Fetal Heart Defects Research Articles

Routine Use of Color Doppler in Fetal Heart Scanning in a Low-Risk Population

Objectives. To investigate the detection rate of major fetal heart defects in a low-risk population implementing routine use of color Doppler. Material and Methods. In a prospective observational study, all women undergoing fetal heart scanning (including 6781 routine examinations in the second trimester) during a three-year period were included. First a gray-scale scanning was performed including assessment of the four-chamber view and the great vessels. Thereafter three cross-sectional planes through the fetal thorax were assessed with color Doppler. Results. Thirty-nine fetuses had major heart defects, and 26 (67%) were prenatally detected. In 9/26 (35%) of cases the main ultrasound finding was related to the use of color Doppler. The survival rate of live born children was 91%. Conclusions. Routine use of color Doppler in fetal heart scanning in a low-risk population may be helpful in the detection of major heart defects; however, still severe malformations were missed prenatally.

21st World Congress on Ultrasound in Obstetrics and Gynecology, 18-22 September 2011, Los Angeles, USA: presentations and awards

21st World Congress on Ultrasound in Obstetrics and Gynecology, 18-22 September 2011, Los Angeles, USA: presentations and awards

Prenatal diagnosis in congenital heart disease of 22q11 microdeletion

Objective To explore the necessity and feasibility of the prenatal diagnosis of 22q11 microdeletion in fetuses with congenital heart disease.Methods Amniocentesis or cordocentesis were used to get the cells of fetuses in 16 pregnant women tested as fetal congenital heart defects by prenatal ultrasound examination.Then the karyotype analysis and two-color fluorescence in situ hybridization were all carried out for detection of 22q11 microdeletion in these fetuses.Results 22q11 microdeletion was detected in I case.Conclusion 22q1 1 microdeletion prenatal diagnosis in fetuses with congenital heart disease is neccessary and feasible.It has great significance for avoiding the birth of children with congenital heart disease caused by 22q11 microdeletion and recurrence birth risk assessment. Key words: 22q11 microdeletion; Fluorescence in situ hybridization; Congenital heart disease; Prenatal diagnosis

Fetal Echocardiography Echoes Normal Ultrasound Results

Pregnant women with risk factors for fetal congenital heart defects (CHDs) — such as family histories of CHDs, maternal diabetes, and extracardiac

OP35.06: Detection of major fetal heart defects with routine use of colour Doppler

OP35.06: Detection of major fetal heart defects with routine use of colour Doppler

Impact of Maternal Obesity and Maternal Overweight on the Detection Rate of Fetal Heart Defects and the Image Quality of Prenatal Echocardiography

The purpose of this study was to compare the prenatal detection of four congenital heart defects (CHDs) and the image quality of five corresponding ultrasound planes among obese, overweight and normal-weight women. This was a retrospective cohort study of 54,846 pregnancies undergoing fetal echocardiography between 18 and 37 weeks of gestation in the years from 2000 to 2007. The women were categorized according to pre-pregnancy body mass index (BMI) as normal-weight (BMI < 25), overweight (BMI 25 - 29.9) and obese (BMI ≥ 30). Image quality and prenatal detection of atrioventricular septal defect (AVSD), double outlet right ventricle (DORV), tetralogy of fallot (TOF) and dextro transposition of the great arteries (D-TGA) were evaluated in the BMI strata. 108 cases with one of the considered CHDs were identified. The prevalence was significantly higher (relative risk = 2.04) in overweight or obese women (57/19,404 vs. 51/35,442, p < 0.0002) than in normal-weight women. In total 86.1% of CHDs were correctly identified prenatally (93/108, CI: 79.6%-92.6%), 84.3% (43/51) in the normal weight group, 88.6% (39/44) in the overweight group and 84.6% (11/13) in the obese group. The rate of insufficient ultrasound images increased from 6.4% in normal-weight patients to 17.4% in obese women within the 108 CHD cases. The prenatal detection of fetal AVSD, DORV, TOF and D-TGA was also satisfactory in overweight and obese patients, but image quality substantially decreases with an increasing maternal BMI. If there is a BMI-associated difference in the detection rate, it probably will not exceed 20%.

Prenatally detectable congenital heart defects in fetuses with Down syndrome

To document the incidence of congenital heart defects (CHD) that are detectable echocardiographically in the fetus with trisomy 21 and the relationship with nuchal translucency, fetal sex and ethnicity. Data on fetuses with a karyotypic diagnosis of trisomy 21 were collected between January 2002 and March 2010. The data were analyzed for the gestational age at examination, maternal age, reason for referral for fetal echocardiography, cardiac diagnosis, fetal sex, ethnicity and outcome. Of 917 fetuses with trisomy 21, 487 had a diagnostic echocardiogram. Cardiac examination was performed before 14 weeks' gestation in 75% of cases. The main reasons for referral were increased nuchal translucency (NT) in 76% of cases, suspected cardiac abnormality in 15% and an extracardiac anomaly in 6%. Structural CHD was found in 164/487 (34%), or 98/412 (24%) if those referred for suspected CHD are removed from the analysis. The most common diagnosis was atrioventricular septal defect (AVSD) (115/487, 24%). The ratio of female to male fetuses with AVSD was 29%:18% (P = 0.003). There was no difference in the incidence of AVSD with ethnicity. The pregnancy continued in 36 cases, but three were lost to follow-up; of the known outcomes there were 10 intrauterine deaths, six of which had structural heart disease, and 23 live births, 15 of which had CHD. Most fetuses (66-76%) with trisomy 21 have a structurally normal heart on echocardiography. The presence of structural CHD was not associated with increased NT. The increased incidence of AVSD in females was confirmed in our study, although an ethnic difference could not be confirmed. CHD does not appear to increase the chance of spontaneous intrauterine loss in ongoing pregnancies.

22q11.2 microduplication in a family with recurrent fetal congenital heart disease

People carrying a 22q11.2 microduplication display a phenotype varying from normal to severely affected. We report a phenotypically normal female presented with a fetus having a severe congenital heart defect with ventricular septal defect, tricuspid atresia, patent ductus arteriosus and interrupted aortic arch. The pregnant woman had a history of overall three consecutive aberrant pregnancies with tetralogy of Fallot. Standard G-banding karyotype analysis of the parents and the actual pregnancy were normal, while array comparative genomic hybridization (arrayCGH) analysis revealed a 22q11.2 microduplication within the fetus’ genome. Fluorescence in situ hybridization (FISH) and short tandem repeat polymorphism (STRP) tests indicated the affected fetus inherited the interstitial 22q11.2 microduplication from the mother. High-resolution oligonucleotide microarray analysis showed this microduplication is located in the common 3 Mb 22q11.2 deletion region between positions 17.298 Mb and 20.246 Mb with a length of 2.948 Mb. This report demonstrates the remarkable intrafamilial variability of a 22q11.2 microduplication phenotype. The 22q11.2 microduplication carried by one of the healthy parents has most likely contributed to the recurrent fetal heart defects.

The thymic–thoracic ratio in fetal heart defects: a simple way to identify fetuses at high risk for microdeletion 22q11

To establish reference ranges for the fetal thymic-thoracic ratio (TT-ratio) and to compare results with those from fetuses with congenital heart defects (CHD) with and without microdeletion 22q11 (del.22q11), a condition known to be associated with a hypoplastic thymus. TT-ratio was defined as the quotient of the anteroposterior thymic to the intrathoracic mediastinal diameters measured in the three vessels and trachea view. This ratio was measured in a prospective cross-sectional study of 302 normal healthy fetuses between 15 and 39 weeks' gestation. The study group comprised two groups: one group (CHDn) consisted of 90 fetuses with CHD and a normal karyotype with no del.22q11 and the other group (CHD(22)) included 20 fetuses with CHD and a normal karyotype but with proven del.22q11. The TT-ratio of the normal fetuses did not show any statistically significant change during gestation, with a mean value of 0.44. The values of all 90 fetuses of the CHDn group were within the normal range and no different from normal fetuses. However, 19 of the 20 (95%) fetuses in the CHD(22) group had a significantly smaller TT-ratio (P < 0.001) compared with both the CHDn group and the normal fetuses, having a mean value of 0.25. The TT-ratio is reliable and easy to obtain during fetal echocardiography. Fetuses with CHD and a low TT-ratio can be considered at high risk of having microdeletion del.22q11.

First‐trimester measurement of the ductus venosus pulsatility index and the prediction of congenital heart defects

This study was carried out to evaluate the additional predictive value of ductus venosus pulsatility index for veins (DV-PIV) in the identification of congenital heart defects (CHDs) in fetuses with an enlarged nuchal translucency (NT) and a normal karyotype. All chromosomally normal fetuses referred to our Fetal Medicine Unit between September 1996 and December 2008 with known NT, DV-PIV and ductus venosus (DV) a-wave measurements were included. Intrafetus variation in DV-PIV was overcome by averaging three recordings. Follow-up included special focus on CHD. The odds of CHD at any NT and DV-PIV value were evaluated using logistic regression analysis. Of 792 fetuses included, the NT was enlarged (equal to or above the 95(th) percentile (P95)) in 318 (40.2%). The DV-PIV was abnormal (≥ P95) in 41.8% of the fetuses with an enlarged NT and the a-wave was abnormal (negative or reversed) in 29.9%. CHD was diagnosed in 35 fetuses, 33 of which had an enlarged NT. Amongst the fetuses with an enlarged NT, the sensitivities for CHD of abnormal DV-PIV and DV a-wave were 73% and 55%, with specificities of 62% and 73%, respectively. Logistic regression analysis showed that in this risk group the DV-PIV multiple of the median (MoM) (as a continuous variable) was significantly associated with the risk of CHD (odds ratio = 2.4), independent of the degree of NT enlargement, whereas the DV a-wave did not significantly add to the prediction of CHD. Two-thirds of fetuses with an enlarged NT, a normal karyotype and CHD have an increased DV-PIV. DV-PIV can be used as continuous variable in combination with NT to increase specificity in the identification of CHD and to refine the individual risk assessment.

Collaborative Study on 4-Dimensional Echocardiography for the Diagnosis of Fetal Heart Defects

Congenital anomalies are the leading cause of infant mortality in the United States, and congenital heart defects (CHDs) are the most common type of birth defects. Recently, 4-dimensional ultrasonography (4DUS) with spatiotemporal image correlation (STIC) has been introduced for fetal echocardiography. Accumulating evidence indicates that 4DUS with STIC may facilitate the examination of the fetal heart. Our objectives were to determine the accuracy of 4DUS for the diagnosis of CHDs and the agreement among centers. This study included 7 centers with expertise in 4D fetal echocardiography. Fetuses with and without confirmed heart defects were scanned between 18 and 26 weeks, and their volume data sets were uploaded onto a centralized file transfer protocol server. Intercenter agreement was determined using a κ statistic for multiple raters. Ninety volume data sets were randomly selected for blinded analysis. Overall, the median (range) sensitivity, specificity, positive and negative predictive values, and false-positive and -negative rates for the identification of fetuses with CHDs were 93% (77%-100%), 96% (84%-100%), 96% (83%-100%), 93% (79%-100%), 4.8% (2.7%-25%), and 6.8% (5%-22%), respectively. The most frequent CHDs were conotruncal anomalies (36%). There was excellent intercenter agreement (κ = 0.97). (1) Four-dimensional volume data sets can be remotely acquired and accurately interpreted by different centers. (2) Among centers with technical expertise, 4DUS is an accurate and reliable method for fetal echocardiography.

Progress of pregestational diabetes mellitus and congenital heart defects

Pregestational diabetes mellitus may cause fetal heart defects,and it is considered to be an important non-genetic risk factors for congenital heart defects. However, the pathogenesis is unclear. Recent studies have shown that hyperglycemia, which acts as a primary teratogen in pregestational diabetes mellitus, may affect the endocardial cushion formation and neural crest cell development. Cardiac oxidative stress damage, increased myocardial cell apoptosis,increased synthesis of extracellular matrix, as well as the alteration of heart development-related genes expression are important pathogenic mechanism. In this paper, we review the progress in the effect and the pathogenesis of pregestational diabetes mellitus on heart development. Key words: Pregestational diabetes mellitus; Congenital heart defects; Endocardial cushion; Neural crest cell

68: Collaborative study on four-dimensional echocardiography for the diagnosis of fetal heart defects: The COFEHD study

Four-dimensional ultrasonography (4DUS) with spatiotemporal image correlation (STIC) has the potential to reduce the operator dependency of 2DUS in the detection of congenital heart defects (CHDs). Our objectives were to determine the accuracy of 4DUS for the diagnosis of CHDs and the agreement among centers.

Zinc Antagonizes Homocysteine-Induced Fetal Heart Defects in Rats

It has been suggested that zinc may have a protective role against heart defects during fetal development. We investigated the effects of zinc on the development of fetal cardiac malformations induced by homocysteine. Pregnant Sprague-Dawley rats were randomized into one of five groups: control (C), homocysteine (H), homocysteine + zinc (Z), homocysteine + folic acid (F), or homocysteine + zinc + folic acid (ZF) (each n = 8). Homocysteine (8 nmol/day) was administered intraperitoneally in the H, Z, F, and ZF groups on gestation days (GD) 8, 9, and 10. Zinc (30 mg/kg day), folic acid (30 mg/kg day), or both (30 mg/kg day each) were administered intragastrically daily in the Z, F, and ZF groups, respectively, throughout the pregnancy. In each group, two fetuses were removed on GD 13, 15, 17, and 19 and examined for cardiac malformations; maternal copper/zinc-containing-superoxide dismutase (Cu/Zn-SOD) activity and metallothionein type I (MT-1) mRNA expression were measured simultaneously. The prevalence of cardiac malformations was significantly higher in group H than in group C, and significantly lower in group Z than in group H at the studied time points. Cu/Zn-SOD activity and MT-1 mRNA levels were significantly lower in group H than in group C, and significantly higher in group Z than in group H. Our data suggest that zinc antagonizes homocysteine-induced teratogenic effects on the fetal heart, possibly via the inhibition of excessive peroxidation.

Relationship between the advanced glycation end products in gestational diabetes mellitus rats and its newborns heart development

Objective To explore the effect of advanced glycation end product(AGE) in serum of maternal rats with gestational diabetes mellitus (GDM) on the heart development of their offsprings. Methods Fifty-four SD rats were randomly assigned into control group (n= 24) and GDM group (n=30) which were established by administration of streptozotocin intra-abdominally. On the gestational age of 13, 16, 19 days, all rats underwent hysterectomy to obtain the fetal heart tissues. Serum level of AGE and blood glucose level of maternal rats were tested. The expression of receptor AGE (RAGE) in fetal cardiac tissue were detected by immunohistoehemistry. Results The incidence of fetal heart defect in GDM group was significantly higher than the control group at each time point (P<0.01). Rats in GDM group had higher blood glucose level at each time point (P<0.01). The AGE levels of GDM group on gestational age of 13, 16 and 19 day [(5.72±0.68) U/mgpr, (7.31±0.29) U/mgpr and (7.77±0.39) U/mgpr] were significantly higher than those of the control group [(4.45±0.27) U/mgpr, (4.71±0. 35) U/mgpr and (4. 37±0. 44) U/rngpr] (t=6. 142, 16. 295, 0. 399,P<0. 01). The number of heart malformation in fetal rats (r=0.994,P=0. 000) and blood glucose (r=0. 717,P=0. 000) had the positive relationship with the maternal serum AGE level. The expression of RAGE in fetal heart was positively related with the number of fetal heart malformation (r= 0. 638,P= 0. 004). Conclusions The increased maternal serum AGE level in GDM rats may be an important factor in fetal heart dysplasia. Key words: Diabetes, gestational; Glyeosylation end products, advanced; Receptor S, immunologic; Diabetes mellitus, experimental; Heart defects, congenital

Extracardiac lesions and chromosomal abnormalities associated with major fetal heart defects: comparison of intrauterine, postnatal and postmortem diagnoses

The clinical outcome of prenatally diagnosed congenital heart defects (CHD) continues to be affected significantly by associated extracardiac and chromosomal abnormalities. We sought to: determine the frequency and type of major extracardiac abnormalities (with impact on quality of life) and chromosomal abnormalities associated with fetal CHD; and compare the extracardiac abnormalities detected prenatally to the postnatal and autopsy findings in affected fetuses, to find the incidence of extracardiac abnormalities missed on prenatal ultrasound. We reviewed the computerized database of the Division of Cardiology of the Hospital for Sick Children in Toronto to identify all cases of major CHD detected prenatally from 1990 to 2002. Medical records, fetal echocardiograms and ultrasound, cytogenetic and autopsy reports were reviewed. The types of CHD detected were grouped into categories and the frequencies of major extracardiac and chromosomal abnormalities in these categories were noted. Prenatal ultrasound findings were compared with those at autopsy or postnatal examination. Of 491 fetuses with major structural CHD, complete data were obtained for 382. Of these, there were 141 (36.9%) with major extracardiac abnormalities at autopsy or postnatal exam, of which 46 had chromosomal abnormalities and 95 did not. In the absence of chromosomal abnormalities, the organ systems most affected were urogenital (12.2%) and gastrointestinal (11.6%). CHDs with the highest incidence of extracardiac abnormalities (>25%) included: heterotaxy, single left ventricle and tricuspid atresia, hypoplastic left heart syndrome and tetralogy of Fallot. Ninety-four of 334 (28.1%) fetuses tested had chromosomal abnormalities. The most common chromosomal abnormalities were trisomies 21 (43.6%), 18 (19.1%) and 13 (9.6%), monosomy X (7.4%) and 22q11.2 deletion (7.4%). Of 289 extracardiac abnormalities from the complete series, 134 (46.4%) were not identified prenatally. Of the missed extracardiac abnormalities, 65 were considered not detectable at prenatal ultrasound, so 23.9% (69/289) of detectable extracardiac abnormalities were missed prenatally. Major extracardiac and chromosomal abnormalities are common in fetuses with major fetal CHD. Many important associated extracardiac abnormalities may be missed prenatally, which should be taken into consideration in the prenatal counseling for fetal CHD.

Sonographic Findings in Trisomy 9

The purpose of this study was to identify the most common prenatal sonographic findings in fetuses with complete trisomy 9. A retrospective review of all cases of trisomy 9 at 5 participating institutions over a 15-year interval was conducted. Indications for referral and sonographic findings in each case were reviewed to identify characteristic fetal structural anomalies. Six cases of trisomy 9 are presented. Most patients were referred for abnormal sonographic findings on screening examinations (66%) or advanced maternal age (33%). Fetal heart defects and central nervous system malformations were the most frequent sonographic anomalies seen. Sonographic findings in trisomy 9 are similar to those found in other autosomal trisomies. Because trisomy 9 is uniformly lethal and is not included as part of the standard prenatal aneuploidy screening by fluorescence in situ hybridization analysis, clinicians should be cautious in counseling patients with structurally abnormal fetuses until the full karyotype is available.

OP12.04: A new algorithm for fetal cardiac scanning using volume reslicing modality (3D extended imaging) and spatiotemporal image correlation (STIC)

To assess the value of a new ultrasound technology, named XI STIC, that is composed of volume reslicing modality 3D XI and STIC for routine fetal cardiac screening in the second trimester. Sixty-two volume datasets of fetuses without fetal heart defects were obtained using ACCUVIX XI (Medison Co Ltd, Korea) and reviewed with the help of 3D XI PC Viewer (laptop PC program). 3D XI modality associated with STIC enables a ‘slice-by-slice’ approach for ultrasound examination of the beating fetal heart and allows simultaneous visualization of transverse cardiac planes from the upper abdomen to the upper mediastinum. The complete offline fetal cardiac survey was based on the criteria of Dr Yagel and Dr Yoo (‘5 short axis’ planes: upper abdomen, four-chamber view, five-chamber view, main pulmonary artery, three-vessel and trachea view). Each volume was resliced to the 12 consecutive planes, whose distances were adjusted for an optimal visualization of the fetal cardiac landmarks. In addition, long-axis views of great outflows and their crisscrossing were acquired by revolving the volumes along the x- or y-axis on 30–45 degrees. The visualization rate of each diagnostic cardiac plane was calculated. In our preliminary study the ‘upper abdomen’ was not visualized in some cases due to the insufficient sweep angle that was not appropriate to capture the ‘stomach level’. The four-chamber view was obtained in all cases, as each volume sweep was initiated after imaging the view in the transverse plane of the fetal chest. The Table lists the diagnostic planes of the fetal heart and the frequency of visualization. With the help of XI STIC it was possible to generate standard diagnostic planes of the beating fetal heart from only a single volume. The new algorithm using XI STIC makes it feasible to evaluate ‘5 short axis’ planes and outflow crisscrossing simultaneously that is not available with the conventional ultrasound approach.

A further case with a small supernumerary marker chromosome (sSMC) derived from chromosome 1—evidence for high variability in mosaicism in different tissues of sSMC carriers

A prenatally ascertained case with a de novo small supernumerary marker chromosome (sSMC) derived from chromosome 1 is reported. Due to a fetal heart defect the parents decided in favour of an induced abortion. Postmortem, a molecular cytogenetic study on eleven formalin fixed, paraffin-embedded tissues of the fetus was performed, to further characterize the levels of mosaicism of the sSMC(1). sSMC presence varied between 13 and 62% within different tissues of sSMC carriers. This finding is something common in sSMC carriers and could explain why up to the present no clinical correlations for sSMC mosaicism and clinical outcome in the corresponding carriers could be established.

Obstetric Outcome of 6346 Pregnancies With Infants Affected by Congenital Heart Defects

This prospective, population-based, cohort study analyzed 6346 singleton pregnancies in Sweden during the years 1992 to 2001 in which the infant had a congenital heart defect. The prevalence of cardiovascular defects in the study population, totaling 770,355 infants, was 9.1 per 1000 births. Cases with known chromosomal abnormalities or preexisting maternal diabetes were excluded. An isolated cardiovascular defect was present in 84% of infants, and in 22%, it was severe. Case mothers did not differ substantially from control subjects with regard to age, parity, or smoking in early pregnancy. Obesity was more frequent in the case group; the crude odds ratio for having a body mass index of 25 kg/m2 or higher was 1.08 (95% confidence interval, 1.02–1.13). Cesarean delivery occurred more often in the case group, especially in cases with severe cardiac defects. The risk of instrumental delivery also was increased, but only when all cardiac defects were considered. In term infants, labor induction was significantly more frequent in the case group (odds ratio [OR], 1.12; 1.02–1.22), and the risk of preterm delivery was increased 2- to 3-fold. Infants with cardiac defects—especially severe ones—had lower birth weights than expected and were significantly more likely to be small for gestational age (OR, 2.46; 1.98–3.05). Those with milder defects, however, were likelier to be large-for-gestational-age infants (OR, 1.45; 1.28–1.64). Severe cardiac defects occurred in 26% of preterm infants compared with 21% of term infants (P < .001). Fetal distress, meconium aspiration, and low Apgar scores all were significantly more frequent in infants with cardiac defects. The incidence of preeclampsia was higher in case pregnancies (OR, 1.21; 1.06–1.37), but the incidence of stillbirth was the same in cases and control subjects. In this large-scale, population-based study, several obstetric and neonatal complications were more frequent when a fetal heart defect was present. A search for congenital cardiac defects is appropriate in neonates who had complicated pregnancies.