Accuracy of prenatal diagnosis of fetal congenital heart disease by different

Transcription

1 Accuracy of prenatal diagnosis of fetal congenital heart disease by different methods with echocardiography Ying Zhang 1* * Corresponding author baogoubei@hotmail.com Ai-Lu Cai 1 caial_us@hotmail.com Miao Fan 2 fanmiao_r@sina.com Wei-dong Ren 1 renweidong_us@hotmail.com Ya-Jun Guo 1 guoyajun_us@hotmail.com Wei Sun 1 sunwei_us@hotmail.com 1 Department of Sonography, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning, China 2 Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou , China 1

2 Abstracts Background: Prenatal screening and accurate evaluation of fetal CHD is of great importance as it contribute to put forward appropriate neonatal management and helps the parents to make the decision about the pregnancy. The aim of our study is to evaluate the accuracy of different methods of fetal echocardiography in detection of fetal congenital heart disease (CHD) and to analyze the reasons of misdiagnosis in each method. Methods: Four chamber view (4CV) screening method, four transverse views scanning method, and systematic scanning method were used to detect fetal congenital heart disease in 442 cases, of which 349 cases of confirmed normal heart were set into the normal heart group, and the remaining 93 cases of confirmed cardiac anomalies were set into the CHD group. The echocardiographic detection of fetal CHD of each method was recorded for later analysis. Results:The sensitivity of systematic scanning method was higher than the 4CV screening method (95.7% VS 53.8%; P<0.0125) and the four transverse views scanning method (95.7% VS 87.1%; P>0.0125) with significance and insignificance respectively. The negative predicative value of systematic scanning method was significantly higher than 4CV screening method (98.9% VS 89.0%; P<0.0125) while higher than the four transverse views scanning method (98.9% VS 96.6%; P>0.0125) with no significance. There was no statistical difference in specificity and positive predicative value between each two method in the detection of fetal CHD. Conclusions: The four transverse views scanning method is best suited to prenatal 2

3 cardiac screening program due to its high sensitivity and specificity and relatively less diagnostic views. Systematic scanning method is the most accurate but demanding for more experience and expertise and is better for further examination after screening. Key Words: prenatal diagnosis; congenital heart disease; fetal echocardiography; sequential segmental analysis 3

4 Background Congenital heart disease (CHD), accounting for about 0.6% of all live births 1,2, is the most common congenital malformation leading to perinatal morbidity and mortality and is considered the leading cause of death in newborn with congenital anomalies 3,4. Corrected prenatal diagnosis could offer appropriate neonatal management and therapeutic strategies that could reduce perinatal mortality in potential. Also, it may provide a better prenatal counseling and helps to make the correct decision about the treatment 5. Fetal two dimensional echocardiography (2DE) and color Doppler echocardiography (CDE) are currently the primary techniques for the diagnosis of fetal CHD. During the past twenty years, the prenatal diagnostic ability of CHD has been promoted dramatically due to the high resolution 2D ultrasound and the advances in Doppler technology 6. The examination could be preceded either by an obstetric screening sonographer or by a specialist fetal echocardiographer yet the fact is that prenatal diagnosis by fetal echocardiography does not guarantee to excluded all the cardiac malformations. The aim of our study is to evaluate the accuracy of different methods of fetal echocardiography in detection of fetal CHD and to analyze the reasons of misdiagnosis in each method. Methods This study was approved by the institutional ethic committee and written informed consent was obtained from all subjects. Subjects 4

5 This is a prospective study. In total, 467 fetuses undergoing fetal echocardiography in our center between January 2007 and December 2009 were included in the current study. Fetal 2DE and CDE were performed in all the fetuses and the data were saved as video clips. All the cases were undergoing follow-up for one year. Twenty five cases lost to follow-up were excluded and the remaining 442 cases constituted the subjects of the study, of which 349 cases of confirmed normal heart were set into the normal heart group, and the remaining 93 cases of confirmed cardiac anomalies were set into the CHD group. The golden standard for the grouping was the result of the follow-up, including postnatal echocardiography, confirmation by the operation, and the postmortem findings. Ultrasonography technique A Doppler ultrasound system (Voluson E8, GE Healthcare, Kretztechnik, Zipf, Austria), equipped with a 4-8MHz transabdominal transducer was used in our study. Three methods were then used to assess the fetal cardiac structure and to exclude cardiac malformations in detail respectively. Ostium secundum atrial septal defect (ASD) or patent ductus arteriousus was not considered as a CHD which should be diagnosed in uterus. All studies were carried out under the supervision of an expert fetal echocardiographer with 6 years experience in performing and interpreting fetal echocardiography. Method 1 Four chamber view (4CV) screening method A clear 4CV was acquired with apical or lateral insonation of the fetal heart. The symmetry of the four chambers, atrioventricular coordination, the position and 5

6 activity of the atrioventricular valves, the continuity of endocardial cushion and interventricular seputm and the left and right pulmonary vein draining into the left atrium could be evaluated in 4CV. Method 2 Four transverse views scanning method The method to acquire 4CV was same to Method one mentioned above. On the basis of 4CV, the probe turned gradually up to the fetal head to acquire the left and right outflow tract view and the three-vessel and trachea view (3VT). Cardiac anomalies associated with conotruncal such as tetrology of Fallot, double outlet right ventricle, common arterial trunk, transposition of the great arteries, coarctation of aorta, interrupted aortic arch and parts of ventricular septal defect (VSD) could be detected by the two outflow tract views and 3VT. Method 3 Systematic scanning method Sequential segmental analysis were systematically used in this method to identify the fetal visceral and cardiac position, morphologic structures at the atrial, ventricle and arterial trunk level orderly and respectively. To identify the cardiac and visceral position of the fetus, the sagittal plane of the fetus was firstly acquired to identify the position of fetal head and spine and then the transverse plane of the fetus was acquired by rotating the beam 90 counterclockwise from the initial sagittal plane to identify the left side and the right side of the fetus. As the relationship of fetal left side, right side, and the spine remains unchanged, the spine could be considered as the landmark to distinguish the left side from the right side in the transverse plane of both thorax level and abdominal level. The position of 6

7 fetal heart and gastric vacuole were then determined correctly. The remaining examination was similar to infant echocardiography. Three basic areas including the atria, ventricles, and great arteries and their connections were analyzed to evaluate the atrial and ventricle arrangement, atrioventricular junction between the atria and ventricles, ventriculoarterial junction between the ventricle and arterial outflow tracts. Four transverse views including 4CV, the left and right outflow tract view, 3VT and three parallel sagittal views orthogonal to the initial 4CV, including aortic arch view, ductal arch view, and bicaval view, were used to evaluate the connections and the relationships of the adjacent segments mentioned above. Statistical analysis The sensitivity, specificity, positive predictive value and negative predicative value among 4CV screening method, four transverse views scanning method and systematic scanning method were compared via chi-square analysis of proportions. The alpha level was set at by Bonferroni correction. P< was considered statistical significant. Results Prenatal diagnosis of CHD with three methods and postnatal confirmation were summarized in Table 1. Total 93 cases of fetal CHD were confirmed by postnatal echocardiography, operation findings or autopsy findings and the classifications of CHD were shown in Figure 1. By means of 4CV screening method, 6 cases of VSD, one case of ASD sinus type, 5 cases of anomalies associated with drainage of superior vena cava (SVC) and inferior vena cava (IVC), 5 cases of anomalies associated with 7

8 cardiac malposition, and all the cases associated with conotruncal anomalies were not visualized prenatally. One patient diagnosed prenatally as having a VSD was found to be normal on postnatal echocardiography assessment. By means of four transverse views scanning method, 4 cases of VSD, one case of ASD sinus type, one case of aberrant IVC drainage, one case of ductus arterious closure in uterus, and 5 cases of anomalies associated with cardiac malposition were not detected prenatally. Three patients diagnosed prenatally as coarctation of aorta (COA) were proved to be normal by neonatal echocardiography. By means of systematic scanning method, only 4 cases of VSD were not detected prenatally while in one case suspected as COA proved to be normal after birth. Table 2 to Table 4 reveals the detection ability of CHD with the three methods respectively. The sensitivity of systematic scanning method in the detection of CHD was the highest among the three methods and was higher than the 4CV screening method (95.7% VS 53.8%; P<0.0125) and the four transverse views scanning method (95.7% VS 87.1%; P>0.0125) with significance and insignificance respectively. Also, the negative predicative value of systematic scanning method was significantly higher than 4CV screening method (98.9% VS 89.0%; P<0.0125) while higher than the four transverse views scanning method (98.9% VS 96.6%; P>0.0125) with no significance. There was no statistical difference in specificity and positive predicative value between each two method in the detection of fetal CHD (Table 5). Discussion Of all congenital anomalies, CHD is the most common and has the worse 8

9 prognosis compared with other disorders due to its high morbidity and mortality 3,4. Prenatal screening and accurate evaluation of fetal CHD is of great importance as it contribute to put forward appropriate neonatal management and helps the parents to make the decision about the pregnancy. Previous studies have shown that fetal echocardiography is of great value in the diagnosis of CHD and several methods were used in these reports CV is considered the most important diagnostic view in fetal echocardiography and is often the initial plane to acquire other planes 13. It is usually easy to obtain the standard 4CV plane if the spinal acoustic shadowing is avoided. The optimal view of 4CV is usually obtained when the cardiac apex is directed toward the maternal wall 14. 4CV screening alone could visualize most cardiac anomalies at the atrial and ventricle level, such as parts of VSD, atrioventricular septal defect (AVSD), Ebstein s anomaly, rhabdomyoma, ventricular diverticulum, and hypoplastic left heart syndrome (HLHS), etc. Yet the conotruncal anomalies could not be evaluated by 4CV as the two outflow tracts could not be visualized in 4CV and this lead to the low sensitivity of 4CV screening method. Previous study had shown that the detection rate of VSD by 4CV is significantly lower than by combination of the two outflow tract views as the fact was that parts of VSD was associated with the development of truncus arteriosus. Though the sensitivity of 4CV screening method is low, the specificity is high enough as 4CV could clearly demonstrate the anomalies in it with no doubt. In our study, only one case of VSD diagnosed prenatally by 4CV screening was proved to be normal heart after birth. 9

10 The sensitivity of four transverse views scanning method is no doubtly higher than 4CV screening method as more diagnostic views were added to evaluate the structures at conotruncal level besides 4CV level. It is easy to understand that most conotruncal anomalies could be detected by the combination of the four transverse views. The missed diagnosis of VSD in four cases maybe because the defect is too small to be visualized and the shunting speed is too low to be detected between the two ventricles. A ductus arteriosus closure was also missed prenatally maybe because of the lesion was not correctly recognized on 3VT. Other missed prenatal diagnosis was due to the lacking of corresponding diagnostic planes that was not included in the four transverse planes. The false positive results of 3 cases of COA with this method is because that the degree of coarctation is not serious and positioned at the aortic isthmus and the situation maybe improve after birth. Overall, the sensitivity and specificity of the four transverse views scanning method is ideal and high enough to fit for prenatal screening program. Systematic scanning method is a modality based on sequential segmental analysis of cardiac malformation. Sequential segmental analysis introduced by Van Praagh 15 is an old-new approach that has been widely used in the diagnosis of CHD in both infants and adults. Indeed, it provides a means of cataloguing and describing all congenital cardiac malformations, even if the combination of lesions has never previously been encountered 16. Detailed scan method of sequential segmental analysis has been widely used 17,18 and we will not repeat here. Yet in the circumstance of fetal cardiac examination, the identification of the visceral and 10

11 cardiac position is different from the postnatal echocardiography due to the variable fetal positions in uterus. The problem could be well resolved by two steps according to the approach proposed in our study. It is then easy to understand that all the cardiac anomalies associated with cardiac malposition that could not be visualized by the four transverse views scanning method were correctly diagnosed prenatally by systematic scanning method. In summary, many more views are included in the fetal echocardiography examination by systematic scanning method. Two views including the longitudinal section of fetal head and spine and the transverse section of fetal abdomen and thorax are used to identify the fetal visceral and cardiac position. Four transverse views including 4CV, the left and right outflow tract view and 3VT are used to confirm the malformations at atrial, ventricle and arterial trunks level. Besides, three sagittal sections including bicaval view, aortic arch view, and ductal arch view are added to the examination to improve the accuracy of the result. We found that parts of CHD that could not be determined by other methods could be diagnosed correctly by systematic scanning method, including abnormal systemic venous connections, ASD sinus type, ductus arteriosus closure, etc. The value of the added saggital views were well confirmed then. As a result, systematic scanning method is nevertheless the best method in detecting fetal CHD. Yet it is a very time-consuming work and demand for much technique and experience that exceed the ability of most ecumenical sonographers. As the four transverse views scanning method has both high sensitivity and specificity that were very closed to systematic scanning method, we believe it is of great value to 11

12 put forward this approach in general obstetric examinations. Conclusion We have made the comparison of the three methods in the detection of fetal CHD. The four transverse views scanning method is best suited to prenatal cardiac screening program as it has high sensitivity and specificity and a requirement of relatively small number of diagnostic views. Systematic scanning method is the most accurate but demanding for more experience and expertise of the sonographers and is better for further examination after a positive result for fetal cardiac screening. Competing interests The authors declare that they have no competing interests. Authors contributions YZ and A-lC designed the whole study. YZ, W-dR, MF, WS, Y-jG and A-lC drafted the manuscript. WS and Y-jG performed the fetal echocardiography. All authors read and approved the final manuscript. Acknowledgement We highly acknowledge the support of professor Wei-dong Ren, chair of our department, for his great help in the study. We also appreciate Dr. Ya-jun Guo and Dr. Wei Sun, for their great effort in performing all the fetal echocardiography examinations in the study. 12

13 References 1. Hoffman JIE, Kaplan S: The incidence of congenital heart disease. J Am Coll Cardiol 2002, 39: Massaro AN, El-Dib M, Glass P, Aly H: Factors associated with adverse neurodevelopmental outcomes in infants with congenital heart disease. Brain Dev 2008, 30: Gillum RF: Epidemiology of congenital heart disease in the United States. Am Heart J. 1994; 127(4 Pt 1): Gembruch U: Prenatal diagnosis of congenital heart disease. Prenat Diagn 1997, 17: Mellander M: Perinatal management, counselling and outcome of fetuses with congenital heart disease. Semin Fetal Neonatal Med 2005, 10: Allan L: Technique of fetal echocardiography. Pediatr Cardiol 2004, 25: Giancotti A, Torcia F, Giampa G, Gallo G, Gallo F, Donati L, De Santo D: Prenatal evaluation of congenital heart disease in high-risk pregnancies. Clin Exp Obstet Gynecol 1995, 22: Berghella V, Pagotto L, Kaufman M, Huhta JC, Wapner RJ: Accuracy of prenatal diagnosis of congenital heart defects. Fetal Diagn Ther 2001, 16: Meyer-Wittkopf M, Cooper S, Sholler G: Correlation between fetal cardiac diagnosis by obstetric and pediatric cardiologist sonographers and comparison with postnatal findings. Ultrasound Obstet Gynecol 2001, 17:

14 10. Forbus GA, Atz AM, Shirali GS: Implications and limitations of an abnormal fetal echocardiogram. Am J Cardiol 2004, 94: Gottliebson WM, Border WL, Franklin CM, Meyer RA, Michelfelder EC: Accuracy of fetal echocardiography: a cardiac segment-specific analysis. Ultrasound Obstet Gynecol 2006, 28: Bakiler AR, Ozer EA, Kanik A, Kanit H, Aktas FN: Accuracy of prenatal diagnosis of congenital heart disease with fetal echocardiography. Fetal Diagn Ther 2007, 22: Allan LD: A practical approach to fetal heart scanning. Semin Perinatol 2000, 24: Fetal Echocardiography Task Force; American Institute of Ultrasound in Medicine Clinical Standards Committee; American College of Obstetricians and Gynecologists; Society for Maternal-Fetal Medicine: AIUM practice guideline for the performance of fetal echocardiography. J Ultrasound Med 2011, 30: Van Praagh R: The segmental approach to diagnosis in congenital heart disease. Birth Defects1972,8: Anderson RH, Shirali G: Sequential segmental analysis. Ann Pediatr Cardio 2009, 2: Yoo SJ, Lee YH, Cho KS, Kim DY: Sequential segmental approach to fetal congenital heart disease. Cardiol Young 1999, 9: Carvalho JS, Ho SY, Shinebourne EA: Sequential segmental analysis in complex fetal cardiac abnormalities: a logical approach to diagnosis. Ultrasound 14

15 Obstet Gynecol 2005, 26:

16 Figure legends Figure 1 Classifications of congenital heart disease in 93 cases in our series 4CV, four chamber view 16

17 Table 1 Comparison of cardiac anomalies diagnosed by three methods prenatal and postnatal confirmation Prenatal Diagnosis 4CV screening method Four transverse views scanning Systematic scanning method Postnatal method VSD AVSD ASD (Sinus type) IVC drainage anomalies SVC drainage anomalies TAPV rhabdomyoma Ventricular diverticulum Ebstein s anomaly HLHS DORV TOF CAT TGA cctga COA

18 IAA Right aortic arch Ductus arteriosus closure PV/PA stenosis AV/AO stensosis dextrocardia levocardia Cardiac shifting Total ASD, atrial septal defect; AVSD, atrioventricular septal defect; CAT, common arterial trunk; cctga, congenital corrected transposition of the great arteries; COA, coarctation of aorta; DORV, double outlet right ventricle; HLHS, hypoplastic left heart syndrome; IAA, interrupted aortic arch; IVC, inferior vena cava; SVC, superior vena cava; TAPV, total anomalous pulmonary venous connection; TGA, transposition of the great arteries; TOF, tetrology of Fallot; VSD, ventricular septal defect 18

19 Table 2 Results of four chamber view screening method in the diagnosis of fetal congenital heart disease CHD group Normal heart group Total Detected Not detected Total CHD, congenital heart disease 19

20 Table 3 Results of four transverse views scanning method in the diagnosis of fetal congenital heart disease CHD group Normal heart group Total Detected Not detected Total CHD, congenital heart disease 20

21 Table 4 Results of systematic scanning method in the diagnosis of fetal congenital heart disease CHD group Normal heart group Total Detected Not detected Total CHD, congenital heart disease 21

22 Table 5 Comparison of the three methods in the diagnosis fetal congenital heart disease by echocardiography Detection of CHD P value m1 m2 m3 m1 & m2 m1 & m3 m2 & m3 Sensitivity 53.8% 87.1% 95.7% * * Specificity 99.7% 99.1% 99.7% Positive predictive value 98.0% 96.4% 98.9% Negative predicative value 89.0% 96.6% 98.9% * * CHD, congenital heart disease; m1, four chamber view screening method; m2, four transverse views scanning method; m3, systematic scanning method *: statistical significant (chi-square analysis with the alpha level set at by Bonferroni correction). 22

23 23

24 Figure 1