Diagnosis of tetralogy of fallot and its variants in the


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Diagnosis of tetralogy of fallot and its variants in the

  1. 1. Diagnosis of Tetralogy of Fallot and Its Variants in the Late First and Early Second Trimester: Details of Initial Assessment and Comparison with Later Fetal Diagnosis Aarti H. Bhat, M.D.,*† Devin W. Kehl, M.D.,*‡ Theresa A. Tacy, M.D.,*§ Anita J. Moon-Grady, M.D.*¶ and Lisa K. Hornberger, M.D.*, ** *Fetal Cardiovascular Program, Pediatric Cardiology, University of California, San Francisco, California; †Division of Pediatric Cardiology, Seattle Children’s Hospital, University of Washington, Seattle, Washington; ‡School of Medicine, University of California, San Francisco, California; §Division of Pediatric Cardiology, Lucille Packard Children’s Hospital, Stanford University, Palo Alto, California; ¶Division of Pediatric Cardiology, University of California San Francisco, Benioff Children’s Hospital, San Francisco, California; and **Division of Pediatric Cardiology, Mazankowski Heart Institute, University of Alberta, Alberta, Canada Objective: We sought to evaluate the completeness of echocardiographic diagnosis of fetal tetralogy of Fallot (fTOF) at 12–17 weeks gestation, and compare assessment and clinical outcomes to diagnoses made at >17 weeks gestation. Methods: We identified all fTOF diagnoses made in our experience from 2003 to 2008. Referral indication, anatomic detail by echocardiography and pregnancy outcomes were compared between fetuses diagnosed at 17 weeks (Group I) and 17 weeks gestation (Group II). A 10-point scoring tool was applied retrospectively to the echocardiograms at initial diagnosis (1 point each was ascribed to visualization of right ventricular outflow obstruction, pulmonary valve, pulmonary arteries including dimensions, pulmonary arterial flow, systemic and pulmonary venous anatomy, atrio- ventricular valves, ductus arteriosus, ductus flow, aortic arch morphology, sidedness and flow). Results: There were 10 pregnancies in Group I (12–17 weeks) and 25 in Group II (mean gestation at diagnosis 23.5 ± 5.7). The most common reason for referral was extracardiac pathology in Group I (80%) and suspected fetal heart disease on obstetric ultrasound in Group II (64%). Transabdominal imaging was adequate in about half of Group I studies. Mean anatomic diagnosis score in Group I was 6.1(range 2.5 –9) and Group II was 8.4 (range 6.5–10). Elective pregnancy termination occurred in 80% in Group I and 33% in Group II. Conclusions: fTOF can be diagnosed in first and early second trimesters with detailed anatomic assessment possible in most. Referral indication and pregnancy outcome differ considerably between early and later prenatal diagnosis of fTOF. (Echocardiography 2013;30:81-87) Key words: fetal cardiology, fetal echocardiography, tetralogy of Fallot, fetal diagnosis Fetal echocardiography permits diagnosis and detailed evaluation of most structural, functional and rhythm-related fetal heart disease (FHD). Fetal echocardiography is typically performed after 17–18 weeks gestation in low-risk pregnan- cies. Pregnancies at increased risk for FHD, including those with advanced maternal age, abnormal maternal serum markers, previously affected pregnancies, significant family histories, and assisted reproductions are now undergo- ing preliminary obstetric scans as early as 10– 14 weeks of gestation to determine fetal viability, gestational age, nuchal translucency (NT), and, in some centers, to assess fetal anatomy. This has led to an interest in evaluation of the fetal heart at this early gestational age and to an increasing acceptance of the role and feasibility of early fetal echocardiography.1–4 Visualization of four cardiac chambers and great arteries has been clearly established in the late first and early second trimesters with success in the majority of patients after 12 weeks.5 Several reports have documented early prenatal diagnosis of FHD, but, most have described the feasibility of a broader anatomic diagnosis.1–4 Address for correspondence and reprint requests: Lisa K. Hornberger M.D., Fetal and Neonatal Cardiology Program, Pediatric Cardiology, Stollery Children’s Hospital, WCMC 4C2, 8440 112th Street, Edmonton, Alberta, Canada, T6G2B7. Fax: 780-407-3952; E-mail: lisa.hornberger@albertahealthservices.ca 81 © 2012, Wiley Periodicals, Inc. DOI: 10.1111/j.1540-8175.2012.01798.x Echocardiography
  2. 2. Fetal tetralogy of Fallot (fTOF) and its variants, like its postnatal counterpart relies on demonstra- tion of a conoventricular septal defect, conal sep- tal malalignment, aortic override, and pulmonary outflow obstruction. While these features are rec- ognizable at echocardiography, the extent and level of pulmonary stenosis, precise measure- ments of the pulmonary arteries, ductal and arch anatomy, source of pulmonary blood flow, and other anatomic features such as systemic and pulmonary venous connections are also critical for making a detailed and complete diagnosis in anticipation of surgical intervention. Such details are deemed necessary for accurate and complete prenatal counseling at any gestational age as they have implications for urgency of postnatal repair as well as for type of repair and potential need for reoperation throughout the lifetime of the individual. In this study, we retrospectively review our experience with fTOF and its variants, comparing early (12–17 weeks gestation) with later (17 completed weeks gestation) diagnosis to deter- mine the efficacy of early fetal echocardiography in defining cardiac anatomy, and impact of early diagnosis on clinical outcome. Methods: Study Design: This was a retrospective review of our experience from 2003 to 2008 with the echocardiographic diagnosis of fTOF and its variants from 12 weeks gestation to term. All echocardiograms with the basic diagnosis of fTOF (large malalignment conoventricular ventricular septal defect (VSD), aortic override, pulmonary outflow obstruction) and variants were reviewed. Fetal cases with a diagnosis of fTOF and pulmonary stenosis, fTOF and pulmonary atresia (also referred to as pulmo- nary atresia with VSD), fTOF-type of double out- let right ventricle, fTOF with absent pulmonary valve syndrome, and fTOF with atrioventricular septal defect were included. Demographic infor- mation, referral indications, chromosomal or extracardiac associations at the time of first or subsequent studies as well as follow-up informa- tion including confirmation of diagnosis and pregnancy outcome were analyzed. The study was approved by the Institutional Review Board at the University of California, San Francisco. Fetal Echo Protocol: The standard fetal echocardiography protocol adopted by our laboratory was used in all cases. This included the following: determination of gestational age using femur length (when appro- priate) and biparietal diameter, visceral and atrial situs, systemic and pulmonary venous anatomy and Doppler flow profiles, axial four chamber views, outflow views, ductal and aortic arch later- ality and Doppler flow patterns, branch pulmo- nary arteries, qualitative assessment of ventricular systolic function and spectral Doppler assessment of ventricular inflows and outflows, inferior vena cava, ductus venosus and umbilical vessel flow, fetal heart rate and rhythm. Most studies were performed using a Siemens Sequoia ultrasound machine (Siemens Medical Solutions, Mountain View, CA, USA) using 6 or 8 MHz curvilinear and 10 MHz phased array transducers for transabdominal imaging and 8 or 10 MHz endovaginal transducers for transvaginal imaging. Transvaginal studies were carried out if the transabdominal study was inconclusive or did not yield adequate diagnostic information to make a definitive diagnosis. Measurements were made off line even if they had been measured in the original study so as to exclude interobserver- or operator-dependant variations. Serial fetal echocardiograms were offered in all pregnancies and recommended in all Group I cases per our institutional protocol for first trimester fetal screening and anomaly diagnosis. Scoring System: We developed a 10-point scoring system to objectify visualization of specific anatomic fea- tures and for comparison between initial and serial echocardiograms in both groups which is detailed in Table I. Diagnosis Confirmation: A Group I diagnosis was considered confirmed if the anatomy on the first/early study was more confidently seen on a mid-trimester study, if an autopsy confirmed the anatomy on termination of pregnancy, or if there was a live birth with confirmed anatomy postnatally. Results: Demographics and Referral Indications: The total study group of fTOF comprised 35 pregnancies. A total of 62 fetal echocardiograms, including 18 pregnancies with a single study and 17 with two or more studies were reviewed. Of the 35, there were 10 pregnancies in Group I (Table II) and 25 pregnancies in Group II (Table III). The mean gestational age at presenta- tion in Group I was 14 weeks (range 12–17 weeks) and 23.5 weeks in Group II (range 18– 36 weeks). Indication for referral for fetal echocardiography was for an omphalocele in two, ectopia cordis in two (Fig. 1), increased NT in four (one a trichorionic quadruplet pregnancy, one a monochorionic twin pregnancy), and suspected FHD in two (both 17-week diagnoses, 82 Bhat, et al.
  3. 3. one with confirmed trisomy 21). In Group II, the most common reason for referral was FHD sus- pected at the time of the routine mid-trimester fetal ultrasound (64%). Fetal Cardiovascular Assessment: While transabdominal approach was adequate in all Group II cases, transvaginal imaging was diagnostic in three with limited transabdominal image resolution and contributory in two cases in Group I (Figs. 2 and 3). VSD, aortic override, and a four-chamber view could be demonstrated in all Group I and Group II fetuses. The three-vessel view was successfully visualized in most cases and great artery discrepancy (ascending aorta larger than main pulmonary artery) revealed in this view. Color Doppler was useful to establish flow in diminutive structures that were difficult to appreciate on two-dimensional (2D) echo, such as the pulmonary outflow (Fig. 2) and the ductus arteriosus (Fig. 3). Multiple views were analyzed for each structure. In Group I, there were seven fetuses with pulmonary stenosis and antegrade flow through the ductus arteriosus. One fTOF referred for increased NT at 14 weeks in a set of monochor- ionic diamniotic twins, had more commitment of the overriding aorta to the right ventricle and additional cardiovascular features consistent with left atrial isomerism. In addition to the basic features of fTOF, the early exam documented interruption of the inferior vena cava, bilateral superior vena cavae, atrioventricular septal defect, and atrial bigeminy. The main pulmonary artery was very diminutive and the source of pul- monary blood flow could not be demonstrated. TABLE I Scoring System Used to Evaluate Completeness of Fetal Echocardiographic Assessment of fTOF Points Given 0 0.5 1 RVOT obstruction (RVOTO) level and severity Not clearly visualized Some but not all of these aspects demonstrated Clearly demonstrated Pulmonary valve (PV) Not clearly visualized Not seen well enough to measure Measurement possible Branch pulmonary artery diameter at origin (PA) Not clearly visualized, PA not measurable One PA demonstrated well and measurable Both PAs measurable RVOT and PA flow with color Doppler Not clearly visualized Partially demonstrated Pulmonary outflow, main and branch PA flow demonstrated Pulmonary and systemic venous anatomy Pulmonary veins not clearly visualized At least one right and one left pulmonary vein demonstrated on 2D imaging AND 2D, Color and pulsed-Doppler flow in at least one pulmonary vein on each side demonstrated AND SVC and IVC not clearly visualized SVC (including LSVC when present) and IVC visualized by 2D imaging SVC, IVC blood flow demonstrated by pulsed and color Doppler (including LSVC when present) Ductus arteriosus anatomy Not clearly visualized Visualized but not measurable Measured close to its origin at PA end Ductus arteriosus blood flow direction by color or pulsed Doppler Not clearly demonstrated Partially demonstrated Clearly demonstrated Aortic and ductal arch sidedness Not demonstrated Partially demonstrated Clearly demonstrated based on relationship with the trachea and position of the descending aorta Atrioventricular valve anatomy Inadequately visualized or not measurable Only one measurable AV valve concordance, annular size, and competence of both mitral and tricuspid valve clearly demonstrated and annulus measurable Ventricular Function Not clearly demonstrated in short axis Qualitative systolic assessment performed, diastolic assessment not possible Biventricular systolic (qualitative) as well as diastolic function (ventricular inflow patterns, systemic venous Dopplers and IVRT) assessed AV = atrioventricular; IVRT = isovolumic relaxation time; IVC = inferior vena cava; LSVC = left superior vena cava; PA = pulmonary artery, RVOT = right ventricular outflow tract; SVC = superior vena cava. 83 Early Fetal Diagnosis of Tetralogy of Fallot
  4. 4. These anatomic details were confirmed later in the mid-trimester prior to selective reduction of the twin. One fetus had fTOF and pulmonary atresia with retrograde ductal blood flow (Fig. 3), and in another that underwent termination, although pulmonary atresia was suspected due to lack of forward flow through the pulmonary artery, the source of pulmonary blood flow could never be demonstrated. In Group II, there were nine cases of fTOF with pulmonary stenosis. Nine others were fTOF pulmonary atresia variants (including three with aortopulmonary collaterals and seven with an identified ductus arteriosus as the source of pul- monary blood flow) (Table III). One pregnancy that was referred at 35 weeks for fetal tachycar- dia and hydrops was found to have, in addition to an incessant supraventricular tachycardia and early hydrops, a large VSD, aortic override, and suspected right ventricular outflow obstruction with a smaller main pulmonary artery compared with the ascending aorta consistent with mild TABLE II Summary of Group I fTOF Cases GA (weeks) Indication for Referral Cardiac Diagnosis Extracardiac Diagnosis Outcome* 12 Increased NT in one of triplets fTOF – Selective reduction 12 Ectopia cordis fTOF – Pregnancy termination 14 Suspected fetal heart disease fTOF Single kidney Pregnancy termination 14 Increased NT fTOF/pulmonary atresia, bilateral SVC – Pregnancy termination 14 Omphalocele fTOF ectopia cordis Pentalogy of Cantrell Pregnancy termination 14.5 Increased NT in monochorionic twin fTOF/pulmonary atresia, left atrial isomerism, bilateral SVC Cystic hygroma Selective reduction 14.5 Omphalocele fTOF Omphalocele Pregnancy termination 17 Multiple anomalies fTOF/DORV, ectopia cordis Pentalogy of Cantrell Intrauterine fetal demise 17 Suspected fetal heart disease fTOF – Live birth at term 17 Suspected fTOF fTOF Trisomy 21 Pregnancy termination *Termination of pregnancies performed in singleton pregnancies and selective reduction in multiple pregnancies leaving a viable fetus. DORV = double outlet right ventricle; fTOF = fetal tetralogy of Fallot (with pulmonary stenosis unless otherwise specified); GA = gestational age in weeks; NT = nuchal translucency; SVC = superior vena cava. TABLE III Summary of Group II fTOF Cases Anatomic Subgroup Gestational Age in Weeks, Range (Mean) Indication for Referral Extracardiac Diagnosis (n) Outcome (n) fTOF/pulmonary stenosis (n = 9) 18.5–36 (23.6) Suspected fetal heart disease including one with tachycardia (6), other fetal anomaly (3) Mosaic polyploidy (1), 22q11.2 deletion with severe cerebellar h ypoplasia (1), trisomy 21 (1), Vermian hypogenesis (1) Pregnancy termination (2), Live birth (6), lost to F/U (1) fTOF/APV (n = 4) 19–33 (23.6) Suspected fetal heart disease (3), other fetal anomaly (1) 22q11.2 deletion (2) IUFD (1), live birth (3) fTOF/pulmonary atresia (n = 9) 19–33 (24) Suspected fetal heart disease (6), other fetal anomaly (3) Trisomy 21 (1), 8p deletion (1) Pregnancy termination (4), IUFD (1), live birth (4) fTOF/DORV variant (n = 3) 18–30 (24) Suspected fetal heart disease (1), other fetal anomaly (2) Pentalogy of Cantrell (1), hydrocephalus and polycystic kidneys (1), trisomy 13 (1) Pregnancy termination (1) APV = absent pulmonary valve; DORV = double outlet right ventricle; fTOF = fetal tetralogy of Fallot; SVT = supraventricular tachy- cardia; TOP = termination of pregnancy; F/U = follow up; IUFD = intrauterine fetal death. 84 Bhat, et al.
  5. 5. fTOF. This pregnancy was treated with sotalol with satisfactory rate control and resolution of hydrops. Following delivery, postnatal echocardi- ography suggested the presence of a single large perimembranous VSD with mild aortic over- ride and no pulmonary outflow obstruction. This was the only confirmed false positive case in our series. Diagnostic Detail at Early versus Late Gestational Age: Group I at a mean gestational age of 14.6 weeks had a mean anatomic score of 6.4 (range 2.5–9, median 7.5). Group II, at a mean gestational age of 23.5 weeks had a mean anatomic score of 8.4 (range 6.5–10, median 9) (Fig. 4). Fetal Echo Follow-Up Data: At serial fetal echocardiography in four Group I pregnancies, the anatomic score remained 8 in one, increased from 8 to 9 in one, from 9 to 10 in one, and substantially improved from 2.5 in a fetus initially seen at 17 weeks with particularly difficult windows to 10 by 19 weeks. The remain- ing six did not have a serial scan. In Group II, serial echo was performed in 14 of 25 cases, with no improvement in score in eight cases and improvement in score in six. Mean score improvement was 1.8 (1–3.5). This change in score did not reflect disease progression, but rather improved visualization of structures. In no cases in either group did the scores decrease on later examination. Outcome and Confirmation: Of the 10 cases in Group I, eight had pregnancy termination, including four with significant extra- Figure 1. Seventeen-week gestational age fetus with pental- ogy of Cantrell. A transabdominal image demonstrating tho- racoabdominal ectopia cordis and an omphalocele in a fetus with tetralogy of Fallot, all features of pentalogy of Cantrell. LV = left ventricle; RV = right ventricle; VSD = ventricular septal defect. A B C D Figure 2. Echocardiographic features in a 14-week gesta- tional age fetus with tetralogy of Fallot. After insufficient images were documented by transabdominal imaging, trans- vaginal approach was used to evaluate this pregnancy referred for increased nuchal translucency of 5 mm. A. The four-chamber view demonstrated symmetric left and right atria and ventricles, but the cardiac axis was significantly lev- orotated. At least one right and one left pulmonary vein are noted to enter the left atrium (arrows). B. The long-axis image of the heart demonstrated the malalignment ventricu- lar septal defect (arrow) and aortic override above it. C. The three-vessel view was clearly abnormal with a dilated ascend- ing aorta and a diminutive main pulmonary artery. D. Color flow Doppler demonstrated patency of the right ventricular outflow tract (arrow). R = right; L = left; VSD = ventricular sep- tal defect; Ao = aorta; PA = pulmonary artery; SVC = superior vena cava. A B Figure 3. Retrograde ductus arteriosus flow in a 14-week fetus with tetralogy of Fallot and pulmonary atresia. Although a primary diagnosis of tetralogy of Fallot was made by trans- abdominal imaging, transvaginal imaging demonstrated a tortuous left-sided ductus arteriosus (arrow) by (A) Two- dimensional imaging with (B) retrograde flow by color flow mapping in keeping with critical pulmonary outflow tract obstruction. 85 Early Fetal Diagnosis of Tetralogy of Fallot
  6. 6. cardiac pathology (three after a confirmatory mid-trimester fetal echocardiography, two others with autopsy confirmation), one had late fetal demise (following late mid-trimester fetal echo- cardiography), and one had postnatal confirma- tion of the fTOF diagnosis. In Group II, of 24 with follow-up, seven had pregnancy termination, two had fetal demise, 15 delivered with con- firmed postnatal anatomy (Table IV). Discussion: Advances in ultrasound technology have pro- vided enhanced resolution, acquisition, and post- processing optimization so that more diminutive fetal structures can be interrogated with greater confidence and late first–early second trimester fetal echocardiography is now considered feasi- ble.1 To be of utility to the managing team and the family, all components of the evaluation need to be as accurate as possible. While several pub- lished studies have addressed feasibility, to our knowledge there has been no publication to date that has focused on the extent of anatomic visu- alization lending weight to a complete diagnosis that compares with the minute detail expected in later fetal echocardiography and postnatally. By adopting a customized scoring system to accom- modate all relevant and additional details, we sought to both objectify our impressions and also apply a standard where a structure was consid- ered adequately imaged if it was actually measur- able (e.g. branch pulmonary arteries) and not just visualized by 2D imaging, and if pulsed- Doppler waveforms could be acquired in addition to color flow mapping. On this basis, our scores for early trimester scans were, as we expected, lower than those achieved in the same pregnancy further on or in later trimesters. Our findings are similar to those of other groups who have docu- mented improvement in fetal anatomic screening of normal pregnancies in the late first trimester with a decrease in inadequate cardiac visuali- zation from 42% at 13-week scans to 1.6% in mid-trimester scans.3 However, our experience suggests that early fetal trimester cardiac scans can yield substantial anatomic detail allowing for accurate diagnosis of cardiac pathology. While the role of fetal echocardiography in prenatal diagnosis is now unequivocally estab- lished and accepted, the timing of this evaluation remains a moving target. In its infancy, fetal echocardiography was predominantly under- taken in mid to late trimester, mostly prompted by a suspicious general fetal scan, extracardiac anomaly, or family history of congenital heart dis- ease. While these indications remain true in the current era, an additional significant number of pregnancies with increased NT, abnormal fetal karyotype, or early examinations for maternal risks demand that the fetal heart be diagnosti- cally evaluated simultaneously, even as early as the first trimester,6–14 or, at the latest by 17–18 weeks. This referral pattern was true in our patient subset. Interestingly, while the pre- dominant indications for referral of our first and early mid-trimester cases were extracardiac con- cerns including the presence of increased NT, the predominant referral indication in the 18-week and higher group and even the two 17-week pregnancies was suspected FHD at obstetric ultrasound. With greater experience in early fetal cardiac screening and recognition of more subtle TABLE IV Outcome Following Prenatal Diagnosis of Tetralogy of Fallot Group Total Pregnancy Termination IUFD Live Birth Lost to Follow-Up I 10 8 1 1 0 II 25 7 2 15 1 All 35 15 3 16 1 IUFD = intrauterine fetal death. Figure 4. Histogram comparing mean scores for the individual components between groups I and II. AV = atrioventricular valves; PA = pulmonary artery; PV = pulmonary valve; RVOT = right ventricular outflow tract; RVOTO = right ventricular outflow tract obstruction. The last pair of columns on this histogram is illustrative of difference in overall mean score in each group. The mean score in Group I was 6.4 (median 7.5) and in Group II, the mean score was 8.4 (median 9). 86 Bhat, et al.
  7. 7. abnormalities of the fetal heart, we suspect the indications for early fetal echocardiography referral may change. fTOF is amenable to early diagnosis on screen- ing obstetric scans as many views can cause suspicion in isolation; the four-chamber view demonstrates a more leftward cardiac axis, angling towards the fetal outflows (Fig. 2) VSD and overriding aorta can be demonstrated, and the outflow sweeps and three-vessel view dem- onstrate discrepancy in great artery size. Due to these factors, as well as the relative frequency of this fetal diagnosis in our institution’s experience resulting in a reasonable cohort size, fTOF was selected as an illustrative lesion for this study. Within the larger scope of early fetal cardiac scans, there is lesser consensus on specifics such as patient selection, timing of first echo, opera- tor, i.e., obstetric sonographer versus pediatric cardiologist, approach, i.e., transabdominal ver- sus transvaginal.3,12 As a tertiary referral center, our study reflects some referral bias, and most low-risk pregnancies would not have been evalu- ated. Studies were performed as soon as a referral request was made, they were all performed by sonographers who are trained in pediatric and fetal cardiology, they were all interpreted by pediatric and fetal cardiologists, and transvaginal approach was used where transabdominal images were limited or inadequate. As such, there is certainly an element of operator depen- dence in that perhaps other centers with novice sonographers or young fetal programs may not be able to completely extrapolate these results. Still, with increased experience in late first trimes- ter and early second trimester fetal cardiac diag- nosis, more detailed evaluation is possible. Due to the small number of patients who underwent transvaginal scanning, we did not utilize our scor- ing system to determine improved visualization from this modality as compared with transab- dominal scanning. With increased use of transva- ginal scanning in fetal echocardiography labs, such comparative information would certainly be useful. Although our study suggests the diagnosis of fTOF can be made in the late first and early sec- ond trimester, permitting counseling regarding this diagnosis, the lack of serial assessment and postnatal follow-up of these early-gestation preg- nancies in general limits our ability to counsel regarding the natural history of fTOF when diag- nosed at an earlier gestational age. fTOF diag- nosed later in gestation has been associated in some with progressive right ventricular outflow tract obstruction, main and branch pulmonary artery hypoplasia, all of which may complicate postnatal care.15 Such information should be considered in both early and late diagnoses. Summary and Conclusions: Fetal fTOF can be diagnosed in first and early sec- ond trimester pregnancy, with reasonable defini- tion of anatomic variables in many. While these early assessments are not always as consistently detailed as those in later gestation due to image resolution limitations, they have considerable potential to impact the management and out- come of fetal cardiac abnormalities. Serial follow- up of continued pregnancies is necessary at this time to better define the natural history of fTOF when diagnosed earlier in pregnancy. References 1. Huggon IC, Ghi T, Cook AC, et al: Fetal cardiac abnor- malities identified prior to 14 weeks gestation. Ultrasound Obstet Gynecol 2002;20:22–29. 2. Carvalho JS: Fetal heart scanning in the first trimester. Prenat Diagn 2004;24:1060–1067. 3. Ebrashy A, El Kateb A, Momtaz M, et al: 13-14 week fetal anatomy scan: A 5-year prospective study. Ultrasound Obstet Gynecol 2010; 35:292–296. 4. Haak MC, Bartelings MM, Gittenberger-de Groot AC, et al: Cardiac malformations in first-trimester fetuses with increased nuchal translucency: Ultrasound diagnosis and postmortem morphology. Ultrasound Obstet Gynecol 2002;20:14–21. 5. Haak MC, Van Vugt JM: Echocardiography in early preg- nancy: Review of literature. J Ultrasound Med 2003;22: 271–280. 6. Hyett JA, Perdu M, Sharland GK, et al: Increased nuchal translucency at 10-14 weeks gestation as a marker for major cardiac defects. Ultrasound Obstet Gynecol 1997;10:242–246. 7. Hyett J, Moscoso G, Papapanagiotou G, et al: Abnormali- ties of the heart and great arteries in chromosomally nor- mal fetuses with increased nuchal translucency thickness at 11-13 weeks of gestation. Ultrasound Obstet Gynecol 1996;7:245–250. 8. Simpson JM, Sharland GK: Nuchal translucency and con- genital heart defects: Heart failure or not? Ultrasound Obstet Gynecol 2000;16:30–36. 9. Hyett J, Moscoso G, Nicolaides K: Abnormalities of the heart and great arteries in first-trimester chromosomally abnormal fetuses. Am J Med Genet 1997;69:207–216. 10. Hyett JA, Perdu M, Sharland GK, et al: Using fetal nuchal translucency to screen for major congenital cardiac defects at 10-14 weeks gestation: Population based cohort study. BMJ 1999;318:81–85. 11. Lombardi CM, Bellotti M, Fesslova V, et al: Fetal echocar- diography at the time of the nuchal translucency scan. Ultrasound Obstet Gynecol 2007;29:249–257. 12. Rustico MA, Benettoni A, D’Ottavio G, et al: Early screening for fetal cardiac anomalies by transvaginal echocardiography in an unselected population: The role of operator experience. Ultrasound Obstet Gynecol 2000; 16: 614–619. 13. Mavrides E, Cobian-Sanchez F, Tekay A, et al: Limitations of using first-trimester nuchal translucency measurement in routine screening for major congenital heart defects. Ultrasound Obstet Gynecol 2001;17:106–110. 14. Weiner Z, Lorber A, Shalev E: Diagnosis of congenital cardiac defects between 11 and 14 weeks’ gestation in high-risk patients. J Ultrasound Med 2002;21:23–29. 15. Hornberger LK, Sanders SP, Sahn DJ, et al: In utero pulmonary artery and aortic growth and potential for progression of pulmonary outflow tract obstruction in tetralogy of Fallot. J Am Coll Cardiol 1995;25:739–745. 87 Early Fetal Diagnosis of Tetralogy of Fallot