Is the Rate of Congenital Heart Defects Detected by Fetal Echocardiography Among Pregnancies Conceived by In Vitro Fertilization Really Increased?

Background and aim of the study: Pregnancies obtained by assisted reproductive technology (ART) are associated with an increased risk of complications and congenital anomalies, particularly congenital heart defects (CHDs). Therefore, our aim is to evaluate, retrospectively, the prevalence of CHD in ART pregnancies in our two centers and analyze their characteristics and outcomes. Methods: Observational study including fetuses conceived by ART referred between June 2011 and September 2020 and undergoing a fetal cardiac ultrasound scan. Cases with genetic, chromosomal abnormalities or extracardiac malformations were excluded. Population included 1511 pregnancies, which consisted of 269 twins and 1242 singletons, 547 IVF (in vitro fertilization), 773 ICSI (intracytoplasmic sperm injection) and 191 oocyte donations (OD). Results: CHDs were found in 29 fetuses, with an overall prevalence of 1.92% (29/1511), 1.85% (23/1242) in singletons and 2.23% in twins (6/269). Thirteen were IVF, eight ICSI and eight OD cases, with a greater risk of CHD after IVF and OD (IVF: 13/29 (44.8%)—one twin; ICSI: 8/29 (27.6%)—three twins); 22 had major and 7 minor defects. Two pregnancies with a hypoplastic left heart were terminated; the majority of live-born cases needed surgery. Three babies died (two post-surgery, one had a late death). Conclusions: Our data show an increased prevalence of CHD after ART with a heterogeneous spectrum of diagnoses, mainly major defects.

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Fetal echocardiography in Lithuania: traditions, significance and problems

Acta medica Lituanica ◽

10.15388/amed.2010.21684 ◽

2010 ◽

Vol 17 (3-4) ◽

pp. 116-122

Author(s):

Ramunė VANKEVIČIENĖ

Keyword(s):

Congenital Heart Defects ◽

Congenital Heart ◽

Heart Diseases ◽

Fetal Echocardiography ◽

Heart Defects ◽

Tertiary Care ◽

Congenital Heart Diseases ◽

Conduction Disturbances ◽

Tertiary Care Centers ◽

Almost All

Background. The discovery of ultrasound has made a revolution in almost all fields of medicine. The past three decades have withessed an intensive development of fetal echocardiography methods and technique. The aim of the paper is to present a review of the results and trends of the last 10 years of fetal echocardiography in Lithuania and to show the spectrum and outcomes of prenatally detected congenital heart diseases. Materials and methods. Fetal echocardiography was performed for 1816 fetuses during the period from 1999 to 2009. Results. Cardiac pathology was diagnosed in 176 (9.7%) fetuses. Heart defects were detected in 112 (63.6%) of them, cardiac rhythm and conduction disturbances in 62 (35.2%), cardiomyopathy in 2 (1.1%) fetuses, and heart rhabdomyoma in 1 (0.6%) fetus. The general rate of the postnatal diagnosis of congenital heart defects in Lithuania was about 10%. Most of fetal cardiac diseases (70.5%) were diagnosed after 22 weeks of gestation. Because most of antenatally diagnosed congenital heart defects (74%) were critical and inconsistent with life, a large part of newborns (40.2%) died in the neonatal period, 10.7% of fetuses died in utero, and 8% of pregnancies were terminated by abortion. The data demonstrate good tendencies: the diagnosis has become earlier, a wider spectrum of diseases have been diagnosed, more newborns have survived. Our survey shows that 41.1% of newborns with prenatally diagnosed congenital heart defects have survived. Conclusions. 10% of severe congenital heart diseases are detected prenatally in Lithuania. The efficacy of antenatal diagnostics depends on the qualification of specialists, the number of tertiary care centers, on a successful collaboration among pediatric cardiologists, obstetricians and geneticists. The main problem is an insufficient preparation of obstetricians, the uncertified favor of pediatric cardiologist. Keywords: congenital heart disease, fetal echocardiography, antenatal diagnostics

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Abstract 2722: Large Scale Mutation Discovery Screen Identifies Functionally Variant UGDH Alleles in Patients with Atrioventricular Valve Defects

Circulation ◽

10.1161/circ.116.suppl_16.ii_604 ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Jeroen Bakkers ◽

Sonja Chocron ◽

Victor Gouriev ◽

Kelly Smith ◽

Ronald Lekanne dit Deprez ◽

...

Keyword(s):

Candidate Genes ◽

Congenital Heart Defects ◽

Congenital Heart ◽

Large Scale ◽

Heart Defects ◽

Glucose Dehydrogenase ◽

Model Organisms ◽

Missense Mutations ◽

Coding Regions

Background: Congenital heart defects are the most common birth defects. Although genetic dispositions are believed to cause CHDs, only few genes have been identified that harbour mutations causing such defects. Studies in model organisms have identified many essential genes for cardiac development. UDP-glucose dehydrogenase (UGDH) enzymatic activity is required for the signal transduction of FGF and Wnt ligands and zebrafish jekyll/ugdh mutations lack AV valves. Methods and Results: From literature candidate genes were selected that are essential for AV canal-, septum-, and valve formation. By large scale sequencing we analysed the coding regions of 36 candidate genes in 192 patients with reported AVSDs. As a result we identified 457 genetic variations of which 207 variants are in flanking non-coding regions, 156 variants are in coding regions but silent and 94 variants are non-synonymous variants that alter the protein sequence. Comparison with the available databases such as HapMap and screening 350 control individuals resulted in the validation of 49 non-synonomous missense mutations in 23 genes only present in the patient group. These included novel GATA4 missense mutations (R285C and M224V) located in the highly conserved DNA binding domains, which by in vitro analysis significantly reduce transcriptional activity of the protein. Three patients with mitral valvar prolapse and mitral regurgitation were identified with novel missense mutations in the UDP-glucose dehydrogenase (UGDH) gene (R141C and E416D). In vitro experiments demonstrated a negative affect on enzyme activity and stability by a change in protein conformation. Furthermore, experiments in zebrafish jekyll/ugdh mutants showed that UGDH R141C and UGDH E416D couldn’t rescue the defects in AV formation demonstrating an inactivating effect of these missense mutations in vivo. Conclusions: A model organism based candidate gene screen in CHD patients resulted in the identification of novel functional missense mutations in the UGDH gene not previously implicated in congenital heart defects.

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Fetal Echocardiography:Short Term Profile from Shahid Gangalal National Heart Centre, Kathmandu, Nepal

Nepalese Heart Journal ◽

10.3126/njh.v13i1.14538 ◽

2016 ◽

Vol 13 (1) ◽

pp. 9-12

Author(s):

Sudhir Regmi ◽

Deewakar Sharma

Keyword(s):

Pregnant Women ◽

Congenital Heart ◽

Fetal Echocardiography ◽

Tertiary Care ◽

Outcome Data ◽

Cross Sectional ◽

Vitro Fertilization ◽

History Of ◽

Sectional Analysis

Background and Aims: Fetal echocardiography is helpful in early detection of Congenital Heart Disease. Our study was conducted to evaluate the most common indications of referral and outcome in a tertiary-care fetal echocardiography practice.Methods: A Cross-sectional analysis of all pregnant women referred by obstetricians to cardiology unit for fetal echocardiography over a 1-year period (July 2014 and July 2015) was performed. The primary indications for referral for fetal echocardiography were obtained from the obstetric referral forms. Outcome data were extracted from performa containing client’s demographic, physical examination and the fetal echocardiograhic data. Postnatal Echocardiography was advised to all cases having positive echocardiographic finding.Results: A series of 251 fetal cardiac studies were reviewed. Average gestational age was 25.6 weeks (range, 18 to 38 weeks). Thirty-eight (15.1%) pregnant women had abnormal fetal cardiac findings. The most common referral for fetal cardiac scan was related to maternal indications (48.6%). Other indications were abnormal prenatal fetal findings in ultrasonography (23.1%), family history of CHD (12%), general screening (15.5%), and follow up of IVF (In-vitro fertilization) (0.8%). The highest yield of significant abnormal findings was there among patients referred with abnormal prenatal fetal finding in ultrasonography (47%).Conclusion: Majority of referral were for abnormal prenatal ultrasonographic findings. So, fetal Echocardiography is an important part of overall management of the pregnancy at risk for producing an infant with congenital heart disease.Nepalese Heart Journal 2016; 13(1): 9-12

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OP35.07: In vitro fertilization does not predict fetal diagnosis of congenital heart disease

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.9584 ◽

2011 ◽

Vol 38 (S1) ◽

pp. 157-157

Author(s):

J. K. Votava-Smith ◽

J. S. Glickstein ◽

L. Simpson ◽

I. A. Williams

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

In Vitro Fertilization ◽

Congenital Heart ◽

Fetal Diagnosis ◽

Vitro Fertilization

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Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease

Nature Communications ◽

10.1038/s41467-021-25329-5 ◽

2021 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Yonatan R. Lewis-Israeli ◽

Aaron H. Wasserman ◽

Mitchell A. Gabalski ◽

Brett D. Volmert ◽

Yixuan Ming ◽

...

Keyword(s):

Congenital Heart Defects ◽

Self Assembly ◽

Human Heart ◽

Congenital Heart ◽

Cardiac Development ◽

Heart Defects ◽

Cell Types ◽

Cellular Level ◽

Cardiac Tissues

AbstractCongenital heart defects constitute the most common human birth defect, however understanding of how these disorders originate is limited by our ability to model the human heart accurately in vitro. Here we report a method to generate developmentally relevant human heart organoids by self-assembly using human pluripotent stem cells. Our procedure is fully defined, efficient, reproducible, and compatible with high-content approaches. Organoids are generated through a three-step Wnt signaling modulation strategy using chemical inhibitors and growth factors. Heart organoids are comparable to age-matched human fetal cardiac tissues at the transcriptomic, structural, and cellular level. They develop sophisticated internal chambers with well-organized multi-lineage cardiac cell types, recapitulate heart field formation and atrioventricular specification, develop a complex vasculature, and exhibit robust functional activity. We also show that our organoid platform can recreate complex metabolic disorders associated with congenital heart defects, as demonstrated by an in vitro model of pregestational diabetes-induced congenital heart defects.

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Abnormal Expression of MST1 and YAP1 in Fetal Heart Tissue in a Hyperglycemic Environment and Their Roles in Mediating Apoptosis

10.21203/rs.3.rs-71423/v1 ◽

2020 ◽

Author(s):

Dongmei Su ◽

Yanhua Li ◽

Lina Guan ◽

Qian Li ◽

Cuige Shi ◽

...

Keyword(s):

Diabetes Mellitus ◽

Western Blot ◽

Congenital Heart Defects ◽

Congenital Heart ◽

Heart Defects ◽

Maternal Diabetes ◽

Cardiomyocyte Apoptosis ◽

Induced Apoptosis

Abstract Background：Gestational diabetes mellitus is a risk factor for congenital heart defects. The article aimed to investigate the expression and roles of Mst1, Yap1, Last1/2 and Survivin in modulating HG-induced cardiomyocyte apoptosis and maternal diabetes-induced heart abnormality. Methods：The gene and protein expression were assessed by quantitative PCR, western blot, and immunohistochemical staining. The protein phosphorylation level were analyzed by western blot .Knockdown of gene expression were assessed by RNA interference. Hoechst 33342 staining assay were performed to explore H9C2 apoptosis. Diabetes mellitus was induced in rats using streptozotocin.Results：Our results revealed that increased MST1 protein levels in the heart tissues of the offspring of diabetic rats in vivo occurred concomitantly with HG-induced apoptosis in H9C2 cardiomyocytes in vitro. Knockdown and overexpression experiments showed that MST1 played a key role in mediating HG-induced apoptosis in cardiomyocytes. Downregulation of YAP1 was associated with HG-induced, MST1-mediated cardiomyocyte apoptosis. Further study showed that MST1 downregulated the protein level of YAP1 through mediation of YAP1 phosphorylation on Ser127 and Ser397; this process also required LATS1/2 participation. MST1 overexpression increased the phosphorylation levels of LATS1/2, which were also shown to be increased in the heart tissues of diabetic offspring. We also found that YAP1 mediated the expression of Survivin during HG-induced apoptosis, and the Survivin-inhibitor YM155 partially inhibited the role of YAP1 in suppressing apoptosis induced by HG in cardiomyocytes. Conclusion：These findings reveal a regulatory mechanism of MST1/YAP1/Survivin signaling in modulating cardiomyocyte apoptosis in vitro and maternal diabetes-induced congenital heart defects in vivo.

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