PEDIATRICS recent issues

Timing of the Diagnosis of Autism in African American Children

OBJECTIVES:

African American (AA) children affected by autism spectrum disorder (ASD) experience delays in diagnosis and obstacles to service access, as well as a disproportionate burden of intellectual disability (ID) as documented in surveillance data recently published by the US Centers for Disease Control and Prevention. Our objective in this study was to analyze data from the largest-available repository of diagnostic and phenotypic information on AA children with ASD, and to explore the wide variation in outcome within the cohort as a function of sociodemographic risk and specific obstacles to service access for the purpose of informing a national approach to resolution of these disparities.

METHODS:

Parents of 584 AA children with autism consecutively enrolled in the Autism Genetic Resource Exchange across 4 US data collection sites completed event history calendar interviews of the diagnostic odysseys for their children with ASD. These data were examined in relation to developmental outcomes of the children with autism and their unaffected siblings.

RESULTS:

The average age of ASD diagnosis was 64.9 months (±49.6), on average 42.3 months (±45.1) after parents’ first concerns about their children’s development. The relationship between timing of diagnosis and ASD severity was complex, and ID comorbidity was not predicted in a straightforward manner by familial factors associated with cognitive variation in the general population.

CONCLUSIONS:

These findings document significant opportunity to expedite diagnosis, the need to further understand causes of ID comorbidity, and the necessity to identify effective approaches to the resolution of disparities in severity-of-outcome for AA children with autism.

Early Life Experiences and Trajectories of Cognitive Development

BACKGROUND:

Multiple factors constrain the trajectories of child cognitive development, but the drivers that differentiate the trajectories are unknown. We examine how multiple early life experiences differentiate patterns of cognitive development over the first 5 years of life in low-and middle-income settings.

METHODS:

Cognitive development of 835 children from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite observational cohort study was assessed at 6, 15, 24 (Bayley Scales of Infant and Toddler Development), and 60 months (Wechsler Preschool and Primary Scale of Intelligence). Markers of socioeconomic status, infection, illness, dietary intake and status, anthropometry, and maternal factors were also assessed. Trajectories of development were determined by latent class-mixed models, and factors associated with class membership were examined by discriminant analysis.

RESULTS:

Five trajectory groups of cognitive development are described. The variables that best discriminated between trajectories included presence of stimulating and learning resources in the home, emotional or verbal responsivity of caregiver and the safety of the home environment (especially at 24 and 60 months), proportion of days (0–24 months) for which the child had diarrhea, acute lower respiratory infection, fever or vomiting, maternal reasoning ability, mean nutrient densities of zinc and phytate, and total energy from complementary foods (9–24 months).

CONCLUSIONS:

A supporting and nurturing environment was the variable most strongly differentiating the most and least preferable trajectories of cognitive development. In addition, a higher quality diet promoted cognitive development while prolonged illness was indicative of less favorable patterns of development.

Enterovirus and Parechovirus Coinfection in a Sudden Unexpected Infant Death

Viruses are suspected to play a role in the multifactorial pathogenesis of sudden infant death. We described a sudden and unexpected death in a 5-month-old boy, with detection of both enterovirus and parechovirus RNA in the blood. This is the first report of a dual viraemia of enterovirus and parechovirus and its potential association with a sudden unexpected infant death. Extensive sampling and testing especially using molecular methods currently available is needed to better understanding the "hypothetical" link between viral infections and sudden infant death.

Household Food Security and Infant Adiposity

OBJECTIVES:

Food insecurity has been associated with obesity, but previous studies are inconsistent and few included infants. We examined associations between household food security and infant adiposity and assessed the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) and Supplemental Nutrition Assistance Program (SNAP) as effect modifiers. We hypothesized that infants from food-insecure households would have greater adiposity, with attenuation by WIC and SNAP.

METHODS:

We repeatedly measured 666 infants from the southeastern United States in 2013–2017. We categorized households as high, marginal, low, or very low using the US Household Food Security Survey Module. Outcomes were BMI z score, subscapular and triceps skinfold-for-age z score, the sum of subscapular and triceps skinfolds, the ratio of subscapular and triceps skinfolds, and BMI z score ≥1 (at risk for overweight). We used covariate-adjusted repeated-measures linear and logistic regressions.

RESULTS:

Of infants, 68.6% were Black and 60.5% had household incomes <$20 000. Interactions between food security and WIC and/or SNAP were not significant. Compared with infants from high food security households, infants from very low food security households had higher BMI z scores (0.18 U; 95% confidence interval [CI] 0.01 to 0.35), higher subscapular skinfold-for-age z scores (0.31 U; 95% CI 0.04 to 0.59), a higher sum of subscapular and triceps skinfolds (0.53 mm; 95% CI 0.002 to 1.07), and greater odds of being at risk for overweight (odds ratio 1.55; 95% CI 1.14 to 2.10). Infants from low food security households had greater odds of being at risk for overweight (odds ratio 1.72; 95% CI 1.17 to 2.10).

CONCLUSIONS:

In larger and longer studies, researchers should examine food security and adiposity in young children.

Severe Maternal Morbidity and Infant Mortality in Canada

BACKGROUND:

Severe maternal morbidity (SMM) comprises an array of conditions and procedures denoting an acutely life-threatening pregnancy-related condition. SMM may further compromise fetal well-being. Empirical data are lacking about the relation between SMM and infant mortality.

METHODS:

This population-based cohort study included 1 892 857 singleton births between 2002 and 2017 in Ontario, Canada, within a universal health care system. The exposure was SMM as an overall construct arising from 23 weeks’ gestation up to 42 days after the index delivery. The primary outcome was infant mortality from birth to 365 days. Multivariable modified Poisson regression generated relative risks and 95% confidence intervals (CIs), adjusted for maternal age, income, rurality, world region of origin, diabetes mellitus, and chronic hypertension.

RESULTS:

Infant mortality occurred among 174 of 19 587 live births with SMM (8.9 per 1000) vs 5289 of 1 865 791 live births without SMM (2.8 per 1000) (an adjusted relative risk of 2.93 [95% CI 2.51–3.41]). Of 19 587 pregnancies with SMM, 4523 (23.1%) had sepsis. Relative to births without SMM, the adjusted odds ratio for infant death from sepsis was 1.95 (95% CI 1.10–3.45) if SMM occurred without maternal sepsis and 6.36 (95% CI 3.50–11.55) if SMM included sepsis.

CONCLUSIONS:

SMM confers a higher risk of infant death. There is also coupling tendency (concurrent event of interest) between SMM with sepsis and infant death from sepsis. Identification of preventable SMM indicators, as well as the development of strategies to limit their onset or progression, may reduce infant mortality.

Implementation of the Helping Babies Breathe Training Program: A Systematic Review

CONTEXT:

Helping Babies Breathe (HBB) is a well-established neonatal resuscitation program designed to reduce newborn mortality in low-resource settings.

OBJECTIVES:

In this literature review, we aim to identify challenges, knowledge gaps, and successes associated with each stage of HBB programming.

DATA SOURCES:

Databases used in the systematic search included Medline, POPLINE, Cumulative Index to Nursing and Allied Health Literature, Latin American and Caribbean Health Sciences Literature, African Index Medicus, Cochrane, and Index Medicus.

STUDY SELECTION:

All articles related to HBB, in any language, were included. Article quality was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation framework.

DATA EXTRACTION:

Data were extracted if related to HBB, including its implementation, acquisition and retention of HBB knowledge and skills, changes in provider behavior and clinical care, or the impact on newborn outcomes.

RESULTS:

Ninety-four articles met inclusion criteria. Barriers to HBB implementation include staff turnover and limited time or focus on training and practice. Researchers of several studies found HBB cost-effective. Posttraining decline in knowledge and skills can be prevented with low-dose high-frequency refresher trainings, on-the-job practice, or similar interventions. Impact of HBB training on provider clinical practices varies. Although not universal, researchers in multiple studies have shown a significant association of decreased perinatal mortality with HBB implementation.

LIMITATIONS:

In addition to not conducting a gray literature search, articles relating only to Essential Care for Every Baby or Essential Care for Small Babies were not included in this review.

CONCLUSIONS:

Key challenges and requirements for success associated with each stage of HBB programming were identified. Despite challenges in obtaining neonatal mortality data, the program is widely believed to improve neonatal outcomes in resource-limited settings.

Machine Learning To Predict Serious Bacterial Infections in Young Febrile Infants

BACKGROUND:

Recent decision rules for the management of febrile infants support the identification of infants at higher risk of serious bacterial infections (SBIs) without the performance of routine lumbar puncture. We derive and validate a model to identify febrile infants ≤60 days of age at low risk for SBIs using supervised machine learning approaches.

METHODS:

We conducted a secondary analysis of a multicenter prospective study performed between December 2008 and May 2013 of febrile infants. Our outcome was SBI, (culture-positive urinary tract infection, bacteremia, and/or bacterial meningitis). We developed and validated 4 supervised learning models: logistic regression, random forest, support vector machine, and a single-hidden layer neural network.

RESULTS:

A total of 1470 patients were included (1014 >28 days old). One hundred thirty-eight (9.3%) had SBIs (122 urinary tract infections, 20 bacteremia, and 8 meningitis; 11 with concurrent SBIs). Using 4 features (urinalysis, white blood cell count, absolute neutrophil count, and procalcitonin), we demonstrated with the random forest model the highest specificity (74.9, 95% confidence interval: 71.5%–78.2%) with a sensitivity of 98.6% (95% confidence interval: 92.2%–100.0%) in the validation cohort. One patient with bacteremia was misclassified. Among 1240 patients who received a lumbar puncture, this model could have prevented 849 (68.5%) such procedures.

CONCLUSIONS:

We derived and internally validated a supervised learning model for the risk-stratification of febrile infants. Although computationally complex, lacking parameter cutoffs, and in need of external validation, this strategy may allow for reductions in unnecessary procedures, hospitalizations, and antibiotics while maintaining excellent sensitivity.

Reducing Antibiotic Prescribing in Primary Care for Respiratory Illness

BACKGROUND:

One-third of outpatient antibiotic prescriptions for pediatric acute respiratory tract infections (ARTIs) are inappropriate. We evaluated a distance learning program’s effectiveness for reducing outpatient antibiotic prescribing for ARTI visits.

METHODS:

In this stepped-wedge clinical trial run from November 2015 to June 2018, we randomly assigned 19 pediatric practices belonging to the Pediatric Research in Office Settings Network or the NorthShore University HealthSystem to 4 wedges. Visits for acute otitis media, bronchitis, pharyngitis, sinusitis, and upper respiratory infection for children 6 months to <11 years old without recent antibiotic use were included. Clinicians received the intervention as 3 program modules containing online tutorials and webinars on evidence-based communication strategies and antibioti c prescribing, booster video vignettes, and individualized antibiotic prescribing feedback reports over 11 months. The primary outcome was overall antibiotic prescribing rates for all ARTI visits. Mixed-effects logistic regression compared prescribing rates during each program module and a postintervention period to a baseline control period. Odds ratios were converted to adjusted rate ratios (aRRs) for interpretability.

RESULTS:

Among 72 723 ARTI visits by 29 762 patients, intention-to-treat analyses revealed a 7% decrease in the probability of antibiotic prescribing for ARTI overall between the baseline and postintervention periods (aRR 0.93; 95% confidence interval [CI], 0.90–0.96). Second-line antibiotic prescribing decreased for streptococcal pharyngitis (aRR 0.66; 95% CI, 0.50–0.87) and sinusitis (aRR 0.59; 95% CI, 0.44–0.77) but not for acute otitis media (aRR 0.93; 95% CI, 0.83–1.03). Any antibiotic prescribing decreased for viral ARTIs (aRR 0.60; 95% CI, 0.51–0.70).

CONCLUSIONS:

This program reduced antibiotic prescribing during outpatient ARTI visits; broader dissemination may be beneficial.

Family Well-being in Grandparent- Versus Parent-Headed Households

BACKGROUND AND OBJECTIVES:

Little is known about the 2% of US children being raised by their grandparents. We sought to characterize and compare grandparent- and parent-headed households with respect to adverse childhood experiences (ACEs), child temperament, attention-deficit/hyperactivity disorder (ADHD), and caregiver aggravation and coping.

METHODS:

Using a combined data set of children ages 3 to 17 from the 2016, 2017, and 2018 National Survey of Children’s Health, we applied survey regression procedures, adjusted for sociodemographic confounders, to compare grandparent- and parent-headed households on composite and single-item outcome measures of ACEs; ADHD; preschool inattention and restlessness; child temperament; and caregiver aggravation, coping, support, and interactions with children.

RESULTS:

Among 80 646 households (2407 grandparent-headed, 78 239 parent-headed), children in grandparent-headed households experienced more ACEs (β = 1.22, 95% confidence interval [CI]: 1.07 to 1.38). Preschool-aged and school-aged children in grandparent-headed households were more likely to have ADHD (adjusted odds ratio = 4.29, 95% CI: 2.22 to 8.28; adjusted odds ratio = 1.72, 95% CI: 1.34 to 2.20). School-aged children in these households had poorer temperament (βadj = .25, 95% CI: –0.63 to 1.14), and their caregivers experienced greater aggravation (βadj = .29, 95% CI: 0.08 to 0.49). However, these differences were not detected after excluding children with ADHD from the sample. No differences were noted between grandparent- and parent-headed households for caregiver coping, emotional support, or interactions with children.

CONCLUSIONS:

Despite caring for children with greater developmental problems and poorer temperaments, grandparent caregivers seem to cope with parenting about as well as parents.

Clinical Management of Staphylococcus aureus Bacteremia in Neonates, Children, and Adolescents

Staphylococcus aureus is a common cause of community and health care–associated bacteremia, with authors of recent studies estimating the incidence of S aureus bacteremia (SAB) in high-income countries between 8 and 26 per 100 000 children per year. Despite this, <300 children worldwide have ever been randomly assigned into clinical trials to assess the efficacy of treatment of SAB. A panel of infectious diseases physicians with clinical and research interests in pediatric SAB identified 7 key clinical questions. The available literature is systematically appraised, summarizing SAB management in children in relation to these priority clinical questions. The management of neonates, children, and adolescents with SAB is predominantly based on clinical experience and trial data extrapolated from adult studies, with limited high-quality evidence available to guide management. The optimal, comprehensive management strategies for SAB in children will remain unknown until the questions outlined are answered through prospective observational cohorts and inclusion of children with SAB in clinical trials.

Nonresponse to Health-Related Social Needs Screening Questions

BACKGROUND AND OBJECTIVES:

Although clinical settings are increasingly screening for social determinants of health, essential questions about optimal screening remain. We aimed to assess primary care contexts of individuals choosing not to answer questions about health-related social needs and to compare screening question response with subsequent use of resource information.

METHODS:

We compared caregiver responses to an electronic survey administered during a child’s emergency department visit and through telephone follow-up 2 weeks later by responses to questions about health-related social needs (no social needs endorsed, ≥1 endorsed, none endorsed but ≥1 question not answered).

RESULTS:

Of 146 respondents, 42 (29%) endorsed ≥1 health-related social need. Additionally, 19 (13%) endorsed no social needs but did not answer ≥1 question. Compared with those denying all social needs and those endorsing ≥1 social need, respondents who did not answer social needs screening questions reported longer duration since their child’s last primary care visit, lower perceptions of primary care, and less social support. For the 61 respondents participating in the 2-week follow-up survey, reported use of a community resource packet was 37% among those who had reported a social need, 26% among those who had denied all social needs, and 0% among those who had not answered ≥1 social needs questions.

CONCLUSIONS:

Clinicians and systems implementing screening for health-related social risks should plan for individuals who choose not to respond to specific items and may also wish to consider strategies that do not rely on screening and disclosure, particularly in communities known to have high prevalence of social needs.

School-Aged Anthropometric Outcomes After Endoscopic or Open Repair of Metopic Synostosis

BACKGROUND AND OBJECTIVES:

Metopic craniosynostosis can be treated by fronto-orbital advancement or endoscopic strip craniectomy with postoperative helmeting. Infants younger than 6 months of age are eligible for the endoscopic repair. One-year postoperative anthropometric outcomes have been shown to be equivalent, with significantly less morbidity after endoscopic treatment. The authors hypothesized that both repairs would yield equivalent anthropometric outcomes at 5-years postoperative.

METHODS:

This study was a retrospective chart review of 31 consecutive nonsyndromic patients with isolated metopic craniosynostosis treated with either endoscopic or open correction. The primary anthropometric outcomes were frontal width, interfrontal divergence angle, the Whitaker classification, and the presence of lateral frontal retrusion. Peri-operative variables included estimated blood loss, rates of blood transfusion, length of stay, and operating time.

RESULTS:

There was a significantly lower rate of lateral frontal retrusion in the endoscopic group. No statistically significant differences were found in the other 3 anthropometric outcomes at 5-years postoperative. The endoscopic group was younger at the time of surgery and had improved peri-operative outcomes related to operating time, hospital stay and blood loss. Both groups had low complication and reoperation rates.

CONCLUSIONS:

In our cohort of school-aged children with isolated metopic craniosynostosis, patients who underwent endoscopic repair had superior or equivalent outcomes on all 4 primary anthropometric measures compared with those who underwent open repair. Endoscopic repair was associated with significantly faster recovery and decreased morbidity. Endoscopic repair should be considered in patients diagnosed with metopic craniosynostosis before 6 months of age.

Screening and Diagnosis of Prediabetes and Diabetes in US Children and Adolescents

BACKGROUND:

The optimal approach to screening and diagnosis of prediabetes and diabetes in youth is uncertain.

METHODS:

We conducted a cross-sectional analysis of 14 119 youth aged 10 to 19 years in the 1999–2016 NHANES. First, we examined the performance of American Diabetes Association risk-based screening criteria. Second, we evaluated the performance of current clinical definitions of prediabetes and diabetes based on hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), either HbA1c or FPG, or both HbA1c and FPG (confirmatory definition) to identify youth at high cardiometabolic risk.

RESULTS:

Overall, 25.5% of US youth (10.6 million in 2016) were eligible for screening. Sensitivity and specificity of the screening criteria for detecting any hyperglycemia were low for both HbA1c ≥5.7% (sensitivity = 55.5%, specificity = 76.3%) and FPG ≥100 mg/dL (sensitivity = 35.8%, specificity = 77.1%). Confirmed undiagnosed diabetes (HbA1c ≥6.5% and FPG ≥126 mg/dL) was rare, <0.5% of youth. Most (>85%) cases of diabetes were diagnosed. Associations with cardiometabolic risk were consistently stronger and more specific for HbA1c-defined hyperglycemia (specificity = 98.6%; sensitivity = 4.0%) than FPG-defined hyperglycemia (specificity = 90.1%; sensitivity = 19.4%).

CONCLUSIONS:

One-quarter of US youth are eligible for screening for diabetes and prediabetes; however, few will test positive, especially for diabetes. Most cases of diabetes in US youth are diagnosed. Regardless of screening eligibility, we found that HbA1c is a specific and useful nonfasting test to identify high-risk youth who could benefit from lifestyle interventions to prevent diabetes and cardiovascular risk in adulthood.

Cerebral Oxygenation in Preterm Infants With Necrotizing Enterocolitis

BACKGROUND AND OBJECTIVES:

Preterm infants with necrotizing enterocolitis (NEC) are known to have worse neurodevelopmental outcomes, but there is no substantial evidence to support an underlying pathophysiology. We aimed to examine whether cerebral oxygenation differs in those infants who develop NEC compared to cerebral oxygenation in those who do not.

METHODS:

We examined 48 infants <30 weeks’ gestation admitted to a tertiary level NICU from October 2016 to May 2018. Infants with birth weight less than or equal to the second percentile, abnormal antenatal dopplers or twin-to-twin-transfusion-syndrome were excluded. Cerebral oximetry measurements were performed by using a near-infrared spectroscopy (NIRS) monitor weekly for 60 minutes, allowing measurement of cerebral tissue oxygenation index from the first week of life to 36 weeks postconceptional age. Weekly clinical status was also recorded. NEC was defined as greater than or equal to Bell stage 2.

RESULTS:

The median birth weight was 884 g (range of 460–1600 g), the median weeks’ gestational age was 26 + 3/7 (23 + 0/7 to 29 + 6/7), and 52% were girls. In total, 276 NIRS measurements were completed, and 7 infants developed NEC. NIRS measurements from 1 infant with NEC and 4 infants without NEC who developed hemorrhagic parenchymal infarcts were excluded from analysis. Infants who developed NEC had significantly lower cerebral tissue oxygenation index than those who did not (P = .011), even when adjusted for confounders, including gestational age, birth weight, patent ductus arteriosus, enteral feeds, sex, ethnicity, and hemoglobin.

CONCLUSIONS:

Infants with NEC have significantly lower cerebral tissue oxygenation throughout their neonatal intensive care stay in comparison with those who did not develop NEC. This is a novel finding and could explain their worse neurodevelopmental outcome.

Legal Performance-Enhancing Substances and Substance Use Problems Among Young Adults

BACKGROUND:

Legal performance-enhancing substance(s) (PES) (eg, creatine) are widely used among adolescent boys and young men; however, little is known about their temporal associations with substance use behaviors.

METHODS:

We analyzed prospective cohort data from the National Longitudinal Study of Adolescent to Adult Health, Waves I to IV (1994–2008). Logistic regressions were used to first assess adolescent substance use (Wave I) and use of legal PES (Wave III) and second to assess use of legal PES (Wave III) and subsequent substance use–associated risk behaviors (Wave IV), adjusting for potential confounders.

RESULTS:

Among the sample of 12 133 young adults aged 18 to 26 years, 16.1% of young men and 1.2% of young women reported using legal PES in the past year. Adolescent alcohol use was prospectively associated with legal PES use in young men (odds ratio 1.39; 95% confidence interval [CI] 1.13–1.70). Among young men, legal PES use was prospectively associated with higher odds of problematic alcohol use and drinking-related risk behaviors, including binge drinking (adjusted odds ratio [aOR] 1.35; 95% CI 1.07–1.71), injurious and risky behaviors (aOR 1.78; 95% CI 1.43–2.21), legal problems (aOR 1.52; 95% CI 1.08–2.13), cutting down on activities and socialization (aOR 1.91; 95% CI 1.36–2.78), and emotional or physical health problems (aOR 1.44; 95% CI 1.04–1.99). Among young women, legal PES use was prospectively associated with higher odds of emotional or physical health problems (aOR 3.00; 95% CI 1.20–7.44).

CONCLUSIONS:

Use of legal PES should be considered a gateway to future problematic alcohol use and drinking-related risk behaviors, particularly among young men.

Telehealth Home Monitoring and Postcardiac Surgery for Congenital Heart Disease

OBJECTIVES:

To test the effect of a 4-month telehealth home monitoring program (REACH), layered on usual care, on postdischarge outcomes in parents of infants recovering from cardiac surgery and their infants.

METHODS:

Randomized trial of infants discharged from the hospital after cardiac surgery for congenital heart disease. Consecutive infants with complex congenital heart disease undergoing cardiac surgery within 21 days of life were enrolled at 3 university-affiliated pediatric cardiac centers.

RESULTS:

From 2012 to 2016, 219 parent-infant dyads were enrolled; 109 were randomly assigned to the intervention group and 110 to the control group. At 4 months postdischarge, parenting stress was not significantly different between groups (total Parenting Stress Index in the intervention group was 220 and in the control group was 215; P = .61). The percentages of parents who met posttraumatic stress disorder (PTSD) criteria and parent quality of life inventory scores were also not significantly different between the 2 groups (PTSD in the intervention group was 18% and was 18% in the control group; P =.56; the mean Ulm Quality of Life Inventory for Parents in the intervention group was 71 andwas 70 in the control group; P = .88). Infant growth in both groups was suboptimal (the mean weight-for-age z scores were –1.1 in the intervention group and –1.2 in the control group; P = .56), and more infants in the intervention group were readmitted to the hospital (66% in the intervention group versus 57% in the control group; P < .001).

CONCLUSIONS:

When added to usual care, the REACH intervention was not associated with an improvement in parent or infant outcomes. Four months after neonatal heart surgery, ~20% of parents demonstrate PTSD symptoms. Suboptimal infant growth and hospital readmissions were common.

Diagnosis Codes and Case Definitions for Neonatal Abstinence Syndrome

BACKGROUND AND OBJECTIVES:

The increase in neonatal abstinence syndrome (NAS) has underscored the need for NAS surveillance programs, but many rely on passive surveillance using unverified diagnosis codes. Few studies have evaluated the validity of these codes, and no study has assessed the recently proposed Council of State and Territorial Epidemiologists (CSTE) case definition. The Florida Birth Defects Registry investigated the accuracy of International Classification of Diseases, 10th Revision, Clinical Modification codes related to NAS (P96.1 and P04.49) and assessed the sensitivity of the CSTE case definition.

METHODS:

We identified a sample of infants born during 2016 coded with P96.1 and/or P04.49. Record review was completed for 128 cases coded with P96.1, 68 with P04.49, and 7 with both codes. Lacking consensus regarding a gold standard definition of NAS, we used clinical data to classify each case using the Florida and CSTE definitions. The code-specific accuracy was measured by using the positive predictive value (PPV). The clinical characteristics indicative of NAS were compared for case classification based on both definitions.

RESULTS:

By using the Florida definition, the overall PPV was 68% but varied by code: 95.3% for P96.1 and 13.2% for P04.49. The overall (47.8%) and code-specific PPVs were lower by using the CSTE definition. Comparison of clinical characteristics demonstrated that 60.7% of cases classified as no NAS by using the CSTE definition had robust clinical signs of NAS. In our sample, the CSTE case definition underestimated NAS prevalence.

CONCLUSIONS:

Only the P96.1 International Classification of Diseases, 10th Revision, Clinical Modification code displayed high accuracy. Discordance in NAS case definitions and surveillance methodologies may result in erroneous comparisons and conclusions that negatively impact NAS-related surveillance and research.

For Victims of Fatal Child Abuse, Who Has the Right to Consent to Organ Donation?

In rare circumstances, children who have suffered traumatic brain injury from child abuse are declared dead by neurologic criteria and are eligible to donate organs. When the parents are the suspected abusers, there can be confusion about who has the legal right to authorize organ donation. Furthermore, organ donation may interfere with the collection of forensic evidence that is necessary to evaluate the abuse. Under those circumstances, particularly in the context of a child homicide investigation, the goals of organ donation and collection and preservation of critical forensic evidence may seem mutually exclusive. In this Ethics Rounds, we discuss such a case and suggest ways to resolve the apparent conflicts between the desire to procure organs for donation and the need to thoroughly evaluate the evidence of abuse.

Gene Therapy for Spinal Muscular Atrophy: Safety and Early Outcomes

BACKGROUND AND OBJECTIVES:

Historically, autosomal recessive 5q-linked spinal muscular atrophy (SMA) has been the leading inherited cause of infant death. SMA is caused by the absence of the SMN1 gene, and SMN1 gene replacement therapy, onasemnogene abeparvovec-xioi, was Food and Drug Administration approved in May 2019. Approval included all children with SMA age <2 years without end-stage weakness. However, gene transfer with onasemnogene abeparvovec-xioi has been only studied in children age ≤8 months.

METHODS:

In this article, we report key safety and early outcome data from the first 21 children (age 1–23 months) treated in the state of Ohio.

RESULTS:

In children ≤6 months, gene transfer was well tolerated. In this young group, serum transaminase (aspartate aminotransferase and alanine aminotransferase) elevations were modest and not associated with glutamyl transpeptidase elevations. Initial prednisolone administration matched that given in the clinical trials. In older children, elevations in aspartate aminotransferase, alanine aminotransferase and glutamyl transpeptidase were more common and required a higher dose of prednisolone, but all were without clinical symptoms. Nineteen of 21 (90%) children experienced an asymptomatic drop in platelets in the first week after treatment that recovered without intervention. Of the 19 children with repeated outcome assessments, 11% (n = 2) experienced stabilization and 89% (n = 17) experienced improvement in motor function.

CONCLUSIONS:

In this population, with thorough screening and careful post–gene transfer management, replacement therapy with onasemnogene abeparvovec-xioi is safe and shows promise for early efficacy.

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