DOI: 10.1002/pd.4372
ORIGINAL ARTICLE
Early fetal echocardiography: congenital heart disease detection and diagnostic accuracy in the hands of an experienced fetal cardiology program Jodi I. Pike, Anita Krishnan and Mary T. Donofrio* Children’s National Heart Institute, Children’s National Medical Center, Washington, DC 20010, USA *Correspondence to: Mary Donofrio. E-mail: [email protected]
ABSTRACT Objective Evaluate the utility of early fetal echocardiography in the hands of an experienced fetal cardiology program for detection of congenital heart disease (CHD) in high-risk pregnancies. Methods Review of fetal echocardiograms 12 to 16 weeks of gestation. Results There were 151 studies in 142 fetuses (mean age 14.5 weeks). Transabdominal imaging was sufficient for 104; transvaginal imaging was used in 38. CHD was found in 32(22.5%). High yield indications were suspected cardiac anomaly (91.7%) and extracardiac anomaly (50%). Lower yield indications were increased nuchal translucency (13.8%) and family history (6.1%). No fetuses referred for advanced maternal age, maternal lupus, or diabetes had CHD. Mid-gestation follow-up was possible in 128 (ten terminated/four lost to follow-up). Three of 19 initially diagnosed with CHD had normal hearts; none diagnosed as normal had CHD (sensitivity 100%/specificity 97.3%). Seven had modification of original diagnoses: three initially diagnosed with possible septal defects had no defect, two had diagnoses that changed, and two had progression different than predicted.
Conclusion Early fetal echocardiography performed in an experienced fetal cardiology program accurately identifies significant CHD. Appropriate referral indications to fetal cardiac specialists include suspected CHD, extracardiac anomaly, increased nuchal translucency, and significant family history. Lesions that may not be diagnosed with accuracy include septal defects and diseases that progress. © 2014 John Wiley & Sons, Ltd.
Funding sources: None Conflicts of interest: None declared
INTRODUCTION Prenatal diagnosis of congenital heart disease (CHD) has been shown to have a significant effect on prenatal and postnatal management and outcomes.1–5 In addition to the potential medical benefits, fetal diagnosis allows for valuable parental counseling, which allows families to make informed decisions regarding the pregnancy, and to prepare emotionally for the birth of the child with significant CHD. Accurate prenatal diagnosis can also lead to additional testing of the fetus, including genetic evaluation and other anatomic imaging, which can yield valuable information in overall assessment of the fetus. Referral for fetal echocardiogram typically occurs between 18 and 22 weeks gestational age. With advances in ultrasound technology, which has allowed for the significant improvements in high-resolution imaging necessary to visualize the developing fetal heart, fetal echocardiography can now be performed in the late first trimester and early second trimester of pregnancy.6–9 In addition, with the wide availability and practice of nuchal translucency (NT) measurements, which typically occurs Prenatal Diagnosis 2014, 34, 1–7
between 11 and 14 weeks gestational age, the demand for early fetal cardiac imaging has increased. Increased NT has been shown to be associated with CHD, even in the presence of normal karyotype,10,11 and early and accurate cardiac diagnosis is an essential part of the evaluation of these fetuses. Despite the potential benefits of early cardiac imaging, it is not the standard of practice in most institutions in the United States. In addition, practice patterns tend to be variable regarding who does the imaging, the imaging protocol, the indications for referral, and the timing of consultation. Given that the utility and accuracy of early fetal cardiac imaging in the hands of experienced fetal cardiologists is undefined, the objective of this study was to evaluate the experience of diagnosing cardiac anomalies using early fetal echocardiography at a large fetal cardiac referral center.
METHODS We conducted a retrospective review of all early fetal echocardiograms performed between July 2007 and December 2010 in the Fetal Heart Program at Children’s National Medical © 2014 John Wiley & Sons, Ltd.
J. I. Pike et al.
Center. Early fetal echocardiograms were defined as studies completed between 12 and 16 weeks estimated gestational age (EGA). Qualifying studies were identified by a database search of all echocardiograms performed during the study period with the summary codes ‘First trimester fetal echocardiogram’, ‘Fetal echocardiogram 3 mm), an increasingly common indication for early fetal echocardiography, yielded a finding of structural cardiac disease in 13.8% of such referrals. (Table 1) No fetuses referred for advanced maternal age, maternal lupus, or maternal diabetes mellitus had cardiac disease. All those referred for maternal lupus had a normal PR interval.
Routine fetal echocardiography follow-up at greater than 20 weeks EGA was available in 128 of 142 fetuses. Of the fetuses that did not return, ten pregnancies were known to have been terminated, and four were lost to follow-up (one normal was lost to follow-up; the remaining three had an abnormal initial early fetal echocardiograms). All of those known to have terminated were diagnosed with significant heart disease and/or notable extracardiac or genetic abnormalities. In those with isolated CHD, the result of the early fetal echocardiogram was the primary reason for termination. In those with additional findings, it could not be ascertained as to the primary reason for termination (Table 2).
Prenatal Diagnosis 2014, 34, 1–7
© 2014 John Wiley & Sons, Ltd.
J. I. Pike et al.
A structural cardiac anomaly was found in 32 out of 142 fetuses (22.5%) (Table 3). One hundred twenty-eight fetuses, 19 with a cardiac anomaly at the initial early study, had a follow-up fetal echocardiograms at greater than 20 weeks EGA. At follow-up evaluation, three of the 19 fetuses initially diagnosed with a cardiac anomaly had a normal heart; conversely, no fetuses initially diagnosed with a normal heart were subsequently found to have cardiac disease. This yielded a sensitivity of 100%, a specificity of 97.3%, a positive predictive value of 84.2%, and a negative predictive value of 100% for major structural heart disease. In total, seven fetuses (5%) had some modification of the initial cardiac diagnosis at follow-up (Table 3; bolded subjects). As stated, three had a structurally normal heart at the followup comprehensive mid-gestation echocardiogram. All three were described as having a ‘suspected’ or ‘possible’ ventricular septal defect at the early fetal echocardiogram. It is unclear whether these ventricular septal defects were inaccurately
diagnosed at initial echocardiogram, or the defect closed and early imaging reveals the potential natural history of small septal defects closing during gestation. Of the remaining fetuses with modified diagnoses, another with a ‘possible ventricular septal defect’ was later found to have an intact ventricular septum, but a thickened right ventricle. One fetus was described as having a ‘possible atrioventricular canal’ at initial early fetal echocardiogram; the diagnosis was changed to a moderate ventricular septal defect at follow-up. Another, referred for significant extracardiac anomalies was thought to have multiple cardiac tumors at initial exam but found to have an echogenic focus and ventricular septal defect at subsequent follow-up examination. Finally, a fetus referred at 13 weeks for increased NT was initially diagnosed with hypoplastic left heart syndrome but was ultimately determined at follow-up scan to have Shone’s syndrome including aortic and mitral stenosis, coarctation of the aorta, and a borderline left ventricle (Figure 1).
Figure 1 Early scans (12 and 16 weeks) and mid-gestation scan (28 weeks) in a fetus originally diagnosed with a hypoplastic left heart syndrome variant, later noted to be Shone’s with mitral and aortic stenosis, coarctation, and borderline left ventricle. RA = right atrium, RV = right ventricle, LA = left atrium, LV = left ventricle. (A) Two-dimensional (2D) four-chamber view at 12 weeks. (B) Color four-chamber view at 12 weeks using transvaginal imaging, note the color difference filling the RV and LV. (C) 2D four-chamber view at 16 weeks. (D) Color four-chamber view at 16 weeks, note the color difference filling the RV and LV. (E) 2D four-chamber view at 28 weeks. (F) Color four-chamber view at 28 weeks
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© 2014 John Wiley & Sons, Ltd.
Early fetal echocardiography
There was no difference between the EGA at initial study of those with a modification of diagnosis at follow-up and those with no change in diagnosis (13.6 vs 14.5 weeks, p = 0.07), though there was a trend towards improved accuracy with no change in diagnosis if the initial early fetal echocardiogram was performed later in gestation. As expected, image quality improved throughout gestation (Figure 2).
Postnatal follow-up In no subjects with an abnormal scan was there a significant change in diagnosis between the mid-gestation fetal echocardiogram and the initial postnatal study, though this information was only available for 14 of the 16 with abnormal fetal echocardiograms at mid-gestation, as there were two subsequent in utero demises. Of the 109 with normal fetal echocardiograms at both initial early study and subsequent mid-gestation study, there were postnatal echocardiograms available in 26; 78 had no postnatal follow-up and 5 were known to have terminated. Normal echocardiograms were found in 24 of the 26 at initial postnatal study. In the remaining two subjects, a small muscular ventricular septal defect was found on postnatal exam. No unexpected severe CHD was identified postnatally (Figure 3).
DISCUSSION Our study shows that early fetal echocardiography, performed between 12 and 16 weeks gestational age, is technically feasible and can identify a wide variety of significant cardiac anomalies
in the hands of experienced providers specializing in cardiac imaging. Such evaluation can be an important part of early prenatal counseling, especially in those fetuses with known genetic abnormalities or other extracardiac defects. In addition, it allows for the assessment of the progression of disease throughout gestation and as in utero interventions become more widespread, this may allow for earlier and more effective intervention.13 In our hands, the detection rate of CHD was high in the group of patients referred for early fetal cardiac exam, specifically those in which a cardiac defect was already suspected, or those in which an extracardiac anomaly had been previously diagnosed. Low yield indications were those referred due to maternal risk profile such as maternal diabetes or lupus, though this may be secondary to small sample size, as the number of those referred for these indications was limited. However, as these indications for referral are typically used for screening in mid-gestation, it is not surprising that the vast majority had no cardiac disease, as opposed to those in which the indication is an already suspected abnormality. Given that referral to a fetal cardiac specialist early in gestation for a fetal echocardiogram is not for screening purposes, these indications with low yield of diagnosis may not warrant referral unless an abnormality is suspected. Another common referral for early fetal echocardiogram is in women with a significant family history of CHD, often in a prior pregnancy. While the yield of heart disease detection was lower (6.1%) than other indications in which abnormalities
Figure 2 Four chamber view of the heart through early gestation. Note improvement in resolution and better delineation of structures from 12 to 17 weeks of gestation. RA = right atrium, RV = right ventricle, LA = left atrium, LV = left ventricle. (A) 12 weeks. (B) 13 weeks. (C) 14 weeks. (D) 15 weeks. (E) 16 weeks. (F) 17 weeks
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© 2014 John Wiley & Sons, Ltd.
J. I. Pike et al.
Figure 3 Summary outcome information for fetal patients having an early fetal echocardiogram
were noted, it is a higher detection rate than what is reported at mid-gestation.14–16 This could be due to different patient characteristics. Though speculative, we believe that it is more likely that a family with a history of severe disease such as heterotaxy syndrome or hypoplastic left heart syndrome would be sent for early imaging, and the recurrence risk for these severe defects may be higher. In these families with significant past experience, the benefit of early fetal cardiac evaluation may actually lie in the reassurance given with a normal study, and the emotional stress that this may ease for the woman and her partner. In these cases, though family history as a reason for referral is considered at mid-gestation to be an indication, the benefits of the early fetal echocardiogram to the family may outweigh the small likelihood of actually identifying significant CHD. For this reason, we believe that family history of significant CHD in a first degree relative is a reasonable indication for referral to a fetal cardiac specialist for early fetal echocardiogram. Even with reassuring accuracy in regards to identifying major CHD as demonstrated by our high sensitivity, specificity, and negative and positive predictive values, it remains vitally important to counsel patients regarding the limitations of early fetal echocardiography. There are technical constraints to image resolution that become particularly important when imaging fetuses in early gestation, and it is for this reason that septal defects may remain difficult to diagnosis with complete accuracy. In addition, there are diseases that progress Prenatal Diagnosis 2014, 34, 1–7
throughout gestation, and early fetal echocardiography can only describe the structure of the heart at the time point of imaging. Other studies have also looked at the usefulness of evaluation of the fetal heart early in gestation.17–19 These studies demonstrated that early imaging of the fetal heart is technically feasible and can identify a wide spectrum of significant CHD; however, unlike our study, there was significant cardiac disease that was missed on the initial early evaluation. Of course, it is expected that not all CHD will be identified, though we believe that with increasing experience and fetal cardiac expertise, improvements in technology, and creation of universal guidelines for fetal cardiac imaging, detection rates and accuracy will continue to improve. This study suggests that in the hands of a fetal cardiac specialist acquiring not only two-dimensional still frames of the fetal heart, but real-time imaging with acquisition of video clips with sweeps, and color and pulsed Doppler interrogation of all cardiac structures, most major defects can be detected if images of the heart can be obtained. Of note is that these same criteria for fetal heart imaging in mid-gestation (18-22 weeks) were recently published as Fetal Echocardiography Guidelines by a multidisciplinary writing group for the American Institute of Ultrasound in Medicine.20 It suffices to say that these same guidelines should apply to early imaging to maximize the likelihood of detection of cardiac abnormalities. In our experience, transabdominal imaging was most often sufficient to acquire all views and sweeps; however, transvaginal imaging © 2014 John Wiley & Sons, Ltd.
Early fetal echocardiography
was a useful adjunct particularly ≤15 weeks. We must caution, however, that limitations in imaging do exist, and we support the recommendation for mid-gestation fetal echocardiograms in all patients. Our study has several important limitations. It is retrospective in nature and therefore follow-up mid-gestation and postnatal echocardiograms were not available in several subjects, most notably the ones with normal first and midtrimester exams. In addition, given the relatively small number of women referred for early fetal echocardiograms, the number of abnormal early fetal echocardiograms available for analysis was limited. The small number of abnormal early studies might especially limit the assessment of the yield of various indications for early fetal echocardiograms. The feasibility of extrapolating these results to a general population without an increased risk for significant disease should not be assumed.
CONCLUSION In summary, early fetal cardiac imaging performed by an experienced fetal cardiac specialist is useful in the evaluation of high-risk pregnancies for diagnosis of CHD and reassurance when normal. Regardless of initial result, early fetal
echocardiography should be followed by a comprehensive cardiac evaluation at 18 to 22 weeks EGA to maximize detection and accuracy of diagnosis.
ACKNOWLEDGEMENT We would like to thank Amanda Fulgium for her expert imaging and Kami Skurow-Todd for her assistance with data management. WHAT’S ALREADY KNOWN ABOUT THIS TOPIC? • Fetal echocardiography is feasible early in gestation. • Reports of experience with early fetal heart imaging in the United States from obstetrics/maternal–fetal medicine imaging laboratories suggest that, in most fetuses, imaging of the four chambers and outflow tracts is possible.
WHAT DOES THIS STUDY ADD? • Report of usefulness of early fetal echocardiography in an experienced fetal cardiac center. • Recommendations of high-risk groups that might benefit from referral to a fetal cardiac specialist for early fetal echocardiogram.
REFERENCES 1. Eapen RS, Rowland DG, Franklin WH. Effect of prenatal diagnosis of critical left heart obstruction on perinatal morbidity and mortality. Am J Perinatol 1998;15(4):237–42. 2. Kumar RK, Newburger JW, Gauvreau K, et al. Comparison of outcome when hypoplastic left heart syndrome and transposition of the great arteries are diagnosed prenatally versus when diagnosis of these two conditions is made only postnatally. Am J Cardiol 1999;83(12):1649–53. 3. Copel JA, Tan AS, Kleinman CS. Does a prenatal diagnosis of congenital heart disease alter short-term outcome? Ultrasound Obstet Gynecol 1997;10(4):237–41. 4. Verheijen PM, Lisowski LA, Stoutenbeek P, et al. Prenatal diagnosis of congenital heart disease affects preoperative acidosis in the newborn patient. J Thorac Cardiovasc Surg 2001;121(4):798–803. 5. Jaeggi ET, Sholler GF, Jones OD, Cooper SG. Comparative analysis of pattern, management and outcome of pre- versus postnatally diagnosed major congenital heart disease: a population-based study. Ultrasound Obstet Gynecol 2001;17(5):380–5. 6. Gembruch U, Shi C, Smrcek JM. Biometry of the fetal heart between 10 and 17 weeks of gestation. Fetal Diagn Ther 2000;15(1):20–31. 7. Haak MC, Twisk JW, Van Vugt JM. How successful is fetal echocardiographic examination in the first trimester of pregnancy? Ultrasound Obstet Gynecol 2002;20(1):9–13. 8. Smrcek JM, Berg C, Geipel A, et al. Detection rate of early fetal echocardiography and in utero development of congenital heart defects. J Ultrasound Med 2006;25(2):187–96. 9. McAuliffe FM, Trines J, Nield LE, et al. Early fetal echocardiography--a reliable prenatal diagnosis tool. Am J Obstet Gynecol. 2005;193(3 Pt 2): 1253–9. 10. Souka AP, Von Kaisenberg CS, Hyett JA, et al. Increased nuchal translucency with normal karyotype. Am J Obstet Gynecol. 2005;192(4): 1005–21.
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11. Bahado-Singh RO, Wapner R, Thom E, Zachary J, et al. Elevated firsttrimester nuchal translucency increases the risk of congenital heart defects. Am J Obstet Gynecol. 2005;192(5):1357–61. 12. Rychik J, Ayres N, Cuneo B, Gotteiner N, Spevak PJ, VanDerVeld M. American Society of Echocardiography guidelines and standards for performance of the fetal echocardiogram. Am Soc Echocardiogr 2004;17:803–10. 13. Tworetzky W, Wilkins-Haug L, Jennings RW, et al. Balloon dilation of severe aortic stenosis in the fetus: potential for prevention of hypoplastic left heart syndrome: candidate selection, technique, and results of successful intervention. Circulation 2004;110(15):2125–31. 14. Cooper MJ, Enderlein MA, Dyson DC, et al. Fetal echocardiography: retrospective review of clinical experience and an evaluation of indications. Obstet Gynecol. 1995;86(4 Pt 1):577–82. 15. Friedberg MK, Silverman NH. Changing indications for fetal echocardiography in a University Center population. Prenat Diagn. 2004;24(10):781–6. 16. Gill HK, Splitt M, Sharland GK, Simpson JM. Patterns of recurrence of congenital heart disease: an analysis of 6,640 consecutive pregnancies evaluated by detailed fetal echocardiography. J Am Coll Cardiol 2003;42(5): 923–9. 17. Volpe P, De Robertis V, Campobasso G, et al. Diagnosis of congenital heart disease by early and second-trimester fetal echocardiography. J Ultrasound Med 2012;31(4):563–8. 18. Persico N, Moratalla J, Lombardi CM, et al. Fetal echocardiography at 11–13 weeks by transabdominal high-frequency ultrasound. Ultrasound Obstet Gynecol 2011;37(3):296–301. 19. Huggon IC, Ghi T, Cook AC, et al. Fetal cardiac abnormalities identified prior to 14 weeks’ gestation. Ultrasound Obstet Gynecol 2002;20(1):22–9. 20. AIUM practice guideline for the performance of fetal echocardiography. J Ultrasound Med 2013;32:1067–82.
© 2014 John Wiley & Sons, Ltd.
ORIGINAL ARTICLE
Early fetal echocardiography: congenital heart disease detection and diagnostic accuracy in the hands of an experienced fetal cardiology program Jodi I. Pike, Anita Krishnan and Mary T. Donofrio* Children’s National Heart Institute, Children’s National Medical Center, Washington, DC 20010, USA *Correspondence to: Mary Donofrio. E-mail: [email protected]
ABSTRACT Objective Evaluate the utility of early fetal echocardiography in the hands of an experienced fetal cardiology program for detection of congenital heart disease (CHD) in high-risk pregnancies. Methods Review of fetal echocardiograms 12 to 16 weeks of gestation. Results There were 151 studies in 142 fetuses (mean age 14.5 weeks). Transabdominal imaging was sufficient for 104; transvaginal imaging was used in 38. CHD was found in 32(22.5%). High yield indications were suspected cardiac anomaly (91.7%) and extracardiac anomaly (50%). Lower yield indications were increased nuchal translucency (13.8%) and family history (6.1%). No fetuses referred for advanced maternal age, maternal lupus, or diabetes had CHD. Mid-gestation follow-up was possible in 128 (ten terminated/four lost to follow-up). Three of 19 initially diagnosed with CHD had normal hearts; none diagnosed as normal had CHD (sensitivity 100%/specificity 97.3%). Seven had modification of original diagnoses: three initially diagnosed with possible septal defects had no defect, two had diagnoses that changed, and two had progression different than predicted.
Conclusion Early fetal echocardiography performed in an experienced fetal cardiology program accurately identifies significant CHD. Appropriate referral indications to fetal cardiac specialists include suspected CHD, extracardiac anomaly, increased nuchal translucency, and significant family history. Lesions that may not be diagnosed with accuracy include septal defects and diseases that progress. © 2014 John Wiley & Sons, Ltd.
Funding sources: None Conflicts of interest: None declared
INTRODUCTION Prenatal diagnosis of congenital heart disease (CHD) has been shown to have a significant effect on prenatal and postnatal management and outcomes.1–5 In addition to the potential medical benefits, fetal diagnosis allows for valuable parental counseling, which allows families to make informed decisions regarding the pregnancy, and to prepare emotionally for the birth of the child with significant CHD. Accurate prenatal diagnosis can also lead to additional testing of the fetus, including genetic evaluation and other anatomic imaging, which can yield valuable information in overall assessment of the fetus. Referral for fetal echocardiogram typically occurs between 18 and 22 weeks gestational age. With advances in ultrasound technology, which has allowed for the significant improvements in high-resolution imaging necessary to visualize the developing fetal heart, fetal echocardiography can now be performed in the late first trimester and early second trimester of pregnancy.6–9 In addition, with the wide availability and practice of nuchal translucency (NT) measurements, which typically occurs Prenatal Diagnosis 2014, 34, 1–7
between 11 and 14 weeks gestational age, the demand for early fetal cardiac imaging has increased. Increased NT has been shown to be associated with CHD, even in the presence of normal karyotype,10,11 and early and accurate cardiac diagnosis is an essential part of the evaluation of these fetuses. Despite the potential benefits of early cardiac imaging, it is not the standard of practice in most institutions in the United States. In addition, practice patterns tend to be variable regarding who does the imaging, the imaging protocol, the indications for referral, and the timing of consultation. Given that the utility and accuracy of early fetal cardiac imaging in the hands of experienced fetal cardiologists is undefined, the objective of this study was to evaluate the experience of diagnosing cardiac anomalies using early fetal echocardiography at a large fetal cardiac referral center.
METHODS We conducted a retrospective review of all early fetal echocardiograms performed between July 2007 and December 2010 in the Fetal Heart Program at Children’s National Medical © 2014 John Wiley & Sons, Ltd.
J. I. Pike et al.
Center. Early fetal echocardiograms were defined as studies completed between 12 and 16 weeks estimated gestational age (EGA). Qualifying studies were identified by a database search of all echocardiograms performed during the study period with the summary codes ‘First trimester fetal echocardiogram’, ‘Fetal echocardiogram 3 mm), an increasingly common indication for early fetal echocardiography, yielded a finding of structural cardiac disease in 13.8% of such referrals. (Table 1) No fetuses referred for advanced maternal age, maternal lupus, or maternal diabetes mellitus had cardiac disease. All those referred for maternal lupus had a normal PR interval.
Routine fetal echocardiography follow-up at greater than 20 weeks EGA was available in 128 of 142 fetuses. Of the fetuses that did not return, ten pregnancies were known to have been terminated, and four were lost to follow-up (one normal was lost to follow-up; the remaining three had an abnormal initial early fetal echocardiograms). All of those known to have terminated were diagnosed with significant heart disease and/or notable extracardiac or genetic abnormalities. In those with isolated CHD, the result of the early fetal echocardiogram was the primary reason for termination. In those with additional findings, it could not be ascertained as to the primary reason for termination (Table 2).
Prenatal Diagnosis 2014, 34, 1–7
© 2014 John Wiley & Sons, Ltd.
J. I. Pike et al.
A structural cardiac anomaly was found in 32 out of 142 fetuses (22.5%) (Table 3). One hundred twenty-eight fetuses, 19 with a cardiac anomaly at the initial early study, had a follow-up fetal echocardiograms at greater than 20 weeks EGA. At follow-up evaluation, three of the 19 fetuses initially diagnosed with a cardiac anomaly had a normal heart; conversely, no fetuses initially diagnosed with a normal heart were subsequently found to have cardiac disease. This yielded a sensitivity of 100%, a specificity of 97.3%, a positive predictive value of 84.2%, and a negative predictive value of 100% for major structural heart disease. In total, seven fetuses (5%) had some modification of the initial cardiac diagnosis at follow-up (Table 3; bolded subjects). As stated, three had a structurally normal heart at the followup comprehensive mid-gestation echocardiogram. All three were described as having a ‘suspected’ or ‘possible’ ventricular septal defect at the early fetal echocardiogram. It is unclear whether these ventricular septal defects were inaccurately
diagnosed at initial echocardiogram, or the defect closed and early imaging reveals the potential natural history of small septal defects closing during gestation. Of the remaining fetuses with modified diagnoses, another with a ‘possible ventricular septal defect’ was later found to have an intact ventricular septum, but a thickened right ventricle. One fetus was described as having a ‘possible atrioventricular canal’ at initial early fetal echocardiogram; the diagnosis was changed to a moderate ventricular septal defect at follow-up. Another, referred for significant extracardiac anomalies was thought to have multiple cardiac tumors at initial exam but found to have an echogenic focus and ventricular septal defect at subsequent follow-up examination. Finally, a fetus referred at 13 weeks for increased NT was initially diagnosed with hypoplastic left heart syndrome but was ultimately determined at follow-up scan to have Shone’s syndrome including aortic and mitral stenosis, coarctation of the aorta, and a borderline left ventricle (Figure 1).
Figure 1 Early scans (12 and 16 weeks) and mid-gestation scan (28 weeks) in a fetus originally diagnosed with a hypoplastic left heart syndrome variant, later noted to be Shone’s with mitral and aortic stenosis, coarctation, and borderline left ventricle. RA = right atrium, RV = right ventricle, LA = left atrium, LV = left ventricle. (A) Two-dimensional (2D) four-chamber view at 12 weeks. (B) Color four-chamber view at 12 weeks using transvaginal imaging, note the color difference filling the RV and LV. (C) 2D four-chamber view at 16 weeks. (D) Color four-chamber view at 16 weeks, note the color difference filling the RV and LV. (E) 2D four-chamber view at 28 weeks. (F) Color four-chamber view at 28 weeks
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© 2014 John Wiley & Sons, Ltd.
Early fetal echocardiography
There was no difference between the EGA at initial study of those with a modification of diagnosis at follow-up and those with no change in diagnosis (13.6 vs 14.5 weeks, p = 0.07), though there was a trend towards improved accuracy with no change in diagnosis if the initial early fetal echocardiogram was performed later in gestation. As expected, image quality improved throughout gestation (Figure 2).
Postnatal follow-up In no subjects with an abnormal scan was there a significant change in diagnosis between the mid-gestation fetal echocardiogram and the initial postnatal study, though this information was only available for 14 of the 16 with abnormal fetal echocardiograms at mid-gestation, as there were two subsequent in utero demises. Of the 109 with normal fetal echocardiograms at both initial early study and subsequent mid-gestation study, there were postnatal echocardiograms available in 26; 78 had no postnatal follow-up and 5 were known to have terminated. Normal echocardiograms were found in 24 of the 26 at initial postnatal study. In the remaining two subjects, a small muscular ventricular septal defect was found on postnatal exam. No unexpected severe CHD was identified postnatally (Figure 3).
DISCUSSION Our study shows that early fetal echocardiography, performed between 12 and 16 weeks gestational age, is technically feasible and can identify a wide variety of significant cardiac anomalies
in the hands of experienced providers specializing in cardiac imaging. Such evaluation can be an important part of early prenatal counseling, especially in those fetuses with known genetic abnormalities or other extracardiac defects. In addition, it allows for the assessment of the progression of disease throughout gestation and as in utero interventions become more widespread, this may allow for earlier and more effective intervention.13 In our hands, the detection rate of CHD was high in the group of patients referred for early fetal cardiac exam, specifically those in which a cardiac defect was already suspected, or those in which an extracardiac anomaly had been previously diagnosed. Low yield indications were those referred due to maternal risk profile such as maternal diabetes or lupus, though this may be secondary to small sample size, as the number of those referred for these indications was limited. However, as these indications for referral are typically used for screening in mid-gestation, it is not surprising that the vast majority had no cardiac disease, as opposed to those in which the indication is an already suspected abnormality. Given that referral to a fetal cardiac specialist early in gestation for a fetal echocardiogram is not for screening purposes, these indications with low yield of diagnosis may not warrant referral unless an abnormality is suspected. Another common referral for early fetal echocardiogram is in women with a significant family history of CHD, often in a prior pregnancy. While the yield of heart disease detection was lower (6.1%) than other indications in which abnormalities
Figure 2 Four chamber view of the heart through early gestation. Note improvement in resolution and better delineation of structures from 12 to 17 weeks of gestation. RA = right atrium, RV = right ventricle, LA = left atrium, LV = left ventricle. (A) 12 weeks. (B) 13 weeks. (C) 14 weeks. (D) 15 weeks. (E) 16 weeks. (F) 17 weeks
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© 2014 John Wiley & Sons, Ltd.
J. I. Pike et al.
Figure 3 Summary outcome information for fetal patients having an early fetal echocardiogram
were noted, it is a higher detection rate than what is reported at mid-gestation.14–16 This could be due to different patient characteristics. Though speculative, we believe that it is more likely that a family with a history of severe disease such as heterotaxy syndrome or hypoplastic left heart syndrome would be sent for early imaging, and the recurrence risk for these severe defects may be higher. In these families with significant past experience, the benefit of early fetal cardiac evaluation may actually lie in the reassurance given with a normal study, and the emotional stress that this may ease for the woman and her partner. In these cases, though family history as a reason for referral is considered at mid-gestation to be an indication, the benefits of the early fetal echocardiogram to the family may outweigh the small likelihood of actually identifying significant CHD. For this reason, we believe that family history of significant CHD in a first degree relative is a reasonable indication for referral to a fetal cardiac specialist for early fetal echocardiogram. Even with reassuring accuracy in regards to identifying major CHD as demonstrated by our high sensitivity, specificity, and negative and positive predictive values, it remains vitally important to counsel patients regarding the limitations of early fetal echocardiography. There are technical constraints to image resolution that become particularly important when imaging fetuses in early gestation, and it is for this reason that septal defects may remain difficult to diagnosis with complete accuracy. In addition, there are diseases that progress Prenatal Diagnosis 2014, 34, 1–7
throughout gestation, and early fetal echocardiography can only describe the structure of the heart at the time point of imaging. Other studies have also looked at the usefulness of evaluation of the fetal heart early in gestation.17–19 These studies demonstrated that early imaging of the fetal heart is technically feasible and can identify a wide spectrum of significant CHD; however, unlike our study, there was significant cardiac disease that was missed on the initial early evaluation. Of course, it is expected that not all CHD will be identified, though we believe that with increasing experience and fetal cardiac expertise, improvements in technology, and creation of universal guidelines for fetal cardiac imaging, detection rates and accuracy will continue to improve. This study suggests that in the hands of a fetal cardiac specialist acquiring not only two-dimensional still frames of the fetal heart, but real-time imaging with acquisition of video clips with sweeps, and color and pulsed Doppler interrogation of all cardiac structures, most major defects can be detected if images of the heart can be obtained. Of note is that these same criteria for fetal heart imaging in mid-gestation (18-22 weeks) were recently published as Fetal Echocardiography Guidelines by a multidisciplinary writing group for the American Institute of Ultrasound in Medicine.20 It suffices to say that these same guidelines should apply to early imaging to maximize the likelihood of detection of cardiac abnormalities. In our experience, transabdominal imaging was most often sufficient to acquire all views and sweeps; however, transvaginal imaging © 2014 John Wiley & Sons, Ltd.
Early fetal echocardiography
was a useful adjunct particularly ≤15 weeks. We must caution, however, that limitations in imaging do exist, and we support the recommendation for mid-gestation fetal echocardiograms in all patients. Our study has several important limitations. It is retrospective in nature and therefore follow-up mid-gestation and postnatal echocardiograms were not available in several subjects, most notably the ones with normal first and midtrimester exams. In addition, given the relatively small number of women referred for early fetal echocardiograms, the number of abnormal early fetal echocardiograms available for analysis was limited. The small number of abnormal early studies might especially limit the assessment of the yield of various indications for early fetal echocardiograms. The feasibility of extrapolating these results to a general population without an increased risk for significant disease should not be assumed.
CONCLUSION In summary, early fetal cardiac imaging performed by an experienced fetal cardiac specialist is useful in the evaluation of high-risk pregnancies for diagnosis of CHD and reassurance when normal. Regardless of initial result, early fetal
echocardiography should be followed by a comprehensive cardiac evaluation at 18 to 22 weeks EGA to maximize detection and accuracy of diagnosis.
ACKNOWLEDGEMENT We would like to thank Amanda Fulgium for her expert imaging and Kami Skurow-Todd for her assistance with data management. WHAT’S ALREADY KNOWN ABOUT THIS TOPIC? • Fetal echocardiography is feasible early in gestation. • Reports of experience with early fetal heart imaging in the United States from obstetrics/maternal–fetal medicine imaging laboratories suggest that, in most fetuses, imaging of the four chambers and outflow tracts is possible.
WHAT DOES THIS STUDY ADD? • Report of usefulness of early fetal echocardiography in an experienced fetal cardiac center. • Recommendations of high-risk groups that might benefit from referral to a fetal cardiac specialist for early fetal echocardiogram.
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