Showing papers in "JAMA Pediatrics in 2016"

Global and national burden of diseases and injuries among children and adolescents between 1990 and 2013: findings from the global burden of disease 2013 study.

Abstract: Importance The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce. Objective To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged Evidence Review Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14 244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35 620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates. Findings Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905 059 deaths; 95% UI, 810 304-998 125), diarrheal diseases among older children (38 325 deaths; 95% UI, 30 365-47 678), and road injuries among adolescents (115 186 deaths; 95% UI, 105 185-124 870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world’s deaths from neonatal encephalopathy. Half of the world’s diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia. Conclusions and Relevance Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.

Association Between Portable Screen-Based Media Device Access or Use and Sleep Outcomes: A Systematic Review and Meta-analysis

Abstract: Importance Sleep is vital to children’s biopsychosocial development. Inadequate sleep quantity and quality is a public health concern with an array of detrimental health outcomes. Portable mobile and media devices have become a ubiquitous part of children’s lives and may affect their sleep duration and quality. Objective To conduct a systematic review and meta-analysis to examine whether there is an association between portable screen-based media device (eg, cell phones and tablet devices) access or use in the sleep environment and sleep outcomes. Data Sources A search strategy consisting of gray literature and 24 Medical Subject Headings was developed in Ovid MEDLINE and adapted for other databases between January 1, 2011, and June 15, 2015. Searches of the published literature were conducted across 12 databases. No language restriction was applied. Study Selection The analysis included randomized clinical trials, cohort studies, and cross-sectional study designs. Inclusion criteria were studies of school-age children between 6 and 19 years. Exclusion criteria were studies of stationary exposures, such as televisions or desktop or personal computers, or studies investigating electromagnetic radiation. Data Extraction and Synthesis Of 467 studies identified, 20 cross-sectional studies were assessed for methodological quality. Two reviewers independently extracted data. Main Outcomes and Measures The primary outcomes were inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness, studied according to an a priori protocol. Results Twenty studies were included, and their quality was assessed. The studies involved 125 198 children (mean [SD] age, 14.5 [2.2] years; 50.1% male). There was a strong and consistent association between bedtime media device use and inadequate sleep quantity (odds ratio [OR], 2.17; 95% CI, 1.42-3.32) (P < .001, I2 = 90%), poor sleep quality (OR, 1.46; 95% CI, 1.14-1.88) (P = .003, I2 = 76%), and excessive daytime sleepiness (OR, 2.72; 95% CI, 1.32-5.61) (P = .007, I2 = 50%). In addition, children who had access to (but did not use) media devices at night were more likely to have inadequate sleep quantity (OR, 1.79; 95% CI, 1.39-2.31) (P < .001, I2 = 64%), poor sleep quality (OR, 1.53; 95% CI, 1.11-2.10) (P = .009, I2 = 74%), and excessive daytime sleepiness (OR, 2.27; 95% CI, 1.54-3.35) (P < .001, I2 = 24%). Conclusions and Relevance To date, this study is the first systematic review and meta-analysis of the association of access to and the use of media devices with sleep outcomes. Bedtime access to and use of a media device were significantly associated with the following: inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness. An integrated approach among teachers, health care professionals, and parents is required to minimize device access at bedtime, and future research is needed to evaluate the influence of the devices on sleep hygiene and outcomes.

Cancer in Adolescents and Young Adults: A Narrative Review of the Current Status and a View of the Future.

Abstract: Importance Although cancer remains the most common cause of disease-related death in adolescents and young adults (AYAs) in high-income countries, their overall survival rates continue to increase and now exceed 80% at 5 years in several high-income countries. This has been accomplished through progressive improvements in active treatment and supportive care, although accrual rates to therapeutic clinical trials remain disappointing. Recognition of the unique distribution of diseases in the AYA population with cancer and further understanding of the distinctive biology of cancers in AYAs will lead to continuing gains in clinical outcomes. Observations Many of the challenges faced by AYAs with a diagnosis of malignant disease are shared by others with chronic medical conditions and even their healthy peers, such as a sense of invulnerability that may contribute to delays in diagnosis. A particular need for psychological support has been identified for AYAs with cancer, even after active therapy has been completed and especially in the context of palliative care. Notable needs also include fertility preservation and navigation through the multiple transitions in the cancer journey. Additionally, there is a “cost of cure.” This is not only in the form of short-term, treatment-related morbidity and mortality but also in the burden of “late effects,” including second cancers, that compromise quality of life and limit life expectancy. Establishing clinical programs devoted to AYAs with cancer, with complementary educational initiatives, will strengthen the advances made. It is anticipated that clinical trial accrual will increase substantially, providing further gains in survival. Likewise, addressing the challenges of survivorship, including secondary prevention of long-term morbidity and mortality, will lead to additional improvements in clinical outcomes. Conclusions and Relevance Transferring this knowledge to the care of an estimated 1 million incident cases of cancer in AYAs worldwide, most of whom do not live in high-income countries, remains a considerable challenge.

Parent-Adolescent Sexual Communication and Adolescent Safer Sex Behavior A Meta-Analysis

Abstract: Importance Parent-adolescent sexual communication has received considerable attention as a factor that can positively affect safer sex behavior among youth; however, the evidence linking such communication to youth contraceptive and condom use has not been empirically synthesized. Objectives To examine the effect of parent-adolescent sexual communication on safer sex behavior among youth and explore potential moderators of this association. Data Sources A systematic search of studies published from database inception through June 30, 2014, using the MEDLINE, PsycINFO, and Communication & Mass Media Complete databases and relevant review articles yielded 5098 studies, of which 52 studies with 25 314 adolescents met the study eligibility criteria. Analysis was conducted from July 1, 2014, to July 27, 2015. Study Selection Studies were included if they sampled adolescents (mean sample age ≤18 years), included an adolescent report of sexual communication with one or both parents, measured safer sex behavior, and were published in English. Data Extraction and Synthesis Correlation coefficients ( r ) and 95% CIs were computed from studies and meta-analyzed using random-effects models. Main Outcomes and Measures Safer sex behavior, including use of contraceptives or condoms. Results Fifty-two articles, including 71 independent effects representing more than 3 decades of research on 25 314 adolescents (weighted mean age, 15.2 years) were synthesized. Across studies, there was a significant weighted mean effect ( r = 0.10; 95% CI, 0.08-0.13) linking parent-adolescent sexual communication with safer sex behavior, which was statistically heterogeneous ( Q = 203.50, P I 2 = 65.60). Moderation analyses revealed larger effects for communication with girls ( r = 0.12) than boys ( r = 0.04) and among youth who discussed sex with their mothers ( r = 0.14) compared with their fathers ( r = 0.03). Effects did not differ for contraceptive vs condom use or among longitudinal vs cross-sectional studies, indicating that parent sexual communication had a similar effect across study designs and outcomes. Several methodological issues were identified in the literature; future studies can improve on these issues by measuring parent-adolescent communication with robust, multi-item measures, clearly specifying the target parent, and applying multimethod longitudinal designs. Conclusions and Relevance Sexual communication with parents, particularly mothers, plays a small protective role in safer sex behavior among adolescents; this protective effect is more pronounced for girls than boys. We discuss the implications for practice and make suggestions for future research on parent-adolescent sexual communication.

Effects of Social Needs Screening and In-Person Service Navigation on Child Health: A Randomized Clinical Trial.

Abstract: Importance Social determinants of health shape both children’s immediate health and their lifetime risk for disease. Increasingly, pediatric health care organizations are intervening to address family social adversity. However, little evidence is available on the effectiveness of related interventions. Objective To evaluate the effects of social needs screening and in-person resource navigation services on social needs and child health. Design, Setting, and Participants Patients were randomized to intervention or active control conditions by the day of the week. Primary outcomes observed at 4 months after enrollment included caregivers’ reports of social needs and child health status. Recruitment occurred between October 13, 2013, and August 27, 2015, in pediatric primary and urgent care clinics in 2 safety-net hospitals. Participants were English-speaking or Spanish-speaking caregivers accompanying minor children to nonacute medical visits. Interventions After standardized screening, caregivers either received written information on relevant community services (active control) or received in-person help to access services with follow-up telephone calls for further assistance if needed (navigation intervention). Main Outcomes and Measures Change in reported social needs and in caregiver assessment of child’s overall health reported 4 months later. Results Among 1809 patients enrolled in the study, evenly split between the 2 sites, 31.6% (n = 572) were enrolled in a primary care clinic and 68.4% (n = 1237) were enrolled in an urgent care setting. The children were primarily Hispanic white individuals (50.9% [n = 921]) and non-Hispanic black individuals (26.2% [n = 473]) and had a mean (SD) age of 5.1 (4.8) years; 50.5% (n = 913) were female. The reported number of social needs at baseline ranged from 0 to 11 of 14 total possible items, with a mean (SD) of 2.7 (2.2). At 4 months after enrollment, the number of social needs reported by the intervention arm decreased more than that reported by the control arm, with a mean (SE) change of −0.39 (0.13) vs 0.22 (0.13) ( P P Conclusions and Relevance To our knowledge, this investigation is the first randomized clinical trial to evaluate health outcomes of a pediatric social needs navigation program. Compared with an active control at 4 months after enrollment, the intervention significantly decreased families’ reports of social needs and significantly improved children’s overall health status as reported by caregivers. These findings support the feasibility and potential effect of addressing social needs in pediatric health care settings. Trial Registration clinicaltrials.gov Identifier:NCT01939704

National Trends in Hospitalizations for Opioid Poisonings Among Children and Adolescents, 1997 to 2012

Abstract: Importance National data show a parallel relationship between recent trends in opioid prescribing practices and hospitalizations for opioid poisonings in adults No similar estimates exist describing hospitalizations for opioid poisonings in children and adolescents Objective To describe the incidence and characteristics of hospitalizations attributed to opioid poisonings in children and adolescents Design, Setting, and Participants Retrospective analysis of serial cross-sectional data from a nationally representative sample of US pediatric hospital discharge records collected every 3 years from January 1, 1997, through December 31, 2012 The Kids’ Inpatient Database was used to identify 13 052 discharge records for patients aged 1 to 19 years who were hospitalized for opioid poisonings Data were analyzed within the collection time frame Main Outcomes and Measures Poisonings attributed to prescription opioids were identified by codes from the International Classification of Diseases, Ninth Revision, Clinical Modification In adolescents aged 15 to 19 years, poisonings attributed to heroin were also identified Census estimates were used to calculate incidence per 100 000 population The Cochran-Armitage test for trend was used to assess for changes in incidence over time Results From 1997 to 2012, a total of 13 052 (95% CI, 12 500-13 604) hospitalizations for prescription opioid poisonings were identified The annual incidence of hospitalizations for opioid poisonings per 100 000 children aged 1 to 19 years rose from 140 (95% CI, 124-156) to 371 (95% CI, 344-398), an increase of 165% ( P for trend, P for trend, P for trend, P for trend, P for trend, Conclusions and Relevance During the course of 16 years, hospitalizations attributed to opioid poisonings rose nearly 2-fold in the pediatric population Hospitalizations increased across all age groups, yet young children and older adolescents were most vulnerable to the risks of opioid exposure Mitigating these risks will require comprehensive strategies that target opioid storage, packaging, and misuse

Antidepressant Use During Pregnancy and the Risk of Autism Spectrum Disorder in Children

Abstract: Importance The association between the use of antidepressants during gestation and the risk of autism spectrum disorder (ASD) in children is still controversial. The etiology of ASD remains unclear, although studies have implicated genetic predispositions, environmental risk factors, and maternal depression. Objective To examine the risk of ASD in children associated with antidepressant use during pregnancy according to trimester of exposure and taking into account maternal depression. Design, Setting, and Participants We conducted a register-based study of an ongoing population-based cohort, the Quebec Pregnancy/Children Cohort, which includes data on all pregnancies and children in Quebec from January 1, 1998, to December 31, 2009. A total of 145 456 singleton full-term infants born alive and whose mothers were covered by the Regie de l’assurance maladie du Quebec drug plan for at least 12 months before and during pregnancy were included. Data analysis was conducted from October 1, 2014, to June 30, 2015. Exposures Antidepressant exposure during pregnancy was defined according to trimester and specific antidepressant classes. Main Outcomes and Measures Children with ASD were defined as those with at least 1 diagnosis of ASD between date of birth and last date of follow-up. Cox proportional hazards regression models were used to estimate crude and adjusted hazard ratios with 95% CIs. Results During 904 035.50 person-years of follow-up, 1054 children (0.7%) were diagnosed with ASD; boys with ASD outnumbered girls by a ratio of about 4:1. The mean (SD) age of children at the end of follow-up was 6.24 (3.19) years. Adjusting for potential confounders, use of antidepressants during the second and/or third trimester was associated with the risk of ASD (31 exposed infants; adjusted hazard ratio, 1.87; 95% CI, 1.15-3.04). Use of selective serotonin reuptake inhibitors during the second and/or third trimester was significantly associated with an increased risk of ASD (22 exposed infants; adjusted hazard ratio, 2.17; 95% CI, 1.20-3.93). The risk was persistent even after taking into account maternal history of depression (29 exposed infants; adjusted hazard ratio, 1.75; 95% CI, 1.03-2.97). Conclusions and Relevance Use of antidepressants, specifically selective serotonin reuptake inhibitors, during the second and/or third trimester increases the risk of ASD in children, even after considering maternal depression. Further research is needed to specifically assess the risk of ASD associated with antidepressant types and dosages during pregnancy.

Association of Cesarean Delivery and Formula Supplementation With the Intestinal Microbiome of 6-Week-Old Infants

Abstract: Importance The intestinal microbiome plays a critical role in infant development, and delivery mode and feeding method (breast milk vs formula) are determinants of its composition. However, the importance of delivery mode beyond the first days of life is unknown, and studies of associations between infant feeding and microbiome composition have been generally limited to comparisons between exclusively breastfed and formula-fed infants, with little consideration given to combination feeding of both breast milk and formula. Objective To examine the associations of delivery mode and feeding method with infant intestinal microbiome composition at approximately 6 weeks of life. Design, Setting, and Participants Prospective observational study of 102 infants followed up as part of a US pregnancy cohort study. Exposures Delivery mode was abstracted from delivery medical records, and feeding method prior to the time of stool collection was ascertained through detailed questionnaires. Main Outcomes and Measures Stool microbiome composition was characterized using next-generation sequencing of the 16S rRNA gene. Results There were 102 infants (mean gestational age, 39.7 weeks; range, 37.1-41.9 weeks) included in this study, of whom 70 were delivered vaginally and 32 by cesarean delivery. In the first 6 weeks of life, 70 were exclusively breastfed, 26 received combination feeding, and 6 were exclusively formula fed. We identified independent associations between microbial community composition and both delivery mode ( P Q P = .01; Q P = .003). Bacterial communities associated with combination feeding were more similar to those associated with exclusive formula feeding than exclusive breastfeeding ( P = .002). We identified 6 individual bacterial genera that were differentially abundant between delivery mode and feeding groups. Conclusions and Relevance The infant intestinal microbiome at approximately 6 weeks of age is significantly associated with both delivery mode and feeding method, and the supplementation of breast milk feeding with formula is associated with a microbiome composition that resembles that of infants who are exclusively formula fed. These results may inform feeding choices and shed light on the mechanisms behind the lifelong health consequences of delivery and infant feeding modalities.

Point of Health Care Entry for Youth With Concussion Within a Large Pediatric Care Network.

Abstract: IMPORTANCE: Previous epidemiologic research on concussions has primarily been limited to patient populations presenting to sport concussion clinics or to emergency departments (EDs) and to those high school age or older. By examining concussion visits across an entire pediatric health care network, a better estimate of the scope of the problem can be obtained. OBJECTIVE: To comprehensively describe point of entry for children with concussion, overall and by relevant factors including age, sex, race/ethnicity, and payor, to quantify where children initially seek care for this injury. DESIGN, SETTING, AND PARTICIPANTS: In this descriptive epidemiologic study, data were collected from primary care, specialty care, ED, urgent care, and inpatient settings. The initial concussion-related visit was selected and variation in the initial health care location (primary care, specialty care, ED, or hospital) was examined in relation to relevant variables. All patients aged 0 to 17 years who received their primary care from The Children's Hospital of Philadelphia's (CHOP) network and had 1 or more in-person clinical visits for concussion in the CHOP unified electronic health record (EHR) system (July 1, 2010, to June 30, 2014) were selected. MAIN OUTCOMES AND MEASURES: Frequency of initial concussion visits at each type of health care location. Concussion visits in the EHR were defined based on International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes indicative of concussion. RESULTS: A total of 8083 patients were included (median age, 13 years; interquartile range, 10-15 years). Overall, 81.9% (95% CI, 81.1%-82.8%; n RESULTS: = 6624) had their first visit at CHOP within primary care, 5.2% (95% CI, 4.7%-5.7%; n = 418) within specialty care, and 11.7% (95% CI, 11.0%-12.4%; n = 947) within the ED. Health care entry varied by age: 52% (191/368) of children aged 0 to 4 years entered CHOP via the ED, whereas more RESULTS: than three-quarters of those aged 5 to 17 years entered via primary care (5-11 years: 1995/2492; 12-14 years: 2415/2820; and 15-17 years: 2056/2403). Insurance status also influenced the pattern of health care use, with more Medicaid patients using the ED for concussion care (478/1290 Medicaid patie RESULTS: nts [37%] used the ED vs 435/6652 private patients [7%] and 34/141 self-pay patients [24%]). CONCLUSIONS AND RELEVANCE: The findings suggest estimates of concussion incidence based solely on ED visits underestimate the burden of injury, highlight the importance of the primary care setting in concussion care management, and demonstrate the potential for EHR systems to advance research in this area. Language: en

Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study

Abstract: Importance Probiotics have been hypothesized to affect immunologic responses to environmental exposures by supporting healthy gut microbiota and could therefore theoretically be used to prevent the development of type 1 diabetes mellitus (T1DM)–associated islet autoimmunity. Objective To examine the association between supplemental probiotic use during the first year of life and islet autoimmunity among children at increased genetic risk of T1DM. Design, Setting, and Participants In this ongoing prospective cohort study that started September 1, 2004, children from 6 clinical centers, 3 in the United States (Colorado, Georgia/Florida, and Washington) and 3 in Europe (Finland, Germany, and Sweden), were followed up for T1DM-related autoantibodies. Blood samples were collected every 3 months between 3 and 48 months of age and every 6 months thereafter to determine persistent islet autoimmunity. Details of infant feeding, including probiotic supplementation and infant formula use, were monitored from birth using questionnaires and diaries. We applied time-to-event analysis to study the association between probiotic use and islet autoimmunity, stratifying by country and adjusting for family history of type 1 diabetes, HLA-DR-DQ genotypes, sex, birth order, mode of delivery, exclusive breastfeeding, birth year, child’s antibiotic use, and diarrheal history, as well as maternal age, probiotic use, and smoking. Altogether 8676 infants with an eligible genotype were enrolled in the follow-up study before the age of 4 months. The final sample consisted of 7473 children with the age range of 4 to 10 years (as of October 31, 2014). Exposures Early intake of probiotics. Main Outcomes and Measures Islet autoimmunity revealed by specific islet autoantibodies. Results Early probiotic supplementation (at the age of 0-27 days) was associated with a decreased risk of islet autoimmunity when compared with probiotic supplementation after 27 days or no probiotic supplementation (hazard ratio [HR], 0.66; 95% CI, 0.46-0.94). The association was accounted for by children with the DR3/4 genotype (HR, 0.40; 95% CI, 0.21-0.74) and was absent among other genotypes (HR, 0.97; 95% CI, 0.62-1.54). Conclusions and Relevance Early probiotic supplementation may reduce the risk of islet autoimmunity in children at the highest genetic risk of T1DM. The result needs to be confirmed in further studies before any recommendation of probiotics use is made.

Neurodevelopmental outcomes among extremely preterm infants 6.5 years after active perinatal care in Sweden

Abstract: IMPORTANCE Active perinatal care increases the rate of survival of extremely preterm infants, but there are concerns that improved survival might increase the rate of disabled survivors. OBJECTIVE ...

Assessing the Diagnostic Properties of a Graded Oral Provocation Challenge for the Diagnosis of Immediate and Nonimmediate Reactions to Amoxicillin in Children

Abstract: Importance The diagnostic properties of a graded provocation challenge (PC) among children presenting with a rash in the course of amoxicillin treatment are currently unknown. Objective To assess the accuracy and the negative predictive value of the PC in a cohort of children referred with suspected allergy to amoxicillin. Design, Setting, and Participants A cohort study was conducted between March 1, 2012, and April 1, 2015, at the allergy clinic of the Montreal Children’s Hospital, Montreal, Quebec, Canada. All children referred with suspected allergy to amoxicillin were approached. In addition, 346 eligible children were followed up to assess reactions to subsequent use of amoxicillin at the time of illness in cases with negative PC results. Data were collected on clinical characteristics, suspected antibiotic exposure, personal and first-degree relatives’ comorbidities, and history of atopy and management of the reaction. Univariate and multivariate logistic regressions were compared to determine factors associated with immediate and nonimmediate reactions to the PC. Interventions All children had a graded PC. Main Outcomes and Measures Reactions to the graded PC, the negative predictive value of the PC for nonimmediate reactions, and factors associated with immediate and nonimmediate reactions to the PC. Results A total of 818 children were assessed (median age, 1.7 years [interquartile range, 1.0-3.9 years]; 441 [53.9%] male). Among all participants, 770 (94.1%) tolerated the PC, 17 (2.1%) developed mild immediate reactions, and 31 (3.8%) developed nonimmediate reactions. The graded PC had a specificity of 100.0% (95% CI, 90.9%-100.0%), a negative predictive value of 89.1% (95% CI, 77.1%-95.5%), and a positive predictive value of 100.0% (95% CI, 86.3%-100.0%). Among all 346 participants eligible for annual follow-up, 250 (72.3%; 95% CI, 67.2%-76.8%) responded, 55 of whom received subsequent full treatment with amoxicillin; 49 of these 55 participants (89.1%) reported tolerance to subsequent full treatment with amoxicillin, while 6 (10.9%) developed nonimmediate cutaneous reactions. History of a reaction occurring within 5 minutes of exposure was associated with immediate reactions to the PC (adjusted odds ratio = 9.6; 95% CI, 1.5-64.0), while a rash that lasted longer than 7 days (adjusted odds ratio = 4.8; 95% CI, 1.4-16.4) and parental history of drug allergy (adjusted odds ratio = 3.0; 95% CI, 1.3-6.8) were associated with nonimmediate reactions to the PC. Conclusions and Relevance Graded PCs provide an accurate and safe confirmatory test for skin-related reactions to amoxicillin. Further studies are required to assess factors associated with the PC outcome groups.

Effect of the INSIGHT Responsive Parenting Intervention on Rapid Infant Weight Gain and Overweight Status at Age 1 Year: A Randomized Clinical Trial

Abstract: Importance Rapid infant weight gain is associated with later obesity, but interventions to prevent rapid infant growth and reduce risk for overweight status in infancy are lacking. Objective To examine the effect of a responsive parenting (RP) intervention on infant weight gain between birth and 28 weeks and overweight status at age 1 year. Design, Setting, and Participants The Intervention Nurses Start Infants Growing on Healthy Trajectories (INSIGHT) study is an ongoing randomized clinical trial comparing an RP intervention designed to prevent childhood obesity with a safety control. The study includes primiparous mother-newborn dyads (n = 291) and was conducted at the Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, in addition to home visits. Enrollment was initiated in January 2012, and evaluable population analyses for this study were conducted between April 2015 and November 2015. Interventions At 2 weeks post partum, initial intervention materials appropriate to the assigned treatment group were mailed to the participant’s home. Research nurses conducted home visits at 3 weeks, 16 weeks, 28 weeks, and 40 weeks, and a research center visit occurred at 1 year. The Intervention Nurses Start Infants Growing on Healthy Trajectories curriculum included messages about infant feeding, sleep hygiene, active social play, emotion regulation, and growth record education. The control group received a developmentally appropriate home safety intervention also delivered by nurse home visitors. Main Outcomes and Measures Conditional weight gain from birth to 28 weeks was calculated. General linear models examined intervention effect on conditional weight gain. The intervention’s effect on infant weight-for-length percentiles was tested using analysis of variance. Logistic regression compared the odds of overweight status (weight for length ≥95th percentile) at 1 year as a function of conditional weight gain. Results Of the mothers included in the study, 246 were white (88%), 260 were non-Hispanic (93%), 210 were married (75%), and 201 were working full time (72%) at time of enrollment. The mean conditional weight gain score was lower among infants in the RP group compared with the control group (−0.18; 95% CI, −0.36 to −0.001), reflecting that the RP infants gained weight more slowly than control group infants (0.18; 95% CI, 0.02-0.34); this effect did not differ by feeding mode (predominantly fed breast milk or not). Infants in the RP group also had lower mean weight-for-length percentiles at 1 year than infants in the control group (57.5%; 95% CI, 52.56%-62.37% vs 64.4%; 95% CI, 59.94%-69.26%; P = .04) and were less likely to be overweight at age 1 year (5.5% vs 12.7%; P = .05). Conclusions and Relevance An RP intervention is associated with reduced rapid weight gain during the first 6 months after birth and overweight status at age 1 year. Trial Registration clinicaltrials.gov Identifier:NCT01167270.

Capitalizing on Advances in Science to Reduce the Health Consequences of Early Childhood Adversity

Abstract: Advances in biology are providing deeper insights into how early experiences are built into the body with lasting effects on learning, behavior, and health. Numerous evaluations of interventions for young children facing adversity have demonstrated multiple, positive effects but they have been highly variable and difficult to sustain or scale. New research on plasticity and critical periods in development, increasing understanding of how gene-environment interaction affects variation in stress susceptibility and resilience, and the emerging availability of measures of toxic stress effects that are sensitive to intervention provide much-needed fuel for science-informed innovation in the early childhood arena. This growing knowledge base suggests 4 shifts in thinking about policy and practice: (1) early experiences affect lifelong health, not just learning; (2) healthy brain development requires protection from toxic stress, not just enrichment; (3) achieving breakthrough outcomes for young children facing adversity requires supporting the adults who care for them to transform their own lives; and (4) more effective interventions are needed in the prenatal period and first 3 years after birth for the most disadvantaged children and families. The time has come to leverage 21st-century science to catalyze the design, testing, and scaling of more powerful approaches for reducing lifelong disease by mitigating the effects of early adversity.

Risk Factors Associated With Pediatric Acute Recurrent and Chronic Pancreatitis: Lessons From INSPPIRE.

Abstract: Importance Pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) are poorly understood. Objective To characterize and identify risk factors associated with ARP and CP in childhood. Design, Setting, and Participants A multinational cross-sectional study of children with ARP or CP at the time of enrollment to the INSPPIRE (International Study Group of Pediatric Pancreatitis: In Search for a Cure) study at participant institutions of the INSPPIRE Consortium. From August 22, 2012, to February 8, 2015, 155 children with ARP and 146 with CP (aged ≤19 years) were enrolled. Their demographic and clinical information was entered into the REDCap (Research Electronic Data Capture) database at the 15 centers. Differences were analyzed using 2-sample t test or Wilcoxon rank sum test for continuous variables and Pearson χ 2 test or Fisher exact test for categorical variables. Disease burden variables (pain variables, hospital/emergency department visits, missed school days) were compared using Wilcoxon rank sum test. Main Outcomes and Measures Demographic characteristics, risk factors, abdominal pain, and disease burden. Results A total of 301 children were enrolled (mean [SD] age, 11.9 [4.5] years; 172 [57%] female); 155 had ARP and 146 had CP. The majority of children with CP (123 of 146 [84%]) reported prior recurrent episodes of acute pancreatitis. Sex distribution was similar between the groups (57% female in both). Hispanic children were less likely to have CP than ARP (17% vs 28%, respectively; odds ratio [OR] = 0.51; 95% CI, 0.29-0.92; P = .02). At least 1 gene mutation in pancreatitis-related genes was found in 48% of patients with ARP vs 73% of patients with CP ( P PRSS1 or SPINK1 mutations were more likely to present with CP compared with ARP ( PRSS1 : OR = 4.20; 95% CI, 2.14-8.22; P SPINK1 : OR = 2.30; 95% CI, 1.03-5.13; P = .04). Obstructive risk factors did not differ between children with ARP or CP (33% in both the ARP and CP groups), but toxic/metabolic risk factors were more common in children with ARP (21% overall; 26% in the ARP group and 15% in the CP group; OR = 0.55; 95% CI, 0.31-0.99; P = .046). Pancreatitis-related abdominal pain was a major symptom in 81% of children with ARP or CP within the last year. The disease burden was greater in the CP group compared with the ARP group (more emergency department visits, hospitalizations, and medical, endoscopic, and surgical interventions). Conclusions and Relevance Genetic mutations are common in both ARP and CP. Ethnicity and mutations in PRSS1 or SPINK1 may influence the development of CP. The high disease burden in pediatric CP underscores the importance of identifying predisposing factors for progression of ARP to CP in children.

Unintentional pediatric exposures to marijuana in Colorado, 2009-2015

Abstract: Importance As of 2015, almost half of US states allow medical marijuana, and 4 states allow recreational marijuana. To our knowledge, the effect of recreational marijuana on the pediatric population has not been evaluated. Objective To compare the incidence of pediatric marijuana exposures evaluated at a children’s hospital and regional poison center (RPC) in Colorado before and after recreational marijuana legalization and to compare population rate trends of RPC cases for marijuana exposures with the rest of the United States. Design, Setting, and Participants Retrospective cohort study of hospital admissions and RPC cases between January 1, 2009, and December 31, 2015, at Children’s Hospital Colorado, Aurora, a tertiary care children’s hospital. Participants included patients 0 to 9 years of age evaluated at the hospital’s emergency department, urgent care centers, or inpatient unit and RPC cases from Colorado for single-substance marijuana exposures. Exposure Marijuana. Main Outcomes and Measures Marijuana exposure visits and RPC cases, marijuana source and type, clinical effects, scenarios, disposition, and length of stay. Results Eighty-one patients were evaluated at the children’s hospital, and Colorado’s RPC received 163 marijuana exposure cases between January 1, 2009, and December 31, 2015, for children younger than 10 years of age. The median age of children’s hospital visits was 2.4 years (IQR, 1.4-3.4); 25 were girls (40%) . The median age of RPC marijuana exposures was 2 years (IQR, 1.3-4.0), and 85 patients were girls (52%). The mean rate of marijuana-related visits to the children's hospital increased from 1.2 per 100 000 population 2 years prior to legalization to 2.3 per 100,000 population 2 years after legalization ( P = .02). Known marijuana products involved in the exposure included 30 infused edibles (48%). Median length of stay was 11 hours (interquartile range [IQR], 6-19) and 26 hours (IQR, 19-38) for admitted patients. Annual RPC pediatric marijuana cases increased more than 5-fold from 2009 (9) to 2015 (47). Colorado had an average increase in RPC cases of 34% ( P P Conclusions and Relevance Colorado RPC cases for pediatric marijuana increased significantly and at a higher rate than the rest of the United States. The number of children’s hospital visits and RPC case rates for marijuana exposures increased between the 2 years prior to and the 2 years after legalization. Almost half of the patients seen in the children’s hospital in the 2 years after legalization had exposures from recreational marijuana, suggesting that legalization did affect the incidence of exposures.

Association Between Antibiotic Use and Neonatal Mortality and Morbidities in Very Low-Birth-Weight Infants Without Culture-Proven Sepsis or Necrotizing Enterocolitis

Abstract: Importance Excessive antibiotic use has been associated with altered bacterial colonization and may result in antibiotic resistance, fungemia, necrotizing enterocolitis (NEC), and mortality. Exploring the association between antibiotic exposure and neonatal outcomes other than infection-related morbidities may provide insight on the importance of rational antibiotic use, especially in the setting of culture-negative neonatal sepsis. Objective To evaluate the trend of antibiotic use among all hospitalized very low-birth-weight (VLBW) infants across Canada and the association between antibiotic use rates (AURs) and mortality and morbidity among neonates without culture-proven sepsis or NEC. Design, Setting, and Participants A retrospective cohort study was conducted among VLBW infants ( Exposure Duration of antibiotic use during the hospitalization period. Main Outcomes and Measures The AUR was defined as the number of days an infant was exposed to 1 or more antimicrobial agents divided by the total length of hospital stay. The composite primary outcome was defined as mortality or major morbidity, including any of the following: persistent periventricular echogenicity or echolucency on neuroimaging, chronic lung disease, and stage 3 or higher retinopathy of prematurity. Multivariable regression analysis was used to calculate adjusted odds ratios (aORs) and 95% CIs for the association between AURs and outcomes. Results Among 13 738 eligible VLBW infants, 11 669 (84.9%) (mean [SD] gestational age, 27.7 [2.5] weeks; 47.4% female) received antibiotics during their hospital course and were included in the study. The annual AUR decreased from 0.29 in 2010 to 0.25 in 2014 (slope for the best-fit line, −0.011; 95% CI, −0.016 to −0.006; P Conclusions and Relevance Antibiotic use in VLBW infants decreased between 2010 and 2014 in Canada. However, among infants without culture-proven sepsis or without NEC, higher AURs were associated with adverse neonatal outcomes.

Implementing a Trauma-Informed Approach in Pediatric Health Care Networks.

Abstract: Pediatric health care networks serve millions of children each year. Pediatric illness and injury are among the most common potentially emotionally traumatic experiences for children and their families. In addition, millions of children who present for medical care (including well visits) have been exposed to prior traumatic events, such as violence or natural disasters. Given the daily challenges of working in pediatric health care networks, medical professionals and support staff can experience trauma symptoms related to their work. The application of a trauma-informed approach to medical care has the potential to mitigate these negative consequences. Trauma-informed care minimizes the potential for medical care to become traumatic or trigger trauma reactions, addresses distress, provides emotional support for the entire family, encourages positive coping, and provides anticipatory guidance regarding the recovery process. When used in conjunction with family-centered practices, trauma-informed approaches enhance the quality of care for patients and their families and the well-being of medical professionals and support staff. Barriers to routine integration of trauma-informed approaches into pediatric medicine include a lack of available training and unclear best-practice guidelines. This article highlights the importance of implementing a trauma-informed approach and offers a framework for training pediatric health care networks in trauma-informed care practices.

Prevalence of Prediabetes and Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease.

Abstract: Importance Nonalcoholic fatty liver disease (NAFLD) is a major chronic liver disease in children in the United States and is associated with insulin resistance. In adults, NAFLD is also associated with type 2 diabetes. To our knowledge, the prevalence of type 2 diabetes in children with NAFLD is unknown. Objective To determine the prevalence of type 2 diabetes and prediabetes in children with NAFLD and assess type 2 diabetes and prediabetes as risk factors for nonalcoholic steatohepatitis (NASH). Design, Setting, and Participants This was a multicenter, cross-sectional study at 12 pediatric clinical centers across the United States participating in the National Institute of Diabetes and Digestive and Kidney Diseases NASH Clinical Research Network. Children younger than 18 years with biopsy-confirmed NAFLD enrolled in the NASH Clinical Research Network. Main Outcomes and Measures The presence of type 2 diabetes and prediabetes as determined by American Diabetes Association screening criteria using clinical history and fasting laboratory values. Results There were 675 children with NAFLD included in the study with a mean age of 12.6 years and mean body mass index (calculated as weight in kilograms divided by height in meters squared) of 32.5. Most of the children were boys (480 of 675) and Hispanic (445 of 675).The estimated prevalence of prediabetes was 23.4% (95% CI, 20.2%-26.6%), and the estimated prevalence of type 2 diabetes was 6.5% (95% CI, 4.6%-8.4%). Girls with NAFLD had 1.6 (95% CI, 1.04-2.40) times greater odds of having prediabetes and 5.0 (95% CI, 2.49-9.98) times greater odds of having type 2 diabetes than boys with NAFLD. The prevalence of NASH was higher in those with type 2 diabetes (43.2%) compared with prediabetes (34.2%) or normal glucose (22%) ( P Conclusions and Relevance In this study, nearly 30% of children with NAFLD also had type 2 diabetes or prediabetes. These children had greater odds of having NASH and thus were at greater long-term risk for adverse hepatic outcomes.

Academic Outcomes 2 Years After Working Memory Training for Children With Low Working Memory : A Randomized Clinical Trial

Abstract: Importance Working memory training may help children with attention and learning difficulties, but robust evidence from population-level randomized controlled clinical trials is lacking. Objective To test whether a computerized adaptive working memory intervention program improves long-term academic outcomes of children 6 to 7 years of age with low working memory compared with usual classroom teaching. Design, Setting, and Participants Population-based randomized controlled clinical trial of first graders from 44 schools in Melbourne, Australia, who underwent a verbal and visuospatial working memory screening. Children were classified as having low working memory if their scores were below the 15th percentile on either the Backward Digit Recall or Mister X subtest from the Automated Working Memory Assessment, or if their scores were below the 25th percentile on both. These children were randomly assigned by an independent statistician to either an intervention or a control arm using a concealed computerized random number sequence. Researchers were blinded to group assignment at time of screening. We conducted our trial from March 1, 2012, to February 1, 2015; our final analysis was on October 30, 2015. We used intention-to-treat analyses. Intervention Cogmed working memory training, comprising 20 to 25 training sessions of 45 minutes’ duration at school. Main Outcomes and Measures Directly assessed (at 12 and 24 months) academic outcomes (reading, math, and spelling scores as primary outcomes) and working memory (also assessed at 6 months); parent-, teacher-, and child-reported behavioral and social-emotional functioning and quality of life; and intervention costs. Results Of 1723 children screened (mean [SD] age, 6.9 [0.4] years), 226 were randomized to each arm (452 total), with 90% retention at 1 year and 88% retention at 2 years; 90.3% of children in the intervention arm completed at least 20 sessions. Of the 4 short-term and working memory outcomes, 1 outcome (visuospatial short-term memory) benefited the children at 6 months (effect size, 0.43 [95% CI, 0.25-0.62]) and 12 months (effect size, 0.49 [95% CI, 0.28-0.70]), but not at 24 months. There were no benefits to any other outcomes; in fact, the math scores of the children in the intervention arm were worse at 2 years (mean difference, −3.0 [95% CI, −5.4 to −0.7]; P = .01). Intervention costs were A$1035 per child. Conclusions and Relevance Working memory screening of children 6 to 7 years of age is feasible, and an adaptive working memory training program may temporarily improve visuospatial short-term memory. Given the loss of classroom time, cost, and lack of lasting benefit, we cannot recommend population-based delivery of Cogmed within a screening paradigm. Trial Registration anzctr.org.au Identifier:ACTRN12610000486022

Use of Mobile Technology to Calm Upset Children: Associations With Social-Emotional Development.

Abstract: 4. National Center for Education Statistics; US Department of Education. Average National Assessment of Educational Progress reading scale scores and percentage distribution of students, by age, amount of reading for school and for fun, and time spent on homework and watching TV/video: selected years, 1984 through 2008. http://nces.ed.gov/programs/digest/d12/tables/dt12_144 .asp. Accessed September 13, 2015.

Use of Procalcitonin Assays to Predict Serious Bacterial Infection in Young Febrile Infants.

Abstract: Importance The procalcitonin (PCT) assay is an accurate screening test for identifying invasive bacterial infection (IBI); however, data on the PCT assay in very young infants are insufficient. Objective To assess the diagnostic characteristics of the PCT assay for detecting serious bacterial infection (SBI) and IBI in febrile infants aged 7 to 91 days. Design, Setting, and Participants A prospective cohort study that included infants aged 7 to 91 days admitted for fever to 15 French pediatric emergency departments was conducted for a period of 30 months (October 1, 2008, through March 31, 2011). The data management and analysis were performed from October 1, 2011, through October 31, 2014. Main Outcomes and Measures The diagnostic characteristics of the PCT assay, C-reactive protein (CRP) concentration, white blood cell (WBC) count, and absolute neutrophil cell (ANC) count for detecting SBI and IBI were described and compared for the overall population and subgroups of infants according to the age and the duration of fever. Laboratory test cutoff values were calculated based on receiver operating characteristic (ROC) curve analysis. The SBIs were defined as a pathogenic bacteria in positive culture of blood, cerebrospinal fluid, urine, or stool samples, including bacteremia and bacterial meningitis classified as IBIs. Results Among the 2047 infants included, 139 (6.8%) were diagnosed as having an SBI and 21 (1.0%) as having an IBI (11.0% and 1.7% of those with blood culture (n = 1258), respectively). The PCT assay offered an area under the curve (AUC) of ROC curve similar to that for CRP concentration for the detection of SBI (AUC, 0.81; 95% CI, 0.75-0.86; vs AUC, 0.80; 95% CI, 0.75-0.85; P = .70). The AUC ROC curve for the detection of IBI for the PCT assay was significantly higher than that for the CRP concentration (AUC, 0.91; 95% CI, 0.83-0.99; vs AUC, 0.77; 95% CI, 0.65-0.89; P = .002). Using a cutoff value of 0.3 ng/mL for PCT and 20 mg/L for CRP, negative likelihood ratios were 0.3 (95% CI, 0.2-0.5) for identifying SBI and 0.1 (95% CI, 0.03-0.4) and 0.3 (95% CI, 0.2-0.7) for identifying IBI, respectively. Similar results were obtained for the subgroup of infants younger than 1 month and for those with fever lasting less than 6 hours. Conclusions and Relevance The PCT assay has better diagnostic accuracy than CRP measurement for detecting IBI; the 2 tests perform similarly for identifying SBI in febrile infants aged 7 to 91 days.

Association Between Cesarean Birth and Risk of Obesity in Offspring in Childhood, Adolescence, and Early Adulthood

Abstract: Importance Cesarean birth has been associated with higher risk of obesity in offspring, but previous studies have focused primarily on childhood obesity and have been hampered by limited control for confounders. Objective To investigate the association between cesarean birth and risk of obesity in offspring. Design, Setting, and Participants A prospective cohort study was conducted from September 1, 1996, to December 31, 2012, among participants of the Growing Up Today Study, including 22 068 offspring born to 15 271 women, followed up via questionnaire from ages 9 to 14 through ages 20 to 28 years. Data analysis was conducted from October 10, 2015, to June 14, 2016. Exposure Birth by cesarean delivery. Main Outcomes and Measures Risk of obesity based on International Obesity Task Force or World Health Organization body mass index cutoffs, depending on age. Secondary outcomes included risks of obesity associated with changes in mode of delivery and differences in risk between siblings whose modes of birth were discordant. Results Of the 22 068 offspring (20 950 white; 9359 male and 12 709 female), 4921 individuals (22.3%) were born by cesarean delivery. The cumulative risk of obesity through the end of follow-up was 13% among all participants. The adjusted risk ratio for obesity among offspring delivered via cesarean birth vs those delivered via vaginal birth was 1.15 (95% CI, 1.06-1.26; P = .002). This association was stronger among women without known indications for cesarean delivery (adjusted risk ratio, 1.30; 95% CI, 1.09-1.54; P = .004). Offspring delivered via vaginal birth among women who had undergone a previous cesarean delivery had a 31% (95% CI, 17%-47%) lower risk of obesity compared with those born to women with repeated cesarean deliveries. In within-family analysis, individuals born by cesarean delivery had 64% (8%-148%) higher odds of obesity than did their siblings born via vaginal delivery. Conclusions and Relevance Cesarean birth was associated with offspring obesity after accounting for major confounding factors. Although additional research is needed to clarify the mechanisms underlying this association, clinicians and patients should weigh this risk when considering cesarean delivery in the absence of a clear indication.

International and Interdisciplinary Identification of Health Care Transition Outcomes

Abstract: Importance There is a lack of agreement on what constitutes successful outcomes for the process of health care transition (HCT) among adolescent and young adults with special health care needs. Objective To present HCT outcomes identified by a Delphi process with an interdisciplinary group of participants. Design, Setting, and Participants A Delphi method involving 3 stages was deployed to refine a list of HCT outcomes. This 18-month study (from January 5, 2013, of stage 1 to July 3, 2014, of stage 3) included an initial literature search, expert interviews, and then 2 waves of a web-based survey. On this survey, 93 participants from outpatient, community-based, and primary care clinics rated the importance of the top HCT outcomes identified by the Delphi process. Analyses were performed from July 5, 2014, to December 5, 2014. Exposures Health care transition outcomes of adolescents and young adults with special health care needs. Main Outcomes and Measures Importance ratings of identified HCT outcomes rated on a Likert scale from 1 (not important) to 9 (very important). Results The 2 waves of surveys included 117 and 93 participants as the list of outcomes was refined. Transition outcomes were refined by the 3 waves of the Delphi process, with quality of life being the highest-rated outcome with broad agreement. The 10 final outcomes identified included individual outcomes (quality of life, understanding the characteristics of conditions and complications, knowledge of medication, self-management, adherence to medication, and understanding health insurance), health services outcomes (attending medical appointments, having a medical home, and avoidance of unnecessary hospitalization), and a social outcome (having a social network). Participants indicated that different outcomes were likely needed for individuals with cognitive disabilities. Conclusions and Relevance Quality of life is an important construct relevant to HCT. Future research should identify valid measures associated with each outcome and further explore the role that quality of life plays in the HCT process. Achieving consensus is a critical step toward the development of reliable and objective comparisons of HCT outcomes across clinical conditions and care delivery locations.

Evolution of Depression and Anxiety Symptoms in Parents of Very Preterm Infants During the Newborn Period

Abstract: Importance Mothers experience heightened depression and anxiety following very preterm (VPT) birth, but how these symptoms evolve during the first months after birth is unknown. Research on the psychological adjustment of fathers following VPT birth is limited. Objectives To describe the trajectory and predictors of distress in parents of VPT infants during the first 12 weeks after birth, and to compare rates of depression and anxiety in parents of VPT infants with those in parents of healthy full-term (FT) infants shortly after birth and at 6 months’ postnatal age. Design, Setting, and Participants Longitudinal, prospective, follow-up cohort study of depression and anxiety symptoms in parents of VPT infants ( 2499 g; born at the Royal Women’s Hospital between August 15, 2012, and March 26, 2014; not admitted to the neonatal nursery) shortly after birth and at age 6 months. Exposure Birth of a VPT infant. Main Outcomes and Measures Symptoms of depression (Center for Epidemiological Studies Depression Scale) and anxiety (Hospital Anxiety and Depression Scale). Results The study included 113 mothers (mean [SD] age at birth, 32.7 [5.3] years) and 101 fathers (mean [SD] age at birth, 34.7 [6.4] years) of 149 VPT infants (49% male; 84 singletons, 65 multiples; mean [SD] birth weight, 1021 [261] g) as well as 117 mothers (mean [SD] age at birth, 32.9 [4.8] years) and 110 fathers (mean [SD] age at birth, 35.9 [5.3] years) of 151 healthy FT infants (50% male; 149 singletons, 2 multiples; mean [SD] birth weight, 3503 [438] g). Mean scores and rates of depression and anxiety reduced over time for parents of VPT infants in the 12 weeks after birth: the mean (95% CI) change in depression score per week was −0.52 (−0.73 to −0.31;P Conclusions and Relevance Mothers and fathers of VPT infants had elevated rates of depression and anxiety symptoms that declined over time, although remaining above expected levels throughout the newborn period and at 6 months.

Early Antibiotic Treatment for Pediatric Febrile Urinary Tract Infection and Renal Scarring.

Abstract: Importance Existing data regarding the association between delayed initiation of antimicrobial therapy and the development of renal scarring are inconsistent. Objective To determine whether delay in the initiation of antimicrobial therapy for febrile urinary tract infections (UTIs) is associated with the occurrence and severity of renal scarring. Design, Setting, and Participants Retrospective cohort study that combined data from 2 previously conducted longitudinal studies (the Randomized Intervention for Children With Vesicoureteral Reflux trial and the Careful Urinary Tract Infection Evaluation Study). Children younger than 6 years with a first or second UTI were followed up for 2 years. Exposure Duration of the child’s fever prior to initiation of antimicrobial therapy for the index UTI. Main Outcomes and Measures New renal scarring defined as the presence of photopenia plus contour change on a late dimercaptosuccinic acid renal scan (obtained at study exit) that was not present on the baseline scan. Results Of the 482 children included in the analysis, 434 were female (90%), 375 were white (78%), and 375 had vesicoureteral reflux (78%). The median age was 11 months. A total of 35 children (7.2%) developed new renal scarring. Delay in the initiation of antimicrobial therapy was associated with renal scarring; the median (25th, 75th percentiles) duration of fever prior to initiation of antibiotic therapy in those with and without renal scarring was 72 (30, 120) and 48 (24, 72) hours, respectively ( P = .003). Older age (OR, 1.03; 95% CI, 1.01-1.05), Hispanic ethnicity (OR, 5.24; 95% CI, 2.15-12.77), recurrent urinary tract infections (OR, 0.97; 95% CI, 0.27-3.45), and bladder and bowel dysfunction (OR, 6.44; 95% CI, 2.89-14.38) were also associated with new renal scarring. Delay in the initiation of antimicrobial therapy remained significantly associated with renal scarring even after adjusting for these variables. Conclusions and Relevance Delay in treatment of febrile UTIs and permanent renal scarring are associated. In febrile children, clinicians should not delay testing for UTI.

Association of Persistent Postconcussion Symptoms With Pediatric Quality of Life.

Abstract: Importance Persistent postconcussion symptoms (PPCS) pose long-term challenges and can negatively affect patients’ health-related quality of life (HRQoL). To date, no large comprehensive study has addressed the association between PPCS and HRQoL. Objectives To determine the association between HRQoL and PPCS at 4 weeks after concussion and assess the degree of impairment of HRQoL in the subsequent 12 weeks. Design, Setting, and Participants In a prospective, multicenter cohort study (Predicting Persistent Postconcussive Problems in Pediatrics [5P]) from August 14, 2013, to September 30, 2014, children aged 5 to 18 years who presented to the emergency department within 48 hours after head injury and were considered to have an acute concussion were enrolled across 9 pediatric emergency departments within the Pediatric Emergency Research Canada Network. Persistent postconcussion symptoms were defined as 3 or more persistent symptoms on the validated Post-Concussion Symptom Inventory at 4 weeks. Linear mixed effects random coefficients models evaluated the association between PPCS and HRQoL, adjusting for potential confounders including age, sex, prior concussions, migraine, anxiety, learning disability, depression, and sleep disorder. Main Outcomes and Measures The primary outcome was HRQoL assessed with the validated Pediatric Quality of Life Inventory version 4.0 (PedsQL-4.0) at 4, 8, and 12 weeks after head injury. Results Of 2006 children enrolled (median age, 11.8 years [interquartile range, 8.9-14.6 years]; 1241 boys and 765 girls), 1667 (83.1%) completed the PedsQL-4.0 at all 3 time points. Of these 1667 children, the 510 with PPCS (30.6%) had lower total PedsQL-4.0 scores (mean, 70.0) than did those without PPCS (mean, 80.3; mean difference, –10.3; 95% CI, −9.4 to −11.2). Patients with PPCS also had significantly lower physical, emotional, social, and school PedsQL-4.0 subscores at 4, 8, and 12 weeks. Patients with PPCS had lower HRQoL than published healthy norms at 4 weeks (mean difference, 13.89; 95% CI, 11.55-16.23), 8 weeks (mean difference, 11.63; 95% CI, 9.34-13.93), and 12 weeks (mean difference, 9.38; 95% CI, 7.01-11.75; P P Conclusions and Relevance Children with PPCS have lower HRQoL compared with those who have recovered from concussion, yet deficits in HRQoL are pervasive across all domains and may persist for months even in children whose symptoms have resolved. Future interventional research should target the effect of concussion on HRQoL.

Thyroid Disorders in Children and Adolescents: A Review

Abstract: Importance Normal thyroid gland function is critical for early neurocognitive development, as well as for growth and development throughout childhood and adolescence. Thyroid disorders are common, and attention to physical examination findings, combined with selected laboratory and radiologic tools, aids in the early diagnosis and treatment. Objective To provide a practical review of the presentation, evaluation, and treatment of thyroid disorders commonly encountered in a primary care practice. Evidence Review We performed a literature review using the PubMed database. Results focused on reviews and articles published from January 1, 2010, through December 31, 2015. Articles published earlier than 2010 were included when appropriate for historical perspective. Our review emphasized evidence-based management practices for the clinician, as well as consensus statements and guidelines. A total of 479 articles for critical review were selected based on their relevance to the incidence, pathophysiology, laboratory evaluation, radiological assessment, and treatment of hypothyroidism, hyperthyroidism, thyroid nodules, and thyroid cancer in children and adolescents. Eighty-three publications were selected for inclusion in this article based on their relevance to these topics. Findings The primary care physician is often the first health care professional responsible for initiating the evaluation of a thyroid disorder in children and adolescents. Patients may be referred secondary to an abnormal newborn screening, self-referred after a caregiver raises concern, or identified to be at risk of a thyroid disorder based on findings from a routine well-child visit. Irrespective of the path of referral, knowledge of the signs and symptoms of hypothyroidism, hyperthyroidism, and thyroid nodules, as well as the general approach to evaluation and management, will help the primary care physician complete an initial assessment and determine which patients would benefit from referral to a pediatric endocrinologist. Conclusions and Relevance Early identification and treatment of thyroid disease in children and adolescents is critical to optimize growth and development. The primary care physician plays a critical role in identifying patients at risk. An understanding of risk factors, clinical signs and symptoms, and interpretation of screening laboratories ensures an efficient and accurate diagnosis of these common disorders. Regular communication between the primary care physician and the subspecialist is critical to optimize outcome because the majority of patients with thyroid disorders will require long-term to lifelong medical therapy and/or surveillance.

Synbiotics for Prevention and Treatment of Atopic Dermatitis: A Meta-analysis of Randomized Clinical Trials

Abstract: Importance Atopic dermatitis (AD) is a highly prevalent condition that may be associated with an altered gastrointestinal microbiota that promotes an immune environment more susceptible to allergic disease. Synbiotics, a mixture of prebiotics and probiotics, have been used for the prevention and treatment of AD. Objective To investigate the efficacy of synbiotics for primary prevention and treatment of AD. Data Sources PubMed/MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the CAB Abstracts Archive searchable database were searched from the inception of all databases to October 15, 2015, with no language restrictions. Study Selection We included all published randomized clinical trials of synbiotics for prevention and/or treatment of AD. To be included, a publication needed to clearly define the intervention as oral administration of synbiotics (combination of probiotics and prebiotics) and must have included an assessment of AD disease severity, such as the Severity Scoring of Atopic Dermatitis (SCORAD) index, or the incidence of AD as an outcome measure. Only 8 of 257 initially identified studies (3%) met selection criteria. Data Extraction and Synthesis Data extraction was independently done by multiple observers and cross-checked to avoid errors. The quality of the selected studies was critically examined following the Cochrane guidelines. Data were pooled using a random-effects model. Main Outcomes and Measures The primary outcomes were the SCORAD index (treatment studies) and the relative risk of AD (prevention studies). The hypothesis was formulated before data collection. Results A total of 257 abstracts were screened to identify 6 treatment studies (369 children enrolled; aged 0 months to 14 years) and 2 prevention studies (1320 children enrolled; up to age 6 months in one study and term neonates aged P = .008). Heterogeneity was significant ( I 2 = 77.1%; P = .001). Subgroup analysis showed that the beneficial effect was significant only when using mixed strains of bacteria (weighted mean difference, −7.32; 95% CI, −13.98 to −0.66; P = .03) and when used in children aged 1 year or older (weighted mean difference, −7.37; 95% CI, −14.66 to −0.07; P = .048). From the 2 prevention studies included, the pooled relative risk ratio of AD in those treated with synbiotics compared with placebo was 0.44 (95% CI, 0.11 to 1.83; P = .26). Conclusions and Relevance This meta-analysis shows evidence that supports the use of synbiotics for the treatment of AD, particularly synbiotics with mixed strains of bacteria and for children aged 1 year or older. Further studies are needed to evaluate the effectiveness of synbiotics for primary prevention of AD.