Major Congenital Heart Defects Research Articles

P06.11: The association of congenital cardiac defects with aneuploidy, extra‐cardiac defects and obstetric outcomes: a prospective study

To document detection of congenital heart defects (CHDs) in relation to (i) the indication for referral for fetal echocardiography, (ii) associated extra-cardiac anomalies, (iii) karyotypic abnormalities and (iv) obstetric and neonatal outcomes. This was a prospective study from 2007-2011 inclusive. Data were recorded for fetal echocardiography and analyzed for referral indication, presence of extra-cardiac anomalies and invasive testing. For analysis of obstetric and neonatal outcomes the fetal echocardiography group were compared to a control group of 45,069 non-anomalous singleton pregnancies. Overall 1244 echocardiographs were recorded, 242 (19.5%) of which had a CHD. The commonest defects were AVSD (n = 36) and VSD (n = 26). Abnormal anatomy scan was the best indicator for detecting the presence of CHDs, compared to all other indications (p < 0.0001). Invasive testing was performed for 44% of those identified with a CHD, of which 54 (51%) were abnormal karyotypes. Thirty-seven percent (n = 89) of those with a CHD also had an extra-cardiac defect. In addition these fetuses were significantly more likely to have a karyotypic abnormality when compared with those with an isolated CHD (p < 0.0001). In terms of obstetric intervention, pregnancies affected by a major CHD were significantly more likely to require an emergency caesarean section (CS) for a non-reassuring fetal heart rate (NRFHR) (p = 0.022) and were more likely to go into preterm labour prior to 34 weeks (p = 0.003). Despite this, fetuses affected by CHD delivered vaginally had higher APGAR scores than those delivered by CS at one (p = 0.01) and five (p = 0.04) minutes. This study suggests most CHDs occur in a low risk population. Significant numbers of chromosomal and extra-cardiac defects in this study emphasize the importance of thorough evaluation of any fetus identified with a cardiac defect. Pregnancies with CHD are more at risk of requiring an emergency CS in labour although vaginal delivery is otherwise a safe option.

Ultrasound soft markers and fetal cardiac structural assessment at 11-14 weeks

To evaluate the detection rate of congenital heart defect (CHD) during the first trimester screening for chromosomal abnormalities, the role of ultrasound soft markers including increased nuchal translucency (NT), tricuspid regurgitation (TR) and abnormal ductus venosus (DV) flow in the screening for cardiac anomalies was also investigated. From January 2009 to January 2012, 4 673 fetuses were scanned at 11-14 weeks at Department of Fetal Medicine, the First Affiliated Hospital of Jinan University. The ultrasound findings and follow up outcomes were recorded, False-positive rate of different first-trimester ultrasound markers for the detection of CHD was calculated, sensitivity of the markers for all major CHD was calculated as well. There was a significant association between major CHD and first trimester ultrasound markers. (1) Overall findings:among the 4 673 fetuses, 31 fetuses were diagnosed CHD prenatally, 17, 12 and 2 of which were detected in the first, second and third trimester, respectively. In 22 of the 31 CHD cases, invasive procedure was performed, fetal karyotype was abnormal in 12 cases, including triosmy 21 (5 cases), trisomy 18 (2 cases), trisomy 13 (2 cases), Turner syndrome (2 cases) and pericentric inversion of chromosome 9 (1 cases). (2) NT measurement and prenatal detected CHD: in 4 673 cases, NT measurement between 95(th)-99(th) percentile were present in 206 (4.41%) , 5 cases were diagnosed CHD prenatally, in 4 of 5 cases were detected in first trimester; NT measurement <95(th) percentile were present in 4 430 (94.80%) , 16 cases were diagnosed CHD prenatally, in 5 of 16 cases were detected in first trimester; NT measurement>99(th) percentile (>3.5 mm) were present in 37 (0.79%, 37/4 673) , 10 cases were diagnosed CHD prenatally, in 8 of 10 cases were detected in first trimester. (3) TR and inverted a-wave at the DV and prenatal detected CHD: among 4 673 cases, TR or inverted a-wave at the DV were present in 51 (1.09%) , 98 (2.10%) respectively. TR was present in 8 of 31 CHD cases, inverted a-wave at the DV was present in 7 of 31 CHD cases. (4) Sensitivity of different first trimester ultrasound markers for detection of major CHD cases:in 31 CHD cases diagnosed prenatally, 23 cased were defined as major CHD. Sensitivity of at least one of the ultrasound markers, NT measurement between 95(th)-99(th) percentile, >99(th) percentile( >3.5 mm), TR or inverted a-wave at the DV for detection of major CHD cases was 74% (17/23), 22% (5/23), 39% (9/23), 35% (8/23), 30% (7/23) , respectively. (5) Specificity of different first trimester ultrasound markers for detection of CHD cases:specificity of NT measurement between 95(th)-99(th) percentile, >99(th) percentile (>3.5 mm), TR or inverted a-wave at the DV for detection of major CHD cases was 4.30% (201/4 673),0.58% (27/4 673),0.92% (43/4 673), 1.94% (91/4 673). Routine first trimester soft markers for chromosomal abnormalities screening combined with cardiac assessment can detect quite a number of major heart defects. Increased NT, TR and abnormal DV flow can be important indicators for echocardiography, which is favorable to early prenatal diagnosis of CHD.

Left atrial ligation alters intracardiac flow patterns and the biomechanical landscape in the chick embryo.

Hypoplastic left heart syndrome (HLHS) is a major human congenital heart defect that results in single ventricle physiology and high mortality. Clinical data indicate that intracardiac blood flow patterns during cardiac morphogenesis are a significant etiology. We used the left atrial ligation (LAL) model in the chick embryo to test the hypothesis that LAL immediately alters intracardiac flow streams and the biomechanical environment, preceding morphologic and structural defects observed in HLHS. Using fluorescent dye injections, we found that intracardiac flow patterns from the right common cardinal vein, right vitelline vein, and left vitelline vein were altered immediately following LAL. Furthermore, we quantified a significant ventral shift of the right common cardinal and right vitelline vein flow streams. We developed an in silico model of LAL, which revealed that wall shear stress was reduced at the left atrioventricular canal and left side of the common ventricle. Our results demonstrate that intracardiac flow patterns change immediately following LAL, supporting the role of hemodynamics in the progression of HLHS. Sites of reduced WSS revealed by computational modeling are commonly affected in HLHS, suggesting that changes in the biomechanical environment may lead to abnormal growth and remodeling of left heart structures.

Nuchal translucency and major congenital heart defects in fetuses with normal karyotype: a meta‐analysis

To pool published data regarding the sensitivity and specificity of nuchal translucency (NT) in the diagnosis of major congenital heart defects (CHDs) in fetuses with normal karyotype. MEDLINE and Scopus searches using combinations of the terms 'nuchal' and 'cardiac*' were complemented by perusal of references of the retrieved articles and an additional automated search using the 'search for related articles' function on PubMed. Only fetuses with normal karyotype and major CHDs were analyzed. Weighted estimates were made and summary receiver-operating characteristics curves were constructed. The analysis included 20 studies (205 232 fetuses; 537 cases with major CHDs). The pooled sensitivity and specificity of NT > 95(th) centile for diagnosis of major CHDs was 44.4% (95% CI, 39.5-49.5) and 94.5% (95% CI, 94.4-94.6), respectively. The pooled sensitivity and specificity of NT > 99(th) centile was 19.5% (95% CI, 15.9-23.5) and 99.1% (95% CI, 99.1-99.2), respectively. For the subgroup of studies in which NT was measured by Fetal Medicine Foundation-certified operators, the pooled sensitivity and specificity of NT > 95(th) centile was 45.6% (95% CI, 39.6-51.7) and 94.7% (95% CI, 94.6-94.9), respectively. The corresponding estimates for NT > 99(th) centile were 21.0% (95%CI, 16.5-26.1) and 99.2% (95% CI, 99.2-99.3). The pooled positive likelihood ratio for NT > 99(th) centile was 30.5 (95% CI, 24.3-38.6). There was high across-studies heterogeneity for most estimates. Approximately 44% of chromosomally normal fetuses with CHDs have NT > 95(th) centile and 20% have NT > 99(th) centile. However, there is high heterogeneity across studies, which largely remains even in subgroup analyses of studies of apparently similar design, potentially indicating the presence of some residual unidentified bias.

Nuchal translucency and cardiac abnormalities in euploid singleton pregnancies

Objective: To investigate different cut-off levels of nuchal translucency (NT) to predict abnormal cardiac findings (ACF) in second trimester ultrasound examination and confirmed postnatal congenital heart defects (CHD) in euploid pregnancies.Methods: A retrospective analysis was performed on singleton pregnancies examined in our ultrasound units from 2006 to 2011. Fetuses with an abnormal karyotype were excluded. Different cut-off levels of NT thickness were analyzed to evaluate its performance to detect the ACF on second trimester ultrasound (2nd US) examination and also the CHD detected in neonatal follow-up evaluation of ACF cases.Results: Of the 12 840 cases, a total number of 8541 euploid pregnancies were included in the study. Thirty-three had ACFs detected by 2nd US (3.86/1000). The mean NT thickness was found to be higher in fetuses with ACFs (p < 0.0001). Of 33 ACFs, 17 (52%, 1.99/1000) had major CHDs in neonatal follow-up. The area under the ROC curves for NT thickness to predict ACFs and CHDs were 0.67 and 0.65, respectively.Conclusions: Higher NT thickness is associated with higher risk of ACF. NT is a weak predictor of ACF and major CHD; however, fetuses with an unexplained increase in NT measurement should be referred for further cardiac investigations.

Pulmonary hypertension in bronchopulmonary dysplasia: Clinical findings, cardiovascular anomalies and outcomes

Pulmonary hypertension (PH) worsens the prognosis of bronchopulmonary dysplasia (BPD). The following items have not been fully established for PH in BPD: clinical characterization, incidence of cardiovascular anomalies (CVAs), response to PH treatment, and outcome. A review of clinical records, computed tomography (CT) images and catheterization data of 36 patients with PH-BPD referred to our PH Unit (March 2006 to December 2011) was performed. Twenty-nine patients without major congenital heart defects and with complete follow-up data were included. The diagnosis of PH was made at a median age of 4.5 months (IQR 2.4-7.8), with an echocardiography estimated median right ventricular pressure/systemic pressure ratio of 70% (IQR 60-80%). CT scanning was performed in 21 patients and catheterization in 14 patients. CVAs were found in 19 patients (65.5%): aortopulmonary collaterals (n = 9), pulmonary vein stenosis (n = 7), ASD (n = 4), and PDA (n = 9). Hemodynamic data: PVRI 4.3 UW m(2) (2.7-7); PVRI/SVRI 0.44 (0.32-0.8); and transpulmonary gradient 28 mmHg (19-40). At a median follow-up of 35 months (IQR 21-91), 6 patients had undergone shunts closure, 22 received specific PH drugs, 3 spontaneously improved of their PH, and 8 (26%) had died. PH in BPD is not always a transient condition; it can be diagnosed at later stages and can have a protracted course. The incidence of associated CVAs is high. Prompt diagnosis, detection, and treatment of CVAs, and specific drug therapy can improve the outcome in these patients, although the mortality rate remains high.

Fetal heart defects: Potential and pitfalls of first-trimester detection

Congenital heart defects (CHDs) are the leading cause of infant mortality due to birth defects. In the last 15 years, with the shift in screening for aneuploidies to the first trimester, extensive research has concentrated on early screening and detection of CHDs. Early detailed assessment of the fetal heart requires a high level of expertise in early anomaly scanning and fetal echocardiography. However, the detection of major CHDs at 11-13 weeks is influenced by their association with easily detectable markers, such as the nuchal translucency, ductus venosus blood flow and tricuspid regurgitation, and a policy decision as to the objectives of this scan and the allocation of resources necessary to achieve them. The use of transvaginal ultrasound and newer techniques are likely to improve the detection rate. However, the limitations of fetal echocardiography in the first trimester must be borne in mind, and follow-up at mid-gestational echocardiography is prudent in some cases.

Patterns in the prevalence of congenital heart defects, metropolitan Atlanta, 1978 to 2005.

Knowledge of patterns in prevalence of congenital heart defects (CHDs) is important for clinical care, etiologic research, and prevention. We evaluated temporal and racial/ethnic trends in the birth prevalence of CHDs in metropolitan Atlanta from 1978 to 2005. Cases of CHDs were obtained from the Metropolitan Atlanta Congenital Defects Program among live born infants, stillborn infants, and pregnancy terminations of at least 20 weeks gestation. We calculated birth prevalence per 10,000 live births and used joinpoint regression analysis to calculate the average annual percent change for total CHDs and for 23 specific subtypes in the total population and among whites and blacks. To evaluate racial/ethnic variations, we calculated prevalence ratios among blacks and Hispanics compared with whites. Between 1978 and 2005, 7301 infants and fetuses with major structural CHDs were ascertained among 1,079,062 live births (67.7 per 10,000). The prevalence of all CHDs in aggregate increased from 50.3 per 10,000 in 1978-1983 to 86.4 per 10,000 in 2000-2005. The prevalence of septal defects and vascular rings increased and the prevalence of tricuspid atresia decreased, while other CHD prevalences were stable. Racial/ethnic prevalence differences were found for all CHDs combined and muscular ventricular septal defects, aortic stenosis, and atrioventricular septal defects. The prevalence of total CHDs, primarily common, less severe types, are increasing, with some racial/ethnic differences. Further studies could clarify the possible reasons for such variations including differences in ascertainment, risk factors, or susceptibility.

Re: Commentary on our original research article

We welcome the introduction of UOG referee commentaries, which we believe in theory to be an excellent concept that will provide additional interest to the readers of the Journal. In the context of our manuscript, we believe it illustrates the different perspectives from which reviewers and readers working in different healthcare systems perceive the aims and designs of a study. The commentary 1 on our study 2 was written by a reviewer who works in a system where obstetricians scan all pregnancies within a private system. The study we published in this Journal requires an understanding of the system in which we work to interpret appropriately its importance. Our study reports on a method to improve specificity of diagnosis of coarctation of the aorta (CoA) at a tertiary center, within a nationalized healthcare system in which anomaly screening is offered free of charge at the point of delivery. Anomaly scans are accepted by > 95% of the population and are performed and reported by technicians. Isolated CoA is an important and potentially lifethreatening duct-dependent lesion, accounting for about 5% of all major congenital heart defects. The fetal cardiologists in this study were able to halve fetal follow-up in the cohort referred with suspected CoA based on sonographic features before cases were enrolled into the study, using previously published sonographic parameters 3 . Normality in this group was confirmed after delivery. Hence, in this study we were not testing our ability to triage referred cases of CoA into normal or suspected CoA, which we have published previously 3 , but to assess whether fetuses with aortic arch measurements below our

Prenatal ultrasound screening for congenital heart defects: current and future strategies

Congenital heart defects (CHDs) affect approximately three to eight out of 1000 live births and are a leading cause of fetal and postnatal mortality. Over the past 30 years, fetal echocardiography has emerged as an accurate tool to diagnose CHDs, and high-experience groups dealing with high-risk patients currently report detection rates of approximately 80–90% for major defects. However, the performance of obstetric ultrasound applied to the general obstetric population is still discouraging, with detection rates of 30–40% of major CHDs. Therefore, it is necessary to improve the results of obstetric ultrasound screening for CHDs. In this article, the authors describe current and future strategies that may be helpful, such as the uniform application of published guidelines for performing the so-called basic and extended-basic cardiac scan through comprehensive training, the implementation of new indications for performing fetal echocardiography and the use of new technologies such as 3D–4D scanning or tele...

OC08.03: Brain metabolism assessed by magnetic resonance spectroscopy in fetuses with major congenital heart defects

OC08.03: Brain metabolism assessed by magnetic resonance spectroscopy in fetuses with major congenital heart defects

Prevalence, timing of diagnosis and mortality of newborns with congenital heart defects: a population-based study

ObjectiveTo assess the prevalence, timing of diagnosis and infant mortality of congenital heart defects (CHD) with population-based data and using a classification that allows regrouping of the International Paediatric and...

Increased frequency of congenital heart defects in Menkes disease

ATP7A is a copper-transporting ATPase critical for central and peripheral nervous system function. Mutations in ATP7A cause Menkes disease and occipital horn syndrome (OHS), allelic X-linked recessive conditions that feature vascular abnormalities ascribed to low activity of lysyl oxidase, a copper-dependent enzyme. From a recently created Menkes disease/OHS patient registry, we identified four of 95 patients with major congenital heart defects (4.2%), a proportion exceeding the general population prevalence (≈1%). In conjunction with mouse models of Menkes disease, OHS, and lysyl oxidase deficiency (which feature aortic aneurysms, irregular attachment between vascular endothelium and mesoderm, and other defects of embryological development) our observation suggests an important role of copper metabolism in cardiac development. Congenital heart disease may be an under-appreciated abnormality in Menkes disease, and should be considered in a broad differential diagnosis of cardiac defects found prenatally in male fetuses. Conversely, newborn infants with suspected or confirmed Menkes disease should be evaluated for heart disease by careful clinical examination and echocardiography, if indicated.

Pulse oximetry as a screening test for congenital heart defects in newborn infants: a test accuracy study with evaluation of acceptability and cost-effectiveness.

Screening for congenital heart defects (CHDs) relies on antenatal ultrasound and postnatal clinical examination; however, life-threatening defects often go undetected. To determine the accuracy, acceptability and cost-effectiveness of pulse oximetry as a screening test for CHDs in newborn infants. A test accuracy study determined the accuracy of pulse oximetry. Acceptability of testing to parents was evaluated through a questionnaire, and to staff through focus groups. A decision-analytic model was constructed to assess cost-effectiveness. Six UK maternity units. These were 20,055 asymptomatic newborns at ≥ 35 weeks' gestation, their mothers and health-care staff. Pulse oximetry was performed prior to discharge from hospital and the results of this index test were compared with a composite reference standard (echocardiography, clinical follow-up and follow-up through interrogation of clinical databases). Detection of major CHDs - defined as causing death or requiring invasive intervention up to 12 months of age (subdivided into critical CHDs causing death or intervention before 28 days, and serious CHDs causing death or intervention between 1 and 12 months of age); acceptability of testing to parents and staff; and the cost-effectiveness in terms of cost per timely diagnosis. Fifty-three of the 20,055 babies screened had a major CHD (24 critical and 29 serious), a prevalence of 2.6 per 1000 live births. Pulse oximetry had a sensitivity of 75.0% [95% confidence interval (CI) 53.3% to 90.2%] for critical cases and 49.1% (95% CI 35.1% to 63.2%) for all major CHDs. When 23 cases were excluded, in which a CHD was already suspected following antenatal ultrasound, pulse oximetry had a sensitivity of 58.3% (95% CI 27.7% to 84.8%) for critical cases (12 babies) and 28.6% (95% CI 14.6% to 46.3%) for all major CHDs (35 babies). False-positive (FP) results occurred in 1 in 119 babies (0.84%) without major CHDs (specificity 99.2%, 95% CI 99.0% to 99.3%). However, of the 169 FPs, there were six cases of significant but not major CHDs and 40 cases of respiratory or infective illness requiring medical intervention. The prevalence of major CHDs in babies with normal pulse oximetry was 1.4 (95% CI 0.9 to 2.0) per 1000 live births, as 27 babies with major CHDs (6 critical and 21 serious) were missed. Parent and staff participants were predominantly satisfied with screening, perceiving it as an important test to detect ill babies. There was no evidence that mothers given FP results were more anxious after participating than those given true-negative results, although they were less satisfied with the test. White British/Irish mothers were more likely to participate in the study, and were less anxious and more satisfied than those of other ethnicities. The incremental cost-effectiveness ratio of pulse oximetry plus clinical examination compared with examination alone is approximately £24,900 per timely diagnosis in a population in which antenatal screening for CHDs already exists. Pulse oximetry is a simple, safe, feasible test that is acceptable to parents and staff and adds value to existing screening. It is likely to identify cases of critical CHDs that would otherwise go undetected. It is also likely to be cost-effective given current acceptable thresholds. The detection of other pathologies, such as significant CHDs and respiratory and infective illnesses, is an additional advantage. Other pulse oximetry techniques, such as perfusion index, may enhance detection of aortic obstructive lesions. The National Institute for Health Research Health Technology programme.

The Effect of Late Preterm Birth on Survival of Infants with Major Congenital Heart Defects

Aim: We evaluated the effect of late preterm delivery on hospital mortality of newborn infants with major congenital heart defects (CHD).

A Population-Based Evaluation of the Specific Risks for Five Major Congenital Heart Defects in Relation to Assisted Reproductive Technologies

A Population-Based Evaluation of the Specific Risks for Five Major Congenital Heart Defects in Relation to Assisted Reproductive Technologies

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Pulse oximetry screening for congenital heart defects in newborn infants (PulseOx): a test accuracy study

Screening for congenital heart defects relies on antenatal ultrasonography and postnatal clinical examination; however, life-threatening defects often are not detected. We prospectively assessed the accuracy of pulse oximetry as a screening test for congenital heart defects. In six maternity units in the UK, asymptomatic newborn babies (gestation >34 weeks) were screened with pulse oximetry before discharge. Infants who did not achieve predetermined oxygen saturation thresholds underwent echocardiography. All other infants were followed up to 12 months of age by use of regional and national registries and clinical follow-up. The main outcome was the sensitivity and specificity of pulse oximetry for detection of critical congenital heart defects (causing death or requiring invasive intervention before 28 days) or major congenital heart disease (causing death or requiring invasive intervention within 12 months of age). 20,055 newborn babies were screened and 53 had major congenital heart disease (24 critical), a prevalence of 2·6 per 1000 livebirths. Analyses were done on all babies for whom a pulse oximetry reading was obtained. Sensitivity of pulse oximetry was 75·00% (95% CI 53·29-90·23) for critical cases and 49·06% (35·06-63·16) for all major congenital heart defects. In 35 cases, congenital heart defects were already suspected after antenatal ultrasonography, and exclusion of these reduced the sensitivity to 58·33% (27·67-84·83) for critical cases and 28·57% (14·64-46·30) for all cases of major congenital heart defects. False-positive results were noted for 169 (0·8%) babies (specificity 99·16%, 99·02-99·28), of which six cases were significant, but not major, congenital heart defects, and 40 were other illnesses that required urgent medical intervention. Pulse oximetry is a safe, feasible test that adds value to existing screening. It identifies cases of critical congenital heart defects that go undetected with antenatal ultrasonography. The early detection of other diseases is an additional advantage. National Institute for Health Research Health Technology Assessment programme.

Observed Prevalence of Congenital Heart Defects From a Surveillance Study in China

The purpose of this study was to estimate the prevalence of major and minor congenital heart defects among fetuses and neonates using sonography in a general population of 4 areas surrounding Shanghai, China. Pregnant women were recruited between April 2004 and December 2005 in Jiaxing City, Suzhou City, Changshu County, and Haining County. All participants could have 3 sonographic examinations performed by specially trained physicians regardless of medical indication: a fetal sonographic screen and fetal echocardiography between 20 and 28 weeks' gestation and neonatal echocardiography. Diagnoses of congenital heart defects were made on the basis of review of all available scans by an international group of experts in pediatric cardiology. Prevalence rates were calculated per 1000 births. Among 4006 scanned fetuses and neonates, there were 75 congenital heart defects, including 12 major defects. The observed prevalence for all congenital heart defects was 18.7 (95% confidence interval, 14.8-23.5) per 1000 births, and the prevalence for major defects was 3.0 (95% confidence interval, 1.6-5.2) per 1000 births. The most common defects were ventricular septal defects (n = 47 [62.7%]), atrial septal defects (n = 14 [18.7%]), tetralogy of Fallot (n = 4 [5.3%]), and hypoplastic left heart syndrome (n = 3 [4.0%]). The prevalence of all congenital heart defects in the 4 areas of China studied was higher than that reported in other countries, with ventricular septal defects being the most frequent defects. Our data likely reflect a better estimate of the total prevalence of congenital heart defects in China than reported previously.

Pulse oximetry as a screening test for congenital heart defects in newborn infants: the pulseox test accuracy study

BackgroundLife-threatening congenital heart defects (CHD) often go undetected. This prospective study assessed the accuracy of pulse oximetry as a screening test for CHD.MethodsPulse oximetry was performed in asymptomatic newborns >34...