Prenatal diagnosis of tricuspid atresia - Wiley Online Library

Ultrasound Obstet Gynecol 2010; 35: 183–190 Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/uog.7499

Prenatal diagnosis of tricuspid atresia: intrauterine course and outcome C. BERG*†, R. LACHMANN*, C. KAISER*, P. KOZLOWSKI†, R. STRESSIG†, M. SCHNEIDER‡, B. ASFOUR§, U. HERBERG¶, J. BREUER¶, U. GEMBRUCH* and A. GEIPEL* Departments of *Obstetrics and Prenatal Medicine and ¶Pediatric Cardiology, University of Bonn, Bonn, †Praenatal.de, Prenatal Medicine and Genetics, Dusseldorf and Departments of ‡Pediatric Cardiology and §Pediatric Thoracic and Cardiovascular Surgery, Congenital ¨ Cardiac Center (‘Deutsches Kinderherzzentrum’), Sankt Augustin, Germany

K E Y W O R D S: congenital heart disease; echocardiography; fetus; prenatal diagnosis; tricuspid atresia

ABSTRACT Objective To evaluate the intrauterine course and outcome of tricuspid atresia detected in the fetus. Methods This was a retrospective review of all confirmed cases of tricuspid atresia detected prenatally between 1998 and 2006 in three tertiary referral centers in Germany. Results Fifty-four cases of tricuspid atresia were detected prenatally during the study period and confirmed postnatally: 28 (51.9%) cases had a concordant ventriculoarterial connection of which 14 also had pulmonary outflow obstruction; 25 (46.3%) cases had a discordant ventriculoarterial connection of which 14 also had aortic outflow obstruction, six had pulmonary outflow tract obstruction and two had other associated intracardiac anomalies; and one (1.9%) had a common arterial trunk. The peak velocity index for veins in the ductus venosus was significantly elevated in 19 of the 37 (51.4%) cases assessed; however, this finding did not correlate with adverse intrauterine outcome. There were associated extracardiac anomalies in 12 cases: five with chromosomal anomalies, two with VACTERL association, one with unilateral renal agenesis, one with hypospadia, one with hydrothorax, one with megacystis and one with agenesis of the ductus venosus. Seventeen of the 54 (31.5%) cases underwent termination of pregnancy, two (3.7%) died in utero, two (3.7%) died in infancy and 33 (61.1%) children survived with a median follow-up of 26 (range, 12–120) months. Prenatal echocardiography correctly anticipated the postnatal course and the need for neonatal intervention in 29/35 (82.9%) continued pregnancies; in the remaining six (17.1%) cases the right outflow tract obstruction had been underestimated.

Conclusions Tricuspid atresia and the frequently associated intracardiac anomalies can be diagnosed in the fetus with considerable accuracy. A thorough search for extracardiac malformations should be performed in order to rule out chromosomal anomalies and multiple malformation syndromes. Elevated pulsatility in the ductus venosus does not indicate cardiac failure. The short-term overall survival in continued pregnancies in our study exceeded 89%, with the greatest rate of loss being in the first year of postnatal life. Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd.

INTRODUCTION Tricuspid atresia (TA) is a rare form of congenital heart disease. The Baltimore-Washington Infant Study showed a prevalence at live birth of 1/25 0001 . In a prenatal screening cohort Tegnander et al. reported a comparable low incidence of 1/15 000 or 0.47% of all cardiac defects detected2 . Even in fetal cardiac series the incidence of TA is low, ranging from 3 to 4%3 – 6 . TA is defined as an absent or, rarely, an imperforate right atrioventricular connection7 . In affected cases, grayscale imaging in the four-chamber view demonstrates no patent tricuspid valve, a small right ventricle and, in most cases, a ventricular septal defect (Figure 1). Color flow mapping demonstrates no flow from right atrium to right ventricle and a marked right to left shunt at the atrial septum3 . The vessel arising from the small right ventricle tends to be hypoplastic. Therefore, pulmonary stenosis or atresia are frequent findings in concordant ventriculoarterial connection, especially when the ventricular septal defect is small. In ventriculoarterial discordance, which occurs in a significant proportion of

¨ Geburtshilfe und Pranatale ¨ ¨ Geburtshilfe und Frauenheilkunde, Correspondence to: Dr C. Berg, Abteilung fur Medizin, Zentrum fur ¨ Sigmund-Freud-Str. 25, 53105 Bonn, Germany (e-mail: [email protected]) Rheinische Friedrich-Wilhelms-Universitat, Accepted: 7 August 2009

Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd.

ORIGINAL PAPER

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Figure 1 Four-chamber view of a fetal heart with tricuspid atresia. The hypoplastic right ventricle (RV) is visualized adjacent to the ventricular septal defect (calipers) and the atretic tricuspid valve (asterisk). LA, left atrium; LV, left ventricle; RA, right atrium.

TA cases, hypoplasia of the aortic arch (Figure 2a and b) or even aortic atresia may occur, depending on the size of the ventricular septal defect. Less frequently associated cardiac defects include double outlet ventricle, anomalous pulmonary venous return and common arterial trunk3,7 . Although the prenatal diagnosis can be made during the basic cardiac scan in the four-chamber view, there are only a few small case series8 – 10 and two larger studies3,11 reporting on the spectrum and outcome of prenatally diagnosed TA. We therefore reviewed the prenatal spectrum and outcome of all cases of TA diagnosed in our three centers over a period of 10 years. The Doppler flow profiles of the ductus venosus (DV) were also analyzed, as we had found significantly altered Doppler flow profiles in a small group of fetuses with TA in our previous study on isolated right heart lesions12 .

PATIENTS AND METHODS We identified patients with a prenatal diagnosis of TA between 1998 and 2007 in the perinatal databases of three tertiary referral centers for prenatal medicine and ¨ ¨ fetal echocardiography ( in Bonn, Dusseldorf and Lubeck, Germany). Due to the different follow-up policies of the three centers, a search for missed cases was only possible in one, and this revealed no misdiagnosed cases. During the study period, the anatomical survey and fetal echocardiography were performed in a standardized fashion at all three centers. Fetal echocardiography was carried out by a segmental approach, as described previously13 – 15 , using standardized anatomical planes incorporating pulsed-wave and color Doppler imaging. All ultrasound examinations were performed using 5MHz, 7.5-MHz or 9-MHz sector or curved-array


Figure 2 Five-chamber view of a fetal heart with tricuspid atresia and transposition of the great arteries in gray scale (a) and color flow mode (b). The right ventricle (RV) adjacent to the ventricular septal defect (asterisk) is severely hypoplastic and gives rise to the narrowed aortic arch (AA). The pulmonary trunk (PT) originates from the left ventricle (LV). LA, left atrium.

probes (ATL HDI 5000 and IU22 Philips, Hamburg, Germany; Voluson 730 Expert and E8, GE Healthcare, Solingen, Germany). Over the study period over 50 000 first-, second- and third-trimester echocardiographic examinations were performed in the three centers. Eighty percent of these were routine scans in high-risk patients (in Germany only patients at risk are referred for a detailed scan) and 20% were referred for suspected fetal anomalies. In all three centers, a pediatric cardiologist attended at least one of each patient’s prenatal ultrasound examinations and subsequently counseled each patient. In all three centers, follow-up scans were performed at 6–8-week intervals when applicable. All patients had a planned delivery near term (induction of labor or Cesarean

Ultrasound Obstet Gynecol 2010; 35: 183–190.

Fetal tricuspid atresia section) in one of three cardiac centers in Germany: the University of Kiel, University of Bonn or Congenital Cardiac Center, Sankt Augustin. Following initial care by the attending neonatologist, all newborns were examined by a pediatric cardiologist within 12 h after birth. Lowdose prostaglandin treatment was initiated after birth in cases in which an immediate postnatal echocardiographic examination was not available and was discontinued after the echocardiographic assessment in cases with unrestricted flow to the aorta and the pulmonary artery. Patient charts and still frames of all cases were reviewed for the type of ventriculoarterial connection, the presence of outflow tract obstruction, the presence of further intra- and extracardiac malformations or aneuploidies and, when available, the Doppler parameters of the DV. The size of the foramen ovale and of the ventricular septal defect were not assessed routinely and could only be measured retrospectively in a few cases; these were therefore not included in the analysis. Ultrasound video recordings were reviewed when available, but only one center routinely taped all cardiac cases. Postnatal follow-up was available for all patients of the study population with a minimum duration of 1 year. The prenatal diagnosis of TA was confirmed during either cardiac surgery, neonatal imaging studies or autopsy in all except 11 cases. These latter cases were excluded from the study. Neonatal reports as well as surgery protocols and the reports from the pediatric cardiologists following up the patients were reviewed in all cases. As the latter follow-up records focused mainly on cardiac function, only scarce information could be obtained on the developmental status or quality of life. In two of the centers, Doppler evaluation of the DV was assessed routinely in cases of cardiac defects. Doppler recordings were obtained as described previously12 and the peak velocity index for veins (PVIV) was converted into Z-scores using published, normative data from a large population of healthy fetuses16 . DV measurements obtained from 585 uneventful pregnancies with normal fetal anatomy and known outcome were used as controls12 . Statistical analysis was performed using the χ2 , Fisher’s exact and Student’s t-tests and one-way ANOVA with post-hoc Bonferroni testing. A P-value < 0.05 was considered statistically significant.

RESULTS Clinical characteristics of the patient population We identified 65 cases of TA diagnosed between 1998 and 2006 in the three tertiary referral centers. Three pregnancies were lost to follow-up, five were terminated without autopsy and in three the diagnosis was not confirmed in the postnatal period. In one of the latter the diagnosis changed from TA with transposition of the great vessels to atrioventricular discordance and ventriculoarterial discordance with mitral atresia. In another, TA with intact ventricular septum, pulmonary


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atresia and a large ventriculocoronary communication was diagnosed in the prenatal period, while after birth, based on the presence of the sinusoid, the diagnosis was changed to pulmonary atresia with intact ventricular septum and secondary occlusion of the tricuspid valve. The remaining case had a membranous TA, an absent pulmonary valve and a patent ductus arteriosus; we excluded it from the study group as in this unusual case the tricuspid valve was occluded rather than absent. It is discussed in a case report later in this issue. In the remaining 54 cases the diagnosis was confirmed during cardiac surgery, neonatal imaging studies or at autopsy. The median gestational age at diagnosis was 22 (range, 12–32) weeks. The median maternal age was 31 (range, 20–41) years. Among the 54 pregnancies there were four pairs of twins, two of which were monochorionic (in each of these two pairs the cotwin also had malformations, sirenomelia in one pair and interruption of the aortic arch in the other). The median gestational age at birth was 38 (range, 36–41) weeks. There were 30 males (55.6%) and 24 females (44.4%). One pregnancy was complicated by premature rupture of the membranes at 20 weeks of gestation but the pregnancy continued uneventfully until delivery at 36 weeks of gestation and the infant recovered well from pulmonary hypoplasia. Another fetus with unilateral clubfoot developed a unilateral hydrothorax at 30 weeks that regressed after singular thoracocentesis and the pregnancy continued uneventfully until term. Mild intrauterine growth restriction was present in five fetuses but all of them delivered after 36 weeks’ gestation.

Cardiac findings A concordant ventriculoarterial connection was diagnosed in 28 (51.9%) cases, a discordant ventriculoarterial connection was diagnosed in 25 (46.3%) cases and one (1.9%) case had a single outlet with common arterial trunk. The associated cardiac lesions and the outcome in our cohort are summarized in Table 1.

Extracardiac findings TA was an isolated finding in 42 (77.8%) cases. Among the remaining 12 cases, five had chromosomal anomalies (two with trisomy 13, one with trisomy 18 and two unrelated cases had a supernumerary bisatellite marker chromosome 22 resulting in a partial tetrasomy 22q11), two cases had VACTERL association, one case had unilateral renal agenesis, one case had hypospadia, one case had unilateral clubfoot and hydrothorax, one case had megacystis and one case had agenesis of the DV. There was a single umbilical artery in nine (16.7%) cases, although this was not regarded as an extracardiac malformation.

Intrauterine evolution of cardiac findings In 14 of the continued pregnancies multiple examinations were performed prior to birth at 6–8-week intervals.


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186 Table 1 Additional cardiac findings and outcome in 54 fetuses with tricuspid atresia Ventriculoarterial connection/ Additional cardiac findings

n

TOP ( n)

IUFD ( n)

Discordant None Pulmonary stenosis Pulmonary atresia Aobst Aortic atresia, intact ventricular septum Dextrocardia, TAPVC Concordant None Pulmonary stenosis Pulmonary atresia Single outlet Truncus arteriosus communis Total

25 4 4 2 12 2 1 28 14 10 4 1 1 54

9 3* — 1† 4‡ 1 — 7 3#¶ 3‡ 1 1 1§ 17

1 — — 1* — — — 1 — — 1∧ — — 2

Childhood death (n) 2 — — — 2 — — — — — — — — 2

Survived ( n) 13 1 4 — 6 1 1 20 11§#◦ 7 2 — — 33

Symbols represent one affected case in each group except for * which represents two cases of monochorionic pregnancies with malformations in the cotwin. †Trisomy 18. ‡Trisomy 13. #Partial tetrasomy 22q11. §VACTERL association. ∧ Agenesis of ductus venosus. ¶Megacystis. ◦ Hydrothorax. Aobst, aortic outflow tract obstruction or aortic arch hypoplasia; CD, childhood death; IUFD, intrauterine fetal death; TAPVC, totally anomalous intracardiac pulmonary venous connection; TOP, termination of pregnancy.

The ventriculoarterial connection was discordant in four of these (three with hypoplasia of the aortic arch and one with aortic atresia) and concordant in 10 (two with pulmonary atresia, six with pulmonary stenosis and two with unobstructed pulmonary outflow tract). Only in two cases was the echocardiographic diagnosis changed at the repeat scan: both had concordant ventriculoarterial connections and the right outflow was unobstructed at the initial scan. In both cases the repeat scan showed significant narrowing of the pulmonary outflow tract and both newborns had a ductus arteriosus-dependent pulmonary circulation.

Doppler findings of the ductus venosus Doppler flow profiles of the DV were available in 37 cases and were compared with 585 controls. Fetuses with TA had significantly higher PVIV in the DV (Figure 3), significantly higher DV-PVIV Z-scores (2.73 ± 3.43 vs. −0.64 ± 0.90; P < 0.001) and significantly higher rates of reversal of flow during atrial contraction (16/21 vs. 0/585; P < 0.001) compared with controls. However, among continued pregnancies, there were no significant differences concerning survival to the perinatal period between the fetuses with abnormal and those with normal DV parameters. No case of hydrops occurred. In both cases which suffered intrauterine death, the DV parameters were normal. Three (8.6%) of the 35 neonates had a restriction of the foramen ovale necessitating balloon septostomy. An abnormal DV flow pattern might have anticipated this need due to the higher right atrial pressures. However, all three fetuses had normal DV flow profiles and PVIV.

Outcome The outcome of our cohort is depicted in Table 1 and Figure 4. Seventeen of the 54 (31.5%) cases underwent


termination of pregnancy. The gestational age at diagnosis was significantly lower in terminated pregnancies than in continued ones (mean ± SD, 21.7 ± 1.0 vs 24.3 ± 0.7 weeks; P < 0.01). The type of ventriculoarterial connection or the presence of extracardiac malformations was not significantly different between continued and terminated cases. Death in utero occurred in two (3.7%) cases; autopsy confirmed the prenatal findings, but the reason for intrauterine demise was not clear. Death in infancy occurred in two (3.7%) cases. Both infants had transposition of the great arteries with tubular hypoplasia of the aortic arch. One underwent reconstruction of the aortic arch with pulmonary artery banding and septostomy in the neonatal period and eventually died due to cardiac failure 2 weeks after Glenn procedure, at the age of 10 months. The other received a Damus–Kaye–Stansel anastomosis with modified Blalock–Taussig (BT) shunt in the neonatal period that was complicated by a mediastinal empyema and required two surgical revisions. Two months after discharge, the infant was readmitted with intractable pneumonia and died shortly thereafter at the age of 3 months. Thirty-three (61.1%) children survived, with a median follow up of 26 (range, 12–120) months. Kaplan–Meier estimates of survival from conception are shown in Figure 5. The greatest loss rate was in the prenatal period, attributable mainly to pregnancy terminations. The survival rate in the intention-to-treat group was 33/37 (89.2%), with all losses prior to the 2nd year of postnatal life. At the latest follow-up 32 survivors had received a bidirectional cavopulmonary anastomosis and 11/33 (33.3%) had completed Fontan palliation. One or more re-interventions were necessary in 8/33 (24.2%) survivors. Following Damus–Kaye–Stansel surgery with BT shunt, the infant with aortic atresia and intact ventricular septum underwent multiple dilatations


Fetal tricuspid atresia (a)

187 (b)

2.0

1.5

DV-PVIV

DV-PVIV

1.5

2.0

1.0

1.0

0.5

0.5

0.0

0.0

20

30 Gestational age (weeks)

20

40

30 Gestational age (weeks)

40

Figure 3 Ductus venosus peak velocity index for veins (DV-PVIV) plotted against gestational age for 585 controls (a) and 37 fetuses with tricuspid atresia (b). Regression lines represent the 5%, 50% and 95% confidence intervals of the control group.

of the aortic arch and the pulmonary arteries; 2 years after Glenn shunt a patch angioplasty of the aortic arch was additionally performed. Another infant underwent dilatation of shunt stenosis with stent placement 4 weeks after Damus–Kaye–Stansel surgery. Following Glenn shunt, two children needed dilatation of the pulmonary arteries with stent placement and another two underwent shunt dilatation. In one child, coil embolization of two aortopulmonary collateral arteries was performed and in the remaining case, secondary sternal reconstruction had to be performed after Fontan operation.

Accuracy of prenatal echocardiographic findings in predicting postnatal course Among 20 newborns with TA and concordant ventriculoarterial connections, 11 had a balanced physiology at prenatal ultrasound (mild or moderate pulmonary artery flow restriction) and nine had a marked right ventricular outflow obstruction. As expected, six of the 11 newborns with balanced physiology at prenatal ultrasound required no surgery prior to Glenn operation and another of the newborns with unrestricted flow into both great arteries at prenatal ultrasound had the expected pulmonary overcirculation after birth and received a pulmonary artery band in early infancy. However, four unexpectedly had a significant right ventricular outflow obstruction after birth and required a BT shunt in the neonatal period. All nine newborns with marked right ventricular outflow obstruction at prenatal ultrasound had the anticipated ductus arteriosus-dependent pulmonary circulation and needed a BT shunt. Among 15 newborns with TA and discordant ventriculoarterial connections, four had a balanced physiology (unrestricted flow into aorta and moderate pulmonary


stenosis) at prenatal ultrasound, nine had aortic stenosis/atresia with variable arch hypoplasia and two had unrestricted flow into both great arteries. As expected, two of the four newborns with balanced physiology at prenatal ultrasound required no surgery prior to Glenn operation. However, two unexpectedly required a BT shunt due to progressive cyanosis in the neonatal period. As anticipated, all nine newborns with right ventricular outflow obstruction at prenatal ultrasound received a Damus–Kaye–Stansel operation with BT shunt (n = 7) or a Norwood operation (n = 2) in the neonatal period. One of the two newborns with unrestricted flow into both great arteries at prenatal ultrasound had the expected pulmonary over-circulation after birth and received a pulmonary artery band in early infancy; the remaining case, in which the only scan was performed at 22 weeks of gestation, had a hypoplastic aortic arch and received a Damus–Kaye–Stansel anastomosis with a shunt in the neonatal period. Therefore, prenatal ultrasound correctly anticipated the postnatal course and the need for neonatal intervention in 29/35 (82.9%) cases. However, six of the 17 (35.3%) patients with balanced physiology or unrestricted flow into both arteries at prenatal ultrasound had a significant outflow obstruction at birth and required neonatal intervention. In these cases, the right outflow tract obstruction had been underestimated at prenatal ultrasound. Of note, only 14/35 cases had a feasible echocardiographic examination within 6 weeks prior to term. In all of these the postnatal physiology was correctly anticipated.

DISCUSSION A prenatal diagnosis of TA including its associated intraand extracardiac anomalies is possible with a high degree


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Prenatal diagnosis of tricuspid atresia (n = 54)

Termination (n = 17)

Intrauterine death (n = 2)

Death in infancy (n = 2)

(including trisomy 13, trisomy 18, partial tetrasomy 22q10, VACTERL association, megacystis and monochorionic twins with sirenomelia of cotwin)

(one monochorionic twin pregnancy at 26 weeks and one case with ductus venosus agenesis at 38 weeks of gestation)

(one case at 3 months after Damus–Kaye– Stansel anastomosis, another at 10 months after Glenn procedure)

Alive (n = 33)

Aortopulmonary shunt (n = 21)

Norwood–Sano procedure (n = 2)

(including six with Damus–Kaye–Stansel procedures and/or six with atrioseptostomy)

(both including atrioseptostomy and aortopulmonary shunt)

n=1

Pulmonary artery banding (n = 2)

No neonatal intervention (n = 8)

n = 20

Glenn shunt (n = 32)

Awaiting total cavopulmonary anastomosis (n = 22) (follow-up: median 24, range 12–72 months)

Total cavopulmonary connection (n = 11) (follow-up: median 36, range 21–120 months)

Figure 4 Outcome of 54 fetuses with prenatally diagnosed tricuspid atresia.

of accuracy. In the cohort of Wald et al.11 the diagnosis changed after birth in only 3/91 (3.3%) cases. Likewise, in our study only three infants had a differing diagnosis after birth. However, due to the rarity of the disease itself, our current knowledge on the spectrum and outcome of prenatally diagnosed TA is scarce. Sharland reported on the outcome of 84 fetuses with TA studied before the end of 19973 ; however, this report lacks details on the specific intra- and extracardiac defects and the follow-up ended in the neonatal period. In their well-designed retrospective study, Wald et al.11 summarized their experience in 88 cases from three centers over a 15-year period; this, to the best of our knowledge, is the only report suitable to be used as a reference in prenatal parental counseling. The spectrum of associated extra- and intracardiac malformations that was found in our cohort is similar


to that previously reported by Wald et al.11 . Our rate of discordant ventriculoarterial connection was similar to theirs (45.5%) and, as expected, most of the patients with pulmonary outflow obstruction had concordant venriculoarterial connections, while all cases with aortic outflow tract obstruction or aortic arch hypoplasia had discordant ventriculoarterial connections. Sharland reported a lower rate of transposition in her series (26%), although, again, the incidence of aortic arch anomalies was high (32%) in this group. Additional cardiac anomalies of hemodynamic significance were present in 3.7% of the cases in our cohort, less than the 18% incidence reported by Wald et al.11 , who, besides common arterial trunk and abnormal pulmonary venous drainage which were present in our cohort, also reported cases with double outlet ventricle,


Fetal tricuspid atresia

1.0

189

54

Cumulative survival

0.8 35

33 20

10

5

0.6

0.4

0.2

0.0 0

9 18 27 36 45 54 63 72 81 90 99 108117126135144

Months

Figure 5 Kaplan–Meier survival curve for 54 fetuses diagnosed with tricuspid atresia. The dotted line represents birth; whiskers represent the individual follow-up periods and numbers represent the total number of cases at the different follow-up periods.

Ebstein’s anomaly, cleft mitral valve and coronary sinus atresia. The important extracardiac anomalies in our cohort encompassed chromosomal defects, VACTERL association, DV agenesis and urogenital malformations. Likewise, Wald et al.11 reported three chromosomal anomalies, one VACTERL association and one multiple malformation syndrome in their series. The two unrelated cases of partial tetrasomy 22q11 in our series are remarkable as the resulting cat eye syndrome has, to the best of our knowledge, never been reported to be associated with TA. However, this genetic syndrome is characterized by large phenotypic variability, ranging from near normal to severe malformations, and has been associated with cardiac defects (namely, total anomalous pulmonary venous return and teralogy of Fallot) in previous reports17 . A ventricular septal defect is usually found in the classic type of TA. In the series of Wald et al.11 all fetuses had an associated ventricular septal defect. In the rare cases of TA with intact ventricular septum there is usually also atresia of the corresponding ventriculoarterial connection and the right ventricle is non-functioning and severely hypoplastic. In our cohort both fetuses with intact ventricular septum had ventriculoarterial discordance with aortic atresia and virtually absent right ventricular cavity at ultrasound. In our cohort, the Doppler flow profiles in the DV were significantly altered compared with controls although none of the fetuses showed additional signs of cardiac failure. Likewise, Wald et al.11 reported abnormal DV flow profiles in seven of the 16 (44%) fetuses with TA in which Doppler measurements were available. In our own previous study we were able to demonstrate that, in the absence of congestive heart failure, the DV flow characteristics are unaltered in most fetuses with isolated cardiac malformations18 . Only in some fetuses with isolated right heart malformations (namely TA) were the venous indices in the DV significantly increased12,18 .


Our current study adds further evidence to our previous conclusions that these alterations of DV blood flow in fetuses with TA are not related to cardiac failure but are attributable primarily to the special hemodynamics of the cardiac defect and therefore do not indicate fetal compromise. The rate of termination in our cohort (31.5%) was similar to that reported by Wald et al.11 (28%) and considerably lower than that reported by Sharland3 (64%). However, the gestational age at diagnosis, local legislation and different attitudes during parental counseling are most likely to be responsible for these differences. In our cohort a diagnosis in early pregnancy was the only factor associated with a higher rate of termination, reflecting the tendency of German patients and physicians to avoid termination after viability. Intrauterine death occurred in two cases in our series; however, both had additional conditions that could also have been responsible for the demise. Monochorionicity and agenesis of the DV both have a well-documented association with intrauterine death19 . Of note, the four intrauterine deaths in the series of Wald et al.11 occurred between 26 and 36 weeks of gestation in the absence of hydrops, arrhythmia and extracardiac malformations. Taking into consideration recent reports on atrial level restriction in the third trimester in fetuses with hypoplastic right heart20 , a closer surveillance of fetuses with TA might be warranted in the third trimester. The survival rate in the intention-to-treat group of our cohort was 89.2% and compares well with the 83% survival reported by Wald et al.11 . However, our followup period was limited and although all surviving infants reached the second step of palliation, only one third has received final palliation. Recent postnatal studies have reported survival rates at 1, 5 and 20 years of 82%, 72% and 61%, respectively21 . In our study, the findings at prenatal echocardiography correctly predicted the need for neonatal intervention in most cases. Although this did not influence the postnatal management in our institutions (as most patients were examined immediately after birth by a pediatric cardiologist who determined the treatment that followed, and in the remainder low-dose prostaglandin treatment was given until the first postnatal echocardiographic examination), this might be helpful for the management of neonates born in less specialized institutions. However, it should be kept in mind that almost one third of the patients with balanced physiology or unrestricted flow to both arteries at prenatal ultrasound had a significant outflow obstruction at birth and required neonatal intervention. This underestimation of right outflow tract obstruction occurred exclusively in cases in which the assessment was made more than 6 weeks prior to birth and emphasizes the need for reevaluation of the physiology near term. In summary, TA and its frequently associated intracardiac anomalies can be diagnosed in the fetus with high accuracy which might facilitate neonatal management. A thorough search for extracardiac malformations should


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be performed in order to rule out chromosomal anomalies and multiple malformation syndromes that are associated in a significant proportion of cases. Elevated pulsatility in the DV does not indicate cardiac failure, as this is attributable primarily to the particular hemodynamics of the cardiac defect. Still, closer surveillance with respect to unobstructed transatrial flow might be warranted in the third trimester. In our series, the overall survival in continued pregnancies exceeded 89%, with the greatest loss rate in the first year of postnatal life. However, an increase in mortality rate in subsequent years has to be expected.

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11.

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13.

REFERENCES 1. Ferencz C, Rubin JD, McCarter RJ, Brenner JI, Neill CA, Perry LW, Hepner SI, Downing JW. Congenital heart disease: prevalence at livebirth. The Baltimore-Washington Infant Study. Am J Epidemiol 1985; 121: 31–36. 2. Tegnander E, Williams W, Johansen OJ, Blaas HG, EikNes SH. Prenatal detection of heart defects in a non-selected population of 30149 fetuses: detection rates and outcome. Ultrasound Obstet Gynecol 2006; 27: 252–265. 3. Sharland G. Tricuspid valve abnormalities. In Textbook of Fetal Cardiology, Allan L, Hornberger LK, Sharland G (eds). Greenwich Medical Media: London, 2000; 133–147. 4. Berg C, Georgiadis M, Geipel A, Gembruch U. The area behind the heart in the four-chamber view and the quest for congenital heart defects. Ultrasound Obstet Gynecol 2007; 30: 721–727. 5. Fesslova V, Nava S, Villa L. Evolution and long term outcome in cases with fetal diagnosis of congenital heart disease: Italian multicentre study. Fetal Cardiology Study Group of the Italian Society of Pediatric Cardiology. Heart 1999; 82: 594–599. 6. Tennstedt C, Chaoui R, Korner H, Dietel M. Spectrum of congenital heart defects and extracardiac malformations associated with chromosomal abnormalities: results of a seven year necropsy study. Heart 1999; 82: 34–39. 7. Freedom RM, Yoo SJ. Tricuspid atresia. In The Natural and Modified History of Congenital Heart Disease, Freedom RM, Yoo SJ, Mikailian H, Williams WG (eds). Blackwell Publishing: New York, 2004; 381–386. 8. Orie JD, Anderson C, Ettedgui JA, Zuberbuhler JR, Anderson RH. Echocardiographic-morphologic correlations in tricuspid atresia. J Am Coll Cardiol 1995; 26: 750–758. 9. De Vore GR, Siassi B, Platt LD. Fetal echocardiography: the


14.

15.

16.

17.

18.

19.

20.

21.

prenatal diagnosis of tricuspid atresia (type Ic) during the second trimester of pregnancy. J Clin Ultrasound 1987; 15: 317–324. Tongsong T, Sittiwangkul R, Wanapirak C, Chanprapaph P. Prenatal diagnosis of isolated tricuspid valve atresia: report of 4 cases and review of the literature. J Ultrasound Med 2004; 23: 945–950. Wald RM, Tham EB, McCrindle BW, Goff DA, McAuliffe FM, Golding F, Jaeggi ET, Hornberger LK, Tworetzky W, Nield LE. Outcome after prenatal diagnosis of tricuspid atresia: a multicenter experience. Am Heart J 2007; 153: 772–778. Berg C, Kremer C, Geipel A, Kohl T, Germer U, Gembruch U. Ductus venosus blood flow alterations in fetuses with obstructive lesions of the right heart. Ultrasound Obstet Gynecol 2006; 28: 137–142. Huhta JC, Hagler DJ, Seward JB, Tajik AJ, Julsrud PR, Ritter DG. Two-dimensional echocardiographic assessment of dextrocardia: a segmental approach. Am J Cardiol 1982; 50: 1351–1360. Yagel S, Cohen SM, Achiron R. Examination of the fetal heart by five short-axis views: a proposed screening method for comprehensive cardiac evaluation. Ultrasound Obstet Gynecol 2001; 17: 367–369. Carvalho JS, Ho SY, Shinebourne EA. Sequential segmental analysis in complex fetal cardiac abnormalities: a logical approach to diagnosis. Ultrasound Obstet Gynecol 2005; 26: 105–111. Rizzo G, Capponi A, Talone PE, Arduini D, Romanini C. Doppler indices from inferior vena cava and ductus venosus in predicting pH and oxygen tension in umbilical blood at cordocentesis in growth-retarded fetuses. Ultrasound Obstet Gynecol 1996; 7: 401–410. Rosias PR, Sijstermans JM, Theunissen PM, Pulles-Heintzberger CF, De Die-Smulders CE, Engelen JJ, Van Der Meer SB. Phenotypic variability of the cat eye syndrome. Case report and review of the literature. Genet Couns 2001; 12: 273–282. Gembruch U, Meise C, Germer U, Berg C, Geipel A. Venous Doppler ultrasound in 146 fetuses with congenital heart disease. Ultrasound Obstet Gynecol 2003; 22: 345–350. Berg C, Kamil D, Geipel A, Kohl T, Knopfle G, Hansmann M, Gembruch U. Absence of ductus venosus – importance of umbilical venous drainage site. Ultrasound Obstet Gynecol 2006; 28: 275–281. Donofrio MT, Bremer YA, Moskowitz WB. Diagnosis and management of restricted or closed foramen ovale in fetuses with congenital heart disease. Am J Cardiol 2004; 94: 1348–1351. Sittiwangkul R, Azakie A, Van Arsdell GS, Williams WG, McCrindle BW. Outcomes of tricuspid atresia in the Fontan era. Ann Thorac Surg 2004; 77: 889–894.
