Fetal Cardiac Defects Research Articles

Maternal-fetal comorbidities and obstetrical outcomes of fetal single ventricle cardiac defects: 10years' experience with a multidisciplinary management protocol at a single center.

To describe and compare maternal and fetal comorbidities and obstetrical outcomes in pregnancies with hypoplastic left and right heart (HLHS and HRH) single ventricle cardiac defects (SVCD) from a single center under a multidisciplinary protocol. A single center retrospective review of fetal SVCD from 2013 to 2022. Maternal-fetal comorbidities, delivery, and postnatal outcomes were compared between HLHS and HRH using descriptive statistics and univariate and multivariate analyses. Of 181 SVCD pregnancies (131 HLHS; 50 HRH), 9% underwent termination, 4% elected comfort care, 5 died in utero and 147/152 liveborns survived to the first cardiac intervention. Cesarean delivery occurred in 57 cases (37%), planned in 36 and unplanned in 21. Comorbidities, which did not differ between HLHS and HRH, included fetal growth restriction (FGR, 17%), prematurity (14%), maternal hypertension (9%), maternal obesity (50%), fetal extracardiac anomalies and chromosome anomalies (12%, 13%). In multivariate analysis, only earlier gestational age at delivery and oligohydramnios predicted decreased odds of survival at one year. Maternal-fetal comorbidities are common in both HLHS and HRH. Earlier gestational age at delivery and oligohydramnios predict lower postnatal survival. FGR, even with severe early onset, did not significantly impact short- or long-term neonatal survival in single ventricle conditions.

The impact of early diagnosis of fetal single-ventricle cardiac defects on reproductive choices

Congenital heart defects are the most common fetal anomaly. Congenital heart defects with single ventricle cardiac defects have high mortality rates, and in pregnancies diagnosed with this condition, patients are often offered termination of pregnancy (TOP) as an option. This study aimed to investigate the relationship between gestational age at diagnosis and reproductive choices in fetuses diagnosed with single ventricle cardiac defects. We conducted a retrospective single-center cohort study in which 158 patients with a fetal diagnosis of single ventricle cardiac defects (SVCD) were reviewed. Cases were categorized as isolated or complex. Complex cases included fetuses with SVCD in addition to other fetal extracardiac anomalies (ECA) or chromosomal abnormalities. 158 patients were diagnosed with SVCDs during the study period. Of those, 37 (23.4%) underwent termination of pregnancy, 113 (71.5%) delivered, and 8 (5.1%) had an intrauterine fetal demise. Gestational age at diagnosis and race were significant predictors of the termination decision. The median gestational age at diagnosis was earlier in the TOP group (20.4 vs. 23.6 weeks) (p < 0.001). SVCD diagnosed in early gestation (11 weeks-14 weeks 5 days) were more likely to terminate compared to Mid (15 weeks-27 weeks 5 days) and late (28+ weeks) gestation (54.2 % vs 23.2% and 2.9%) (p<0.001). Earlier gestational age at diagnosis was correlated with earlier gestational age at termination (r= 0.92, p < 0.001). Termination of pregnancy is more common when the SVCD is diagnosed earlier in gestation. This could be explained by the fact that early diagnoses allow parents to make deliberate and informed decisions.

Clinical characteristics of cardiac defects fetuses and the impact of multi-disciplinary team cooperation approach on the pregnancy decision making

Objective: To analysis the clinical characteristics of 400 fetuses with heart defects and the impactors of pregnancy decision making, and explore the influence of a multi-disciplinary team (MDT) cooperation approach on it. Methods: Clinical data of 400 fetuses with abnormal cardiac structure diagnosed at Peking University First Hospital from January 2012 to June 2021 were collected, which were divided into 4 groups according to the characteristics of fetal heart defects and the presence of extracardiac abnormalities or not: single cardiac defects without extracardiac abnormalities (122 cases), multiple cardiac defects without extracardiac abnormalities (100 cases), single cardiac defects with extracardiac abnormalities (115 cases), and multiple cardiac defects with extracardiac abnormalities (63 cases). The types of fetal cardiac structural abnormalities and genetic test results, and the detection rate of pathogenic genetic abnormalities, MDT consultation and management situation, and pregnancy decision of fetuses in each group were retrospectively analyzed. A logistics regression was used to analyze the influencing factors of fetal heart defects pregnancy decision. Results: (1) Among the 400 fetal heart defects, the four most common major types were ventricular septal defect 96 (24.0%, 96/400), tetralogy of Fallot 52 (13.0%, 52/400), coarctation of the aorta 34 (8.5%, 34/400), and atrioventricular septal defect 26 (6.5%, 26/400). (2) Among the 204 fetuses undergoing genetic examination, 44 (21.6%, 44/204) pathogenic genetic abnormalities were detected. (3) Detection rate of pathogenic genetic abnormalities (39.3%, 24/61) and pregnancy termination rate (86.1%, 99/115) in the single cardiac defects with extracardiac abnormalities group were significantly higher than those in the single cardiac defects without extracardiac abnormalities group [15.1% (8/53), 44.3% (54/122), respectively] and the multiple cardiac defects without extracardiac abnormalities group [6.1% (3/49), 70.0% (70/100), respectively, both P<0.05], and the pregnancy termination rate in the multiple cardiac defects without extracardiac abnormalities group and the multiple cardiac defects with extracardiac abnormalities group (82.5%,52/63) were significantly higher than that of the single cardiac abnormalities without extracardiac abnormalities group (both P<0.05). (4) After adjusting for age, gravity, parity and performed prenatal diagnosis, maternal age, the diagnosis of gestational age, prognosis grades, co-existence of extracardiac abnormalities, presence of pathogenic genetic abnormalities, and receiving MDT consultation and management were still independent influencing factors of termination of pregnancy of fetuses with cardiac defects (all P<0.05). A total of 29 (7.2%, 29/400) fetal cardiac defects received MDT consultation and management, and compared with those without MDT management, the pregnancy termination rate in the multiple cardiac defects without extracardiac abnormalities group [74.2%(66/89) vs 4/11] and the multiple cardiac defects with extracardiac abnormalities group [87.9%(51/58) vs 1/5] were lower, the differences were statistically significant respectively (all P<0.05). Conclusions: Maternal age, diagnosed gestational age, severity of cardiac defects, extracardiac abnormalities, pathogenic genetic abnormalities and MDT counseling and management are the influencing factors of fetal heart defects pregnancy decision. MDT cooperation approach influences pregnancy decision-making and should be recommended for the management of fetal cardiac defect to reduce unnecessary termination of pregnancy and improve pregnancy outcomes.

Analysis on echocardiographic data of fetal heart defects at high altitude in Yunnan province and surrounding high altitude areas

Objective: To explore the current situation of fetal heart defects in Yunnan Province and surrounding high altitude areas and the social factors affecting pregnancy outcome. Methods: This is a retrospective study. Pregnant woman who underwent fetal echocardiography and diagnosed as fetal cardiac defects in Yunnan Fuwai Cardiovascular Hospital from June 2017 to January 2021 were included. According to the clinical prognostic risk scoring system and grading criteria of fetal cardiac birth defects, the cases were divided into grade Ⅰ to Ⅳ. The disease distribution and proportion of each prognostic grade, pregnancy outcomes were analyzed and compared. The cases were divided into continued pregnancy group and terminated pregnancy group according to pregnancy outcome. The social factors that may affect the selection of pregnancy outcomes were analyzed by multivariate logistic regression analysis. Results: A total of 4 929 fetal echocardiography examination data were collected, and 4 464 cases (90.57%) were from Yunnan Province and surrounding high altitude areas. 2 166 cases of heart defects were finally analyzed, including 998 cases of congenital heart disease (CHD), 93 cases of cardiac tumors, cardiomyopathy and arrhythmia, 1 075 cases of foramen ovale, ductus arteriosus abnormalities and normal variations. The pregnant women were (29.2±5.0) years old with (25.6±3.8) gestational weeks. The number of cases with prognostic grade from Ⅰ to Ⅳ was 1 037 (47.88%), 620 (28.62%), 314 (14.50%), and 44 (2.03%), respectively. And 151 cases (6.97%) were not classified. The cases of normal variation and thin aortic arch development accounted for 42.66% (924/2 166), 5.22% (113/2 166), respectively. The top 3 diseases of grade Ⅱ were ventricular septal defect, coarctation of aorta and mild-moderate pulmonary stenosis, respectively, and their distribution was 11.63% (252/2 166), 3.92% (85/2 166) and 2.35% (51/2 166) respectively in all cases of heart defects, and 25.25% (252/998), 8.52% (85/998) and 5.11% (51/998) respectively in cases of CHD. Among the cases rated as grade Ⅲ and Ⅳ, most of them were complicated congenital heart disease, and the disease types are scattered. The more common cases in grade Ⅲ were complete transposition of great arteries (accounting for 2.40% (52/2 166) of all cases with heart defects, 5.21% (52/998) of all cases with CHD) and pulmonary artery occlusion (type Ⅰ to Ⅲ) with ventricular septal defect (accounting for 2.17% (47/2 166) of all cases with heart defects, and 4.71% (47/998) of all cases with CHD). In grade Ⅳ, single ventricle (0.74% (16/2 166) of all cases with heart defects, 1.60% (16/998) of all cases with CHD) and left ventricular dysplasia syndrome (0.65% (14/2 166) of all cases with heart defects, 1.40% (14/998) of all cases with CHD) are more common. A total of 1 084 cases were successfully followed up, and 675 cases were born, 392 cases were terminated, spontaneous abortion occurred in 17 cases. The proportion of terminated pregnancy cases was significantly increased from grade Ⅰ to Ⅳ, accounting for 5.24% (21/401), 27.78% (70/252), 89.54% (214/239) and 95.56% (43/45), respectively. Among the terminated pregnancy cases, those with grade Ⅲ accounted for the highest proportion (54.59% (214/392)). The distribution of terminated pregnancy cases was mainly complex congenital malformations or diseases with very poor prognosis (pregnancy outcome grade Ⅲ and Ⅳ), and proportion of terminated pregnancy with pregnancy outcome grade Ⅰ and Ⅱ cases (normal variation or good prognosis) accounted for 5.36% (21/392) and 17.86% (70/392), respectively. The results of multivariate logistic regression analysis showed that pregnant women with low education (high school and below: OR=2.73, 95%CI 1.26-5.93, P<0.001; illiteracy: OR=3.27, 95%CI 1.29-7.10, P<0.001) and low family income (Annual income<100 000 yuan: OR=2.47, 95%CI 1.69-5.12, P<0.001) were more likely to choose termination of pregnancy in case of fetal heart defect. Conclusion: In Yunnan province and the surrounding high altitude areas, the disease distribution of fetal heart defect is mainly simple or low-risk disease, but the complex malformation, especially the disease with poor pregnancy outcome, accounts for a relative high proportion. Pregnancy termination also occurs in some cases with good pregnancy outcome. The education level and family income of pregnant women may affect their choice of pregnancy outcome in case of fetal heart defect.

Delivery outcomes of fetal single ventricle cardiac defects: Results of a multi-disciplinary approach

Delivery outcomes of fetal single ventricle cardiac defects: Results of a multi-disciplinary approach

Increased Nuchal Translucency Without Aneuploidy in a Fetus: Abnormal Postnatal Radiograph and a Novel Mutation.

Increased Nuchal Translucency Without Aneuploidy in a Fetus: Abnormal Postnatal Radiograph and a Novel Mutation.

Genetic characteristics and prognostic analysis of 162 fetal cardiac abnormalities

Objective: To analyze the type and characteristics of fetal cardiac abnormalities and their relationships with genetic abnormalities and clinical prognosis. Methods: The clinical data of 162 pregnant women with fetal cardiac abnormalities who came to the prenatal diagnosis center of Peking University First Hospital and performed genetic tests from February 2013 to February 2021 were reviewed. Genetic testing methods included chromosome karyotype analysis, array-based comparative genomic hybridization (aCGH) and pathogenic gene detection. Fetuses with isolated cardiac abnormalities and no fatal genetic abnormalities were assessed using the fetal cardiac birth defects clinical outcome score and followed up. Results: (1) Ultrasonography results: among the 162 fetuses, 86 cases (53.1%, 86/162) had isolated cardiac abnormalities, and 76 cases (46.9%, 76/162) had extra-cardiac abnormalities; single cardiac abnormalities were in 84 (51.9%,84/162) cases, and multiple cardiac abnormalities occurred in 78 cases (48.1%,78/162). (2) Genetic examination results: there were 39 cases (24.1%, 39/162) of pathogenic genetic abnormalities, including 35 cases (21.6%, 35/162) of pathogenic chromosome karyotype abnormality, 3 cases (1.9%, 3/162) of pathogenic copy number variant (CNV), and 1 case (0.6%, 1/162) of pathogenic gene variation. The detection rates of pathogenic genetic abnormalities were 16.3% (14/86) in fetuses with isolated cardiac abnormalities and 32.9% (25/76) in fetuses with cardiac abnormalities and extra-cardiac abnormalities, and the difference was statistically significant (χ2=6.094, P=0.014). The detection rate of genetic abnormalities was 28.6% (24/84) in the single cardiac abnormalities, among which ventricular septal defect was 36.7% (11/30), atrioventricular septal defect was 8/13, tetralogy of Fallot was 3/17, persistent trancus arteriosus was 1/1, cardiac tumor was 1/1; no genetic abnormality was detected in the other single cardiac abnormality types (22 cases in total). The main types of pathogenic genetic abnormalities were trisomy 21 (41.7%, 10/24) and trisomy 18 (41.7%, 10/24). (3) Pregnancy outcome and fetal prognosis: among 72 fetuses with isolated heart abnormalities without pathogenic genetic abnormalities, there were 4 cases of grade Ⅰ, all of which continued pregnancy; 39 cases of grade Ⅱ, with 21 cases induced labor, 18 cases continued pregnancy; 26 cases of grade Ⅲ, with 23 cases induced labor, 3 cases continued pregnancy; 3 cases of grade Ⅳ, all of which induced labor. Totally, there were 47 cases induced labor and 25 cases continued pregnancy, 24 cases (96.0%, 24/25) of which were alive. Conclusions: When fetal cardiac abnormalities are detected by prenatal ultrasound, comprehensive cardiac and extra-cardiac ultrasound assessment and further genetic testing are recommended. Fetuses excluded pathogenic genetic abnormalities and extra-cardiac abnormalities should perform clinical prognostic score evaluation through multidisciplinary collaboration, to improve maternal and fetal outcomes.

Impact of Planned Delivery on the Perinatal Outcome of Term Fetuses with Isolated Heart Defects

ObjectivePregnancies complicated by fetal heart defects often undergo a planned delivery prior to term by either induction of labour or cesarean delivery to ensure optimal availability of neonatal care. We aimed to assess whether such planned deliveries achieve their goal of better perinatal care. MethodsWe conducted a retrospective case-control study of pregnancies complicated by isolated fetal cardiac defects, without other fetal comorbidities, managed at a single fetal medicine unit over a 10-year period. Only pregnancies delivered past 37 weeks gestation were included. Patients undergoing elective delivery for care planning reasons only were compared with patients in whom planned delivery was clinically indicated and patients who laboured spontaneously. Obstetric and perinatal outcomes were recorded. ResultsOf the 180 pregnancies included in the study, 59 (32.8%) were in the elective group, 49 (27.2%), in the indicated group, and 72 (40%), in the spontaneous group. Mean gestational age at delivery was 39.0 ± 1.1 weeks overall and did not differ between the groups. For the elective group, only 35.6% of deliveries occurred during office hours, which was similar to the 2 other groups. The rate of adverse obstetric or postnatal outcomes was not statistically significantly different between groups. ConclusionTimed delivery at term does not seem to be associated with an increased risk of poor perinatal outcomes. It may improve perinatal care by providing proximity to a neonatal intensive care unit and convenience for patients and providers.

Follow-up study of fetal cardiac birth defects after prenatal diagnosis and graded counseling

Objective: To explore accurate prenatal diagnosis, full-coverage graded counseling and follow-up for the fetus with cardiac birth defects (CBD). Methods: CBD fetus diagnosed prenatal by echocardiography from January 2018 to December 2020 in Guangdong Provincial People's Hospital were enrolled. Fetal CBD was graded (Ⅰ-Ⅵ) according to prognosis and possible operation time after birth, and the classification criteria and common diseases included were proposed. After the prenatal grading counseling, the outcome of the fetus was followed-up. The induced labor rate, live birth rate, prenatal and postnatal ultrasound diagnosis coincidence rate and other indicators were calculated. The disease composition ratio, prognosis of fetus with different grades and the outcome of integrated treatment were analyzed. Results: The detection rate of fetal CBD was up to 16.2% (1 971/12 188), 30 cases of which were excluded. A total of 1 941 cases were included in this study, including 196 cases (10.1%) of gradeⅠ, 433 cases (22.3%) of gradeⅡ, 615 cases (31.7%) of grade Ⅲ, 261 cases (13.4%) of grade Ⅳ, 388 cases (20.0%) of gradeⅤ, 48 cases (2.5%) of grade Ⅵ. Grade Ⅱ and gradeⅢ (the operation time was within 1 year after birth) accounted for 54.0% (1 048/1 941). The distribution of some diseases in different grades had obvious proportion advantage, which was representative. Among 1 747 CBD fetus, 736 cases (induced labor rate 42.1%) chose to terminate pregnancy due to CBD. Of the 1 010 live births, 975 cases (96.5%) had the same prenatal and postnatal diagnosis, 3 cases were missed diagnosis and 32 cases were misdiagnosed. The diagnostic accuracy of live births with severe and complex congenital heart disease was 383 out of 389 (98.5%). A total of 258 cases have received surgery or intervention. The age at the time of surgery or intervention was different among grades（χ²=47.3，P<0.001）. With the improvement of prognosis from gradeⅠ to Ⅴ, the live birth rate increased and the induced labor rate decreased accordingly; the difference between grades was significant（χ²=623.6，P<0.001）. Conclusions: Prenatal diagnosis and graded counseling is important in the integrated model. Fetal CBD grading could refine post-natal treatment strategies, guide delivery decisions and become an evaluation standard.

Brainstem and cerebellar volumes at magnetic resonance imaging are smaller in fetuses with congenital heart disease

Congenital heart disease is associated with an increased risk of smaller brain volumes and structural brain damage, and impaired growth of supratentorial brain structures in utero has been linked to poor neurodevelopmental outcomes. However, little is known on brainstem and cerebellar volumes in fetuses with congenital heart disease. Moreover, it is not clear whether impaired infratentorial growth, if present, is associated with only certain types of fetal cardiac defects or with supratentorial brain growth, and whether altered biometry is already present before the third trimester. This study aimed to investigate brainstem and cerebellar volumes in fetuses with congenital heart disease and to compare them to infratentorial brain volumes in fetuses with normal hearts. Secondarily, the study aimed to identify associations between infratentorial brain biometry and the type of cardiac defects, supratentorial brain volumes, and gestational age. In this retrospective case-control study, 141 magnetic resonance imaging studies of 135 fetuses with congenital heart disease and 141 magnetic resonance imaging studies of 125 controls with normal hearts at 20 to 37 gestational weeks (median, 25 weeks) were evaluated. All cases and controls had normal birthweight and no evidence of structural brain disease or genetic syndrome. Six types of congenital heart disease were included: tetralogy of Fallot (n=32); double-outlet right ventricle (n=22); transposition of the great arteries (n=27); aortic obstruction (n=24); hypoplastic left heart syndrome (n=22); and hypoplastic right heart syndrome (n=14). First, brainstem and cerebellar volumes of each fetus were segmented and compared between cases and controls. In addition, transverse cerebellar diameters, vermian areas, and supratentorial brain and cerebrospinal fluid volumes were quantified and differences assessed between cases and controls. Volumetric differences were further analyzed according to types of cardiac defects and supratentorial brain volumes. Finally, volume ratios were created for each brain structure ([volume in fetus with congenital heart disease/respective volume in control fetus]× 100) and correlated to gestational age. Brainstem (cases, 2.1 cm3 vs controls, 2.4 cm3; P<.001) and cerebellar (cases, 3.2 cm3 vs controls, 3.4 cm3; P<.001) volumes were smaller in fetuses with congenital heart disease than in controls, whereas transverse cerebellar diameters (P=.681) and vermian areas (P=.947) did not differ between groups. Brainstem and cerebellar volumes differed between types of cardiac defects. Overall, the volume ratio of cases to controls was 80.8% for the brainstem, 90.5% for the cerebellum, and 90.1% for the supratentorial brain. Fetuses with tetralogy of Fallot and transposition of the great arteries were most severely affected by total brain volume reduction. Gestational age had no effect on volume ratios. The volume of the infratentorial brain, which contains structures considered crucial to brain function, is significantly smaller in fetuses with congenital heart disease than in controls from midgestation onward. These findings suggest that impaired growth of both supra- and infratentorial brain structures in fetuses with congenital heart disease occurs in the second trimester. Further research is needed to elucidate associations between fetal brain volumes and neurodevelopmental outcomes in congenital heart disease.

Performance of Ductus Venosus Doppler (at 11–13 + 6 Weeks) in Predicting Adverse Fetal Outcomes in Indian Population

The objective of this study is to examine the performance of Ductus venosus (DV) Doppler done at the routine first trimester screening (11-13 + 6 weeks) in predicting the adverse fetal outcomes in Indian population. This observational study was conducted between 2013 and 2019, on 4340 singleton pregnancies. Ductus Doppler were considered abnormal if DV pulsatility index values were >95th centile for that gestation or with a reversed "a" wave. Anatomical survey was done to rule out other abnormalities. Women were followed up till delivery and outcomes were divided into 4 groups: 1) aneuploidies; 2) cardiac defects; 3) non-cardiac structural abnormalities; and 4) miscarriages before 24 weeks or fetal deaths after 24 weeks. Prevalence of abnormal DV Doppler is 5.12% (205/4004). There were significantly higher number of fetal losses (4.4 versus 0.3%), aneuploidies (10.2 versus 1.7%), fetal cardiac defects (5.9 versus 1.4%), and non-cardiac structural defects (5.4 versus 1.4%) among the pregnancies with abnormal DV Doppler in comparison to those with normal flow (P < .001). Logistic regression analysis has shown that significant contribution to fetal chromosomal abnormalities and cardiac defects was associated with abnormal DV. Other factors which were found to have a significant association with adverse fetal outcome were increased nuchal translucency and increased body mass index (BMI). DV Doppler in first trimester can be used as a screening tool for cardiac defects and fetal deaths. Women with abnormal DV Dopplers should be offered fetal echocardiography at 18-22 weeks and third trimester growth scans with Dopplers.

261. The diagnostic accuracy of fetal cardiac anomaly scans to postnatal cardiac defects

Introduction and aim: To evaluate the diagnostic accuracy, including sensitivity and specificity of routine anomaly ultrasound, performed between 18 to 24 weeks of gestation, in detecting fetal cardiac defects. The antenatal cardiac defects were compared to the gold standard, which was defined as the postnatal echocardiography and the post-mortem findings from autopsy reports. The study also identified the number and type of cardiac anomalies detected antenatally on ultrasound and those detected postnatally, together with maternal and fetal risk factors for CHDs. Method: A hospital based retrospective, observational, quantitative and comparative research method was adopted. The cardiac defects detected on anomaly ultrasound scan, from the initiation of the anomaly screening programme in January 2016 up to August 2018 (with births occurring by January 2019), were compared to the postnatal echoes performed by the Paediatric cardiologist or to the post-mortem findings derived from autopsy results.Results: In the study period, 139 babies were diagnosed with CHD postnatally of which 93 had had a fetal anomaly scan. A total of 29 cases of CHD were detected antenatally, from which 28 were confirmed postnatally with complete agreement in 20 cases. The sensitivity of anomaly scans in the detection of CHDs was observed to be 30.43% and the specificity of 99.98%. The positive predictive value (PPV) was observed at 96.55% and the negative predictive value (NPV) at 99.24%. The commonest diagnosed CHD was a ventricular septal defect (VSD) while the incidence of CHDs was 18.15 per 1000 live births. Conclusion: There was complete agreement in 68.97% of cases when the antenatal findings on anomaly ultrasound scan were compared to the gold standard. A moderate sensitivity was obtained with an excellent specificity, PPV and NPV. In the population the incidence of total CHDs was observed to be 18.15 per 1000 live births.

Genome-wide methylation analysis reveals differentially methylated CpG sites and altered expression of heart development-associated genes in fetuses with cardiac defects.

DNA methylation, as an epigenetic mechanism, has a vital role in heart development. An increasing number of studies have investigated aberrant DNA methylation in pediatric or adult heart samples from patients with congenital heart defects (CHD). Placenta tissue, umbilical cord blood, or newborn blood have also been used to detect DNA methylation biomarkers for CHD. However, few studies have compared the methylation levels in fetal heart tissue with cardiac defects with that in normal controls. The present study conducted an integrative whole-genome and CpG site-specific DNA methylation analysis of fetal heart samples from 17 isolated cardiac defect cases, 14 non-isolated cardiac defect cases, and 22 controls with normal hearts, using methylated DNA immunoprecipitation microarray and MassARRAY EpiTYPER assays. Expression of genes adjacent to differentially methylated regions (DMRs) was measured by RT-qPCR and western blot analysis. The results revealed that fetuses with cardiac defects presented global hypomethylation. Genomic analysis of DMRs revealed that a proportion of DMRs were located in exons (12.4%), distal intergenic regions (11.14%), and introns (8.97%). Only 55.7% of DMRs were observed at promoter regions. Functional enrichment analysis for genes adjacent to these DMRs revealed that hypomethylated genes were involved in embryonic heart tube morphogenesis and immune-related regulation functions. Intergenic hypermethylation of EGFR and solute carrier family 19 member 1 (SLC19A1), and intragenic hypomethylation of NOTCH1 were validated in fetal heart tissues with cardiac defects. Only SLC19A1 expression was significantly decreased at the mRNA level, while EGFR, NOTCH1, and SLC19A1 expression were all significantly decreased at the protein level. In conclusion, the present study demonstrated that fetal cardiac defects may be associated with alterations in regional and single CpG site methylation outside of promoter regions, resulting in differentiated expression of corresponding genes associated with heart development. These results present new insights into the epigenetic mechanisms underlying abnormal heart development.

Detection of fetal arrhythmia by adaptive single channel electrocardiogram extraction.

Fetal arrhythmia, the abnormal heartbeat of a fetus is broadly classified as tachy arrhythmia (too fast > 160 beats/min) and brady arrhythmia (too slow < 120 beats/min). Detection of this irregular heart beat rhythm of the fetus during pregnancy is still a challenging task for the clinicians. Heart rate detection through electrocardiography has always been accurate for identifying cardiac defect in humans. Adult ECG has achieved several developments in the modern medicine whereas noninvasive fetal ECG (FECG) continues to be a big challenge. Automatic detection of fetal heart rate is vital for monitoring the unborn infant during pregnancy. The non-invasive placement of electrodes over the abdomen region of pregnant women records the ECG signal of both mother and fetus. The arrhythmia affected FECG signals (n = 14) are processed from the physionet database. This raw ECG signal is preprocessed using a Savitzky-Golay filter and symlet wavelet transform to remove the basic noises. Adaptive recursive least square filter is preferably chosen for extracting the FECG, using mother's thorax ECG as a reference. An accurate PQRST wave-shape of the FECG is required for the proper diagnosis of fetal cardiac defects. Using a single channel abdominal ECG signal, the proposed work generates extracted fetal ECG and an automated visual display of fetal heart rate. The presence of arrhythmia and fetal distress can be analyzed through fetal heart rate display and abnormal conductivity of PQRST wave respectively. We have analyzed fetal arrhythmias through ECG extraction and the same was compared with the echocardiograph results given by pediatric cardiologist. This study helps to identify the fetal distress at early gestational age that helps the obstetricians to make quick decisions before or immediately after delivery.

Fetal counseling for congenital heart disease: is communication effective?

Purpose To assess the accuracy of maternal understanding of fetal cardiac defects following initial fetal counseling. Methods Pregnant women with a fetal diagnosis of congenital heart disease (CHD) were surveyed regarding understanding of their fetus’s heart defect. The survey asked: (1) for a description of the heart condition; (2) how confident they were in the diagnosis; (3) whether their fetus would require heart surgery. Two fetal cardiologists evaluated the maternal qualitative description. Partners were excluded from the study. Results Fifty-one participants consented and 39 completed the survey. Mean age was 31 years, 60% had some college level or post-graduate education, 48% had Medicaid insurance, and 81% were Caucasian. More than three-quarters of participants, stated they had either “quite a bit” or “very much” understanding of their fetus’s diagnosis. Maternal assessment matched the physician’s assessment of accuracy with 77% (N = 30) demonstrating either “quite a bit” or a “very accurate” description of the diagnosis. All women correctly understood if their fetus would require heart surgery. Highest level of maternal education positively correlated with the accuracy of diagnosis (regression coefficient 0.48, p < .002). However, confidence in the diagnosis was independent of both education (0.30, p = .167) and maternal age (−0.03, p = .234). Conclusions Fetal counseling is effective in conveying anatomy and the need for surgery; however, accuracy amongst women with lower levels of education and maternal confidence in understanding can be improved.

The Association of Fetal Congenital Cardiac Defects and Placental Vascular Malperfusion.

Abnormal early angiogenesis appears to impact both placental disorders and fetal congenital heart defects (CHD). We sought to assess the association of placental perfusion defects (PPD) and fetal (CHD). Singleton pregnancies with isolated severe fetal CHD were compared to controls without congenital anomalies or maternal malperfusion (MVM) risk factors. CHD was categorized into group 1: single left ventricle morphology and transposition of the great vessels (TGA) and group 2: single right ventricle and two ventricle morphology. Malperfusion was defined as fetal vascular malperfusion (FVM), MVM, and both FVM and MVM. PPD was increased for all CHD (n = 47), CHD with or without risk factors, and CHD groups compared to controls (n = 92). Overall CHD cases and CHD with risk factors had an increased risk of FVM (30% and 80% vs 14%), and MVM (43% and 50% vs 21%), respectively. MVM rates were similar in CHD with and without maternal risk factors. FVM (38% vs 14%) and MVM (44% vs 21%) were increased in Group 1. MVM (42% vs 21%) and both FVM and MVM (16% vs 3%) were increased in Group 2. PPD risk is increased in severe isolated fetal CHD. The highest risk is seen in fetal CHD with maternal risk factors.

Anatomical Survey Versus Fetal Echocardiograms for Diagnosis of Cardiac Defects with a Single Umbilical Artery Cases: A Retrospective Cohort Study and Diagnostic Meta-analysis.

To determine the utility of fetal echocardiography in diagnosing cardiac defects in fetuses with a single umbilical artery (SUA). A retrospective cohort study of prenatally diagnosed SUA was conducted over a 10-year period at a single institution. Cardiac anatomy on detailed anatomical survey was compared with fetal echocardiogram for fetuses with prenatally diagnosed SUA. A diagnostic meta-analysis of studies comparing fetal anatomical survey to fetal echocardiogram in fetuses with SUA between 2010 to 2019 was also performed. Three hundred and twenty fetuses with SUA were identified, 113 of which had completed both ultrasound and echocardiography. There were 36 cases of cardiac defects on prenatal echocardiogram and all had abnormal anatomical ultrasounds. There were zero cases of abnormal cardiac exams (0%) when the cardiac views on anatomical survey were normal. The sensitivity, specificity, positive predictive value and negative predictive value of ultrasound were 100%, 77%, 73% and 100%, respectively. A summary ROC curve demonstrated a high predictive value of routine anatomic survey for cardiac defects (AUC: 0.99). Anatomic survey is highly predictive in the detection of cardiac defects in fetuses with SUA. Fetal echocardiogram is unnecessary in SUA when cardiac views are normal on ultrasound.

Clinical value of isolated intracardiac echogenic focus in the fetal heart: A retrospective study in Chinese women

Purpose: To assess the resolution of intracardiac echogenic focus in gestation and to evaluate its association with fetal cardiac structural defects. Materials and Methods: Retrospective data of fetal echocardiography from January 2014 to December 2016 in low-risk pregnancies were collected. The study variables included observation resolution data of fetuses with intracardiac echogenic foci detected in the second-trimester, and follow-up data in the third-trimester. The Chi-square test was used to determine the association between intracardiac echogenic foci and fetal cardiac defects. Additionally, several statistical measures of performance for the foci as predictive markers were calculated. Results: The authors examined 8,120 fetuses. Among 531 fetuses with intracardiac echogenic foci, the overall incidence rate was 6.5% on a sonogram at 22-28 gestational weeks. The left ventricle was the most common site. Significant differences were observed between the locations and features of changes in the foci (χ2 = 18.68, p = 0.0009). No significant associations were found between the foci locations and fetal cardiac structural defects (Pfisher=0.28), or between the foci and cardiac defects [χ2 = 0.91, p = 0.34, OR = 0.72 with 95% confidence interval (0.40, 1.30)]. Conclusions: In most cases, isolated intracardiac echogenic focus was a transient sonographic marker during the gestational period. However, foci in the right ventricle were more stable than in the other locations. Intracardiac echogenic foci were not associated with cardiac defects, despite persistence in the third trimester.

Trichloroethylene in drinking water throughout gestation did not produce congenital heart defects in Sprague Dawley rats.

BackgroundTrichloroethylene (TCE) was negative for developmental toxicity after inhalation and oral gavage exposure of pregnant rats but fetal cardiac defects were reported following drinking water exposure throughout gestation. Because of the deficiencies in this latter study, we performed another drinking water study to evaluate whether TCE causes heart defects.MethodsGroups of 25 mated Sprague Dawley rats consumed water containing 0, 0.25, 1.5, 500, or 1,000 ppm TCE from gestational day 1–21. TCE concentrations were measured at daily formulation, when placed into water bottles each day and when water bottles were removed from cages. Four additional mated rats per group were used for plasma measurements. At termination, fetal hearts were carefully dissected fresh and examined.ResultsAll TCE concentrations were >90% of target when initially placed in water bottles and when bottles were placed on cages. All dams survived with no clinical signs. Rats in the two higher dose groups consumed less water/day than other groups but showed no changes in maternal or fetal weights. The only fetal cardiac observation was small (<1 mm) membranous ventricular septal defect occurring in all treated and water control groups; incidences were within the range of published findings for naive animals. TCE was not detected in maternal blood, but systemic exposure was confirmed by detecting its primary oxidative metabolite, trichloroacetic acid, although only at levels above the quantitation limit in the two higher dose groups.ConclusionsIngesting TCE in drinking water ≤1,000 ppm throughout gestation does not cause cardiac defects in rat offspring.

Chromosome 15q13 microduplication in a fetus with cardiac rhabdomyoma: a case report

BackgroundCopy number variation (CNV) is a complex genomic rearrangement that has been linked to a large number of human diseases. Chromosome 15q13 microduplication is a rare form of CNV, which has been proved to be associated with multiple human disorders; however, the association between chromosome 15q13 microduplication and cardiac disorders has not been fully understood.Case presentationA fetus with fetal cardiac developmental defects was detected by Color Doppler ultrasound imaging; however, further chromosomal G-banding revealed no abnormal karyotype. Then, chromosomal microarray analysis (CMA) was performed and revealed a 1.8 Mb-duplication of the chromosome 15q13.2q13.3 region containing 7 genes (TRPM1, KLF13, OTUD7A, CHRNA7, FAN1, MIR211 and RAHGAP11A). Cardiac ultrasound follow-up displayed significant enlargement of the space-occupying lesion in the fetal heart with extension of the gestational age, and the space-occupying lesion was finally pathologically diagnosed as cardiac rhabdomyoma. Next-generation sequencing revealed no mutations in the TSC1 or TSC2 gene in the fetus, the mother or the father.ConclusionsThis is the first report to demonstrate the potential association between chromosome 15q13 microduplication and fetal cardiac rhabdomyoma. It is recommended that CMA be employed in fetuses with abnormal cardiac development diagnosed by routine cardiac color Doppler ultrasound imaging for early detection of congenital genetic abnormality, which may provide valuable information for prenatal diagnostic consultation and the decision on pregnancy termination.