Fetal Cardiac Defects Research Articles

Association of the C677T methylenetetrahydrofolate reductase mutation and elevated homocysteine levels with congenital cardiac malformations

Objective: The aim of this study was determine whether the cytosine-to-thymine mutation at base 677 of the gene for methylenetetrahydrofolate reductase (C677T MTHFR ), which has been associated with neural tube defects, is also associated with congenital cardiac malformations. Study Design: Amniotic fluid homocysteine levels were measured and the presence or absence of the C677T MTHFR mutation in amniocytes was determined in stored amniotic fluid obtained from 26 pregnancies complicated by isolated (presumed multifactorial) fetal cardiac defects and from 116 normal pregnancies. Results: The pregnancies affected by fetal cardiac defects had higher amniotic fluid homocysteine levels (1.7 ± 1.7 vs 1.0 ± 0.7 μmol/L; P =.07) and included more samples with homocysteine levels >90th percentile (27% vs 9%; P =.02) and more cases with the C677T MTHFR mutation (35% vs 13%; P =.01). Fifty percent of cases had either a high homocysteine level or the C677T MTHFR mutation (50% vs 20%; P =.003) and 12% had both (12% vs 0%; P =.0006). Conclusion: Fifty percent of these isolated congenital cardiac defects were associated with either the C677T MTHFR mutation or elevated amniotic fluid homocysteine levels, or both. This finding adds to what is already known about the multiple and complex biochemical and developmental functions of the homocysteine pathway. (Am J Obstet Gynecol 2001;184:806-17.)

F125Fetal pulmonary venous Doppler flow velocity waveforms in congenital heart defects

Aim of the studyis to analyze blood flow velocity waveforms (FVW) in the pulmonary veins using pulsed Doppler ultrasound in fetuses with a prenatally detected congenital heart defect (CHD).MethodsIn 96 fetuses with various CHD Doppler FVW from the pulmonary veins were assessed. Gestational age varied between 18 and 38 weeks. Following Doppler parameters were analyzed and compared to reference ranges: systolic (S), diastolic (D) peak velocity, end‐diastolic velocity during atrial contraction (A), peak velocity index for veins (PVIV) and Pulsatility Index for veins (PIV).ResultsWe could distinguish 5 different patterns of FVW reflecting different stages of pulsatility and preload within the left atrium. Abnormal patterns were mainly observed in fetuses with left atrial obstruction and a restrictive foramen ovale having a reversed A‐wave as well as in mitral regurgitation.ConclusionsAbnormal FVW in fetal cardiac defects depend from the left atrial pressure rather than on the cardiac defect itself. Patterns of FVW can help in quick differentiation of increased interatrial pressure, which can impair early neonatal outcome.

REVERSED DIASTOLIC UMBILICAL ARTERY FLOW IN THE FIRST TRIMESTER ASSOCIATED WITH CHROMOSOMAL FETAL ABNORMALITIES OR CARDIAC DEFECTS

In Brief Background Six cases have been reported of reversed end-diastolic umbilical artery (UA) blood flow at 10–14 weeks' gestation. Four were associated with chromosomal anomalies, and one showed congenital heart disease. Cases This report describes two cases of reversed end-diastolic UA flow at 10 and 12 weeks' gestation with increased nuchal translucency in which cytogenetic analysis by chorionic villus sampling showed triploidy (69,XXX) and trisomy 9, respectively. In second case, the fetus had a ventricular septal defect. Conclusion Reversed end-diastolic UA flow in the first trimester might be an important sign of chromosomal abnormalities in early pregnancy and might be a useful signal for the diagnosis of early cardiac defects. Reversed end-diastolic umbilical artery blood flow potentially predicts chromosomal fetal abnormalities or cardiac defects in the first trimester.

Reversed diastolic umbilical artery flow in the first trimester associated with chromosomal fetal abnormalities or cardiac defects

Background: Six cases have been reported of reversed end-diastolic umbilical artery (UA) blood flow at 10–14 weeks’ gestation. Four were associated with chromosomal anomalies, and one showed congenital heart disease. Cases: This report describes two cases of reversed end-diastolic UA flow at 10 and 12 weeks’ gestation with increased nuchal translucency in which cytogenetic analysis by chorionic villus sampling showed triploidy (69,XXX) and trisomy 9, respectively. In second case, the fetus had a ventricular septal defect. Conclusion: Reversed end-diastolic UA flow in the first trimester might be an important sign of chromosomal abnormalities in early pregnancy and might be a useful signal for the diagnosis of early cardiac defects.

Reversed diastolic umbilical artery flow in the first trimester associated with chromosomal fetal abnormalities or cardiac defects

Reversed diastolic umbilical artery flow in the first trimester associated with chromosomal fetal abnormalities or cardiac defects

Antenatal detection of congenital heart disease

Summary Fetal cardiac defects are detectable by antenatal ultrasonic imaging. Fetal echocardiography is sensitive and specific, but has only a limited impact on the disease as a whole due to the poor sensitivity of routine obstetric screening. Further advances in the training of obstetric and radiology staff and ultrasonic image resolution should produce future improvements. There is a need for more rigorous assessment of the cost-effectiveness of fetal echocardiography. Developments in fetal cardiac intervention highlight the need for accurate diagnosis and knowledge of the natural history of congenital heart disease in the fetus.

A review: trichloroethylene metabolites: potential cardiac teratogens.

This review is a a series of the authors' studies designed to test the hypothesis that administration of trichloroethylene (TCE), dichloroethylene (DCE), their metabolites, and related compounds are responsible for fetal cardiac teratogenesis when given to pregnant rats during organogenesis. Identification of teratogenic compounds will allow more accurate assessment of environmental contaminants and public health risks. Epidemiologic studies and previous teratogenic studies using chick embryos and fetal rats have reported an increased number of congenital cardiac defects when exposed to TCE or DCE during fetal development. Metabolites of TCE and DCE studied in the drinking-water exposure study include trichloroacetic acid TCAA), monochloroacetic acid, trichloroethanol, carboxymethylcysteine, trichloroacetaldehyde, dichloroacetaldehyde, and dichlorovinyl cysteine. Varying doses of each were given in drinking water to pregnant rats during the period of fetal heart development. Rats receiving 2730 ppm TCAA in drinking water were the only metabolite group demonstrating a significant increase in the number of cardiac defects in fetuses on a per-litter basis (p = 0.0004 Wilcoxon test and p =0.0015 exact permutation test). Maternal and fetal variables showed no statistically significant differences between treated and untreated groups. When treated with TCAA the increased cardiac defects, as compared to controls, do not preclude the involvement of other metabolites as cardiac teratogens, but indicates TCAA as a specific cardiac teratogen. Further studies of drinking-water exposure and potential mechanisms of action on the developing heart are proceeding.

Maternal diabetes mellitus: Which views are essential for fetal echocardiography?

To determine which fetal echocardiography views are essential to detect the majority of cardiac defects in fetuses of women with diabetes mellitus. Fetal echocardiograms performed from February 1990 through May 1996 on insulin-requiring women with diabetes were reviewed. Individual component views of the examination were analyzed for the detection of fetal congenital heart defects. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Multiple gestations and patients with additional risk factors for congenital heart defects were excluded. A total of 223 patients were included in the study. There were 11 (4.9%) congenital heart defects, eight of which were conotruncal. When the four-chamber view and outflow tracts appeared normal, additional views such as the ductal and aortic arches did not detect a cardiac defect. The sensitivity of the four-chamber view for detecting an abnormal heart increased from 73% to 82% with the addition of the aortic outflow tract. There were two false-negative and no false-positive diagnoses. The four-chamber and outflow tracts are the essential views that will detect most cardiac defects in fetuses of women with insulin-requiring diabetes mellitus.

Increased nuchal translucency at 10-14 weeks of gestation as a marker for major cardiac defects.

Screening for fetal cardiac defects is traditionally based on the ultrasonographic examination of the four-chamber view of the fetal heart at mid-gestation, which has been shown to identify 26% of major cardiac defects. Pathological studies in fetuses with increased nuchal translucency at 10-14 weeks of gestation, a sonographic marker for chromosomal abnormalities, have shown an association between increased nuchal translucency and congenital abnormalities of the heart. This study reports the prevalence of cardiac defects in 1427 chromosomally normal fetuses with increased nuchal translucency thickness, and examines the potential value of this sonographic marker in screening for major cardiac defects. The diagnosis of cardiac defects was made either by postmortem examination in terminations of pregnancy and intrauterine or neonatal deaths or by clinical examination and appropriate investigations in live births. The prevalence of major cardiac defects was 17 per 1000 (24 of 1427 fetuses) and increased with translucency thickness from 5.4 per 1000 for translucency of 2.5-3.4 mm to 233 per 1000 for translucency of > or = 5.5 mm. These findings suggest that measurement of nuchal translucency thickness at 10-14 weeks may prove to be a useful method of screening for abnormalities of the heart and great arteries in addition to its role in screening for chromosomal defects.

Extended fetal echocardiographic examination for detecting cardiac malformations in low risk pregnancies

OBJECTIVE--To improve the rate of prenatal detection of cardiac malformations in a low risk population. DESIGN--Comparison of extended fetal echocardiography with the standard four chamber view in detecting abnormalities. Extended echocardiography comprised the four chamber view and visualisation of the left ventricular outflow tract, the right ventricular outflow tract, and the main pulmonary artery and its branches. In cases with abnormal results complete echocardiographic studies were performed by a paediatric cardiologist using M mode, Doppler, and colour flow mapping techniques. SETTING--Obstetric ultrasonographic unit at Shaare-Zedek Medical Centre, Jerusalem. SUBJECTS--5400 fetuses in low risk pregnancies between 18 and 24 weeks' gestation (mean 21 weeks); 53 were lost to follow up. MAIN OUTCOME MEASURES--Detection of abnormality before and after birth. RESULTS--During the study 23 infants (0.4%) were born with cardiac abnormalities, 21 of whom had major structural and functional heart disease. 18 fetuses had heart disease diagnosed prenatally, 11 by the four chamber view alone (sensitivity 48%) and a further seven by extended echocardiography (sensitivity 78%). Five fetal cardiac defects were missed prenatally (false negative rate 22%). These included coarctation of aorta, persistent truncus arteriosus, tetralogy of Fallot, ventricular septal defect, and pulmonic stenosis. Only one false positive diagnosis (coarctation of aorta) was made (specificity 99.9%, false positive rate 0.1%). The abnormality was correctly identified in 17 out of 18 cases. CONCLUSIONS--The extended fetal heart examination detected 86% (18/21) of major abnormalities in a low risk population. The examination should be incorporated into routine prenatal ultrasonographic investigations.

Extended Fetal Echocardiographic Examination for Detecting Cardiac Malformations in Low-Risk Pregnancies

OBJECTIVE--To improve the rate of prenatal detection of cardiac malformations in a low risk population. DESIGN--Comparison of extended fetal echocardiography with the standard four chamber view in detecting abnormalities. Extended echocardiography comprised the four chamber view and visualisation of the left ventricular outflow tract, the right ventricular outflow tract, and the main pulmonary artery and its branches. In cases with abnormal results complete echocardiographic studies were performed by a paediatric cardiologist using M mode, Doppler, and colour flow mapping techniques. SETTING--Obstetric ultrasonographic unit at Shaare-Zedek Medical Centre, Jerusalem. SUBJECTS--5400 fetuses in low risk pregnancies between 18 and 24 weeks' gestation (mean 21 weeks); 53 were lost to follow up. MAIN OUTCOME MEASURES--Detection of abnormality before and after birth. RESULTS--During the study 23 infants (0.4%) were born with cardiac abnormalities, 21 of whom had major structural and functional heart disease. 18 fetuses had heart disease diagnosed prenatally, 11 by the four chamber view alone (sensitivity 48%) and a further seven by extended echocardiography (sensitivity 78%). Five fetal cardiac defects were missed prenatally (false negative rate 22%). These included coarctation of aorta, persistent truncus arteriosus, tetralogy of Fallot, ventricular septal defect, and pulmonic stenosis. Only one false positive diagnosis (coarctation of aorta) was made (specificity 99.9%, false positive rate 0.1%). The abnormality was correctly identified in 17 out of 18 cases. CONCLUSIONS--The extended fetal heart examination detected 86% (18/21) of major abnormalities in a low risk population. The examination should be incorporated into routine prenatal ultrasonographic investigations.

Fetal echocardiography in multiple gestations.

We reviewed fetal echocardiograms from 36 multiple gestations from 20 weeks gestation to term. Seven sets of twins plus one set of triplets were referred because of a suspect cardiac anomaly in one fetus; heart disease was confirmed in one fetus of six sets of twins and in one triplet. Six sets were referred because of extracardiac malformations and heart disease was confirmed in two sets (including both twins in one set). The remaining case was detected in a patient sent for evaluation of karyotypic abnormality. Thus 11 fetal cardiac defects were detected in ten pregnancies. Chromosomes were abnormal in three of the anomalous fetuses. Two sets discordant for heart disease were monochorionic. Intervention, including a change in the planned location of delivery, or maternal digitalization for fetal congestive failure, occurred in six. We conclude that fetal echocardiography is feasible and useful in appropriate multiple gestations. Although often ethically complex, the information gained can be applied to patient management.

Color flow mapping in obstetrics.

Blood flow studies are now used extensively in evaluating fetal peripheral circulation. By using continuous and pulsed Doppler ultrasonic equipment the raw Doppler shifts caused by blood moving in the vessels can be analyzed in different ways. Spectral data can be used to estimate blood velocity and volume in the vessel, and pulsatility characteristics and turbulence. All these data are obtained from very restricted areas within the body so that aiming of the probe is critical, and obtaining data from an area requires long and tedious effort. Color flow mapping which has recently been introduced into clinical practice provides an overview of flow velocities and directions within an area. Color coded flow can be displayed by applying the moving target identification principle (as in radar) to an ultrasonic diagnostic instrument where sound waves are used instead of radio waves. The value of flow mapping has already been recognized in the diagnosis of congenital and acquired heart disease in adults and children. Direct visualization of intracardiac flow provides for a fast and accurate diagnosis of various cardiac defects, such as the ventricular septal defect, without cardiac catheterization. In the present study we have investigated the potential of color flow mapping in obstetrics. 211 pregnant women were examined between the 15th and 40th weeks of pregnancy. 193 of them had normal pregnancies; 18 were abnormal, including 11 cases of insulin dependent diabetes, 2 cases of Rh-immunization, 2 cases of nonimmunologic fetal hydrops, 2 cases of fetal cardiac structural defects and 1 case of intrauterine growth retardation. Intracardiac flow was clearly seen in 78% (35/45) of cases at the gestational age between the 20th and 24th weeks. After the 24th week the heart flow visualization rate gradually decreased to 31% (11/36) before term. In 2 cases of congenital heart abnormality flow mapping enabled clear visualization of reverse flow through the tricuspid valve and diagnosis of valvular insufficiency. The best results in studies of flow in peripheral vessels were obtained from umbilical vessels which were seen in all cases after the 15th week. The flow visualization rate was much lower when the fetal aorta, intrahepatic umbilical vein and internal carotid artery were studied. The comparison between the diameter of the umbilical vein measured on the B-scan and flow width in the same vessel showed no significant difference (t = 0.26; p less than 0.01; N = 209).(ABSTRACT TRUNCATED AT 400 WORDS)

Prenatal echocardiography.

Congenital cardiac defects are not common, but their serious consequences make early detection and treatment essential. In developing a set of workable criteria for selective screening of serious abnormalities, the authors used commercially available ultrasound equipment in more than 500 high-risk pregnancies. Possible future applications include elucidation of causes of fetal cardiac defects.