PEDIATRICS recent issues

Pharmacogenetics to Predict Adverse Events Associated With Antidepressants

OBJECTIVES:

To determine the association between cytochrome P450 2C19 (CYP2C19) metabolizer status and risk for escitalopram and citalopram, collectively termed (es)citalopram, and sertraline adverse events (AEs) in children.

METHODS:

In this retrospective cohort study, we used deidentified electronic health records linked to DNA. The cohort included children ≤18 years with ≥2 days of (es)citalopram or ≥7 days of sertraline exposure. The primary outcome was AEs assessed by manual chart review. CYP2C19 was genotyped for functional variants (*2, *3, *4, *6, *8, and *17), and individuals were assigned metabolizer status. Association between AEs and metabolizer status was determined by using Cox regression adjusting for age, race, ethnicity, dose, and concomitant CYP2C19-inhibiting medications.

RESULTS:

The cohort included 249 sertraline-exposed and 458 (es)citalopram-exposed children, with a median age of 14.2 years (interquartile range 11.2–16.2) and 13.4 years (interquartile range 10.1–15.9), respectively. Sertraline AEs were more common in normal metabolizers (NMs) compared to poor metabolizers (PMs) or intermediate metabolizers (IMs) (hazard ratio [HR] 1.8; 95% confidence interval [CI] 1.01–3.2; P = .047) in unadjusted analysis and after adjustment (HR 1.9; CI 1.04–3.4; P = .04). For (es)citalopram, more AEs were observed in NMs than PMs and IMs without statistically significant differences (unadjusted HR 1.6; CI 0.95-2.6; P = .08; adjusted HR 1.6; CI 0.95-2.6; P = .08).

CONCLUSIONS:

In contrast to adults, in our pediatric cohort, CYP2C19 NMs experienced increased sertraline AEs than PMs and IMs. (Es)citalopram AEs were not associated with CYP2C19 status in the primary analysis. The mechanism underlying this pediatric-specific finding is unknown but may be related to physiologic differences of adolescence. Further research is required to inform genotype-guided prescribing for these drugs in children.

Kindergarten Readiness, Later Health, and Social Costs

OBJECTIVES:

To estimate associations between kindergarten readiness and academic, psychological, and health risks by end of high school.

METHODS:

This study is based on 966 Canadian children. At age 5, trained examiners assessed child number knowledge and receptive vocabulary. Teachers reported kindergarten classroom engagement. At age 17, participants reported academic grades, school connectedness, anxiety sensitivity, substance abuse, physical activity involvement, and height and weight. High school dropout risk was also estimated for each participant on the basis of grades, school engagement, and grade retention.

RESULTS:

Kindergarten math skills contributed to better end-of high school grades (β = .17, P < .01) and lower dropout risk (β = –.20, P < .001), whereas receptive vocabulary predicted lower anxiety sensitivity (β = –.11, P < .01). Kindergarten classroom engagement predicted higher end of high school grades (β = .17, P < .001), lower dropout risk (β = –.20, P < .01), better school connectedness (β = .15, P < .01), lower risk of substance abuse (β = –.21, P < .001), and more physical activity involvement (β = .09, P < .05). Kindergarten classroom engagement was also associated with a 65% reduction (odds ratio = 0.35) in the odds of being overweight at age of 17. Analyses were adjusted for key child (sex, weight per gestational age, nonverbal IQ, and internalizing and externalizing behaviors) and family (parental involvement, maternal depression and immigrant status, family configuration, and socioeconomic status) characteristics.

CONCLUSIONS:

Early childhood readiness forecasts a protective edge by emerging adulthood. With these findings, we build links between education and health indicators, suggesting that children who start school prepared gain a lifestyle advantage. Promoting kindergarten readiness could reduce the health burden generated by high school dropout.

Well-Child Care Attendance and Risk of Asthma Exacerbations

BACKGROUND:

Asthma remains a leading cause of hospitalization in US children. Well-child care (WCC) visits are routinely recommended, but how WCC adherence relates to asthma outcomes is poorly described.

METHODS:

We conducted a retrospective longitudinal cohort study using electronic health records among 5 to 17 year old children residing in Durham County with confirmed asthma and receiving primary care within a single health system, to compare the association between asthma exacerbations and previous WCC exposure. Exacerbations included any International Classification of Diseases, Ninth Revision, or International Classification of Diseases, 10th Revision, coded asthma exacerbation encounter with an accompanying systemic glucocorticoid prescription. Exacerbations were grouped by severity: ambulatory encounter only, urgent care, emergency department, hospital encounters <24 hours, and hospital admissions ≥24 hours. In the primary analysis, we assessed time to asthma exacerbation based on the presence or absence of a WCC visit in the preceding year using a time-varying covariate Cox model.

RESULTS:

A total of 5656 children met eligibility criteria and were included in the primary analysis. Patients with the highest WCC visit attendance tended to be younger, had a higher prevalence of private insurance, had greater asthma medication usage, and were less likely to be obese. The presence of a WCC visit in the previous 12 months was associated with a reduced risk of all-cause exacerbations (hazard ratio: 0.90; 95% confidence interval: 0.83–0.98) and severe exacerbations requiring hospital admission (hazard ratio: 0.53; 95% confidence interval: 0.39–0.71).

CONCLUSIONS:

WCC visits were associated with a lower risk of subsequent severe exacerbations, including asthma-related emergency department visits and hospitalizations. Poor WCC visit adherence predicts pediatric asthma morbidity, especially exacerbations requiring hospitalization.

Randomized Controlled Trial of High-Flow Nasal Cannula in Preterm Infants After Extubation

OBJECTIVES:

Our aim is to compare the efficacy and safety of high-flow nasal cannula (HFNC) against those of nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive-pressure ventilation (NIPPV) after extubation in preterm infants.

METHODS:

This prospective, randomized, noninferiority trial was conducted in 6 tertiary NICUs. Infants born at <34 weeks who needed noninvasive ventilation after extubation were enrolled. We randomly assigned infants to an HFNC group when HFNC was used or to an NCPAP/NIPPV group when NCPAP or NIPPV was used. The primary outcome was treatment failure within 7 days after extubation. We then examined clinical aspects of treatment failure with HFNC use.

RESULTS:

In total, 176 and 196 infants were assigned to the HFNC and NCPAP/NIPPV groups, respectively. The HFNC group showed a significantly higher rate of treatment failure than that of the NCPAP/NIPPV group, with treatment failure occurring in 54 infants (31%) compared with 31 infants (16%) in the NCPAP/NIPPV group (risk difference, 14.9 percentage points; 95% confidence interval, 6.2–23.2). Histologic chorioamnionitis (P = .02), treated patent ductus arteriosus (P = .001), and corrected gestational age at the start of treatment (P = .007) were factors independently related to treatment failure with HFNC use.

CONCLUSIONS:

We found HFNC revealed a significantly higher rate of treatment failure than NCPAP or NIPPV after extubation in preterm infants. The independent factors associated with treatment failure with HFNC use were histologic chorioamnionitis, treated patent ductus arteriosus, and a younger corrected gestational age at the start of treatment.

COVID-19 in 17 Italian Pediatric Emergency Departments

BACKGROUND:

Variability in presentation of children with coronavirus disease 2019 (COVID-19) is a challenge in emergency departments (EDs) in terms of early recognition, which has an effect on disease control and prevention. We describe a cohort of 170 children with COVID-19 and differences with the published cohorts.

METHODS:

Retrospective chart reviews on children (0–18 years) evaluated in 17 Italian pediatric EDs.

RESULTS:

In our cohort (median age of 45 months; interquartile range of 4 months–10.7 years), we found a high number of patients <1 year with COVID-19 disease. The exposure happened mainly (59%) outside family clusters; 22% had comorbidities. Children were more frequently asymptomatic (17%) or with mild diseases (63%). Common symptoms were cough (43%) and difficulty feeding (35%). Chest computed tomography, chest radiograph, and point-of-care lung ultrasound were used in 2%, 36%, and 8% of cases, respectively. Forty-three percent of patients were admitted because of their clinical conditions. The minimal use of computed tomography and chest radiograph may have led to a reduced identification of moderate cases, which may have been clinically classified as mild cases.

CONCLUSIONS:

Italian children evaluated in the ED infrequently have notable disease symptoms. For pediatrics, COVID-19 may have rare but serious and life-threatening presentations but, in the majority of cases, represents an organizational burden for the ED. These data should not lower the attention to and preparedness for COVID-19 disease because children may represent a source of viral transmission. A clinically driven classification, instead of a radiologic, could be more valuable in predicting patient needs and better allocating resources.

Health of Newborns and Infants Born to Women With Disabilities: A Meta-analysis

CONTEXT:

Women with disabilities are at elevated risk for pregnancy, delivery, and postpartum complications. However, there has not been a synthesis of literature on the neonatal and infant health outcomes of their offspring.

OBJECTIVE:

We examined the association between maternal disability and risk for adverse neonatal and infant health outcomes.

DATA SOURCES:

Cumulative Index to Nursing and Allied Health Literature, Embase, Medline, and PsycINFO were searched from database inception to January 2020.

STUDY SELECTION:

Studies were included if they reported original data on the association between maternal physical, sensory, or intellectual and/or developmental disabilities and neonatal or infant health outcomes; had a referent group of women with no disabilities; were peer-reviewed journal articles or theses; and were written in English.

DATA EXTRACTION:

We used standardized instruments to extract data and assess study quality. DerSimonian and Laird random effects models were used for pooled analyses.

RESULTS:

Thirty-one studies, representing 20 distinct cohorts, met our inclusion criteria. Meta-analyses revealed that newborns of women with physical, sensory, and intellectual and/or developmental disabilities were at elevated risk for low birth weight and preterm birth, with smaller numbers of studies revealing elevated risk for other adverse neonatal and infant outcomes.

LIMITATIONS:

Most studies had moderate (n = 9) or weak quality (n = 17), with lack of control for confounding a common limitation.

CONCLUSIONS:

In future work, researchers should explore the roles of tailored preconception and perinatal care, along with family-centered pediatric care particularly in the newborn period, in mitigating adverse outcomes among offspring of women with disabilities.

Follow-up Blood Cultures in Children With Staphylococcus aureus Bacteremia

BACKGROUND:

Staphylococcus aureus is a common pathogen seen in pediatric bloodstream infections. Currently, no evidence-based recommendations are used to guide decisions on the number of follow-up blood cultures (FUBCs) needed to demonstrate infection clearance. Unnecessary cultures increase the risk of false-positives, add to health care costs, and create additional trauma to children and their families. In this study, we examined risk factors for persistent S aureus bacteremia (SAB) and intermittent positive blood cultures (positive cultures obtained after a documented negative FUBC result) to determine the number of FUBCs needed to demonstrate infection clearance in children.

METHODS:

Patients ≤18 years who were hospitalized with SAB at Texas Children’s Hospital in 2018 were reviewed. We assessed the impact of an infectious disease diagnosis (central line–associated bloodstream infection, osteomyelitis, soft tissue infection, endocarditis, etc) and medical comorbidities on bacteremia duration. Patients with intermittent positive blood cultures were studied to determine the characteristics of this group and overall frequency of reversion to positive cultures.

RESULTS:

A total of 122 subjects met the inclusion criteria. The median duration of bacteremia was 1 day (interquartile range: 1–2 days). Only 19 patients (16%) had bacteremia lasting ≥3 days, all of whom had a diagnosis of central line–associated bloodstream infection, osteomyelitis, or endocarditis. Intermittent positive cultures occurred in 5% of patients, with positive cultures after 2 negative FUBC results seen in <1% of patients. Intermittent positive cultures were strongly associated with osteomyelitis and endocarditis.

CONCLUSIONS:

On the basis of our sample of children with SAB, additional blood cultures to document sterility are not necessary after 2 FUBC results are negative in well-appearing patients.

Group Sessions or Home Visits for Early Childhood Development in India: A Cluster RCT

OBJECTIVES:

Poor early childhood development in low- and middle-income countries is a major public health problem. Efficacy trials have shown the potential of early childhood development interventions but scaling up is costly and challenging. Guidance on effective interventions’ delivery is needed. In an open-label cluster-randomized control trial, we compared the effectiveness of weekly home visits and weekly mother-child group sessions. Both included nutritional education, whose effectiveness was tested separately.

METHODS:

In Odisha, India, 192 villages were randomly assigned to control, nutritional education, nutritional education and home visiting, or nutritional education and group sessions. Mothers with children aged 7 to 16 months were enrolled (n = 1449). Trained local women ran the two-year interventions, which comprised demonstrations and interactions and targeted improved play and nutrition. Primary outcomes, measured at baseline, midline (12 months), and endline (24 months), were child cognition, language, motor development, growth and morbidity.

RESULTS:

Home visiting and group sessions had similar positive average (intention-to-treat) impacts on cognition (home visiting: 0.324 SD, 95% confidence interval [CI]: 0.152 to 0.496, P = .001; group sessions: 0.281 SD, 95% CI: 0.100 to 0.463, P = .007) and language (home visiting: 0.239 SD, 95% CI: 0.072 to 0.407, P = .009; group sessions: 0.302 SD, 95% CI: 0.136 to 0.468, P = .001). Most benefits occurred in the first year. Nutrition-education had no benefit. There were no consistent effects on any other primary outcomes.

CONCLUSIONS:

Group sessions cost $38 per child per year and were as effective on average as home visiting, which cost $135, implying an increase by a factor of 3.5 in the returns to investment with group sessions, offering a more scalable model. Impacts materialize in the first year, having important design implications.

Smoking Intention and Progression From E-Cigarette Use to Cigarette Smoking

OBJECTIVES:

To investigate whether the prospective association between electronic cigarette (e-cigarette) use and cigarette smoking is dependent on smoking intention status.

METHODS:

Waves 2 and 3 data of the Population Assessment of Tobacco and Health (PATH) Study, a US nationally representative prospective cohort study of tobacco use. Data were collected in 2014–2015 (wave 2) and 2015–2016 (wave 3) and analyzed in 2019.

RESULTS:

At wave 2, 12.8% of adolescent never-smokers of conventional cigarettes had intention to smoke and 8.5% had ever used an e-cigarette. At wave 3, 3.2% had ever smoked a cigarette. Both smoking intention and ever using e-cigarettes at wave 2 were positively associated with cigarette smoking at wave 3 (adjusted odds ratio [aOR] = 3.03; 95% confidence interval [CI] = 1.97–4.68, P < .001; aOR = 4.62, 95% CI = 2.87–7.42, P < .001, respectively). The interaction between smoking intention and ever using e-cigarettes was significant (aOR = 0.34, 95% CI = 0.18–0.64, P < .01). Among adolescents who had expressed intention to smoke conventional cigarettes at wave 2, the odds of cigarette smoking at wave 3 did not significantly differ for e-cigarette users and never e-cigarette users (aOR = 1.57; 95% CI 0.94–2.63; P = .08). Among adolescents who had no intention to smoke at wave 2, e-cigarette users, compared with never e-cigarette users, had >4 times the odds of cigarette smoking (aOR = 4.62; 95% CI 2.87–7.42; P < .0001).

CONCLUSIONS:

E-cigarette use is associated with increased odds of cigarette smoking among adolescents who had no previous smoking intention. E-cigarette use may create intention to smoke and/or nicotine use disorder that lead to onset of cigarette smoking.

International Medical Graduates in the Pediatric Workforce in the United States

BACKGROUND AND OBJECTIVES:

To describe the supply, distribution, and characteristics of international medical graduates (IMGs) in pediatrics who provide patient care in the United States.

METHODS:

Cross-sectional study, combining data from the 2019 Physician Masterfile of the American Medical Association and the Educational Commission for Foreign Medical Graduates database.

RESULTS:

In total, 92 806 pediatric physicians were identified, comprising 9.4% of the entire US physician workforce. Over half are general pediatricians. IMGs account for 23.2% of all general pediatricians and pediatric subspecialists. Of all IMGs in pediatrics, 22.1% or 4775 are US citizens who obtained their medical degree outside the United States or Canada, and 15.4% (3246) attended medical school in the Caribbean. Fifteen non-US medical schools account for 29.9% of IMGs currently in active practice in pediatrics in the United States. IMGs are less likely to work in group practice or hospital-based practice and are more likely to be employed in solo practice (compared with US medical school graduates).

CONCLUSIONS:

With this study, we provide an overview of the pediatric workforce, quantifying the contribution of IMGs. Many IMGs are US citizens who attend medical school abroad and return to the United States for postgraduate training. Several factors, including the number of residency training positions, could affect future numbers of IMGs entering the United States. Longitudinal studies are needed to better understand the implications that workforce composition and distribution may have for the care of pediatric patients.

An Uninfected Preterm Newborn Inadvertently Fed SARS-CoV-2-Positive Breast Milk

There are increasing concerns regarding coronavirus disease, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approaches to breastfeeding and the management of neonates born to pauci-symptomatic mothers with coronavirus disease vary worldwide, although some scientific societies across Europe and the United States have emphasized the benefits of breastfeeding, even with expressed breast milk. Because SARS-CoV-2 has been, thus far, only exceptionally detected in breast milk, the risk of disease transmission has remained hypothetical.

We herein report the case of a healthy preterm newborn who was inadvertently fed SARS-CoV-2–positive breast milk. Two different samples, collected with and without strict hygiene precautions, were both confirmed to be SARS-CoV-2 positive. However, the newborn was not infected, supporting the protective role of breast milk. Furthermore, in this report, we highlight the difficulties in the practical management of a neonate whose breastfeeding mother was confirmed as positive for SARS-CoV-2 after delivery.

"It's My Job to Love Him": Parenting Adolescents and Young Adults With Advanced Cancer

BACKGROUND:

Parents of adolescents and young adults (AYAs) with serious illness experience enormous stress as they navigate their child’s illness. In this study, we aimed to elucidate AYA parental perspectives on the advanced cancer experience, including what parents find challenging and their sources of strength.

METHODS:

Parents of AYAs aged 14 to 24 years old being treated for recurrent or refractory advanced cancer at a large academic center completed demographic surveys and 1:1 semi-structured interviews between December 2017 and July 2018. Conventional content analysis was used by 2 coders to analyze transcriptions, with a third reviewer adjudicating. Thematic networks analysis was then used to extrapolate basic and organizing themes.

RESULTS:

A total of 22 parents participated. The majority were female, non-Hispanic, and married; 23% (n = 5) were from racial minority groups. We identified 3 organizing themes related to navigating parents’ experiences: (1) what we do to love our child, (2) what challenges us, and (3) how we keep our heart focused on what matters most. Despite substantial uncertainty about their child’s future, parents endorsed growth and gratitude as they focused on the ways they showed love for their child during this difficult time.

CONCLUSIONS:

Parents of AYAs with advanced cancer experience many parenting challenges, elucidating some of the vulnerabilities and magnifying the sources of strength among parents of children transitioning to adulthood during serious illness. This research has important implications for how we build programs that support and sustain parents’ well-being during their child’s serious illness.

Parental Vaccine Hesitancy and Childhood Influenza Vaccination

OBJECTIVES:

To quantify the prevalence of parental vaccine hesitancy (VH) in the United States and examine the association of VH with sociodemographics and childhood influenza vaccination coverage.

METHODS:

A 6-question VH module was included in the 2018 and 2019 National Immunization Survey-Flu, a telephone survey of households with children age 6 months to 17 years.

RESULTS:

The percentage of children having a parent reporting they were "hesitant about childhood shots" was 25.8% in 2018 and 19.5% in 2019. The prevalence of concern about the number of vaccines a child gets at one time impacting the decision to get their child vaccinated was 22.8% in 2018 and 19.1% in 2019; the prevalence of concern about serious, long-term side effects impacting the parent’s decision to get their child vaccinated was 27.3% in 2018 and 21.7% in 2019. Only small differences in VH by sociodemographic variables were found, except for an 11.9 percentage point higher prevalence of "hesitant about childhood shots" and 9.9 percentage point higher prevalence of concerns about serious, long-term side effects among parents of Black compared with white children. In both seasons studied, children of parents reporting they were "hesitant about childhood shots" had 26 percentage points lower influenza vaccination coverage compared with children of parents not reporting hesitancy.

CONCLUSIONS:

One in 5 children in the United States have a parent who is vaccine hesitant, and hesitancy is negatively associated with childhood influenza vaccination. Monitoring VH could help inform immunization programs as they develop and target methods to increase vaccine confidence and vaccination coverage.

Behavior Change, Egg Consumption, and Child Nutrition: A Cluster Randomized Controlled Trial

BACKGROUND AND OBJECTIVES:

Malnutrition is a significant contributor to child morbidity and mortality globally. Egg consumption has been associated with improved child nutrition yet is rare in rural, resource-poor settings. We test the effects of a culturally tailored behavior change intervention to increase child egg consumption.

METHODS:

A 3-arm cluster randomized controlled trial was conducted in rural Burkina Faso with 260 mother-child dyads. Children aged 4 to 17 months from 18 villages were included; those with reported history of malnutrition or egg allergy were excluded. Each child in the full intervention arm received 4 chickens, and mothers received the 10-month behavior change package. Participants in the partial intervention arm received only the behavior change package.

RESULTS:

In this analysis of 250 children, the full (β = 4.3; P = 6.6 x 10–12) and the partial (β = 1.0; P = .02) interventions significantly increased egg consumption. The full intervention also significantly increased poultry production (β = 11.6; 95% confidence interval 8.3–15; P = 1.1 x 10–5) and women’s decision-making about eggs (β = .66; P = .02), and significantly decreased wasting (β = .58; P = .03) and underweight (β = .47; P = .02).

CONCLUSIONS:

The culturally tailored behavior change package significantly increased child egg consumption. When coupled with the gift of chickens, the behavior change intervention yielded a greater increase in egg consumption and significantly reduced wasting and underweight. Behavior change strategies to increase egg consumption should be considered among nutrition and health programs in resource-poor settings where poultry is available.

MIS-C and Cardiac Conduction Abnormalities

OBJECTIVES:

Multisystem inflammatory syndrome in children (MIS-C) has spread through the pediatric population during the coronavirus disease 2019 pandemic. Our objective for the study was to report the prevalence of conduction anomalies in MIS-C and identify predictive factors for the conduction abnormalities.

METHODS:

We performed a single-center retrospective cohort study of pediatric patients <21 years of age presenting with MIS-C over a 1-month period. We collected clinical outcomes, laboratory findings, and diagnostic studies, including serial electrocardiograms, in all patients with MIS-C to identify those with first-degree atrioventricular block (AVB) during the acute phase and assess for predictive factors.

RESULTS:

Thirty-two patients met inclusion criteria. Median age at admission was 9 years. Six of 32 patients (19%) were found to have first-degree AVB, with a median longest PR interval of 225 milliseconds (interquartile range 200–302), compared with 140 milliseconds (interquartile range 80–178) in patients without first-degree AVB. The onset of AVB occurred at a median of 8 days after the initial symptoms and returned to normal 3 days thereafter. No patients developed advanced AVB, although 1 patient developed a PR interval >300 milliseconds. Another patient developed new-onset right bundle branch block, which resolved during hospitalization. Cardiac enzymes, inflammatory markers, and cardiac function were not associated with AVB development.

CONCLUSIONS:

In our population, there is a 19% prevalence of first-degree AVB in patients with MIS-C. All patients with a prolonged PR interval recovered without progression to high-degree AVB. Patients admitted with MIS-C require close electrocardiogram monitoring during the acute phase.

When a Family Seeks to Exclude Residents From Their Childs Care

A primary goal of our medical education system is to produce physicians qualified to promote health, prevent and treat disease, and relieve suffering. Although some aspects of the practice of medicine can be learned in classrooms, from textbooks, or with simulators, other aspects can only be learned through the direct provision of patient care. Residency programs therefore offer essential educational experiences that support residents’ acquisition of knowledge, skills, and professional judgment through the assumption of progressive responsibility under an appropriate level of supervision. Yet, ethical questions can arise when medical education is integrated with patient care. How should we balance the educational needs of residents and the social benefits of medical education against obligations to patients and families? In this article, we present the case of a child whose family requests that residents not be allowed to perform any procedures on their child and then ask experts (a pediatric residency program director, a pediatrics resident, and an ethicist) to comment.

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