Australian National Standards of Care for Childhood-onset Heart Disease (CoHD Standards). 1st Edition.

These first Australian National Standards of Care for Childhood-onset Heart Disease (CoHD Standards) have been developed to inform the healthcare requirements for CoHD services and enable all Australian patients, families and carers impacted by CoHD (paediatric CoHD and adult congenital heart disease [ACHD]) to live their best and healthiest lives. The CoHD Standards are designed to provide the clarity and certainty required for healthcare services to deliver excellent, comprehensive, inclusive, and equitable CoHD care across Australia for patients, families and carers, and offer an iterative roadmap to the future of these services. The CoHD Standards provide a framework for excellent CoHD care, encompassing key requirements and expectations for whole-of-life, holistic and connected healthcare service delivery. The CoHD Standards should be implemented in health services in conjunction with the National Safety and Quality Health Service Standards developed by the Australian Commission on Safety and Quality in Health Care. All healthcare services should comply with the CoHD Standards, as well as working to their organisation's or jurisdiction's agreed clinical governance framework, to guide the implementation of structures and processes that support safe care.

Mother-Infant Dyadic Synchrony and Interaction Patterns After Infant Cardiac Surgery.

OBJECTIVE: Parents and their infants with complex congenital heart disease (CHD) face relational challenges, including marked distress, early separations, and infant hospitalizations and medical procedures, yet the prevalence of parent-infant interaction difficulties remains unclear. Using a standardized observational paradigm, this study investigated mother-infant dyadic synchrony, interactional patterns, and associated predictors in mother-infant pairs affected by CHD, compared with typically-developing pairs. METHODS: In this prospective, longitudinal cohort study, mothers and their infants requiring cardiac surgery before age 6-months (n=110 pairs) and an age- and sex-matched Australian community sample (n=85 pairs) participated in a filmed, free-play interaction at 6.9±1.0 months. Mother-infant dyadic synchrony, maternal and infant interactional patterns, and relational risk were assessed using the Child-Adult Relationship Experimental (CARE) Index. Maternal and infant predictors were assessed at 32 weeks gestation, 3- and 6-months postpartum. RESULTS: Most mother-infant interactions were classified as "high risk" or "inept" (cardiac: 94%, control: 81%; p=.007). Dyadic synchrony (p<.001), maternal sensitivity (p=.001), and infant cooperativeness (p=.001) were lower for cardiac than control pairs. Higher maternal traumatic stress at 6-months postpartum predicted lower dyadic synchrony for mother-infant pairs affected by CHD (B=-.04, p=.03). Dyadic synchrony was higher among older infants in the total (B=.40, p=.003) but not cardiac sample (B=.24, p=.06). CONCLUSIONS: Relational difficulties were almost universal among mother-infant pairs affected by CHD and were also high in the Australian community sample. Widespread education initiatives are recommended to increase awareness of heightened mother-infant relational risk in congenital heart care and well-child settings, alongside relationally-focused prevention and early intervention programs.

"The usual challenges of work are all magnified": Australian paediatric health professionals' experiences during the COVID-19 pandemic.

Background: The COVID-19 pandemic has significantly increased stress and strain on health professionals. With a focus on paediatric cardiac care, this study explored health professionals' concerns about COVID-19, perceptions of the impact of pandemic on healthcare, and experiences of psychological stress. Methods: Paediatric health professionals working at a large quaternary hospital in Australia were invited to complete a survey between June 2020 and February 2021. Demographic factors, clinical role characteristics, and anxiety and depressive symptoms were assessed. Qualitative data on experiences and perceived effects of the pandemic on paediatric cardiac care were also collected. Results: 228 health professionals (152 nurses, 37 medical doctors, 22 allied and mental health professionals, 17 medical research and administrative staff) participated in the survey (54.4% response rate, 85% women). Half the sample (52.2%) endorsed 'moderate' to 'extreme' worry about COVID-19 and 38% of participants perceived healthcare services as adversely impacted by the pandemic to a 'great' or 'very great' extent. Almost one in five health professionals reported anxiety (18%) and 11% reported depressive symptoms indicative of a need for clinical intervention. Six themes were identified in the qualitative data: (1) Concern about the consequences of visitor restrictions and disrupted patient services, (2) Intensified strain on healthcare workers, (3) Feelings of fear and loss, (4) Social isolation and disconnection, (5) Adapting to change, and (6) Gratitude. Conclusion: Timely, tailored policies, supports, and interventions are needed to address health professionals' mental health needs during and beyond the pandemic, to minimize the far-reaching impact of situational stressors.

Insights into the genetic architecture underlying complex, critical congenital heart disease.

Congenital heart disease (CHD) has a multifactorial aetiology, raising the possibility of an underlying genetic burden, predisposing to disease but also variable expression, including variation in disease severity, and incomplete penetrance. Using whole genome sequencing (WGS), the findings of this study, indicate that complex, critical CHD is distinct from other types of disease due to increased genetic burden in common variation, specifically among established CHD genes. Additionally, these findings highlight associations with regulatory genes and environmental "stressors" in the final presentation of disease.

The Australian and New Zealand Fontan Registry Quality of Life Study: Protocol for a population-based assessment of quality of life among people with a Fontan circulation, their parents, and siblings.

INTRODUCTION: Advances in the care of patients with single-ventricle congenital heart disease have led to a new generation of individuals living with a Fontan circulation. For people with Fontan physiology, physical, psychological and neurodevelopmental challenges are common. The objective of this study is to describe and develop a deeper understanding of the factors that contribute to quality of life (QOL) among children, adolescents and adults living with a Fontan circulation across Australia and New Zealand, their parents and siblings. METHODS AND ANALYSIS: This article presents the protocol for the Australian and New Zealand Fontan Registry (ANZFR) QOL Study, a cross-sectional, population-based study designed to examine QOL among people of all ages with a Fontan circulation, their parents and siblings. Study eligibility criteria includes (1) individuals with a Fontan circulation aged ≥6 years, at least 12 months post-Fontan procedure and enrolled in the ANZFR; (2) parents of individuals enrolled in the ANZFR; and (3) siblings aged ≥6 years of an individual enrolled in the ANZFR. A novel, online research platform is used to distribute personalised assessments tailored to participant age and developmental stage. A suite of validated psychometric self-report and parent-proxy report instruments capture potential correlates and predictors of QOL, including symptoms of psychological distress, personality attributes, coping and cognitive appraisals, family functioning, healthcare experiences and costs, access to emotional support and socioeconomic factors. Clinical characteristics are captured via self-report and parent-proxy report, as well as the ANZFR. Descriptive analyses and multilevel models will be used to examine QOL across groups and to investigate potential explanatory variables. ETHICS AND DISSEMINATION: Approval has been obtained from all relevant Human Research Ethics Committees (HRECs), including the Sydney Children's Hospitals Network and the Royal Children's Hospital Melbourne HRECs. Study findings will be published in peer-reviewed journals and presented at national and international meetings and seminars.

A new era of genetic testing in congenital heart disease: A review.

Genetic and genomic testing in pediatric CHD is becoming increasingly routine, and can have important psychosocial, clinical and reproductive implications. In this paper we highlight important challenges and considerations when providing genetics consults and testing in pediatric CHD and illustrate the role of a dedicated CHD genetics clinic. Key lessons include that a) a genetic diagnosis can have clinical utility that justifies testing early in life, b) adequate genetic counselling is crucial to ensure families are supported, understand the range of possible results, and are prepared for new or unexpected health information, and c) further integration of the clinical genetics and cardiology workflows will be required to effectively manage the burgeoning information arising from genetic testing. Our experience demonstrates that a dedicated CHD genetics clinic is a valuable addition to a multidisciplinary team providing care to children with CHD.

The Ross/Ross-Konno procedure in infancy is a safe and durable solution for aortic stenosis.

OBJECTIVE: The objective of this study was to characterize early and midterm outcomes after the Ross/Ross-Konno procedure performed in infancy for severe aortic valve disease. METHODS: Between January 1995 and December 2018, 35 infants younger than 1 year (13 neonates) underwent a Ross/Ross-Konno procedure. Patients were followed up to a median of 4.1 years (interquartile range [IQR], 2.6-9.5). Primary outcome measures were survival, early morbidity, freedom from reintervention and long-term functional and echocardiographic status. RESULTS: Median age at operation was 49 days (IQR, 17-135) and weight was 4 kg (IQR, 3.4-5.2). Thirty-one (89%) had undergone a previous procedure, including balloon valvuloplasty in 26 (74%). Thirty (86%) required annular enlargement (Konno incision). Five required concomitant aortic arch surgery (2 neonates, 3 infants). There were no early deaths, and 1 late death at 18 months. Freedom from reoperation was 85% (95% confidence interval [CI], 68%-93%) at 1 year, 76% (95% CI, 54%-88%) at 5 years, and 62% (95% CI, 36%-79%) at 10 years. One modified Konno was performed at 5 years after a Ross in infancy. Ten right ventricle to pulmonary artery conduits have required reintervention (2 percutaneous pulmonary valve implantations). One child required a permanent pacemaker for complete heart block. At latest follow-up, 32 (94%) of 34 survivors were asymptomatic. There was no significant change in neoaortic Z-scores between 6 weeks and latest follow-up. CONCLUSIONS: The neonatal and infant Ross/Ross-Konno procedure can be performed with low mortality and achieves a stable left ventricular outflow tract. Significant early morbidity reflects the preoperative condition of the patients but definitive surgery of this type can be considered as a primary approach.

Whole genome sequencing in transposition of the great arteries and associations with clinically relevant heart, brain and laterality genes.

BACKGROUND: The most common cyanotic congenital heart disease (CHD) requiring management as a neonate is transposition of great arteries (TGA). Clinically, up to 50% of TGA patients develop some form of neurodevelopmental disability (NDD), thought to have a significant genetic component. A "ciliopathy" and links with laterality disorders have been proposed. This first report of whole genome sequencing in TGA, sought to identify clinically relevant variants contributing to heart, brain and laterality defects. METHODS: Initial whole genome sequencing analyses on 100 TGA patients focussed on established disease genes related to CHD (n = 107), NDD (n = 659) and heterotaxy (n = 74). Single variant as well as copy number variant analyses were conducted. Variant pathogenicity was assessed using the American College of Medical Genetics and Genomics-Association for Molecular Pathology guidelines. RESULTS: Fifty-five putatively damaging variants were identified in established disease genes associated with CHD, NDD and heterotaxy; however, no clinically relevant variants could be attributed to disease. Notably, case-control analyses identified significantly more predicted-damaging, silent and total variants in TGA cases than healthy controls in established CHD genes (P < .001), NDD genes (P < .001) as well as across the three gene panels (P < .001). CONCLUSION: We present compelling evidence that the majority of TGA is not caused by monogenic rare variants and is most likely oligogenic and/or polygenic in nature, highlighting the complex genetic architecture and multifactorial influences on this CHD sub-type and its long-term sequelae. Assessment of variant burden in key heart, brain and/or laterality genes may be required to unravel the genetic contributions to TGA and related disabilities.

Rapidly Enlarging Aortic Root Pseudoaneurysm in a Child With Endocarditis and Repaired Congenital Heart Disease.

A child with repaired double outlet right ventricle presented with Staphylococcus aureus bacteremia. Despite unsuspecting echocardiography on admission and clinical improvement on antibiotics, repeat routine echocardiography detected an aortic pseudoaneurysm, requiring a Ross-Konno operation. In repaired congenital heart defects with bacteremia, close echocardiographic surveillance is required to detect aortic pseudoaneurysm. (Level of Difficulty: Intermediate.).

Outcomes Following Heterotopic Placement of Right Ventricle to Pulmonary Artery Conduits.

BACKGROUND: We sought to evaluate the outcomes following right ventricle to pulmonary artery (RV-PA) conduit placement in pediatric patients, excluding those with a RV-PA conduit for the Ross procedure which is associated with improved conduit durability, partly related to its orthotopic position. METHODS: Outcomes for 119 patients who underwent RV-PA conduit placement at a single institution from January 2004 to December 2016 were reviewed. Primary outcome measures were reintervention-free survival (RFS) and overall survival. Survival analyses were performed using the Kaplan-Meier method, and risk factors associated with reintervention were evaluated. RESULTS: The median age at the time of conduit placement was 6 months (interquartile range, IQR: 1-14), and the median length of follow-up was 63 months (range: 0-156). During follow-up, 39 patients required conduit-related reintervention, while 6 patients died perioperatively with an overall survival of 90% at 10 years. Among the remaining 113 patients, the RFS at one, five, and ten years was 91% (84%-95%), 72% (60%-80%), and 33% (16%-50%), respectively. The median time to conduit replacement in the series was 43.5 months (IQR: 19.3-76.2). The use of a pulmonary homograft was associated with improved RFS (P = .03), and this was particularly pronounced in comparison with aortic homografts in neonates. Infection was the indication for replacement in only one patient. CONCLUSIONS: The majority of the conduits placed during the neonatal period required conduit replacement before the age of five years. Endocarditis was not a common indication for replacement. In neonates and infants, we prefer pulmonary homografts for most indications.

Selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitors and epidemiological characteristics associated with prenatal diagnosis of congenital heart disease.

OBJECTIVE: Identify early pregnancy associations of congenital heart disease (CHD) in a multiethnic cohort. METHODS: This retrospective observational cohort study compared the general obstetric population to women who gave birth at a referral centre in Australia between 2012 and 2017, after 20 weeks' of gestation, with a pregnancy affected by CHD. We defined mood disorder and anxiety as a history of self-reported or medically diagnosed anxiety, depression, postpartum depression or bipolar disorder. RESULTS: We compared epidemiological factors between 30 842 general obstetric patients and 470 obstetric patients with a foetus affected by CHD. Multivariate analysis showed independent associations between CHD and use of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in the first trimester (relative risk [RR] 4.14, 95% CI 2.58-6.65), history of anxiety or mood disorder with no SSRI/SNRI first trimester (RR 2.20, 95% CI 1.77-2.74), folate and/or pregnancy multivitamin use in the first trimester (RR 0.69, 95% CI 0.55-0.87) and increased risk with maternal age >40 years (RR 2.30, 95% CI 1.57-3.38). CONCLUSIONS: Our data show maternal mood disorders with and without SSRI or SNRI use, maternal age >40 years and lack of multivitamin/folate use to be independently associated with CHD in pregnancy.

Health-Related Quality of Life in Children, Adolescents, and Adults With a Fontan Circulation: A Meta-Analysis.

Background People with a Fontan circulation experience a range of physical, psychosocial and neurodevelopmental challenges alongside, or caused by, their cardiac condition, with significant consequences for health-related quality of life (HRQOL). We meta-analyzed HRQOL outcomes reported by people with a Fontan circulation or their proxies and evaluated predictors of poorer HRQOL. Methods and Results Six electronic databases were searched for peer-reviewed, English-language articles published before March 2019. Standardized mean differences (SMD) were calculated using fixed and random-effects models. Fifty articles reporting on 29 unique studies capturing HRQOL outcomes for 2793 people with a Fontan circulation and 1437 parent-proxies were analyzed. HRQOL was lower in individuals with a Fontan circulation compared with healthy referents or normative samples (SMD, -0.92; 95% CI, -1.36 to -0.48; P<0.001). Lower scores were reported across all HRQOL domains, with the largest differences found for physical (SMD, -0.90; 95% CI, -1.13 to -0.67; P<0.001) and school/work functioning (SMD, -0.71; 95% CI, -0.90 to -0.52; P<0.001). Meta-regression analyses found no significant predictors of self-reported physical functioning, but older age at Fontan operation was associated with poorer emotional functioning (ß=-0.124; P=0.004), and diagnosis of hypoplastic left heart was associated with poorer social functioning (ß=-0.007; P=0.048). Sensitivity analyses showed use of the PedsQL Core Module was associated with lower HRQOL scores compared with the Short-Form Health Survey-36. Conclusions HRQOL outcomes for people with a Fontan circulation are lower than the general population. Optimal care acknowledges the lifelong impact of the Fontan circulation on HRQOL and offers targeted strategies to improve outcomes for this growing population.

Outcomes of the Fontan Operation for Patients With Heterotaxy: A Meta-Analysis of 848 Patients.

BACKGROUND: Heterotaxy is considered a risk factor for adverse events at all stages in the pre-Fontan pathway, and Fontan outcomes are expected to be worse in patients with heterotaxy. The aim of this study was to review existing literature reporting outcomes of the Fontan operation systematically in patients with heterotaxy. METHODS: A systematic review and meta-analysis was performed to identify and synthesize early mortality and medium- and long-term survival in heterotaxy patients after the Fontan procedure. Subsequent outcome analyses were stratified by study period era, cohort size, and proportion of right versus left atrial isomerism to explore predictors of outcome. RESULTS: A total of 21 studies were included for analysis, which were composed of 848 post-Fontan heterotaxy patients. Early mortality varied between 1% and 30% with a weighted event rate of 14% (95% confidence interval [CI], 10%-19%). Survival at 1, 5, and 10 years was 86% (95% CI, 79%-91%), 80% (95% CI, 71%-87%), and 74% (95% CI, 59%-85%), respectively. Stratification by study period highlighted that studies with a median study period year of 1995 or later had similar early mortality and 1- and 5-year survival, but superior 10-year survival (P = .02) compared with earlier studies. Stratification by cohort size and right versus left atrial isomerism did not reveal subgroup differences. CONCLUSIONS: Compared with existing literature, in patients with heterotaxy, early mortality after Fontan is higher than for the overall Fontan population. Long-term survival is comparable to the overall Fontan cohort. When heterotaxy patients are successfully transitioned to Fontan, subsequent survival is acceptable and predictable. Long-term follow-up is lacking.

Heterotaxy Is Not a Risk Factor for Adverse Long-Term Outcomes After Fontan Completion.

BACKGROUND: Heterotaxy is considered a risk factor for poor outcomes after the Fontan operation. However, long-term data to support this notion are lacking. The aims of this study were to ascertain the long-term outcomes of patients with heterotaxy after hospital discharge after Fontan completion and to compare these outcomes with those of a contemporary nonheterotaxy cohort. METHODS: A binational Fontan registry (n = 1540) was analyzed to identify patients with heterotaxy and compare them with patients without heterotaxy. The primary composite end point was Fontan failure, encompassing death, heart transplantation, Fontan takedown or conversion, protein-losing enteropathy, plastic bronchitis, or New York Heart Association functional class III or IV. RESULTS: A total of 109 patients with heterotaxy were identified and they were compared with 1431 nonheterotaxy patients after Fontan completion. There was no difference in unadjusted 15-year freedom from Fontan failure (heterotaxy, 78% vs nonheterotaxy, 85%; P = .2). Patients in the heterotaxy group had a significantly higher cumulative incidence of post-Fontan arrhythmias (P < .001). Propensity-score matching for confounders yielded 73 patients with heterotaxy matched with 439 patients without heterotaxy, in whom 15-year freedom from Fontan failure was also not different (heterotaxy, 76% vs nonheterotaxy, 81%; P = .2). There was no difference in 15-year freedom from Fontan failure in patients with right vs left isomerism (right isomerism, 80% vs left isomerism, 76%; P = .7). CONCLUSIONS: Although heterotaxy may complicate the pre-Fontan course, once the Fontan procedure is successfully completed, heterotaxy does not appear to be an important risk factor for Fontan failure. Patients with heterotaxy are at a higher risk of post-Fontan arrhythmias compared with patients without heterotaxy.

Impact of High-Risk Characteristics in Hypoplastic Left Heart Syndrome.

BACKGROUND: Management of hypoplastic left heart syndrome (HLHS) presents many challenges. We describe our institutional outcomes for management of patients with HLHS over the past 12 years and highlight our strategy for those with highly restrictive/intact interatrial septum (R/I-IAS). METHODS: Eighty-eight neonates with HLHS underwent surgical treatment, divided equally into Era-I (n = 44, April 2006 to February 2013) and Era-II (n = 44, March 2013 to June 2018). Up to 2013, all patients with R/I-IAS were delivered at an adjacent adult hospital and then moved to our hospital for intensive care and management. From 2014, these patients were delivered at a co-located theatre in our hospital with immediate atrial septectomy. The hybrid approach was occasionally used with preference for the Norwood procedure for suitable candidates. RESULTS: One-year survival after Norwood procedure was 62.5% and 80% for Era-I and Era-II (P = not significant (ns)), respectively, and 41% of patients were categorized as high risk using conventional criteria. Survival at 1 year differed significantly between high-risk and standard-risk patients (P = 0.01). For high-risk patients, survival increased from 42% to 65% between eras (P = ns). In the R/I-IAS subgroup (n = 15), 11 underwent Norwood procedure after emergency atrial septectomy. Of these, seven born at the adjacent adult hospital had 40% survival to stage II versus 60% for the four born at the colocated theatre. Delivery in a colocated theatre reduced the birth-to-cardiopulmonary bypass median time from 445 (150-660) to 62 (52-71) minutes. CONCLUSION: Reported surgical outcomes are comparable to multicenter reports and international databases. Proactive management for risk factors such as R/I-IAS may contribute to improved overall outcomes.

Psychological interventions for people affected by childhood-onset heart disease: A systematic review.

OBJECTIVE: Guidelines recommend psychological intervention for children, adolescents, and adults with childhood-onset heart disease and their families, yet a comprehensive review of interventions is lacking. We aimed to determine the efficacy of psychological interventions for this population. METHOD: We searched 6 electronic databases until August, 2017 for English-language, controlled trials of psychological interventions for children, adolescents, or adults with congenital heart disease, inherited arrhythmias, or cardiomyopathies, or their family members. Outcomes of interest included: anxiety, depression, psychological stress and distress, health-related quality of life, coping and adjustment, developmental outcomes, physical health, and parent and family outcomes. RESULTS: Of 7,660 identified articles, 11 articles reporting on 9 unique interventions met inclusion criteria. Four interventions included adolescents or adults with congenital heart disease, 2 of which also included individuals with cardiomyopathies, valvular heart conditions, or inherited arrhythmias. Five interventions targeted parents, predominantly mothers, of children with congenital heart disease. Clinical and methodological diversity was observed across trials. Parent-focused interventions demonstrated some improvements in maternal mental health, including anxiety and worry, coping, and family functioning. Evidence for the efficacy of interventions for adolescents and adults was limited. Most trials (8/9) were at "high" or "serious" risk of bias. CONCLUSIONS: Despite an established evidence-base for psychological interventions in other chronic illness populations, evidence of efficacy for children and adults with childhood-onset heart disease and their families was limited. Interventions using conceptual frameworks tested in methodologically robust trials are needed to enhance the provision of mental health care for people of all ages with childhood-onset heart disease. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Two Ventricles Are Not Better Than One in the Fontan Circulation: Equivalent Late Outcomes.

BACKGROUND: A subset of patients who underwent Fontan operations has two adequate-sized ventricles, but an anatomic biventricular circulation cannot be achieved because of complex morphology or for technical reasons. This study sought to determine whether these patients with two-ventricle Fontan circulation had superior outcomes compared with those with a single ventricle. METHODS: A binational Fontan Registry of patients (n = 1,377) was analyzed to identify those patients with two adequate ventricles. This cohort was compared with patients with single-ventricle Fontan circulation. The primary end point was a composite end point called "Fontan failure" encompassing death, heart transplantation, Fontan takedown or conversion, protein-losing enteropathy, plastic bronchitis, or New York Heart Association functional class III or IV. RESULTS: A total of 79 Fontan patients with two adequate ventricles (2V) were compared with 1,291 single ventricle (1V) Fontan patients. Median follow-up for the entire cohort was 11.5 years (interquartile range, 5.1 to 18.8 years). There was no difference in unadjusted 15-year freedom from Fontan failure (2V: 81% [95% confidence interval (CI), 69% to 94%] vs 1V: 86% [95% CI, 83% to 88%], p = 0.4). Propensity-score matching for potential confounding factors yielded 75 two-ventricle Fontan patients matched with 604 single-ventricle Fontan patients, in which 15-year freedom from Fontan failure was also not different (2V: 79% [95% CI, 67% to 94%] vs 1V: 87% [95% CI, 84% to 91%], p = 0.3). CONCLUSIONS: The two-ventricle Fontan circulation does not have better outcomes compared with the single-ventricle Fontan circulation. Late outcomes may depend more on other characteristics of the Fontan circulation. This finding is relevant when the Fontan procedure is being considered as an alternative to anatomic repair in patients with complex two-ventricle morphologies.

Identification of clinically actionable variants from genome sequencing of families with congenital heart disease.

PURPOSE: Congenital heart disease (CHD) affects up to 1% of live births. However, a genetic diagnosis is not made in most cases. The purpose of this study was to assess the outcomes of genome sequencing (GS) of a heterogeneous cohort of CHD patients. METHODS: Ninety-seven families with probands born with CHD requiring surgical correction were recruited for genome sequencing. At minimum, a proband-parents trio was sequenced per family. GS data were analyzed via a two-tiered method: application of a high-confidence gene screen (hcCHD), and comprehensive analysis. Identified variants were assessed for pathogenicity using the American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines. RESULTS: Clinically relevant genetic variants in known and emerging CHD genes were identified. The hcCHD screen identified a clinically actionable variant in 22% of families. Subsequent comprehensive analysis identified a clinically actionable variant in an additional 9% of families in genes with recent disease associations. Overall, this two-tiered approach provided a clinically relevant variant for 31% of families. CONCLUSIONS: Interrogating GS data using our two-tiered method allowed identification of variants with high clinical utility in a third of our heterogeneous cohort. However, association of emerging genes with CHD etiology, and development of novel technologies for variant assessment and interpretation, will increase diagnostic yield during future reassessment of our GS data.

School-Age Developmental and Educational Outcomes Following Cardiac Procedures in the First Year of Life: A Population-Based Record Linkage Study.

The purpose of the study was to evaluate school-age developmental and educational outcomes for children with and without a cardiac procedure in the first year of life to improve understanding of longer-term neurodevelopmental outcomes in children who have had a cardiac procedure for congenital heart disease, the most common serious congenital anomaly. A population-based cohort study using record linkage of state-wide data was undertaken, evaluating children born in New South Wales, Australia, 2001-2007. Those with and without a cardiac procedure in the first year of life with a linked developmental (Australian version Early Development Instrument testing result, age 4-6 years) and/or educational outcome (Australian National Assessment Program result, age 7-9 years) were included. Perinatal, perioperative and sociodemographic factors were examined using multivariable logistic regression models. Of 468,329 eligible children, 768 had a cardiac procedure in the first year of life and 582 were included. For those with a cardiac procedure and developmental outcome (n = 260), 13.1% were classified as having 'special needs' compared to 4.4% without a cardiac procedure. Of those with an educational outcome, after adjusting for perinatal, perioperative and demographic variables, children with a cardiac procedure (n = 396) were twice as likely to score below National Minimum Standard in school literacy and numeracy tests compared to their peers. Significant predictors included low birthweight, parent not completing school and having > 4 re-hospitalisations in their first six years. The developmental and educational trajectory of children who have had a cardiac procedure in their first year remains altered into primary school years. While perioperative factors did not impact outcomes, ongoing health and sociodemographic factors were important in identifying those children at greatest risk.