Extracardiac anomalies in prenatally diagnosed heterotaxy syndrome.

OBJECTIVE: To assess the incidence and impact of extracardiac anomalies on the prognosis of fetuses with heterotaxy syndrome. METHODS: All fetuses diagnosed with heterotaxy syndrome by three experienced examiners over a period of 14 years (1999-2013) were reviewed retrospectively. RESULTS: In total, 165 fetuses with heterotaxy syndrome were diagnosed in the study period. One hundred and fifty (90.9%) had cardiac defects; extracardiac anomalies that did not involve the spleen were present in 26/165 (15.8%) cases. Of the total study cohort, termination of pregnancy was performed in 49 (29.7%) cases, intrauterine death occurred in 11 (6.7%), postnatal death occurred in 38 (23.0%) and 67 (40.6%) were alive at the latest follow-up, resulting in a total perinatal and pediatric mortality of 59.4%. Among the 105 liveborn neonates, 15 (14.3%) had extracardiac anomalies with significant impact on the postnatal course: one neonate died following repair of an encephalocele, six had successful treatment for various types of intestinal malrotation and/or atresia and one underwent hiatal hernia repair; the remaining seven had biliary atresia, of which five died and the two survivors are awaiting liver transplantation. The status of the spleen was assessed in 93/105 liveborn children and was found to be abnormal in 84/93 (90.3%). There were three cases of lethal sepsis, all associated with asplenia. Of the 38 postnatal deaths, 29 (76.3%) had a cardiac cause, seven (18.4%) had an extracardiac cause and in two (5.2%) the reason was uncertain. CONCLUSIONS: Although the leading causes of death in fetuses and children with heterotaxy syndrome are cardiac, a small subset of fetuses have extracardiac anomalies with significant impact on outcome. These anomalies often escape prenatal detection, and therefore neonates at risk should be monitored for bowel obstruction, biliary atresia and immune dysfunction in order to allow timely intervention through a multidisciplinary approach. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Evaluation of right ventricular function in fetal hypoplastic left heart syndrome by color tissue Doppler imaging.

OBJECTIVE: Postnatal outcome of fetuses with hypoplastic left heart syndrome (HLHS) is determined mainly by right ventricular function. Our study examines whether there are differences in right ventricular function during gestation of fetuses with HLHS compared with healthy fetuses. METHODS: A prospective study was conducted including 20 fetuses with HLHS and 20 gestational age-matched controls. Peak systolic and diastolic right ventricular free wall velocities were assessed using color tissue Doppler imaging (c-TDI). Subsequently, isovolumic time intervals, ejection time (ET'), E'/A' ratio and tissue Doppler-derived myocardial performance index (MPI') were calculated. Possible changes to c-TDI indices during the course of pregnancy in both the HLHS group and the control group were investigated. RESULTS: Examination of right ventricular function revealed significantly lower E' velocities (13.6 vs 21.0 cm/s; P = 0.017) and E'/A' ratios (0.55 vs 0.76; P = 0.012) and prolonged isovolumic contraction time (ICT') (57.0 vs 45.7 ms; P = 0.008) in the HLHS group compared with healthy fetuses. Furthermore, isovolumic relaxation time and MPI' increased significantly with gestational age in HLHS fetuses but not in controls. Values for systolic and diastolic peak velocities (E', A', S'), ET' and ICT' did not change significantly during gestation in either group. CONCLUSION: Right ventricular function in HLHS is altered as early as in fetal life, well before palliative surgery is performed. Future research should provide further insight into ventricular remodeling during gestation in cases of HLHS. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Evaluation of right ventricular function in fetuses with hypoplastic left heart syndrome using tissue Doppler techniques.

OBJECTIVE: The outcome of patients with hypoplastic left heart syndrome (HLHS) is influenced by right ventricular function. This study aimed to investigate whether differences in right ventricular function of fetuses with HLHS are present during gestation. METHODS: This was a prospective study comprising 14 fetuses with HLHS (28 measurements obtained in total) and 28 normal control fetuses (31 measurements obtained in total). The two groups were matched for gestational age. Ultrasound M-mode was used to assess displacement of the tricuspid annulus. Spectral Doppler and myocardial tissue Doppler-derived inflow and outflow velocities were assessed. Tricuspid valve peak early wave to peak active wave (E/A) ratio, the early wave to early diastolic annular relaxation velocity (E/E') ratio and the tissue Doppler-derived myocardial performance index (MPI') were calculated. RESULTS: E-wave velocity was significantly higher in fetuses with HLHS than in control fetuses (mean, 40.14 cm/s vs 35.47 cm/s; P < 0.05, respectively), and A-wave velocity in fetuses with HLHS showed a tendency for higher values in the right ventricle compared with normal control fetuses, but this did not reach statistical significance (61.16 cm/s vs 54.64 cm/s; P = 0.08). The E/A ratio increased during gestation in controls, but this increase was not seen in HLHS fetuses. Peak annular velocity during atrial contraction (A') and the E/E' ratio were significantly lower in controls than in HLHS fetuses: 9.50 cm/s vs 10.39 cm/s (P < 0.05) and 5.77 vs 7.37 (P < 0.05), respectively. There were no differences for right-ventricular MPI' or tricuspid annular plane systolic excursion between HLHS fetuses and controls. CONCLUSION: The results of this study show that altered right ventricular function in HLHS infants may develop antenatally. It is hoped that confirmation of these findings using Doppler-independent techniques will lead to further exploration of ventricular function in HLHS fetuses. Consequently, parental counseling and postnatal management strategies could be influenced.

Assessment of cardiac function in monochorionic diamniotic twin pregnancies with twin-to-twin transfusion syndrome before and after fetoscopic laser photocoagulation using Speckle tracking.

PURPOSE: To assess cardiac function with Speckle tracking in fetuses with twin-to-twin transfusion syndrome (TTTS) before and after laser therapy. MATERIALS AND METHODS: A prospective case control study was conducted on 11 monochorionic diamniotic twin pairs with TTTS. Based on normal curves derived from healthy controls, global systolic longitudinal myocardial velocity, strain and strain rate values were transformed to z-scores. RESULTS: Right and left ventricular systolic global strain (-27.45 % and -22.41 %) and strain rate (-4.13/sec and -3.27/sec) were reduced in recipients compared with normal values and all parameters tended to decrease even more after treatment (RV and LV: strain -23.79 % and -20.21 %; strain rate: -3.67/sec and -2.87/sec). The corresponding measurements in donor fetuses revealed no statistical difference compared to reference values. CONCLUSION: The global systolic myocardial function of donor twins before and after laser therapy was in the normal ranges. In contrast, recipient twins exhibited global cardiac dysfunction with decreased pre- and postoperative strain and strain rate. Speckle tracking can identify compromised ventricular myocardial function in fetuses with TTTS.

Assessment of left ventricular global and regional longitudinal peak systolic strain, strain rate and velocity with feature tracking in healthy fetuses.

PURPOSE: The aim of this study was to evaluate the correlation of feature-tracking-derived measurements of the left ventricular myocardium in healthy fetuses with gestational age. MATERIALS AND METHODS: The global and segmental longitudinal peak systolic strain, strain rate and velocity values of the left ventricular myocardium for each gestational age were assessed by a novel feature tracking technique in 150 healthy fetuses (gestational age range 13 - 39 weeks of gestation). The interobserver and intraobserver variability was analyzed. RESULTS: The global longitudinal peak systolic velocity exhibited a segmental base to apex gradient (p < 0.001). From 13 to 39 weeks of gestation, the global and segmental longitudinal peak systolic velocities increased significantly throughout gestation (p < 0.001), while the global longitudinal peak systolic strain remained constant (p = 0.34) and the strain rate exhibited only a tendency to decrease (p = 0.045). The interobserver and intraobserver variability of the global LV peak systolic strain, strain rate and velocity was acceptable. The standard deviations of measurement error between the two observers were 2.5 %, 0.7 s (-1) and 0.5 cm/sec, respectively. CONCLUSION: The global myocardial peak systolic velocities of the left ventricle increase with gestational age, while the global myocardial peak systolic strain and strain rate remained nearly constant throughout gestation. This novel angle-independent, noninvasive technique offers a new objective approach to quantify global and segmental fetal myocardial performance throughout gestation.

Assessment of fetal global and regional ventricular function in congenital heart disease using a novel feature tracking technique.

PURPOSE: The aim of this study was to assess global and regional longitudinal peak systolic ventricular function in fetuses with congenital heart disease (CHD) and compare measurements derived from feature tracking with reference values of healthy fetuses with a matching gestational age. MATERIALS AND METHODS: Global and segmental longitudinal peak systolic strain (LPSS), strain rate and velocity values of the left (LV) ventricular myocardium and right (RV) ventricular myocardium were assessed by a novel feature tracking technique in 17 fetuses with congenital heart disease (10 fetuses with left heart obstruction (LHO), 5 fetuses with tetralogy of Fallot (TOF) and 2 fetuses with double outlet right ventricle (DORV)) and were compared in a second step with 24 matched healthy fetuses (gestational age range 21 - 36 weeks of gestation). RESULTS: The global LPSS of both ventricles was slightly elevated in fetuses with TOF or DORV compared with controls (RV: p = 0.055; LV: p = 0.063). The RV strain rate presented a trend toward higher values (p = 0.09). Corresponding global LV velocity values of fetuses with TOF or DORV revealed a tendency to decrease compared to healthy controls (p = 0.054). In contrast, all measurements of fetuses with LHO did not show any statistical difference regarding deformation parameters or velocity compared to healthy controls. CONCLUSION: Global longitudinal peak systolic measurements in fetuses with congenital heart disease revealed slightly higher strain (RV/LV) and strain rate (RV) values in the subgroup of fetuses with TOF or DORV compared to healthy controls. Whether the application of this new angle-independent technique is suitable for discriminating between healthy and diseased fetuses has to be verified in further investigations.

Fetal aberrant right subclavian artery (ARSA) - a potential new soft marker in the genetic scan?

PURPOSE: The aim of this study was to evaluate the prevalence of an aberrant right subclavian artery (ARSA) in a mixed-risk population in the second trimester and to assess its potential as a new soft marker in the genetic scan. MATERIALS AND METHODS: Fetal echocardiography was performed prospectively in 1337 fetuses at 16 - 28 weeks of gestation during a 12-month period at two referral centers for prenatal diagnosis. The presence of ARSA was verified by visualization of the transverse 3-vessel trachea view with color Doppler sonography. RESULTS: The total rate of fetuses with an ARSA was 1.05 % (14 / 1337). The spectrum of associated findings in affected fetuses included: one trisomy 21, one unbalanced inversion of chromosome 9, one triploidy and two non-chromosomally related structural defects. Nine fetuses had no anomalies. The calculated odds ratio for the presence of an ARSA in the case of Down syndrome compared with healthy fetuses was 12.6 (95 % CI, 1.93 - 86.10). CONCLUSION: The presence of an ARSA is more common in fetuses with trisomy 21 and other chromosomal defects than in healthy fetuses. Although it can be considered as a weak marker, the second trimester diagnosis of an ARSA should prompt a detailed search for additional "soft markers" and structural defects.

[Speckle tracking--a new ultrasound tool for the assessment of fetal myocardial function]. / Speckle tracking--ein neues Ultraschallverfahren zur Beurteilung der fetalen Myokardfunktion.

Speckle tracking is a new ultrasound tool to assess 2D ventricular global and segmental myocardial velocity and deformation (strain, strain rate). Multiple factors such as fetal motion, high heart rates, low blood pressure, small size of the heart, physiological cardiac translation, filling and maturational changes of myocardium, polyhydramnion, maternal obesity and aortic pulsation can degrade the image quality and result in artifacts and measurement errors which may have an impact on the final analysis. Therefore deformation indices such as strain and strain rate offer a quantitative technique for the estimation of global and segmental myocardial function and contractility. At present longitudinal peak systolic strain is the most commonly applied deformation parameter used to analyse segmental and global myocardial contractility in adults. When obtained using Doppler methods, these measurements are angle dependent, whereas speckle tracking techniques overcome the limitations of Doppler echocardiography which is a particular advantage in foetal echocardiography. Nevertheless, the time and training necessary to acquire high-quality video clips limit the implementation of speckle tracking into clinical routine. It is not yet clear whether this new technique will identify subclinical myocardial impairment earlier than with current techniques or allow for better discrimination between healthy fetuses and fetuses with congenital heart disease. The clinical use of speckle tracking will have to be demonstrated in larger groups of complicated pregnancies.

Assessment of right ventricular global and regional longitudinal peak systolic strain, strain rate and velocity in healthy fetuses and impact of gestational age using a novel speckle/feature-tracking based algorithm.

OBJECTIVE: To evaluate the correlation between feature tracking-derived measurements of the right ventricular myocardium and gestational age in healthy fetuses. METHODS: Global and segmental longitudinal peak systolic strain, strain rate and velocity values of the right ventricular myocardium were assessed by a novel feature-tracking technique in 150 healthy fetuses at between 13 and 39 weeks' gestation. Reference ranges were constructed with respect to gestational age, and inter- and intraobserver variability was analyzed. RESULTS: Strain, strain rate and velocity exhibited a segmental base to apex gradient (P < 0.001). Global longitudinal peak systolic velocities increased significantly across the gestational age range considered (P < 0.001), whereas global longitudinal peak systolic strain and strain rate (taken as absolute values) decreased significantly (P < 0.001 and P < 0.001). Inter- and intraobserver variability of global right ventricular peak systolic strain, strain rate and velocity was acceptable. The SDs of measurement error between the two observers were 5.9%, 0.7/s and 0.5 cm/s, respectively. CONCLUSIONS: Global myocardial peak systolic velocities of the right ventricle increase with gestational age whereas global myocardial peak absolute systolic strain and strain rate significantly decrease throughout gestation. This novel angle-independent technique offers a new non-invasive approach for quantifying and monitoring fetal myocardial function throughout gestation.

Reference ranges for Doppler assessment of uterine artery resistance and pulsatility indices in dichorionic twin pregnancies.

OBJECTIVES: To construct reference ranges of uterine artery Doppler parameters against gestation in twin pregnancies and to present charts of the pulsatility index (PI) and resistance index (RI) for clinical use. METHODS: This was an observational study of the uterine circulation in 557 women with dichorionic twin pregnancies at 17-38 weeks' gestation. Uterine artery measurements were performed by color and pulsed Doppler imaging. The uterine artery PI and RI were calculated as a mean of both sides. Reference ranges were constructed by regression of each index on gestational age. For this purpose, a regression model with fractional polynomials was fitted to the data. Furthermore, the presence of uterine artery notching was recorded. RESULTS: New reference curves and tables of percentiles of the uterine artery PI and RI are presented. The calculated indices both showed a significant decrease with gestational age. Compared with singleton values, mean twin PI values were lower during the whole course of pregnancy. The prevalence of bilateral notching was 4.6% at 17-19 weeks' gestation and 3.1% at 20-24 weeks. CONCLUSIONS: Uterine artery Doppler indices in twin pregnancies are lower than in singleton pregnancies. Therefore, the use of uterine artery reference ranges adapted to twin gestations seems more appropriate for identifying low- and high-risk groups.

Nuchal fold thickness, nasal bone absence or hypoplasia, ductus venosus reversed flow and tricuspid valve regurgitation in screening for trisomies 21, 18 and 13 in the early second trimester.

OBJECTIVE: To investigate the performance of nuchal fold thickness, nasal bone hypoplasia, reversed flow in the ductus venosus and tricuspid valve regurgitation in the prediction of fetal aneuploidies in the early second trimester. METHODS: This was a prospective study of 870 fetuses at 14 + 0 to 17 + 6 weeks of gestation, performed from 2005 to 2007. In all cases we assessed classical structural anomalies, second-trimester markers of aneuploidy including nuchal fold thickness and nasal bone length, as well as ductus venosus blood flow pattern and tricuspid valve regurgitation. RESULTS: The study group included 37 fetuses with trisomy 21, eight with trisomy 18 and four with trisomy 13. Nasal bone hypoplasia was the single most sensitive parameter to identify fetuses with trisomy 21. Independent from maternal age, screening by assessment of nuchal fold and nasal bone identified 64.9% of cases with trisomy 21 and 66.7% of cases with trisomy 18/13 (false-positive rate (FPR), 5.8%). By including ductus venosus and tricuspid flow evaluation, the detection rate increased to 75.7% for trisomy 21 and 83.3% for trisomy 18/13 (FPR, 10.8%). Identification of fetuses with structural abnormalities combined with assessment of all four markers under investigation raised the detection rate of trisomy 21 to 83.9% and that of trisomy 18/13 to 100%. The sensitivity of classical second-trimester markers was 62.2% for trisomy 21 and 70.6% for other autosomal aneuploidies (FPR, 11.3%). CONCLUSION: The combination of assessment of nuchal fold thickness, nasal bone hypoplasia, ductus venosus reversed flow and tricuspid regurgitation in the early second trimester is associated with a higher detection rate of autosomal trisomies compared with classical second-trimester marker screening.

Decision making and attitudes towards invasive prenatal diagnosis in the early second trimester.

PURPOSE: To investigate the impact of the a priori attitude, nondirective counselling and targeted second trimester ultrasound examination on the decision process concerning invasive prenatal diagnosis in the second trimester. MATERIAL AND METHODS: A prospective study including 696 high-risk pregnancies at 15 to 18 weeks' gestation, performed from 2005-2007. Attitudes towards invasive prenatal testing were explored before and after genetic counselling and targeted ultrasound examination in a tertiary referral centre. RESULTS: Initially, 311 (44.7%) women intended to have an invasive testing (group 1), 150 women (21.5%) were against an invasive procedure (group 2), and 235 women (33.8%) wanted to make their final decision depending on the sonographic result (group 3). The total rate of amniocentesis was 87.1%, 5.3% and 13.6%, respectively. Overall, the a priori decision was sparsely influenced by the ultrasound examination. Only 12.9% (40/311) and 5.3% (8/150) of the primarily determined women (group 1, 2) changed their opinion. However, in the initially undecided group, 86.7% declined an amniocentesis after a normal ultrasound scan. CONCLUSION: The referral indication and the a priori opinion are the strongest influencing factors with regard to invasive testing and the ultrasound scan has a low impact in those preselected patients. However, ultrasound has an important reassuring aspect in women willing to use ultrasound as assistance in the process of decision making.

ETV6-NTRK3 gene fusion in a secretory carcinoma of the breast of a male-to-female transsexual.

Secretory carcinomas of the breast were first described as "juvenile carcinoma" by McDivitt and Stewart in a cohort of children. This term has been replaced by the term "secretory breast carcinoma", because the entity can occur at any time of life. Carcinoma of the male breast is uncommon and accounts for approximately 1% of all cancers in men. Recently, it has been reported that human secretory breast carcinoma expresses the ETV6-NTRK3 gene fusion that was previously cloned in pediatric mesenchymal cancers. We present the case of a 46-year-old male-to-female transsexual in whom a secretory breast carcinoma was an incidental finding. As confirmation of the histopathological diagnosis we detected the novel ETV6-NTRK3 gene fusion in this tumor.

Imaging in fetal cardiology.

Early detection and accurate diagnosis of fetal cardiac disease is a central approach in perinatal medicine. The purpose of this review is to evaluate current imaging modalities for the assessment of the fetal heart and its function. Conventional fetal 2D- and color-Doppler echocardiography as a screening tool as well as a diagnostic modality has been proven to be safe, easy and cost-effective for the diagnosis of structural heart disease. Cardiac function can be assessed by M-mode and intra- and extra-cardiac Doppler-echocardiography on a routine basis, but remains challenging in subclinical pathology. Tissue-Doppler, speckle tracking, dynamic three-dimensional (4D) echocardiography, and fetal cardiac magnetic resonance imaging are advanced modalities for the assessment of cardiac structure and function. Implementation of these new technologies is far from routine, but these approaches have already shown promising results and may allow a more detailed evaluation of cardiac function. In this review, we provide a brief overview of currently available techniques, and their benefits and limitations in the clinical assessment of the fetal heart.

[External cephalic version in cases of breech presentation: renaissance of a well-known procedure?]. / Die äussere Wendung bei Beckenendlage: Renaissance eines altbekannten Verfahrens?

OBJECTIVE: About 3-4% of all pregnant women will have a fetus presenting by the breech at term. External cephalic version offers the opportunity to reduce the rate of caesarean sections caused by breech presentation. We analysed retrospectively 51 cases of external cephalic version at our clinic. METHODS: External cephalic version was performed 51 times between 37 and 41 weeks of pregnancy. RESULTS: External cephalic version was successful in 32/51 cases (62,7%) with a consecutive rate of vaginal delivery of 71,9%. The best results were seen at 37 weeks of pregnancy with 81,25% of successful versions followed by 76,9% of vaginal deliveries. Complications were rare. There was just 1 case of emergency caesarean section due to persisting fetal bradycardia. CONCLUSION: External cephalic version is an effective and safe treatment to enable vaginal delivery of cephalic presentation. For this operation, 37 weeks of pregnancy can be considered the best time.