Incidence Of Cardiac Malformations Research Articles

Heart malformation is an early response to valproic acid in developing zebrafish.

Valproic acid (VPA) is a branched short-chain fatty acid primarily used in epilepsy, but is also used in bipolar disorder, migraine, and psychotic disorders. Despite its wide range of use, it is a teratogen resulting in various congenital abnormalities. Although a large number of scientific studies evidenced the teratogenic effects, there are limited data on embryonic exposure to VPA at specific or different stages of early embryogenesis. Based on this, the present study was planned to investigate the embryonic exposure to VPA at specific and different hours post fertilization (hpf) in zebrafish embryonic model. In first set of experiments, embryos from spawning groups of adult zebrafish were exposed to different molar concentrations of VPA at 2.5 hpf, and in the second set of experiments, embryos were exposed to VPA 100μM at 24 hpf, 36 hpf, 48 hpf, 72 hpf, and 96 hpf. The parameters examined were hatching rate, mortality, morphology, body length, pericardial sac size, heartrate, anatomical changes in heart, skeletal and notochord till 120 hpf. It was observed that the embryos exposed to VPA at 2.5 hpf suffered from cardiac abnormalities including heart malformation, bradycardia, circulatory failure, and pericardial sac enlargement which was more apparent in embryos exposed to 100μM VPA. In the second set of experiments, embryos exposed to VPA 100μM at 24 hpf and 36 hpf suffered from heart malformations, but there was no incidence of cardiac malformation in embryos exposed to VPA at 48 hpf, 72 hpf, and 96hpf. From the results, it was evident that exposure to VPA at early developmental stage of embryogenesis produced congenital cardiac abnormalities. Since VPA is a selective HDAC inhibitor, histone acetylation with aberrant gene expression during cardiogenesis might be the underlying cause of cardiac malformation.

1264Genetic investigation of gap junction protein, alpha 5 of in Russian families with sick sinus syndrome

Abstract Background Connexin 40 (Cx40) is a gap-junction protein expressed in the heart where it mediates the coordinated electrical activation of the atria and ventricular conduction tissues, facilitates cell-to-cell adhesion, and provides pathways for direct intercellular communication. Recent studies have shown that Cx40 null mice have cardiac conduction abnormalities with a very high incidence of cardiac malformations in heterozygous (18%) and homozygous (33%) animals, indicating that Cx40 plays a vital role in cardiomorphogenesis.The process that mediates interactions between an AV node cell and its surroundings that contributes to the process of the AV node cell communicating with a bundle of His cell in cardiac conduction. Encompasses interactions such as signaling or attachment between one cell and another cell, between a cell and an extracellular matrix, or between a cell and any other aspect of its environment. Methods This first study of SSS in a Russian population comprises the clinical and genetic investigation of 30 Russian families, including 67 members. The involvement of the Cx40 genes was investigated. The control group consisted of 615 patients without clinical ECG manifestations of cardiac diseases. All the examinees have undergone ECG, echocardioscopy, electrophysiological examination of the heart. Results We conclude that polymorphism 44AG has mutation-specific effects on Cx40-related SSS. Conclusions Mutation Cx40 impairs gap junction formation at cell-cell interfaces. This is the first demonstration of a germ line mutation in a connexin gene that emphasizes the importance of Cx40 in normal propagation in the specialized conduction system. This study provides further evidence of the genetic heterogeneity of SSS.

Cardiovascular malformations in infants of diabetic mothers: a retrospective study

Background: Despite improvements in medical care provided during pregnancy to diabetic mothers, the cardiac complications in their infants are still more frequent than in infants of general population.Methods: A retrospective case-control study was performed between the years 2017-2018 on two groups of newborns, recording details of outcome of live born babies born to diabetic and non-diabetic mothers.Results: Data were extracted from medical records, and the descriptive and analytical statistics of this information was duly applied. in a total of 50 studied infants, 40 cases (80%) of cardiovascular anomalies have been diagnosed. Most of the cardiac anomaly was hypertrophic cardiomyopathy. The incidence of cardiovascular anomalies in infants of diabetic mothers is significantly higher than the infants of non-diabetic mothers (P=0.002). The type of maternal diabetes (diabetes mellitus, overt or gestational diabetes) did not bring about any significant difference in the incidence of cardiac malformations in infants (P=0.406).Conclusions: The incidence of cardiovascular anomalies in infants of diabetic mothers is significantly higher than the infants of non-diabetic mothers. Many of the infants were asymptomatic and therefore clinical examination and follow up in infants of diabetic mothers is important.

Clinical analysis of prenatal ultrasound diagnosis of fetal cardiovascular malformations in the first and second trimesters of pregnancy: A CARE-compliant article.

Fetal cardiovascular malformations is widely focused and screened, but the accuracy of screening is not satisfactory. In this study, we compared the types of congenital heart malformation, accompanying diseases and fetal outcomes in the first and second trimesters of pregnancy to clarify the advantage of early screening.From January 2013 to June 2018, 230 fetuses were diagnosed with congenital heart malformations using ultrasound method in Qilu Hospital of Shandong University, and divided into 2 groups:the first trimester fetuses (group A) and the second trimester fetuses (group B). In addition, we collected and organized medical data of 347 cases diagnosed with congenital heart disease during 1998 to 2005 (group C). We compared the spectrum of congenital heart disease, associated comorbidities and outcome of fetuses diagnosed with congenital heart disease.There were differences in the types and incidence of cardiac malformations between the first and second trimesters of pregnancy. The number of cases of non-cardiac malformation, congenital heart disease with single ventricular circulation, fetal intrauterine death and premature pregnancy termination was significantly lower in the late stage (group A and group B) than that in the early stage (group C). More patients were screened for trisomy 21, 18, 13 syndromes and Turner syndrome in group A than group B (P <.001). More fetuses with a 22q11 deletion were screened in group B than group C.Early pregnancy screening using ultrasound diagnosis is very important for fetuses with congenital heart disease.

Ovarian Stimulation Increases the Risk of Fetal Cardiac Defects of Pups Exposed to Severe Maternal Hyperglycemia

To study the incidence of congenital heart defects (CHD) in offspring born to hyperglycemic mothers with and without ovarian stimulation. Reproductive biology. Mouse model. N/A. Hyperglycemia was induced in CD-1 wild type female mice using a single intraperitoneal dose of 150 mg/kg of streptozotocin. Stimulated dams (SD); (n=3) were injected with pregnant mare serum and human chorionic gonadotropin 48 hours apart. Non-stimulated dams (NSD); (n=4) were not injected. Both groups were mated with normal male CD-1 mice for timed pregnancies. Fetal hearts were extracted on embryonic day 16.5 and histological analyses was performed. Student's t-tests were employed to compare the incidence of cardiac defects in the SD and NSD groups. P ≤ 0.05 was significant. The incidence of CHD in progeny of diabetic dams with and without ovarian hyperstimulation. The average litter size was higher in SD compared to NSD. The average blood glucose for the SD and NSD was similar. Overall, the incidence of cardiac malformations did not differ between the two groups. However, in severe maternal hyperglycemia (>400 mg/dL), there was a higher incidence of fetal cardiac malformations in the pups born to SD vs NSD.

Prenatal ultrasonic diagnosis of fetal isolated levocardia

Objective To investigate the clinical application valve of prenatal ultrasound in diagnosis of fetal isolated levocardia(IL). Methods Thirty-eight IL fetuses diagnosed in three prenatal diagnosis centers from 2000 to 2016 were reviewed with their prenatal ultrasound features and cardiac and extracardiac malformations. Results Thirty-eight IL cases included 19 cases of left isomerism(LI), 14 cases of right isomerism(RI) and 5 non-classified cases. The overall incidence of malformations in IL patients was 97.4% with 94.7% in LI patients and 100% in RI patients. The incidence of cardiac malformations was 92.1% with 84.2% in LI patients and 100% in RI patients. The most common congenital heart diseases were: right ventricle outlet obstruction, univentricular physiology and atrioventricular septal defect. Anomalous pulmonary venous connection was more commonly seen in LI patients than in RI patients. The most common extracardiac malformation was duodenal obstruction(86.9%). Inferior vena cava interruption and polysplenia were more commonly seen in LI patients.Juxtaposition of aorta and inferior vena cava and asplenia were more commonly seen in RI patients. Conclusions IL is very rarely seen in population with high incidence of congenital heart diseases and extracardiac malformations. Key words: Ultrasonography, prenatal; Isolated levocardia; Heart defect, congenital; Fetal malformation

Incidence and anatomy of cardiac malformations in children conceived by assisted reproduction techniques - A review.

The aim of this study is to identify the occurrence of cardiac malformations occurred in children conceived by assisted reproduction techniques (ART) in the international literature in Medline database from 1999 to 2012.The search returned data on 32,000 births, whose 21,000 were conceived naturally and 11,000 were conceived by ICSI and/or IVF. The incidence of cardiac malformations in general population situations was 0.4%.The incidence of cardiac malformations by ART was 1.8% from ICSI and IVF. Among the situations of conceived naturally was observed 88 cases of cardiac malformations, which were: Atrial Septal Defect: 26 cases 29.55%, Change in the interventricular septum: 18 cases 20.45%, coarctation of the aorta: 13 cases 14.77%, aortic stenosis: 11 cases 12.5%, tetralogy of Fallot: 5.68% 5 cases, stenosis of the pulmonary trunk: 5 cases 5.68% other: 11.37% 10 cases. In cases of cardiac malformations in children conceived by IVF and ICSI, 198 cases were found, which were: CIA: 58 cases 29.30%, Change in the interventricular septum: 37 cases 18.69%, coarctation of the aorta: 20 cases 10.10%, aortic stenosis: 18 cases 9.09%, tetralogy of Fallot: 11 cases 5.55%, stenosis of the pulmonary trunk: 6 cases 3.03%, Other: 48 cases 24.24%. There remain opened questions about infertility and risk factors involving ART. Further research is clearly required. Health care providers should counsel infertile couples seeking assisted reproduction by IVF and technology.

Genetic Screening of the Canine Connexin 40 Gene in Dogs with Inherited Cardiac Conduction Defects

Connexin 40 (Cx40) is a gap-junction protein expressed in the heart where it mediates the coordinated electrical activation of the atria and ventricular conduction tissues, facilitates cell-to-cell adhesion, and provides pathways for direct intercellular communication. Recent studies have shown that Cx40 null mice have cardiac conduction abnormalities with a very high incidence of cardiac malformations in heterozygous (18%) and homozygous (33%) animals, indicating that Cx40 plays a vital role in cardiomorphogenesis. Since several inherited cardiac conduction defects have also been found in dogs, we hypothesized that the clinical findings are genetically linked to a tissue-specific mutation or mutations in the canine Cx40 gene. We therefore screened the Cx40 gene in dogs with inherited cardiac conduction defects for mutations. In this study, we have identified three heterozygous base changes (C384G, C402T, C837T) in the dogs screened and determined them to be synonymous mutations. These mutations, however, have recently been found in an unrelated group of normal dogs.

High incidence of cardiac malformations in connexin40-deficient mice.

Gap junctions are intercellular channels formed by oligomerization of a protein called connexin (Cx). The heart expresses at least three connexin isotypes: Cx40, Cx43, and Cx45. A possible role for Cx40 in cardiac morphogenesis remains to be determined. We have characterized the anatomy and histology of fetal and newborn hearts obtained from crossing Cx40-deficient mice of mixed genetic background (C57BL/6x129Sv). Hearts were serial-sectioned (5 microm) along the coronal plane, stained with hematoxylin-eosin, and visualized by conventional light microscopy. Cardiac malformations in mice lacking Cx40 in one allele (Cx40+/-) included bifid atrial appendage, ventricular septal defect, tetralogy of Fallot (TOF), and an aortic arch abnormality. In Cx40-/- mice resulting from crossing of Cx40+/- mice, the most common cardiac malformations were double-outlet right ventricle (DORV), TOF, and endocardial cushion defects. Overall incidence of cardiac malformations was 6/33 (18%) in Cx40+/- mice and 4/12 (33%) in Cx40-/- mice. No cardiac malformations were observed in 15 wild-type mice studied. In addition, we examined 39 hearts from offspring of Cx40-/- matings. Frequency of cardiac malformations was even higher in this group (44%). Over one third of the hearts (14 of 39) showed conotruncal malformations corresponding to either DORV or TOF. Endocardial cushion defects were found in 3 out of 39 hearts. Our results suggest that Cx40 participates in cardiac morphogenesis, likely in association with other (unknown) products whose expression may vary with the genetic background of the mice.

Embryotoxicity of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin in the ring‐necked pheasant

AbstractFertilized eggs of ring‐necked pheasants (Phasianus colchicus) were injected into the albumin or yolk with vehicle or graded doses of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) (0.01, 0.1, 1, 10, 100, 1,000, 10,000, or 100,000 pg TCDD/g egg) on day 0 of embryonic development and toxicity was assessed in 1‐d‐old hatchlings and 28‐d‐old chicks. The most sensitive effect of in ovo TCDD exposure was induction of hepatic ethoxyresorufin‐O‐deethylase (EROD) activity in 1‐d‐old hatchlings. The ED50 for this response was 312 pg TCDD/g egg. Embryo mortality was the most sensitive sign of toxicity. The TCDD dose that caused 50% mortality above control (LD50) when injected into the egg albumin or yolk was 1,354 and 2,182 pg TCDD/g egg, respectively. At egg TCDD doses up to and including 1,000 pg TCDD/g egg, no effect was detected in 1‐d‐old hatchlings and 28‐d‐old chicks in body growth, organ weights, carcass morphometrics, incidence of edema, or incidence of histological alterations in the liver, spleen, heart, Bursa of Fabricius, or thymus. Egg TCDD doses as high as 1,000 pg TCDD/g egg also had no effect on cardiac morphometrics or incidence of cardiac malformations in 1‐d‐old hatchlings, or on antibody‐mediated immunity in 28‐d‐old chicks. We conclude that embryo mortality is the most sensitive sign of TCDD toxicity in the ring‐necked pheasant following in ovo exposure. The ring‐necked pheasant embryo is less sensitive than the chicken (Gallus domesticus) embryo and more sensitive than the eastern bluebird (Sialia sialis) embryo to TCDD toxicity.

The causes and underlying developmental mechanisms of congenital cardiovascular malformations: a critical review.

Cardiovascular malformations are the second most common type of birth defect, occurring in 5-8/1,000 livebirths with a still higher prevalence among stillborn infants and spontaneously aborted embryos and fetuses. Dealing effectively with the high frequency of heart defects means reducing the incidence of cardiac malformations in the world. In this paper we cite some of the genetic and environmental risk factors associated with congenital cardiovascular malformations, describe the putative biochemical nature of the genetic predisposition relative to environmentally induced teratogenesis, and either support or discourage the use of available methods as strategies in preventing cardiovascular anomalies.

Congenital heart diseases in swine.

One hundred twenty-two congenital cardiac anomalies were diagnosed in 83 pigs (4.35%) during necropsies of 1906 pigs from one day to four years of age during an 11-month period. The incidence of cardiac malformation was higher at 29 to 56 days of age. Of the 83 pigs with cardiac anomalies, 47 (56%) were male and 36 (44%) were female, and of these, 15 (18%) were purebred and 68 (82%) were crossbred pigs. Of the 15 purebred pigs with cardiac malformation, there were seven Landrace pigs, four Large White pigs, three Duroc Jersey pigs, and one Yorkshire pig; whereas 94% of the 68 crossbred pigs were crossbred among Landrace, Duroc Jersey, and Large White. The 122 cardiac anomalies found in the 83 pigs were: dysplasia of the tricuspid valve in 42 pigs, atrial septal defect in 31 pigs, subaortic stenosis in 22 pigs, ventricular septal defect in nine pigs, persistent common atrioventricular canal in eight pigs, malformation of the moderator band in seven pigs, persistent vena cava in one pig, persistent truncus arteriosus in one pig, and pulmonary stenosis in one pig. The pathological features of the anomalies in swine were similar to those described in small animals and in man. The findings indicate that spontaneous porcine cardiac anomalies might provide models for cardiovascular investigators to study the etiology and pathogenesis of congenital heart diseases in man and other animals.

Heart Disease in Infancy

Infants with heart disease have unique problems that can usually be accurately diagnosed. Furthermore, in the majority of cases, surgical treatment, corrective or palliative, is successful. This text is welcome because it is one of the few dedicated to the problems of the infant. After consideration of the incidence of cardiac malformations, six chapters are devoted to methods of diagnosis. The rest of the text describes specific cardiac anomalies, which are grouped by their hemodynamic abnormalities. These are divided according to the presence or absence of cyanosis in association with the degree of pulmonary blood flow. These four chapters are completed by a section on pulmonary venous obstruction. The authors' style makes the book easy to read, in contradistinction to the usual multiauthored texts. However, the book is uneven in its emphasis and there is uncertainty about the optimum audience. The chapter on cardiac catheterization and angiocardiography is detailed and

Incidence of cardiac malformations at birth and later, and neonatal mortality.

Incidence of cardiac malformations at birth and later, and neonatal mortality.

Incidence of cardiac malformations in Greenlandic Eskimos.

757 eskimo children born in Godthab, Greenland, in the years 1957–1964 have been reexamined 1966. 10 certain and 4 probable cases of congenital heart disease were diagnosed, mostly cases of ventricular septal defect. The incidence of 1.3–1.9% is the highest registered in any ethnic group. The average mother's age of the patients was 32.1 years, the average mother's age of the total material was 26.8 years (0.01> P>0.001). The patients' average number in the sibship was 6.3, differing significantly (0.01> P>0.001). The patients' average number in the sibship was 6.3, differing significantly (0.01> P>0.001) from that of 3.2 in the total material. The social standard of the families of the patients was low. There is some indication that the incidence of cardiac malformations in the Greenlandic population is decreasing. This may be due either to improved social conditions or to a changing reproductive pattern with relatively fewer children born to old mothers.

The incidence of cardiac malformations in Greenlandic eskimos.

Abstract. 757 children born in Godthåb, Greenland, in the years 1957–1964 were reexamined in 1966. Ten certain and four probable cases of congenital heart disease were diagnosed, mostly cases of ventricular septal defect. The incidence of 1.3‐1.9% is the highest registered in any ethnic group. The average mother's age of the patients was 32.1 years, the average mother's age of the total material 26.8 years. This difference is significant. The patients' average number in the sibship was 6.3, differing significantly from that of 3.2 in the total material. The social standard of the families of the patients was low. There is some indication that the incidence of cardiac malformations in the Greenlandic population is decreasing. This may be due either to improved social conditions or to a changing reproductive pattern with relatively fewer children born to old mothers.

Cardiac malformations in rats induced by exposure of the mother to carbon dioxide during pregnancy.

Seventy-one pregnant rats of a Sprague-Dawley strain were exposed for a single 24-hour period to a gas mixture of 6 per cent carbon dioxide, 20 per cent oxygen and 74 per cent nitrogen on different days during gestation. There were 530 offspring and these were compared with 159 newborn rats from 21 control dams. The incidence of cardiac malformations was 23.4 per cent in the test group and 6.8 per cent in the control group with the highest incidence in the test group occurring when the exposure was on the tenth day of gestation. Isolated ventricular septal defects, situated in the lower and posterior part of the muscle septum, were found in 8 cases, ventricular septal defects with overriding aorta in 24 cases and ventricular septal defects with partial transposition in 20 cases. Forty-seven of the abnormal hearts had a myocardial thickening accompanied by narrowing of the pulmonic or aortic outflow channel with or without other abnormalities, such as atresia of the mitral or tricuspid valves and hypoplasia of the aorta or pulmonary artery. There was a slight increase in perinatal mortality in the test group, and a lower frequency of male offspring. The average body weight was 18.9 per cent higher in the test group.