PEDIATRICS recent issues

Urine Specific Gravity and the Accuracy of Urinalysis

BACKGROUND:

A recent study in young infants found that different cutoffs maximized the accuracy of the urine white blood cell count in dilute versus concentrated urine samples. We aimed to confirm this finding and to determine its impact on clinical care.

METHODS:

We conducted a retrospective analysis of data gathered on consecutive children <24 months of age with visits to the emergency department during a 5-year period. We evaluated the accuracy of screening tests for urinary tract infection (UTI) in dilute and concentrated urine samples. We also calculated the number of children who would have been treated differently in a hypothetical cohort of 1000 children presenting with fever had urine specific gravity (SG) been taken into consideration.

RESULTS:

We included 10 078 children. The ability to rule in UTI (as measured by the positive likelihood ratio [LR]) was similar in dilute and concentrated urine for the leukocyte esterase test (11.76 vs 10.71, respectively). The positive LR for urine white blood cell count per high-powered field was higher in dilute urine (9.83 vs 6.12). In contrast, the positive LR for the nitrite test was lower in dilute urine (20.54 vs 47.44). Despite these differences, we found little change in the number of children treated with antibiotics in predictive models that took urine SG into consideration.

CONCLUSIONS:

Although we found that urine SG influences the accuracy of some components of the urinalysis, its inclusion in the decision-making process had negligible effect on the clinical care of children with UTI.

Associations Between Opioid Prescribing Patterns and Overdose Among Privately Insured Adolescents

OBJECTIVES:

Little is known about the risk for overdose after opioid prescription. We assessed associations between the type of opioid, quantity dispensed, daily dose, and risk for overdose among adolescents who were previously opioid naive.

METHODS:

Retrospective analysis of 1 146 412 privately insured adolescents ages 11 to 17 years in the United States captured in the Truven MarketScan commercial claims data set from January 2007 to September 2015. Opioid overdose was defined as any emergency department visit, inpatient hospitalization, or outpatient health care visit during which opioid overdose was diagnosed.

RESULTS:

Among our cohort, 725 participants (0.06%) experienced an opioid overdose, and the overall rate of overdose events was 28 events per 100 000 observed patient-years. Receiving ≥30 opioid tablets was associated with a 35% increased risk for overdose compared to receiving ≤18 tablets (hazard ratio [HR] = 1.35; 95% confidence interval: 1.05–1.73; P = .02). Daily prescribed opioid dose was not independently associated with an increased risk for overdose. Tramadol exposure was associated with a 2.67-fold increased risk for opioid overdose compared to receiving oxycodone (adjusted HR = 2.67; 95% confidence interval: 1.90–3.75; P < .0001). Adolescents with preexisting mental health conditions demonstrated increased risk for overdose, with HRs ranging from 1.65 (anxiety) to 3.09 (substance use disorders).

CONCLUSIONS:

One of 1600 (0.06%) previously opioid-naive adolescents who received a prescription for opioids experienced an opioid overdose a median of 1.75 years later that resulted in medical care. Preexisting mental health conditions, use of tramadol, and higher number of dispensed tablets (>30 vs <18) were associated with an increased risk of opioid overdose.

Congenital Heart Disease and Autism: A Case-Control Study

OBJECTIVES:

There has long been an association between congenital heart disease (CHD) and general neurodevelopmental delays. However, the association between CHD and autism spectrum disorders (AuSDs) is less well understood. Using administrative data, we sought to determine the association between CHD and AuSD and identify specific CHD lesions with higher odds of developing AuSD.

METHODS:

We performed a 1:3 case-control study of children enrolled in the US Military Health System from 2001 to 2013. Children with International Classification of Disease, Ninth Revision, Clinical Modification codes for AuSD were identified as cases and matched with controls on the basis of date of birth, sex, and enrollment time frame. Each child’s records were reviewed for CHD lesions and associated procedures. Conditional logistic regression determined odds ratios (ORs) and 95% confidence intervals (CIs) for comparative associations.

RESULTS:

There were 8760 cases with AuSD and 26 280 controls included in the study. After adjustment for genetic syndrome, maternal age, gestational diabetes, short gestation, newborn epilepsy, birth asphyxia, and low birth weight, there were increased odds of AuSD in patients with CHD (OR 1.32; 95% CI 1.10–1.59). Specific lesions with significant OR included atrial septal defects (n = 82; OR 1.72; 95% CI 1.07–2.74) and ventricular septal defects (n = 193; OR 1.65; 95% CI 1.21–2.25).

CONCLUSIONS:

Children with CHD have increased odds of developing AuSD. Specific lesions associated with increased risk include atrial septal defects and ventricular septal defects. These findings will be useful for counseling parents of children with CHD.

A Test for More Accurate Diagnosis of Pulmonary Tuberculosis

OBJECTIVES:

Xpert Mycobacterium tuberculosis and rifampicin (MTB/RIF) Ultra assay has increasingly been used in adult tuberculosis diagnosis, but data relating to its diagnostic accuracy in children are lacking. Because a qualified sputum specimen is difficult to obtain in children, this study evaluated the diagnostic value of Ultra in childhood tuberculosis using bronchoalveolar lavage fluid.

METHODS:

The accuracy of Ultra was calculated by using bacteriologic results and clinical evidence as reference standards. Concordance between Ultra and Xpert MTB/RIF assays was assessed by using coefficients.

RESULTS:

In total, 93 children with pulmonary tuberculosis and 128 children with respiratory tract infections were enrolled. The sensitivity of Ultra, in all pulmonary tuberculosis cases and in bacteriologically confirmed tuberculosis cases, was 70% and 91%, respectively. Ultra could detect Mycobacterium tuberculosis in 58% of cases with negative culture or acid-fast–staining results. The specificity of Ultra was 98%. There was no significant difference in sensitivity between samples with a volume ≤1 and >1 mL (66% vs 73%; P = .50; odds ratio [OR] = 0.71). Among 164 children for which Ultra and Xpert were simultaneously performed, the sensitivity was 80% and 67%, respectively, indicating good agreement ( = 0.84). An additional 6 children were identified as Ultra-positive but Xpert-negative. The positive rate decreased from 93% to 63% after 1 month (P = .01; OR = 0.12) and to 71% after 2 months (P = .03; OR = 0.18) of antituberculosis treatment.

CONCLUSIONS:

Ultra using bronchoalveolar lavage fluid has good sensitivity compared with bacteriologic tests and adds clinical value by assisting the rapid and accurate diagnosis of pulmonary tuberculosis in children.

A Child With Pancytopenia and Optic Disc Swelling

A previously healthy 16-year-old adolescent boy presented with pallor, blurry vision, fatigue, and dyspnea on exertion. Physical examination demonstrated hypertension and bilateral optic nerve swelling. Laboratory testing revealed pancytopenia. Pediatric hematology, ophthalmology and neurology were consulted and a life-threatening diagnosis was made.

Dietary Interventions for Autism Spectrum Disorder: A Meta-analysis

CONTEXT:

Dietary interventions such as restrictive diets or supplements are common treatments for young people with autism spectrum disorder (ASD). Evidence for the efficacy of these interventions is still controversial.

OBJECTIVE:

To assess the efficacy of specific dietary interventions on symptoms, functions, and clinical domains in subjects with ASD by using a meta-analytic approach.

DATA SOURCES:

Ovid Medline, PsycINFO, Embase databases.

STUDY SELECTION:

We selected placebo-controlled, double-blind, randomized clinical trials assessing the efficacy of dietary interventions in ASD published from database inception through September 2017.

DATA EXTRACTION:

Outcome variables were subsumed under 4 clinical domains and 17 symptoms and/or functions groups. Hedges’ adjusted g values were used as estimates of the effect size of each dietary intervention relative to placebo.

RESULTS:

In this meta-analysis, we examined 27 double-blind, randomized clinical trials, including 1028 patients with ASD: 542 in the intervention arms and 486 in the placebo arms. Participant-weighted average age was 7.1 years. Participant-weighted average intervention duration was 10.6 weeks. Dietary supplementation (including omega-3, vitamin supplementation, and/or other supplementation), omega-3 supplementation, and vitamin supplementation were more efficacious than the placebo at improving several symptoms, functions, and clinical domains. Effect sizes were small (mean Hedges’ g for significant analyses was 0.31), with low statistical heterogeneity and low risk of publication bias.

LIMITATIONS:

Methodologic heterogeneity among the studies in terms of the intervention, clinical measures and outcomes, and sample characteristics.

CONCLUSIONS:

This meta-analysis does not support nonspecific dietary interventions as treatment of ASD but suggests a potential role for some specific dietary interventions in the management of some symptoms, functions, and clinical domains in patients with ASD.

Mental Health Conditions and Hyperthyroidism

OBJECTIVES:

To evaluate the proportion of pediatric patients with concurrent diagnoses of hyperthyroidism and mental health conditions (MHCs) by using the Military Health System database. We hypothesized that the prevalence of mental health disorders would be higher in patients with hyperthyroidism compared with in the nonhyperthyroid population.

METHODS:

The prevalence of hyperthyroidism and MHCs was calculated by using data extracted from the Military Health System Data Repository on military beneficiaries between 10 and 18 years old who were eligible to receive care for at least 1 month during fiscal years 2008 through 2016. Prevalence ratios were used to compare MHC diagnoses in those with versus without a diagnosis of hyperthyroidism.

RESULTS:

There were 1894 female patients and 585 male patients diagnosed with hyperthyroidism during the study period. Prevalence ratios for MHCs in those with versus without hyperthyroidism ranged from 1.7 (attention-deficit/hyperactivity disorder [ADHD]) to 4.9 (bipolar disorder). Strikingly, suicidality was nearly 5 times more likely in patients diagnosed with hyperthyroidism than in patients who were never diagnosed with hyperthyroidism. For each of the MHCs examined, with the exception of suicidality, the MHC diagnosis was more commonly made before the diagnosis of hyperthyroidism, with the highest proportion of patients being diagnosed with ADHD before receiving a diagnosis of hyperthyroidism (68.3%).

CONCLUSIONS:

There is a clear association between hyperthyroidism and each of the following MHCs: ADHD, adjustment disorder, anxiety, bipolar disorder, depression, and suicidality. This study highlights the need to consider this association when evaluating patients with overlapping symptoms and for effective mental health screening tools and resources for clinicians.

Prevalence and Trends of Developmental Disabilities among Children in the United States: 2009-2017

OBJECTIVES:

To study the national prevalence of 10 developmental disabilities in US children aged 3 to 17 years and explore changes over time by associated demographic and socioeconomic characteristics, using the National Health Interview Survey.

METHODS:

Data come from the 2009 to 2017 National Health Interview Survey, a nationally representative survey of the civilian noninstitutionalized population. Parents reported physician or other health care professional diagnoses of attention-deficit/hyperactivity disorder; autism spectrum disorder; blindness; cerebral palsy; moderate to profound hearing loss; learning disability; intellectual disability; seizures; stuttering or stammering; and other developmental delays. Weighted percentages for each of the selected developmental disabilities and any developmental disability were calculated and stratified by demographic and socioeconomic characteristics.

RESULTS:

From 2009 to 2011 and 2015 to 2017, there were overall significant increases in the prevalence of any developmental disability (16.2%–17.8%, P < .001), attention-deficit/hyperactivity disorder (8.5%–9.5%, P < .01), autism spectrum disorder (1.1%–2.5%, P < .001), and intellectual disability (0.9%–1.2%, P < .05), but a significant decrease for any other developmental delay (4.7%–4.1%, P < .05). The prevalence of any developmental disability increased among boys, older children, non-Hispanic white and Hispanic children, children with private insurance only, children with birth weight ≥2500 g, and children living in urban areas and with less-educated mothers.

CONCLUSIONS:

The prevalence of developmental disability among US children aged 3 to 17 years increased between 2009 and 2017. Changes by demographic and socioeconomic subgroups may be related to improvements in awareness and access to health care.

Food Insecurity, Health, and Development in Children Under Age Four Years

BACKGROUND AND OBJECTIVES:

Food insecurity and pediatric obesity affect young children. We examine how food insecurity relates to obesity, underweight, stunting, health, and development among children <4 years of age.

METHODS:

Caregivers of young children participated in a cross-sectional survey at medical centers in 5 US cities. Inclusion criteria were age of <48 months. Exclusion criteria were severely ill or injured and private health insurance. The Household Food Security Survey Module defined 3 exposure groups: food secure, household food insecure and child food secure, and household food insecure and child food insecure. Dependent measures were obesity (weight-age >90th percentile), underweight (weight-age <5th percentile), stunting (height/length-age <5th percentile), and caregiver-reported child health and developmental risk. Multivariable logistic regression analyses, adjusted for demographic confounders, maternal BMI, and food assistance program participation examined relations between exposure groups and dependent variables, with age-stratification: 0 to 12, 13 to 24, 25 to 36, and 37 to 48 months of age.

RESULTS:

Within this multiethnic sample (N = 28 184 children, 50% non-Hispanic African American, 34% Hispanic, 14% non-Hispanic white), 27% were household food insecure. With 1 exception at 25 to 36 months, neither household nor child food insecurity were associated with obesity, underweight, or stunting, but both were associated with increased odds of fair or poor health and developmental risk at multiple ages.

CONCLUSIONS:

Among children <4 years of age, food insecurity is associated with fair or poor health and developmental risk, not with anthropometry. Findings support American Academy of Pediatrics recommendations for food insecurity screening and referrals to help families cope with economic hardships and associated stressors.

Depression, Anxiety, and Emergency Department Use for Asthma

BACKGROUND AND OBJECTIVES:

Asthma is responsible for ~1.7 million emergency department (ED) visits annually in the United States. Studies in adults have shown that anxiety and depression are associated with increased asthma-related ED use. Our objective was to assess this association in pediatric patients with asthma.

METHODS:

We identified patients aged 6 to 21 years with asthma in the Massachusetts All-Payer Claims Database for 2014 to 2015 using International Classification of Diseases, Ninth and 10th Revision codes. We examined the association between the presence of anxiety, depression, or comorbid anxiety and depression and the rate of asthma-related ED visits per 100 child-years using bivariate and multivariable analyses with negative binomial regression.

RESULTS:

Of 65 342 patients with asthma, 24.7% had a diagnosis of anxiety, depression, or both (11.2% anxiety only, 5.8% depression only, and 7.7% both). The overall rate of asthma-related ED use was 17.1 ED visits per 100 child-years (95% confidence interval [CI]: 16.7–17.5). Controlling for age, sex, insurance type, and other chronic illness, patients with anxiety had a rate of 18.9 (95% CI: 17.0–20.8) ED visits per 100 child-years, patients with depression had a rate of 21.7 (95% CI: 18.3–25.0), and patients with both depression and anxiety had a rate of 27.6 (95% CI: 24.8–30.3). These rates were higher than those of patients who had no diagnosis of anxiety or depression (15.5 visits per 100 child-years; 95% CI: 14.5–16.4; P < .001).

CONCLUSIONS:

Children with asthma and anxiety or depression alone, or comorbid anxiety and depression, have higher rates of asthma-related ED use compared with those without either diagnosis.

Trends in Off-Label Drug Use in Ambulatory Settings: 2006-2015

BACKGROUND:

Off-label drug use in children is common and potentially harmful. In most previous off-label use research, authors studied hospitalized children, specific drug classes, or non-US settings. We characterized frequencies, trends, and reasons for off-label systemic drug orders for children in ambulatory US settings.

METHODS:

Using nationally representative surveys of office-based physicians (National Ambulatory Medical Care Surveys, 2006–2015), we studied off-label orders of systemic drugs for children age <18 based on US Food and Drug Administration–approved labeling for age, weight, and indication. We characterized the top classes and diagnoses with off-label orders and analyzed factors and trends of off-label orders using logistic regression.

RESULTS:

Physicians ordered ≥1 off-label systemic drug at 18.5% (95% confidence interval: 17.7%–19.3%) of visits, usually (74.6%) because of unapproved conditions. Off-label ordering was most common proportionally in neonates (83%) and in absolute terms among adolescents (322 orders out of 1000 visits). Off-label ordering was associated with female sex, subspecialists, polypharmacy, and chronic conditions. Rates and reasons for off-label orders varied considerably by age. Relative and absolute rates of off-label orders rose over time. Among common classes, off-label orders for antihistamines and several psychotropics increased over time, whereas off-label orders for several classes of antibiotics were stable or declined.

CONCLUSIONS:

US office-based physicians have ordered systemic drugs off label for children at increasing rates, most often for unapproved conditions, despite recent efforts to increase evidence and drug approvals for children. These findings can help inform education, research, and policies around effective, safe use of medications in children.

Rotavirus Epidemiology and Monovalent Rotavirus Vaccine Effectiveness in Australia: 2010-2017

BACKGROUND:

Rotavirus vaccine has been funded for infants under the Australian National Immunisation Program since 2007, with Rotarix vaccine used in New South Wales, Australia, from that time. In 2017, New South Wales experienced a large outbreak of rotavirus gastroenteritis. We examined epidemiology, genotypic profiles, and vaccine effectiveness (VE) among cases.

METHODS:

Laboratory-confirmed cases of rotavirus notified in New South Wales between January 1, 2010 and December 31, 2017 were analyzed. VE was estimated in children via a case-control analysis. Specimens from a sample of hospitalized case patients were genotyped and analyzed.

RESULTS:

In 2017, 2319 rotavirus cases were reported, representing a 3.1-fold increase on the 2016 notification rate. The highest rate was among children aged <2 years. For notified cases in 2017, 2-dose VE estimates were 88.4%, 83.7%, and 78.7% in those aged 6 to 11 months, 1 to 3 years, and 4 to 9 years, respectively. VE was significantly reduced from 89.5% within 1 year of vaccination to 77.0% at 5 to 10 years postvaccination. Equinelike G3P[8] (48%) and G8P[8] (23%) were identified as the most common genotypes in case patients aged ≥6 months.

CONCLUSIONS:

Rotarix is highly effective at preventing laboratory-confirmed rotavirus in Australia, especially in infants aged 6 to 11 months. Reduced VE in older age groups and over time suggests waning protection, possibly related to the absence of subclinical immune boosting from continuously circulating virus. G8 genotypes have not been common in Australia, and their emergence, along with equinelike G3P[8], may be related to vaccine-induced selective pressure; however, further strain-specific VE studies are needed.

Polysomnography and Treatment-Related Outcomes of Childhood Sleep Apnea

BACKGROUND:

Polysomnography is central to the diagnosis and management of childhood obstructive sleep apnea (OSA). However, it is not known whether the treatment-related outcomes of OSA are causally associated with its resolution or changes in severity as determined by polysomnography.

METHODS:

Polysomnographic, cognitive, behavioral, quality-of life, and health outcomes at baseline and at 7 months were obtained from the Childhood Adenotonsillectomy Trial, a randomized trial comparing the outcomes of early adenotonsillectomy to watchful waiting in children with OSA. We used causal mediation analysis to measure the changes in 18 outcomes independently attributable to polysomnographic resolution or changes in severity after adjusting for confounding variables.

RESULTS:

A total of 398 children aged 5 to 9 years were included. A total of 244 (61%) experienced resolution of OSA at follow-up. Polysomnographic resolution of the condition accounted for small but significant proportions of changes in symptoms (proportion mediated [95% confidence interval] 0.13 [0.07 to 0.21]; P < .001) and disease-specific quality of life (0.11 [0.04 to 0.20]; P = .004). Changes in polysomnographic severity similarly mediated symptom score (proportion mediated 0.18 [0.11 to 0.26]; P < .001) and disease-specific quality-of-life outcomes (0.20 [0.10 to 0.31]; P = .004). Importantly, significant mediation effects were not identified for any of the other 16 outcomes. No significant interactions were observed between the trial arms.

CONCLUSIONS:

The majority of the treatment-related changes in outcomes of OSA in school-aged children are not causally attributable to polysomnographic resolution or changes in its severity. These results underscore the limited utility of polysomnographic thresholds in the management of childhood OSA.

Successful Medical Management of Life-threatening Hepatic Hemangioma in Neonates

Hepatic hemangioma (HH) is a common asymptomatic, self-limiting benign vascular tumor of the liver in neonates. Although complicated HHs are rare, they have significant risks of morbidity and mortality, especially during the perinatal period. Because of the high risks of complications from surgical interventions, there is an unmet need for effective medical therapy. We report 2 neonates with life-threatening HH who were evaluated for a liver transplant before being treated successfully with combined medical therapy, which included sirolimus, corticosteroids, and propranolol.

Moving Beyond the Stethoscope: Diagnostic Point-of-Care Ultrasound in Pediatric Practice

Diagnostic point-of-care ultrasound (POCUS) is a growing field across all disciplines of pediatric practice. Machine accessibility and portability will only continue to grow, thus increasing exposure to this technology for both providers and patients. Individuals seeking training in POCUS should first identify their scope of practice to determine appropriate applications within their clinical setting, a few of which are discussed within this article. Efforts to build standardized POCUS infrastructure within specialties and institutions are ongoing with the goal of improving patient care and outcomes.

HPV Vaccine Delivery Practices by Primary Care Physicians

BACKGROUND AND OBJECTIVES:

To examine, among pediatricians and family physicians (FPs) (1) human papillomavirus (HPV) vaccine delivery practices, (2) delivery experiences, and (3) attitudes regarding new 2-dose HPV vaccination schedules.

METHODS:

We surveyed nationally representative networks of pediatricians and FPs by Internet or mail from July 2018 to September 2018. Multivariable regression was used to assess factors associated with refusal or deferral rates of ≥50% among 11- to 12-year-old patients.

RESULTS:

The response rate was 65% (302 pediatricians and 228 FPs included). Pediatricians who strongly recommended the HPV vaccine ranged from 99% for patients ≥15 years old (female) to 83% for those 11 to 12 years old (male); FPs ranged from 90% for patients ≥15 years old (female) to 66% for those 11 to 12 years old (male) (P < .0001 between specialties). Sixty-five percent of pediatricians and 42% of FPs always or almost always used presumptive style when discussing the HPV vaccine (P < .0001). Overall, 40% used standing orders and 42% had electronic alerts. Among pediatricians, the proportion reporting a refusal or deferral rate ≥50% was 19% for female patients and 23% for male patients 11 to 12 years old; FPs reported 27% and 36%, respectively. In the multivariable regression (both sexes), refusal or deferral was associated with physicians not strongly recommending the HPV vaccine to 11- to 12-year-old patients, not using a presumptive style, perceiving less resistance when introducing the HPV vaccine to a 13-year-old patient versus an 11- or 12-year-old patient, and anticipating an uncomfortable conversation when recommending the HPV vaccine to an 11- or 12-year-old patient. Eighty-nine percent of pediatricians and 79% of FPs reported that more adolescents <15 years old are completing the HPV series now that only 2 doses are recommended.

CONCLUSIONS:

Although most physicians strongly recommend the HPV vaccine to 11- to 12-year-old patients, our data reveal areas for improvement in recommendation and delivery methods. Most physicians perceive that the 2-dose schedule is resulting in higher HPV completion rates.

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