Neurodevelopmental Outcomes for Individuals With Congenital Heart Disease: Updates in Neuroprotection, Risk-Stratification, Evaluation, and Management: A Scientific Statement From the American Heart Association.

Over the past decade, new research has advanced scientific knowledge of neurodevelopmental trajectories, factors that increase neurodevelopmental risk, and neuroprotective strategies for individuals with congenital heart disease. In addition, best practices for evaluation and management of developmental delays and disorders in this high-risk patient population have been formulated based on literature review and expert consensus. This American Heart Association scientific statement serves as an update to the 2012 statement on the evaluation and management of neurodevelopmental outcomes in children with congenital heart disease. It includes revised risk categories for developmental delay or disorder and an updated list of factors that increase neurodevelopmental risk in individuals with congenital heart disease according to current evidence, including genetic predisposition, fetal and perinatal factors, surgical and perioperative factors, socioeconomic disadvantage, and parental psychological distress. It also includes an updated algorithm for referral, evaluation, and management of individuals at high risk. Risk stratification of individuals with congenital heart disease with the updated categories and risk factors will identify a large and growing population of survivors at high risk for developmental delay or disorder and associated impacts across the life span. Critical next steps must include efforts to prevent and mitigate developmental delays and disorders. The goal of this scientific statement is to inform health care professionals caring for patients with congenital heart disease and other key stakeholders about the current state of knowledge of neurodevelopmental outcomes for individuals with congenital heart disease and best practices for neuroprotection, risk stratification, evaluation, and management.

Evidence-Based Interventions in Autism.

Pediatricians have a critically important role in the care of children with autism, including conducting developmental screening to support early diagnosis and intervention, advising families about evidence-based treatments for autism spectrum disorder, and supporting families' emotional health as they care for a child with a developmental disability. The purpose of this article is to provide pediatricians with information about evidence-based autism treatments and how to determine which interventions are appropriate for children across the autism spectrum at different ages and developmental stages.

Stimulant Medication Treatment in Children with Congenital Heart Disease and Attention-Deficit/Hyperactivity Disorder: Cardiovascular Outcomes.

OBJECTIVE: Children with congenital heart disease (CHD) are at increased risk for attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to determine whether children with CHD and ADHD clinically treated with stimulant medication were at increased risk for changes in cardiovascular parameters or death compared with CHD-matched controls. METHODS: In this retrospective cohort study, patients with CHD + ADHD treated with stimulant medication (exposed group [EG]) were matched by CHD diagnosis and visit age to patients not on stimulants (nonexposed group [NEG]). Cardiovascular parameters (heart rate [HR] and systolic and diastolic blood pressure [SBP and DBP]) and electrocardiograms (ECGs) from medical records over 12 months were compared using mixed effects models. RESULTS: Cardiovascular parameters for 151 children with CHD (mean age 8 ± 4 years) were evaluated (N = 46 EG and N = 105 NEG). Stimulant medication use was not associated with sudden cardiac death. HR and SBP did not significantly change over time in the EG and remained similar between groups. EG children had higher DBP compared with NEG children over time ( p = 0.001). Group × time interactions for HR, SBP, and DBP were not different between the EG and NEG. QTc was not significantly different between the EG and NEG (447 ms vs 439 ms, p = 0.23). EG children demonstrated improvement in ADHD symptoms. CONCLUSION: Stimulant medication use in children with CHD was not associated with clinically significant changes in cardiovascular parameters compared with controls. Stimulants should be considered for ADHD treatment in children with CHD when prescribed with appropriate monitoring and coordination with the cardiologist.

Altered white matter connectivity in children with congenital heart disease with single ventricle physiology.

Children born with congenital heart disease (CHD) have seen a dramatic decrease in mortality thanks to surgical innovations. However, there are numerous risk factors associated with CHD that can disrupt neurodevelopment. Recent studies have found that psychological deficits and structural brain abnormalities persist into adulthood. The goal of the current study was to investigate white matter connectivity in early school-age children (6-11 years), born with complex cyanotic CHD (single ventricle physiology), who have undergone Fontan palliation, compared to a group of heart-healthy, typically developing controls (TPC). Additionally, we investigated associations between white matter tract connectivity and measures on a comprehensive neuropsychological battery within each group. Our results suggest CHD patients exhibit widespread decreases in white matter connectivity, and the extent of these decreases is related to performance in several cognitive domains. Analysis of network topology showed that hub distribution was more extensive and bilateral in the TPC group. Our results are consistent with previous studies suggesting perinatal ischemia leads to white matter lesions and delayed maturation.

Characterisation of neurodevelopmental and psychological outcomes in CHD: a research agenda and recommendations from the cardiac neurodevelopmental outcome collaborative.

The Neurodevelopmental and Psychological Outcomes Working Group of the Cardiac Neurodevelopmental Outcome Collaborative was formed in 2018 through support from an R13 grant from the National Heart, Lung, and Blood Institute with the goals of identifying knowledge gaps regarding the neurodevelopmental and psychological outcomes of individuals with CHD and investigations needed to advance science, policy, clinical care, and patient/family outcomes. Accurate characterisation of neurodevelopmental and psychological outcomes in children with CHD will drive improvements in patient and family outcomes through targeted intervention. Decades of research have produced a generalised perspective about neurodevelopmental and psychological outcomes in this heterogeneous population. Future investigations need to shift towards improving methods, measurement, and analyses of outcomes to better inform early identification, prevention, and intervention. Improved definition of underlying developmental, neuropsychological, and social-emotional constructs is needed, with an emphasis on symptom networks and dimensions. Identification of clinically meaningful outcomes that are most important to key stakeholders, including patients, families, schools and providers, is essential, specifically how and which neurodevelopmental differences across the developmental trajectory impact stakeholders. A better understanding of the discontinuity and patterns of neurodevelopment across the lifespan is critical as well, with some areas being more impactful at some ages than others. Finally, the field needs to account for the impact of race/ethnicity, socio-economic status, cultural and linguistic diversity on our measurement, interpretation of data, and approach to intervention and how to improve generalisability to the larger worldwide population of patients and families living with CHD.

Pattern of head circumference growth following bidirectional Glenn in infants with single ventricle heart disease.

BACKGROUND: Infants with single ventricle congenital heart disease demonstrate increasing head growth after bidirectional Glenn; however, the expected growth trajectory has not been well described. AIMS: 1) We will describe the pattern of head circumference growth in the first year after bidirectional Glenn. 2) We will determine if head growth correlates with motor developmental outcomes approximately 12 months after bidirectional Glenn. METHODS: Sixty-nine single ventricle patients underwent bidirectional Glenn between 2010 and 2016. Patients with structural brain abnormalities, grade III-IV intra-ventricular haemorrhage, significant stroke, or obstructive hydrocephalus were excluded. Head circumference and body weight measurements from clinical encounters were evaluated. Motor development was measured with Psychomotor Developmental Index of the Bayley Scales of Infant Development, Third Edition. Generalised estimating equations assessed change in head circumference z-scores from baseline (time of bidirectional Glenn) to 12 months post-surgery. RESULTS: Mean age at bidirectional Glenn was 4.7 (2.3) months and mean head circumference z-score based on population-normed data was -1.13 (95% CI -1.63, -0.63). Head circumference z-score increased to 0.35 (95% CI -0.20, 0.90) (p < 0.0001) 12 months post-surgery. Accelerated head growth, defined as an increase in z-score of >1 from baseline to 12 months post-surgery, was present in 46/69 (66.7%) patients. There was no difference in motor Psychomotor Developmental Index scores between patients with and without accelerated head growth. CONCLUSION: Single ventricle patients demonstrated a significant increase in head circumference after bidirectional Glenn until 10-12 months post-surgery, at which time growth stabilised. Accelerated head growth did not predict sub-sequent motor developmental outcomes.

Long-Term Neurocognitive and Psychosocial Outcomes After Acute Myeloid Leukemia: A Childhood Cancer Survivor Study Report.

BACKGROUND: Survivors of childhood acute myeloid leukemia (AML) are vulnerable to medical late effects of treatment; however, less is known about their psychosocial outcomes. This study evaluated neurocognitive and psychosocial outcomes in long-term AML survivors treated with bone marrow transplantation (BMT) or intensive chemotherapy (IC) without BMT. METHODS: AML survivors (N = 482; median age at diagnosis = 8 [range = 0-20] years; median age at evaluation = 30 [range = 18-49] years) treated with BMT (n = 183) or IC (n = 299) and sibling controls (N = 3190; median age at evaluation = 32 [range = 18-58] years) from the Childhood Cancer Survivor Study were compared on emotional distress (Brief Symptom Inventory-18), neurocognitive problems (Childhood Cancer Survivor Study Neurocognitive Questionnaire), health-related quality of life (SF-36), and social attainment. Outcomes were dichotomized (impaired vs nonimpaired) using established criteria, and relative risks (RRs) were estimated with multivariable Poisson regression, adjusted for age at evaluation and sex. RESULTS: AML survivors were more likely than siblings to report impairment in overall emotional (RR = 2.19, 95% confidence interval [CI] = 1.51 to 3.18), neurocognitive (RR = 2.03, 95% CI = 1.47 to 2.79), and physical quality of life (RR = 2.71, 95% CI = 1.61 to 4.56) outcomes. Survivors were at increased risk for lower education (RR = 1.15, 95% CI = 1.03 to 1.30), unemployment (RR = 1.41, 95% CI = 1.16 to 1.71), lower income (RR = 1.39, 95% CI = 1.17 to 1.65), and not being married or having a partner (RR = 1.33, 95% CI = 1.17 to 1.51). BMT-treated survivors did not differ statistically significantly from IC-treated on any outcome measure. CONCLUSIONS: AML survivors are at increased risk for psychosocial impairment compared with siblings; however, BMT does not confer additional risk for psychosocial late effects compared with treatment without BMT.

The Fontan outcomes network: first steps towards building a lifespan registry for individuals with Fontan circulation in the United States.

The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.

Improving Behavior Challenges and Quality of Life in the Autism Learning Health Network.

OBJECTIVES: To summarize baseline data and lessons learned from the Autism Learning Health Network, designed to improve care and outcomes for children with autism spectrum disorder (ASD). We describe challenging behaviors, co-occurring medical conditions, quality of life (QoL), receipt of recommended health services, and next steps. METHODS: A cross-sectional study of children 3 to 12 years old with ASD receiving care at 13 sites. Parent-reported characteristics of children with ASD were collected as outcome measures aligned with our network's aims of reducing rates of challenging behaviors, improving QoL, and ensuring receipt of recommended health services. Parents completed a survey about behavioral challenges, co-occurring conditions, health services, and the Patient-Reported Outcomes Measurement Information System Global Health Measure and the Aberrant Behavior Checklist to assess QoL and behavior symptoms, respectively. RESULTS: Analysis included 530 children. Challenging behaviors were reported by the majority of parents (93%), frequently noting attention-deficit/hyperactivity disorder symptoms, irritability, and anxiety. Mean (SD) scores on the Aberrant Behavior Checklist hyperactivity and irritability subscales were 17.9 (10.5) and 13.5 (9.2), respectively. The Patient-Reported Outcomes Measurement Information System Global Health Measure total score of 23.6 (3.7) was lower than scores reported in a general pediatric population. Most children had received recommended well-child (94%) and dental (85%) care in the past 12 months. CONCLUSIONS: This baseline data (1) affirmed the focus on addressing challenging behaviors; (2) prioritized 3 behavior domains, that of attention-deficit/hyperactivity disorder, irritability, and anxiety; and (3) identified targets for reducing severity of behaviors and strategies to improve data collection.

Transforming an Autism Pediatric Research Network into a Learning Health System: Lessons Learned.

INTRODUCTION: The Autism Speaks Autism Treatment Network that serves as the Autism Intervention and Research Network on Physical Health (ATN/AIR-P) has a mission to improve the health and well-being of children with Autism Spectrum Disorder and determine the best practices that lead to improved outcomes and expedite the translation of findings to practice. To better achieve this mission, the ATN/AIR-P is engaging in a design process to transition to a Learning Network (LN), the Autism Learning Health Network. The purpose of this paper is to: (1) make the medical and patient communities aware of an Autism LN that is based on the Institute of Medicine's definition of a Learning Health System; (2) describe how and why the ATN/AIR-P transformed to an LN; and (3) share lessons learned that might inform the transition of future existing networks surrounding other conditions. METHODS: Design methods included: an in-person design session with various stakeholders, the development of a Key Driver Diagram and redesign of organizational processes, network governance, and data collection and analytics. RESULTS: We realized many benefits in making the transition to an LN along with many lessons that can inform the design and implementation of the LN model when transforming existing networks to learning health systems. CONCLUSIONS: Transitioning a well-established research network requires a complex redesign of existing processes, data infrastructure, and cultural shifts compared with developing a new LN. We identified factors that may inform the transition of future established networks to expedite the process.

Improving Access to Diagnostic Assessments for Autism Spectrum Disorder Using an Arena Model.

OBJECTIVE: To improve access to diagnostic evaluations for children younger than 3 years with concerns for possible autism spectrum disorder. METHODS: A multidisciplinary "arena model" for children younger than 3 years was developed, tested, and implemented over an approximately 2-year period. Arena assessment teams comprised a developmental behavioral pediatrician (DBP), psychologist, and speech language pathologist (SLP). Quality improvement methods were used during the design phase, conducting Plan-Do-Study-Act (PDSA) cycles and collecting feedback from key stakeholders, and during implementation, plotting data on run charts to measure outcomes of the time to initial visit and time to diagnosis. RESULTS: Over the 9-month implementation period, 6 arena assessment teams were formed to provide 60 evaluation slots per month for children younger than 3 years. The time to first visit was reduced from a median of 122 days to 19 days, and the time to final diagnosis was reduced from 139 days to 14 days, maintaining these outcomes at <35 and <18 days, respectively, over a 2-year period. Total visits required decreased from 4 to 5 visits to just 2 visits, and the average assessment cost was reduced by $992 per patient. Feedback from both providers and families participating in this model was overwhelmingly positive. CONCLUSION: Access for young children referred for developmental assessments can be improved through an understanding of supply and demand and the development of creative and flexible care delivery models.

Ambient ozone and fine particulate matter exposures and autism spectrum disorder in metropolitan Cincinnati, Ohio.

BACKGROUND: Epidemiological studies report fairly consistent associations between various air pollution metrics and autism spectrum disorder (ASD), with some elevated risks reported for different prenatal and postnatal periods. OBJECTIVES: To examine associations between ASD and ambient fine particulate matter (PM2.5) and ozone concentrations during the prenatal period through the second year of life in a case-control study. METHODS: ASD cases (n = 428) diagnosed at Cincinnati Children's Hospital Medical Center were frequency matched (15:1) to 6420 controls from Ohio birth records. We assigned daily PM2.5 and ozone estimates for 2005-2012 from US EPA's Fused Air Quality Surface Using Downscaling model to each participant for each day based on the mother's census tract of residence at birth. We calculated adjusted odds ratios (aORs) using logistic regression across continuous and categorical exposure window averages (trimesters, first and second postnatal years, and cumulative measure), adjusting for maternal- and birth-related confounders, both air pollutants, and multiple temporal exposure windows. RESULTS: We detected elevated aORs for PM2.5 during the 2nd trimester, 1st year of life, and a cumulative period from pregnancy through the 2nd year (aOR ranges across categories: 1.41-1.44, 1.54-1.84, and 1.41-1.52 respectively), and for ozone in the 2nd year of life (aOR range across categories: 1.29-1.42). Per each change in IQR, we observed elevated aORs for ozone in the 3rd trimester, 1st and 2nd years of life, and the cumulative period (aOR range: 1.19-1.27) and for PM2.5 in the 2nd trimester, 1st year of life, and the cumulative period (aOR range: 1.11-1.17). DISCUSSION: We saw limited evidence of linear exposure-response relationships for ASD with increasing air pollution, but the elevated aORs detected for PM2.5 in upper exposure categories and per IQR unit increases were similar in magnitude to those reported in previous studies, especially for postnatal exposures.

Identifying Associations Among Co-Occurring Medical Conditions in Children With Autism Spectrum Disorders.

OBJECTIVE: Children with autism spectrum disorder (ASD) have a high prevalence of co-occurring medical conditions, including speech, sleep, and gastrointestinal disorders (constipation and feeding difficulties); developmental delay; attention deficit/hyperactivity disorder; hypotonia; epilepsy; anxiety; disruptive behavior; pica; and eczema. Less is known about whether these commonly coexist in the same children. We sought to determine clinically meaningful, statistically significant associations among co-occurring medical conditions in children with ASD that could lead to better understanding, identification, and treatment of these disorders. METHODS: We studied 2114 children with ASD aged 17 months to 5years and 1221 children aged 6 to 17years at 15 Autism Speaks Autism Treatment Network Registry sites. Clinician-reported diagnoses and problems were grouped into 12 core conditions. We determined the observed prevalence (O) of co-occurring conditions and the estimated expected prevalence (E) across the network, adjusting for sitevariability in the prevalence of individual conditions. Pvalues were calculated using a Cochran-Mantel-Haenszel test stratified by site. We identified pairs of conditions co-occurring more frequently than expected (O/E >1) and less frequently than expected (O/E <1) and highlighted statisticallysignificant differences. RESULTS: Among the 66 condition pairs for each age group, we confirmed previously identified associations, such as sleep disorders and anxiety symptoms, in older children. We found some associations not previously described, including feeding with sleep disorders (younger children only), constipation with sleep disorders, feeding with speech disorders, and constipation with speech disorders. CONCLUSIONS: We have identified new associations among co-occurring medical conditions in children with ASD, offering the potential to examine common pathways.

Evidenced-Based Interventions for Children With Autism Spectrum Disorder.

This paper reviews evidenced-based interventions for children with autism spectrum disorders (ASD) across the disciplines of psychology, speech-language pathology, occupational therapy, and developmental pediatrics. BACKGROUND: rates of ASD diagnoses have been steadily rising over the past 2 decades. There are a wide range of therapies and interventions, of varying levels of evidence, across disciplines that are now available to treat children with ASD. The field has moved toward a greater emphasis on the identification and utilization of evidenced-based treatments. METHODS: a review and summary of recent literature was conducted by professionals in an interdisciplinary autism center. An emphasis was placed on results of the National Autism Center's National Standards Project. RESULTS AND CONCLUSIONS: within each discipline, interventions exist that vary in level of evidenced-based support. Although disciplines may differ in their definitions of evidence-based treatments, it is important for each discipline to strive to offer and promote practices with the best evidenced-based support according to each field's standards.

Characteristics of Treatment Decisions to Address Challenging Behaviors in Children with Autism Spectrum Disorder.

OBJECTIVE: To describe the characteristics of treatment decisions to address challenging behaviors in children with autism spectrum disorder (ASD). METHODS: Parents of children aged 4 to 15 years with ASD seen in a developmental behavioral pediatric (DBP) clinic completed validated measures to characterize their child's behaviors and their own level of stress. Parents reported their treatment priority before the visit. During the visit, we assessed shared decision making (SDM) using the Observing Patient Involvement (OPTION) scale and alignment of the clinician's treatment plan with the parent's priority. Before and after the visit, parents rated their uncertainty about the treatment plan using the Decisional Conflict Scale (DCS). We calculated descriptive statistics for the measures. RESULTS: Fifty-four families participated. Children were a mean (SD) age of 8.8 (3.3) years, and 87% were male. Children had a variety of behavioral challenges, and parents reported high levels of stress. Commonly reported parent treatment priorities were hyperactivity, tantrums, anxiety, and poor social skills. Levels of SDM were low, with a mean (SD) OPTION score of 24.5 (9.7). Parent priorities were addressed in 65% of treatment plans. Approximately 69% of parents had elevated DCS scores before the visit. Although levels of decisional conflict were lower after the visit compared with before the visit (p < 0.03), 46% of parents continued to report high scores on the DCS. CONCLUSION: Parents leave DBP visits with feelings of uncertainty about treatment decisions and with treatment plans that do not always address their priorities. SDM interventions hold promise to improve the quality of ASD treatment decisions.

Comparing treatments for children with ADHD and word reading difficulties: A randomized clinical trial.

OBJECTIVE: This trial compared attention-deficit/hyperactivity disorder (ADHD) treatment alone, intensive reading intervention alone, and their combination for children with ADHD and word reading difficulties and disabilities (RD). METHOD: Children (n = 216; predominantly African American males) in Grades 2-5 with ADHD and word reading/decoding deficits were randomized to ADHD treatment (medication + parent training), reading treatment (reading instruction), or combined ADHD + reading treatment. Outcomes were parent and teacher ADHD ratings and measures of word reading/decoding. Analyses utilized a mixed models covariate-adjusted gain score approach with posttest regressed onto pretest. RESULTS: Inattention and hyperactivity/impulsivity outcomes were significantly better in the ADHD (parent Hedges's g = .87/.75; teacher g = .67/.50) and combined (parent g = 1.06/.95; teacher g = .36/41) treatment groups than reading treatment alone; the ADHD and Combined groups did not differ significantly (parent g = .19/.20; teacher g = .31/.09). Word reading and decoding outcomes were significantly better in the reading (word reading g = .23; decoding g = .39) and combined (word reading g = .32; decoding g = .39) treatment groups than ADHD treatment alone; reading and combined groups did not differ (word reading g = .09; decoding g = .00). Significant group differences were maintained at the 3- to 5-month follow-up on all outcomes except word reading. CONCLUSIONS: Children with ADHD and RD benefit from specific treatment of each disorder. ADHD treatment is associated with more improvement in ADHD symptoms than RD treatment, and reading instruction is associated with better word reading and decoding outcomes than ADHD treatment. The additive value of combining treatments was not significant within disorder, but the combination allows treating both disorders simultaneously. (PsycINFO Database Record

High burden of genetic conditions diagnosed in a cardiac neurodevelopmental clinic.

BACKGROUND: There is a known high prevalence of genetic and clinical syndrome diagnoses in the paediatric cardiac population. These disorders often have multisystem effects, which may have an important impact on neurodevelopmental outcomes. Taken together, these facts suggest that patients and families may benefit from consultation by genetic specialists in a cardiac neurodevelopmental clinic. OBJECTIVE: This study assessed the burden of genetic disorders and utility of genetics evaluation in a cardiac neurodevelopmental clinic. METHODS: A retrospective chart review was conducted of patients evaluated in a cardiac neurodevelopmental clinic from 6 December, 2011 to 16 April, 2013. All patients were seen by a cardiovascular geneticist with genetic counselling support. RESULTS: A total of 214 patients were included in this study; 64 of these patients had a pre-existing genetic or syndromic diagnosis. Following genetics evaluation, an additional 19 were given a new clinical or laboratory-confirmed genetic diagnosis including environmental such as teratogenic exposures, malformation associations, chromosomal disorders, and single-gene disorders. Genetic testing was recommended for 112 patients; radiological imaging to screen for congenital anomalies for 17 patients; subspecialist medical referrals for 73 patients; and non-genetic clinical laboratory testing for 14 patients. Syndrome-specific guidelines were available and followed for 25 patients with known diagnosis. American Academy of Pediatrics Red Book asplenia guideline recommendations were given for five heterotaxy patients, and family-based cardiac screening was recommended for 23 families affected by left ventricular outflow tract obstruction. CONCLUSION: Genetics involvement in a cardiac neurodevelopmental clinic is helpful in identifying new unifying diagnoses and providing syndrome-specific care, which may impact the patient's overall health status and neurodevelopmental outcome.