History Of Congenital Heart Defects Research Articles

Interaction between ozone and paternal smoking on fetal congenital heart defects among pregnant women at high risk: a multicenter maternal-fetal medicine study.

Evidence remains limited on the association between maternal ozone (O3) exposure and congenital heart defects (CHDs) in offspring, and few studies have investigated the interaction and modification of paternal smoking on this association. Using a sample including pregnant women at high risk of fetal CHD (with metabolic disease, first-trimester viral infection, family history of CHD, etc.) from a maternal-fetal medicine study covering 1313 referral hospitals in China during 2013-2021, we examined the associations between maternal O3 exposure during 3-8 weeks of gestational age and fetal CHD in offspring and investigated the interaction and modification of paternal smoking on this association. CHD was diagnosed by fetal echocardiograms, maximum daily 8-hour average O3 exposure data at a 10 km × 10 km spatial resolution came from the Tracking Air Pollution in China dataset, and paternal smoking was collected using questionnaires. Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Among 27,834 pregnant women at high risk of fetal CHD, 17.4% of fetuses were diagnosed with CHD. Each 10 μg/m3 increase in maternal O3 exposure was associated with a 17% increased risk of CHD in offspring (OR= 1.17, 95% CI =1.14-1.20). Compared with paternal nonsmoking and maternal low O3 exposure, the ORs (95% CI) of CHD for smoking and low O3 exposure, nonsmoking and high O3 exposure, and smoking and high O3 exposure were 1.25 (1.08-1.45), 1.81 (1.56-2.08), and 2.23 (1.84-2.71), respectively. Paternal smoking cessation seemingly mitigated the increased risk of CHD. Maternal O3 exposure and paternal smoking were interactively associated with an increased risk of fetal CHD in offspring, which calls for effective measures to decrease maternal exposure to O3 pollution and secondhand smoke for CHD prevention.

Co-occurring conditions in children with Down syndrome and autism: a retrospective study

BackgroundDown syndrome (DS) is one of the most common genetic causes of intellectual disability, and it is associated with an increased incidence of numerous co-occurring conditions. Autism spectrum disorder (ASD) is common in persons with DS, with rates reported as high as 39%. However, little is known regarding co-occurring conditions in children with both DS and ASD.MethodsA single-center retrospective review of prospective longitudinally collected clinical data was performed. Any patient with a confirmed diagnosis of DS evaluated at a large, specialized Down Syndrome Program in a tertiary pediatric medical center between March 2018 and March 2022 was included. A standardized survey which included demographic and clinical questions was administered during each clinical evaluation.ResultsIn total, 562 individuals with DS were included. The median age was 10 years (IQR: 6.18–13.92). Of this group, 72 (13%) had a co-occurring diagnosis of ASD (DS+ASD). Individuals with DS+ASD were more likely to be male (OR 2.23, CI 1.29–3.84) and had higher odds of a current or prior diagnosis of constipation (OR 2.19, CI 1.31–3.65), gastroesophageal reflux (OR 1.91, CI 1.14–3.21), behavioral feeding difficulties (OR 2.71, CI 1.02–7.19), infantile spasms (OR 6.03, CI 1.79–20.34) and scoliosis (OR 2.73, CI 1.16–6.40). There were lower odds of congenital heart disease in the DS+ASD group (OR 0.56, CI 0.34–0.93). There was no observed difference in prematurity or Neonatal Intensive Care Unit complications between groups. Individuals with DS+ASD had similar odds of having a history of congenital heart defect requiring surgery to those with DS only. Furthermore, there was no difference in rates of autoimmune thyroiditis or celiac disease. There was also no difference in rates of diagnosed co-occurring neurodevelopmental or mental health conditions in this cohort, including anxiety disorders and attention-deficit/hyperactivity disorder.ConclusionsThis study identifies a variety of medical conditions which are more frequent in children with DS+ASD than DS alone, providing important information for the clinical management of these patients. Future research should investigate the role of some of these medical conditions in the development of ASD phenotypes, and whether there may be distinct genetic and metabolic contributions towards these conditions.

An Exploratory Analysis of Maternal Health Variables Increasing the Severity of Congenital Heart Disease in Infants.

Congenital heart defects (CHD) are the most prevalent birth anomaly and leading cause of infant morbidity and mortality worldwide. Heart defects are often attributed to chromosomal abnormality or environmental factors, but most causes remain unknown. The purpose of this analysis was to explore maternal health variables and the relationships to birth outcomes in infants with CHD. Secondary analysis of data from the Wisconsin Pediatric Cardiac Registry. Maternal history of CHDs (odds ratio [OR] = 2.38; 95% confidence interval [CI], 1.42-3.98) and serious health conditions (OR = 1.537; 95%: CI, 1.08-2.17) increase infant risk and CHD severity. Maternal history of hypertension, serious health conditions, CHD, obesity, and income were predictors of birth weight (R² = 0.049, P < .05). Maternal history of hypertension, influenza, serious health conditions, and housing were predictors of gestational age (R2 = 0.045, P < .05). Birth weight (BW) and gestational age (GA) did not correlate to the severity of CHD in this study (simple vs complex, BW = -0.014, GA = 0.011, r). Maternal well-being influences the health of infants born with CHD. Positive maternal health contributes to near-normal birth weight and gestational age. Nurses must discuss optimal reproductive life planning strategies for decreasing risk of CHD and other infant disorders.

Diagnostic Accuracy of Ultrasound in Detection of Spina Bifida in the First and Second Trimester Using Post-Natal MRI as Gold Standard

Introduction: Antenatal ultrasound has been reported to be an effective tool for detecting neural tube defects including spina bifida. Moreover, major structural abnormalities can be detected by ultrasound examination, depending on the time of ultrasound scan. Objectives: To determine the diagnostic accuracy of ultrasound in detection of spina bifida in the first and second trimester using post-natal MRI as gold standard. Study Design: Descriptive, Cross-sectional study Study duration: 11th February 2019 to 10th August 2019 Settings: Department of Radiology, Jinnah Hospital, Lahore. Materials &amp; Methods: A total of 125 pregnant patients/Gravida presenting in first trimester (11 to 13 weeks) &amp; second trimester (14 to 22 weeks) assessed on dating scan, at risk for spina bifida were included. Women with pre-eclempsia and eclempsia determined on systolic BP &gt; 140 and protein urea and history of congenital heart defects were excluded. A standard ultrasound scan was performed by the same Radiologist on the same ultrasound machine and any findings associated with the spina bifida would be noted &amp; recorded on a predesigned Performa (Attached). Patients were followed till delivery and post-natal MRI was done to evaluate spina bifida. Presence of absence of spina bifida on USG &amp; MRI was noted. Results: All the patients were subjected to first ultrasonography and then MRI. USG supported the diagnosis of spina bifida in 62 patients. MRI confirmed spina bifida in 63 cases. In USG positive cases, 58 were true positive and 04 were false positive. While in USG negative patients, 58 were true negative and 05 were false negative. Overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of ultrasound in detection of spina bifida in the first and second trimester using post-natal MRI as gold standard is 92.06%, 93.55%, 93.55%, 92.06% and 92.80% respectively. Conclusion: This study concludes that ultrasonography is a highly sensitive and accurate modality for diagnosing spina bifida, and has not only dramatically improved our ability of diagnosing spina bifida but also be a simple, economical and readily available alternative to MRI. Keywords: Spina Bifida, Ultrasonography, Sensitivity

Hemodynamic and Structural Comparison of Human Fetal Heart Development Between Normally Growing and Hypoplastic Left Heart Syndrome-Diagnosed Hearts.

Congenital heart defects (CHDs) affect a wide range of societies with an incidence rate of 1.0–1.2%. These defects initiate at the early developmental stage and result in critical health disorders. Although genetic factors play a role in the formation of CHDs, the occurrence of cases in families with no history of CHDs suggests that mechanobiological forces may also play a role in the initiation and progression of CHDs. Hypoplastic left heart syndrome (HLHS) is a critical CHD, which is responsible for 25–40% of all prenatal cardiac deaths. The comparison of healthy and HLHS hearts helps in understanding the main hemodynamic differences related to HLHS. Echocardiography is the most common imaging modality utilized for fetal cardiac assessment. In this study, we utilized echocardiographic images to compare healthy and HLHS human fetal hearts for determining the differences in terms of heart chamber dimensions, valvular flow rates, and hemodynamics. The cross-sectional areas of chamber dimensions are determined from 2D b-mode ultrasound images. Valvular flow rates are measured via Doppler echocardiography, and hemodynamic quantifications are performed with the use of computational fluid dynamics (CFD) simulations. The obtained results indicate that cross-sectional areas of the left and right sides of the heart are similar for healthy fetuses during gestational development. The left side of HLHS heart is underdeveloped, and as a result, the hemodynamic parameters such as flow velocity, pressure, and wall shear stress (WSS) are significantly altered compared to those of healthy hearts.

Clinical utility of fetal echocardiography: an Egyptian center experience

BackgroundThe impact of early diagnosis of fetal cardiac abnormalities on the postnatal outcome has been controversial in literature. We aimed to evaluate the role of fetal echocardiography (FE) as a diagnostic tool for early detection and proper management of fetal cardiac abnormalities, study the indications of referral and detect the perinatal outcome in our institution.ResultsThis is a cross-sectional observational and descriptive study that included one hundred and one singleton pregnant women (101 fetuses) who were referred for FE over a period of one year. Indications for referral and perinatal risk factors were documented. FE and postnatal transthoracic echocardiography were done. Fetal cardiac abnormalities were detected in 46.5% of cases. Congenital heart defects (CHDs) in 34.6%, fetal arrythmias in 9.9%, cardiomyopathy in 2.9% and cardiac mass (Rhabdomyoma) in 1% (combined structural and rhythm abnormalities were observed in two fetuses). Of the CHDs, complex heart lesions were diagnosed in 57.1%, common atrioventricular canal in 28.6% and conotrunchal anomalies in 14.3%. Of the ten cases with fetal arrythmias, five fetuses had tachyarrhythmias, four had ectopics and one fetus had congenital heart block in association with maternal lupus. The indications for referral were abnormal obstetric ultrasound (52.5%), maternal medical illnesses (23.8%), multiple neonatal deaths (13.9%) and positive family history of CHD (10.9%). The number of fetuses with cardiac abnormalities was significantly higher than those without cardiac abnormalities in mothers not exposed to perinatal risk factors (p = 0.009) and was statistically lower in mothers exposed to perinatal risk factors (p = 0.005). FE showed 100% accuracy in diagnosing complex lesions, common atrio-ventricular canals, cono-truncal anomalies, cardiac masses and fetal arrhythmias. It missed two cases of tiny muscular ventricular septal defects and one case of aortic coarctation. Cases of fetal supraventricular tachycardia were successfully treated in-utero.ConclusionsCHDs exist in fetuses with no underlying perinatal risk factors. FE can accurately diagnose most of the cardiac anomalies though few errors remain challenging (aortic coarctation). It also offers a good chance for successful early life-saving management of some types of fetal arrhythmia.

Accuracy of the Standardized Early Fetal Heart Assessment in Excluding Major Congenital Heart Defects in High-Risk Population: A Single-Center Experience.

To evaluate the ability of standardized early fetal heart assessment (EFHA) that includes the 4-chamber view, outflow tract relationship (OTR), and transverse arches views (TAV) of the great arteries in excluding major congenital heart defects (CHDs) in high-risk populations. This retrospective study included high-risk pregnancies for CHDs undergoing EFHA at 11-14 weeks of gestation. Risk factors for CHDs were diabetes mellitus, a family history of CHDs, a history of a CHD use of teratogenic medications, seizure disorder, assisted reproductive treatment-conceived pregnancy, presence of at least one of the ultrasound markers: enlarged nuchal translucency (>95th percentile), tricuspid regurgitation, and reversed a-wave in the ductus venosus, presence of an extracardiac or a suspected cardiac anomaly, a high-risk first trimester combined screen result, and multiple pregnancies. EFHA consisted of visualization of 4ChV, OTR, and TAV, with and without power Doppler ultrasound. The primary outcome was the negative predictive value of EFHA in excluding major CHDs. EFHA was performed on 1055 fetuses. Of these, 1024 were used for the final analysis. Of these, 94.9% (n=923) were singleton. The most common indication for EFHA was maternal DM (n=231, 22.6%). The sensitivity, specificity, false positive, false negative, and accuracy of EFHA were 93.2%, 99.9%, 1.4%, 0.4%, and 99.5% (P < .0001), respectively, in entire included cases. The performance of EFHA was 88%, 99.9%, 1.4%, 0.4%, and 99.5% (P < .0001) respectively when the terminated cases were excluded. Early fetal heart assessment is feasible for screening for major CHDs in high-risk populations. This approach may be expanded to the general obstetric population.

Utility of routine screening fetal echocardiogram in pregnancies conceived by in vitro fertilization

To study the incidence and clinical significance of congenital heart defects (CHDs) detected by fetal echocardiography in pregnancies conceived by invitro fertilization (IVF). Cohort study comparing a prospectively maintained database of all fetal echocardiograms from 2012 to 2018 and pooled data from the Connecticut Birth Defects Registry and statewide hospital discharge data. Large tertiary care center. A total of 181,749 live births and 9,252 fetal echocardiograms were analyzed. Fetal echocardiograms in patients with a previous child with a CHD, a family history of CHD, medication exposure, diabetes, anomaly in previous pregnancy, cardiac or other abnormality noted on previous ultrasound, or monochorionic twins were excluded from the final analysis. Treatment with IVF. Incidence of CHD and odds ratios with 95% confidence intervals (CIs). Infant outcomes for cases of CHD were evaluated for clinically significant disease, defined a priori as disease requiring any medical or surgical intervention or continued follow-up with pediatric cardiology. Fetal echocardiography was performed in 2,230 IVF pregnancies, of which 2,040 were without other known risk factors for CHD. The mean gestational age at the time of fetal echocardiography was 22.2 ± 1.4 weeks. The odds ratio for CHD in the IVF group compared with statewide population rates was 1.4 (95% CI 0.9-2.1). CHD was diagnosed in 26 fetuses, of which 21 were clinically insignificant ventricular septal defects. One fetal echocardiogram was concerning for pulmonary stenosis that was not present at birth. Four defects were clinically significant, indicating that 510 fetal echocardiograms were performed for every diagnosis of one clinically significant CHD in the IVF group. The incidence of CHD in IVF pregnancies without other risk factors is not significantly different from baseline population rates, and most CHDs diagnosed by fetal echocardiography in this group are clinically insignificant. Routine screening with fetal echocardiography in all IVF pregnancies provides limited utility beyond routine prenatal care and need not be recommended without the presence of other risk factors.

148 Discordant congenital heart defects in monochorionic twins: risk factors and proposed pathophysiology

There is a six-fold increase in congenital heart defects (CHD) among monochorionic (MC) twins compared to singleton or dichorionic twin pregnancies. Though MC twins share a genotype, discordant phenotypes related to CHD have been described. Our objective was to characterize the spectrum of CHD in MC twins in the context of genetic results and clinical demographics for a modern cohort to provide insight into risk factors and pathophysiology of discordant CHD in MC twins. Retrospective analysis of all twins receiving prenatal fetal echocardiography at a single institution from January 2010 – March 2020 (N=163) yielded 24 MC twin pairs (48 neonates) with CHD (n=6 concordant CHD, n=18 discordant CHD). Descriptive analysis including frequencies, means, and standard deviations were conducted for all maternal, CHD diagnoses, and neonatal variables. Continuous variables were analyzed using the Student t-test and categorical variables were analyzed using the Fisher Exact test. The most common lesions were septal defects (50% and 45% in concordant and discordant cohort) and right heart lesions (33% and 18% in concordant and discordant cohort). Diagnostic genetic testing was abnormal for 17% of the concordant and 6% of the discordant pairs, with no difference between the groups (p=0.45). Six (25%) twin pairs, 2 concordant and 4 discordant, were complicated by twin-to-twin transfusion syndrome, with all recipient twins acquiring diagnosis of CHD and no twins with abnormal genetic testing. No significant association was found between clinical risk factors and development of discordant CHD (p>0.05). This data supports environmental and epigenetic influences versus genotypic factors in the development of discordant CHD, pertinent for early diagnosis and postnatal prognosis. This is illustrated by the higher rates of discordant (75%) versus concordant (25%) CHD in MC twin pairs in this population, low incidence of family history of CHD, and the low incidence of genetic abnormalities (8.3%) in our MC cohort with CHD.

Genes and Pathways Implicated in Tetralogy of Fallot Revealed by Ultra-Rare Variant Burden Analysis in 231 Genome Sequences

Recent genome-wide studies of rare genetic variants have begun to implicate novel mechanisms for tetralogy of Fallot (TOF), a severe congenital heart defect (CHD). To provide statistical support for case-only data without parental genomes, we re-analyzed genome sequences of 231 individuals with TOF (n = 175) or related CHD. We adapted a burden test originally developed for de novo variants to assess ultra-rare variant burden in individual genes, and in gene-sets corresponding to functional pathways and mouse phenotypes, accounting for highly correlated gene-sets and for multiple testing. For truncating variants, the gene burden test confirmed significant burden in FLT4 (Bonferroni corrected p-value < 0.01). For missense variants, burden in NOTCH1 achieved genome-wide significance only when restricted to constrained genes (i.e., under negative selection, Bonferroni corrected p-value = 0.004), and showed enrichment for variants affecting the extracellular domain, especially those disrupting cysteine residues forming disulfide bonds (OR = 39.8 vs. gnomAD). Individuals with NOTCH1 ultra-rare missense variants, all with TOF, were enriched for positive family history of CHD. Other genes not previously implicated in CHD had more modest statistical support in gene burden tests. Gene-set burden tests for truncating variants identified a cluster of pathways corresponding to VEGF signaling (FDR = 0%), and of mouse phenotypes corresponding to abnormal vasculature (FDR = 0.8%); these suggested additional candidate genes not previously identified (e.g., WNT5A and ZFAND5). Results for the most promising genes were driven by the TOF subset of the cohort. The findings support the importance of ultra-rare variants disrupting genes involved in VEGF and NOTCH signaling in the genetic architecture of TOF, accounting for 11–14% of individuals in the TOF cohort. These proof-of-principle data indicate that this statistical methodology could assist in analyzing case-only sequencing data in which ultra-rare variants, whether de novo or inherited, contribute to the genetic etiopathogenesis of a complex disorder.

A Nonsense GATA6 Mutation Explains History of Congenital Heart Defects and 10 Years of Poorly-Controlled Diabetes Lacking DKA in a Non-Obese 30 Year-Old Incidentally Found to Have Pancreatic Hypoplasia

To report a case of diabetes mellitus (DM) associated with partial pancreatic agenesis and congenital heart disease (CHD) in a patient found to have a nonsense mutation of the GATA6 gene. We present the imaging, laboratory, and genetic findings, and describe the clinical course of a patient with an atypical presentation of DM as well as CHD, who was found to have partial pancreatic agenesis on computed tomography (CT) imaging. Genetic testing was performed to identify monogenic DM. A 30-year-old nonobese female with a waxing and waning pattern of insulin-dependent DM diagnosed at the age of 20 was found to have partial pancreatic agenesis on CT scan. It was unclear whether the patient was experiencing undetected hyperglycemia prior to initial diagnosis of DM. She had no history of diabetic ketoacidosis (DKA) despite poorly-controlled diabetes and years without insulin treatment. The patient also had congenital tricuspid atresia, ventricular septal defect, and transposition of the great vessels with surgical correction in childhood. Partial pancreatic agenesis and CHD with atypical DM prompted genetic testing for monogenic DM, and a nonsense mutation of the GATA6 (c.1242C>A, p.C414*) gene was found. GATA6 mutations are associated with a broad spectrum of diabetic phenotypes, pancreatic agenesis, and a variety of CHDs. This case highlights the importance of considering monogenic diabetes in young, nonobese patients with diabetes, particularly with negative pancreatic antibodies and no history of DKA. Further, this case demonstrates the importance of testing for GATA6 mutations in any young patient with diabetes and CHD.

Herding CATs? The Incidence and Prevention of Catheter-Associated Thromboses (CATs) in Pediatric Patients after Cardiac Transplant

The presence of central venous lines (CVLs) post cardiac transplant increases the risk of catheter-associated thromboses (CATs) impacting vascular access. CATs also contribute to the need for prolonged anticoagulation increasing the risk of bleeding and diminished quality of life. Little data exists quantifying the incidence of CATs or associated risk factors after cardiac transplantation in pediatric patients. We aimed to study the incidence of CATs and the impact of a risk-stratified anticoagulation protocol in reducing their development. This is a single-center, retrospective review of patients less than 18 years of age with CVLs after cardiac transplantation from 2009-2018. Data collected included demographic data, CVL location, thrombosis data, anticoagulant use, and adverse events. Patients were started on an anticoagulation (AC) protocol (see Table 1) after 2016 and were compared to pre-protocol patients. CATs were noted in 39 (42%) of 93 patients analyzed. Eight (8.6%) patients experienced major bleeding which was associated with older age (p=0.021) and history of congenital heart defect (p=0.067). There were 76 patients prior to AC protocol implementation compared to 17 post-protocol. Preliminary analyses showed no difference in the rate of CATs (42.1% vs. 41.2%, p=0.54); however, of clots that developed after implementation, there were significantly fewer occlusive thromboses (15.8% vs. 35.3%, p=0.05) decreasing the need for further anticoagulation by 13.3%. This study highlights the significant risk of CATs after heart transplantation in pediatric patients. In an attempt to decrease the rate of CATs, a risk-stratified AC protocol was developed and implemented. Though initial data is limited, patients who received early post-operative anticoagulation after transplant had less severe CATs and decreased need for therapy after line removal.

P1452 A rare case of embolic blindness in an adult patient with univentricular heart after fontan operation

Abstract Background Thromboembolic complications following Fontan procedure are one of the major causes of mortality and morbidity among patients with univentricular heart. We may classify thromboembolic complications into two groups: systemic- and nonsystemic. We present a case of a patient with a manifestation of both. Case report 24-year old female, foreign student was admitted to Ophthalmology Department due to sudden blindness of the left eye. Performed studies revealed embolus in the left central retinal artery. Because the patient had the history of congenital heart defect she was referred to our department. Analysis of medical documentation showed that the patient has combined congenital heart defect including right ventricle hypoplasia, tricuspid atresia, pulmonic stenosis, ventricular septal defect, atrial septal defect and persistent ductus arteriosus. She had a history of two surgeries: modified left-side Blalock-Tausing connection (in 4th month of life) and total cavo-pulmonary connection with the closure of Blalock-Tausing and excision of interatrial septum (in 2,5 year of life). On admission she presented with left-eye blindness. She had no dyspnoea or palpitations. However she reported very severe migraines from a few days preceding the admission to hospital. Echocardiography revealed tricuspid atresia, hypoplastic right ventricle, preserved systolic and diastolic function of left ventricle, atrial septal defect with no restriction. We observed enlarged diameter of vena cava inferior with no respirophasic variations and massive thrombus in inside with very low flow. The connection between inferior vena cava and right pulmonary artery was working properly with no visible fenestration. We also observed a winding vessel between ascending aorta and truncus pulmonalis/pulmonary artery with continuous flow of blood from left to right side. Computer tomography confirmed the diagnosis of massive thrombosis of vena cava inferior. Patient had anticoagulation started. Two days later we the flow in inferior vena cava returned – we did not observe any thrombus. Patient was referred to catheterization and had chronic anticoagulation initiated. Three months follow-up revealed no changes in clinical condition of a patient. Discussion The palliative Fontan operation predispose to the increased risk of thromboembolic complication. Despite the risk factors of such complications have been identified, there are no guidelines about prophylactic anticoagulation in that group of patients. As a result, chronic anticoagulation is initiated in patients who have other indications e.g. atrial fibrillation. It seems that it would be beneficial to define the group of patients after Fontan procedure with indications to chronic anticoagulation therapy despite arrhythmias.

Potential risk factors for Ebstein anomaly, National Birth Defects Prevention Study, 1997-2011.

Ebstein anomaly is a rare congenital heart defect (CHD) that, when severe, requires corrective surgery or other catheter-based intervention in the first year of life. Due to its rarity, risk factors for Ebstein anomaly remain largely unknown. Using national data, we examined 18 potential risk factors for Ebstein anomaly. Using 1997-2011 data from the National Birth Defects Prevention Study, a population-based case-control study, we calculated crude and adjusted odds ratios and 95% confidence intervals for paternal age, maternal socio-demographics, reproductive history, and modifiable risk factors, and infant characteristics reported by mothers of 135 Ebstein anomaly cases and 11,829 controls. Mothers of Ebstein anomaly cases had 4.1 (95% confidence interval: 1.8, 9.5) times the odds of reporting a family history of CHD compared with mothers of controls. Ebstein anomaly was associated with maternal second-hand cigarette smoke exposure at home (odds ratio = 2.2 [95% confidence interval: 1.1, 4.4]), but not maternal cigarette smoking (odds ratio = 1.3 [95% confidence interval: 0.8, 2.1]). Odds were elevated, but the 95% confidence interval included 1.0, for maternal marijuana use (odds ratio = 1.8 [95% confidence interval: 0.9, 3.8]) and paternal age ≥40 years at delivery (odds ratio = 1.9 [95% confidence interval: 1.0, 3.5]). Maternal exposure to second-hand cigarette smoke at home and a family history of CHD were associated with elevated odds of Ebstein anomaly. Genetic analyses could clarify the potential heritability of Ebstein anomaly.

Congenital heart defects according to the types of the risk factors – a single center experience

Objective: The main aim of this study was to compare the prevalence of congenital heart defects (CHDs) between pregnant women with and those without the risk factors. The secondary aim was to determine the influence of the specific risk factors, divided into subgroups, on the development of the CHD.Methods: The presented results were obtained over the course of a 15-year study between years 2002 and 2016. Fetal echocardiography was performed as a planned screening examination during the second trimester of gravidity. A total of 35,831 singleton pregnancies were examined at our center. Risk factors for the development of CHDs were analyzed and divide into the following groups: (i) maternal age ≥35 years; (ii) mother-related risk factors; (iii) pregnancy- and fetus-related risk factors; (iv) pregnancy after in vitro fertilization (IVF); (v) history of CHDs in the first-degree family member; (vi) history of CHDs in the second-degree family member; and (vii) positive genetic family history.Results: The risk factors were identified in 25% (8990/35,831) of pregnancies. In total, CHDs were detected in 1.1% (394/35,831) of fetuses. The prevalence rate of CHDs was higher in the pregnancies with than in those without the risk factors (2.5% [221/8990] versus 0.6% [173/26,841]; p < .0001). The presence of pregnancy- and fetus-related risk factors (odds ratio [OR], 6.5; 95% confidence interval [CI], 4.3–9.7) and pregnancy after IVF (OR, 2.8; 95% CI, 1.5–5.2) were found to be independent risk factors of CHDs.Conclusions: The presence of specific risk factors is related to the increasing prevalence of CHDs. Pregnancy- and fetus-related risk factors and in vitro fertilization were found to be the independent risk factors of CHD.

Abnormal Longitudinal Growth of the Aorta in Children with Familial Bicuspid Aortic Valve.

Bicuspid aortic valve (BAV) is the most common type of congenital heart defect (CHD) and is associated with clinically significant cardiovascular complications including valve calcification and ascending aortopathy (AscAo), predominantly occurring in adulthood. While a limited number of genetic etiologies for BAV have been defined, family members of affected individuals display BAV along with other left-sided CHD. This has led to guidelines from the American Heart Association and American College of Cardiology that recommend echocardiographic screening of first-degree relatives of affected adults. While potentially beneficial in adults, the yield of such screening in children is unknown. The purpose of this study was to investigate a cohort of children with familial BAV to determine the frequency of development of AscAo, and to identify risk factors that contribute to abnormal aortic growth. Echocardiograms over a 10-year follow-up period were reviewed on 26 patients with familial BAV [22 male, 4 female; 22 with isolated BAV, 6 with BAV and aortic coarctation (CoA)]. All had a family history of CHD and were recruited from 2005 to 2010 as part of a genetics research study. Four aortic segments (annulus, root, sinotubular junction, ascending aorta) on parasternal long-axis echocardiographic images were measured by a single observer. The mean age at first echocardiogram was 7.1±5.5 and that was 13.8±6.2years at the last echocardiogram. Only patients with >2 echocardiograms in the 10-year period were included. Z score measurements of the aorta were plotted over time and based on these the cohort was divided into two groups: Group 1 (abnormal)-Z score for any segment >2 or a change in Z score >2 over follow-up; Group 2 (normal)-Z score <2 throughout follow-up and change in Z score <2. Nineteen out of 26 children displayed abnormal aortic growth or dilation of the aorta. BAV with right/left cusp fusion was more frequent in Group 1 (15/18) versus Group 2 (3/7) (p<0.05). There were no significant differences in gender, aortic valve dysfunction, presence of CoA, family history, cardiac function, presence of left ventricular hypertrophy, or medication use between the 2 groups. In our longitudinal study of children with familial BAV, the majority display evidence of abnormal growth of the ascending aorta during the follow-up period consistent with AscAo and support the extension of current adult guidelines to the pediatric population. While we find that right/left cusp fusion is a risk factor for abnormal aortic growth, additional studies are needed to identify other factors to better select children who require serial screening.

Abnormal maternal biomarkers of homocysteine and methionine metabolism and the risk of congenital heart defects

BackgroundRecent advances in genetic technology have had a significant impact on the practice of clinical genetics and the diagnosis of genetic syndromes associated with cardiac malformations. AimThe present study was aimed to determine whether biomarkers of the folic acid pathway, including homocysteine and methionine metabolism are altered among non pregnant women who have had a previous pregnancy affected by congenital heart defects. Subjects and methodsThe study was conducted on 50 women attending the Medical Genetics center and the Pediatric Cardiology Clinic, Faculty of Medicine, Ain Shams University for follow up. Mothers were subdivided into: Group 1 (Cases): 25 mothers with a history of congenital heart defects in previous children. Group 2 (Controls): 25 mothers and their children didn’t have any birth defects including congenital heart defects. In both groups women will be excluded: If they were pregnant or taking folate antagonist medications (antiepileptic drugs) or vitamin supplementations at the time of the study. Measurement of plasma concentration of: Vitamin B-12, folic acid, Homocysteine, Methionine, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), by using Radio immunoassay kit was done. ResultsThere is a significant difference between cases and controls as regards history of early neonatal deaths (28%) in cases versus (4%) in controls (P<0.05). The study also revealed that the most frequent congenital cardiovascular malformation is VSD (32%) followed by ASD (20%).As regards biomarker concentrations all, were significantly different between case and control subjects except for methionine. ConclusionAn elevated levels of maternal homocysteine is an independent risk factor for congenital heart defects. Finally: There is an increasing need for professionals to apply and interpret genetic testing in a clinically meaningful way for prevention of congenital heart defects.

Early Evaluation of the Fetal Heart

Evaluation of the fetal heart at 11-13 + 6 weeks of gestation is indicated for women with a family history of congenital heart defects (CHD), a previous child with CDH, or an ultrasound finding associated with cardiac anomalies. The accuracy for early detection of CHD is highly related to the experience of the operator. The 4-chamber view and outflow tracts are the most important planes for identification of an abnormal heart, and can be obtained in the majority of fetuses from 11 weeks of gestation onward. Transvaginal ultrasound is the preferred route for fetal cardiac examination prior to 12 weeks of gestation, whereas, after 12 weeks, the fetal heart can be reliably evaluated by transabdominal ultrasound. Cardiac defects, such as ventricular septal defects, tetralogy of Fallot, Ebstein's anomaly, or cardiac tumors, are unlikely to be identified at ≤14 weeks of gestation. Additional ultrasound techniques such as spatiotemporal image correlation and the evaluation of volumes by a fetal-heart expert can improve the detection of congenital heart disease. The evaluation of the fetal cardiac function at 11-13 + 6 weeks of gestation can be useful for early identification of fetuses at risk of anemia due to hemoglobinopathies, such as hemoglobin Bart's disease.

Rates of autism and potential risk factors in children with congenital heart defects.

Atypical development, behavioral difficulties, and academic underachievement are common morbidities in children with a history of congenital heart defects and impact quality of life. Language and social-cognitive deficits have been described, which are associated with autism spectrum disorders. The current study aimed to assess the rates of autism spectrum disorders in a large sample of children with a history of congenital heart defects and to assess medical, behavioral, and individual factors that may be associated with the risk of autism spectrum disorders. Participants included 195 children with a history of congenital heart defects, who are followed in a large-scale longitudinal study. Measures included behavioral data from 4-year-old neurodevelopmental evaluations and parent-report data from a later annual follow-up. Using established cutoffs on an autism spectrum disorder screener, children with congenital heart defects showed higher rates of "possible" autism spectrum disorders than national rates, (Chi-square Test of Equal Proportions), all Ps < .05. A stepwise variable selection method was used to create a "best prediction model" and multivariable logistic regression was used to identify variables predicting diagnostic status. Factors associated with diagnostic risk included medical (delayed sternal closure, prematurity, positive genetic findings), behavioral (cognitive, language, attention issues), and individual (socioeconomic, cultural/racial) variables. ROC analyses identified a cutoff of 7 to maximize sensitivity/specificity based on parent-reported diagnosis. Risk of autism spectrum disorder screening status in children with congenital heart defects was higher than expected from population rates. Findings highlight the need for referral to a specialist to assess the presence and severity of social-communication issues and congenital heart defects population-specific screening thresholds for children with concern for autism spectrum disorders.

Prevalence and risk factors of congenital heart defects among live births: a population-based cross-sectional survey in Shaanxi province, Northwestern China

BackgroundNearly half of the population of Northwest China live in Shaanxi province, but population-based data on the epidemiologic characteristics of congenital heart defects (CHD) in this population is limited. The study aimed to investigate the prevalence and epidemiologic characteristics of the CHD among infants born between 2010 and 2013 in Shaanxi province.MethodsInfants born between 2010 and 2013 in Shaanxi province were surveyed using a stratified multi-stage sampling method. Participant characteristics were recorded by questionnaire, medical records were reviewed and CHD was diagnosed using a specialized neonatal echocardiography. A Poisson regression model was applied to assess the association between any CHD and possible risk factors.ResultsA total of 29098 live infants were surveyed with an overall prevalence of 76.0 (95% CI: 66.3, 86.7) per 10000 live infants. The prevalence of major and minor CHD were 26.1 and 49.8 per 10000 live infants, respectively, in surveyed areas. Poisson regression analysis indicated that, compared with singleton infants, the prevalence rate ratio of CHD was higher in twin and multi-fetal infants (PRR:3.1, 95% CI:1.6, 6.1). Using southern Shaanxi as a reference, the PRR of CHD were lower in northern (PRR:0.4, 95% CI:0.3, 0.6) and central Shaanxi province (PRR:0.5, 95% CI:0.4, 0.7). PRR was higher in mothers over 30 years of age than in those under 25 years (PRR:1.6, 95% CI:1.0, 2.5), and in mothers with ≥3 parity than that in mothers with only one parity (PRR:2.2, 95% CI:1.2, 4.2). The risk for CHD among live infants was positively associated with family history of CHD (PRR: 9.8, 95% CI: 5.3, 18.1). Additionally, CHD was less common in the floating population than the permanent population (PRR: 0.6, 95% CI: 0.4, 0.9).ConclusionThe CHD among live infants seemed to be a serious health problem in Shaanxi province as well as in Northwestern China. Our research have important policy implications for recommendations on CHD intervention in Northwest China.