Disruption of the Circulating Proteome in Neonates Receiving Extracorporeal Membrane Oxygenation Following Congenital Heart Disease Surgery: A Nested Case-Control Study.

This nested case-control study identified broad dysregulation of the circulating proteome in neonates receiving postoperative extracorporeal membrane oxygenation support after congenital heart disease surgery, including differential responses in those not surviving to hospital discharge. Tissue hypoxia and mitochondrial-associated proteins may represent novel candidate biomarkers for poor extracorporeal membrane oxygenation outcomes.

Factors Associated With Attendance for Cardiac Neurodevelopmental Evaluation.

BACKGROUND AND OBJECTIVES: Neurodevelopmental evaluation of toddlers with complex congenital heart disease is recommended but reported frequency is low. Data on barriers to attending neurodevelopmental follow-up are limited. This study aims to estimate the attendance rate for a toddler neurodevelopmental evaluation in a contemporary multicenter cohort and to assess patient and center level factors associated with attending this evaluation. METHODS: This is a retrospective cohort study of children born between September 2017 and September 2018 who underwent cardiopulmonary bypass in their first year of life at a center contributing data to the Cardiac Neurodevelopmental Outcome Collaborative and Pediatric Cardiac Critical Care Consortium clinical registries. The primary outcome was attendance for a neurodevelopmental evaluation between 11 and 30 months of age. Sociodemographic and medical characteristics and center factors specific to neurodevelopmental program design were considered as predictors for attendance. RESULTS: Among 2385 patients eligible from 16 cardiac centers, the attendance rate was 29.0% (692 of 2385), with a range of 7.8% to 54.3% across individual centers. In multivariable logistic regression models, hospital-initiated (versus family-initiated) scheduling for neurodevelopmental evaluation had the largest odds ratio in predicting attendance (odds ratio = 4.24, 95% confidence interval, 2.74-6.55). Other predictors of attendance included antenatal diagnosis, absence of Trisomy 21, higher Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery mortality category, longer postoperative length of stay, private insurance, and residing a shorter distance from the hospital. CONCLUSIONS: Attendance rates reflect some improvement but remain low. Changes to program infrastructure and design and minimizing barriers affecting access to care are essential components for improving neurodevelopmental care and outcomes for children with congenital heart disease.

Neuropsychological Screening in Pediatric Multidisciplinary Clinics: Group Characteristics and Predictive Utility.

OBJECTIVE: To evaluate the feasibility of administering caregiver-report neuropsychological screening measures in pediatric multidisciplinary clinics (MDCs) and investigate predictive utility for cognitive and academic difficulties on follow-up testing. METHOD: The Pediatric Perceived Cognitive Functioning (Peds PCF) and Colorado Learning Difficulties Questionnaire (CLDQ) were administered to caregivers of youth with history of brain tumor (BT), non-central nervous system (CNS) cancer, or Fontan circulation as part of routine neuropsychological consultation in MDCs from 2017 to 2019. We examined cross-sectional differences on screening measures, and relationships between screening and intellectual and academic test performance in a subset who presented for follow-up neuropsychological evaluation. Receiver operating characteristic (ROC) curve analysis was used to identify suggested cut scores on screening measures for predicting who would most benefit from further evaluation. RESULTS: Screening was completed with 192 families. Children with history of non-CNS cancer (n = 29) had fewer parent-reported cognitive and academic concerns compared with either BT (n = 88) or Fontan (n = 75) groups. Peds PCF and CLDQ scores were related to intellectual and academic test performance in the group presenting for neuropsychological evaluation (n = 68). ROC curve analysis identified cut scores across screening measures with maximal sensitivity and specificity for detecting neuropsychological difficulties. CONCLUSIONS: It is feasible to utilize parent rating measures during neuropsychological consultation in pediatric MDCs. The Peds PCF and CLDQ demonstrated sensitivity to intellectual and academic difficulties in children with significant medical histories. Screening may be a helpful tool for pediatric neuropsychologists and other professionals during MDC consultation to inform clinical management.

Oxygen saturations and neurodevelopmental outcomes in single ventricle heart disease.

OBJECTIVES: To evaluate whether the degree of hypoxemia following stage-I and stage-II palliative surgeries predicts neurodevelopmental outcomes at 14 months of age in children with single ventricle congenital heart disease (SVCHD). DESIGN: We analyzed longitudinal data from two Pediatric Heart Network (PHN) randomized controlled trials, with a total of 328 subjects. Oxygen saturations, measured via pulse oximetry, at time of discharge from stage-I and stage-II surgeries were the primary predictors of interest, and Bayley Scales of Infant Development-II (BSID-II) scores at 14 months old were the primary outcome measure. Relevant covariates from previously-published PHN studies were also included in regression models. RESULTS: Oxygen saturations at time of discharge from stage-I and stage-II surgeries were not related to BSID-II scores. Having one or more oxygen saturation measurements below 80% was also not associated with BSID-II scores, and neither was change in oxygen saturations over time. These relationships were not altered by inclusion of relevant covariates. CONCLUSIONS: In this large cohort of children with SVCHD, oxygen saturations post-stage-I and post-stage-II palliation surgeries as measured via pulse oximetry were not associated with neurodevelopmental outcomes at 14 months of age. The relationship between oxygen saturations and neurodevelopment in SVCHD is likely complex, and neurodevelopment is known to be affected by a number of factors. Pulse oximetry may also be an insufficient proxy for cerebral oxygen delivery. Clinically, pulse oximetry readings during the interstage and post-stage-II surgery periods are not a reliable predictor of future neurodevelopmental risk.

Pulmonary Screening in Subjects after the Fontan Procedure.

OBJECTIVES: To review the pulmonary findings of the first 51 patients who presented to our interdisciplinary single-ventricle clinic after undergoing the Fontan procedure. STUDY DESIGN: We performed an Institutional Review Board-approved retrospective review of 51 patients evaluated following the Fontan procedure. Evaluation included history, physical examination, pulmonary function testing, and 6-minute walk. Descriptive statistics were used to describe the population and testing data. RESULTS: Sixty-one percent of the patients had a pulmonary concern raised during the visit. Three patients had plastic bronchitis. Abnormal lung function testing was present in 46% of patients. Two-thirds (66%) of the patients had significant desaturation during the 6-minute walk test. Patients who underwent a fenestrated Fontan procedure and those who underwent unfenestrated Fontan were compared in terms of saturation and 6-minute walk test results. Sleep concerns were present in 45% of the patients. CONCLUSIONS: Pulmonary morbidities are common in patients after Fontan surgery and include plastic bronchitis, abnormal lung function, desaturations with walking, and sleep concerns. Abnormal lung function and obstructive sleep apnea may stress the Fontan circuit and may have implications for cognitive and emotional functioning. A pulmonologist involved in the care of patients after Fontan surgery can assist in screening for comorbidities and recommend interventions.

Predicting changes in adaptive functioning and behavioral adjustment following treatment for a pediatric brain tumor: A report from the Brain Radiation Investigative Study Consortium.

BACKGROUND: Children are at risk for behavioral and adaptive difficulties following pediatric brain tumor. This study explored whether familial/demographic, developmental, diagnostic, or treatment-related variables best predict posttreatment behavioral and adaptive functioning. METHODS: Participants included 40 children (mean age = 12.76 years, SD = 4.01) posttreatment (mean time since diagnosis = 1.99 years, SD = 0.21) for pediatric brain tumor. Parents rated children's behavioral adjustment and adaptive functioning and provided demographic and developmental histories. Diagnostic and treatment-related information was abstracted from medical records. RESULTS: Ratings of adaptive and behavioral functioning approximately 2 years postdiagnosis were within the average range, although the percentage of children exceeding clinical cutoffs for impairment in adaptive skills exceeded expectation, particularly practical skills. Premorbid behavior problems and tumor size predicted posttreatment adaptive functioning. After accounting for adaptive functioning near diagnosis, premorbid behavior problems predicted declines in adaptive functioning 2 years postdiagnosis. After accounting for adjustment near diagnosis, no variables predicted declines in behavioral adjustment. CONCLUSIONS: Children may be vulnerable to reduced adaptive functioning following pediatric brain tumor treatment, especially in practical skills. Assessing prediagnosis functioning and diagnostic and treatment-related variables may improve our ability to predict those at greatest risk, although those factors may be less helpful in identifying children likely to develop behavioral difficulties. Screening of these factors in tertiary care and long-term follow-up settings may improve identification of those at greatest need for support services.

Predictors of adaptive functioning and psychosocial adjustment in children with pediatric brain tumor: a report from the Brain Radiation Investigative Study Consortium.

BACKGROUND: Children are at risk for psychosocial and adaptive morbidities following diagnosis of and treatment for a pediatric brain tumor. This study examined whether familial/demographic, developmental, diagnostic, or treatment-related variables best predict the acute psychosocial adjustment and adaptive functioning of children soon after an initial diagnosis. PROCEDURE: Participants included 56 children (mean age = 10.72, SD = 4.02) newly diagnosed with a pediatric brain tumor. Parents completed background/demographic forms and completed ratings of children's behavioral and emotional symptoms, and adaptive behavior. Diagnostic and treatment-related information was abstracted from medical records. RESULTS: Parent ratings of behavioral symptoms and adaptive functioning were within normative expectation, although rates of clinical impairment in adaptive functioning exceeded expected rates. A combination of familial/demographic and diagnostic variables were associated with acute functioning. In multiple regressions, tumor size best predicted adaptive functioning after initial diagnosis, whereas tumor location best predicted variance in behavioral symptoms. CONCLUSIONS: Children may be more vulnerable to acute impairment in adaptive functioning following diagnosis of a pediatric brain tumor, but rates of behavioral symptoms were within expectation. Familial, sociodemographic, and diagnostic variables may help to identify those most at risk of impairment. Screening of these factors within tertiary care settings will be useful to identify those most in need of psychosocial care during the initial phases of treatment.

Executive functions, social information processing, and social adjustment in young children born with very low birth weight.

Children born with very low birth weight (VLBW) are at risk for neurocognitive and behavioral sequelae. Although VLBW infants are at higher risk for deficits in executive functions (EFs) and social functioning during school-age years, few studies have investigated those sequelae or their association in young children born VLBW. We examined the associations between EFs and social functioning in preterm, VLBW children age 4-6 years (n = 20) and matched, term-born, normal birth weight controls admitted to the neonatal intensive care unit (NICU) after birth (n = 18). The groups did not differ significantly on measures of EFs, social information processing, or parent-reported social adjustment. The VLBW group had lower IQs than controls, though both group means were in the average range. Within the VLBW group, medical predictors of better EFs included older gestational age at birth and no history of bronchopulmonary dysplasia. Across groups, EFs and social information processing were positively correlated. Deficits in EFs and social functioning may emerge after the preschool years in VLBW children, or improved care of children born VLBW may be reducing the cognitive and psychosocial sequelae observed in earlier cohorts. Among children born VLBW, early EFs may be directly related to social information processing.

Executive functions and social skills in survivors of pediatric brain tumor.

Medical advances have resulted in increased survival rates for children with brain tumors. Consequently, issues related to survivorship have become more critical. The use of multimodal treatment, in particular cranial radiation therapy, has been associated with subsequent cognitive decline. Specifically, deficits in executive functions have been reported in survivors of various types of pediatric brain tumor. Survivors are left with difficulties, particularly in self-monitoring, initiation, inhibition, and planning, to name a few. Another domain in which survivors of pediatric brain tumor have been reported to show difficulty is that of social skills. Parents, teachers, and survivors themselves have reported decreased social functioning following treatment. Deficits in executive functions and social skills are likely interrelated in this population, as executive skills are needed to navigate various aspects of social interaction; however, this has yet to be studied empirically. Twenty-four survivors of pediatric brain tumor were assessed using a computerized task of executive functions, as well as paper-and-pencil measures of social skills and real-world executive skills. Social functioning was related to a specific aspect of executive functions, that is, the survivors' variability in response time, such that inconsistent responding was associated with better parent-reported and survivor-reported social skills, independent of intellectual abilities. Additionally, parent-reported real-world global executive abilities predicted parent-reported social skills. The implications of these findings for social skills interventions and future research are discussed.

An fMRI investigation of working memory and its relationship with cardiorespiratory fitness in pediatric posterior fossa tumor survivors who received cranial radiation therapy.

BACKGROUND: The present study investigated the relationship between cardiorespiratory fitness and executive functioning in pediatric brain tumor survivors who received cranial radiation. This population is known to show executive dysfunction and lower rates of aerobic exercise compared to peers. PROCEDURE: Nine adolescent survivors of pediatric posterior fossa tumor completed an n-back working memory task during a functional MRI scan, as well as cardiorespiratory fitness testing on a cycle ergometer. RESULTS: Neuroimaging findings indicated typical activation patterns associated with working memory, mainly in the frontal-parietal network. Higher cardiorespiratory fitness was related to better performance on a behavioral measure of working memory and more efficient neural functioning. CONCLUSIONS: This study provides preliminary evidence that cardiorespiratory fitness may be related to executive functioning, particularly working memory, in pediatric brain tumor survivors. Descriptions of the brain regions recruited for working memory by pediatric brain tumor survivors may be used to inform future interventions or indicators of treatment efficacy.

Cardiorespiratory fitness in survivors of pediatric posterior fossa tumor.

Advances in medical therapies have greatly improved survivorship rates in children diagnosed with brain tumor; as a result, morbidities associated with survivorship have become increasingly important to identify and address. In general, pediatric posterior fossa tumor survivors tend to be less physically active than peers. This may be related to late effects of diagnosis and treatment, including cardiovascular, endocrine, psychological, and neurocognitive difficulties. Exercise has been shown to be effective in improving physical functioning, mood, and even cognitive functioning. Consequently, the benefits of physical exercise need to be explored and incorporated into the daily lives of pediatric posterior fossa tumor survivors. The primary aim of the present study was to establish the feasibility and safety of cardiorespiratory fitness testing in pediatric posterior fossa tumor survivors who had received cranial radiation therapy. In addition, comparing our cohort with previously published data, we found that pediatric posterior fossa tumor survivors tended to be less fit than children with pulmonary disease and healthy controls and approximately as fit as children with chronic heart disease and survivors of other types of childhood cancer. The importance of cardiorespiratory fitness in pediatric posterior fossa tumor survivors is discussed along with implications for future directions.

Executive dysfunction in pediatric posterior fossa tumor survivors: a systematic literature review of neurocognitive deficits and interventions.

Improved medical therapies have increased survivorship rates for children with posterior fossa tumors; resultantly, morbidities associated with survivorship, such as executive function deficits, have become increasingly important to identify and address. Executive dysfunction can impact academic achievement as well as functional outcomes. We summarize studies describing executive functioning deficits in pediatric posterior fossa tumor survivors who received cranial radiation therapy and intervention studies that have targeted executive functioning deficits. Previous theoretical models describing the etiology of these deficits are reviewed, and a new, more comprehensive model is proposed. Future research should move toward incorporating neuroimaging, longitudinal designs, and multiple informants.