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Objectives: To assess 6-year neurodevelopmental outcomes in a current cohort of children with congenital heart disease (CHD) who underwent cardiopulmonary bypass surgery (CPB), and to determine risk factors for adverse outcomes.Study Design: Outcomes were examined in 233 prospectively enrolled children with CHD (including 64 with a recognized genetic disorder) who underwent CPB between 2004 and 2009. Follow-up assessment included standardized neurologic, motor, and cognitive tests. Variables were collected prospectively, and multiple regression analysis was performed to determine independent risk factors for adverse outcome.Results: The mean patient age at assessment was 6.3 years (range, 5.1-6.8 years). IQ was lower in children with a genetic disorder (median, 55; range, 17-115) compared with children without a genetic disorder (median, 95; range, 47-135; P < .001). Cognitive and motor performance also were lower in children without a genetic disorder compared with the norm (P < .01 for both). The prevalence of children without a genetic disorder performing below -2 SD (IQ 70) was higher than the norm (5.3% vs 2.3%; P = .008), and the prevalence of poor motor performance (<10th percentile) ranged from 21.2% to 41.1% (P < .01 for all). Significant independent risk factors for poor neurodevelopmental outcome included a genetic disorder, longer length of intensive care stay, lower birth weight, postoperative seizures, and lower socioeconomic status.Conclusions: Current cohorts of children with CHD undergoing CPB show favorable outcomes but remain at risk for long-term neurodevelopmental impairments, particularly those with a genetic disorder and a complicated postoperative course. Close neurodevelopmental surveillance is necessary to provide early therapeutic support. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to compare the use of neonatal conventional brain magnetic resonance imaging (MRI) with that of clinical factors and socioeconomic status (SES) to predict long-term neurodevelopment in children with severe congenital heart disease (CHD).Study Design: In this prospective cohort study, perioperative MRIs were acquired in 57 term-born infants with CHD undergoing cardiopulmonary bypass surgery during their first year of life. Total brain volume (TBV) was measured using an automated method. Brain injury severity (BIS) was assessed by an established scoring system. The neurodevelopmental outcome was assessed at 6 years using standardized test batteries. A multiple linear regression model was used for cognitive and motor outcomes with postoperative TBV, perioperative BIS, CHD complexity, length of hospital stay, and SES as covariates.Results: CHD diagnoses included univentricular heart defect (n = 15), transposition of the great arteries (n = 33), and acyanotic CHD (n = 9). Perioperative moderate-to-severe brain injury was detected in 15 (26%) patients. The total IQ was similar to test norms (P = .11), whereas the total motor score (P < .001) was lower. Neither postoperative TBV nor perioperative BIS predicted the total IQ, but SES (P < .001) and longer hospital stay (P = .004) did. No factor predicted the motor outcome.Conclusion: Although the predictive value of neonatal conventional MRIs for long-term neurodevelopment is low, duration of hospital stay and SES better predict the outcome in this CHD sample. These findings should be considered in initiating early therapeutic support. [ABSTRACT FROM AUTHOR]

Objective: To describe the similarities and differences in the neurodevelopmental outcome of children with congenital heart disease (CHD) undergoing cardiopulmonary bypass surgery compared with children born very preterm (VPT) at school entry.Study Design: IQ, motor abilities, behavior, and therapy use were assessed in 155 children with CHD as part of a prospective, single-center, longitudinal study, and in 251 children born VPT as part of a national follow-up register at the same center. Group differences were tested using independent t-tests and χ2-tests. Equivalence testing was used to investigate similarities between the groups.Results: Mild (ie, 70 ≤ IQ < 85) and severe intellectual impairments (ie, IQ < 70) occurred in 17.4% and 4.5% of children with CHD compared with 22.1% and 5.5% in children VPT, respectively. Motor and behavioral functions were impaired in 57.0% and 15.3% of children with CHD compared with 37.8% and 11.5% of children born VPT, respectively. Children with CHD had poorer global motor abilities (d = -0.26) and poorer dynamic balance (d = -0.62) than children born VPT, and children born VPT had poorer fine motor abilities than children with CHD (d = 0.34; all P < .023). Peer problems were statistically similar between the groups (P = .020). Therapies were less frequent in children with CHD compared with children born VPT (23.4% vs 40.3%; P < .001).Conclusions: Children with CHD undergoing cardiopulmonary bypass surgery and children born VPT share an overall risk for neurodevelopmental impairments that manifest in different domains. Despite this, children with CHD receive fewer therapies, indicating a lack of awareness of the neurodevelopmental burden these children face. [ABSTRACT FROM AUTHOR]

Objective To investigate the risk of communication impairments at age 18 and 36 months in children born early term (gestational weeks 37-38) and late preterm (gestational weeks 34-36). Study design A total of 39?423 children and their mothers participated in the Norwegian Mother and Child Cohort Study. The sample included 7109 children (18%) born early term and 1673 (4.2%) born late preterm. Information on gestational age and prenatal and postnatal risk factors was obtained from the Medical Birth Registry of Norway. Information on communication impairments was assessed using standardized questionnaires filled out by the mothers. Stepwise logistic regression analysis was applied to explore the associations between early term/late preterm birth and communication impairments at age 18 and 36 months. Results Compared with children born at term, children born early term and late preterm had an increased risk of communication impairments at age 18 and 36 months. In early term, the aOR was 1.27 (95% CI, 1.12-1.44) at 18 months for communication impairments and 1.22 (95% CI, 1.07-1.39) at 36 months for expressive language impairments. In late preterm, the aOR was 1.74 (95% CI, 1.41-2.14) at 18 months and 1.37 (95% CI, 1.09-1.73) at 36 months. Conclusion Not only children born late preterm, but also those born early term, are at increased risk for communication impairments. Given the large number of children potentially affected, this may result in significant health care costs. [ABSTRACT FROM AUTHOR]

Objectives: To assess long-term neurodevelopmental outcome of adolescents with congenital heart disease after open-heart surgery and to evaluate whether deficits are associated with cerebral injury detectable on magnetic resonance imaging (MRI). Study design: We conducted a cohort study with longitudinal follow-up of 53 adolescents (mean age, 13.7 years; range, 11.4 to 16.9 years) who had undergone open-heart surgery with full-flow cardiopulmonary bypass during childhood and compared them with 41 age-matched controls. Assessment included conventional MRI and neurodevelopmental testing. Results: MRI abnormalities were detected in 11 of the 53 patients (21%), comprising predominately white matter abnormalities and volume loss. Neurodevelopmental outcome was impaired in several domains, including neuromotor, intellectual, and executive functions, as well as visuomotor perception and integration. Adolescents with cerebral abnormalities had greater impairment in most neurodevelopmental domains compared with those without cerebral abnormalities. Conclusions: Cerebral abnormalities can be detected in a significant proportion of adolescents with corrected congenital heart disease. These abnormalities are found predominately in the white matter and are apparently of hypoxic-ischemic origin, most likely acquired during the neonatal period. [ABSTRACT FROM AUTHOR]

Objective: To prospectively assess parental health-related quality of life (HRQoL) and its predictors after child open heart surgery. Study design: Mothers (n = 135) and fathers (n = 97) of 138 children were assessed at discharge from hospital and 6 months after open heart surgery of their child. Parental HRQoL was compared with population norms. Medical, demographic, and psychosocial predictors of HRQoL were examined. Results: In both parents, several domains of HRQoL were decreased at their child''s hospital discharge with mothers showing lower HRQoL than fathers. Mental domains were more affected than physical domains. At 6 months, parental HRQoL was within or above population norms. At discharge, symptoms of post-traumatic stress and at 6 months a high impact of the child''s disease on family life were associated with low mental HRQoL in both parents. In mothers, lower socioeconomic status and foreign nationality were also associated with a higher risk for low mental HRQoL at discharge. Conclusions: Parents'' mental HRQoL is low in the immediate period after their child''s open heart surgery but normalizes after 6 months. However, parents in whom the child''s disease has a high impact on their family life are at increased risk for persistent low mental HRQoL. [Copyright &y& Elsevier]

Objective: To assess cohort and individual neurodevelopmental stability in children with congenital heart disease across childhood.Study Design: The Reachout Study is a cohort study at the University Children's Hospital Zurich. Data from 148 children with congenital heart disease who underwent cardiopulmonary bypass surgery and 1-, 4-, and 6-year neurodevelopmental assessment were analyzed using mixed models.Results: Cognitive and motor functions of the total cohort improved over time (cognitive: P = .01; motor: P <.001). The prevalence of children with cognitive impairment at age 6 years was 22.3%. Socioeconomic status showed a significant interaction with age on cognitive and motor development (cognitive: P <.001; motor: P = .001): higher socioeconomic status was associated with better neurodevelopmental outcome over time. Weight and head circumference at birth showed a significant interaction with age on motor development (weight: P = .048; head: P = .006). The correlation between test scores at different ages was weak to moderate (cognition: age 1-6 years: rho = 0.20, age 4-6 years: rho = 0.56, motor: age 1-6 years: rho = 0.23, age 4-6 years: rho = 0.50).Conclusions: Children with congenital heart disease show a mild improvement in cognitive and motor functions within the first 6 years of life, particularly those with higher socioeconomic status and larger head circumference and weight at birth. However, individual stability is moderate at best. Therefore, follow-up assessments are crucial to target therapeutic intervention effectively. [ABSTRACT FROM AUTHOR]

Objective: To determine growth and its relationship to IQ in children with congenital heart disease (CHD) undergoing cardiopulmonary bypass surgery within the first year of life.Study Design: Prospective single-center cohort study on 143 children (91 males) with different types of CHD (29 univentricular). Children with recognized genetic disorders were excluded. Growth (weight, height, and head circumference [HC]) was assessed at birth, before surgery, and at 1, 4, and 6 years and compared with Swiss growth charts. IQ was assessed at 6 years using standardized tests. Univariate and multivariable linear regressions were performed to determine predictors of HC and IQ at 6 years.Results: HC at birth was in the low average range (33rd percentile, P = .03), and weight (49th percentile, P = .23) and length (47th percentile, P = .06) were normal. All growth measures declined until the first surgery, with a catch-up growth until 6 years for height (44th percentile, P = .07) but not for weight (39th percentile, P = .003) or for HC (23rd percentile, P < .001). Children undergoing univentricular palliation showed poorer height growth than other types of CHD (P = .01). Median IQ at 6 years was 95 (range 50-135). Lower IQ at 6 years was independently predicted by lower HC at birth, lower socioeconomic status, older age at first bypass surgery, and longer length of intensive care unit stay.Conclusions: Smaller HC at birth and postnatal factors are predictive of impaired intellectual abilities at school age. Early identification should alert clinicians to provide early childhood interventions to optimize developmental potential. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the predictive value of pre- and postoperative amplitude-integrated electroencephalography (aEEG) on neurodevelopmental outcomes in children operated for congenital heart disease (CHD).Study Design: Prospectively enrolled cohort of 60 infants with CHD who underwent cardiac surgery with cardiopulmonary bypass in the first 3 months of life. Infants with a genetic comorbidity were excluded. aEEG was assessed for 12 hours pre- and 48 hours postoperatively. Background pattern was classified by the use of standard categories, and the presence of seizures and sleep-wake cycles (SWCs) was noted. Outcome at 1 and 4 years of age was assessed with standardized developmental tests.Results: Preoperatively, infants either showed continuous normal voltage (n = 56) or discontinuous normal voltage (n = 4). Postoperatively, abnormal background pattern (flat trace, burst suppression, or continuous low voltage) was detected in 7 (12%), discontinuous normal voltage in 37 (61%), and continuous normal voltage in 16 (27%) infants. Nineteen infants (32%) did not return to normal SWCs within the recording period. Seizures were detected in 4 infants preoperatively and in another 4 postoperatively. After we controlled for surgical and postoperative risk factors, abnormal postoperative background pattern and lack of return to SWCs independently predicted poorer intelligence quotient at 4 years (P = .03 and P = .04 respectively) but was not related to motor outcome.Conclusion: aEEG is a useful bedside tool that helps to predict outcome in infants undergoing open-heart surgery for CHD. Abnormal postoperative background pattern and lack of return to SWCs are markers for subsequent impaired cognitive development. [ABSTRACT FROM AUTHOR]

Objectives: To determine neonatal global and regional brain volumes in infants with congenital heart disease (CHD) in comparison with healthy controls and to determine brain growth.Study Design: Prospective cohort study in infants undergoing open-heart surgery for complex CHD. Global and regional volumetric measurements on preoperative cerebral magnetic resonance imaging were manually segmented in children without overt brain lesions.Results: Preoperative brain volumetry of 19 patients demonstrates reduction in total and regional brain volumes, without any specific regional predilection compared with 19 healthy control infants (total brain volume reduction: 21%, regional brain volume reduction 8%-28%, all P < .001).Conclusions: Infants with CHD undergoing bypass surgery have smaller brain volumes prior to surgery without a specific regional predilection. This suggests a fetal origin of reduced brain growth. [ABSTRACT FROM AUTHOR]

Objectives: To study the long-term neurodevelopmental effects of hyperglycemia in infant bypass surgery for congenital heart disease (CHD).Study Design: Prospective cohort study on neurodevelopmental outcome after infant cardiac bypass surgery.Exclusion Criteria: age older than 1 year at first surgery, genetic comorbidity, and birth weight <2000 g. Of 167 eligible infants, follow-up examination at 4 years was completed in 150 children (90%). Intraoperative and postoperative highest and lowest glucose levels within 24 hours after bypass surgery were prospectively collected. Neurodevelopmental outcome at 4 years of age was assessed using standardized IQ tests and the Movement Assessment Battery for Children-second version for motor outcome assessment.Results: Mean age at surgery was 2.8 months (0.1-10.7 months), 33% of children had an acyanotic CHD and 67% a cyanotic CHD. Glucose levels were elevated (>8 mmol/L) in 21 (14%) children in the first 24 postoperative hours. Glucose levels normalized in all children within 48 hours, 7 children (4%) received insulin infusions. Mean total IQ was within the normal range, but significantly lower than the normal population (92.5 [SD 15.0], P < .001). Higher postoperative glucose levels were related to better cognitive performance in the univariate analysis (P < .03), but not when other risk factors were taken into account. Independent risk factors for adverse outcome were lower socioeconomic status, higher risk adjustment for congenital heart surgery score, and longer duration of intensive care stay.Conclusion: Hyperglycemia is common in the early postoperative course after infant bypass surgery for CHD and normalizes within 48 hours. Hyperglycemia has no adverse effect on long-term neurodevelopmental outcome. [ABSTRACT FROM AUTHOR]

Objectives: To determine health-related quality of life (HRQoL) in 1-year-old infants with congenital heart disease (CHD), to follow-up with these children at age 4 years, and to examine predictors of HRQoL. Study design: Parents of 144 infants who had undergone cardiopulmonary bypass surgery for CHD before age 6 months were prospectively included in this cohort study. Parents completed a standardized questionnaire on child HRQoL at 1 year and 4 years of age; medical data were extracted from the patients' hospital records. Results: Parents reported a significant reduction of the children's physical functioning compared with healthy controls at age 1 year. At age 4 years, children with CHD had poorer cognitive functioning but better social functioning compared with healthy controls. Lower HRQoL at age 4 years was not significantly predicted by univentricular or biventricular CHD but was predicted by the presence of an underlying genetic defect, tube feeding at 1 year, and lower HRQoL at 1 year. Conclusion: This study shows that HRQoL of infants and preschool-age children with CHD is impaired in physical and cognitive dimensions. Children with lower overall HRQoL at age 1 year, an underlying genetic defect, and tube feeding need to be monitored carefully to provide appropriate and timely interventions. [Copyright &y& Elsevier]

Objectives: To determine the long-term neurodevelopmental outcome for children after hypoxic-ischemic encephalopathy (HIE) without major disability, and to examine neonatal injury patterns detected on cerebral magnetic resonance imaging (MRI) in relation to later deficits. Study design: Prospectively enrolled children with HIE and neonatal cerebral MRI data (n = 68) were examined at a mean age of 11.2 years (range, 8.2-15.7 years). Eleven children had a major disability (ie, cerebral palsy or mental retardation). Brain injury was scored according to the region and extent of injury. Results: Children without major disability (n = 57) had lower full-scale and performance IQ scores compared with norms (P = .02 and .01, respectively), and the proportion of children with an IQ <85 was higher than expected (P = .04). Motor performance on the Zurich Neuromotor Assessment was affected in the pure motor, adaptive fine motor, and gross motor domains, as well as in the movement quality domain (all P < .001). Watershed injury pattern on neonatal MRI correlated with full-scale and verbal IQ scores (P = .006 and <.001, respectively), but neonatal MRI pattern did not correlate with motor performance in children without major disability. Conclusion: Children who sustained neonatal HIE without major disability are at increased risk for long-term intellectual, verbal, and motor deficits. The severity of watershed injury is correlated with later intellectual performance. Long-term follow-up examinations are necessary for early detection of neurodevelopmental impairment and early initiation of adequate therapies. [Copyright &y& Elsevier]

Objectives: To assess health-related quality of life (HRQoL) and behavior of triplets compared with matched singletons at adolescent age and to identify medical and sociodemographic predictors of outcome. Study design: Fifty-four triplets (19 sets, mean [SD] gestational age 32.0 [2.4] weeks, birth weight 1580 [450] g) and 51 gestational age-, birth weight-, and sex-matched singleton controls self-rated their HRQoL at age 14.5 (0.3) years. Proxy reports about HRQoL and behavior were obtained by parents and teachers. HRQoL was measured with the Kidscreen-52 questionnaire child and parent form, and behavior with the Achenbach Child Behavior Checklist. Results: Self- and parent-reported HRQoL values was similar in both groups except for the dimensions “mood and emotions” and “autonomy,” which were better (P = .001, P = .03) in triplets. Parents reported significantly less behavioral problems in triplets compared with controls. Compared with community norms, both HRQoL and behavior measures in triplets were in the normal range. Parent-reported HRQoL was predicted by dichorionicity. Conclusions: HRQoL and behavioral outcome in adolescent triplets was good in our study and was, in some aspects, better than in matched singleton controls. Dichorionicity is an important outcome determinant. [ABSTRACT FROM AUTHOR]

Objective: To examine the relationship between perioperative brain injury and neurodevelopment during early childhood in patients with severe congenital heart disease (CHD)., Study Design: One hundred and seventy children with CHD and born at term who required cardiopulmonary bypass surgery in the first 6 weeks after birth were recruited from 3 European centers and underwent preoperative and postoperative brain MRIs. Uniform description of imaging findings was performed and an overall brain injury score was created, based on the sum of the worst preoperative or postoperative brain injury subscores. Motor and cognitive outcomes were assessed with the Bayley Scales of Infant and Toddler Development Third Edition at 12 to 30 months of age. The relationship between brain injury score and clinical outcome was assessed using multiple linear regression analysis, adjusting for CHD severity, length of hospital stay (LOS), socioeconomic status (SES), and age at follow-up., Results: Neither the overall brain injury score nor any of the brain injury subscores correlated with motor or cognitive outcome. The number of preoperative white matter lesions was significantly associated with gross motor outcome after correction for multiple testing (P = .013, β = -0.50). SES was independently associated with cognitive outcome (P < .001, β = 0.26), and LOS with motor outcome (P < .001, β = -0.35)., Conclusion: Preoperative white matter lesions appear to be the most predictive MRI marker for adverse early childhood gross motor outcome in this large European cohort of infants with severe CHD. LOS as a marker of disease severity, and SES influence outcome and future intervention trials need to address these risk factors., Competing Interests: Declaration of Competing Interest Financial relationships/disclosures/grants: This research was funded by a Consolidator Grant of the European Society of Paediatric Research (ESPR). WKZ: This research was funded by the Hartekind Foundation and Vrienden van het Wilhelmina Kinderziekenhuis Foundation. CRUCIAL-TRIAL by ZonMw. KCL: This research was funded by the Medical Research Council UK (MR/L011530/1 and MR/V002465/1), the British Heart Foundation (FS/15/55/31649), and Action Medical Research (GN2630) and was supported by the Wellcome Engineering and Physical Sciences Research Council Centre for Medical Engineering at Kings College London (WT 203148/Z/16/Z). UCZ: This research was funded by the Mäxi-Foundation Switzerland, the Anna Müller Grocholski Foundation Switzerland and the EMDO Foundation Switzerland. The sponsors were not involved in the study design, the collection, analysis, and interpretation of data, the writing of the report; and the decision to submit the paper for publication., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)