Journals

Pediatrics

Pediatrics

PEDIATRICS current issue

  • Pediatric Antibacterial and Antifungal Trials From 2007 to 2017
    BACKGROUND AND OBJECTIVES:
    The impact of the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) on pediatric antibacterial or antifungal drug trials is unknown. Our objective was to identify and characterize trials conducted under the BPCA and/or the PREA.
    METHODS:
    Pediatric antibacterial and antifungal drug trials with industry or US federal funding registered in clinicaltrials.gov from 2007 to 2017 were identified. Those conducted under BPCA and/or PREA were identified through US Food and Drug Administration and National Institute of Child Health and Human Development databases.
    RESULTS:
    Of 17 495 pediatric trials registered on clinicaltrials.gov between October 2007 and September 2017, 122 systemic antibacterial or antifungal drug trials with industry or US federal funding were identified. Of these 122 trials, 98 (80%) involved antibacterials only, 23 (19%) antifungals only, and 1 (1%) both antibacterials and antifungals. These represented


  • ADA2 Deficiency Mimicking Idiopathic Multicentric Castleman Disease
    Multicentric Castleman disease (MCD) is a rare entity that, unlike unicentric Castleman disease, involves generalized polyclonal lymphoproliferation, systemic inflammation, and multiple-organ system failure resulting from proinflammatory hypercytokinemia, including, in particular, interleukin-6. A subset of MCD is caused by human herpesvirus-8 (HHV-8), although the etiology for HHV-8–negative, idiopathic MCD (iMCD) cases is unknown at present. Recently, a consensus was reached on the diagnostic criteria for iMCD to aid in diagnosis, recognize mimics, and initiate prompt treatment. Pediatric iMCD remains particularly rare, and differentiation from MCD mimics in children presenting with systemic inflammation and lymphoproliferation is a challenge. We report on a young boy who presented with a HHV-8–negative, iMCD-like phenotype and was found to suffer from the monogenic disorder deficiency of adenosine deaminase 2 (DADA2), which is caused by loss-of-function mutations in CECR1. DADA2 prototypic features include early-onset ischemic and hemorrhagic strokes, livedoid rash, systemic inflammation, and polyarteritis nodosa vasculopathy, but marked clinical heterogeneity has been observed. Our patient’s presentation remains unique, with predominant systemic inflammation, lymphoproliferation, and polyclonal hypergammaglobulinemia but without apparent immunodeficiency. On the basis of the iMCD-like phenotype with elevated interleukin-6 expression, treatment with tocilizumab was initiated, resulting in immediate normalization of clinical and biochemical parameters. In conclusion, iMCD and DADA2 should be considered in the differential diagnosis of children presenting with systemic inflammation and lymphoproliferation. We describe the first case of DADA2 that mimics the clinicopathologic features of iMCD, and our report extends the clinical spectrum of DADA2 to include predominant immune activation and lymphoproliferation.




  • Fertility Preservation for a Transgender Teenager
    In this article, we discuss a case in which a 16-year-old birth-assigned male came out to her parents as transgender. She is referred to the gender management program at a large pediatric academic center to discuss hormone therapy. She was initially evaluated by a psychiatrist, diagnosed with gender dysphoria and anxiety, and treated with medication and psychotherapy. When her anxiety was well controlled and she met eligibility and readiness criteria, she was referred to 1 of 2 pediatric endocrinologists in the gender management program to discuss hormone therapy. As part of the discussion about the risks/benefits of estrogen therapy, the pediatric endocrinologist discussed options for fertility preservation (FP) before potentially gonadotoxic therapy. The patient stated that she was not interested in FP. Her mother requested procedures to preserve the possibility that the daughter could have biological children someday. We asked experts in the care of transgender youth to discuss ways in which the doctor could respond to this disagreement between parents and a teenager about FP.


  • Family-Driven Goals to Improve Care for Children With Autism Spectrum Disorder
    OBJECTIVES:
    Constipation and insomnia are not consistently identified and treated in children with autism spectrum disorder (ASD) despite their high prevalence and deleterious impact in this population. To standardize care, a constipation practice pathway and an insomnia practice pathway were previously developed by Autism Treatment Network clinicians. Our objective was to implement and refine these practice pathways in clinical settings.
    METHODS:
    Eleven Autism Treatment Network sites participated in a Learning Collaborative (ie, multidisciplinary quality improvement team) and chose to implement either the constipation or insomnia practice pathway in the clinical setting. Families set intervention goals (eg, increase stool frequency, decrease nighttime awakenings) before treatment. Each site began implementation with 1 patient and then increased implementation by factors of 5. Before each increase, the Learning Collaborative evaluated progress and refined the practice pathways. Process improvement was measured primarily by duration until goal attainment and by percentage of families who meet their goals.
    RESULTS:
    Across sites, 82 children with ASD and constipation and 101 children with ASD and insomnia were managed. Difficulties with intervention adherence and communication between providers and families were reported and were subsequently improved with parallel refinements to both practice pathways. The most notable modification was incorporating a goal-setting session in which families generated their own intervention goals (ie, family-driven goals). In this quality improvement initiative, 75% of families met at least 1 constipation or insomnia goal, with the median time to improvement being 6 weeks.
    CONCLUSIONS:
    By integrating a family-centered approach into the standardization of care, constipation and insomnia practice pathways may improve engagement, adherence, and management of medical conditions in children with ASD.


  • A 14-Year-Old Boy With Fevers, Cytopenias, and Neurocognitive Decline
    A 14-year-old boy presented to our institution with a 1-month history of neurocognitive decline and intermittent fevers. His history was significant for fevers, headaches, and a 10-lb weight loss. Previous examinations by multiple medical providers were significant only for bilateral cervical lymphadenopathy. Previous laboratory workup revealed leukopenia, neutropenia, and elevated inflammatory markers. Despite improvement in his laboratory values after his initial presentation, his fevers persisted, and he developed slowed and “jerky” movements, increased sleep, slurred speech, delusions, visual hallucinations, and deterioration in his school performance. A brain MRI performed at an outside hospital before admission at our institution was concerning for patchy, increased T2 and fluid-attenuated inversion recovery signal intensity in multiple areas, including the basal ganglia. After transfer to our institution and admission to the pediatric hospital medicine team, the patient had an acute decompensation. Our subspecialists will discuss the initial evaluation, workup, differential diagnosis, definitive diagnosis, and subsequent management of this patient.


  • Use of Oximetry to Determine Need for Adenotonsillectomy for Sleep-Disordered Breathing
    OBJECTIVES:
    We evaluated the efficacy of adenotonsillectomy (T/A) in children with sleep-disordered breathing (SDB) in a controlled study using oximetry. We hypothesized that children with SDB and abnormal nocturnal oximetry in a community setting will have improved hypoxemia indices after T/A.
    METHODS:
    Children with snoring and tonsillar hypertrophy (4–10 years old) who were candidates for T/A were randomly assigned to 2 oximetry sequences (baseline and 3-month follow-up): (1) oximetry immediately before T/A and at the 3-month follow-up, which occurred postoperatively (T/A group); or (2) oximetry at the initial visit and at the end of the usual 3-month waiting period for surgery (control group). Outcomes were (1) proportion of subjects with McGill oximetry score (MOS) >1 at baseline acquiring MOS of 1 at follow-up and (2) proportion of subjects achieving oxygen desaturation (≥3%) of hemoglobin index (ODI3) 1 in the T/A group and 10 of 21 (47.6%) children with MOS >1 in the control group had MOS of 1 at follow-up (P = .14). More subjects in the T/A than in the control group achieved ODI3


  • Infant Analgesia With a Combination of Breast Milk, Glucose, or Maternal Holding
    OBJECTIVES:
    We studied neonatal cortical brain response to 4 types of nonpharmacological analgesia (oral glucose, expressed breast milk, maternal holding plus oral glucose, breastfeeding). We aimed to assess the differential effect of oral solutions (glucose, breast milk) given alone or combined with the maternal-infant relationship (holding, breastfeeding).
    METHODS:
    Eighty healthy term newborns undergoing a heel stick were randomly assigned to 4 parallel groups of 20 infants each: group 1, infants received a glucose solution on a changing table; group 2, infants received expressed breast milk on a changing table; group 3, infants received a glucose solution in their mothers’ arms; and group 4, infants were breastfed by their mothers. Cortical activation in parietal, temporal, and frontal cortices was assessed by multichannel near-infrared spectroscopy. Pain expression was also evaluated.
    RESULTS:
    Oral glucose alone or combined with maternal holding was associated with no cortical activation during heel stick. Expressed breast milk was associated with localized bilateral activation of somatosensory and motor cortices (P < .01). Breastfeeding was associated with extensive bilateral activation of somatomotor, somatosensory, and right parietal cortices (P < .01). Pain expression was lower with the maternal-infant relationship (P = .007).
    CONCLUSIONS:
    Oral glucose, either alone or combined with maternal holding, appears to block or weaken cortical pain processing. Breast milk alone is associated with localized cortical activation. Breastfeeding is associated with extensive activation and may act by extending cortical processing. Maternal relationship, both combined with oral glucose and in breastfeeding, shows the greatest analgesic effect, although the neural patterns involved are distributed differently.


  • Controversy About a High-Risk and Innovative Fetal Cardiac Intervention
    A 20-week-old fetus was diagnosed with critical pulmonary valve stenosis. Given the ultrasound findings, the outcome was difficult to predict. The fetal cardiologists discussed the possibility of a pulmonary valvuloplasty (an experimental procedure) with the parents, wherein the fetal right ventricle would be punctured with a long 18G needle, and through it, a wire advanced across the pulmonary valve, allowing for balloon dilation of the valve. The experimental procedure had been performed at a handful of centers. There were some reports of success. The parents sought an opinion at one of the referral centers that had tried the procedure. The doctors there recommended against it. The doctors at the original center were unsure whether they should try the procedure. The parents wanted it. In this ethics rounds, doctors and the parents discuss the arguments for and against a high-risk, innovative in utero procedure.


  • Adolescent E-Cigarette, Hookah, and Conventional Cigarette Use and Subsequent Marijuana Use
    OBJECTIVES:
    Noncigarette tobacco products may confer a risk of marijuana use similar to combustible cigarettes. We examined whether adolescent electronic cigarette (e-cigarette), hookah, or combustible cigarette use is associated with initiating and currently using marijuana as well as using both tobacco and marijuana concurrently.
    METHODS:
    Adolescents from 10 public schools in Los Angeles, California, completed in-classroom surveys at baseline (fall 2013, ninth grade) and at a 24-month follow-up (fall 2015, 11th grade). Among adolescents who never used marijuana at baseline (N = 2668), associations of baseline e-cigarette, hookah, or combustible cigarette use with ever marijuana use (initiation), current marijuana use (past 30 days), and current dual use of marijuana and these tobacco products at the 24-month follow-up were examined.
    RESULTS:
    Baseline ever versus never e-cigarette use was associated with initiation (odds ratio [OR] 3.63; 95% confidence interval [CI] 2.69–4.90) and current (OR 3.67; 95% CI 2.51–5.36) marijuana use 24 months later. Ever versus never hookah use was associated with initiation (OR 3.55; 95% CI 2.49–5.08) and current (OR 4.10; 95% CI 2.69–6.25) marijuana use 24 months later. Similar associations were observed for combustible cigarette smoking and initiation (OR 4.30; 95% CI 2.79–6.63) and current use of marijuana (OR 1.97; 95% CI 1.05–3.68). Current use of any of these tobacco products at baseline was associated with current use of both tobacco and marijuana (OR 2.28; 95% CI 1.47–3.55) 24 months later.
    CONCLUSIONS:
    The association between tobacco use and subsequent marijuana use across adolescence extends to multiple tobacco products.


  • Surgeries and Health Outcomes Among Patients With Spina Bifida
    BACKGROUND AND OBJECTIVES:
    Patients with spina bifida (SB) typically develop serious secondary conditions and undergo surgical procedures related to neurologic disorders, orthopedic abnormalities, bladder and bowel dysfunction, and skin breakdown. In this study, we describe the age distribution of common surgical procedures and health outcomes in patients with SB.
    METHODS:
    Using serial cross-sectional data from the National Spina Bifida Patient Registry (2009–2013; n = 4664), we examined surgical procedures (gastrointestinal, neurologic, orthopedic, skin, urologic, and other) and health outcomes (fecal continence, urinary continence, skin breakdown, and ambulation status) of patients with SB by age and SB type (myelomeningocele and nonmyelomeningocele).
    RESULTS:
    All patients who were enrolled had available health outcome data, and 81.5% (n = 3801) of patients had complete surgical procedure data, which totaled 18 891 procedures across their lifetimes. Almost all procedures (91.4%) occurred among participants with myelomeningocele SB. For both types of SB, the distribution of procedures varied by age. The most frequent procedures were neurologic, with approximately half (53%) occurring in patients


  • Efficacy of Propranolol Between 6 and 12 Months of Age in High-Risk Infantile Hemangioma
    BACKGROUND AND OBJECTIVES:
    There is no consensus on optimal treatment duration for propranolol in infantile hemangioma (IH). We evaluated the efficacy and safety of oral propranolol solution administered for a minimum of 6 months up to a maximum of 12 months of age in high-risk IH.
    METHODS:
    This single-arm, open-label, phase 3 study was conducted in patients aged 35 to 150 days with high-risk IH in 10 hospitals between 2015 and 2017. The study comprised a 6-month initial treatment period (ITP) plus continuation up to 12 months of age if complete success was not achieved, a follow-up, and a retreatment period. Patients received oral propranolol twice daily (3 mg/kg per day). The primary end point was the success rate at the end of the ITP. Furthermore, the persistence of IH response and efficacy of retreatment was evaluated.
    RESULTS:
    The success rate after 6 months of treatment was 47%, increasing to 76% at the end of the ITP. Of the patients who achieved success, 68% sustained success for 3 months without treatment, and 24% required retreatment. Of the 8 patients who were retreated, 7 achieved success. Adverse events, reported by 80% of patients, were mild, which were expected in this population or known propranolol side effects.
    CONCLUSIONS:
    Oral propranolol administered beyond 6 months and up to 12 months of age meaningfully increases the success rate in high-risk IH. Success was sustained in most patients up to 3 months after stopping treatment. Retreatment was efficacious, and the safety profile satisfactory.


  • Use of Electronic Health Record Integration for Down Syndrome Guidelines
    OBJECTIVES:
    Established guidelines from the American Academy of Pediatrics for the care of patients with Down syndrome are often not followed. Our goal was to integrate aspects of the guidelines into the electronic health record (EHR) to improve guideline adherence throughout a child’s life span.
    METHODS:
    Two methods of EHR integration with age-based logic were created and implemented in June 2016: (1) a best-practice advisory that prompts an order for referral to genetics; and (2) a health maintenance record that tracks completion of complete blood cell count and/or hemoglobin testing, thyrotropin testing, echocardiogram, and sleep study. Retrospective chart review of patients with Down syndrome and visits to locations with EHR integration (NICUs, primary care centers, and genetics clinics) assessed adherence to the components of EHR integration; the impact was analyzed through statistical process control charts.
    RESULTS:
    From July 2015 to October 2017, 235 patients with Down syndrome (ages 0 to 32 years) had 466 visits to the EHR integration locations. Baseline adherence for individual components ranged from 51% (sleep study and hemoglobin testing) to 94% (echocardiogram). EHR integration was associated with a shift in adherence to all select recommendations from 61.6% to 77.3% (P < .001) including: genetic counseling, complete blood cell count and/or hemoglobin testing, thyrotropin testing, echocardiogram, and sleep study.
    CONCLUSIONS:
    Integrating specific aspects of Down syndrome care into the EHR can improve adherence to guideline recommendations that span the life of a child. Future quality improvement should be focused on older children and adults with Down syndrome.


  • Neurodevelopment After Perinatal Arterial Ischemic Stroke
    BACKGROUND AND OBJECTIVES:
    Perinatal arterial ischemic stroke (PAIS) leads to cerebral palsy in ~30% of affected children and has other neurologic sequelae. Authors of most outcome studies focus on middle cerebral artery (MCA) stroke without differentiating between site and extent of affected tissue. Our aim with this study was to report outcomes after different PAIS subtypes.
    METHODS:
    Between 1990 and 2015, 188 term infants from 2 centers (London [n = 79] and Utrecht [n = 109]) had PAIS on their neonatal MRI. Scans were reevaluated to classify stroke territory and determine specific tissue involvement. At 18 to 93 (median 41.7) months, adverse neurodevelopmental outcomes were recorded as 1 or more of cerebral palsy, cognitive deficit, language delay, epilepsy, behavioral problems, or visual field defect.
    RESULTS:
    The MCA territory was most often involved (90%), with posterior or anterior cerebral artery territory strokes occurring in 9% and 1%, respectively. Three infants died, and 24 had scans unavailable for reevaluation or were lost to follow-up. Of 161 infants seen, 54% had an adverse outcome. Outcomes were the same between centers. Main branch MCA stroke resulted in 100% adverse outcome, whereas other stroke subtypes had adverse outcomes in only 29% to 57%. The most important outcome predictors were involvement of the corticospinal tracts and basal ganglia.
    CONCLUSIONS:
    Although neurodevelopmental outcome was adverse in at least 1 domain with main branch MCA stroke, in other PAIS subtypes outcome was favorable in 43% to 71% of children. Site and tissue involvement is most important in determining the outcome in PAIS.


  • Longitudinal BMI Growth Curves for Surviving Preterm NICU Infants Based on a Large US Sample
    BACKGROUND:
    Longitudinal growth curves, based on repeated measurements from the same group of infants, exist for preterm infant weight and length but not for BMI. Our existing BMI (weight divided by length squared) curves are based on cross-sectional birth data obtained from a different group of infants at each gestational age (GA).
    METHODS:
    We calculated BMI over time for 68 693 preterm infants between 24 and 36 weeks GA. Stratifying infants by sex, GA at birth, and quintiles based on birth BMI, we created longitudinal median curves using R and validated the resulting curves for empirical fit, proper classification, and normality of z scores.
    RESULTS:
    We created 2 sets of BMI growth charts. The first set displays fitted median curves for all 5 percentile groups in each GA group by sex. The second set displays fitted median curves with their corresponding third and 97th percentiles by percentile group, GA, and sex. In the validation analysis, percentage of daily observations below the median curve approximated the expected 50th percentile after the initial 3 days. Unlike the cross-sectional curves, the longitudinal curves reveal the pattern of change corresponding to nadir; postnadir, these curves remained consistently below the cross-sectional curves and varied by GA and sex as expected. The percentage of observations falling below the 50th percentile for cross-sectional curves (revealing optimal growth) was generally much higher than for longitudinal curves (revealing actual growth).
    CONCLUSIONS:
    These new longitudinal curves provide clinicians data on how premature infants’ body proportionality changes over time.


  • Meningococcal B Vaccine Immunogenicity in Children With Defects in Complement and Splenic Function
    BACKGROUND:
    The capsular group B meningococcal vaccine (4CMenB) is recommended for children with complement deficiencies, asplenia, and splenic dysfunction; however, data on the immunogenicity of 4CMenB in these “at-risk” children are missing.
    METHODS:
    Participants aged 2 to 17 years in Italy, Spain, Poland, the United Kingdom, and Russia with complement deficiencies, asplenia, or splenic dysfunction received 2 doses of 4CMenB 2 months apart, as did healthy children in the control group. Exogenous and endogenous human complement serum bactericidal activity (SBA) was determined at baseline and 1 month after the second immunization against 4 test strains: H44/76 (assessing vaccine antigen factor H binding protein), 5/99 (Neisserial adhesion A), NZ98/254 (Porin A), and M10713 (Neisserial heparin binding antigen).
    RESULTS:
    Of 239 participants (mean age 10.3 years, 45% female), 40 children were complement deficient (9 eculizumab therapy, 4 terminal-chain deficiencies, 27 “other”), 112 children had asplenia or splenic dysfunction (8 congenital asplenia, 8 functional asplenia, 96 splenectomy), and 87 children were in the control group. After immunization, the proportions of complement-deficient participants with exogenous complement SBA titers ≥1:5 were 87% (H44/76), 95% (5/99), 68% (NZ98/254), and 73% (M10713), compared with 97%, 100%, 86%, and 94%, respectively, for asplenic children and 98%, 99%, 83%, and 99% for children in the control group. When testing with endogenous complement, strain-specific bactericidal activity was evident in only 1 eculizumab-treated participant and 1 terminal chain complement-deficient participant.
    CONCLUSIONS:
    4CMenB administration is similarly immunogenic in healthy children and those with asplenia or splenic dysfunction. The significance of the trend to lower responses of SBA titers in complement-deficient children (especially those with terminal chain complement deficiency or those on eculizumab therapy) must be determined by ongoing surveillance for vaccine failures.


  • Predicting Escalated Care in Infants With Bronchiolitis
    BACKGROUND AND OBJECTIVES:
    Early risk stratification of infants with bronchiolitis receiving airway support is critical for focusing appropriate therapies, yet the tools to risk categorize this subpopulation do not exist. Our objective was to identify predictors of “escalated care” in bronchiolitis. We hypothesized there would be a significant association between escalated care and predictors in the emergency department. We subsequently developed a risk score for escalated care.
    METHODS:
    We conducted a retrospective cohort study of previously healthy infants aged


  • Health Care Use and Health Behaviors Among Young Adults With History of Parental Incarceration
    OBJECTIVES:
    To determine if longitudinal associations exist between parental incarceration (PI) and health care use or health behaviors among a national sample of young adults.
    METHODS:
    We used the National Longitudinal Survey of Adolescent to Adult Health to examine associations between history of mother incarceration (MI) and father incarceration (FI), health care use, and 3 dimensions of health behaviors (eg, general health behaviors, substance use, and other risky behaviors) (N = 13 084). Multivariable logistic regression models accounted for individual, family, and geographic factors and generated adjusted odds ratios (aORs).
    RESULTS:
    Over 10% of the sample had a history of PI before the age of 18. History of MI and FI were both associated with forgone health care (aOR = 1.65 [95% confidence interval (CI), 1.20–2.27], aOR = 1.22 [95% CI, 1.02–1.47], respectively), prescription drug abuse (MI aOR = 1.61 [95% CI, 1.02–2.55], FI aOR = 1.46 [95% CI, 1.20–1.79]), and 10 or more lifetime sexual partners (MI aOR = 1.55 [95% CI, 1.08–2.22], FI aOR = 1.19 [95% CI, 1.01–1.41]). MI was associated with higher likelihood of emergency department use (aOR = 2.36 [95% CI, 1.51–3.68]), and FI was associated with illicit injection drug use (aOR = 2.54 [95% CI, 1.27–5.12]).
    CONCLUSIONS:
    The effects of incarceration extend beyond incarcerated individuals. PI histories are associated with lower health care use and unhealthy behaviors in young adulthood. By addressing barriers to health care and health-harming behaviors, health care providers and policy makers may reduce health disparities among this population.


  • Prenatal Diet and Child Growth at 18 Months
    OBJECTIVE:
    Our objective was to evaluate the effect of an antenatal dietary and lifestyle intervention in pregnant women who are overweight or obese on child outcomes at age 18 months.
    METHODS:
    We conducted a follow-up study of children at 18 months of age who were born to women who participated in the Limiting Weight Gain in Overweight and Obese Women during Pregnancy to Improve Health Outcomes randomized trial. The primary follow-up study outcome was prevalence of child BMI z scores >85th percentile. Secondary study outcomes included a range of anthropometric measures, neurodevelopment, general health, and child feeding. Intention to treat principles were used in analyses, according to the treatment group allocated at randomization.
    RESULTS:
    A total of 1602 children were assessed at age 18 months (lifestyle advice, n = 816; standard care, n = 786), representing 75.0% of the eligible sample (n = 2136). There were no statistically significant differences in the prevalence of child BMI z scores >85th percentile for children born to women in the lifestyle advice group, compared with the standard care group (lifestyle advice, 505 [47.11%] versus standard care, 483 [45.36%]; adjusted relative risk: 1.04; 95% confidence interval: 0.94 to 1.16; P = .45). There was no evidence of effects on child growth, adiposity, neurodevelopment, or dietary and physical activity patterns.
    CONCLUSIONS:
    There is no evidence that providing pregnant women who were overweight or obese with an antenatal dietary and lifestyle intervention altered 18-month child growth and adiposity.


  • Variations in Neonatal Antibiotic Use
    OBJECTIVES:
    We sought to identify whether and how the NICU antibiotic use rate (AUR), clinical correlates, and practice variation changed between 2013 and 2016 and attempted to identify AUR ranges that are consistent with objectively determined bacterial and/or fungal disease burdens.
    METHODS:
    In a retrospective cohort study of >54 000 neonates annually at >130 California NICUs from 2013 to 2016, we computed nonparametric linear correlation and compared AURs among years using a 2-sample test of proportions. We stratified by level of NICU care and participation in externally organized stewardship efforts.
    RESULTS:
    By 2016, the overall AUR declined 21.9% (95% confidence interval [CI] 21.9%–22.0%), reflecting 42 960 fewer antibiotic days. Among NICUs in externally organized antibiotic stewardship efforts, the AUR declined 28.7% (95% CI 28.6%–28.8%) compared with 16.2% (95% CI 16.1%–16.2%) among others. The intermediate NICU AUR range narrowed, but the distribution of values did not shift toward lower values as it did for other levels of care. The 2016 AUR correlated neither with proven infection nor necrotizing enterocolitis. The 2016 regional NICU AUR correlated with surgical volume ( = 0.53; P = .01), mortality rate ( = 0.57; P = .004), and average length of stay ( = 0.62; P = .002) and was driven by 3 NICUs with the highest AUR values (30%–57%).
    CONCLUSIONS:
    Unexplained antibiotic use has declined but continues. Currently measured clinical correlates generally do not help explain AUR values that are above the lowest quartile cutpoint of 14.4%.


  • Prenatal Tetanus, Diphtheria, Acellular Pertussis Vaccination and Autism Spectrum Disorder
    BACKGROUND:
    Increasing vaccination of pregnant women makes it important to assess safety events potentially linked to prenatal vaccination. This study investigates the association between prenatal tetanus, diphtheria, acellular pertussis (Tdap) vaccination and autism spectrum disorder (ASD) risk in offspring.
    METHODS:
    This is a retrospective cohort study of mother-child pairs with deliveries January 1, 2011 to December 31, 2014 at Kaiser Permanente Southern California hospitals. Maternal Tdap vaccination from pregnancy start to delivery date was obtained from electronic medical records. A diagnosis of ASD was obtained by using International Classification of Diseases, Ninth and Tenth Revision codes. Children were managed from birth to first ASD diagnosis, end of membership, or end of follow-up (June 30, 2017). Cox proportional hazards models estimated the unadjusted and adjusted hazard ratios (HRs) for the association between maternal Tdap vaccination and ASD, with inverse probability of treatment weighting to adjust for confounding.
    RESULTS:
    Women vaccinated were more likely to be Asian American or Pacific Islander, be nulliparous, have a higher education, receive influenza vaccination prenatally, and give birth at term. ASD was diagnosed in 1341 (1.6%) children, and the incidence rate was 3.78 per 1000 person years in the Tdap exposed and 4.05 per 1000 person years in the unexposed group (HR: 0.98, 95% confidence interval: 0.88–1.09). The inverse probability of treatment weighting–adjusted analyses revealed that prenatal Tdap vaccination was not associated with an increased ASD risk (HR: 0.85, 95% confidence interval: 0.77–0.95).
    CONCLUSIONS:
    Prenatal Tdap vaccination was not associated with an increased ASD risk. We support recommendations to vaccinate pregnant women to protect infants, who are at highest risk of death after pertussis infection.


  • Prevalence of Autism Spectrum Disorder in Preterm Infants: A Meta-analysis
    CONTEXT:
    Evidence is emerging that preterm infants are at risk for autism spectrum disorder (ASD).
    OBJECTIVES:
    To conduct a systematic review and meta-analysis to estimate the prevalence of ASD in preterm infants.
    DATA SOURCES:
    Medline (via PubMed and Ovid), Embase, PsycINFO, and relevant conference proceedings were searched in May 2017.
    STUDY SELECTION:
    Original studies in which researchers report on the prevalence of ASD using diagnostic tests in children born preterm were included. Studies in which researchers used only ASD screening tools were excluded.
    DATA EXTRACTION:
    Relevant data were extracted independently by 3 authors.
    RESULTS:
    Researchers in a total of 18 studies (3366 preterm infants) used ASD diagnostic tools. The median gestation, birth weight, and age at assessment were 28.0 weeks (range: 25.1–31.3 weeks), 1055 g (range: 719–1565 g), and 5.7 years (range: 1.5–21 years), respectively. Meta-analysis revealed that the overall prevalence rate for ASD was 7% (95% confidence interval: 4% to 9%). The funnel plot and Egger’s test revealed that there was probably no evidence of publication bias.
    LIMITATIONS:
    The limitations were significant heterogeneity and a lack of studies from middle- and low-income countries.
    CONCLUSIONS:
    The prevalence of ASD is significantly high in the preterm population. Adequate resources are needed to improve the outcomes of these children.


  • Treatment of Ventricular Fibrillation Due to Ammonium Bifluoride Poisoning With Hemodialysis
    Ammonium bifluoride is an inorganic, fluoride-containing compound found in glass and metal etching products, as well as wheel cleaners. Fluoride toxicity is a common cause of preventable poisoning and has been reported to cause life-threatening ventricular dysrhythmias. Here, we report a case of recurrent ventricular fibrillation secondary to ingestion of ammonium bifluoride. The patient presented with vomiting and coma. She was intubated for altered mental status and respiratory failure and subsequently had 5 episodes of ventricular fibrillation, each resolving with a single defibrillation. She developed metabolic acidosis and hypocalcemia, which were treated with sodium bicarbonate and calcium gluconate, respectively. During transfer to a tertiary care children’s hospital, ventricular fibrillation recurred despite electrolyte correction. Hemodialysis (HD) was initiated emergently. No further dysrhythmia occurred after initiation of HD. The result of a basic urine drug screen was negative, and a comprehensive drug screen (gas chromatography and mass spectroscopy) revealed only a nonsignificant peak for diphenhydramine. Subsequent laboratory evaluation revealed an elevated serum fluoride level. Diagnostic laryngoscopy and upper endoscopy did not reveal evidence of caustic injury. She was successfully extubated on hospital day 2 and discharged from the hospital on day 4 with no neurologic sequelae. With this example, we demonstrate a potential therapeutic approach to this potentially lethal poisoning. Fluoride toxicity is typically treated with calcium. However, dysrhythmia may result from calcium-independent direct myocardial toxicity. The kinetics of fluoride are amenable to HD, and renal clearance is slow. The potential use of HD in cases of fluoride poisoning refractory to other therapies warrants further study.


  • Lost Earnings and Nonmedical Expenses of Pediatric Hospitalizations
    BACKGROUND AND OBJECTIVES:
    Hospitalization-related nonmedical costs, including lost earnings and expenses such as transportation, meals, and child care, can lead to challenges in prioritizing postdischarge decisions. In this study, we quantify such costs and evaluate their relationship with sociodemographic factors, including family-reported financial and social hardships.
    METHODS:
    This was a cross-sectional analysis of data collected during the Hospital-to-Home Outcomes Study, a randomized trial designed to determine the effects of a nurse home visit after standard pediatric discharge. Parents completed an in-person survey during the child’s hospitalization. The survey included sociodemographic characteristics of the parent and child, measures of financial and social hardship, household income and also evaluated the family’s total nonmedical cost burden, which was defined as all lost earnings plus expenses. A daily cost burden (DCB) standardized it for a 24-hour period. The daily cost burden as a percentage of daily household income (DCBi) was also calculated.
    RESULTS:
    Median total cost burden for the 1372 households was $113, the median DCB was $51, and the median DCBi was 45%. DCB and DCBi varied across many sociodemographic characteristics. In particular, single-parent households (those with less work flexibility and more financial hardships experienced significantly higher DCB and DCBi. Those who reported ≥3 financial hardships lost or spent 6-times more of their daily income on nonmedical costs than those without hardships. Those with ≥1 social hardships lost or spent double their daily income compared with those without social hardships.
    CONCLUSIONS:
    Nonmedical costs place burdens on families of children who are hospitalized, disproportionately affecting those with competing socioeconomic challenges.


  • Down Syndrome and the Risk of Severe RSV Infection: A Meta-analysis
    CONTEXT:
    Down syndrome (DS) is the most common chromosomal condition in live-born infants worldwide, and lower respiratory infection caused by respiratory syncytial virus (RSV) is a leading cause of hospital admissions.
    OBJECTIVE:
    To evaluate RSV-associated morbidity among children with DS compared with a population without DS.
    DATA SOURCES:
    Four electronic databases were searched.
    STUDY SELECTION:
    All cohorts or case-control studies of DS with an assessment of RSV infection and the associated morbidity or mortality were included without language restriction.
    DATA EXTRACTION:
    Two reviewers independently reviewed all studies. The primary outcomes were hospital admission and mortality. Secondary outcomes included length of hospital stay, oxygen requirement, ICU admission, need for respiratory support, and additional medication use.
    RESULTS:
    Twelve studies (n = 1 149 171) from 10 different countries met the inclusion criteria; 10 studies were cohort studies, 1 study was retrospective, and 1 study had both designs. DS was associated with a higher risk of hospitalization (odds ratio [OR]: 8.69; 95% confidence interval [CI]: 7.33–10.30; I2 = 11%) and mortality (OR: 9.4; 95% CI: 2.26–39.15; I2 = 38%) compared with what was seen in controls. Children with DS had an increased length of hospital stay (mean difference: 4.73 days; 95% CI: 2.12–7.33; I2 = 0%), oxygen requirement (OR: 6.53; 95% CI: 2.22–19.19; I2 = 0%), ICU admission (OR: 2.56; 95% CI: 1.17–5.59; I2 = 0%), need for mechanical ventilation (OR: 2.56; 95% CI: 1.17–5.59; I2 = 0%), and additional medication use (OR: 2.65 [95% CI: 1.38–5.08; I2 = 0%] for systemic corticosteroids and OR: 5.82 [95% CI: 2.66–12.69; I2 = 0%] for antibiotics) than controls.
    LIMITATIONS:
    DS subgroups with and without other additional risk factors were not reported in all of the included studies.
    CONCLUSIONS:
    Children with DS had a significantly higher risk of severe RSV infection than children without DS.


  • Negative Chest Radiography and Risk of Pneumonia
    BACKGROUND AND OBJECTIVES:
    The ability of the chest radiograph (CXR) to exclude the diagnosis of pneumonia in children is unclear. We sought to determine the negative predictive value of CXR in children with suspected pneumonia.
    METHODS:
    Children 3 months to 18 years of age undergoing CXRs for suspected pneumonia in a tertiary-care pediatric emergency department (ED) were prospectively enrolled. Children currently receiving antibiotics and those with underlying chronic medical conditions were excluded. The primary outcome was defined as a physician-ascribed diagnosis of pneumonia independent of radiographic findings. CXR results were classified as positive, equivocal, or negative according to radiologist interpretation. Children with negative CXRs and without a clinical diagnosis of pneumonia were managed for 2 weeks after the ED visit. Children subsequently diagnosed with pneumonia during the follow-up period were considered to have had false-negative CXRs at the ED visit.
    RESULTS:
    There were 683 children enrolled during the 2-year study period, with a median age of 3.1 years (interquartile range 1.4–5.9 years). There were 457 children (72.8%) with negative CXRs; 44 of these children (8.9%) were clinically diagnosed with pneumonia, and 42 (9.3%) were given antibiotics for other bacterial syndromes. Of the 411 children with negative CXRs who were managed without antibiotics, 5 were subsequently diagnosed with pneumonia within 2 weeks (negative predictive value of CXR 98.8%; 95% confidence interval 97.0%–99.6%).
    CONCLUSIONS:
    A negative CXR excludes pneumonia in the majority of children. Children with negative CXRs and low clinical suspicion for pneumonia can be safely observed without antibiotic therapy.


  • The Healthy Neighborhood, Healthy Families Initiative

    Extreme poverty and the associated effects, such as blight, housing insecurity, and crime, have debilitating consequences on child development. Health care institutions are largely ineffective in changing those outcomes 1 child at a time. We present a case study of a hospital treating the adjacent neighborhood as a “patient” to address social determinants. The community represents a largely impoverished and housing-unstable neighborhood that underwent an assessment by community partners and treatment with a multifaceted housing intervention. Marked improvement in vacancy rates occurred, although outcome assessments for children are still being gathered. Several case learnings are presented, but the involvement and investment of pediatric health care clinicians and institutions increased the speed and size of neighborhood development after 80 years of redlining and institutional racism.


  • Adolescent Tobacco Smoke Exposure, Respiratory Symptoms, and Emergency Department Use
    OBJECTIVES:
    Our objective was to examine the relationship between distinct tobacco smoke exposure (TSE) measures and TSE-related symptoms and emergency department (ED) and/or urgent care (UC) use among nonsmoking adolescents without asthma diagnoses.
    METHODS:
    We performed a secondary analysis of 7389 adolescents who completed the Population Assessment of Tobacco and Health Study wave 2. Logistic regression and Poisson regression models were built.
    RESULTS:
    Adolescents with TSE were at increased risk of reporting: shortness of breath, finding it hard to exercise, wheezing during or after exercise, and dry cough at night. Adolescents who lived with a smoker and had home TSE were at increased odds of reporting wheezing or whistling in the chest, and only adolescents with home TSE were at increased risk of reporting wheezing that disturbed sleep. Adolescents with TSE were less likely to report very good or excellent overall health and physical health but were more likely to report they sometimes, often, or very often missed school because of illness. Participants who lived with a smoker and had TSE ≥1 hour were more likely to have had an ED and/or UC visit. Participants with any TSE were at increased risk of having a higher number of ED and/or UC visits.
    CONCLUSIONS:
    Different TSE measures uniquely increased the risk of TSE-related symptoms, but any TSE increased the risk of having a higher number of ED and/or UC visits. The providers at these high-volume settings should offer interventions to adolescents who are exposed to tobacco smoke and their families to decrease these symptoms and related morbidity.


  • Sociodemographic Factors and Survival of Infants With Congenital Heart Defects
    OBJECTIVES:
    To examine the first-year survival of infants with congenital heart defects (CHDs) and investigate the potential role of socioeconomic and demographic factors on survival.
    METHODS:
    Subjects included 15 533 infants with CHDs born between 2004 and 2013 ascertained by the NC Birth Defects Monitoring Program. We classified CHDs into the following 3 groups: critical univentricular (n = 575), critical biventricular (n = 1494), and noncritical biventricular (n = 13 345). We determined vital status and age at death through linkage to state vital records and used geocoded maternal residence at birth to obtain census information for study subjects. We calculated Kaplan–Meier survival estimates by maternal and infant characteristics and derived hazard ratios from Cox proportional hazard models for selected exposures.
    RESULTS:
    Among all infants with CHDs, there were 1289 deaths (8.3%) in the first year. Among infants with univentricular defects, 61.6% (95% confidence interval [CI]: 57.7%–65.7%) survived. Survival among infants with univentricular defects was considerably better for those whose fathers were ≥35 years old (71.6%; 95% CI: 63.8%–80.3%) compared with those whose fathers were younger (59.7%; 95% CI: 54.6%–65.2%). Factors associated with survival among infants with any biventricular defect included maternal education, race and/or ethnicity, marital status, and delivery at a heart center. The hazard of infant mortality was greatest among non-Hispanic African American mothers.
    CONCLUSIONS:
    Survival among infants with critical univentricular CHDs was less variable across sociodemographic categories compared with survival among infants with biventricular CHDs. Sociodemographic differences in survival among infants with less severe CHDs reinforces the importance of ensuring culturally effective pediatric care for at-risk infants and their families.



  • D-lactic Acidosis: Successful Suppression of D-lactate-Producing Lactobacillus by Probiotics
    Intestinal microbiota composition in children with short bowel syndrome (SBS) is an important factor influencing the clinical outcome. An increase of D-lactate–producing bacteria can lead to D-lactic acidosis, also referred to as D-lactate encephalopathy, with severe neurologic impairment. Antibiotic treatments for D-lactic acidosis in children with SBS offer often only short-term relief. Here, we present the case of a boy with SBS who developed recurrent episodes of D-lactic acidosis even under continuous cycling antibiotic treatment. Microbiological analyses were used to detect the presence of D-lactate–producing Lactobacillus species in the stool samples. A probiotic cocktail was introduced to alter the intestinal microbiota. During follow-up under treatment with probiotics, the patient remained stable, and there was no additional need for antibiotic therapy for more than a year. Stool composition of the patient was sequenced regularly over that period. His microbiota profile changed completely in species richness, and a clustering of species according to probiotic usage was seen. Importantly, D-lactate–producing Lactobacillus strains disappeared within a few weeks after probiotic introduction and were no longer detected in the subsequent follow-up specimens.


  • Adoption of Serogroup B Meningococcal Vaccine Recommendations
    BACKGROUND AND OBJECTIVES:
    In 2015, the Advisory Committee on Immunization Practices recommended that 16- to 23-year-olds may be vaccinated with the serogroup B meningococcal (MenB) vaccine on the basis of individual clinical decision-making (Category B). We assessed the following among US pediatricians and family physicians (FPs): (1) practices regarding MenB vaccine delivery, (2) factors influencing a decision to recommend the MenB vaccine, and (3) factors associated with discussing the MenB vaccine.
    METHODS:
    We surveyed a nationally representative sample of pediatricians and FPs via e-mail and Internet from October 2016 to December 2016.
    RESULTS:
    The response rate was 72% (660 of 916). During routine visits, 51% of pediatricians and 31% of FPs reported always or often discussing MenB vaccine. Among those who discussed often or always, 91% recommended vaccination; among those who never or rarely discussed, 11% recommended. We found that 73% of pediatricians and 41% of FPs currently administered the MenB vaccine. Although many providers reported not knowing about factors influencing recommendation decisions, MenB disease outbreaks (89%), disease incidence (62%), and effectiveness (52%), safety (48%), and duration of protection of MenB vaccine (39%) increased the likelihood of recommendation, whereas the Category B recommendation (45%) decreased likelihood. Those somewhat or not at all aware of the MenB vaccine (risk ratio 0.32 [95% confidence interval 0.25–0.41]) and those practicing in a health maintenance organization (0.39 [0.18–0.87]) were less likely, whereas those aware of disease outbreaks in their state (1.25 [1.08–1.45]) were more likely to discuss MenB vaccine.
    CONCLUSIONS:
    Primary care physicians have significant gaps in knowledge about MenB disease and the MenB vaccine, and this appears to be a major driver of the decision not to discuss the vaccines.


  • Repeat Head CT for Expectant Management of Traumatic Epidural Hematoma
    BACKGROUND AND OBJECTIVES:
    Guidelines regarding the role of repeated head computed tomography (CT) imaging in the nonoperative management of traumatic epidural hematomas (EDHs) do not exist. Consequently, some children may be exposed to unnecessary additional ionizing radiation. We describe the frequency, timing, and utility of reimaging of EDHs to identify patients who might avoid reimaging.
    METHODS:
    A retrospective cohort study of subjects aged 0 to 18 years with a traumatic EDH treated at a level I pediatric trauma center from 2003 to 2014. Radiographic and clinical findings, the frequency and timing of reimaging, and changes in neurologic status were compared between subjects whose management changed because of a meaningful CT scan and those whose did not.
    RESULTS:
    Of the 184 subjects who were analyzed, 19 (10%) had a meaningful CT. There was no difference in the frequency of CT scans between the meaningful CT scan and no meaningful CT groups (median 1 [interquartile range 1–2] in no meaningful CT and median 1 [interquartile range 1–2] in meaningful CT scans; P = .7). Only 7% of repeated CTs changed management. Neurologic status immediately before the repeat scan (odds ratio 45; 95% confidence interval 10–200) and mass effect on the initial CT (odds ratio 4; 95% confidence interval 1.5–13) were associated with a meaningful CT. Reimaging only subjects with concerning pre-CT neurologic findings or mass effect on initial CT would have decreased imaging by 54%.
    CONCLUSIONS:
    Reimaging is common, but rarely changes management. Limiting reimaging to patients with concerning neurologic findings or mass effect on initial evaluation could reduce imaging by >50%.


  • Legislation to Increase Uptake of HPV Vaccination and Adolescent Sexual Behaviors
    BACKGROUND:
    Despite preventive health benefits of the human papillomavirus (HPV) vaccination, uptake in the United States remains low. Twenty-four states have enacted legislation regarding HPV vaccination and education. One reason these policies have been controversial is because of concerns that they encourage risky adolescent sexual behaviors. Our aim in this study is to determine if state HPV legislation is associated with changes in adolescent sexual behaviors.
    METHODS:
    This is a difference-in-difference study in which we use data on adolescent sexual behaviors from the school-based state Youth Risk Behavior Surveillance System from 2001 to 2015. Sexual behaviors included ever having sexual intercourse in the last 3 months and condom use during last sexual intercourse. We compared changes in sexual behaviors among high school students before and after HPV legislation to changes among high school students in states without legislation.
    RESULTS:
    A total of 715 338 participants reported ever having sexual intercourse in the last 3 months, and 217 077 sexually active participants reported recent condom use. We found no substantive or statistically significant associations between HPV legislation and adolescent sexual behaviors. Recent sexual intercourse decreased by 0.90 percentage points (P = .21), and recent condom use increased by 0.96 percentage points (P = .32) among adolescents in states that enacted legislation compared with states that did not. Results were robust to a number of sensitivity analyses.
    CONCLUSIONS:
    Implementation of HPV legislation was not associated with changes in adolescent sexual behaviors in the United States. Concern that legislation will increase risky adolescent sexual behaviors should not be used when deciding to pass HPV legislation.


  • Lung Ultrasound Score Predicts Surfactant Need in Extremely Preterm Neonates
    BACKGROUND AND OBJECTIVES:
    There are several lung ultrasound scores (LUS) for evaluating lung aeration in critically ill adults with restrictive lung disorders. A modified LUS adapted for neonates correlates well with oxygenation and is able to be used to predict the need for surfactant in preterm neonates with respiratory distress syndrome (RDS). However, no data are available for extremely preterm neonates for whom timely surfactant administration is especially important. We hypothesized that LUS might be reliable in extremely preterm neonates with RDS who are treated with continuous positive airway pressure. We aimed to determine the diagnostic accuracy of LUS in predicting the need for surfactant treatment and re-treatment in this population.
    METHODS:
    We performed a prospective cohort diagnostic accuracy study between 2015 and 2016 in a tertiary-care academic center. Inborn neonates at ≤30 weeks’ gestation with RDS treated with continuous positive airway pressure were eligible. Surfactant was given on the basis of oxygen requirement thresholds derived from European guidelines, and a LUS was not used to guide surfactant treatment. We calculated the LUS after admission and analyzed its diagnostic accuracy to predict surfactant treatment and re-treatment.
    RESULTS:
    We enrolled 133 infants; 68 (51%) received 1 dose of surfactant and 19 (14%) received 2 surfactant doses. A LUS is significantly correlated with oxygenation index ( = 0.6; P < .0001) even after adjustment for gestational age (P < .0001). A LUS can be used to accurately predict the need for the first surfactant dose (area under the curve = 0.94; 95% confidence interval: 0.90–0.98; P < .0001) and also the need for surfactant redosing (area under the curve = 0.803; 95% confidence interval: 0.72–0.89; P < .0001). The global accuracy for the prediction of surfactant treatment and re-treatment is 89% and 72%, respectively.
    CONCLUSIONS:
    LUS may be used to predict the need for surfactant replacement in extremely preterm neonates with RDS.



  • Educational Disabilities Among Children Born With Neonatal Abstinence Syndrome
    BACKGROUND:
    Neonatal abstinence syndrome (NAS) is a postnatal drug withdrawal syndrome that can occur after intrauterine opioid exposure. Adverse neurobehavioral outcomes have been documented in infants with NAS; however, educational outcomes have not been thoroughly examined. We analyzed Tennessee data to understand the need for special educational services among infants who are born with NAS.
    METHODS:
    By using Tennessee Medicaid and birth certificate data, infants who were born in Tennessee between 2008 and 2011 with a history of NAS were matched (1:3) to infants who were born during the same period without a history of NAS. Groups were matched on the basis of sex, race and/or ethnicity, age, birth region of residence, and Medicaid enrollment status. Data were linked to Tennessee Department of Education special education data during early childhood (3–8 years of age). Conditional multivariable logistic regression was used to assess associations between NAS and selected special education outcomes.
    RESULTS:
    A total of 1815 children with a history of NAS and 5441 children without NAS were assessed. Children with NAS were significantly more likely to be referred for a disability evaluation (351 of 1815 [19.3%] vs 745 of 5441 [13.7%]; P < .0001), to meet criteria for a disability (284 of 1815 [15.6%] vs 634 of 5441 [11.7%]; P < .0001), and to require classroom therapies or services (278 of 1815 [15.3%] vs 620 of 5441 [11.4%]; P < .0001). These findings were sustained in a multivariable analysis, with multiple models controlling for maternal tobacco use, maternal education status, birth weight, gestational age, and/or NICU admission.
    CONCLUSIONS:
    Results of this novel analysis linking health and education data revealed that children with a history of NAS were significantly more likely to have a subsequent educational disability.


  • Sport Specialization and Risk of Overuse Injuries: A Systematic Review With Meta-analysis
    CONTEXT:
    Sport specialization is theorized to increase the risk of sustaining overuse musculoskeletal injuries.
    OBJECTIVE:
    To complete a systematic review and meta-analysis of the literature to determine if sport specialization is associated with overuse musculoskeletal injuries.
    DATA SOURCES:
    An electronic search was conducted using the search terms “specialization,” “year-round,” “overuse,” “repetitive stress,” “injury,” “young,” “pediatric,” and “sports.”
    STUDY SELECTION:
    Studies were included if their population was ≤18 years of age, if they compared athletes with high or single-sport specialization with athletes with low or multisport specialization, and focused on overuse injuries.
    DATA EXTRACTION:
    Of the 12 articles that were identified for full-text review, 5 studies met all the inclusion criteria. Four studies provided adequate data for the meta-analysis. Quality scores on the modified Downs and Black scale ranged from 69% to 81%.
    RESULTS:
    Athletes with high specialization were at an increased risk of sustaining an overuse injury compared with athletes with low (pooled relative risk [RR] ratio: 1.81; 95% confidence interval [CI]: 1.26–2.60) and moderate (pooled RR: 1.18; 95% CI: 1.05–1.33) specialization. Athletes with moderate specialization were at a higher risk of injury compared with athletes with low specialization (RR: 1.39 [95% CI: 1.04–1.87]).
    LIMITATIONS:
    Four of the 5 studies included in this systematic review were included in the meta-analysis because of the lack of access to the original data set for 1 article.
    CONCLUSIONS:
    Sport specialization is associated with an increased risk of overuse musculoskeletal injuries (Strength of Recommendation Taxonomy grade: B).


  • Neuroimaging of Early Life Epilepsy
    OBJECTIVES:
    We assessed the adherence to neuroimaging guidelines and the diagnostically relevant yield of neuroimaging in newly presenting early life epilepsy (ELE).
    METHODS:
    There were 775 children with a new diagnosis of epilepsy (


  • Recruitment and Retention of Community Preceptors
    BACKGROUND:
    Recruiting and retaining community-based pediatricians for teaching medical students has been explored through the lens of preceptors and educational leaders. The purpose of this study was to explore the perspective of pediatric department chairs, a key stakeholder group charged with maintaining teaching capacity among a faculty.
    METHODS:
    In 2015, members of the Association of Medical School Pediatric Department Chairs and Council on Medical Student Education in Pediatrics joint task force disseminated a 20-item survey to pediatric department chairs in the United States and Canada. Topics included demographics, incentives offered to community pediatricians, and the perceived value and feasibility of such incentives. Data were analyzed using descriptive statistics and 2 to compare categorical variables.
    RESULTS:
    Pediatric department chairs from 92 of 145 (63% response rate) medical schools returned the survey. Sixty-seven percent reported difficulty recruiting or retaining preceptors, and 51% reported high-reliance on preceptors for the ambulatory portion of the pediatrics clerkship. Almost all (92%) cited competition from other programs for the services of community preceptors. The provision of incentives was correlated with perceived feasibility (R2 = 0.65) but not their perceived value (R2 = 0.12). Few (21%) chairs reported providing financial compensation to preceptors. The provision of compensation was not related to reliance but did vary significantly by geographical region (P < .001).
    CONCLUSIONS:
    Pediatric departments rely heavily on community-based pediatricians but face competition from internal and external training programs. The perspective of department chairs is valuable in weighing interventions to facilitate continued recruitment and retention of community preceptors.



  • The Risk of Offspring Psychiatric Disorders in the Setting of Maternal Obesity and Diabetes
    BACKGROUND:
    Prenatal exposure to metabolic disturbances is associated with increased risk of offspring neurodevelopmental impairment and autism spectrum disorder, while little is known about the joint effect of maternal obesity and diabetes. With this study, we aim to assess the joint effect of maternal obesity and diabetes on the risk for offspring psychiatric and mild neurodevelopmental disorders.
    METHODS:
    Nationwide registries were used to link data of all live births in Finland between 2004 and 2014 (n = 649 043). Cox proportional hazards modeling adjusting for potential confounders was applied to estimate the effect of maternal obesity, pregestational diabetes mellitus (PGDM), and gestational diabetes mellitus, as well as their joint effects, on the outcomes of offspring psychiatric and mild neurodevelopmental diagnoses and offspring prescription of psychotropic drugs.
    RESULTS:
    Among mothers without diabetes, severely obese mothers had 67% to 88% increased risk of having a child with mild neurodevelopmental disorders (hazard risk ratio [HR] = 1.69; 95% confidence interval [CI] = 1.54–1.86), attention-deficit/hyperactivity disorder or conduct disorder (HR = 1.88; 95% CI = 1.58–2.23), and psychotic, mood, and stress-related disorders (HR = 1.67; 95% CI = 1.31–2.13) compared with mothers with a normal BMI. PGDM implied a further risk increase for all groups of psychiatric diagnoses with onset in childhood or adolescence in mothers with severe obesity. Marked effects were found particularly for autism spectrum disorder (HR = 6.49; 95% CI = 3.08–13.69), attention-deficit/hyperactivity disorder and conduct disorder (HR = 6.03; 95% CI = 3.23–11.24), and mixed disorders of conduct and emotions (HR = 4.29; 95% CI = 2.14–8.60). Gestational diabetes mellitus did not increase the risk highly for these offspring disorders.
    CONCLUSIONS:
    Maternal PGDM combined with severe maternal obesity markedly increases the risk of several children’s psychiatric and mild neurodevelopmental disorders.


  • A Healthy Life for a Child With Medical Complexity: 10 Domains for Conceptualizing Health
    BACKGROUND AND OBJECTIVES:
    Defining and measuring health for children with medical complexity (CMC) is poorly understood. We engaged a diverse national sample of stakeholder experts to generate and then synthesize a comprehensive list of health outcomes for CMC.
    METHODS:
    With national snowball sampling of CMC caregiver, advocate, provider, researcher, and policy or health systems experts, we identified 182 invitees for group concept mapping (GCM), a rigorous mixed-methods approach. Respondents (n = 125) first completed Internet-based idea generation by providing unlimited short, free-text responses to the focus prompt, “A healthy life for a child or youth with medical complexity includes: ___.” The resulting 707 statements were reduced to 77 unique ideas. Participants sorted the ideas into clusters based on conceptual similarity and rated items on perceived importance and measurement feasibility. Responses were analyzed and mapped via GCM software.
    RESULTS:
    The cluster map best fitting the data had 10 outcome domains: (1) basic needs, (2) inclusive education, (3) child social integration, (4) current child health-related quality of life, (5) long-term child and family self-sufficiency, (6) family social integration, (7) community system supports, (8) health care system supports, (9) a high-quality patient-centered medical home, and (10) family-centered care. Seventeen outcomes representing 8 of the 10 domains were rated as both important and feasible to measure (“go zone”).
    CONCLUSIONS:
    GCM identified a rich set of CMC outcome domains. Go-zone items provide an opportunity to test and implement measures that align with a broad view of health for CMC and potentially all children.


  • Understanding FDA-Approved Labeling and CDC Recommendations for Use of Vaccines
    Adherence to recommendations for the use of licensed vaccines ensures maximum individual and societal benefits from the national immunization program. The US Food and Drug Administration (FDA) licenses a vaccine once it determines that data submitted by the manufacturer reveal that the vaccine is safe and effective for its intended use. For each US-licensed vaccine, the FDA-approved prescribing information contains detailed information for health care providers to ensure safe and effective use. Centers for Disease Control and Prevention recommendations for the use of a licensed vaccine often are based on additional considerations, such as disease epidemiology, public acceptance, vaccine supply, and cost. Our objective in this article is to explain the reasons for the differences between FDA-approved prescribing information and Centers for Disease Control and Prevention recommendations for vaccine use.


  • Preventable Adverse Drug Events Among Inpatients: A Systematic Review
    CONTEXT:
    Patient harm resulting from medication errors drives prevention efforts, yet harm associated with medication errors in children has not been systematically reviewed.
    OBJECTIVE:
    To review the incidence and severity of preventable adverse drug events (pADEs) resulting from medication errors in pediatric inpatient settings.
    DATA SOURCES:
    Data sources included Cumulative Index of Nursing and Allied Health Literature, Medline, Scopus, the Cochrane Library, and Embase.
    STUDY SELECTION:
    Selected studies were published between January 2000 and December 2017, written in the English language, and measured pADEs among pediatric hospital inpatients by chart review or direct observation.
    DATA EXTRACTION:
    Data extracted were medication error and harm definitions, pADE incidence and severity rates, items required for quality assessment, and sample details.
    RESULTS:
    Twenty-two studies were included. For children in general pediatric wards, incidence was at 0 to 17 pADEs per 1000 patient days or 1.3% of medication errors (of any type) compared with 0 to 29 pADEs per 1000 patient days or 1.5% of medication errors in ICUs. Hospital-wide studies contained reports of up to 74 pADEs per 1000 patient days or 2.6% of medication errors. The severity of pADEs was mainly minor.
    LIMITATIONS:
    Limited literature on the severity of pADEs is available. Additional study will better illuminate differences among hospital wards and among those with or without health information technology.
    CONCLUSIONS:
    Medication errors in pediatric settings seldom result in patient harm, and if they do, harm is predominantly of minor severity. Implementing health information technologies was associated with reduced incidence of harm.


  • Home Medication Readiness for Preschool Children With Asthma
    BACKGROUND:
    Having a medication available in the home is a prerequisite to medication adherence. Our objectives with this study are to assess asthma medication readiness among low-income urban minority preschool-aged children, and the association between beliefs about medications and medication readiness.
    METHODS:
    During a baseline assessment, a research assistant visited the home to administer a caregiver survey and observe 5 criteria in the medication readiness index: the physical presence and expiration status of medications, the counter status of metered-dose inhalers, and caregiver knowledge of medication type and dosing instructions.
    RESULTS:
    Of 288 enrolled children (mean age 4.2 years [SD: 0.7], 92% African American, 60% boys), 277 (96%) of their caregivers reported a rescue medication, but only 79% had it in the home, and only 60% met all 5 of the medication readiness criteria. Among the 161 children prescribed a controller medication, only 79% had it in the home, and only 49% met all 5 readiness criteria. Fewer worries and concerns about medications were associated with higher odds of meeting all 5 readiness criteria for controller medications.
    CONCLUSIONS:
    Inadequate availability of asthma medications in the home is a barrier to adherence among low-income urban preschoolers. Assessment of medication readiness should be incorporated into clinical care because this is an underrecognized barrier to adherence, and interventions are needed to improve medication management and knowledge to increase adherence.



  • Emergency Department Revisits After an Initial Parenteral Antibiotic Dose for UTI
    BACKGROUND:
    Although oral antibiotics are recommended for the management of most urinary tract infections (UTIs), the administration of parenteral antibiotics before emergency department (ED) discharge is common. We investigated the relationship between the administration of a single dose of parenteral antibiotics before ED discharge and revisits requiring admission among children with UTIs.
    METHODS:
    A retrospective analysis of administrative data from 36 pediatric hospitals was performed. Patients aged 29 days to 2 years who were evaluated in the ED with a UTI between 2010 and 2016 were studied. Primary outcome was adjusted 3-day ED revisit rates resulting in admission. All revisits, regardless of disposition, served as a secondary outcome. Average treatment effects were estimated by using inverse probability weighted regression, with adjustment for demographic factors, diagnostic testing, ED medications, and hospital-level factors.
    RESULTS:
    We studied 29 919 children with a median age of 8.6 (interquartile range: 5.1–13.8) months. Of those studied, 36% of the children received parenteral antibiotics before discharge. Patients who received parenteral antibiotics had similar adjusted rates of revisits leading to admission as those who did not receive parenteral antibiotics (1.3% vs 1.0%, respectively; risk difference: 0.3% [95% confidence interval: –0.01% to 0.6%]), although overall revisit rates were higher among patients who received parenteral antibiotics (4.8% vs 3.3%; risk difference 1.5% [95% confidence interval: 0.9% to 2.1%]).
    CONCLUSIONS:
    Among discharged patients, a parenteral dose of antibiotics did not reduce revisits leading to admission, supporting the goal of discharging patients with oral antibiotics alone for most children with UTIs.


  • Behavioral Health and Adult Milestones in Young Adults With Perinatal HIV Infection or Exposure
    BACKGROUND:
    Young adults living with perinatally acquired HIV infection (PHIVYAs) are at risk for poor biomedical and behavioral health outcomes. Few studies offer a comprehensive overview of the functioning of this population in young adulthood and the role of HIV.
    METHODS:
    Data come from the Child and Adolescent Self-Awareness and Health Study, a longitudinal behavioral health cohort study of PHIVYAs and perinatally HIV–exposed but uninfected young adults (PHEUYAs) who are compared on psychiatric and neurocognitive functioning, sexual and substance use behaviors, health and reproductive outcomes, and young adult milestones.
    RESULTS:
    Overall, 27% of participants met criteria for a psychiatric disorder, including mood (11%), anxiety (22%), and substance use (28%), with no HIV status differences. PHIVYAs performed worse on 2 neurocognitive tests. There were no HIV status differences in condomless sex (41%) or pregnancies (41% women; 38% men). Both groups exhibited similar adult milestones: 67% graduated high school or an equivalent, 19% were in college, and 42% were employed. However, 38% were neither in school or working, 12% reported incarceration, and 16% were ever homeless. Among PHIVYAs, 36% were viremic (>200 copies per mL), and 15% were severely immunocompromised (CD4+ cell count


  • Primary Ovarian Insufficiency and Adolescent Vaccination
    BACKGROUND:
    Published case series have suggested a potential association between human papillomavirus (HPV) vaccination and primary ovarian insufficiency (POI). We describe POI incidence and estimate POI risk after HPV; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap); inactivated influenza (II); and meningococcal conjugate (MenACWY) vaccination.
    METHODS:
    We searched Kaiser Permanente Northwest electronic health records for outpatient diagnoses suggestive of POI in female patients aged 11 to 34 years between 2006 and 2014. We reviewed and adjudicated the medical record to confirm diagnoses and estimate symptom onset dates. We excluded cases with known causes and calculated the incidence of idiopathic POI. We estimated risk by calculating hazard ratios and 95% confidence intervals (CIs).
    RESULTS:
    From a cohort of 199 078 female patients, we identified 120 with diagnoses suggestive of POI. After adjudication and exclusion of 26 POI cases with known causes, we confirmed 46 idiopathic POI cases. POI incidence was low in 11- to 14-year-olds (0.87 per 1 000 000 person-months) and increased with age. One confirmed case patient received the HPV vaccine 23 months before the first clinical evaluation for delayed menarche. The adjusted hazard ratio was 0.30 (95% CI: 0.07–1.36) after HPV, 0.88 (95% CI: 0.37–2.10) after Tdap, 1.42 (95% CI: 0.59–3.41) after II, and 0.94 (95% CI: 0.27–3.23) after MenACWY vaccination.
    CONCLUSIONS:
    We did not find a statistically significant elevated risk of POI after HPV, Tdap, II, or MenACWY vaccination in this population-based retrospective cohort study. These findings should lessen concern about POI risk after adolescent vaccination.


  • Prescription Medication Use Among Children and Adolescents in the United States
    BACKGROUND AND OBJECTIVES:
    Information on the use of prescription medications among children and adolescents in the United States is lacking. We estimate the prevalence of prescription medication use, concurrent use, and potential major drug–drug interactions (DDIs) in this population.
    METHODS:
    We conducted descriptive analyses using nationally representative data for people ≤19 years old from NHANES. Data were derived from a medication log administered by direct observation during in-home interviews. Acute medications were used for ≤30 days. Concurrent use was defined as use of ≥2 prescription medications. Micromedex was used to identify potentially major DDIs.
    RESULTS:
    During 2013–2014, 19.8% of children and adolescents used at least 1 prescription medication, and 7.1% used acute medications. Concurrent use of prescription medications was 7.5% overall and was highest among boys 6 to 12 years old (12%) and among boys and girls ages 13 to 19 years old (10% for both). Using pooled 2009–2014 data, we found that 8.2% of concurrent users of prescription medications were at risk for a potentially major DDI. The vast majority of interacting regimens involved antidepressants and were more common among adolescent girls than boys (18.1% vs 6.6%; P < .05), driven largely by greater rates of use of acute medications.
    CONCLUSIONS:
    Many US children and adolescents use prescription medications with nearly 1 in 12 concurrent users of prescription medications potentially at risk for a major DDI. Efforts to prevent adverse drug events in children and adolescents should consider the role of interacting drug combinations, especially among adolescent girls.


  • Marijuana Use by Breastfeeding Mothers and Cannabinoid Concentrations in Breast Milk
    BACKGROUND AND OBJECTIVE:
    Marijuana is the most commonly used recreational drug among breastfeeding women. With legalization of marijuana in several US states and a 1990 study in which authors documented psychomotor deficits in infants breastfed by mothers using marijuana, there is a need for information on potential exposure to the breastfed infant. Our objective with this study was to quantify cannabinoids in human milk after maternal marijuana use.
    METHODS:
    Between 2014 and 2017, 50 breastfeeding women who reported marijuana use provided 54 breast milk samples to a research repository, Mommy’s Milk. Concentrations of −9-tetrahydrocannabinol (9-THC), 11-hydroxy—9-tetrahydrocannabinol, cannabidiol, and cannabinol were measured by using liquid chromatography mass spectrometry electrospray ionization.
    RESULTS:
    9-THC was detectable in 34 (63%) of the 54 samples up to ~6 days after last reported use; the median concentration of 9-THC was 9.47 ng/mL (range: 1.01–323.00). Five samples had detectable levels of 11-hydroxy—9-tetrahydrocannabinol (range: 1.33–12.80 ng/mL) or cannabidiol (range: 1.32–8.56 ng/mL). The sample with the highest concentration of cannabidiol (8.56 ng/mL) did not have measurable 9-THC. Cannabinol was not detected in any samples. The number of hours since last use was a significant predictor of log 9-THC concentrations (–0.03; 95% confidence interval [CI] –0.04 to –0.01; P = .005). Adjusted for time since last use, the number of daily uses and time from sample collection to analysis were also significant predictors of log 9-THC concentrations (0.51; 95% CI 0.03 to 0.99; P = .039; 0.08; 95% CI 0.00 to 0.15; P = .038, respectively).
    CONCLUSIONS:
    9-THC was measurable in a majority of breast milk samples up to ~6 days after maternal marijuana use.


  • Hypertonic Saline in Bronchiolitis and Type I Error: A Trial Sequential Analysis
    BACKGROUND AND OBJECTIVES:
    Meta-analyses of nebulized hypertonic saline (HS) for acute viral bronchiolitis have yielded disparate conclusions. Trial sequential analysis (TSA) is a novel method designed to account for potential sources of error in conventional meta-analysis. We sought to use TSA to determine if the existing literature base is sufficient to draw firm conclusions about the effectiveness of HS in bronchiolitis.
    METHODS:
    We used the cohort of studies identified in previously published conventional meta-analyses. Included studies were those in which authors compared treatment with HS versus normal saline (or supportive care) in children with bronchiolitis to reduce hospital length of stay (LOS) or hospitalizations. TSA results are used to provide a required information size and monitoring boundaries for statistical significance.
    RESULTS:
    For the LOS outcome, 17 studies including 1866 patients analyzed in which authors used conventional meta-analysis reveal a statistically significant benefit (mean difference = –0.41 days; 95% confidence interval = –0.07 to –0.75); however, TSA suggests that those conclusions are premature because of failure to reach the adequate information size of 2665 individuals. For the risk of hospitalization outcome, 8 studies including 1728 patients analyzed in which authors used conventional meta-analysis reveal a reduction in the relative risk of hospitalization (relative risk = 0.86; 95% confidence interval = 0.76 to 0.98); however, TSA suggests these conclusions are premature because of failure to reach the adequate information size of 4770. Both LOS and hospitalization results from conventional meta-analysis would be considered potentially false-positives by TSA.
    CONCLUSIONS:
    TSA reveals that concluding benefit from HS for children with bronchiolitis potentially represents type I error.











  • Marijuana Use During Pregnancy and Breastfeeding: Implications for Neonatal and Childhood Outcomes
    Marijuana is one of the most widely used substances during pregnancy in the United States. Emerging data on the ability of cannabinoids to cross the placenta and affect the development of the fetus raise concerns about both pregnancy outcomes and long-term consequences for the infant or child. Social media is used to tout the use of marijuana for severe nausea associated with pregnancy. Concerns have also been raised about marijuana use by breastfeeding mothers. With this clinical report, we provide data on the current rates of marijuana use among pregnant and lactating women, discuss what is known about the effects of marijuana on fetal development and later neurodevelopmental and behavioral outcomes, and address implications for education and policy.












  • The Power of Play: A Pediatric Role in Enhancing Development in Young Children
    Children need to develop a variety of skill sets to optimize their development and manage toxic stress. Research demonstrates that developmentally appropriate play with parents and peers is a singular opportunity to promote the social-emotional, cognitive, language, and self-regulation skills that build executive function and a prosocial brain. Furthermore, play supports the formation of the safe, stable, and nurturing relationships with all caregivers that children need to thrive.

    Play is not frivolous: it enhances brain structure and function and promotes executive function (ie, the process of learning, rather than the content), which allow us to pursue goals and ignore distractions.

    When play and safe, stable, nurturing relationships are missing in a child’s life, toxic stress can disrupt the development of executive function and the learning of prosocial behavior; in the presence of childhood adversity, play becomes even more important. The mutual joy and shared communication and attunement (harmonious serve and return interactions) that parents and children can experience during play regulate the body’s stress response. This clinical report provides pediatric providers with the information they need to promote the benefits of play and and to write a prescription for play at well visits to complement reach out and read. At a time when early childhood programs are pressured to add more didactic components and less playful learning, pediatricians can play an important role in emphasizing the role of a balanced curriculum that includes the importance of playful learning for the promotion of healthy child development.


  • Diagnosis, Evaluation, and Management of High Blood Pressure in Children and Adolescents
    Systemic hypertension is a major cause of morbidity and mortality in adulthood. High blood pressure (HBP) and repeated measures of HBP, hypertension (HTN), begin in youth. Knowledge of how best to diagnose, manage, and treat systemic HTN in children and adolescents is important for primary and subspecialty care providers.
    OBJECTIVES:
    To provide a technical summary of the methodology used to generate the 2017 “Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents,” an update to the 2004 “Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents.”
    DATA SOURCES:
    Medline, Cochrane Central Register of Controlled Trials, and Excerpta Medica Database references published between January 2003 and July 2015 followed by an additional search between August 2015 and July 2016.
    STUDY SELECTION:
    English-language observational studies and randomized trials.
    METHODS:
    Key action statements (KASs) and additional recommendations regarding the diagnosis, management, and treatment of HBP in youth were the product of a detailed systematic review of the literature. A content outline establishing the breadth and depth was followed by the generation of 4 patient, intervention, comparison, outcome, time questions. Key questions addressed: (1) diagnosis of systemic HTN, (2) recommended work-up of systemic HTN, (3) optimal blood pressure (BP) goals, and (4) impact of high BP on indirect markers of cardiovascular disease in youth. Once selected, references were subjected to a 2-person review of the abstract and title followed by a separate 2-person full-text review. Full citation information, population data, findings, benefits and harms of the findings, as well as other key reference information were archived. Selected primary references were then used for KAS generation. Level of evidence (LOE) scoring was assigned for each reference and then in aggregate. Appropriate language was used to generate each KAS based on the LOE and the balance of benefit versus harm of the findings. Topics that could not be researched via the stated approach were (1) definition of HTN in youth, and (2) definition of left ventricular hypertrophy. KASs related to these stated topics were generated via expert opinion.
    RESULTS:
    Nearly 15 000 references were identified during an initial literature search. After a deduplication process, 14 382 references were available for title and abstract review, and 1379 underwent full text review. One hundred twenty-four experimental and observational studies published between 2003 and 2016 were selected as primary references for KAS generation, followed by an additional 269 primary references selected between August 2015 and July 2016. The LOE for the majority of references was C. In total, 30 KASs and 27 additional recommendations were generated; 12 were related to the diagnosis of HTN, 13 were related to management and additional diagnostic testing, 3 to treatment goals, and 2 to treatment options. Finally, special additions to the clinical practice guideline included creation of new BP tables based on BP values obtained solely from children with normal weight, creation of a simplified table to enhance screening and recognition of abnormal BP, and a revision of the criteria for diagnosing left ventricular hypertrophy.
    CONCLUSIONS:
    An extensive and detailed systematic approach was used to generate evidence-based guidelines for the diagnosis, management, and treatment of youth with systemic HTN.