Single-center outcome analysis of 46 fetuses with megacystis after intrauterine vesico-amniotic shunting with the Somatex®intrauterine shunt.

OBJECTIVES: To assess the spectrum of underlying pathologies, the intrauterine course and postnatal outcome of 46 fetuses with megacystis that underwent intrauterine vesico-amniotic shunting (VAS) with the Somatex® shunt in a single center. METHODS: Retrospective analysis of 46 fetuses with megacystis that underwent VAS either up to 14 + 0 weeks (early VAS), between 14 + 1 and 17 + 0 weeks (intermediate VAS) or after 17 + 0 weeks of gestation (late VAS) in a single tertiary referral center. Intrauterine course, underlying pathology and postnatal outcome were assessed and correlated with the underlying pathology and gestational age at first VAS. RESULTS: 46 fetuses underwent VAS, 41 (89%) were male and 5 (11%) were female. 28 (61%) fetuses had isolated and 18 (39%) had complex megacystis with either aneuploidy (n = 1), anorectal malformations (n = 6), cloacal malformations (n = 3), congenital anomalies overlapping with VACTER association (n = 6) or Megacystis-Microcolon Intestinal-Hypoperistalsis Syndrome (MMIHS) (n = 2). The sonographic 'keyhole sign' significantly predicted isolated megacystis (p < 0.001). 7 pregnancies were terminated, 4 babies died in the neonatal period, 1 baby died at the age of 2.5 months and 34 (74%) infants survived until last follow-up. After exclusion of the terminated pregnancies, intention-to-treat survival rate was 87%. Mean follow-up period was 24 months (range 1-72). The underlying pathology was highly variable and included posterior urethral valve (46%), hypoplastic or atretic urethra (35%), MMIHS or prune belly syndrome (10%) and primary vesico-ureteral reflux (2%). In 7% no pathology could be detected postnatally. No sonographic marker was identified to predict the underlying pathology prenatally. 14 fetuses underwent early, 24 intermediate and 8 late VAS. In the early VAS subgroup, amnion infusion prior to VAS was significantly less often necessary (7%), shunt complications were significantly less common (29%) and immediate kidney replacement therapy postnatally became less often necessary (0%). In contrast, preterm delivery ≤ 32 + 0 weeks was more common (30%) and survival rate was lower (70%) after early VAS compared to intermediate or late VAS. Overall, 90% of liveborn babies had sufficient kidney function without need for kidney replacement therapy until last follow-up, and 95% had sufficient pulmonary function without need for mechanical respiratory support. 18% of babies with complex megacystis suffered from additional health restrictions due to their major concomitant malformations. CONCLUSIONS: Our data suggest that VAS is feasible from the first trimester onward. Early intervention has the potential to preserve neonatal kidney function in the majority of cases and enables neonatal survival in up to 87% of cases. Despite successful fetal intervention, parents should be aware of the potential of mid- or long-term kidney failure and of additional health impairments due to concomitant extra-renal anomalies that cannot be excluded at time of intervention.

D-Transposition of the great arteries with restrictive foramen ovale in the fetus: the dilemma of predicting the need for postnatal urgent balloon atrial septostomy.

OBJECTIVE: Restrictive foramen ovale (FO) in dextro-transposition of the great arteries (d-TGA) with intact ventricular septum may lead to severe life-threatening hypoxia within the first hours of life, making urgent balloon atrial septostomy (BAS) inevitable. Reliable prenatal prediction of restrictive FO is crucial in these cases. However, current prenatal echocardiographic markers show low predictive value, and prenatal prediction often fails with fatal consequences for a subset of newborns. In this study, we described our experience and aimed to identify reliable predictive markers for BAS. METHODS: We included 45 fetuses with isolated d-TGA that were diagnosed and delivered between 2010 and 2022 in two large German tertiary referral centers. Inclusion criteria were the availability of former prenatal ultrasound reports, of stored echocardiographic videos and still images, which had to be obtained within the last 14 days prior to delivery and that were of sufficient quality for retrospective re-analysis. Cardiac parameters were retrospectively assessed and their predictive value was evaluated. RESULTS: Among the 45 included fetuses with d-TGA, 22 neonates had restrictive FO postnatally and required urgent BAS within the first 24 h of life. In contrast, 23 neonates had normal FO anatomy, but 4 of them unexpectedly showed inadequate interatrial mixing despite their normal FO anatomy, rapidly developed hypoxia and also required urgent BAS ('bad mixer'). Overall, 26 (58%) neonates required urgent BAS, whereas 19 (42%) achieved good O2 saturation and did not undergo urgent BAS. In the former prenatal ultrasound reports, restrictive FO with subsequent urgent BAS was correctly predicted in 11 of 22 cases (50% sensitivity), whereas a normal FO anatomy was correctly predicted in 19 of 23 cases (83% specificity). After current re-analysis of the stored videos and images, we identified three highly significant markers for restrictive FO: a FO diameter < 7 mm (p < 0.01), a fixed (p = 0.035) and a hypermobile (p = 0.014) FO flap. The maximum systolic flow velocities in the pulmonary veins were also significantly increased in restrictive FO (p = 0.021), but no cut-off value to reliably predict restrictive FO could be identified. If the above markers are applied, all 22 cases with restrictive FO and all 23 cases with normal FO anatomy could correctly be predicted (100% positive predictive value). Correct prediction of urgent BAS also succeeded in all 22 cases with restrictive FO (100% PPV), but naturally failed in 4 of the 23 cases with correctly predicted normal FO ('bad mixer') (82.6% negative predictive value). CONCLUSION: Precise assessment of FO size and FO flap motility allows a reliable prenatal prediction of both restrictive and normal FO anatomy postnatally. Prediction of likelihood of urgent BAS also succeeds reliably in all fetuses with restrictive FO, but identification of the small subset of fetuses that also requires urgent BAS despite their normal FO anatomy fails, because the ability of sufficient postnatal interatrial mixing cannot be predicted prenatally. Therefore, all fetuses with prenatally diagnosed d-TGA should always be delivered in a tertiary center with cardiac catheter stand-by, allowing BAS within the first 24 h after birth, regardless of their predicted FO anatomy.

Postnatal surgical treatment and complications following intrauterine vesicoamniotic shunting with the SOMATEX® intrauterine shunt. A single center experience.

INTRODUCTION: Intrauterine vesicoamniotic shunting (VAS) using a Somatex® shunt was shown to significantly affect survival of male fetuses with megacystis in suspected lower urinary tract obstruction (LUTO) [Figure 1]. Data on postnatal surgical management and complications are largely lacking. OBJECTIVE: To describe the postnatal management of patients with prenatal VAS for megacystitis in suspected severe LUTO. STUDY DESIGN: All male newborns with previous intrauterine VAS using a Somatex® shunt treated in our institution were retrospectively analyzed. We evaluated the spectrum of urethral pathologies and postnatal surgical management, especially focusing on shunt removal. RESULTS: Between 2016 and 2022, 17 patients (all male) were treated postnatally in our institution after VAS for suspected severe LUTO. Five fetuses with dislocated shunts underwent re-implantation in utero. Overall, premature birth before the 38th week of gestation was observed in eight patients (8/17). Seven shunts could be removed without further anesthesia as a bedside procedure. Ten patients required surgical shunt removal under general anesthesia due to migration (59%). Laparoscopic shunt extraction was performed in 8/10 cases. Most frequently, dislocated shunts were located incorporated in the detrusor in eight cases and the removal required a bladder suture in 2/8 patients. In one case, the shunt was removed from the abdominal wall and in one case from the intestine wall [Figure 2]. Posterior urethral valves were found in 8/17 patients, 6/17 patients showed a urethral atresia and one patient had urethral duplication. In two patients, we identified a high grade bilateral vesicoureteral reflux without LUTO. CONCLUSION: In our observation, more than half of the newborns with megacystis in suspected LUTO require a shunt removal surgery after early VAS using a Somatex® shunt. Urethral atresia may be found more frequently in these patients. These data should be taken into consideration for prenatal counselling of parents and planning of postnatal management.

Prenatal diagnosis, associated findings and postnatal outcome of fetuses with truncus arteriosus communis (TAC).

PURPOSE: To assess the spectrum of associated anomalies, the intrauterine course, postnatal outcome and management of fetuses with truncus arteriosus communis (TAC) METHODS: All cases of TAC diagnosed prenatally over a period of 8 years were retrospectively collected in two tertiary referral centers. All additional prenatal findings were assessed and correlated with the outcome. The accuracy of prenatal diagnosis was assessed. RESULTS: 39 cases of TAC were diagnosed prenatally. Mean gestational age at first diagnosis was 22 weeks (range, 13-38). Two cases were lost follow-up. Correct prenatal diagnosis of TAC was made in 21 of 24 (87.5%) cases and of TAC subtype in 19 of 21 (90.5%) cases. Prenatal diagnosis of TAC was incorrect in three cases: one newborn had aortic atresia with ventricular septal defect postnatally, one had hypoplastic right ventricle with dextro Transposition of the Great Arteries with coartation of the aorta and a third newborn had Tetralogy of Fallot with abnormal origin of the left pulmonary artery arising from the ascending aorta postnatally. These three cases were excluded from further analysis. In 9 of 34 (26.5%) cases, TAC was an isolated finding. 13 (38.2%) fetuses had additional chromosomal anomalies. Among them, microdeletion 22q11.2 was most common with a prevalence of 17.6% in our cohort. Another 3 fetuses were highly suspicious for non-chromosomal genetic syndromes due to their additional extra-cardiac anomalies, but molecular diagnosis could not be provided. Major cardiac and extra-cardiac anomalies occurred in 3 (8.8%) and in 20 (58.8%) cases, respectively. Predominantly, extra-cardiac anomalies occurred in association with chromosomal anomalies. Additionally, severe IUGR occurred in 6 (17.6%) cases. There were 14 terminations of pregnancy (41.2%), 1 (2.9%) intrauterine fetal death, 5 postnatal deaths (14.7%) and 14 (41.2%) infants were alive at last follow-up. Intention-to-treat survival rate was 70%. Mean follow-up among survivors was 42 months (range, 6-104). Postoperative health status among survivors was excellent in 11 (78.6%) infants, but 5 (46.2%) of them needed repeated re-interventions due to recurrent pulmonary artery or conduit stenosis. The other 3 (21.4%) survivors were significantly impaired due to non-cardiac problems. CONCLUSION: TAC is a rare and complex cardiac anomaly that can be diagnosed prenatally with high precision. TAC is frequently associated with chromosomal and extra-cardiac anomalies, leading to a high intrauterine and postnatal loss rate due to terminations and perioperative mortality. Without severe extra-cardiac anomalies, postoperative short- and medium-term health status is excellent, independent of the subtype of TAC, but the prevalence of repeated interventions due to recurrent stenosis is high.

Prenatal diagnosis, associated findings and postnatal outcome of fetuses with truncus arteriosus communis (TAC).

PURPOSE: To assess the spectrum of associated anomalies, the intrauterine course, postnatal outcome and management of fetuses with truncus arteriosus communis (TAC) METHODS: All cases of TAC diagnosed prenatally over a period of 8 years were retrospectively collected in two tertiary referral centers. All additional prenatal findings were assessed and correlated with the outcome. The accuracy of prenatal diagnosis was assessed. RESULTS: Thirty nine cases of TAC were diagnosed prenatally. Mean gestational age at first diagnosis was 22 weeks (range 13-38). Two cases were lost follow-up. Correct prenatal diagnosis of TAC was made in 87.5% and of TAC subtype in 90.5%. Prenatal diagnosis was incorrect in three cases: one newborn had aortic atresia with ventricular septal defect (VSD) postnatally, one had hypo-plastic right ventricle with dextro transposition of the great arteries (d-TGA) with coarctation of the aorta and a third newborn had tetralogy of fallot (TOF) with abnormal origin of the left pulmonary artery arising from the ascending aorta postnatally. These 3 cases were excluded from further analysis. In 26.5% of cases, TAC was an isolated finding. 38.2% of fetuses had additional chromosomal anomalies. Among them, microdeletion 22q11.2 was most common with a prevalence of 17.6% in our cohort. Another 3 fetuses were highly suspicious for non-chromosomal genetic syndromes due to their additional extra-cardiac anomalies, but molecular diagnosis could not be provided. Major cardiac and extra-cardiac anomalies occurred in between 8.8% and 58.8%, respectively. Predominantly, extra-cardiac anomalies occurred in association with chromosomal anomalies. Additionally, severe IUGR occurred in 17.6%. There were 14 terminations of pregnancy (41.2%), 1 (2.9%) intrauterine fetal death, 5 postnatal deaths (14.7%) and 14 (41.2%) infants were alive at last follow-up. Intention-to-treat survival rate was 70%. Mean follow-up among survivors was 42 months (range 6-104). Postoperative health status among survivors was excellent in 78.6%, but 46.2% needed repeated re-interventions due to recurrent pulmonary artery or conduit stenosis. The other 21.4% of survivors were significantly impaired due to non-cardiac problems. CONCLUSION: Truncus arteriosus communis is a rare and complex cardiac anomaly that can be diagnosed prenatally with high precision. TAC is frequently associated with chromosomal and extra-cardiac anomalies, leading to a high intrauterine and postnatal loss rate due to terminations and perioperative mortality. Without severe extra-cardiac anomalies, postoperative health status is excellent, independent of the subtype of TAC, but the prevalence of repeated interventions due to recurrent stenosis is high.

Outcome of pregnancies with recent primary cytomegalovirus infection in first trimester treated with hyperimmunoglobulin: observational study.

OBJECTIVE: To examine the efficacy of hyperimmunoglobulin (HIG) treatment in women with a recent primary cytomegalovirus (CMV) infection up to 14 weeks' gestation. METHODS: This is an ongoing observational study conducted at the prenatal medicine departments of the University Hospitals of Tübingen, Bonn, Cologne and Erlangen, Germany, as well as at the Laboratory Prof. Gisela Enders and Colleagues in Stuttgart, Germany and the Institute for Medical Virology at the University of Tübingen, Tübingen, Germany. Enrolment criteria were the presence of confirmed recent primary CMV infection in the first trimester and a gestational age at first HIG administration of ≤ 14 weeks. The following inclusion criteria indicated a recent primary infection: low anti-immunoglobulin (Ig)-G levels, low anti-CMV-IgG avidity in the presence of a positive CMV-IgM test and no positive reactivity or just seroconversion anti-gB2-IgG-reactivity. HIG administration was started as soon as possible within a few days after the first visit. HIG was administered intravenously at a dose of 200 IU/kg maternal body weight and repeated every 2 weeks until about 18 weeks' gestation. The primary outcome was maternal-fetal transmission at the time of amniocentesis. Multivariate logistic regression analysis was used to determine significant covariates that could predict maternal-fetal transmission. RESULTS: We included 149 pregnancies (153 fetuses) that completed the treatment. Median maternal age and weight were 32.0 years and 65.0 kg, respectively. Median gestational age at the time of first referral to one of the four centers was 9.4 weeks. Median anti-CMV-IgG level, anti-CMV-IgM index and CMV-IgG avidity were 5.7 U/mL, 2.5 and 22.3%, respectively. HIG treatment was started at a median gestational age of 10.6 weeks and ended at a median of 17.9 weeks. Within this time frame, HIG was administered on average four times in each patient. Amniocentesis was carried out at a median gestational age of 20.4 weeks. In 143 (93.5%) of the 153 cases, the fetus was not infected. Maternal-fetal transmission occurred in 10 cases (6.5% (95% CI, 3.2-11.7%)). On uni- and multivariate logistic regression analysis, the level of anti-IgM index was the only factor associated significantly with maternal-fetal transmission at amniocentesis. However, only four (40.0%) of the 10 cases with maternal-fetal transmission had an anti-IgM index above 11.4, which corresponds to the 95th centile of pregnancies without transmission. CONCLUSIONS: HIG is a treatment option to prevent maternal-fetal transmission in pregnancy with a primary CMV infection. However, HIG treatment seems to be beneficial primarily in women with a recent primary infection in the first trimester or during the periconceptional period, and when it is administered at a biweekly dose of 200 IU/kg. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal diagnosis, associated findings and postnatal outcome in fetuses with congenitally corrected transposition of the great arteries.

PURPOSE: To analyze anatomic features and associated malformations in 37 prenatally detected cases of congenitally corrected transposition of the great arteries (ccTGA) and to evaluate the prenatal course, neonatal outcome and mid-term follow-up. METHODS: Retrospective analysis of prenatal ultrasound of 37 patients with ccTGA in two tertiary centers between 1999 and 2019. All fetuses received fetal echocardiography and a detailed anomaly scan. Postnatal outcome and follow-up data were retrieved from pediatric reports. RESULTS: Isolated ccTGA without associated cardiac anomalies was found in 13.5% (5/37), in all other fetuses additional defects such as VSD (73.0%), pulmonary obstruction (35.1%), tricuspid valve anomalies (18.9%), aortic arch anomalies (13.5%), ventricular hypoplasia (5.4%) or atrioventricular block (5.4%) were present. The rate of extracardiac malformations or chromosomal aberrations was low. There were 91.9% (34/37) live births and postnatal survival rates reached 91.2% in a mean follow-up time of 4.98 years. The prenatal diagnosis of ccTGA was confirmed postnatally in all but one documented live birth and the prenatal counselling regarding the expected treatment after birth (uni- versus biventricular repair) was reassured in the majority of cases. The postnatal intervention rate was high, 64.7% (22/34) received surgery, the intervention-free survival was 36.7%, 35.0% and 25.0% at 1 month, 1 year and 10 years, respectively. CONCLUSIONS: ccTGA is a rare heart defect often associated with additional heterogeneous cardiac anomalies that can be diagnosed prenatally. The presented study demonstrates a favorable outcome in most cases but the majority of patients require surgical treatment early in life.

Vesicoamniotic shunting for fetal megacystis in the first trimester with a Somatex® intrauterine shunt.

PURPOSE: The objective was to evaluate the feasibility of vesicoamniotic shunting (VAS) in the first trimester with the Somatex® intrauterine shunt and report on complications and neonatal outcome. METHODS: Retrospective cohort study of all VAS before 14 weeks at two tertiary fetal medicine centres from 2015 to 2018 using a Somatex® intrauterine shunt. All patients with a first trimester diagnosis of megacystis in male fetuses with a longitudinal bladder diameter of at least 15 mm were offered VAS. All patients that opted for VAS after counselling by prenatal medicine specialists, neonatologists and pediatric nephrologists were included in the study. Charts were reviewed for complications, obstetric and neonatal outcomes. RESULTS: Ten VAS were performed during the study period in male fetuses at a median GA of 13.3 (12.6-13.9) weeks. There were two terminations of pregnancy (TOP) due to additional malformations and one IUFD. Overall there were four shunt dislocations (40%); three of those between 25-30 weeks GA. Seven neonates were born alive at a median GA of 35.1 weeks (31.0-38.9). There was one neonatal death due to pulmonary hypoplasia. Neonatal kidney function was normal in the six neonates surviving the neonatal period. After exclusion of TOP, perinatal survival was 75%, and 85.7% if only live-born children were considered. CONCLUSION: VAS in the first trimester is feasible with the Somatex® Intrauterine shunt with low fetal and maternal complication rates. Neonatal survival rates are high due to a reduction in pulmonary hypoplasia and the rate of renal failure at birth is very low. VAS can be safely offered from the late first trimester using the Somatex® intrauterine shunt.

First-trimester intervention in twin reversed arterial perfusion sequence: does size matter?

OBJECTIVE: To evaluate the outcome of first-trimester intervention (12 + 0 to 14 + 0 weeks of gestation) in pregnancies complicated by twin reversed arterial perfusion (TRAP) sequence. METHODS: All monochorionic diamniotic twin pregnancies diagnosed with TRAP sequence that underwent intrafetal laser ablation (IFL) of the feeding vessels before 14 + 0 weeks of gestation at the University of Bonn between 2010 and 2015 were analyzed retrospectively for intrauterine course and outcome. RESULTS: In the study period, 12 pregnancies with TRAP sequence were treated by IFL. Median gestational age at intervention was 13.2 (interquartile range (IQR), 12.6-13.6) weeks. In all cases, one intervention sufficed to disrupt the perfusion of the TRAP twin. There was no case of miscarriage, preterm prelabor rupture of membranes or hemorrhage. In five (41.7%) pregnancies, intrauterine death of the pump twin occurred at a median of 72.0 (IQR, 54.0-90.0; range, 48-96) h after intervention. The remaining seven pregnancies continued uneventfully resulting in birth of a healthy infant at term. A comparison of survivors and non-survivors identified a significant difference in median discordance between crown-rump length (CRL) of the pump twin and upper pole-rump length (URL) of the TRAP twin ((CRL - URL)/CRL ratio, 0.56 vs 0.31; P < 0.05 and URL/CRL ratio, 0.44 vs 0.68; P < 0.05). Survivors were treated at a significantly later gestational age than were non-survivors (median, 13.4 (IQR, 12.9-14.1) vs 12.6 (IQR, 12.5-13.1); P < 0.05). However, none of these parameters independently predicted survival. CONCLUSIONS: Although technically feasible, IFL performed in the first trimester for TRAP sequence is associated with a significant fetal loss rate. Gestational age at intervention, (CRL - URL)/CRL ratio and URL/CRL ratio are potential predictors of pregnancy outcome. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal diagnosis of absent pulmonary valve syndrome from first trimester onwards: novel insights into pathophysiology, associated conditions and outcome.

OBJECTIVE: To assess the spectrum of associated anomalies, intrauterine course and outcome in fetuses with absent pulmonary valve syndrome (APVS). METHODS: All cases with a prenatal diagnosis of APVS at two centers over a period of 13 years were analyzed retrospectively. APVS was diagnosed in the presence of rudimentary or dysplastic pulmonary valve leaflets with to-and-fro blood flow in the pulmonary trunk on color and pulsed-wave Doppler ultrasound. Data on demographic characteristics, presence of associated conditions, Doppler studies and pregnancy outcome were reviewed. RESULTS: During the study period, 40 cases of APVS were diagnosed prenatally. Thirty-seven (92.5%) cases were associated with tetralogy of Fallot (TOF) and three (7.5%) had an intact ventricular septum. Patency of the ductus arteriosus (DA) was found in 17/37 (45.9%) TOF cases and in all three cases with an intact ventricular septum. Mean gestational age at diagnosis was 19.7 (range, 12-34) weeks with 10 (25.0%) cases (all with TOF) diagnosed in the first trimester. TOF was an isolated finding in 15 (37.5%) cases. Chromosomal anomalies, cardiac defects and extracardiac anomalies were present in 18 (45.0%), four (10.0%) and three (7.5%) cases, respectively. Among the 40 cases, there were 19 (47.5%) terminations of pregnancy, six (15.0%) intrauterine deaths, four (10.0%) neonatal deaths and 11 (27.5%) survivors. Patency of the DA, reversed flow during atrial contraction in the ductus venosus, umbilical artery or fetal middle cerebral artery, and hydrops/increased nuchal translucency thickness were significantly associated with non-survival. All 10 cases diagnosed in the first trimester had a patent DA and abnormal Doppler parameters, eight had hydrops and/or increased nuchal translucency, six were associated with trisomy 13 or 18 and none survived. CONCLUSION: APVS diagnosed in the first trimester is significantly associated with TOF, patency of the DA, abnormal Doppler parameters, lethal trisomies and intrauterine mortality. Cases of APVS with isolated TOF and agenesis of the DA have a better outcome than those with additional anomalies, with > 80% survival. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Intrauterine vesicoamniotic shunting for fetal megacystis.

OBJECTIVE: To examine the outcome of fetuses with megacystis treated with vesicoamniotic shunting (VAS) from 14 weeks onward. METHODS: Retrospective review of all fetuses that received VAS at two centres from 2004 to 2012. RESULTS: 53 fetuses with megacystis were included in the study. Mean gestational age at diagnosis was 16.4 weeks. Mean gestational age at first shunt placement was 17.8 weeks. The first shunt placement was performed before 16 weeks in 18 (34 %) cases. The mean number of shunts was 1.38. Dislocation occurred in 35 (66 %). TOP was performed in 21 (39.6 %), intrauterine death occurred in two (3.8 %) and spontaneous abortion in three cases (5.7 %). Of the 27 (50.9 %) live births, 17 (32.1 %) infants survived. Normal renal function was present in 10 cases, 4 have compensated renal failure and 3 infants had renal transplantation. Oligohydramnios was significantly associated with non-survival and renal insufficiency. The gestational age at VAS was neither correlated with renal function after birth nor with the survival in our cohort. Conversely, the interval between first shunt placement and delivery was positively correlated with survival and normal renal function. The gestational age at delivery was significantly higher in survivors and those born with normal renal function. CONCLUSION: Despite intervention, the morbidity and mortality of megacystis is still high. We failed to demonstrate that early intervention is associated with an improved rate of normal renal function after birth. Oligohydramnios was the only parameter identifying fetuses with unfavourable outcome, while all other parameters were inconclusive.

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.

Bronchopulmonary sequestration with massive pleural effusion: pleuroamniotic shunting vs intrafetal vascular laser ablation.

OBJECTIVE: To assess the incidence of complications among a relatively large cohort of fetuses with bronchopulmonary sequestration (BPS) and the success of two different intrauterine treatment modalities. METHODS: All cases with a prenatal diagnosis of BPS detected in a 10-year period (2002-2011) in two tertiary referral centers were reviewed retrospectively for intrauterine course and outcome. Up to May 2010 severe pleural effusions were treated with pleuroamniotic shunting. Thereafter, they were treated with ultrasound-guided laser coagulation of the feeding artery. RESULTS: A total of 41 fetuses with BPS were included in the study. In 29 (70.7%) there was no pleural effusion or hydrops and they were treated conservatively. In 19/29 (65.5%) there was partial or complete regression of the lesion during the course of pregnancy. All were born alive (median age at delivery, 38.3 (interquartile range (IQR), 34.0-39.6) weeks) and 16 (55.2%) required sequestrectomy. Intrauterine intervention was performed in all 12 (29.3%) fetuses with pleural effusion. Seven fetuses were treated with pleuroamniotic shunting. One fetus with severe hydrops died in utero. There was no complete regression in any case of BPS in this group. Six infants were born alive (median age, 37.2 (IQR, 30.3-37.4) weeks), of which five (83.3%) required sequestrectomy. Five fetuses were treated with laser ablation of the feeding vessel. In all cases of BPS there was regression after laser ablation. All infants were delivered at term (median age, 39.1 (IQR, 38.0-40.0) weeks). One (20.0%) neonate required sequestrectomy after birth. Following intrauterine shunt placement complete regression of the lesion was significantly less frequent (0/7 (0%) with shunt placement vs 4/5 (80%) with intrafetal laser treatment) and gestational age at birth was significantly lower, compared to treatment with intrafetal laser. Complete regression of the lesion was also significantly more frequent in the laser group compared to cases without intervention. CONCLUSION: In the absence of pleural effusion, the likelihood of spontaneous regression of BPS is high and the prognosis is therefore favorable. In cases with massive pleural effusion, treatment by laser ablation of the feeding vessel seems to be more effective than is pleuroamniotic shunting, with fewer complications. It might also reduce the need for postnatal surgery.

Early vs late intervention in twin reversed arterial perfusion sequence.

OBJECTIVE: To compare two different management approaches in prenatally diagnosed twin reversed arterial perfusion (TRAP) sequence. METHODS: Retrospective analysis of all cases with TRAP sequence diagnosed in one center over a period of 10 years. Prior to 2010, all cases were managed expectantly until 19 weeks' gestation; thereafter, patients could choose either radiofrequency ablation (RFA) or expectant management (Group A). From 2010 onward all patients were offered interstitial laser at the time of diagnosis (12 weeks at the earliest) or expectant management (Group B). RESULTS: Forty cases were included in the study. In Group A, 23 cases were diagnosed at a mean gestational age of 19.9 ± 6.3 weeks. Sixteen patients were managed expectantly (13 survivors, 81%), while six underwent RFA at the time of diagnosis and one later in pregnancy (six survivors, 86%). In Group B, 17 cases were diagnosed at a mean gestational age of 16.4 ± 4.7 weeks. Six patients chose expectant management (five survivors, 83%) and 11 had interstitial laser therapy at the time of diagnosis (eight survivors, 73%). The loss rate of the pump twin was not significantly different between Group A and Group B (three of 23 vs four of 17; P = 0.3). In Group B the rates of preterm premature rupture of membranes (PPROM) and delivery < 34 weeks were significantly lower, and gestational age at birth as well as birth weight were significantly higher than in Group A. CONCLUSION: Despite the limitations resulting from its retrospective design, our study on management of TRAP sequence adds some evidence in favor of prophylactic intervention by intrafetal laser from 12 weeks onward.

[Disorders of laterality and heterotaxy in the foetus]. / Fetale Lageanomalien und Heterotaxien.

Disorders of laterality and heterotaxy syndromes are rare diseases with an incidence of 1-1.5/10,000 live births. They are associated with numerous viscerocardiac anomalies and malformations. In particular, heterotaxy syndromes are associated with complex cardiac and extracardiac malformations that have an important impact on the prenatal and postnatal course. A prenatal differentiation between the 2 main variants of heterotaxy--left and right isomerism--is possible by assessment of cardiac rhythm, anomalies of caval veins and descending aorta and concomittant cardiac and extracardiac anomalies. An exact diagnosis is mandatory for adequate counselling of the parents and planning of postnatal care. Left isomerism has a high intrauterine mortality, caused by early atrioventricular block with subsequent cardiac failure and hydrops. In contrast, right isomerism has a high postnatal mortality due to the more complex type of cardiac defects and splenic disorders. The type of associated cardiac and extracardiac anomalies determines the postnatal morbidity and mortality. Polysplenia and asplenia may be associated with immunological disorders, that cannot be ruled out in the prenatal period, and further complicate the postnatal course.

Conversion between two cytochalasin B-binding states of the human GLUT1 glucose transporter.

Two cytochalasin B-binding states of the human red blood cell facilitative glucose transporter GLUT1 were studied, one exhibiting one cytochalasin B-binding site on every second GLUT1 monomer (state 1) and the other showing one site per monomer (state 2). Quantitative affinity chromatography of cytochalasin B was performed on (a) biotinylated red blood cells, (b) cytoskeleton-depleted red blood cell membrane vesicles, and (c) GLUT1 proteoliposomes. The cells were adsorbed on streptavidin-derivatized gel beads, and the vesicles and proteoliposomes entrapped in dextran-grafted agarose gel beads. Cytochalasin B binding to free vesicles and proteoliposomes was analyzed by Hummel and Dreyer size-exclusion chromatography and ultracentrifugation. Analysis of the biotinylated cells indicated an equilibrium between the two GLUT1 states. GLUT1 in free membrane vesicles attained state 2, but was converted into state 1 on entrapment of the vesicles. Purification of GLUT1 in the presence of non-ionic detergent followed by reconstitution produced GLUT1 in state 1. This state was maintained after entrapment of the proteoliposomes. Finally, GLUT1 showed slightly higher affinity for cytochalasin B in state 1 than in state 2. In summary, the cytochalasin B-binding state of GLUT1 seemed to be affected by (a) biotinylation of the cell surface, (b) removal of the cytoskeleton at high pH and low ionic strength, (c) interaction between the dextran-grafted agarose gel matrix and the membrane vesicles, and (d) reconstitution to form proteoliposomes.

Chromatography on cells: analyses of solute interactions with the glucose transporter Glut1 in human red cells adsorbed on lectin-gel beads.

The affinities of the human red cell glucose transporter Glut1 for D-glucose and cytochalasin B (CB) and the stoichiometry of CB binding vary with the Glut1 environment. In order to study the native state of Glut1 we adsorbed human red cells to wheat germ lectin agarose gel beads for frontal affinity chromatographic analyses. Glut1 showed relatively high affinities for D-glucose (Kd 12+/-1 mM) and CB (Kd 59+/-17 nM). The number of CB-binding sites per Glut1 monomer, 0.46+/-0.16, was approximately doubled upon coating the cells with polylysine, which induced cell association.

Chromatographic approaches to liposomes, proteoliposomes and biomembrane vesicles.

Size-exclusion chromatography has been used for fractionation of liposomes, proteoliposomes and biomembrane vesicles of up to approximately 500 nm in size and for separation of these entities from smaller components. Liposome sizes, encapsulation stability, and solute affinities for membrane proteins have been determined. Counter-current distribution in aqueous two-phase systems has widened the range of applications to larger structures. Immobilized biomembrane vesicles and (proteo)liposomes provide stationary phases for chromatographic analysis of specific or nonspecific membrane-solute interactions.