Incidence Of Congenital Heart Defects Research Articles

Magnitude of Stress among Parents of Children with Cardiac Malformation in Tertiary Care Hospitals Peshawar

Background: Congenital Heart Defects (CHDs) are inborn anomalies or mal-formations of heart. These are the most common type of birth anomalies, approximately 1-2% babies are delivered with cardiac anomalies all over the world. CHDs are some of these deformities that disturb the lives of effected child as well as parents of the effected child. Studies from Pakistan have only reported incidence and risk factors of CHDs and have not identified their association with parental stress. Aim: The aim of this study was to identify the magnitude of parental stress caused by child diseased status. Methodology: This was a descriptive cross-sectional study. 387 participants was the sample size, calculated through online software open-epi. Every parent fulfilling the inclusion criteria was selected through Consecutive Sampling technique. And, data was collected through an adopted questionnaire. Results: Majorities (60.2%) of the study participants were male. The mean overall score of stress was 64.36 with a Standard Deviation of ±6.24534. A strong association was identified in the category of gender, females were more in stress than the male (Chi-square = 42.66, P < 0.001). Conclusion: The outcomes of the current study show that parents of the CHD diagnosed kids were in stress. There was a major role of demographical variable in the level of outcome variable “stress” among parents of CHD diagnosed children, such as gender, age, income, occupation, and education level.

Relationship between maternal exposure to heavy metal titanium and offspring congenital heart defects in Lanzhou, China: A nested case-control study.

BackgroundPrevious studies have found that exposure to heavy metals increased the incidence of congenital heart defects (CHDs). However, there is a paucity of information about the connection between exposure to titanium and CHDs. This study sought to examine the relationship between prenatal titanium exposure and the risk of CHDs in offspring.MethodsWe looked back on a birth cohort study that was carried out in our hospital between 2010 and 2012. The associations between titanium exposure and the risk of CHDs were analyzed by using logistic regression analysis to investigate titanium concentrations in maternal whole blood and fetal umbilical cord blood.ResultsA total of 97 case groups and 194 control groups were included for a nested case-control study. The [P50 (P25, P75)] of titanium were 371.91 (188.85, 659.15) μg/L and 370.43 (264.86, 459.76) μg/L in serum titanium levels in pregnant women and in umbilical cord serum titanium content in the CHDs group, respectively. There was a moderate positive correlation between the concentration of titanium in pregnant women's blood and that in umbilical cord blood. A higher concentrations of maternal blood titanium level was associated with a greater risk of CHDs (OR 2.706, 95% CI 1.547–4.734), the multiple CHDs (OR 2.382, 95% CI 1.219–4.655), atrial septal defects (OR 2.367, 95% CI 1.215–4.609), and patent ductus arteriosus (OR 2.412, 95% CI 1.336–4.357). Dramatically higher concentrations of umbilical cord blood levels had an increased risk of CHDs and different heart defects.ConclusionTitanium can cross the placental barrier and the occurrence of CHDs may be related to titanium exposure.

Surgical and Cardiac Catheterization Outcomes of Scimitar Syndrome Patients: A Three Decade Single-Center Experience.

Scimitar syndrome (SS) is a rare congenital condition which includes partial anomalous pulmonary venous return (PAPVR) and a variable degree of pulmonary hypoplasia. We describe the clinical features, therapeutic approach and outcomes of patients who underwent cardiac catheterization and/or surgical repair of the scimitar vein at a single institutionin the United States. This retrospective cohort study included all patients with SS who underwent scimitar vein surgical repair or cardiac catheterization from October 1989 through August 2021 in a tertiary care center. A total of 84 patients with SS were included and median follow-up time was 74months. Patients diagnosed with SS under the age of one year had a significantly greater incidence of congenital heart defects (CHD) (p < 0.001), non-cardiac anomalies (p = 0.02), pulmonary hypertension (p = 0.02), and mortality (p = 0.04) compared to those diagnosed over the age of 1year. Twenty-eight patients underwent surgical repair of the scimitar vein. Overall, eight (10%) patients died. Compared to surviving patients, deceased patients had a significantly higher incidence of pulmonary hypertension (PH), neonatal SS diagnosis, and extracorporeal membrane oxygenation (ECMO) support. Median scimitar vein pressure (20mmHg) of deceased patients was significantly higher compared to pressures in surviving patients (11mmHg; p = 0.02). PH, CHD, neonatal SS diagnosis, ECMO support, and markedly elevated scimitar vein pressure are associated with mortality. Scimitar vein surgical repair during infancy is commonly associated with PH and restenosis that requires re-intervention.

Maternal binge alcohol consumption leads to distinctive acute perturbations in embryonic cardiac gene expression profiles.

Excessive alcohol consumption during pregnancy is associated with high risk of congenital heart defects, but it is unclear how alcohol specifically affects heart development during the acute aftermath of a maternal binge drinking episode. We hypothesize that administration of a single maternal binge dose of alcohol to pregnant mice at embryonic day 9.5 (E9.5) causes perturbations in the expression patterns of specific genes in the developing heart in the acute period (1-3 days) following the binge episode. To test this hypothesis and identify strong candidate ethanol-sensitive target genes of interest, we adapted a mouse binge alcohol model that is associated with a high incidence of congenital heart defects as described below. Pregnant mice were administered a single dose of alcohol (2.5g/kg in saline) or control (saline alone) via oral gavage. To evaluate the impact of maternal binge alcohol on cardiac gene expression profiles, we isolated embryonic hearts from both groups (n=5/group) at 24, 48, and 72 h post-gavage for transcriptomic analyses. RNA was extracted and evaluated using quantitative RNA-sequencing (RNA-Seq) methods. To identify a cohort of binge-altered cardiac genes, we set the threshold for change at >2.0-fold difference with adjusted p < 0.05 versus control. RNA-Seq analysis of cardiac gene expression revealed that of the 17 genes that were altered within the first 48 h post-binge, with the largest category consisting of transcription factors (Alx1, Alx4, HoxB7, HoxD8, and Runx2), followed by signaling molecules (Adamts18, Dkk2, Rtl1, and Wnt7a). Furthermore, multiple comparative and pathway analyses suggested that several of the candidate genes identified through differential RNA-Seq analysis may interact through certain common pathways. To investigate this further, we performed gene-specific qPCR analyses for three representative candidate targets: Runx2, Wnt7a, and Mlxipl. Notably, only Wnt7a showed significantly (p < 0.05) decreased expression in response to maternal binge alcohol in the qPCR assays. These findings identify Wnt7a and a short list of potential other candidate genes and pathways for further study, which could provide mechanistic insights into how maternal binge alcohol consumption produces congenital cardiac malformations.

Differences in Congenital Anomalies in In-Vitro Fertilization (IVF) Versus Non-IVF Dichorionic-Diamniotic Twin Pregnancies [A333

INTRODUCTION: The aim of this study was to evaluate the incidence of congenital anomalies in dichorionic-diamniotic twins conceived with in-vitro fertilization (IVF) versus non-IVF in a large geographically diverse population. METHODS: This is a secondary analysis of data from a retrospective cohort study of twin pregnancies seen at 17 centers between 12/2011-2/2020. Institutional review board approval was obtained. Monochorionic, vanishing twins, triplets, and cases with chromosomal abnormalities or incomplete follow-up were excluded. Neonates with an abnormal newborn exam were evaluated for having a major or minor congenital anomaly, and anomalies were further classified by organ system (cardiac, renal/genitourinary, gastrointestinal, and musculoskeletal). Chi-squared, Fisher’s exact tests, and multivariate logistic regression were used. RESULTS: Of the 1,112 dichorionic-diamniotic twin pregnancies included, 523 (47.0%) were conceived with IVF and 589 (53.0%) were conceived spontaneously or with other assisted reproductive technology (ART). Congenital anomalies were found in 91 pregnancies (8.18%). Of those, 42 were found in IVF pregnancies (8.03%) versus 49 non-IVF pregnancies (8.32%; P=.86). There were no significant differences between IVF and non-IVF for major anomalies (P=.57) or minor anomalies (P=.62). There was no significant difference between IVF and non-IVF pregnancies when classifying anomalies by system, and this held true when adjusting for maternal age, race, BMI, and parity. CONCLUSION: In this large cohort of twin pregnancies, there is no significant difference in the incidence of anomalies for pregnancies conceived by IVF versus non-IVF. Given that previous data has shown increased incidence of congenital heart defects in IVF pregnancies, this should be further evaluated specifically in dichorionic-diamniotic twin pregnancies.

Laryngeal pathologies in dysphonic children with Down Syndrome

IntroductionDown syndrome is the most common chromosomal abnormality and is associated with a higher incidence of congenital heart defects, which often require surgery within the first year of life. Previous studies have found that children with Down syndrome are at higher risk for subglottic stenosis, vocal fold paralysis, and laryngomalacia. The goal of this study is to review children with Down syndrome presenting with dysphonia and to characterize their laryngeal pathologies. MethodsA retrospective review was performed of patients with Down syndrome seen at a tertiary pediatric hospital's department of otolaryngology from Jan. 2007–Jul. 2021 for voice-related concerns. Inclusion criteria included age less than 18 years, diagnosis of Trisomy 21, and complaint of dysphonia. The data extracted included history of dysphonia, co-morbidities, demographic information, age at presentation, perceptual voice assessments, voice quality of life scores, acoustic data, laryngoscopic and/or videostroboscopic exams, and surgical procedures. ResultsTwenty-three total patients met the study criteria. Of these children, 13 (57%) were male and 10 (43%) were female. The mean age at first presentation was 4.08 years (range 12 days–16.3 years). Eleven of the 23 patients presented within the first 12 months of life. Sixteen patients were diagnosed with vocal fold immobility, 13 of which were left-sided unilateral immobility and the remaining 3 were bilateral immobility. 5 patients were diagnosed with vocal fold nodules. 12 children in the immobility group had a history of cardiothoracic surgery at our institution. Only 3 patients had Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) assessments, though all three showed overall dysphonia ratings of severely deviant, with roughness and strain scores being the most severe. DiscussionThe most common etiology of dysphonia in our Down syndrome patient population was vocal fold immobility and hypomobility, as opposed to vocal fold nodules (which is the most common in the general pediatric population). The higher likelihood of cardiac surgery in patients with Trisomy 21 may result in the increased incidence of vocal fold immobility. There should be a low threshold to refer dysphonic patients with Down syndrome for laryngoscopic evaluation, as treatment options may be available.

Maternal Zinc, Copper, and Selenium Intakes during Pregnancy and Congenital Heart Defects.

The effects of zinc, copper, and selenium on human congenital heart defects (CHDs) remain unclear. This study aimed to investigate the associations of the maternal total, dietary, and supplemental intakes of zinc, copper, and selenium during pregnancy with CHDs. A hospital-based case-control study was performed, including 474 cases and 948 controls in Northwest China. Eligible participants waiting for delivery were interviewed to report their diets and characteristics in pregnancy. Mixed logistic regression was adopted to examine associations and interactions between maternal intakes and CHDs. Higher total intakes of zinc, selenium, zinc to copper ratio, and selenium to copper ratio during pregnancy were associated with lower risks of total CHDs and the subtypes, and the tests for trend were significant (all p < 0.05). The significantly inverse associations with CHDs were also observed for dietary intakes of zinc, selenium, zinc to copper ratio, selenium to copper ratio, and zinc and selenium supplements use during pregnancy and in the first trimester. Moreover, high zinc and high selenium, even with low or high copper, showed a significantly reduced risk of total CHDs. Efforts to promote zinc and selenium intakes during pregnancy need to be strengthened to reduce the incidence of CHDs in the Chinese population.

“INCIDENCE AND PATTERNS OF CONGENITAL HEART DISEASES AMONG NEONATES ADMITTED IN SPECIAL NEW BORN CARE UNITS OF DISTRICT HOSPITAL NANDYAL, KURNOOL”

Objective: To nd out the pattern and incidence of congenital Heart defects among neonates in SNCU, District Hospital, Nandyal. Methods: This is a retrospectic hospital-based study conducted over a period of 12 months in the Special new born care unit of District Hospital, Nandyal from 01th January 2021 to 31st December 2021. Neonates (new born up to 28 days of age) admitted are examined in the unit irrespective of their condition comprised the study population. They were rst examined by the medical ofcer at the time of admission and subsequently by a pediatrician. Information of gender, weight, gestational age, were recorded on a predesigned Performa. After clinical examination, relevant investigations like ultrasonography, radiology, echocardiography, laboratory and genetic studies were done to conrm diagnosis if it was needed. Results: Out of 2185 total admissions, 51 (2.28%) neonates were having congenital heart defect. Of them, 23 (45.1%) were male and 28 (54.90%) females. CHD was observed in 76% full-term and 24% pre-term infants. CHD was observed in 32 infants weighing &gt;2,500 g (64% of corresponding birth weight infants); 17 weighing 1,500 to 2,500 g (34%); and 1 weighing &lt;1,500 g (2%). The incidence of CHD was higher in the full-term group. However, the incidence of complex CHD in full-term neonates was high. Conclusion: Findings from our study suggest that the recent incidence and disease pattern of CHD might have changed for both complex and simple forms of CHD in District Hospital, Nandyal.

Congenital heart defects in children of Chelyabinsk: regional aspects of the 20-year monitoring

The problem of congenital heart defects (CHD) in children, it is determined not only by a severe course, early development of disability, high-cost methods of treatment, but also by regional peculiarities. On the basis of the register of CHD in children in Chelyabinsk, the monitoring of prevalence and morbidity indicators from 2000 to 2020, calculated per 1000 children’s population, taking into account its average number, was carried out. During the analyzed period, there was an almost 3-fold increase in the total number of children with CHD: from 691 people in 2000 to 1903 people in 2020. A stable growth of this pathology was revealed in the first year of their life: 3.9 % in 2000, 11.0 % in 2012, 12.3 % in 2020. The prevalence and primary incidence of CHD over the past 20 years have been characterized by a steady increase: from 3.68 and 0.72 in 2000 to 8.04 and 1.48 in 2020, respectively. Septal defects and open ductus arteriosus occupy leading positions in the structure of all CHD, accounting for 61 % in 2000 and 74 % in 2020. An increase in the number of early surgical interventions, especially during the first year of a child’s life (from 11 % in 2000 up to 31 % in 2020) is associated with a decrease in disability (from 15.7 % in 2000 to 4.8 % in 2020). Monitoring of registry data, especially at the regional level, can be a useful mechanism for assessing the situation of CHD, monitoring the effectiveness of both conservative and cardiac surgical treatment.

Concomitant genetic defects potentiate the adverse impact of prenatal alcohol exposure on cardiac outflow tract maturation.

Prenatal alcohol exposure (PAE) is associated with an increased incidence of congenital heart defects (CHD), in particular outflow tract (OFT) defects. However, the variability in the incidence of CHD following PAE has not been fully explored. We hypothesize that a concomitant, relevant genetic defect would potentiate the adverse effect of PAE and partially explain the variability of PAE-induced CHD incidence. The OFT is formed by the second heart field (SHF). Our PAE model consisted of two intraperitoneal injections (3 g/kg, separated by 6 hr) of 30% ethanol on E6.5 during SHF specification. The impact of genetic defects was studied by SHF-specific loss of Delta-like ligand 4 (Dll4), fibroblast growth factor 8 (Fgf8) and Islet1. Acute PAE alone significantly increased CHD incidence (4% vs. 26%, p= .015) with a particular increase in OFT alignment defects, viz., double outlet right ventricle (0 vs. 9%, p= .02). In embryos with a SHF genetic defect, acute PAE significantly increased CHD incidence (14 vs. 63%, p< .001), including double outlet right ventricle (6 vs. 50%, p< .001) compared to controls. PAE (p= .01) and heterozygous loss of Dll4 (p= .04) were found to independently contribute to CHD incidence, while neither Islet1 nor Fgf8 defects were found to be significant. Our model recapitulates the increased incidence of OFT alignment defects seen in the clinic due to PAE. The presence of a concomitant SHF genetic mutation increases the incidence of PAE-related OFT defects. An apparent synergistic interaction between PAE and the loss of DLL4-mediated Notch signaling in OFT alignment requires further analysis.

Evaluation of Second-Trimester Maternal Serum AFP Value in the Detection of Congenital Heart Defects

Background: Congenital heart diseases, as the most common congenital anomaly, are a major cause of serious morbidity and mortality. Objectives: This study aimed to evaluate the level of alpha-fetoprotein in the second trimester of pregnancy and its association with congenital heart defects. Methods: Following a cross-sectional design, singleton pregnant women in the second-trimester were enrolled for the α-fetoprotein (AFP) screening test. Those with normal screening results at the first and second tests were assigned to the control group. Mothers with nuchal translucency (NT) screening equal or greater than 3% of the 99th percentile, without chromosomal anomalies, confirmed with amniocentesis, were referred for a fetal echocardiogram and in presence of congenital heart defects symptoms, assigned to the intervention group. The study groups were compared concerning the serum AFP level and maternal and neonatal outcomes in the second trimester of pregnancy. Statistical significance was considered when P-value &lt; 0.05. Results: A total of 270 women were enrolled in the study, with a mean AFP level of 1.868 ± 0.87 and 1.374 ± 0.39 in the case and control groups, respectively. The mean level of AFP was significantly different between the two groups (P &lt; 0.001). In the second trimester, an AFP level lower than 1 was associated with a significant increase in the likelihood of developing congenital heart anomalies in the fetus. Conclusions: This study demonstrated that the value of maternal AFP level in the second trimester can be considered as an appropriate screening test to predict the incidence of congenital heart defects in neonates.

Important aspects of the development of the children’s cardiological services of the Grodno region. Analysis of sixty years of activity

Introduction.The relatively young science of pediatric cardiology has made enormous breakthroughs in recent years: the labor intensity and complexity of modern diagnostic techniques have increased, and interventional methods of treatment are widely used. Modern pediatric cardiology covers a wide range of diseases: from intrauterine pathology, such as congenital heart and vascular defects, fibroelastosis, various arrhythmias, to acquired diseases represented by arterial hyperand hypotension, systemic vasculitis, autonomic dysfunction, juvenile rheumatoid arthritis.Purpose.To demonstrate the important stages of the development of the children’s cardiological service in Grodno region over a sixty-year period, assess its current state and analyze the dynamics of the incidence rate of children’s heart and vascular diseases during 2005–2019 in this region.Material and methods. During the period of 1960–2019 a retrospective research was carried out using the statistics: report of the chief substitute pediatric cardiologist, report of medical treatment for children during 2005–2019, analytical and conjunctral reports, reviews and references of chief doctors and local pediatricians.Results and discussion. The sixty-years of activity of the children’s cardiological service in Grodno region were analyzed. It was found that over the past 15 years there has been an annual increase in the overall incidence of diseases of the circulatory system (classes I00-I99 ICD 10), while the primary incidence decreased from 331.06 to 265.63 per 100,000 of the child population. The overall incidence of congenital heart defects over the past 15 years was characterized by a low decrease from 916.40 to 800.16 cases against the stabilization of the primary incidence rate.Conclusion.The obtained results indicate the well-organized work of the diagnostic, hospital, dispensary and prophylactic stages of medical assistance to children with cardiovascular pathology.

The current state of prenatal detection of genetic conditions in congenital heart defects.

The incidence of congenital heart defect (CHD) has increased over the past fifty years, partly attributed to routine fetal anatomical examination by sonography during obstetric care and improvements in ultrasound technology and technique. Fetal findings on ultrasound in addition to maternal biomarkers are the backbone of first- and second-trimester screening for common genetic conditions, namely aneuploidy. Since the introduction of non-invasive prenatal testing (NIPT) using next-generation sequencing to sequence cell-free fetal DNA, the detection rate of common trisomies as well as sex chromosomal aneuploidies have markedly increased. As the use of NIPT continues to broaden, the best means of incorporating NIPT into prenatal care is less clear and complicated by misunderstanding of the limitations and non-diagnostic role of NIPT by clinicians and families. In other advancements in prenatal genetic testing, recommendations on the role of chromosomal microarray (CMA) for prenatal diagnosis has led to its increasing use to identify genetic conditions in fetuses diagnosed with CHD. Lastly, as whole exome sequencing (WES) becomes more available and affordable, the next clinical application of next-generation sequencing in prenatal diagnostic testing is on the horizon. While newer genetic tests may provide answers in terms of genetic diagnosis, even more questions will likely ensue for clinicians, researchers, and parents. The objective of this review is to provide the perspective of the evolution of maternal and fetal obstetric care against the backdrop of advancing genetic technology and its impact on families and clinicians.

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.

A Functional Variant Rs492554 Associated With Congenital Heart Defects Modulates SESN2 Expression Through POU2F1.

Hypoxia exposure is responsible for the high incidence of congenital heart defects (CHDs) in high-altitude areas, which is nearly 20 times higher than that in low-altitude areas. However, the genetic factors involved are rarely reported. Sestrin2 (SESN2), a hypoxia stress-inducible gene, protects cardiomyocyte viability under stress; thus, SESN2 polymorphism may be a potential risk factor for CHD. We performed an association study of the SESN2 polymorphisms with CHD risk in two independent groups of the Han Chinese population from two different altitude areas. The allele-specific effects of lead single-nucleotide polymorphisms (SNPs) were assessed by expression quantitative trait locus, electrophoretic mobility shift, and luciferase reporter assays. The molecular mechanism of Sesn2 action against hypoxia-induced cell injury was investigated in embryonic rat-heart-derived H9c2 cells treated with or without hypoxia-mimetic cobalt chloride. SNP rs492554 was significantly associated with reduced CHD risk in the high-altitude population, but not in the low-altitude population. The protective T allele of rs492554 was correlated with higher SESN2 expression and showed a preferential binding affinity to POU2F1. We then identified SNP rs12406992 in strong linkage disequilibrium with rs492554 and mapped it within the binding motif of POU2F1. The T-C haplotype of rs492554-rs12406992 could increase luciferase expression, whereas POU2F1 knockdown effectively suppressed it. Mechanistically, increased Sesn2 protects against oxidative stress and cell apoptosis and maintains cell viability and proliferation. In summary, CHD-associated SNP rs492554 acts as an allele-specific distal enhancer to modulate SESN2 expression via interaction with POU2F1, which might provide new mechanistic insights into CHD pathogenesis.

Novel Autosomal Recessive Splice-Altering Variant in PRKD1 Is Associated with Congenital Heart Disease

Congenital heart defects (CHDs) are the most common types of birth defects, and global incidence of CHDs is on the rise. Despite the prevalence of CHDs, the genetic determinants of the defects are still in the process of being identified. Herein, we report a consanguineous Saudi family with three CHD affected daughters. We used whole exome sequencing (WES) to investigate the genetic cause of CHDs in the affected daughters. We found that all affected individuals were homozygous for a novel splice-altering variant (NM_001330069.1: c.265-1G>T) of PRKD1, which encodes a calcium/calmodulin-dependent protein kinase in the heart. The homozygous variant was found in the affected patients with Pulmonary Stenosis (PS), Truncus Arteriosis (TA), and Atrial Septal Defect (ASD). Based on the family’s pedigree, the variant acts in an autosomal recessive manner, which makes it the second autosomal recessive variant of PRKD1 to be identified with a link to CHDs, while all other previously described variants act dominantly. Interestingly, the father of the affected daughters was also homozygous for the variant, though he was asymptomatic of CHDs himself. Since both of his sisters had CHDs as well, this raises the possibility that the novel PRKD1 variant may undergo autosomal recessive inheritance mode with gender limitation. This finding confirms that CHD can be associated with both dominant and recessive mutations of the PRKD1 gene, and it provides a new insight to genotype–phenotype association between PRKD1 and CHDs. To our knowledge, this is the first report of this specific PRKD1 mutation associated with CHDs.

Incidence, Distribution, Disease Spectrum, and Genetic Deficits of Congenital Heart Defects in China: Implementation of Prenatal Ultrasound Screening Identified 18,171 Affected Fetuses From 2,452,249 Pregnancies

Background: Congenital heart defects (CHDs) are the most common cause of birth defects. Assessment of the incidence, distribution, disease spectrum, and genetic deficits of fetal CHDs in China is urgently needed. Methods: A national echocardiography screening program for fetal CHDs was implemented in 92 prenatal screening–diagnostic centers in China. Findings: A total of 18,171 fetal CHD cases were identified from 2,452,249 pregnancies, resulting in 7·4/1,000 as the national incidence rate of fetal CHD. The incidences of fetal CHD in the six geographical regions, the southern, central, eastern, southwestern, northern, and northwestern, were 8·174 (CI: 7·802–8·554), 7·839 (CI: 7·680–8·000), 7·647 (CI: 7·383–7·915), 7·562 (CI: 7·225–7·907), 5·618 (CI: 5·337–5·906), and 4·716 (CI: 4·341–5·108), respectively, per 1,000 pregnancies. A total of 76·24% cases of fetal CHD were found to be an isolated intracardiac single defect. Among all extracardiac malformations, the CNS was the most common tissue with extracardiac anomalies associated with CHD, accounting for 22·89% of fetal CHD cases. Chromosomal karyotyping identified trisomy 18 as the most common chromosomal abnormality in fetal CHD. Molecular genetic study of copy number variations characterized microdeletion and/or microrepetition/duplication and uniparental disomy. CHD-associated syndromes could be identified with a comprehensive approach integrating prenatal ultrasound, MRI, pathological autopsy, and cytogenetics and molecular genetics. Interpretation: Implementation of prenatal echocardiography is a practically feasible platform to screen fetal CHD, which may reduce the financial and emotional burden of CHD. Funding: This study was supported in part by the Key Project of Science and Technology Planning Project of Hubei Province (2010CDA038), the Hubei Province Natural Science Foundation (2012FFB01203), the Key Project of Hubei Province Natural Science Foundation (2011CDA012 and 2014CFA062), and the New York State Research Foundation for Mental Hygiene (914-3280, 914-3257). Declaration of Interest: All authors have declared that there are no financial conflicts or conflicts of interest with other individuals or organizations. Ethical Approval: The procedures and protocols implemented were reviewed and approved by the Ethics Committees of Maternal and Child Health Hospital of Hubei Province.

The Incidence of Congenital Heart Defects in Offspring Among Women With Diabetes in Saudi Arabia.

Background: The risk of congenital anomalies is increased in infants of diabetic mothers (IDM). The most frequent cardiac anomalies in IDMs include ventricular septal defect, transposition of great arteries, and aortic stenosis.Objective: Estimating the incidence of infants with congenital heart defects (CHD) whose mothers have diabetes in Saudi Arabia at a tertiary hospital in the National Guard Health Affairs (NGHA) system.Materials and methods: This study was a retrospective cohort. The population was all births of type 1 and type 2 diabetic mothers and non-diabetic mothers (also mothers with gestational diabetes) in NGHA by following the exclusion criteria, which were mothers over 40 and below 20 years of age, and other risk factors such as drug-induced congenital disease. The data was from deliveries from January 1st 2018 to January 1st 2019. Data were collected by chart review using the Best-Care system at NGHA hospital. Statistical Package for the Social Sciences (SPSS) version 20 (IBM Corp., Armonk, NY, USA) was used for the statistical analysis.Results: A total of 1838 diabetic mothers and non-exposure, non-diabetic mothers, with the outcome of whether the infant had CHD, were included in this study. Most of the mothers (544, 30.11%) were aged 30-34 years old. About two-thirds of mothers, 1161 (63.24%), weren't diabetic, 500 (27.23%) had gestational diabetes, 132 (7.19%) were type 2 diabetes (T2DM), and 43 (2.34%) were type 1 diabetes (T1DM). Two hundred eighteen (11.82%) offspring had CHD, and the remaining 1625 (88.17%) did not. The most frequent echocardiographic abnormalities in infants of diabetic mothers were patent ductus arteriosus (PDA) (31.75%), patent foramen ovale (PFO) (31.75%), and atrial septal defect (ASD) (23.64%).Conclusion: The incidence of CHD among infants of included mothers in this cohort study was 11.82%. The most frequent echocardiographic abnormalities in the infants of diabetics were PDA and PFO. The incidence of CHD was higher among mothers who had T1DM followed by T2DM, and whose ages were between 30-34.

Congenital Heart Disease: causes and risk factors

Congenital Heart Defect (CHD) is a multifactorial disorder based on both genetic and environmental factors involved in development. The basic problem lies in the structure of heart leading to CHD that occurs in walls, valves, arteries and veins of heart. During cell cycle, the gene that controls this process may mutate, causing disturbance in any portion of heart leading to disturbed blood flow, blood flow in wrong direction or complete blockage. Defect may range from simple with no manifestations to complex with severe symptoms. Simple defects need no treatment while some babies with complex birth defects during birth require special care, vaccination, medication or otherwise treated with surgery. The incidence of CHD has declined from 80 to 20% due to progress in heart surgery techniques, medical treatment and interventional cardiology. Various genetic and non-genetic increase the susceptibility for CHD. The diagnosis and treatment of CHD has greatly improved in recent years. Almost all the children with CHD survive to adulthood and spend healthy and active lives after being treated

The Axenfeld-Rieger Syndrome Gene FOXC1 Contributes to Left-Right Patterning.

Precise spatiotemporal expression of the Nodal-Lefty-Pitx2 cascade in the lateral plate mesoderm establishes the left–right axis, which provides vital cues for correct organ formation and function. Mutations of one cascade constituent PITX2 and, separately, the Forkhead transcription factor FOXC1 independently cause a multi-system disorder known as Axenfeld–Rieger syndrome (ARS). Since cardiac involvement is an established ARS phenotype and because disrupted left–right patterning can cause congenital heart defects, we investigated in zebrafish whether foxc1 contributes to organ laterality or situs. We demonstrate that CRISPR/Cas9-generated foxc1a and foxc1b mutants exhibit abnormal cardiac looping and that the prevalence of cardiac situs defects is increased in foxc1a−/−; foxc1b−/− homozygotes. Similarly, double homozygotes exhibit isomerism of the liver and pancreas, which are key features of abnormal gut situs. Placement of the asymmetric visceral organs relative to the midline was also perturbed by mRNA overexpression of foxc1a and foxc1b. In addition, an analysis of the left–right patterning components, identified in the lateral plate mesoderm of foxc1 mutants, reduced or abolished the expression of the NODAL antagonist lefty2. Together, these data reveal a novel contribution from foxc1 to left–right patterning, demonstrating that this role is sensitive to foxc1 gene dosage, and provide a plausible mechanism for the incidence of congenital heart defects in Axenfeld–Rieger syndrome patients.