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Background: Given the pervasive issues of obesity and diabetes both in Puerto Rico and the broader United States, there is a compelling need to investigate the intricate interplay among BMI, pregestational, and gestational maternal diabetes, and their potential impact on the occurrence of congenital heart defects (CHD) during neonatal development. Methods: Using the comprehensive System of Vigilance and Surveillance of Congenital Defects in Puerto Rico, we conducted a focused analysis on neonates diagnosed with CHD between 2016 and 2020. Our assessment encompassed a range of variables, including maternal age, gestational age, BMI, pregestational diabetes, gestational diabetes, hypertension, history of abortion, and presence of preeclampsia. Results: A cohort of 673 patients was included in our study. The average maternal age was 26 years, within a range of 22 to 32 years. The mean gestational age measured 39 weeks, with a median span of 38 to 39 weeks. Of the 673 patients, 274 (41%) mothers gave birth to neonates diagnosed with CHD. Within this group, 22 cases were linked to pre-gestational diabetes, while 202 were not; 20 instances were associated with gestational diabetes, compared to 200 without; and 148 cases exhibited an overweight or obese BMI, whereas 126 displayed a normal BMI. Conclusion: We identified a statistically significant correlation between pre-gestational diabetes mellitus and the occurrence of CHD. However, our analysis did not show a statistically significant association between maternal BMI and the likelihood of CHD. These results may aid in developing effective strategies to prevent and manage CHD in neonates.

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Sex determination in monomorphic birds is a precondition for captive breeding programs and management and conservation strategies for threatened species. Most species of the order Psittaciformes often present complications since these birds lack external sexual phenotypic traits, making it impossible to differentiate males and females. In the present study, we used molecular techniques to determine the sex of 31 individuals belonging to nine species of the order Psittaciformes kept under human care at the Akumal Monkey Sanctuary & Rescued Animals in Quintana Roo, Mexico. This is a useful and low-cost methodology based on the analysis of the conserved region of the CHD1 gene, which was amplified by PCR with two sets of primers: P8/P2 and 2550F/2718 R. All individuals were successfully sexed with the first set of primers, while only 28 out of 31 samples (90%) could be amplified with the second set. Out of the 31 individuals analyzed, fifteen are female, and seventeen are male. This information represents a handy tool for adequately managing birds under human care, resulting in their reproduction and eventual reintegration into their natural habitat.

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Introduction: In resource-limited settings, patients with uncommon phenotypes often face prolonged diagnostic journeys and potential misdiagnoses. Coloboma, heart defects, atresia choanae, restricted growth and development, genital and ear abnormalities syndrome (CHARGE) syndrome, a congenital condition affecting various body parts such as the heart, ears, eyes, and genitals, exemplifies this challenge. Case presentation: We present the case of a 21-year-old male patient from Ecuador who exhibited hypogonadism, facial deformities, and stunted growth. Due to the scarcity of genetic specialists and limited access to genetic testing in Ecuador, the patient received a misdiagnosis of Noonan syndrome. However, a correct diagnosis of CHARGE syndrome was ultimately reached after eight years, facilitated by genetic sequencing that identified a novel mutation in the Chromodomain helicase DNA binding protein 7 gene. Conclusion: This case highlights the critical role of meticulously assessing patients' symptoms and emphasizes the necessity for enhanced collaboration among physicians and researchers. Such efforts are pivotal in advancing healthcare access and equity for individuals in developing nations.

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CHARGE syndrome is a rare autosomal dominant syndrome characterized by multiple congenital anomalies including coloboma, heart defects, ear anomalies, and developmental delay, caused by pathogenic variants in the CHD7 gene. The discovery of the molecular basis of this syndrome increased the number of cases reported and expanded the phenotype and clinical variability. Limb anomalies are occasional clinical findings in this syndrome, present in about 30% of reported cases. The occurrence of limb anomalies in this syndrome suggests that it should be considered as part of the phenotypic spectrum. Here, we describe an individual with CHARGE syndrome presenting unilateral monodactyly.

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BACKGROUND: Tetralogy of Fallot (ToF) is a cyanotic congenital heart disease, composed of four malformations: persistent communication between the right and the left ventricle, pulmonary stenosis, overriding aorta, and right ventricle hypertrophy. The etiology of this disease is not entirely known as yet, but it has been proposed that the pathology has genetic components. During embryonic development, the fetus is exposed to a physiological hypoxia to facilitate the formation of blood vessels and blood cells through de novo processes. METHODS: After researching scientific databases on the implications of oxygen on the normal and abnormal development of organs, especially the heart, we were able to propose that oxygen deprivation may be the cause of the disease. RESULTS: During this period, the hypoxia-inducible factor is activated and triggers transcriptional responses that enable adaptation to the hypoxic environment through angiogenic activation. High levels of this protein can alter certain physiological pathways, such as those related to the vascular endothelial growth factor. Research has shown that prolonged oxygen deprivation during embryological development can lead to the occurrence of congenital heart diseases, such as ToF. CONCLUSIONS: Studies using animal models have demonstrated that the deficiency or disruption of a protein called "CITED2," which plays an important role in cardiac morphogenesis and its loss, results in the alteration of pluripotent, cardiac, and neural lineage differentiation, thereby disrupting the normal development of the heart and other tissues.

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BACKGROUND: The Fontan procedure is considered one of the most remarkable achievements in paediatric cardiology and cardiac surgery. Its final anatomical objective is a venous return through the superior and inferior vena cava. The complications inherent to this procedure and subsequent failure are its limitations. OBJECTIVE: To describe the clinical and haemodynamic characteristics of patients with Fontan failure and define the risk factors associated with it, with its short- and long-term outcomes during a 21-year observation period. METHODS: This is a retrospective follow-up study in which 15 patients diagnosed with Fontan failure in the single-ventricle programme of a high-complexity hospital in Medellín, Colombia, between 2001 and 2022 were included. RESULTS: One hundred and eight patients were identified in whom the Fontan procedure was performed, and 17 met the failure criteria. 82.4% were men, with a median age of 4.3 years. Ebstein's anomaly was the most common diagnosis, 29.4%. All patients underwent Fontan with an extracardiac tube following the procedure. According to the type of failure, 58.8% of patients presented protein-losing enteropathy and 17.6% plastic bronchitis. During follow-up, 5.9% of patients died. CONCLUSION: Fontan surgery in our centre is an option for patients with univentricular physiology. The correct selection of the patient is essential to mitigate failure risks.

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OBJECTIVE: To report the prevalence of cerebral palsy (CP) in children with severe congenital heart defects (sCHD) and the outcome/severity of the CP. METHODS: Population-based, data linkage study between CP and congenital anomaly registers in Europe and Australia. The EUROCAT definition of severe CHD (sCHD) was used. Linked data from 4 regions in Europe and 2 in Australia were included. All children born in the regions from 1991 through 2009 diagnosed with CP and/or sCHD were included. Linkage was completed locally. Deidentified linked data were pooled for analyses. RESULTS: The study sample included 4989 children with CP and 3684 children with sCHD. The total number of livebirths in the population was 1 734 612. The prevalence of CP was 2.9 per 1000 births (95% CI, 2.8-3.0) and the prevalence of sCHD was 2.1 per 1000 births (95% CI, 2.1-2.2). Of children with sCHD, 1.5% (n = 57) had a diagnosis of CP, of which 35 (61%) children had prenatally or perinatally acquired CP (resulting from a brain injury at ≤28 days of life) and 22 (39%) children had a postneonatal cause (a brain injury between 28 days and 2 years). Children with CP and sCHD more often had unilateral spastic CP and more intellectual impairments than children with CP without congenital anomalies. CONCLUSIONS: In high-income countries, the proportion of children with CP is much higher in children with sCHD than in the background population. The severity of disease in children with CP and sCHD is milder compared with children with CP without congenital anomalies.

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The clinical heterogeneity in 22q11.2 deletion syndrome (22q11.2DS) underlies complex genetic mechanisms including variants in other regions of the genome, known as genetic modifiers. Congenital heart disease (CHD) is one of the most relevant phenotypes in the syndrome and copy number variants (CNVs) outside the 22q11.2 region could play a role in its variable expressivity. Since those described loci account for a small proportion of the variability, the CNV analysis in new cohorts from different ancestry-based populations constitutes a valuable resource to identify a wider range of modifiers. We performed SNP-array in 117 Brazilian patients with 22q11.2DS, with and without CHD, and leveraged genome-wide CNV analysis. After quality control, we selected 50 CNVs in 38 patients for downstream analysis. CNVs' genetic content and implicated biological pathways were compared between patients with and without CHD. CNV-affected genes in patients with CHD were enriched for several functional terms related to ubiquitination, transcription factor binding sites and miRNA targets, highlighting the complexity of the phenotype's expressivity. Cardiac-related genes were identified in both groups of patients suggesting that increasing risk and protective mechanisms could be involved. These genes and enriched pathways could indicate new modifiers to the cardiac phenotype in 22q11.2DS patients.

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INTRODUCTION: Without participating in a contractile chamber, the Fontan procedure seeks to create a separation of oxygenated and deoxygenated blood in patients with univentricular heart, reducing the risks of long-term hypoxemia and improving their survival. This study describes the clinical outcomes of children undergoing the Fontan procedure between 2000 and 2020 in a tertiary referral hospital care centre in southwestern Colombia. MATERIALS AND METHODS: A retrospective observational descriptive study. The 81 patients who underwent the Fontan procedure were included. Categorical variables were presented with percentages and continuous variables with measures of central tendency according to the distribution of the data evaluated through the Shapiro-Wilk test. Sociodemographic, clinical, surgical variables, complications, and mortality were described. RESULTS: Between 2000 and 2020, 81 patients underwent the Fontan procedure: 43 (53.1%) males and a median age of 5.3 years (interquartile range 4.3-6.6). The most common diagnosis was tricuspid atresia (49.4%). The median mean pulmonary arterial pressure was 12 mmHg (interquartile range 10-15), the Nakata index 272 mm2/m2 (interquartile range 204-327), and the McGoon index (interquartile range 1.86-2.3). Seventy-two (88.9%) patients underwent extracardiac Fontan and 44 (54.3%) patients underwent fenestration. The median hospitalisation days were 19 days. The main complication was coagulopathy (19.8%), mortality in the first month between 2000 and 2010 was 8.6%, and after 2010 was 1.2%. CONCLUSION: The Fontan procedure is a palliative surgery for children with complex heart disease. According to anatomical and physiological variables, the proper choice of patients determines the short- and long-term results.

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During the tumorigenic process, cancer cells may become overly dependent on the activity of backup cellular pathways for their survival, representing vulnerabilities that could be exploited as therapeutic targets. Certain molecular vulnerabilities manifest as a synthetic lethality relationship, and the identification and characterization of new synthetic lethal interactions may pave the way for the development of new therapeutic approaches for human cancer. Our goal was to investigate a possible synthetic lethal interaction between a member of the Chromodomain Helicase DNA binding proteins family (CHD4) and a member of the histone methyltransferases family (SETDB1) in the molecular context of a cell line (Hs578T) representing the triple negative breast cancer (TNBC), a subtype of breast cancer lacking validated molecular targets for treatment. Therefore, we employed the CRISPR-Cas9 gene editing tool to individually or simultaneously introduce indels in the genomic loci corresponding to the catalytic domains of SETDB1 and CHD4 in the Hs578T cell line. Our main findings included: a) introduction of indels in exon 22 of SETDB1 sensitized Hs578T to the action of the genotoxic chemotherapy doxorubicin; b) by sequentially introducing indels in exon 22 of SETDB1 and exon 23 of CHD4 and tracking the percentage of the remaining wild-type sequences in the mixed cell populations generated, we obtained evidence of the existence of a synthetic lethality interaction between these genes. Considering the lack of molecular targets in TNBC, our findings provided valuable insights for development of new therapeutic approaches not only for TNBC but also for other cancer types.

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The Stage 1 Norwood procedure is the first of 3 stages in the surgical palliation of hypoplastic left heart syndrome and certain other single ventricle lesions with systemic outflow obstruction. In this article, we address some technical aspects and common pitfalls of the Norwood procedure with systemic to pulmonary shunt for HLHS palliation. We report our results with the Norwood with Blalock Taussig shunt in a cohort of 44 patients over a 7-year period in 2 institutions in Argentina. The results of the Norwood procedure have improved significantly through the understanding and refinement of the surgical techniques. Procedures must be technically perfect since residual lesions are poorly tolerated. Norwood with a modified Blalock Taussig shunt can be performed with low mortality and may provide excellent long-term outcomes.

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Objective: The molecular pathways underlying hypoxemia-induced alterations in neurodevelopment of infants with congenital heart disease have not been delineated. We used transcriptome analysis to investigate differential gene expression induced by hypoxemia in an ovine artificial-womb model. Methods: Mid-gestation fetal sheep (median [interquartile range] 109 [107-112] days' gestation) were cannulated via the umbilical vessels, attached to a pumpless, low-resistance oxygenator circuit, and incubated in a sterile, fluid environment for 22 [21-23] days. Fetuses were maintained with an oxygen delivery of 20-25 mL/kg/min (normoxemia, n = 3) or 14-16 mL/kg/min (hypoxemia, n = 4). Transcriptional profiling by RNA sequencing was carried out on left frontal brains and hypoxemia-regulated genes were identified by differential gene expression analysis. Results: A total of 228 genes whose expression was up or down regulated by ≥1.5-fold (false discovery rate ≤0.05) were identified. The majority of these genes were induced in hypoxemic animals compared to normoxemic controls, and functional enrichment analysis identified respiratory electron transport as a pathway strongly upregulated in the brain during chronic hypoxemia. Further examination of hypoxemia-induced genes showed robust induction of all 7 subunits of the mitochondrial NADH:ubiquinone oxidoreductase (complex I). Other hypoxemia-induced genes included cytochrome B, a component of complex III, and ATP6, ATP8, both of which are components of complex V. Conclusions: Chronic fetal hypoxemia leads to upregulation of multiple mitochondrial respiratory complex genes critical for energy production and reactive oxygen species generation, including complex I. These data provide valuable insight into potential pathways involved in chronic hypoxemia-induced neuropathology and offers potential therapeutic targets for fetal neuroprotection in fetuses with congenital heart defects.

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Introduction: Although the diurnal fluctuation of motor dysfunction, reversible with small doses of dopamine, is a cornerstone for the phenotype of the autosomal dominant Segawa syndrome, the non-motor symptoms of this neurotransmitter deficiency have still received limited attention. Objective: This study aims to evaluate non-motor symptoms of this dopa-responsive dystonia through an intrafamilial comparative cross-sectional study. Methods: Seventeen individuals with a c.IVS5 + 3insT (c.626 + 3insT) variation in the GTP cyclohydrolase-1 gene (GCH1, HGNC: 4193) and 34 intrafamilial controls were studied using the Beck Depression Inventory-II, the Wiener Matrizen Test 2, the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the MINI/MINI PLUS Questionnaires, the World Health Organization Quality of Life - BREF Instrument and a drug use assessment questionnaire. Results: No significant difference was found between the groups in the prevalence of sleep disorders and in cognitive function. Nevertheless, generalized anxiety disorder (p = 0.050) and attention-deficit/hyperactivity disorder in childhood (p = 0.011) were observed only in individuals without the molecular variation. The group with the GCH1 variation presented a worse perception about how safe they feel in their daily lives (p = 0.034), less satisfaction with themselves (p = 0.049) and with their relationships (p = 0.029), and a higher prevalence of past major depressive episodes before use of L-Dopa (p = 0.046). Conclusion: Low dopamine could have been protective against generalized anxiety disorder and attention-deficit/hyperactivity disorder in childhood in Segawa group individuals. The prevalence of depression was higher in individuals with the molecular variant prior to the L-Dopa treatment. Considering it, the penetrance estimates for the variant carriers increased from 58.8% to up to 88% in this large studied family. Additionally, neuropsychiatric tests of all individuals with a molecular diagnosis in an affected family are a valuable instrument for its clinical management.

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Congenital heart disease is one of the most common causes of death derived from malformations. Historically, its treatment has depended on timely diagnosis and early pharmacological and surgical interventions. Survival rates for patients with this disease have increased, primarily due to advancements in therapeutic choices, but mortality remains high. Since this disease is a time-sensitive pathology, pharmacological interventions are needed to improve clinical outcomes. Therefore, we analyzed the applications, dosage, and side effects of drugs currently used for treating congenital heart disease. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and potassium-sparing diuretics have shown a mortality benefit in most patients. Other therapies, such as endothelin receptor antagonists, phosphodiesterase-5 inhibitors, prostaglandins, and soluble guanylyl cyclase stimulators, have benefited patients with pulmonary artery hypertension. Likewise, the adjunctive symptomatic treatment of these patients has further improved the outcomes, since antiarrhythmics, digoxin, and non-steroidal anti-inflammatory drugs have shown their benefits in these cases. Conclusively, these drugs also carry the risk of troublesome adverse effects, such as electrolyte imbalances and hemodynamic compromise. However, their benefits for survival, symptom improvement, and stabilization outweigh the possible complications from their use. Thus, cases must be assessed individually to accurately identify interventions that would be most beneficial for patients.

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CHARGE syndrome is a complex developmental disorder caused by mutations in the chromodomain helicase DNA-binding protein-7 (CHD7) and characterized by retarded growth and malformations in the heart and nervous system. Despite the public health relevance of this disorder, relevant cellular pathways and targets of CHD7 that relate to disease pathology are still poorly understood. Here we report that chd-7, the nematode ortholog of Chd7, is required for dauer morphogenesis, lifespan determination, stress response, and body size determination. Consistent with our discoveries, we found chd-7 to be allelic to scd-3, a previously identified dauer suppressor from the DAF-7/ tumor growth factor-ß (TGF-ß) pathway. Epistatic analysis places CHD-7 at the level of the DAF-3/DAF-5 complex, but we found that CHD-7 also directly impacts the expression of multiple components of this pathway. Transcriptomic analysis revealed that chd-7 mutants fail to repress daf-9 for execution of the dauer program. In addition, CHD-7 regulates the DBL-1/BMP pathway components and shares roles in male tail development and cuticle synthesis. To explore a potential conserved function for chd-7 in vertebrates, we used Xenopus laevis embryos, an established model to study craniofacial development. Morpholino-mediated knockdown of Chd7 led to a reduction in col2a1 messenger RNA (mRNA) levels, a collagen whose expression depends on TGF-ß signaling. Both embryonic lethality and craniofacial defects in Chd7-depleted tadpoles were partially rescued by overexpression of col2a1 mRNA. We suggest that Chd7 has conserved roles in regulation of the TGF-ß signaling pathway and pathogenic Chd7 could lead to a defective extracellular matrix deposition.

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BACKGROUND: Glenn procedure is performed for patients with cyanotic CHD and univentricular physiology and has a survival rate above 90%. AIM: To evaluate the risk factors associated with a poor outcome after Glenn procedure. METHODS: The data for this retrospective analysis were collected from a regional Brazilian registry of congenital heart surgeries (ASSIST initiative) from 2014 to 2019. Data from 97 patients who underwent the Glenn procedure were considered. The primary outcomes were prolonged mechanical ventilation (>24 hours post-operatively) or in-hospital death, alone and combined. RESULTS: The overall in-hospital mortality was 13.4% (n = 13). Prolonged mechanical ventilation occurred in 52% (n = 51) of the patients. Our analysis found that risk factors for death or prolonged post-operative mechanical ventilation were cardiopulmonary bypass duration and post-operative lactate, whereas weight-for-age z-score and age at surgery were risk factors for prolonged mechanical ventilation. Cardiopulmonary bypass duration increased (adjusted odds ratio: 1.02; 95 % CI: 1.01, 1.03) and age at surgery decreased (adjusted odds ratio: 0.96; 95 % CI: 0.93, 0.99) the odds of the combined outcome. CONCLUSIONS: Age at surgery, post-operative lactate, and low-weight-for-age z-score are associated with prolonged mechanical ventilation and death following the Glenn procedure.

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INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) pandemic negatively impacted global healthcare. Consequences in Pediatric and Congenital Heart Surgery programmes and mortality of congenital heart patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) is still to be determined. OBJECTIVE: To study the COVID-19 pandemic implications in Brazilian Pediatric and Congenital Heart Surgery programmes. METHODS: We conducted a national online survey covering all states that perform Pediatric and Congenital Heart Surgery from 10 November to 22 November, 2020, using a Google forms questionnaire. We formulated questions related to impact on surgical volume, case-mix, and mortality. Then we asked about short-term post-operative COVID-19 infection and outcomes. RESULTS: We received responses from 46 centres representing all states where there were a Pediatric and Congenital Heart Surgery programme and all high-volume centres across the country. All but one centre experienced a significant decrease in surgical volume, and 23.9% of the responders revealed less than one-quarter of volume decrement. On the other hand, in over 70% of the centres, there was a significant surgical volume reduction. In addition to this, there was a shift in case-mix in 41 centres (89.1%) towards more complex cases. More than one-third of the responders revealed increased mortality in 2020 compared to previous years, and 43.5% of the programmes (20 centres) had at least one patient contaminated by SARS-Cov-2, accounting for 48 patients. Mortality in post-operative infected patients was 45.8% (22 patients). CONCLUSIONS: In general, Brazilian Pediatric and Congenital Heart Surgery programmes were severely affected by decreased surgical volume, unbalanced case-mix towards more complex cases, and increased mortality. Almost half of the programmes related post-operative COVID-19 contamination with high mortality.

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Intensive research on biodegradable films based on natural raw materials such as carboxymethyl cellulose (CMC) has been performed because it enables the production of transparent films with suitable barrier properties against oxygen and fats. Considering the importance of the production of this type of film at the industrial level, a scalable and continuous drying method is required. Refractance window-conductive hydro drying (RW-CHD) is a sustainable and energy-efficient method with high potential in drying this kind of compound. The objective of this study was to evaluate the factors (CMC thickness, heating water temperature, and film type) and radiation penetration depth that affect drying time and energy consumption. It was found that drying time decreased with increasing temperature and decreasing thickness. Similarly, energy consumption decreased with decreasing temperature and thickness. However, the drying time and energy consumed per unit weight of product obtained were equivalent when drying at any of the thicknesses evaluated. Film type had little effect on time and energy consumption compared to the effects of temperature and CMC thickness. The radiation penetration depth into the CMC was determined to be 1.20 ± 0.19 mm. When the thickness was close to this value, the radiation energy was better utilized, which was reflected in a higher heating rate at the beginning of drying.

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PURPOSE: Papillary thyroid carcinoma (PTC) represents the most common subtype of thyroid cancer (TC). This study was set out to explore the potential effect of CHD1L on PTC and type 2 diabetes mellitus (T2DM). METHODS: We searched for T2DM susceptibility genes through the GWAS database and obtained T2DM-related differentially expressed gene from the GEO database. The expression and clinical data of TC and normal samples were collated from the TCGA database. Receiver operating characteristic (ROC) curve analysis was subsequently applied to assess the sensitivity and specificity of the CHD1L for the diagnosis of PTC. The MCP-counter package in R language was then utilized to generate immune cell score to evaluate the relationship between CHD1L expression and immune cells. Then, we performed functional enrichment analysis of co-expressed genes and DEGs to determine significantly enriched GO terms and KEGG to predict the potential functions of CHD1L in PTC samples and T2DM adipose tissue. RESULTS: From two genes (ABCB9, CHD1L) were identified to be DEGs (p < 1 * 10-5) that exerted effects on survival (HR > 1, p < 0.05) in PTC and served as T2DM susceptibility genes. The gene expression matrix-based scoring of immunocytes suggested that PTC samples with high and low CHD1L expression presented with significant differences in the tumor microenvironment (TME). The enrichment analysis of CHD1L co-expressed genes and DEGs suggested that CHD1L was involved in multiple pathways to regulate the development of PTC. Among them, Kaposi sarcoma-associated herpesvirus infection, salmonella infection and TNF signaling pathways were highlighted as the three most relevant pathways. GSEA analysis, employed to analyze the genome dataset of PTC samples and T2DM adipose tissue presenting with high and low expression groups of CHD1L, suggests that these differential genes are related to chemokine signaling pathway, leukocyte transendothelial migration and TCELL receptor signaling pathway. CONCLUSION: CHD1L may potentially serve as an early diagnostic biomarker for PTC, and a target of immunotherapy for PTC and T2DM.

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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.

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