Untangling the Complex Associations between Socioeconomic and Demographic Characteristics and Prenatal Detection and Outcomes in Congenital Heart Disease.

Recent literature has established a strong foundation examining the associations between socioeconomic/demographic characteristics and outcomes for congenital heart disease. These associations are found beginning in fetal life and influence rates of prenatal detection, access to timely and appropriate delivery room and neonatal interventions, and surgical and other early childhood outcomes. This review takes a broad look at the existing literature and identifies gaps in the current body of research, particularly as it pertains to disparities in the prenatal detection of congenital heart disease within the United States. It also proposes further research and interventions to address these health disparities.

Survival benefits of the wait-and-grow approach in small babies (≤2000 g) requiring heart surgery.

Objective: The best approach to minimize the observed higher mortality of newborn infants with low birth weight who require congenital heart surgery is unclear. This retrospective study was designed to review outcomes of newborn infants weighing <2000 g who have undergone cardiovascular surgery to identify patient parameters and clinical strategies for care associated with higher survival. Methods: A retrospective chart review of 103 patients who underwent cardiovascular surgery from 2010 to 2021 who were identified as having low birth weight (≤2000 g). Patients who underwent only patent ductus arteriosus ligation or weighing >3500 g at surgery were excluded. Results: Median age was 24 days and weight at the time of surgery was 1920 g. Twenty-six (25%) operative mortalities were recorded. Median follow-up period was 2.7 years. The 1- and 3-year overall Kaplan-Meier survival estimate was 72.4% ± 4.5% and 69.1% ± 4.6%. The 1-year survival of patients who had a weight increase >300 g from birth to surgery was far superior to the survival of those who did not achieve such a weight gain (81.4% ± 5.6% vs 64.0% ± 6.7%; log-rank P = .04). By multivariable Cox-hazard regression analysis, the independent predictor of 1-year mortality was genetic syndrome (hazard ratio, 3.54; 95% CI, 1.67-7.82; P < .001), whereas following a strategy of increasing weight from birth to surgery resulted in lower mortality (hazard ratio, 0.49; 95% CI, 0.24-0.90; P = .02). Conclusions: A strategy of wait and grow for newborn infants with very low birth weight requiring heart surgery results in better survival than immediate surgery provided that the patient's condition allows for this waiting period.

Brain injury and neurodevelopmental outcomes in children undergoing surgery for congenital heart disease.

Objectives: Brain injury is commonly seen on magnetic resonance imaging in infants with complex congenital heart disease. The impact of perioperative brain injury on neurodevelopmental outcomes is not well understood. We evaluate the association of brain injury and other markers on neurodevelopmental outcomes in patients undergoing surgery for congenital heart surgery during infancy. Methods: Term newborns with infant cardiac surgery performed between 2008 and 2019 at a single tertiary center, and both preoperative and postoperative brain magnetic resonance imaging were included. Those with underlying genetic conditions were excluded. Brain injury was characterized using an magnetic resonance imaging scoring system. Neurodevelopmental outcomes were assigned using the Pediatric Stroke Outcome Measure and Glasgow Outcome Scale Extended. Independent risk factors for poor neurodevelopmental outcomes were determined by multivariable Cox regression. Results: A total of 122 patients were included. New or progressive postoperative brain injury was noted in 69 patients (57%). A total of 101 patients (83%) had at least 1 neurodevelopmental assessment (median age 36 months) with an early assessment (5-24 months) performed in 95 children. Multivariable Cox regression analysis of early neurodevelopmental outcomes identified new stroke on postoperative magnetic resonance imaging to be an independent predictor of poor neurodevelopmental outcome. Postoperative peak lactate was an independent predictor of poor outcome assessed by the Pediatric Stroke Outcome Measure and Glasgow Outcome Scale Extended. Conclusions: Our study reveals that evidence of new stroke on magnetic resonance imaging after infant congenital heart surgery is a predictor of poor neurodevelopmental outcomes in early childhood. Postoperative lactic acidosis is associated with poor neurodevelopmental outcome and may be a surrogate biomarker for ischemic brain injury.

Prospective Evaluation of High Titer Autoantibodies and Fetal Home Monitoring in the Detection of Atrioventricular Block Among Anti-SSA/Ro Pregnancies.

OBJECTIVE: This prospective study of pregnant patients, Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), addresses the impact of anti-SSA/Ro titers and utility of ambulatory monitoring in the detection of fetal second-degree atrioventricular block (AVB). METHODS: Women with anti-SSA/Ro autoantibodies by commercial testing were stratified into high and low anti-52-kD and/or 60-kD SSA/Ro titers applying at-risk thresholds defined by previous evaluation of AVB pregnancies. The high-titer group performed fetal heart rate and rhythm monitoring (FHRM) thrice daily and weekly/biweekly echocardiography from 17-26 weeks. Abnormal FHRM prompted urgent echocardiography to identify AVB. RESULTS: Anti-52-kD and/or 60-kD SSA/Ro met thresholds for monitoring in 261 of 413 participants (63%); for those, AVB frequency was 3.8%. No cases occurred with low titers. The incidence of AVB increased with higher levels, reaching 7.7% for those in the top quartile for anti-60-kD SSA/Ro, which increased to 27.3% in those with a previous child who had AVB. Based on levels from 15 participants with paired samples from both an AVB and a non-AVB pregnancy, healthy pregnancies were not explained by decreased titers. FHRM was considered abnormal in 45 of 30,920 recordings, 10 confirmed AVB by urgent echocardiogram, 7 being second-degree AVB, all <12 hours from normal FHRM and within another 0.75 to 4 hours to echocardiogram. The one participant with second/third-degree and two participants with third-degree AVB were diagnosed by urgent echocardiogram >17 to 72 hours from an FHRM. Surveillance echocardiograms detected no AVB when the preceding interval FHRM recordings were normal. CONCLUSION: High-titer antibodies are associated with an increased incidence of AVB. Anti-SSA/Ro titers remain stable over time and do not explain the discordant recurrence rates, suggesting that other factors are required. Fetal heart rate and rhythm (FHRM) with results confirmed by a pediatric cardiologist reliably detects conduction abnormalities, which may reduce the need for serial echocardiograms.

Narrowing Down the Symptomatology of Isolated Vascular Rings in Children.

Vascular rings may cause respiratory or gastrointestinal symptoms due to compression of the trachea and/or esophagus. Advances in imaging have enabled early detection in asymptomatic patients posing new management dilemmas. Surgery is expected to relieve symptoms, although this has not been well studied. We sought to evaluate the presence and pattern of symptoms associated with vascular rings before surgical intervention and to detail symptom resolution after surgery. A 10-year retrospective review of patients diagnosed with an isolated vascular ring was performed between January 2010 and December 2019. 100 patients were identified; 35 double aortic arch (DAA) and 65 right aortic arch and left ligamentum arteriosum (RALL). 73 patients were symptomatic on presentation; 47 had respiratory, 5 had gastrointestinal, and 21 had both types of symptoms. Surgical repair was performed in 75 patients; 74 were symptomatic. Respiratory symptoms were more likely in patients with preoperative tracheal narrowing (p < 0.001). Moderate-severe respiratory symptoms led to surgery in RALL patients (OR 10.6, p = 0.0001). DAA patients were more likely to undergo surgery (p < 0.001) irrespective of symptom severity. At a median post-surgical follow-up of 4 months, there was a significant reduction in symptom burden (p < 0.001), except for asthma symptoms (p = 0.131). Symptom resolution was not dependent on the vascular ring anatomy (p = 0.331) or the age at operation (p = 0.158). Vascular rings are typically accompanied by respiratory symptoms and less commonly GI symptoms, both of which resolve in most patients after surgery. Those who present predominantly with asthma-like symptoms may not achieve resolution after surgery.

Magnetic Resonance Spectroscopy of Brain Metabolism in Fetuses With Congenital Heart Disease.

BACKGROUND: Congenital heart disease (CHD) remains a significant risk factor for neurologic injury because altered fetal hemodynamics may be unable to support typical brain development during critical periods of growth and maturation. OBJECTIVES: The primary objective was to assess differences in the cerebral biochemical profile between healthy fetuses and fetuses with complex CHD and to relate these with infant outcomes. METHODS: Pregnant participants underwent fetal magnetic resonance imaging with cerebral proton magnetic resonance spectroscopy acquisitions as part of a prospective observational study. Cerebral metabolites of N-acetyl aspartate, creatine, choline, myo-inositol, scyllo-inositol, lactate, and relevant ratios were quantified using LCModel. RESULTS: We acquired 503 proton magnetic resonance spectroscopy images (controls = 333; CHD = 170) from 333 participants (controls = 221; CHD = 112). Mean choline levels were higher in CHD compared with controls (CHD 2.47 IU [Institutional Units] ± 0.44 and Controls 2.35 IU ± 0.45; P = 0.02), whereas N-acetyl aspartate:choline ratios were lower among CHD fetuses compared with controls (CHD 1.34 ± 0.40 IU vs controls 1.44 ± 0.48 IU; P = 0.001). Cerebral lactate was detected in all cohorts but increased in fetuses with transposition of the great arteries and single-ventricle CHD (median: 1.63 [IQR: 0.56-3.27] in transposition of the great arteries and median: 1.28 [IQR: 0-2.42] in single-ventricle CHD) compared with 2-ventricle CHD (median: 0.79 [IQR: 0-1.45]). Cerebral lactate also was associated with increased odds of death before discharge (OR: 1.75; P = 0.04). CONCLUSIONS: CHD is associated with altered cerebral metabolites in utero, particularly in the third trimester period of pregnancy, which is characterized by exponential brain growth and maturation, and is associated with survival to hospital discharge. The long-term neurodevelopmental consequences of these findings warrant further study.

The Role of the Neonatologist in Fetuses Diagnosed with Congenital Heart Disease.

Prenatal diagnosis of congenital heart disease (CHD) can decrease preoperative morbidity and mortality. Delivery room planning can improve cardiac hemodynamics and time to critical catheter and surgical interventions. Care algorithms have defined lesion-specific level-of-care assignments and delivery room action plans that can facilitate team-based approaches to safe deliveries. Neonatologists play critical roles in the care of fetuses diagnosed with CHD, from the time of diagnosis through the postnatal intensive care unit (ICU) stays. Prenatally, neonatologists are members of the multidisciplinary counseling teams, with expertise to counsel expectant parents about what to expect during the ICU stay, which is especially valuable in CHD associated with extracardiac or genetic anomalies. Neonatologists' role in delivery planning includes identification of the optimal delivery location and allocation of appropriate personnel and resources. After delivery, postnatal care considerations include hemodynamic stability, optimization of end-organ function, genetics consultation, developmentally appropriate care practices to encourage caregiver bonding, and optimization of care to improve neurodevelopmental outcomes of neonates with CHD.

The current state and potential innovation of fetal cardiac MRI.

Fetal cardiac MRI is a rapidly evolving form of diagnostic testing with utility as a complementary imaging modality for the diagnosis of congenital heart disease and assessment of the fetal cardiovascular system. Previous technical limitations without cardiac gating for the fetal heart rate has been overcome with recent technology. There is potential utility of fetal electrocardiography for direct cardiac gating. In addition to anatomic assessment, innovative technology has allowed for assessment of blood flow, 3D datasets, and 4D flow, providing important insight into fetal cardiovascular physiology. Despite remaining technical barriers, with increased use of fCMR worldwide, it will become an important clinical tool to improve the prenatal care of fetuses with CHD.

Congenitally Corrected Transposition of the Great Arteries: Fetal Diagnosis, Associations, and Postnatal Outcome: A Fetal Heart Society Research Collaborative Study.

Background Fetal diagnosis of congenitally corrected transposition of the great arteries (ccTGA) has been increasingly reported; however, predictors of clinical outcomes remain underexplored. We undertook a multicenter, retrospective study to investigate natural history, associated anomalies, and outcomes of fetal ccTGA. Methods and Results Fetuses with ccTGA diagnosed from January 2004 to July 2020 within 20 North American programs were included. Fetuses with severe ventricular hypoplasia thought to definitively preclude biventricular repair were excluded. We included 205 fetuses diagnosed with ccTGA at a median gestational age of 23 (interquartile range, 21-27) weeks. Genetic abnormalities were found in 5.9% tested, with extracardiac anomalies in 6.3%. Associated cardiac defects were diagnosed in 161 (78.5%), with atrioventricular block in 23 (11.3%). On serial fetal echocardiogram, 39% demonstrated a functional or anatomic change, most commonly increased tricuspid regurgitation (6.7%) or pulmonary outflow obstruction (11.1%). Of 194 fetuses with follow-up, 26 were terminated, 3 experienced fetal death (2 with atrioventricular block), and 165 were live-born. Of 158 with postnatal data (median follow-up 3.7 years), 10 (6.6%) had death/transplant before 1 year. On univariable analysis, fetal factors associated with fetal death or death/transplant by 1 year included ≥ mild tricuspid regurgitation, pulmonary atresia, aortic obstruction, fetal arrhythmia, and worsening hemodynamics on serial fetal echocardiogram (defined as worse right ventricular function, tricuspid regurgitation, or effusion). Conclusions Associated cardiac lesions and arrhythmias are common in fetal ccTGA, and functional changes commonly occur through gestation. Worse outcomes are associated with fetal tricuspid regurgitation (≥mild), any arrhythmia, pulmonary atresia, aortic obstruction, and worsening hemodynamics on serial echocardiograms. These findings can inform prenatal counseling and perinatal management planning.

Fetal Echocardiographic Z Score Pilot Project: Study Design and Impact of Gestational Age and Variable Type on Reproducibility of Measurements Within and Across Investigators.

BACKGROUND: Fetal echocardiography is widely available, but normative data are not robust. In this pilot study, the authors evaluated (1) the feasibility of prespecified measurements in a normal fetal echocardiogram to inform study design and (2) measurement variability to assign thresholds of clinical significance and guide analyses in larger fetal echocardiographic Z score initiatives. METHODS: Images from predefined gestational age groups (16-20, >20-24, >24-28, and >28-32 weeks) were retrospectively analyzed. Fetal echocardiography expert raters attended online group training and then independently analyzed 73 fetal studies (18 per age group) in a fully crossed design of 53 variables; each observer repeated measures for 12 fetuses. Kruskal-Wallis tests were used to compare measurements across centers and age groups. Coefficients of variation (CoVs) were calculated at the subject level for each measurement as the ratio of SD to mean. Intraclass correlation coefficients were used to show inter- and intrarater reliabilities. Cohen's d > 0.8 was used to define clinically important differences. Measurements were plotted against gestational age, biparietal diameter, and femur length. RESULTS: Expert raters completed each set of measurements in a mean of 23 ± 9 min/fetus. Missingness ranged from 0% to 29%. CoVs were similar across age groups for all variables (P < .05) except ductus arteriosus mean velocity and left ventricular ejection time, which were both higher at older gestational age. CoVs were >15% for right ventricular systolic and diastolic widths despite fair to good repeatability (intraclass correlation coefficient > 0.5); ductal velocities and two-dimensional measures, left ventricular short-axis dimensions, and isovolumic times all had high CoVs and high interobserver variability despite good to excellent intraobserver agreement (intraclass correlation coefficient > 0.6). CoVs did not improve when ratios (e.g., tricuspid/mitral annulus) were used instead of linear measurements. Overall, 27 variables had acceptable inter- and intraobserver repeatability, while 14 had excessive variability between readers despite good intraobserver agreement. CONCLUSIONS: There is considerable variability in fetal echocardiographic quantification in clinical practice that may affect the design of multicenter fetal echocardiographic Z score studies, and not all measurements may be feasible for standard normalization. As missingness was substantial, a prospective design will be needed. Data from this pilot study may aid in the calculation of sample sizes and inform thresholds for distinguishing clinically significant from statistically significant effects.

Utility of Fetal Echocardiography with Acute Maternal Hyperoxygenation Testing in Assessment of Complex Congenital Heart Defects.

Fetal echocardiography is an excellent tool for accurately assessing the anatomy and physiology of most congenital heart defects (CHDs). Knowledge gathered from a thorough initial fetal echocardiogram and serial assessment assists with appropriate perinatal care planning, resulting in improved postnatal outcomes. However, fetal echocardiography alone provides limited information about the status of the pulmonary vasculature, which can be abnormal in certain complex CHDs with obstructed pulmonary venous flow (hypoplastic left heart syndrome with restrictive atrial septum) or excessive pulmonary artery flow (d-transposition of the great arteries, usually with a restrictive ductus arteriosus). Fetuses with these CHDs are at high risk of developing severe hemodynamic instability with the immediate transition from prenatal to postnatal circulatory physiology at the time of birth. Adjunctive use of acute maternal hyperoxygenation (MH) testing in such cases can help determine pulmonary vascular reactivity in prenatal life and better predict the likelihood of postnatal compromise and the need for emergent intervention. This comprehensive review discusses the findings of studies describing acute MH testing in a diverse spectrum of CHDs and congenital diagnoses with pulmonary hypoplasia. We review historical perspectives, safety profile, commonly used clinical protocols, limitations, and future directions of acute MH testing. We also provide practical tips on setting up MH testing in a fetal echocardiography laboratory.

[Formula: see text] Trajectories of neurodevelopment and opportunities for intervention across the lifespan in congenital heart disease.

Children with congenital heart disease (CHD) are at increased risk for neurodevelopmental challenges across the lifespan. These are associated with neurological changes and potential acquired brain injury, which occur across a developmental trajectory and which are influenced by an array of medical, sociodemographic, environmental, and personal factors. These alterations to brain development lead to an array of adverse neurodevelopmental outcomes, which impact a characteristic set of skills over the course of development. The current paper reviews existing knowledge of aberrant brain development and brain injury alongside associated neurodevelopmental challenges across the lifespan. These provide a framework for discussion of emerging and potential interventions to improve neurodevelopmental outcomes at each developmental stage.

Predicting Cardiac Anatomy, Physiology, and Surgical Management Based on Fetal Echocardiography in Heterotaxy Syndrome.

OBJECTIVE: Heterotaxy syndrome (HS) is often associated with complex congenital heart disease (CHD). While fetal echocardiography (FE) permits accurate prenatal identification of most CHD, the high level of disease complexity in HS may pose challenges in predicting postnatal findings and outcomes. This study aimed to define the accuracy of FE in predicting postnatal anatomy, physiology, and surgical management of CHD in the setting of HS. STUDY DESIGN: Retrospective single-center cohort study including all patients with a prenatal diagnosis of HS from 2003 to 2018. Anatomic diagnoses from FE reports were compared with postnatal echocardiogram, catheterization, and operative reports. Prenatal predictions were compared with postnatal outcomes with a focus on ductal dependence, time to first intervention (immediate, neonatal period, 1-6 months, or older than 6 months), and surgical approach (single or biventricular). RESULTS: There were 102 pregnancies with fetal HS resulting in 21 terminations, 5 fetal losses, and 76 live births. Of the live births, 55 had significant CHD and available postnatal data for review. Among this group, survival to 1 year was 62% and was no different comparing single versus biventricular surgical approach. FE diagnostic accuracy varied by anatomic feature and was the lowest for diagnosis of venous anatomy. Determination of postnatal care was most accurate for predicting single versus biventricular surgical approach (91%), followed by ductal dependence (75%). Accuracy for predicting time to first intervention was the lowest at 69%. The most common reason for an incorrect prediction was difficulty in assessing the severity of pulmonary stenosis. CONCLUSION: FE permits accurate predictions regarding surgical approach. Characterizing systemic and pulmonary veins is challenging, as is predicting ductal dependence and time to first intervention. These data suggest that despite the high diagnostic accuracy of CHD in HS, a circumspect approach may be reasonable with regard to predicting some anatomic details and postnatal management decisions. KEY POINTS: · In HS, FE was most accurate for intracardiac anatomy.. · Diagnostic accuracy of venous anatomy was less reliable.. · Predicting surgical approach (single ventricle vs. biventricular) was highly accurate.. · Predicting ductal dependence and time-to-intervention were more challenging in some instances..

Prevalence of neurodevelopmental disorders in a clinically referred sample of children with CHD.

Youth with CHD are at greater risk for neurodevelopmental disorders compared to healthy controls. The aetiology is multi-factorial but includes medical and demographic factors. We sought to characterise the prevalence of neurodevelopmental disorders in patients with CHD. Our population included 206 patients with CHD, aged 3-21, who were referred for neuropsychological evaluation. Neurodevelopmental diagnoses were determined by a licensed psychologist. Rates of neurodevelopmental diagnoses were compared to national prevalence rates. Exploratory analyses (chi-square) examined which medical factors (i.e., cardiac diagnosis, genetic condition, prematurity, seizures, and stroke) were associated with neurodevelopmental diagnosis. There was higher prevalence of neurodevelopmental disorders in CHD when compared to the general population (44%). Rates of attention-deficit/hyperactivity disorder (27.3%), autism spectrum disorder (9.6%), and intellectual disability (5.9%) were notably higher than those seen in the general population (p < .01). Children with a history of aortic obstruction were more likely to be diagnosed with autism (p < .05), and children with genetic conditions were more likely to be diagnosed with an intellectual disability (p < .05). Neurodevelopmental diagnoses were not significantly associated with any other specific medical variables (e.g., cardiac diagnosis, seizures, stroke, prematurity, and antenatal diagnosis). School-aged children were more likely to be diagnosed with any neurodevelopmental disorder and attention-deficit/hyperactivity disorder (31.7%; p < .01) than preschool-age children. In summary, our results confirm that children and adolescents with CHD are at high risk for neurodevelopmental disorders and require ongoing monitoring, care, and support. Children with genetic disorders and those with aortic obstruction may be more at risk for certain neurodevelopmental disorders.

Care of the Fetus With Congenital Cardiovascular Disease: From Diagnosis to Delivery.

BACKGROUND: The majority of congenital cardiovascular disease including structural cardiac defects, abnormalities in cardiac function, and rhythm disturbances can be identified prenatally using screening obstetrical ultrasound with referral for fetal echocardiogram when indicated. METHODS: Diagnosis of congenital heart disease in the fetus should prompt assessment for extracardiac abnormalities and associated genetic abnormalities once maternal consent is obtained. Pediatric cardiologists, in conjunction with maternal-fetal medicine, neonatology, and cardiothoracic surgery subspecialists, should counsel families about the details of the congenital heart defect as well as prenatal and postnatal management. RESULTS: Prenatal diagnosis often leads to increased maternal depression and anxiety; however, it decreases morbidity and mortality for many congenital heart defects by allowing clinicians the opportunity to optimize prenatal care and plan delivery based on the specific lesion. Changes in prenatal care can include more frequent assessments through the remainder of the pregnancy, maternal medication administration, or, in selected cases, in utero cardiac catheter intervention or surgical procedures to optimize postnatal outcomes. Delivery planning may include changing the location, timing or mode of delivery to ensure that the neonate is delivered in the most appropriate hospital setting with the required level of hospital staff for immediate postnatal stabilization. CONCLUSIONS: Based on the specific congenital heart defect, prenatal echocardiogram assessment in late gestation can often aid in predicting the severity of postnatal instability and guide the medical or interventional level of care needed for immediate postnatal intervention to optimize the transition to postnatal circulation.