0.49 U/mL (similar for both genders). The range of scores among neurodevelopment subtests was 5.9 to 10.7 U (standard deviation: 2.6–4.9 U). Girls had a greater mean attention/executive functioning domain score than boys. In boys only, there were increased odds ratios of low (<9th percentile) neurodevelopment among those in the lowest tertile versus the highest tertile of AChE activity (odds ratios: total neurodevelopment: 5.14 [95% confidence interval (CI): 0.84 to 31.48]; attention/executive functioning domain: 4.55 [95% CI: 1.19 to 17.38], memory/learning domain: 6.03 [95% CI: 1.17 to 31.05]) after adjustment for socioeconomic and demographic factors, height-for-age, and hemoglobin. Within these domains, attention, inhibition and long-term memory subtests were most affected.
CONCLUSIONS:
Low AChE activity was associated with deficits in neurodevelopment, particularly in attention, inhibition, and memory in boys but not in girls. These critical cognitive skills affect learning and academic performance. Added precautions regarding secondary occupational pesticide exposure would be prudent.
doi:10.1542/peds.2013-0108
PMCID: PMC3838526  PMID: 24249815
acetylcholinesterase; AChE; ADD; ADHD; agriculture; agricultural communities; attention; boys; children; Ecuador; floriculture; flower; girls; growth; inhibition; inhibitory control; memory; neurobehavioral development; neurodevelopment; plantation; pesticide
13.  Potential Asphyxia and Brainstem Abnormalities in Sudden and Unexpected Death in Infants 
Pediatrics  2013;132(6):e1616-e1625.
OBJECTIVE:
Sudden and unexplained death is a leading cause of infant mortality. Certain characteristics of the sleep environment increase the risk for sleep-related sudden and unexplained infant death. These characteristics have the potential to generate asphyxial conditions. We tested the hypothesis that infants may be exposed to differing degrees of asphyxia in sleep environments, such that vulnerable infants with a severe underlying brainstem deficiency in serotonergic, γ-aminobutyric acid-ergic, or 14-3-3 transduction proteins succumb even without asphyxial triggers (eg, supine), whereas infants with intermediate or borderline brainstem deficiencies require asphyxial stressors to precipitate death.
METHODS:
We classified cases of sudden infant death into categories relative to a “potential asphyxia” schema in a cohort autopsied at the San Diego County Medical Examiner’s Office. Controls were infants who died with known causes of death established at autopsy. Analysis of covariance tested for differences between groups.
RESULTS:
Medullary neurochemical abnormalities were present in both infants dying suddenly in circumstances consistent with asphyxia and infants dying suddenly without obvious asphyxia-generating circumstances. There were no differences in the mean neurochemical measures between these 2 groups, although mean measures were both significantly lower (P < .05) than those of controls dying of known causes.
CONCLUSIONS:
We found no direct relationship between the presence of potentially asphyxia conditions in the sleep environment and brainstem abnormalities in infants dying suddenly and unexpectedly. Brainstem abnormalities were associated with both asphyxia-generating and non–asphyxia generating conditions. Heeding safe sleep messages is essential for all infants, especially given our current inability to detect underlying vulnerabilities.
doi:10.1542/peds.2013-0700
PMCID: PMC3838527  PMID: 24218471
14-3-3 proteins; bed-sharing; GABA receptors; prone sleep; serotonin; sudden infant death syndrome
14.  Adiposity and Different Types of Screen Time 
Pediatrics  2013;132(6):e1497-e1505.
OBJECTIVE:
Few prospective studies have examined separate forms of screen time in relation to adiposity. Our objective was to assess independent relations of television, electronic games (video/computer), and digital versatile disc (DVD)/videos and total screen time with change in adolescent BMI.
METHODS:
Using data from the 2004, 2006, and 2008 waves of the ongoing Growing up Today Study II, we assessed baseline and 2-year change in reported screen time in relation to concurrent change in BMI among 4287 girls and 3505 boys aged 9 to 16 years in 2004. Gender-specific models adjusted for previous BMI, age, race/ethnicity, growth/development, months between questionnaires, and physical activity.
RESULTS:
Among girls and boys, each hour per day increase in reported television viewing was associated with a 0.09 increase in BMI (Ps < .001), and each hour per day increase in total screen time was associated with a 0.07 increase among girls and 0.05 increase among boys (Ps < .001). Among girls only, greater baseline television, games, and total screen time and change in DVDs/videos were associated with gains in BMI (Ps < .05). BMI gains associated with change in television and total screen time were stronger among overweight girls than lean girls (Ps-heterogeneity < .001).
CONCLUSIONS:
Television, which remains the steadiest source of food advertising, was most consistently associated with BMI gains. Among girls, electronic games and DVDs/videos were also related to increased BMI, possibly due to influences of product placements and advergames on diet and/or distracted eating. Adolescents, especially overweight adolescents, may benefit from reduced time with multiple types of media.
doi:10.1542/peds.2013-0887
PMCID: PMC3838528  PMID: 24276840
television; video games; sedentary lifestyle; BMI; body weight; adolescent; adiposity; longitudinal studies
15.  Resuscitation of Preterm Neonates With Limited Versus High Oxygen Strategy 
Pediatrics  2013;132(6):e1488-e1496.
OBJECTIVE:
To determine whether a limited oxygen strategy (LOX) versus a high oxygen strategy (HOX) during delivery room resuscitation decreases oxidative stress in preterm neonates.
METHODS:
A randomized trial of neonates of 24 to 34 weeks’ gestational age (GA) who received resuscitation was performed. LOX neonates received room air as the initial resuscitation gas, and fraction of inspired oxygen (Fio2) was adjusted by 10% every 30 seconds to achieve target preductal oxygen saturations (Spo2) as described by the 2010 Neonatal Resuscitation Program guidelines. HOX neonates received 100% O2 as initial resuscitation gas, and Fio2 was adjusted by 10% to keep preductal Spo2 at 85% to 94%. Total hydroperoxide (TH), biological antioxidant potential (BAP), and the oxidative balance ratio (BAP/TH) were analyzed in cord blood and the first hour of life. Secondary outcomes included delivery room interventions, respiratory support on NICU admission, and short-term morbidities.
RESULTS:
Forty-four LOX (GA: 30 ± 3 weeks; birth weight: 1678 ± 634 g) and 44 HOX (GA: 30 ± 3 weeks; birth weight: 1463 ± 606 g) neonates were included. LOX decreased integrated excess oxygen (∑Fio2 × time [min]) in the delivery room compared with HOX (401 ± 151 vs 662 ± 249; P < .01). At 1 hour of life, BAP/TH was 60% higher for LOX versus HOX neonates (13 [9–16] vs 8 [6–9]) µM/U.CARR, P < .01). LOX decreased ventilator days (3 [0–64] vs 8 [0–96]; P < .05) and reduced the incidence of bronchopulmonary dysplasia (7% vs 25%; P < .05).
CONCLUSIONS:
LOX is feasible and results in less oxygen exposure, lower oxidative stress, and decreased respiratory morbidities and thus is a reasonable alternative for resuscitation of preterm neonates in the delivery room.
doi:10.1542/peds.2013-0978
PMCID: PMC3838529  PMID: 24218465
newborn; oxidative stress; oxygen; preterm; resuscitation
16.  Child Exposure to Parental Violence and Psychological Distress Associated With Delayed Milestones 
Pediatrics  2013;132(6):e1577-e1583.
OBJECTIVE:
To examine the association between parental report of intimate partner violence (IPV) and parental psychological distress (PPD) with child attainment of developmental milestones.
METHODS:
By using data collected from a large cohort of primary care patients, this cross-sectional study examined the relationship between parental report of IPV and/or PPD and the attainment of developmental milestones within the first 72 months of a child’s life. Multivariate logistic regression analyses were used to adjust for parental report of child abuse concern and sociodemographic characteristics.
RESULTS:
Our study population included 16 595 subjects. Children of parents reporting both IPV and PPD (n = 88; 0.5%) were more likely to fail at least 1 milestone across the following developmental domains: language (adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI] 1.3–3.3), personal-social (aOR 1.9; 95% CI 1.2–2.9), and gross motor (aOR 3.0; 95% CI 1.8–5.0). Significant associations for those reporting IPV-only (n = 331; 2.0%) were found for language (aOR 1.4; 95% CI 1.1–1.9), personal-social (aOR 1.7; 95% CI 1.4–2.2), and fine motor-adaptive (aOR 1.7; 95% CI 1.0–2.7). Significant associations for those reporting PPD-only (n = 1920; 11.6%) were found for: language (aOR 1.5; 95% CI 1.3–1.7), personal-social (aOR 1.6; 95% CI 1.5–1.8), gross motor (aOR 1.6; 95% CI 1.4–1.8), and fine-motor adaptive (aOR 1.6; 95% CI 1.3–2.0).
CONCLUSIONS:
Screening children for IPV and PPD helps identify those at risk for poor developmental outcomes who may benefit from early intervention.
doi:10.1542/peds.2013-1020
PMCID: PMC3838530  PMID: 24190682
child development; computerized clinical decision support; developmental milestones; intimate partner violence; parental psychological distress
17.  SUPPORTing Premature Infants 
Pediatrics  2013;132(6):e1661-e1663.
doi:10.1542/peds.2013-1292
PMCID: PMC3838531  PMID: 24218459
ethics; oxygen toxicity; prematurity; research
18.  The Political History of PKU: Reflections on 50 Years of Newborn Screening 
Pediatrics  2013;132(6):987-989.
doi:10.1542/peds.2013-1441
PMCID: PMC3838532  PMID: 24276841
history; phenylketonuria; newborn screening; genetics
19.  Catheter Dwell Time and CLABSIs in Neonates With PICCs: A Multicenter Cohort Study 
Pediatrics  2013;132(6):e1609-e1615.
OBJECTIVE:
To determine whether the daily risk of central line–associated bloodstream infections (CLABSIs) increases over the dwell time of peripherally inserted central catheters (PICCs) in high-risk neonates.
METHODS:
Multicenter retrospective cohort including NICU patients with a PICC inserted between January 2005 and June 2010. We calculated incidence rates and used Poisson regression models to assess the risk of developing CLABSI as a function of PICC dwell time.
RESULTS:
A total of 4797 PICCs placed in 3967 neonates were included; 149 CLABSIs occurred over 89 946 catheter-days (incidence rate 1.66 per 1000 catheter-days). In unadjusted analysis, PICCs with a dwell time of 8 to 13 days, 14 to 22 days, and ≥23 days each had an increased risk of infection compared with PICCs in place for ≤7 days (P < .05). In adjusted analysis, the average predicted daily risk of CLABSIs after PICC insertion increased during the first 2 weeks after PICC insertion and remained elevated for the dwell time of the catheter. There was an increased risk of CLABSIs in neonates with concurrent PICCs (adjusted incidence rate ratio 2.04, 1.12–3.71). The incidence of Gram-negative CLABSIs was greater in PICCs with dwell times >50 days (incidence rate ratio 5.26, 2.40–10.66).
CONCLUSIONS:
The risk of CLABSIs increased during the 2 weeks after PICC insertion and then remained elevated until PICC removal. Clinicians should review PICC necessity daily, optimize catheter maintenance practices, and investigate novel CLABSI prevention strategies in PICCs with prolonged dwell times.
doi:10.1542/peds.2013-1645
PMCID: PMC3838533  PMID: 24218474
infection; catheter-related infections; NICU; central venous catheters; peripheral venous catheterization
20.  Serum Tocopherol Levels in Very Preterm Infants After a Single Dose of Vitamin E at Birth 
Pediatrics  2013;132(6):e1626-e1633.
OBJECTIVE:
Our aim was to examine the impact of a single enteral dose of vitamin E on serum tocopherol levels. The study was undertaken to see whether a single dose of vitamin E soon after birth can rapidly increase the low α-tocopherol levels seen in very preterm infants. If so, this intervention could be tested as a means of reducing the risk of intracranial hemorrhage.
METHODS:
Ninety-three infants <27 weeks’ gestation and <1000 g were randomly assigned to receive a single dose of vitamin E or placebo by gastric tube within 4 hours of birth. The vitamin E group received 50 IU/kg of vitamin E as dl-α-tocopheryl acetate (Aquasol E). The placebo group received sterile water. Blood samples were taken for measurement of serum tocopherol levels by high-performance liquid chromatography before dosing and 24 hours and 7 days after dosing.
RESULTS:
Eighty-eight infants received the study drug and were included in the analyses. The α-tocopherol levels were similar between the groups at baseline but higher in the vitamin E group at 24 hours (median 0.63 mg/dL vs 0.42 mg/dL, P = .003) and 7 days (2.21 mg/dL vs 1.86 mg/dL, P = .04). There were no differences between groups in γ-tocopherol levels. At 24 hours, 30% of vitamin E infants and 62% of placebo infants had α-tocopherol levels <0.5 mg/dL.
CONCLUSIONS:
A 50-IU/kg dose of vitamin E raised serum α-tocopherol levels, but to consistently achieve α-tocopherol levels >0.5 mg/dL, a higher dose or several doses of vitamin E may be needed.
doi:10.1542/peds.2013-1684
PMCID: PMC3838534  PMID: 24218460
vitamin E; preterm infants
21.  The Architecture of Provider-Parent Vaccine Discussions at Health Supervision Visits 
Pediatrics  2013;132(6):1037-1046.
OBJECTIVE:
To characterize provider-parent vaccine communication and determine the influence of specific provider communication practices on parent resistance to vaccine recommendations.
METHODS:
We conducted a cross-sectional observational study in which we videotaped provider-parent vaccine discussions during health supervision visits. Parents of children aged 1 to 19 months old were screened by using the Parent Attitudes about Childhood Vaccines survey. We oversampled vaccine-hesitant parents (VHPs), defined as a score ≥50. We developed a coding scheme of 15 communication practices and applied it to all visits. We used multivariate logistic regression to explore the association between provider communication practices and parent resistance to vaccines, controlling for parental hesitancy status and demographic and visit characteristics.
RESULTS:
We analyzed 111 vaccine discussions involving 16 providers from 9 practices; 50% included VHPs. Most providers (74%) initiated vaccine recommendations with presumptive (eg, “Well, we have to do some shots”) rather than participatory (eg, “What do you want to do about shots?”) formats. Among parents who voiced resistance to provider initiation (41%), significantly more were VHPs than non-VHPs. Parents had significantly higher odds of resisting vaccine recommendations if the provider used a participatory rather than a presumptive initiation format (adjusted odds ratio: 17.5; 95% confidence interval: 1.2–253.5). When parents resisted, 50% of providers pursued their original recommendations (eg, “He really needs these shots”), and 47% of initially resistant parents subsequently accepted recommendations when they did.
CONCLUSIONS:
How providers initiate and pursue vaccine recommendations is associated with parental vaccine acceptance.
doi:10.1542/peds.2013-2037
PMCID: PMC3838535  PMID: 24190677
immunization; health communication; preventive health services
22.  The Effect of Obesity in Adolescence on Adult Health Status 
Pediatrics  2013;132(6):1098-1104.
OBJECTIVE:
To test the hypothesis that adolescent obesity would be associated with greater risks of adverse health in severely obese adults.
METHODS:
Before weight loss surgery, adult participants in the Longitudinal Assessment of Bariatric Surgery-2 underwent detailed anthropometric and comorbidity assessment. Weight status at age 18 was retrospectively determined. Participants who were ≥80% certain of recalled height and weight at age 18 (1502 of 2308) were included. Log binomial regression was used to evaluate whether weight status at age 18 was independently associated with risk of comorbid conditions at time of surgery controlling for potential confounders.
RESULTS:
Median age and adult body mass index (BMI) were 47 years and 46, respectively. At age 18, 42% of subjects were healthy weight, 29% overweight, 16% class 1 obese, and 13% class ≥2 obese. Compared with healthy weight at age 18, class ≥2 obesity at age 18 independently increased the risk of lower-extremity venous edema with skin manifestations by 435% (P < .0001), severe walking limitation by 321% (P < .0001), abnormal kidney function by 302% (P < .0001), polycystic ovary syndrome by 74% (P = .03), asthma by 48% (P = .01), diabetes by 42% (P < .01), obstructive sleep apnea by 25% (P < .01), and hypertension (by varying degrees based on age and gender). Conversely, the associated risk of hyperlipidemia was reduced by 61% (P < .01).
CONCLUSIONS:
Severe obesity at age 18 was independently associated with increased risk of several comorbid conditions in adults undergoing bariatric surgery.
doi:10.1542/peds.2013-2185
PMCID: PMC3838536  PMID: 24249816
obesity; bariatric; weight history
23.  Longitudinal Validation of a Tool for Asthma Self-Monitoring 
Pediatrics  2013;132(6):e1554-e1561.
OBJECTIVES:
To establish longitudinal validation of a new tool, the Asthma Symptom Tracker (AST). AST combines weekly use of the Asthma Control Test with a color-coded graph for visual trending.
METHODS:
Prospective cohort study of children age 2 to 18 years admitted for asthma. Parents or children (n = 210) completed baseline AST assessments during hospitalization, then over 6 months after discharge. Concurrent with the first 5 AST assessments, the Asthma Control Questionnaire (ACQ) was administered for comparison.
RESULTS:
Test–retest reliability (intraclass correlation) was moderate, with a small longitudinal variation of AST measurements within subjects during follow-ups. Internal consistency was strong at baseline (Cronbach’s α 0.70) and during follow-ups (Cronbach’s α 0.82–0.90). Criterion validity demonstrated a significant correlation between AST and ACQ scores at baseline (r = −0.80, P < .01) and during follow-ups (r = −0.64, −0.72, −0.63, and −0.69). The AST was responsive to change over time; an increased ACQ score by 1 point was associated with a decreased AST score by 2.65 points (P < .01) at baseline and 3.11 points (P < .01) during follow-ups. Discriminant validity demonstrated a strong association between decreased AST scores and increased oral corticosteroid use (odds ratio 1.13, 95% confidence interval, 1.10–1.16, P < .01) and increased unscheduled acute asthma visits (odds ratio 1.23, 95% confidence interval, 1.18–1.28, P < .01).
CONCLUSIONS:
The AST is reliable, valid, and responsive to change over time, and can facilitate ongoing monitoring of asthma control and proactive medical decision-making in children.
doi:10.1542/peds.2013-1389
PMCID: PMC4074668  PMID: 24218469
asthma control; pediatrics; self-monitoring; self-management
24.  National, Regional, and State Abusive Head Trauma: Application of the CDC Algorithm 
Pediatrics  2013;132(6):e1546-e1553.
OBJECTIVE:
To examine national, regional, and state abusive head trauma (AHT) trends using child hospital discharge data by applying a new coding algorithm developed by the Centers for Disease Control and Prevention (CDC).
METHODS:
Data from 4 waves of the Kids’ Inpatient Database and annual discharge data from North Carolina were used to determine trends in AHT incidence among children <1 year of age between 2000 and 2009. National, regional, and state incidence rates were calculated. Poisson regression analyses were used to examine national, regional, and state AHT trends.
RESULTS:
The CDC narrow and broad algorithms identified 5437 and 6317 cases, respectively, in the 4 years of KID weighted data. This yielded average annual incidences of 33.4 and 38.8 cases per 100 000 children <1 year of age. There was no statistically significant change in national rates. There were variations by region of the country, with significantly different trends in the Midwest and West. State data for North Carolina showed wide annual variation in rates, with no significant trend.
CONCLUSIONS:
The new coding algorithm resulted in the highest AHT rates reported to date. At the same time, we found large but statistically insignificant annual variations in AHT rates in 1 large state. This suggests that caution should be used in interpreting AHT trends and attributing changes in rates as being caused by changes in policies, programs, or the economy.
doi:10.1542/peds.2013-2049
PMCID: PMC4074669  PMID: 24276842
abusive head trauma; abuse; children
25.  Family History in Primary Care Pediatrics 
Pediatrics  2013;132(Suppl 3):S203-S210.
The family history has been called the first genetic test; it was a core element of primary care long before the current wave of genetics technologies and services became clinically relevant. Risk assessment based on family history allows providers to personalize and prioritize health messages, shifts the focus of health care from treatment to prevention, and can empower individuals and families to be stewards of their own health. In a world of rising health care costs, the family history is an important tool, with its primary cost being the clinician’s time. However, a recent National Institutes of Health conference highlighted the lack of substantive evidence to support the clinical utility of family histories. Annual collection of a comprehensive 3-generation family history has been held up as the gold standard for practice. However, interval family histories targeted to symptoms and family histories tailored to a child’s life stage (ie, age-based health) may be important and underappreciated methods of collecting family history that yield clinically actionable data and supplement existing family history information. In this article, we review the various applications, as well as capabilities and limitations, of the family history for primary care providers.
doi:10.1542/peds.2013-1032D
PMCID: PMC4075136  PMID: 24298128
family history; primary care; pediatrics

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