Human Genetics of d-Transposition of Great Arteries.

Although several genes underlying occurrence of transposition of the great arteries have been found in the mouse, human genetics of the most frequent cyanotic congenital heart defect diagnosed in neonates is still largely unknown. Development of the outflow tract is a complex process which involves the major genes of cardiac development, acting on myocardial cells from the anterior second heart field, and on mesenchymal cells from endocardial cushions. These genes, coding for transcription factors, interact with each other, and their differential expression conditions the severity of the phenotype. A precise description of the anatomic phenotypes is mandatory to achieve a better comprehension of the complex mechanisms responsible for transposition of the great arteries.

Risk Factors for Perioperative Brain Lesions in Infants With Congenital Heart Disease: A European Collaboration.

BACKGROUND: Infants with congenital heart disease are at risk of brain injury and impaired neurodevelopment. The aim was to investigate risk factors for perioperative brain lesions in infants with congenital heart disease. METHODS: Infants with transposition of the great arteries, single ventricle physiology, and left ventricular outflow tract and/or aortic arch obstruction undergoing cardiac surgery <6 weeks after birth from 3 European cohorts (Utrecht, Zurich, and London) were combined. Brain lesions were scored on preoperative (transposition of the great arteries N=104; single ventricle physiology N=35; and left ventricular outflow tract and/or aortic arch obstruction N=41) and postoperative (transposition of the great arteries N=88; single ventricle physiology N=28; and left ventricular outflow tract and/or aortic arch obstruction N=30) magnetic resonance imaging for risk factor analysis of arterial ischemic stroke, cerebral sinus venous thrombosis, and white matter injury. RESULTS: Preoperatively, induced vaginal delivery (odds ratio [OR], 2.23 [95% CI, 1.06-4.70]) was associated with white matter injury and balloon atrial septostomy increased the risk of white matter injury (OR, 2.51 [95% CI, 1.23-5.20]) and arterial ischemic stroke (OR, 4.49 [95% CI, 1.20-21.49]). Postoperatively, younger postnatal age at surgery (OR, 1.18 [95% CI, 1.05-1.33]) and selective cerebral perfusion, particularly at ≤20 °C (OR, 13.46 [95% CI, 3.58-67.10]), were associated with new arterial ischemic stroke. Single ventricle physiology was associated with new white matter injury (OR, 2.88 [95% CI, 1.20-6.95]) and transposition of the great arteries with new cerebral sinus venous thrombosis (OR, 13.47 [95% CI, 2.28-95.66]). Delayed sternal closure (OR, 3.47 [95% CI, 1.08-13.06]) and lower intraoperative temperatures (OR, 1.22 [95% CI, 1.07-1.36]) also increased the risk of new cerebral sinus venous thrombosis. CONCLUSIONS: Delivery planning and surgery timing may be modifiable risk factors that allow personalized treatment to minimize the risk of perioperative brain injury in severe congenital heart disease. Further research is needed to optimize cerebral perfusion techniques for neonatal surgery and to confirm the relationship between cerebral sinus venous thrombosis and perioperative risk factors.

Parietal bone agenesis and athelia in retinoic acid embryopathy: An expansion of the phenotype.

BACKGROUND: Retinoic acid signaling plays a critical role during embryogenesis and requires tight regulation. Exposure to exogenous retinoic acid during fetal development is known to have teratogenic effects, producing a recognizable embryopathy. CASE: We describe a case of retinoic acid embryopathy secondary to maternal isotretinoin use until the ninth week of gestation and expand the phenotype to include the rare features of parietal bone agenesis and athelia. Histology of the parietal region showed fibrous tissue with no intramembranous ossification. The fetus also had multiple craniofacial dysmorphisms, thymic agenesis, and transposition of the great arteries with double outlet right ventricle and subaortic perimembranous ventricular septal defect. Neuropathology revealed enlarged ventricles with agenesis of the cerebellar vermis, focal duplication of the central canal and scattered parenchymal ependymal rests, and possible cerebral heterotopias with associated abnormal neuronal lamination. A chromosomal microarray was normal. CONCLUSION: Parietal bone agenesis and athelia are both rare congenital anomalies not previously reported in retinoic acid embryopathy. However, retinoic acid or its degrading enzyme has been demonstrated to exert effects in both of these developmental pathways, offering biological plausibility. We propose that this case may represent an expansion of the phenotype of retinoic embryopathy.

Modeling Transposition of the Great Arteries with Patient-Specific Induced Pluripotent Stem Cells.

The dextro-transposition of the great arteries (d-TGA) is one of the most common congenital heart diseases. To identify biological processes that could be related to the development of d-TGA, we established induced pluripotent stem cell (iPSC) lines from two patients with d-TGA and from two healthy subjects (as controls) and differentiated them into endothelial cells (iPSC-ECs). iPSC-EC transcriptome profiling and bioinformatics analysis revealed differences in the expression level of genes involved in circulatory system and animal organ development. iPSC-ECs from patients with d-TGA showed impaired ability to develop tubular structures in an in vitro capillary-like tube formation assay, and interactome studies revealed downregulation of biological processes related to Notch signaling, circulatory system development and angiogenesis, pointing to alterations in vascular structure development. Our study provides an iPSC-based cellular model to investigate the etiology of d-TGA.

Regional Brain Growth Trajectories in Fetuses with Congenital Heart Disease.

OBJECTIVE: Congenital heart disease (CHD) is associated with abnormal brain development in utero. We applied innovative fetal magnetic resonance imaging (MRI) techniques to determine whether reduced fetal cerebral substrate delivery impacts the brain globally, or in a region-specific pattern. Our novel design included two control groups, one with and the other without a family history of CHD, to explore the contribution of shared genes and/or fetal environment to brain development. METHODS: From 2014 to 2018, we enrolled 179 pregnant women into 4 groups: "HLHS/TGA" fetuses with hypoplastic left heart syndrome (HLHS) or transposition of the great arteries (TGA), diagnoses with lowest fetal cerebral substrate delivery; "CHD-other," with other CHD diagnoses; "CHD-related," healthy with a CHD family history; and "optimal control," healthy without a family history. Two MRIs were obtained between 18 and 40 weeks gestation. Random effect regression models assessed group differences in brain volumes and relationships to hemodynamic variables. RESULTS: HLHS/TGA (n = 24), CHD-other (50), and CHD-related (34) groups each had generally smaller brain volumes than the optimal controls (71). Compared with CHD-related, the HLHS/TGA group had smaller subplate (-13.3% [standard error = 4.3%], p < 0.01) and intermediate (-13.7% [4.3%], p < 0.01) zones, with a similar trend in ventricular zone (-7.1% [1.9%], p = 0.07). These volumetric reductions were associated with lower cerebral substrate delivery. INTERPRETATION: Fetuses with CHD, especially those with lowest cerebral substrate delivery, show a region-specific pattern of small brain volumes and impaired brain growth before 32 weeks gestation. The brains of fetuses with CHD were more similar to those of CHD-related than optimal controls, suggesting genetic or environmental factors also contribute. ANN NEUROL 2021;89:143-157.

Abnormalities of placental development and function are associated with the different fetal growth patterns of hypoplastic left heart syndrome and transposition of the great arteries.

BACKGROUND: Birthweight is a critical predictor of congenital heart disease (CHD) surgical outcomes. Hypoplastic left heart syndrome (HLHS) is cyanotic CHD with known fetal growth restriction and placental abnormalities. Transposition of the great arteries (TGA) is cyanotic CHD with normal fetal growth. Comparison of the placenta in these diagnoses may provide insights on the fetal growth abnormality of CHD. METHODS: Clinical data and placental histology from placentas associated with Transposition of the Great Arteries (TGA) were analyzed for gross pathology, morphology, maturity and vascularity and compared to both control and previously analyzed HLHS placentas [1]. RNA was isolated from HLHS, TGA and control placentas and sequenced by Illumina HiSeq.Transcriptome analysis was performed using AltAnalyze. Immunohistochemistry was utilized to assess placental nutrient transporter expression in all three groups. RESULTS: Placental weight was reduced in TGA cases, and demonstrated reduced villous vasculature, immature terminal villi in the parenchyma compared to controls and reflected our previous data from HLHS placentas. However, birth weight was not reduced in TGA cases compared to controls in contrast to the HLHS cohort and birthweight:placental weight ratio was significantly increased in TGA cases but not HLHS compared to control. Transcriptomic and histologic analysis demonstrates reduced cell activity and nutrient transport capability in HLHS but not TGA placentas which appear to increase/maintain these mechanisms. CONCLUSIONS: Despite common vascular disturbances in placentas from HLHAs and TGA, these do not account for the disparities in birthweights frequently seen between these CHD subtypes, in contrast our transcriptomic and histologic analyses reveal differentially regulated mechanisms between the subtypes that may explain these disparities.

Congenitally Corrected Transposition of the Great Arteries: Anatomic, Physiologic Repair, and Palliation.

Congenitally corrected transposition of the great arteries (ccTGA) is a lesion that rarely occurs in isolation. The presenting physiology of ccTGA is predominantly secondary to the concurrent cardiac lesions; however, as the child ages, unrepaired ccTGA results in progressive failure of the morphologic right ventricle under the strain of maintaining a systemic pressure. Repair of ccTGA was initially focused on rectification of the underlying physiologic aberrations, but in recent years, the focus of repair has shifted toward anatomic correction to avoid failure of the morphologic right ventricle. This anatomic repair is commonly associated with improved long-term mortality at the cost of increased short-term mortality. Key preoperative considerations such as morphologic left ventricular pressure, tricuspid valve competency, and out flow tract obstructions can assist in determining the optimal repair for individual patients. An alternative, single ventricle, pathway has been proposed for any patient without optimal preoperative anatomy to improve long-term survival. Adjunctive repair options including pulmonary artery banding and one-and-a-half ventricle repairs have also been proposed to augment the survival curves.

Anatomically corrected malposition of the great arteries: a challenging fetal diagnosis.

Anatomically corrected malposed great arteries are uncommon and benign entity. Basically, this occurs with ventriculoarterial concordance in which the great vessels arise parallel instead of a twisting fashion. In this manuscript, we described two cases in which the antenatal diagnosis of anatomically corrected malposition of great arteries was suspected and confirmed during the postnatal period. During the fetal life, this diagnosis remains a challenge and this condition is often misdiagnosed as the transposition of the great arteries (TGA). Differently to TGA, anatomically corrected malposition of the great arteries may not require any cardiac surgical intervention depending on the associated cardiac anomalies. Indeed, postnatal examination for concerns related to anomalies that can be associated with this condition, such as anomalous origins of coronary arteries and left ventricular outflow tract obstruction, should be performed.

Complex Congenital Heart Malformation Including Transposition of the Great Vessels, Presenting as Sudden Unexplained Infant Death.

Transposition of the great vessels (TGV) is a common congenital heart defect that is difficult to diagnose before birth. Antenatal diagnosis is associated with increased survival. Unusual features such as anomalous pulmonary artery origin may delay cyanosis, decreasing clinical suspicion. A three-week old female infant who had never been cyanotic presented for forensic autopsy due to onset of unresponsiveness at home. History included risk factors for TGV and signs of heart enlargement that were not recognized during life. Cardiac pathology consultation identified D-type TGV with additional rare anomalies. TGV may present as sudden unexplained infant death (SUID) for forensic autopsy if variant features prevent development of cyanosis. Cardiac pathology consultation is helpful in clarifying these features.

Aortopulmonary window with pumonary atresia with ventricular septal defect with D-transposition of great arteries: extremely rare anomaly.

Aortopulmonary window (APW) is rare a congenital heart disease accounting for 0.1%-0.2% of all congenital heart defects. The 35% of the APW has been associated with wide variety of other structural heart diseases such as ventricular septal defect, persistent ductus arteriosus, arch anomalies and coronary artery anomalies. To the best of our knowledge, only six cases of APW with pulmonary atresia with ventricular septal defect has been described in the literature. It resembles the type 1 truncus arteriosus, and differentiation from this condition is important prior to surgical correction. We present a case of 14-year-old girl child; she was diagnosed with APW with pulmonary atresia with ventricular septal defect and D transposition of great arteries with the help of echocardiography, cardiac catheterisation and cardiac CT.

Inter- and intra-ventricular dyssynchrony in the systemic right ventricle is a surrogate marker of major cardiac events in mildly symptomatic patients.

The aim of the study was to evaluate systemic right ventricular (RV) dyssynchrony in patients with congenitally corrected transposition of the great arteries (CCTGA) and transposition of the great arteries (TGA) with New York Heart Association functional class (NYHA FC) < III. We used cardiac magnetic resonance (CMR) to evaluate the dyssynchrony and assessed whether RV dyssynchrony can be predictive of major cardiac events in their early stages in these patients. We enrolled 71 consecutive, NYHA FC < III patients with systemic RV who underwent CMR between April 1995 and December 2016. We measured intra- and inter-ventricular dyssynchrony using a feature-tracking method of cine magnetic resonance imaging. The predictors of major cardiac events were analyzed using the Cox hazard analysis. The data from 36 patients with CCTGA and 35 patients with TGA after an atrial switch were analyzed. Seven (19.4%) patients with CCTGA and 6 (17.1%) patients with TGA showed a QRS duration of ≥ 130 ms. There were significant intra- and inter-dyssynchrony in the systemic RV groups, compared to healthy controls. The average follow-up period was 5.1 ± 3.9 years. From among patients with CCTGA, 9 (25.0%) had major cardiac events. The parameters including NYHA FC, indexed RV volume, longitudinal early diastolic strain rate, and intra- and inter-ventricular dyssynchrony were predictive of major cardiac events. From among patients with TGA, 12 (34.3%) had major cardiac events. Age, NYHA FC, QRS duration, RV volume, RV mass index, LV volume, global longitudinal/circumferential strain and intraventricular dyssynchrony, were all predictive of major cardiac events. Systemic RV in NYHA FC < III patients with CCTGA and TGA, have obvious intra- and inter-dyssynchrony, suggesting ineffective wall motion and potential RV dysfunction. Intraventricular dyssynchrony can be an adjunct predictor of major cardiac events in mildly symptomatic patients with both CCTGA and TGA.

Decreased oxygen saturation levels in neonates with transposition of great arteries: Impact on appearance of cerebral veins in susceptibility-weighted imaging.

Purpose of this study was to investigate a potential correlation between the pattern of cerebral veins (CV) on susceptibility-weighted imaging (SWI) and blood oxygen saturation, as well as preoperative brain injury, in neonates with transposition of the great arteries (TGA). Eleven neonates with TGA underwent MRI preoperatively, including SWI, T1- and T2-weighted scans. Images were retrospectively evaluated and appearance of CV was graded from 0 (normal appearance) to 3 (severe prominent appearance). White matter injuries (WMI) and strokes were analysed. Results were correlated with preductal arterial oxygen saturation. As findings one subject showed a normal CV appearance (grade 0) whereas 10 showed pathological prominent CV (grades 1-3); median 2. Mean oxygen saturation ranged between 67.5% and 89.0% (median 81.0%). CV grade and mean oxygen saturation correlated significantly (p = 0.011). WMI were absent in 5 cases, mild in 4, and moderate in 2 cases. We conclude, that SWI has the potential to be used to estimate the current hypoxic burden on brain tissue in TGA newborns by assessing the prominence of the CV.

Collagen turnover biomarkers and systemic right ventricle remodeling in adults with previous atrial switch procedure for transposition of the great arteries.

BACKGROUND: Myocardial fibrosis is a potential pathophysiological mechanism leading to systemic right ventricular (SRV) deterioration. We hypothesize that circulating levels of collagen deposition markers are elevated in patients with SRV remodeling and this elevation may have a predictive value. METHODS: We prospectively evaluated 56 patients with D-TGA after the atrial switch procedure (mean age 25.6 ± 4.8, range 18-37 years; 67% males). Serum levels of procollagen type III amino-terminal propeptide (PIIINP), collagen type I carboxy-terminal telopeptide (CITP), procollagen type I N-terminal propeptide (PINP), matrix metalloproteinase (MMP 1, MMP 9) and a tissue inhibitor of matrix metalloproteinase (TIMP 1) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) were measured and compared with healthy controls. The relationship between these serum markers, echocardiographic and cardiac magnetic resonance parameters and the outcome at a follow-up of 61 months (range, 24-85 months) was determined. RESULTS: Compared with the healthy control group, the study group had significantly higher levels of TIMP1, PIIINP, CITP, PINP and NT-pro-BNP (p<0.05, each). The levels of PIIINP and CITP were significantly higher among patients with an SRV mass index above the mean value. The level of PIIINP was significantly higher among patients with an SRV EDV index above the mean value. CITP was significantly elevated in SRV late gadolinium enhanced (LGE) positive patients, compared to patients without SRV LGE. MMP9 and TIMP1 predicted an adverse clinical outcome on univariate Cox proportional hazard survival analysis in addition to well proven predictors of outcome (SRV EF and NYHA). CONCLUSIONS: We demonstrated a pattern of altered collagen turnover adversely related with the indices of SRV remodeling and an adverse clinical outcome in patients with SRV.

Costs, mortality, and hospital usage in relation to prenatal diagnosis in d-transposition of the great arteries.

BACKGROUND: The impact of prenatal diagnosis of d-transposition of the great arteries (dTGA) on health-care usage is largely unknown. We evaluated a population-based cohort to assess costs, mortality and inpatient encounters by whether dTGA was prenatally diagnosed or not. METHODS: The dTGA cases (born 1997-2011) identified at the Utah Birth Defect Network, which includes data on timing of diagnosis, were linked to statewide inpatient discharge data. We excluded preterm cases or cases with additional major heart defects. We evaluated hospitalizations and costs for infants (first year of life) and mothers (10 months before birth) using multivariable models adjusted for demographic and clinical risk factors. RESULTS: Of 119 cases, 14 (12%) were prenatally diagnosed. Birth weight, surgical complexity and extracardiac defects/syndromes were similar between groups. Of 7 deaths (6%), two occurred pre-intervention in postnatally diagnosed infants. Prenatal diagnosis was associated with more in-hospital days (estimate 13 additional days, p = 0.03) and higher mean costs for mothers ($4,141 vs $12,148) and infants (90,419 vs $49,576). Prenatal diagnosis independently predicted higher adjusted costs for the overall cohort ($22,570, p = 0.045). After excluding deaths, total costs were no longer significantly different. CONCLUSION: Mothers of prenatally diagnosed infants with dTGA had higher inpatient costs compared with those postnatally diagnosed. Costs trended higher for their infants, although were not significantly different. Linkage of population-based surveillance systems and outcome databases can be a powerful tool to further explore the complex relationship of prenatal diagnosis to costs and outcomes in other types of congenital heart diseases. Birth Defects Research 109:262-270, 2017. © 2017 Wiley Periodicals, Inc.

Five-year experience with immediate extubation after arterial switch operations for transposition of great arteries.

Objectives: We sought to identify preoperative, intraoperative and anatomical factors associated with immediate extubation (IE) after arterial switch operation for d-transposition of great arteries (dTGA). Methods: This was a single-centre retrospective study performed from 1 January 2010 to 30 June 2015. IE was defined as successful extubation in the operating room (OR). Univariate/bivariate regression of preoperative, intraoperative and anatomical variables was used to determine associations with IE. Results: Of 32 patients in the dTGA spectrum (age at operation 6 days), 18 (56%) underwent IE. Twelve (71%) of the 17 patients with an intact ventricular septum and 6 (43%) of the 14 patients with ventricular septal defect (VSD) underwent IE, whereas none of the patients with double outlet right ventricle or aortic arch obstruction ( n = 4) did. Patients who had cardiopulmonary bypass time (CPB) >173 min ( P = 0.01), lowest temperature on CPB (T min) ≤ 30.4°C ( P = 0.04) and aortic cross-clamp time >86 min ( P = 0.04) were more likely to be left intubated at the end of the procedure. There was no significant difference in patient's chronological age, gestational age, post-conceptual age, weight, coronary anatomy or prevalence of VSD between those who did and did not undergo IE. There was a median increase in intensive care unit (ICU) length of stay (LOS) by 1 day (33%, P = 0.03) and ICU costs by $12 338 (15%, P = 0.06) in non-IE patients. The OR turnover time ( P = 0.09) and reintubation rate ( P = 1) at 24 h post-extubation did not differ between those who did and did not have IE. There was no myocardial dysfunction evident on predismissal echocardiography in either group. Conclusions: In this cohort of infants, post repair for TGA, 56% were extubated immediately in the OR. Greater CPB and cross-clamp times and T min ≤ 30.4°C were associated with a lesser likelihood of IE. IE was associated with shorter ICU length of stay.

Cognitive and attentional functioning in adolescents and young adults with Tetralogy of Fallot and d-transposition of the great arteries.

The objective of this study is to investigate cognitive and attentional function in adolescents and young adults with operated congenital heart disease. Previous research has indicated that children with congenital heart disease have deficits in broad areas of cognitive function. However, less attention has been given to survivors as they grow into adolescence and early adulthood. The participants were 18 non-syndromic adolescents and young adults with tetralogy of Fallot and d-transposition of the great arteries that required cardiac surgery before the age of 5 years, and 18 healthy, unaffected siblings (11-22 years of age for both groups). Cases with congenital heart disease and their siblings were administered Wechsler Intelligence scales and reported attention problems using the Achenbach System of Empirically Based Assessments. Cases were compared to both healthy siblings and established norms. Cases performed significantly lower than siblings on full scale IQ and processing speed, and significantly lower than norms on perceptual reasoning. Cases also reported more attention problems compared to both siblings and norms. Effect sizes varied with medium-to-large effects for processing speed, perceptual reasoning, working memory, and attention problems. Findings suggest that neurocognitive function may continue to be affected for congenital heart disease survivors in adolescence and young adulthood, and that comparisons to established norms may underestimate neurocognitive vulnerabilities.

Anatomical Classifications of the Coronary Arteries in Complete Transposition of the Great Arteries and Double Outlet Right Ventricle with Subpulmonary Ventricular Septal Defect.

Objective To discuss the anatomical morphologies of the coronary arteries and frequencies of unusual coronary arteries in complete transposition of the great arteries and double outlet right ventricle (DORV) associated with a subpulmonic ventricular septal defect (VSD). Methods Between March 1999 and August 2012, 1,078 patients with complete transposition of the great arteries or DORV with subpulmonary VSD underwent arterial switch operations (ASOs) and were visually evaluated to classify their coronary artery morphology during open heart surgery. Results The coronary arteries could be classified into five patterns with several subtypes. Unusual coronary arteries were observed in 248 of the 1,078 cases, providing a frequency of 23.01%. The frequencies of the patients with transposition of the great arteries with intact ventricular septum (TGA/IVS), TGA/VSD, and DORV with subpulmonary VSD were 17.65, 23.28, and 31.84%, respectively. The most common morphologies were the right coronary artery (RCA) originating from sinus 1 and circumflex (CX) originating from sinus 2 (1R, AD; 2CX; 26.50%); the CX originating from sinus 2 (1AD; 2R, CX; 21.36%); the RCA, left anterior descending artery, and CX originating from single sinus 2 (2R, AD, CX; 13.24%). The in-hospital mortalities of the patients with or without unusual coronary arteries after ASO were 14.1 and 6.02%, respectively. Conclusion Patients with complete transposition of the great arteries or DORV with subpulmonary VSD have a high frequency of unusual coronary arteries, which might greatly impact on the mortality for ASO. Improving the preoperative diagnostic criteria for coronary artery morphology may significantly increase the success rate for ASOs.

Twenty-five-year survival for aboriginal and caucasian children with congenital heart defects in Western Australia, 1980 to 2010.

BACKGROUND: Australian Aboriginal children have increased infant and childhood mortality compared with Caucasian children, but their mortality related to congenital heart defects (CHDs) throughout life is unknown. METHODS: We conducted a retrospective cohort study using data on 8,110 live born, singleton infants with CHDs born January 1980 to December 2010 from the Western Australian Register of Developmental Anomalies. Vital status was determined from death and medical records. Data for infants with chromosomal anomalies (except Down syndrome) were excluded. Kaplan-Meier Product-Limit estimates and 95% confidence intervals (CIs) were computed by Aboriginality. Hazard ratios (HRs) and 95% CIs were calculated from multivariable Cox-Proportional Hazard Regression models. RESULTS: Aboriginal children had lower survival than Caucasians for all CHDs combined but most notably during the neonatal period for functional single ventricle (50.0% vs. 86.1%; p = 0.015) and during the postneonatal period for tetralogy of Fallot (87.0% vs. 97.4%; p = 0.021) and atrioventricular septal defect (60.0% vs. 94.6%; p = 0.010). After adjusting for covariates except remoteness and socioeconomic status (SES), Aboriginal children with all CHDs combined (HR = 1.4; 95% CI, 1.0-1.9), with transposition of the great arteries (HR = 4.3; 95% CI, 1.0-18.9) or functional single ventricle (HR = 8.6; 95% CI, 1.3-57.9) had increased risk of mortality compared with Caucasian children. When remoteness and SES were included, the risks were not statistically significant. CONCLUSION: Long-term survival was lower for Aboriginal children with CHDs, and Aboriginal children with specific CHD phenotypes had increased risk of mortality throughout life. Increased risk may be due to SES and environmental factors. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1016-1031, 2016. © 2016 Wiley Periodicals, Inc.

Hemodynamic consequences of a restrictive ductus arteriosus and foramen ovale in fetal transposition of the great arteries.

D-transposition of the great arteries (D-TGA) is the most commonly diagnosed cyanotic congenital heart disease presenting in the neonatal period. The survival after an arterial switch operation, with freedom from adverse cardiovascular events, has been reported to be as high as 93% at 25 years. However, despite excellent surgical outcomes, there continues to be significant preoperative morbidity and potential mortality due to compromise in the delivery room from foramen ovale closure requiring urgent balloon atrial septostomy for stabilization in the first minutes of life. The prenatal diagnosis of D-TGA using fetal echocardiography has aided in the perinatal management and delivery planning of these infants, lowering preoperative morbidity and mortality and preventing delivery room compromise. Fetuses with D-TGA have more highly oxygenated blood supplying the pulmonary arteries and ductus arteriosus which likely results in ductal constriction and increased pulmonary blood flow. This may be the cause of foramen ovale restriction or closure in-utero, which then increases the risk for postnatal compromise at delivery. Theories regarding the cause of the abnormal pulmonary vasculature that may be seen in D-TGA, including aorto-pulmonary collateral formation, have been proposed but to our knowledge, observation of the ultrasound findings throughout mid and late gestation describing the progression of the abnormal fetal physiology have not been previously described. We present a case of D-TGA in which serial assessment using fetal echocardiography enabled observation of the in-utero progression of disease, predicting postnatal compromise and facilitating the planning of life-saving specialized delivery room care and intervention.