Neurodevelopmental outcomes of preterm and growth-restricted neonate with congenital heart defect: a systematic review and meta-analysis.

The purpose of the study is to assess the risks of neurodevelopmental morbidity among preterm and growth restricted youth with congenital heart defects (CHD). This systematic review and meta-analysis included observational studies assessing neurodevelopmental outcomes among children with CHD born preterm (i.e., before 37 weeks of gestation) or growth restricted (small-for-gestational age (SGA) with a birthweight < the 10th percentile or with low birthweight (LBW) < 2500 g). Studies were identified in Medline and Embase databases from inception until May 2022, with data extracted by two blinded reviewers. Risk of bias was assessed using the Critical Appraisal Skills Programme cohort checklist. Meta-analysis involved the use of random-effects models. Main outcome measures were neurodevelopmental outcomes including overall cognitive impairment and intellectual disability, IQ, communication, and motor skills scores. From 3573 reports, we included 19 studies in qualitative synthesis and 6 meta-analysis studies. Risk of bias was low in 8/19 studies. Cognitive impairment and intellectual disability were found in 26% (95% CI 20-32, I2 = 0%) and 19% (95% CI 7-35, I2 = 82%) of preterm children with CHD, respectively. Two studies documented a lower IQ score for SGA children who underwent CHD operations in comparison to non-SGA children who also underwent CHD operations. Two studies have reported lower IQ, communication, and motor skills in children with hypoplastic left heart syndrome (HLHS) and low birth weight compared to those with HLHS and expected birth weight. CONCLUSIONS: Based on a low level of evidence, prematurity and/or growth retardation appear to accentuate specific neurodevelopmental outcomes in certain CHD subgroups. Further evidence is needed to confirm these findings. TRIAL REGISTRATION: PROSPERO [CRD42020201414]. WHAT IS KNOWN: • Children born with CHD, preterm birth, or growth restriction at birth are independently at higher risk for neurodevelopmental impairment. • The additional effect of preterm birth and/or growth restriction on neurodevelopmental outcomes in children with CHD remains unclear. WHAT IS NEW: • Prematurity and/or growth retardation appear to accentuate specific neurodevelopmental outcomes in certain CHD subgroups. • Children with CHD, particularly those born preterm or with growth restriction, should undergo lifelong systematic comprehensive neurodevelopmental assessment.

Neurological and Psychological Sequelae Associated With Multisystem Inflammatory Syndrome in Children.

Importance: Acute neurological involvement occurs in some patients with multisystem inflammatory syndrome in children (MIS-C), but few data report neurological and psychological sequelae, and no investigations include direct assessments of cognitive function 6 to 12 months after discharge. Objective: To characterize neurological, psychological, and quality of life sequelae after MIS-C. Design, Setting, and Participants: This cross-sectional cohort study was conducted in the US and Canada. Participants included children with MIS-C diagnosed from November 2020 through November 2021, 6 to 12 months after hospital discharge, and their sibling or community controls, when available. Data analysis was performed from August 2022 to May 2023. Exposure: Diagnosis of MIS-C. Main Outcomes and Measures: A central study site remotely administered a onetime neurological examination and in-depth neuropsychological assessment including measures of cognition, behavior, quality of life, and daily function. Generalized estimating equations, accounting for matching, assessed for group differences. Results: Sixty-four patients with MIS-C (mean [SD] age, 11.5 [3.9] years; 20 girls [31%]) and 44 control participants (mean [SD] age, 12.6 [3.7] years; 20 girls [45%]) were enrolled. The MIS-C group exhibited abnormalities on neurological examination more frequently than controls (15 of 61 children [25%] vs 3 of 43 children [7%]; odds ratio, 4.7; 95% CI, 1.3-16.7). Although the 2 groups performed similarly on most cognitive measures, the MIS-C group scored lower on the National Institutes of Health Cognition Toolbox List Sort Working Memory Test, a measure of executive functioning (mean [SD] scores, 96.1 [14.3] vs 103.1 [10.5]). Parents reported worse psychological outcomes in cases compared with controls, particularly higher scores for depression symptoms (mean [SD] scores, 52.6 [13.1] vs 47.8 [9.4]) and somatization (mean [SD] scores, 55.5 [15.5] vs 47.0 [7.6]). Self-reported (mean [SD] scores, 79.6 [13.1] vs 85.5 [12.3]) and parent-reported (mean [SD] scores, 80.3 [15.5] vs 88.6 [13.0]) quality of life scores were also lower in cases than controls. Conclusions and Relevance: In this cohort study, compared with contemporaneous sibling or community controls, patients with MIS-C had more abnormal neurologic examinations, worse working memory scores, more somatization and depression symptoms, and lower quality of life 6 to 12 months after hospital discharge. Although these findings need to be confirmed in larger studies, enhanced monitoring may be warranted for early identification and treatment of neurological and psychological symptoms.

Social cognition and behavioral outcomes in congenital heart disease: profiles and neuropsychiatric comorbidities.

Autism spectrum disorders are more prevalent in children with congenital heart disease (CHD) than in the general population. Children with CHD without diagnosed autism are also at increased risk for neurodevelopmental and psychiatric impairments. We characterized social and behavioral outcomes in children with CHD and examined neurodevelopmental and psychiatric comorbidities. Children without diagnosed autism who underwent infant open-heart surgery were eligible. Parent-reports assessed social communication, unusual behaviors, self-regulation, anxiety, and executive function (EF). Neuropsychological tests assessing theory of mind (ToM), working memory, and verbal comprehension were administered. Outcomes were compared to normative data. Linear regressions were estimated with parent-reported scores and ToM abilities as outcomes. Predictors were anxiety symptoms, parent-reported EF, and working memory scores. Covariates were age, parental education, ADHD diagnosis, and verbal comprehension. Clinically relevant comorbidities were identified (N children scoring ≥1SD below the norm). Fifty-six children (10.8 ± 1.8 years) participated virtually. Compared to norms, children with CHD had impaired ToM, more unusual behaviors (p = .002), and less self-regulation (p = .018), but better social communication (p = .014). "Autism-like" traits were positively associated with anxiety symptoms (ß(95% CI) = 0.28(0.08-0.49), p = .008) and worse working memory (ß(95% CI) = -0.36(-0.59-0.13), p = .003). Twenty-one out of 22 children who displayed clinically relevant social and behavioral scores also showed anxiety symptoms (n = 4), impaired EF (n = 7), or both (n = 10). Children with CHD without diagnosed autism have elevated unusual behaviors, lower self-regulation, and impaired ToM. There is a high risk of co-existing anxiety and impaired EF which may increase disease burden. Targeted therapeutic interventions are needed to reduce long-term psychosocial risks in these children.AbbreviationAttention deficit/hyperactivity disorder (ADHD), Autism Spectrum Rating Scale (ASRS), Behavior Rating Inventory of Executive Functions for school-aged children, 2nd Edition (BRIEF-2), cardiopulmonary bypass (CPB), congenital heart disease (CHD), Empathy/Systematizing Quotient Child Version (ESQ-C), Multidimensional Anxiety Scale for Children, 2nd Edition (MASC-2), Social Responsiveness Scale (School-age form), 2nd Edition (SRS-2), theory of mind (ToM), Theory of Mind Task Battery (ToM-TB), Wechsler Intelligence Scale for Children, 5th edition (WISC-V).

Prevalence and associated factors of post-traumatic stress disorder in parents whose infants have single ventricle heart disease.

INTRODUCTION: Post-traumatic stress disorder occurs in parents of infants with CHD, contributing to psychological distress with detrimental effects on family functioning and well-being. We sought to determine the prevalence and factors associated with post-traumatic stress disorder symptoms in parents whose infants underwent staged palliation for single ventricle heart disease. MATERIALS AND METHODS: A large longitudinal multi-centre cohort study evaluated 215 mothers and fathers for symptoms of post-traumatic stress disorder at three timepoints, including post-Norwood, post-Stage II, and a final study timepoint when the child reached approximately 16 months of age, using the self-report questionnaire Impact of Event Scale - Revised. RESULTS: The prevalence of probable post-traumatic stress disorder post-Norwood surgery was 50% of mothers and 39% of fathers, decreasing to 27% of mothers and 24% of fathers by final follow-up. Intrusive symptoms such as flashbacks and nightmares and hyperarousal symptoms such as poor concentration, irritability, and sudden physical symptoms of racing heart and difficulty breathing were particularly elevated in parents. Higher levels of anxiety, reduced coping, and decreased satisfaction with parenting were significantly associated with symptoms of post-traumatic stress disorder in parents. Demographic and clinical variables such as parent education, pre-natal diagnosis, medical complications, and length of hospital stay(s) were not significantly associated with symptoms of post-traumatic stress disorder. DISCUSSION: Parents whose infants underwent staged palliation for single ventricle heart disease often reported symptoms of post-traumatic stress disorder. Symptoms persisted over time and routine screening might help identify parents at-risk and prompt referral to appropriate supports.

Sleep Patterns in Young Children with Congenital Heart Disease.

Sleep patterns of 419 toddlers with congenital heart disease were comparable with the normative population except for increased likelihood across the cohort of sleeping in parents' room and increased disrupted sleep in children aged 18-23 months. Disrupted sleep patterns were associated with lower maternal education and increased medical complexity.

Neurodevelopmental and Mental Health Outcomes in Patients With Fontan Circulation: A State-of-the-Art Review.

Children, adolescents and adults living with Fontan circulation face numerous neurological and developmental challenges. As the population with complex CHD increases thanks to outstanding improvement in medical and surgical care, the long-term developmental and mental health sequelae have become a public health priority in pediatric and congenital cardiology. Many patients with a Fontan circulation experience difficulty in areas of cognition related to attention and executive functioning, visual spatial reasoning and psychosocial development. They are also at high risk for mental health morbidities, particularly anxiety disorders and depression. Several hemodynamic risk factors, beginning during the fetal period, may influence outcomes and yield to abnormal brain growth and development. Brain injury such as white matter lesions, stroke or hemorrhage can occur before, during, or after surgery. Other sociodemographic and surgical risk factors such as multiple catheterizations and surgeries and prolonged hospital stay play a detrimental role in patients' neurodevelopmental prognosis. Prevention and intervention to optimize long-term outcomes are critical in the care of this vulnerable population with complex CHD.

Fetal Brain Volume Predicts Neurodevelopment in Congenital Heart Disease.

BACKGROUND: Neurodevelopmental impairment is common in children with congenital heart disease (CHD), but postnatal variables explain only 30% of the variance in outcomes. To explore whether the antecedents for neurodevelopmental disabilities might begin in utero, we analyzed whether fetal brain volume predicted subsequent neurodevelopmental outcome in children with CHD. METHODS: Fetuses with isolated CHD and sociodemographically comparable healthy control fetuses underwent fetal brain magnetic resonance imaging and 2-year neurodevelopmental evaluation with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) and the Adaptive Behavior Assessment System, Third Edition (ABAS-3). Hierarchical regression evaluated potential predictors of Bayley-III and ABAS-3 outcomes in the CHD group, including fetal total brain volume adjusted for gestational age and sex, sociodemographic characteristics, birth measures, and medical history. RESULTS: The CHD group (n=52) had lower Bayley-III cognitive, language, and motor scores than the control group (n=26), but fetal brain volumes were similar. Within the CHD group, larger fetal total brain volume correlated with higher Bayley-III cognitive, language, and motor scores and ABAS-3 adaptive functioning scores (r=0.32-0.47; all P<0.05), but this was not noted in the control group. Fetal brain volume predicted 10% to 21% of the variance in neurodevelopmental outcome measures in univariate analyses. Multivariable models that also included social class and postnatal factors explained 18% to 45% of the variance in outcome, depending on developmental domain. Moreover, in final multivariable models, fetal brain volume was the most consistent predictor of neurodevelopmental outcome across domains. CONCLUSIONS: Small fetal brain volume is a strong independent predictor of 2-year neurodevelopmental outcomes and may be an important imaging biomarker of future neurodevelopmental risk in CHD. Future studies are needed to support this hypothesis. Our findings support inclusion of fetal brain volume in risk stratification models and as a possible outcome in fetal neuroprotective intervention studies.

Quality of Life of Children Born with a Congenital Heart Defect.

OBJECTIVES: To identify subgroups with a congenital heart defect (CHD) at risk of health-related quality of life (QoL) impairment at 8 years of age according to their medical and surgical management. STUDY DESIGN: From a prospective population-based cohort study, 598 patients with CHD were subdivided according to their medical and surgical management: (1) CHD followed-up in an outpatient clinic, (2) complete repair before age 3 years, (3) complete repair after age 3 years, (4) palliative repair, or (5) CHD with spontaneous resolution (reference subgroup). Self-reported QoL and parent-reported QoL were measured using the Pediatric Quality of Life Inventory version 4.0 (score range, 0-100) at age 8 years. Multivariable regression analysis and Cohen effect size were used to compare outcomes across the CHD groups. RESULTS: Self-reported and parent-reported QoL scores for the palliative repair subgroup were lower (ß = -2.1 [95% CI, -3.9 to -0.2] and ß = -16.0 [95% CI, -22.4 to -9.5], respectively), with a large effect size (δ = -0.9 [95% CI, -1.4 to -0.4] and δ = -1.3 [95% CI, -1.8 to -0.7], respectively). Parent-reported QoL scores for the complete repair after age 3 years subgroup were lower (ß = -9.2; 95% CI, -15.0 to -3.5), with a large effect size (δ = -0.9; 95% CI, -1.4 to -0.5). Self-reported QoL scores for the complete repair before age 3 years subgroup was lower (ß = -1.3; 95% CI, -1.9 to -0.6), with a small effect size (δ = -0.4; 95% CI, -0.6 to -0.2). CONCLUSIONS: The QoL of children with CHD who experienced a hospital intervention is reduced at age 8 years. Patient age at the last cardiac intervention might influence QoL at 8 years.

Neurological features in infants with congenital heart disease.

AIM: To report neurological examination findings at 5 to 12 months of age in infants with congenital heart disease (CHD) and to identify predictors of abnormal neurological examination. METHOD: This retrospective observational study included infants who required cardiac surgery at less than 3 months of age and underwent a standard neurological examination from a neurologist in the cardiac neurodevelopmental outpatient clinic between age 5 months and 12 months. Predictors for abnormal neurological examination (concerns on structured developmental history, demographic factors, medical history, and newborn neurodevelopmental assessment) were considered for multivariate regression. RESULTS: The sample included 127 infants (mean age 7mo 2wks), who underwent first cardiac surgery at 7 days (4-49 interquartile range [IQR]) of age and were seen for a neurological examination in the cardiac neurodevelopmental clinic. Neurological abnormalities were common; 88% of infants had an abnormal neurological examination in at least one domain assessed. The most common abnormalities were abnormal axial (48%) and extremity (44%) tone, mostly hypotonia. Abnormal neurological examination was associated with concerns on the concurrent structured developmental history, genetic condition, extracardiac anomaly, longer length of stay, more than one cardiac surgery, ongoing early intervention services, and abnormalities on newborn neurodevelopmental assessment. INTERPRETATION: Neurological examination abnormalities are common in infants with CHD after infant heart surgery, supporting the need for early and ongoing therapeutic developmental services and adherence to American Heart Association recommendations for developmental follow-up for children with CHD. What this paper adds Neurological examination abnormalities are common in infants who undergo open-heart surgery. Medical complications in infancy increase risk for neurological abnormalities. Family-reported concerns on structured developmental history may predict abnormal neurological examination at 5 to 12 months of age. Abnormal newborn neurodevelopmental assessment may predict abnormal neurological examination at 5 to 12 months of age.

Physical activity and aerobic fitness in children with inherited cardiac diseases.

BACKGROUND: Because of sports and exercise restrictions, children with inherited cardiac disease are at risk of physical deconditioning. Guidelines on sports participation in cardiovascular disease have become less restrictive over time, but their real-life application and behavioural impact have seldom been evaluated in children. AIMS: We aimed to evaluate adherence to the 2020 European Society of Cardiology guidelines on sports and exercise in children with inherited cardiac arrhythmia and inherited cardiomyopathy; we also sought to evaluate their aerobic fitness, and the behavioural impact of inherited cardiac diseases on physical activity in children. METHODS: Children aged 6-18 years with inherited cardiomyopathy or inherited cardiac arrhythmia were eligible for this cross-sectional study. Clinical, demographic and qualitative data were analysed. RESULTS: A total of 32 children were included in the study (mean age 12.7±3.5 years). Most children (81.3%) complied with the 2020 European Society of Cardiology guidelines; they were physically active and had good overall aerobic fitness, with a mean peak oxygen uptake (VO2) value of 36.5±8.0mL/kg/min (84.0±17.2% of theoretical value). As a result of personal or parental behaviour, some children at risk of sudden cardiac death did not comply with the recommended upper limit of physical activity intensity, whereas others at low risk did not comply with the lower limit. CONCLUSION: Most children with inherited cardiac arrhythmia or inherited cardiomyopathy complied with current 2020 European Society of Cardiology guidelines on sports cardiology and exercise in cardiovascular disease.

Health-related quality of life and physical activity in children with inherited cardiac arrhythmia or inherited cardiomyopathy: the prospective multicentre controlled QUALIMYORYTHM study rationale, design and methods.

BACKGROUND: Advances in paediatric cardiology have improved the prognosis of children with inherited cardiac disorders. However, health-related quality of life (QoL) and physical activity have been scarcely analysed in children with inherited cardiac arrhythmia or inherited cardiomyopathy. Moreover, current guidelines on the eligibility of young athletes with inherited cardiac disorders for sports participation mainly rely on expert opinions and remain controversial. METHODS: The QUALIMYORYTHM trial is a multicentre observational controlled study. The main objective is to compare the QoL of children aged 6 to 17 years old with inherited cardiac arrhythmia (long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, or arrhythmogenic right ventricular dysplasia), or inherited cardiomyopathy (hypertrophic, dilated, or restrictive cardiomyopathy), to that of age and gender-matched healthy subjects. The secondary objective is to assess their QoL according to the disease's clinical and genetic characteristics, the level of physical activity and motivation for sports, the exercise capacity, and the socio-demographic data. Participants will wear a fitness tracker (ActiGraph GT3X accelerometer) for 2 weeks. A total of 214 children are required to observe a significant difference of 7 ± 15 points in the PedsQL, with a power of 90% and an alpha risk of 5%. DISCUSSION: After focusing on the survival in children with inherited cardiac disorders, current research is expanding to patient-reported outcomes and secondary prevention. The QUALIMYORYTHM trial intends to improve the level of evidence for future guidelines on sports eligibility in this population. Trial registration ClinicalTrials.gov Identifier: NCT04712136, registered on January 15th, 2021 ( https://clinicaltrials.gov/ct2/show/NCT04712136 ).

Long-Term Neurodevelopmental Outcomes of Children with Congenital Heart Defects.

OBJECTIVE: To assess whether children with symptomatic congenital heart defects (CHDs) at birth (cyanosis and/or heart failure) are at greater risk of adverse neurodevelopmental outcomes at 8 years of age. STUDY DESIGN: From a prospective population-based cohort study of newborns with CHDs (EPICARD), we included 473 children with available neurodevelopmental assessments at 8 years of age. We grouped the CHD based on symptoms at birth and need for early neonatal intervention. Ventricular septal defects that closed spontaneously within the first year of life were considered the control group. Neurodevelopmental outcomes were assessed using the Kauffman Assessment Battery Test for Children, Second Edition, for IQ (mean 100 ± 15), and the Developmental NEuroPSYchological Assessment Battery, Second Edition, for detailed assessment of specific neurocognitive domains (mean 10 ± 3). Multivariable regression analysis was used to compare the outcomes across the CHD groups after considering potentially confounding variables. RESULTS: Compared with the control group, children with cyanotic CHD without heart failure had lower scores for IQ, -7.2 (95% CI -13.4 to -1.2). Children with noncyanotic CHD with heart failure had lower scores in the specific domains of language -1.5 (95% CI -2.2 to -0.7), and memory and learning -1.3 (95% CI -2.4; -0.3). Those with both cyanotic CHD and heart failure had lower scores for IQ, -7.6 (95% CI -13.5 to -1.8), as well as the specific domains of language and memory and learning, -2.0 (95% CI -2.9 to -1.0) and -1.1 (95% CI -2.3 to -0.1), respectively. CONCLUSIONS: Children with symptomatic CHD at birth are at greater risk of adverse neurodevelopmental outcomes at 8 years of age, with the greatest risk for those who were born with both cyanosis and heart failure.

Neurodevelopmental and psychosocial interventions for individuals with CHD: a research agenda and recommendations from the Cardiac Neurodevelopmental Outcome Collaborative.

In 2018, the Neurodevelopmental and Psychosocial Interventions Working Group of the Cardiac Neurodevelopmental Outcome Collaborative convened through support from an R13 grant from the National Heart, Lung, and Blood Institute to survey the state of neurodevelopmental and psychosocial intervention research in CHD and to propose a slate of critical questions and investigations required to improve outcomes for this growing population of survivors and their families. Prior research, although limited, suggests that individualised developmental care interventions delivered early in life are beneficial for improving a range of outcomes including feeding, motor and cognitive development, and physiological regulation. Interventions to address self-regulatory, cognitive, and social-emotional challenges have shown promise in other medical populations, yet their applicability and effectiveness for use in individuals with CHD have not been examined. To move this field of research forward, we must strive to better understand the impact of neurodevelopmental and psychosocial intervention within the CHD population including adapting existing interventions for individuals with CHD. We must examine the ways in which dedicated cardiac neurodevelopmental follow-up programmes bolster resilience and support children and families through the myriad transitions inherent to the experience of living with CHD. And, we must ensure that interventions are person-/family-centred, inclusive of individuals from diverse cultural backgrounds as well as those with genetic/medical comorbidities, and proactive in their efforts to include individuals who are at highest risk but who may be traditionally less likely to participate in intervention trials.

Executive functions in children with heart disease: a systematic review and meta-analysis.

CONTEXT: People with CHD are at increased risk for executive functioning deficits. Meta-analyses of these measures in CHD patients compared to healthy controls have not been reported. OBJECTIVE: To examine differences in executive functions in individuals with CHD compared to healthy controls. DATA SOURCES: We performed a systematic review of publications from 1 January, 1986 to 15 June, 2020 indexed in PubMed, CINAHL, EMBASE, PsycInfo, Web of Science, and the Cochrane Library. STUDY SELECTION: Inclusion criteria were (1) studies containing at least one executive function measure; (2) participants were over the age of three. DATA EXTRACTION: Data extraction and quality assessment were performed independently by two authors. We used a shifting unit-of-analysis approach and pooled data using a random effects model. RESULTS: The search yielded 61,217 results. Twenty-eight studies met criteria. A total of 7789 people with CHD were compared with 8187 healthy controls. We found the following standardised mean differences: -0.628 (-0.726, -0.531) for cognitive flexibility and set shifting, -0.469 (-0.606, -0.333) for inhibition, -0.369 (-0.466, -0.273) for working memory, -0.334 (-0.546, -0.121) for planning/problem solving, -0.361 (-0.576, -0.147) for summary measures, and -0.444 (-0.614, -0.274) for reporter-based measures (p < 0.001). LIMITATIONS: Our analysis consisted of cross-sectional and observational studies. We could not quantify the effect of collinearity. CONCLUSIONS: Individuals with CHD appear to have at least moderate deficits in executive functions. Given the growing population of people with CHD, more attention should be devoted to identifying executive dysfunction in this vulnerable group.

Randomized Controlled Trial of Working Memory Intervention in Congenital Heart Disease.

OBJECTIVES: To evaluate the efficacy of Cogmed Working Memory Training compared with the standard of care to improve executive function and social outcomes in adolescents with congenital heart disease (CHD) who underwent open-heart surgery in infancy and to identify factors associated with changes in outcomes following the intervention. STUDY DESIGN: In a single-center, randomized controlled trial, adolescents (13-16 years) with CHD were randomly assigned to either Cogmed (home-based 45-minutes sessions for 5-8 weeks) or to a control group. The primary outcome was working memory. Secondary outcomes included inhibitory control and cognitive flexibility as well as parent-reported executive function, symptoms of attention deficit hyperactivity disorder, and social outcomes. All measures were assessed at baseline, post-treatment (1-3 weeks post-training) and at 3-month follow-up. Data were analyzed using an intention-to-treat approach. RESULTS: Sixty adolescents with CHD participated (28 assigned to Cogmed). No improvement at the post-treatment or 3-month follow-up assessments was found for the primary outcome measure of working memory. Compared with the control group, participants assigned to the intervention demonstrated benefits in inhibitory control and attention at the 3-month follow-up (P = .02) and in parent-reported cognitive regulatory skills at post-treatment and 3-month follow-up (P = .02 and P = .04, respectively). Preterm birth, biventricular CHD, and history of attention deficit hyperactivity disorder diagnosis were associated with improved response to the intervention. CONCLUSIONS: Cogmed intervention produced improvements in the self-regulatory control abilities of adolescents with CHD. The training did not enhance other areas of executive function or behavioral outcomes. Further studies are needed to evaluate the longer-term potential benefits to other domains. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02759263.

Improving neurodevelopmental outcomes in children with congenital heart disease: protocol for a randomised controlled trial of working memory training.

INTRODUCTION: Executive function (EF) impairments are among the most prevalent neurodevelopmental morbidities in youth with congenital heart disease (CHD). To date, no studies have investigated the efficacy of cognitive interventions to improve EF outcomes in children with CHD. METHODS AND ANALYSIS: This is a single-centre, single-blinded, two-arm randomised controlled trial to test the efficacy of Cogmed Working Memory Training (Cogmed) versus standard of care in children with CHD after open-heart surgery in infancy. Participants will consist of 100 children with CHD aged 7-12 years who underwent open-heart surgery before the age of 12 months. Participants are randomly allocated to either an intervention group including training on the home-based Cogmed intervention for a duration of approximately 5 weeks or a control group who receive the standard of care. We will evaluate the efficacy of Cogmed at post-treatment and 3 months after completion of the intervention. Baseline, post-treatment and 3-month follow-up assessments will include specific measures of EF, cognitive and social functioning, and attention deficit hyperactivity disorder (ADHD) symptoms. The primary outcome of this study is the change in standardised mean score on the List Sorting Working Memory test from the National Institutes of Health Toolbox for the Assessment of Neurological and Behavioral Function. Secondary outcomes include measures of social skills, inhibitory control, cognitive flexibility and behavioural EF as well as ADHD symptoms as measured by the Behavior Rating Inventory of Executive Function, Second Edition, and the Conners Third Edition. The efficacy of the intervention will be evaluated by comparing within-subject differences (baseline to post-treatment, baseline to 3-month follow-up) between the two groups using an intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has received Institutional Review Board (IRB) approval from Boston's Children's Hospital IRB (P00022440) and the Human Protection Agency from the US Department of Defense. TRIAL REGISTRATION NUMBER: NCT03023644; Pre-results.

Neurotoxicity of general anesthetics in children: evidence and uncertainties.

PURPOSE OF REVIEW: Compelling evidence in animal models that, under some conditions, general anesthetics and sedatives produce changes in the brain and persistent impairments in learning, memory, and behavior. The present review summarizes recent clinical studies investigating whether the use of these agents in children causes similar neurotoxicities. RECENT FINDINGS: Although the results of retrospective studies are somewhat mixed, multiple exposures to general anesthesia were generally found to confer greater risk than single exposures with regard to learning disability, attention deficit hyperactivity disorder, school readiness, and academic achievement. Recent clinical studies, including a large randomized controlled trial, are consistent in confirming that a single exposure in infancy to general anesthesia lasting less than 1 h is not associated with neurodevelopmental impairments in later childhood. These studies do not, however, clarify the potential impacts of longer exposures or multiple exposures. SUMMARY: Given that approximately half of the anesthetic exposures in young US children are 1 h or less in duration, the results of the recent clinical studies are reassuring. Because of the clinical necessity of administering general anesthetics and sedatives for longer periods for many surgical, procedural, or diagnostic purposes, the identification of adjuvants that prevent or reduce the potential neurotoxicity of these agents is an area of active research.

Outcomes Research in Vulnerable Pediatric Populations.

The Pediatric Anesthesia and Neurodevelopment Assessment (PANDA) study team held its biennial symposium in April 2018 to discuss issues on anesthetic neurotoxicity in the developing brain. One of the sessions invited speakers with different areas of expertise to discuss "Outcomes Research in Vulnerable Pediatric Populations." The vulnerable populations included neonates, children with congenital heart disease, children from low socioeconomic status, and children with incarcerated parents. Each speaker presented some of the ongoing research efforts in these groups as well as the challenges encountered in studying them.