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Fetal megacystis (MC) can be severe and is mainly caused by fetal lower urinary tract obstruction (LUTO). Mortality of fetal LUTO can be high as a result of pulmonary hypoplasia and/or (chronic) renal insufficiency. Several technical procedures for vesicoamniotic shunting (VAS) were developed to improve fetal MC outcomes.We present the outcome of nine fetuses with MC who received VAS in the prenatal period (14 + 6 to 27 + 6 weeks GA) using the SomatexEight Fetuses had uncomplicated VAS intervention. One case developed PPROM 24 h after VAS leading to abortion. Pregnancy was later terminated in further two cases. All six live-born infants received intensive care treatment. Invasive-mechanical ventilation was necessary in one case who died 24 h post-partum of severe cardiac depression. Five infants who survived the follow-up time developed chronic renal insufficiency (CRI), with one infant developing end-stage renal failure requiring peritoneal dialysis.Overall, 5 of 9 LUTO fetuses (55%) undergoing VAS with the Somatex

Introduction A case of spontaneous fetal bladder rupture occurring in a woman with SARS-CoV-2 pneumonia receiving invasive ventilatory support is reported. Case A 33-year-old woman was admitted at 30.6 weeks' gestation with the diagnosis of severe pneumonia due to COVID-19. The patient required invasive mechanical ventilation on day 2. Propofol, fentanyl, midazolam, and dexmedetomidine were administered for sedation, pain relief, and to improve patient-ventilator interaction. A bedside ultrasound on day 3 revealed fetal megacystis. Follow-up scan two days later showed urinary ascites and a collapsed bladder. The diagnosis of fetal bladder rupture was confirmed postpartum. Bladder repair was performed on day 5, with an uneventful recovery. Discussion Transplacental transfer of opioids during invasive ventilatory support in pregnancy may cause acute fetal bladder atony leading to severe urine retention and, potentially, bladder rupture. This can be a serious complication of adjunctive therapy in women with severe SARS-CoV-2 pneumonia.

Objectives: Fetal megacystis is very rare; however this problem may be associated with other structural or chromosomal abnormalities leading to morbidity and mortality. Due to renal injury and pulmonary hypoplasia, prognosis is poor especially in fetuses with early onset oligohydramnios. In this study, we evaluated the management strategies and outcomes of fetal megacystis in our hospital.Study Design: The data of cases who were prenatally diagnosed with megacystis between 1 January 2017 and 31 December 2019 were analyzed. Ultrasonography findings and antennal interventions were withdrawn from computerized database. Information about postpartum status was also received. The data were analyzed in terms of diagnostic methods, fetal interventions (vesicosynthesis (VS), vesicoamniotic shunt (VAS)), potential prognostic markers and short/long-term prognostic results.Results: A total of 15 megacystis patients were detected. One of the fetuses was female and the remaining cases were male. Six of the patients were isolated. Ten patients underwent invasive procedures for prenatal aneuploidy diagnosis and one of them diagnosed with trisomy 18. Totally, 4 patients underwent VS; however no VAS was recorded. Four fetuses were terminated and intrauterine fetal demise occurred in 2 fetuses. Four patients were lost during follow up. Survival rate was 33.3%.Conclusion: Fetal megacystis is an important ultrasonographic finding which may be a component of chromosomal / genetic anomalies. This problem may also be isolated in some cases. Because of the poor outcome, parents should be well informed and all interventions should be offered to families.

OBJECTIVES To evaluate aneuploidy rate, prognostic factors, and perinatal outcomes following a diagnosis of fetal megacystis at 11-14 week's gestation. METHODS A retrospective study of first trimester fetal megacystis from 2010 to 2020 was performed, including ultrasound finding, perinatal outcomes, pathology reports, genetic tests, and neonatal investigations. RESULTS A total of 98 cases of first trimester fetal megacystis was identified with an overall aneuploidy rate of 12%. There were 54% live births and 46% fetal losses including spontaneous fetal demise and elective termination. Among the 45 fetal losses, 64% had additional structural abnormalities at index ultrasound and final diagnoses were achievable in 64% cases. Among the 53 livebirths, additional ultrasound abnormalities were detected in only 1 fetus and spontaneous resolution of megacystis was detected in 96% of cases. The two cases where fetal megacystis persisted had major postnatal diagnoses: cloacal malformation and megacystis-microcolon-intestinal hypoperistalsis syndrome, respectively. Our data showed LBD ≥ 12 mm was the best individual predictor of adverse perinatal outcome and all 11 cases of lower urinary tract obstruction (LUTO) were diagnosed in fetuses with LBD ≥ 12 mm. CONCLUSIONS First trimester ultrasound provides important prognostic factors and isolated megacystis

Megacystis-microcolon-intestinal-hypoperistalsis syndrome (MMIHS) is a severe congenital visceral myopathy characterized by an abdominal distension due to a large non-obstructed urinary bladder, a microcolon and intestinal hypo- or aperistalsis. Most of the patients described to date carry a sporadic heterozygous variant in ACTG2. More recently, recessive forms have been reported and mutations in MYH11, LMOD1, MYLK and MYL9 have been described at the molecular level. In the present report, we describe five patients carrying a recurrent heterozygous variant in ACTG2. Exome sequencing performed in four families allowed us to identify the genetic cause in three. In two families, we identified variants in MMIHS causal genes, respectively a nonsense homozygous variant in MYH11 and a previously described homozygous deletion in MYL9. Finally, we identified compound heterozygous variants in a novel candidate gene, PDCL3, c.[143_144del];[380G>A], p.[(Tyr48Ter)];[(Cys127Tyr)]. After cDNA analysis, a complete absence of PDLC3 expression was observed in affected individuals, indicating that both mutated transcripts were unstable and prone to mediated mRNA decay. PDCL3 encodes a protein involved in the folding of actin, a key step in thin filament formation. Presumably, loss-of-function of this protein affects the contractility of smooth muscle tissues, making PDCL3 an excellent candidate gene for autosomal recessive forms of MMIHS.

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.

Los primeros procedimientos fetales considerados quirúrgicos fueron realizados en 1961, por Liley, al transfundir sangre a fetos con anemia por isoinmunización Rh. En 1974, se realizó la primera fetoscopia diagnóstica, en la Universidad de Yale, EE. UU. Un hito histórico sucede en 1981, cuando Harrison en la Universidad de California realizó por primera vez drenaje en un caso de mega vejiga causado por valva uretral; colocó, bajo control ecográfico, un catéter desde la vejiga a la cavidad amniótica. Por este hecho, se le reconoce como el ‘padre de la cirugía fetal’. En 1982, se reunieron especialistas de 5 países, vinculados a la cirugía fetal, y liderados por Harrison publicaron las primeras normas a regir en este campo nuevo de la medicina. Posteriormente, grupos colaborativos europeos revisaron las aplicaciones de esta cirugía, así como las normas éticas y de seguridad que debían ser prioritarias en estas técnicas. En el 2011, instituciones académicas y de ética de los EE. UU. reafirmaron los principios, ya reconocidos, en los que debían basarse los nuevos centros de alta calidad en cirugía fetal. En 2015, se establecieron las reglas para la innovación tecnológica y la investigación en este campo, remarcando la necesidad de crear los comités de ética. En el 2017, los especialistas involucrados, nuevamente convocados por organizaciones académicas de los EE. UU., emitieron opinión sobre el contexto global de esta cirugía, las obligaciones éticas, de infraestructura, implementación tecnológica, investigación conjunta y capacitación integral del equipo; remarcaron la necesidad de crear los comités de supervisión en estos centros. En América Latina, el desarrollo de la cirugía fetal se encuentra en una etapa intermedia, de acuerdo a los reportes actuales. En el Perú, se ha publicado artículos sobre los primeros casos de cirugía prenatal.

Objective To explore the outcomes and prognostic factors associated with fetal megacystis (enlarged bladder). Study design The MEDLINE and EMBASE databases were searched for studies reporting on outcomes of fetal megacystis. The outcomes observed were chromosomal abnormalities, associated structural anomalies, spontaneous resolution, and survival rates. We also evaluated the potential role of fetal gender, oligohydramnios, gestational age at diagnosis, and intrauterine intervention as prenatal prognostic factors. Results The search identified 558 articles in total, and 13 studies (1675 fetuses) were included in this systematic review. The overall incidences of chromosomal abnormalities and associated structural anomalies in fetal megacystis were 10% and 24%, respectively. Spontaneous resolution of megacystis occurred in 32% of fetuses, and 44% of fetuses were born alive and survived until the follow-up. The odds ratio of survival with oligohydramnios was 0.14, and the mean difference in gestational age at diagnosis between survival and non-survival was 3.43 weeks. No significant difference in survival rate was observed between the genders, and an intrauterine intervention did not significantly improve the prognosis. Conclusions A considerable proportion of fetuses with megacystis are born with a good prognosis. Oligohydramnios and lower gestational age at diagnosis are associated with worse outcomes.

OBJECTIVE To construct reference values for fetal urinary bladder distension in pregnancy and use Z-scores as a diagnostic tool to differentiate posterior urethral valves (PUV) from urethral atresia (UA). METHODS This was a prospective cross-sectional study in healthy singleton pregnancies aimed at constructing nomograms of fetal urinary bladder diameter and volume between 15 and 35 weeks' gestation. Z-scores of longitudinal bladder diameter (LBD) were calculated and validated in a cohort of fetuses with megacystis with ascertained postnatal or postmortem diagnosis, collected from a retrospective, multicenter study. Correlations between anatomopathological findings, based on medical examination of the infant or postmortem examination, and fetal megacystis were established. The accuracy of the Z-scores was evaluated by receiver-operating-characteristics (ROC)-curve analysis. RESULTS Nomograms of fetal urinary bladder diameter and volume were produced from three-dimensional ultrasound volumes in 225 pregnant women between 15 and 35 weeks of gestation. A total of 1238 urinary bladder measurements were obtained. Z-scores, derived from the fetal nomograms, were calculated in 106 cases with suspected lower urinary tract obstruction (LUTO), including 76 (72%) cases with PUV, 22 (21%) cases with UA, four (4%) cases with urethral stenosis and four (4%) cases with megacystis-microcolon-intestinal hypoperistalsis syndrome. Fetuses with PUV showed a significantly lower LBD Z-score compared to those with UA (3.95 vs 8.83, P

Objective To propose a clinical score for the optimal antenatal diagnosis of fetal lower urinary tract obstruction (LUTO) in the second and third trimesters of pregnancy, as an alternative to the commonly used ultrasound triad of megacystis, keyhole sign and hydronephrosis.Methods This was a national retrospective study carried out at the eight tertiary fetal medicine units (FMUs) in The Netherlands. Only cases referred for megacystis from the second trimester onwards and with a clear postnatal diagnosis were included in the study. At referral, data were collected on amniotic fluid volume, renal cortical appearance, bladder volume, hydronephrosis, fetal ascites, ureteral size, keyhole sign, fetal sex and gestational age. Multivariate analysis was performed, starting by including all antenatal variables, and then excluding the weakest predictors using the backward stepwise strategy.Results Over a 7-year period, 312 fetuses with a diagnosis of megacystis were referred to the eight Dutch tertiary FMUs. A final diagnosis was achieved in 143 cases, including 124 of LUTO and 19 reclassified after birth as non-obstructive megacystis. The optimal bladder volume cut-off for prediction of LUTO was 35 cm(3) (area under the curve (AUC) = 0.7, P = 0.03). The clinical score formulated on the basis of the multivariate analysis included fetal sex, degree of bladder distension, ureteral size, oligo-or anhydramnios and gestational age at referral. The combination of these five variables demonstrated good accuracy in discriminating LUTO from non-obstructive megacystis (AUC = 0.84, P Conclusions We propose a clinical score that combines five antenatal variables for the prospective diagnosis of congenital LUTO. This score showed good discriminative capacity in predicting LUTO, and better diagnostic accuracy compared with that of the classic ultrasound triad. Future studies to validate these results should be carried out in order to refine antenatal management of LUTO and prevent inappropriate fetal interventions. (C) 2017 The Authors.

Objective: To evaluate the best management of fetal megacystis diagnosed in the first trimester and define the prognosis and the most appropriate follow-up as early as possible. Methods: This is a retrospective study of first-trimester fetal megacystis diagnosed in pregnant women who performed a combined screening for fetal aneuploidy. Megacystis was defined as a longitudinal bladder diameter (LBD) greater than 7 mm. All fetuses were divided into two groups according to the LBD: Group A with LBD > 15 mm and Group B with LBD Results: Twenty-six cases were identified between 2011 and 2016; three cases of aneuploidy were excluded from the study. Of the remaining 23 cases, 11 were included in Group A and 12 in Group B. All Group A fetuses had an adverse outcome. In Group B: five (41.7%) cases had an adverse outcome and seven (58.3%) had a spontaneous resolution of megacystis. The ultrasound findings of both the ultrasound scans, the second and the third, were 100% concordant. Conclusion: An ultrasound scan performed 2 weeks after the megacystis diagnosis can predict the outcome in fetuses with an LBD

To assess prenatal prognostic criteria for fetuses with megacystis in order to counsel parents. In a retrospective observational study at a single tertiary referral center, we assessed the clinical course of 53 fetuses with megacystis cared for at the Department of Obstetrics of the University Hospital Zurich between 1995 and 2008 and followed them up for 2 to 12 years. We determined fetal karyotype, amniotic fluid volume and fetal urinary biochemistry as prenatal prognostic factors. The renal function of survivors was grouped according to age-related creatinine values. Using logistic regression analysis, gestational age-dependent discrimination curves and corresponding ROC curves for fetal urine, beta-2 microglobulin, osmolarity and chloride were calculated. 43 out of 53 fetuses underwent vesicocentesis, and spontaneous remission occurred in 3 fetuses. 15 fetuses survived, termination of pregnancy was requested in 23 cases, and 12 neonatal and 3 intrauterine deaths were observed. Reduced amniotic fluid volume showed a significant (p = 0.0027) increase of impaired renal function or perinatal death. Discrimination between survivors and non-survivors was complete for fetal urine beta-2 microglobulin with an area under the curve (AUC) of 1.0. For fetal urine osmolarity and fetal urinary chloride, the AUC was 0.81 and 0.76, respectively. The assessment of prognosis for fetal megacystis should include fetal k aryotyping, determination of amniotic fluid and assessment of fetal urine biochemistry. Gestational age-dependent regression lines disclose clinically relevant discrimination and can be used as selection criteria for fetal interventions and parental counselling.ZIEL: Zur Beratung der Eltern, deren Feten eine Megavesika aufweisen, sollen prognostische Kriterien evaluiert werden. In einer retrospektiven Beobachtungsstudie am Perinatalzentrum des Universitätsspitals Zürich wurden zwischen 1995 und 2008 53 Feten mit Megavesika betreut und für 2 bis 12 Jahre nachuntersucht. Als Prognosefaktoren wurden der fetale Karyotyp, die Fruchtwassermenge und die Biochemie des fetalen Urins bestimmt. Die Nierenfunktion der Überlebenden wurde aufgrund der altersabhängigen Kreatininwerte klassiert. Mittels logistischer Regression wurden schwangerschaftsalterabhängige Regressionskurven und die zugehörigen ROC-Kurven für das fetale beta-2 Mikroglobulin im Urin, die Urin-Osmolarität und das Urin-Chlorid bestimmt. 43 von 53 Feten wurden einer Vesicozentese unterzogen und in 3 Fällen kam es zu einer Spontanremission. 15 Feten überlebten, ein Schwangerschaftsabbruch wurde in 23 Fällen durchgeführt und 12 neonatale und 3 intrauterine Todesfälle wurden beobachtet. Eine verminderte Fruchtwassermenge war signifikant (p = 0.0027) mit einer verminderten Nierenfunktion oder einem perinatalen Tod assoziiert. Die Trennung von Überlebenden und Nicht-Überlebenden war mittels fetalem Urin beta-2 Mikrogloblulin bei einer Fläche unter der Kurve (AUC) von 1,0 komplett möglich. Für die fetale Urin-Osmolarität wurde eine AUC von 0.81 und das fetale Urin-Chlorid von 0.76 kalkuliert. Zur Prognoseeinschätzung bei fetaler Megavesika sollten eine fetale Karyotypisierung, die Bestimmung der Fruchtwassermenge und die Analyse der fetalen Urinbiochemie erfolgen. Schwangerschaftsalterabhängige Regressionskurven ermöglichen eine klinisch hilfreiche Trennung zwischen Überlebenden und Nicht-Überlebenden und sind somit wertvolle Kriterien für die Indikationsstellung vor fetalen Interventionen und zur Beratung der Eltern.

Objectives: To investigate the natural history of fetal megacystis from diagnosis in utero to postnatal outcome, and to identify prognostic indicators of spontaneous resolution and postnatal outcome after resolution. Methods: This was a national retrospective cohort study. Fetal megacystis was defined in the first trimester as a longitudinal bladder diameter (LBD) ≥ 7 mm, and in the second and third trimesters as an enlarged bladder failing to empty during the entire extended ultrasound examination. LBD and gestational age (GA) at resolution were investigated with respect to likelihood of resolution and postnatal outcome, respectively. Sensitivity, specificity and area under the receiver–operating characteristics curve (AUC) were calculated. Results: In total, 284 cases of fetal megacystis (93 early megacystis, identified before the 18th week, and 191 late megacystis, identified at or after the 18th week) were available for analysis. Spontaneous resolution occurred before birth in 58 (20%) cases. In cases with early megacystis, LBD was predictive of the likelihood of spontaneous resolution (sensitivity, 80%; specificity, 79%; AUC, 0.84), and, in the whole population, GA at regression was predictive of postnatal outcome, with an optimal cut-off at 23 weeks (sensitivity, 100%; specificity, 82%; AUC, 0.91). In the group with early megacystis, the outcome was invariably good when resolution occurred before the 23rd week of gestation, whereas urological sequelae requiring postnatal surgery were diagnosed in 3/8 (38%) cases with resolution after 23 weeks. In the group with late megacystis, spontaneous resolution was associated with urological complications after birth, ranging from mild postnatal hydronephrosis in infants with resolution before 23 weeks, to more severe urological anomalies requiring postnatal surgery in those with resolution later in pregnancy. This supports the hypothesis that an early resolution of megacystis is often related to a paraphysiological bladder enlargement that resolves early in pregnancy without consequences, while antenatal resolution occurring later in pregnancy (after the 23rd week of gestation) should suggest a pathological condition with urological sequelae. Conclusions: In fetal megacystis, LBD and GA at regression can be used as predictors of resolution and outcome, respectively. These parameters could help in fine-tuning the prognosis and optimizing the frequency of follow-up scans.

Summary Fetal megacystis is variably defined and understood. The literature on fetal megacystis was systematically reviewed, focusing on prenatal diagnosis, associations and outcomes. This yielded a total of 18 primary references and eight secondary references. Fetal megacystis has an estimated first-trimester prevalence of between 1:330 and 1:1670, with a male to female ratio of 8:1. In the first trimester, megacystis is most commonly defined as a longitudinal bladder dimension of ≥7 mm. Later in pregnancy, a sagittal dimension (in mm) greater than gestational age (in weeks) + 12 is often accepted. Megacystis can be associated with a thickened bladder wall, which has been objectively defined as >3 mm. Oligohydramnios is present in approximately half of all cases. The most common underlying diagnosis is posterior urethral valves (57%), followed by urethral atresia/stenosis (7%), prune belly syndrome (4%), megacystis-microcolon-intestinal-hypoperistalsis syndrome (MMIHS) (1%), and cloacal anomalies (0.7%). Karyotype anomalies are found in 15%, and include trisomy 18, trisomy 13 and trisomy 21. Ultrasound imaging alone is often insufficient to enable a definitive diagnosis, although it may indicate that a specific diagnosis is more likely. Overall, about 50% of reported fetuses with megacystis are terminated, but this proportion varies considerably between countries and over time. Prognostic stratification is evolving, with the most important factors being oligohydramnios, gestational age at diagnosis, degree of bladder enlargement, renal hyperechogenicity, karyotype, and sex. Conclusions This review demonstrated some consensus on the ultrasound criteria for defining fetal megacystis, and illustrated the spectrum of pathologies and their relative frequencies that can cause this condition. It also underlined important associated karyotype anomalies. To progress understanding of the natural history of enlarged fetal bladders, more accurate diagnostics are required, and risk stratification needs to be refined to facilitate prenatal counseling.

Congenital anomalies of the kidney and urinary tract (CAKUT) include isolated kidney malformations and urinary tract malformations. They have also been reported in Prune-Belly syndrome (PBS) and associated genetic syndromes, mainly 13, 18 and 21 trisomy. The AA focuses on bladder and urethral malformations, evaluating the structural and histological differences between two different cases of megacystis. Both bladders were examined by routine prenatal ultrasound screening and immunohistochemistry, comparing the different expression of smooth muscular actin (SMA), S100 protein and WT1c in megacystis and bladders of normal control from fetuses of XXI gestational age. Considering the relationship between the enteric nervous system and urinary tract development, the AA evaluated S100 and WT1c expression both in bladder and bowel muscular layers. Both markers were not expressed in the bladder and bowel of PBS associated with anencephaly. In conclusion, megacystis could be considered only a macroscopic definition, concerning the size of the fetal bladder rather than the embryologic origin, it may be a single or multiple malformation, the possible association with the bowel and/or encephalic malformations will decide the outcome and prognosis in fetal megacystis.

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a rare congenital disorder, acknowledged as the most debilitating form of chronic intestinal pseudoobstruction disorders. Because the disease is often fatal in the first years of life and the surviving individuals are dependent on supportive medical or surgical treatment, definite antenatal diagnosis is desirable. We report a case of prenatally diagnosed MMIHS and discuss the suspicious findings and diagnostic criteria that allow a rapid and definite prenatal diagnosis.

Monozygote Zwillinge gelten gemeinhin als „identische Klone“. Es gibt jedoch eine zunehmende Anzahl an Fallberichten uber diskordante eineiige Zwillinge und Ursachen fur Diskordanz werden vermehrt untersucht. Wir berichten uber monozygote Zwillingsfruhgeborene, diskordant fur die seltene fetale Megazystis bei Kloakenfehlbildung. Durch Konzeption mittels intrazytoplasmatischer Spermieninjektion entstand nach Transfer von 2 Embryonen ein monochoriales, diamniales Zwillingspaar. Im ersten Trimenon wurde eine diskordante fetale Megazystis mit konsekutivem Oligohydramnion und Lungenhypoplasie bei unauffalligem Karyotyp diagnostiziert. Das betroffene Kind wurde bei 25+3 SSW geboren, palliativ behandelt und verstarb rasch. Post mortem wurde eine Kloakenfehlbildung festgestellt. Typische Ursache fur die Megazystis beim mannlichen Geschlecht ist eine obstruktive Uropathie. Bei den seltener betroffenen weiblichen Feten liegt meist ein komplexes urogenitales Fehlbildungssyndrom vor, wie die Kloakenfehlbildung, deren Entstehung auf eine Storung der Gastrulation zuruckgeht. Wir fanden 10 Fallberichte/-serien uber mono- oder dizygote Zwillinge mit Diskordanz entweder fur eine Megazystis oder fur eine Kloakenfehlbildung. Die Vergleichbarkeit mit unserem Fall war eingeschrankt, da Aspekte wie Konzeptionsmechanismus, Geschlecht, Karyotyp oder Atiologie der Fehlbildung nicht in allen Fallen aufgefuhrt wurden. Diskordanz monozygoter Zwillinge fur strukturelle Fehlbildungen hangt nach bisherigem Verstandnis eng mit den Vorgangen der Zwillingsentstehung selbst zusammen. Bei kunstlicher Befruchtung wird eine erhohte Inzidenz von (monozygoten) Zwillingsschwangerschaften und Fehlbildungen diskutiert. Im Hinblick auf Konzeptionsmechanismus, Zygotie, Geschlecht und Fehlbildungskonstellation ist unser Fall einzigartig.

Objective To propose a clinical score for the optimal antenatal diagnosis of fetal lower urinary tract obstruction (LUTO) in the second and third trimesters of pregnancy, as an alternative to the commonly used ultrasound triad of megacystis, keyhole sign and hydronephrosis. Methods This was a national retrospective study carried out at the eight tertiary fetal medicine units (FMUs) in The Netherlands. Only cases referred for megacystis from the second trimester onwards and with a clear postnatal diagnosis were included in the study. At referral, data were collected on amniotic fluid volume, renal cortical appearance, bladder volume, hydronephrosis, fetal ascites, ureteral size, keyhole sign, fetal sex and gestational age. Multivariate analysis was performed, starting by including all antenatal variables, and then excluding the weakest predictors using the backward stepwise strategy. Results Over a 7-year period, 312 fetuses with a diagnosis of megacystis were referred to the eight Dutch tertiary FMUs. A final diagnosis was achieved in 143 cases, including 124 of LUTO and 19 reclassified after birth as non-obstructive megacystis. The optimal bladder volume cut-off for prediction of LUTO was 35 cm(3) (area under the curve (AUC) = 0.7, P = 0.03). The clinical score formulated on the basis of the multivariate analysis included fetal sex, degree of bladder distension, ureteral size, oligo-or anhydramnios and gestational age at referral. The combination of these five variables demonstrated good accuracy in discriminating LUTO from non-obstructive megacystis (AUC = 0.84, P

Objective: To investigate the best criteria for discriminating fetuses with isolated posterior urethral valves from those theoretically not eligible for fetal treatment because of complex megacystis, high chance of spontaneous resolution, and urethral atresia. Methods: A retrospective national study was conducted in fetuses with megacystis detected before 17 weeks’ gestation (early megacystis). Results: In total, 142 cases with fetal megacystis were included in the study: 52 with lower urinary tract obstruction, 29 with normal micturition at birth, and 61 with miscellaneous syndromal associations, chromosomal and multiple structural abnormalities (complex megacystis). Only a nuchal translucency > 95th centile, and not a longitudinal bladder diameter ≤15 mm (p = 0.24), significantly increased the risk of complex megacystis (p < 0.01). Cases with a high chance of spontaneous resolution were identified by using the cut-off of 12 mm, as demonstrated in a previous study, and the finding of an associated umbilical cord cyst carried a high-risk of urethral atresia (odds ratio: 15; p = 0.026), an unfavorable condition for antenatal treatment. An algorithm encompassing these three criteria demonstrated good accuracy in selecting fetuses theoretically eligible for fetal treatment (specificity 73%; sensitivity 92%). Conclusions: Cases theoretically eligible for early fetal therapy are those with normal nuchal translucency, a longitudinal bladder diameter > 12 mm, and without ultrasound evidence of umbilical cord cysts.

Objective: To propose a clinical score for the optimal antenatal diagnosis of fetal lower urinary tract obstruction (LUTO) in the second and third trimesters of pregnancy, as an alternative to the commonly used ultrasound triad of megacystis, keyhole sign and hydronephrosis. Methods: This was a national retrospective study carried out at the eight tertiary fetal medicine units (FMUs) in The Netherlands. Only cases referred for megacystis from the second trimester onwards and with a clear postnatal diagnosis were included in the study. At referral, data were collected on amniotic fluid volume, renal cortical appearance, bladder volume, hydronephrosis, fetal ascites, ureteral size, keyhole sign, fetal sex and gestational age. Multivariate analysis was performed, starting by including all antenatal variables, and then excluding the weakest predictors using the backward stepwise strategy. Results: Over a 7-year period, 312 fetuses with a diagnosis of megacystis were referred to the eight Dutch tertiary FMUs. A final diagnosis was achieved in 143 cases, including 124 of LUTO and 19 reclassified after birth as non-obstructive megacystis. The optimal bladder volume cut-off for prediction of LUTO was 35 cm3 (area under the curve (AUC) = 0.7, P = 0.03). The clinical score formulated on the basis of the multivariate analysis included fetal sex, degree of bladder distension, ureteral size, oligo- or anhydramnios and gestational age at referral. The combination of these five variables demonstrated good accuracy in discriminating LUTO from non-obstructive megacystis (AUC = 0.84, P < 0.001), compared with the poor performance of the ultrasound triad (AUC = 0.63, P = 0.07). Conclusions: We propose a clinical score that combines five antenatal variables for the prospective diagnosis of congenital LUTO. This score showed good discriminative capacity in predicting LUTO, and better diagnostic accuracy compared with that of the classic ultrasound triad. Future studies to validate these results should be carried out in order to refine antenatal management of LUTO and prevent inappropriate fetal interventions. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Measurement of urinary β2M (beta 2-microglobulin) is a sensitive and reliable assay for detecting tubular injury, renal toxicity, lymphomas, leukemia, or myeloma. Some chemical substrates may increase the level of β2M in-vivo. Elevated β2M level in urine is unusual because it rapidly degrades when pH is below 6. The level of β2M in the bladder can also be used as a marker to assess renal tubular maturation in neonates. β2M in the bladder could be a result of fetal megacystis, which is an abnormally enlarged bladder appearing after 10 weeks of gestation, when the fetus begins to produce urine. Identification of the pregnant women instead of the fetus is a common pre-analytical error with samples sent from the gynecology clinic to the laboratory. Here we present the case of a 24-year-old pregnant woman whose urine analysis results indicated excessively high β2M level in the urine. The present study could improve the understanding of urinary β2M analysis, laboratory errors, and the interpretation of test results.

Evaluation of the kidneys, bladder, and amniotic fluid volume forms part of any standard obstetrical ultrasound. When a fetal genitourinary anomaly is suspected, a more detailed evaluation is necessary. This detailed imaging can be challenging in the setting of decreased or absent amniotic fluid or large maternal body habitus, and in complex malformations. In these situations, magnetic resonance imaging can help to better define the fetal anatomy and provide a more confident and specific prenatal diagnosis.

Objective: To identify the molecular basis for prenatally suspected cases of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) (MIM 249210) in 3 independent families with clinical and radiographic evidence of MMIHS. Methods: Whole-exome sequencing (WES) and Sanger sequencing of the ACTG2 gene. Results: We identified a novel heterozygous de novo missense variant in ACTG2 c.770G>A (p.Arg257His) encoding γ-2 smooth muscle actin (ACTG2) in 2 siblings with MMIHS, suggesting gonadal mosaicism of one of the parents. Two additional de novo missense variants (p.Arg257Cys and p.Arg178His) in ACTG2 were identified in 2 additional MMHIS patients. All of our patients had evidence of fetal megacystis and a normal or slightly increased amniotic fluid volume. Additional findings included bilateral renal hydronephrosis, an enlarged fetal stomach, and transient dilated bowel loops. ACTG2 immunostaining of the intestinal tissue showed an altered muscularis propria, a markedly thinned longitudinal muscle layer, and a reduced amount and abnormal distribution of ACTG2. Conclusion: Our study demonstrates that de novo mutations in ACTG2 are a cause of fetal megacystis in MMIHS and that gonadal mosaicism may be present in a subset of cases. These findings have implications for the counseling of families with a diagnosis of fetal megacystis with a preserved amniotic fluid volume and associated gastrointestinal findings.

Rationale: The pathogenesis of fetal megacystis is divided into obstructive and nonobstructive. Megacystis combined with chromosomal abnormalities is rare and most of the cases are nonobstructive. Patient concerns: The fetus showed posterior urethral obstructive megacystis with features of bladder enlargement, “keyhole” feature, and thick bladder wall. Diagnoses: Here, we present a case of fetal megacystis diagnosed by ultrasound at pregnancy week 15+2 and with multisystem abnormalities. Outcomes: Moreover, the fetus showed edema, umbilical cord cyst, cardiac dysplasia, hook-shaped hand, and strephenopodia. These abnormalities strongly suggested chromosomal abnormalities. The fetus was diagnosed with trisomy 18 by amniocentesis. Posterior urethral obstructive megacystis was confirmed by pathology. Lessons: In conclusion, this case suggests that in the presence of fetal megacystis and multisystem abnormalities, causes should be investigated and the possibility of chromosomal abnormalities should be considered in the presence of multisystem developmental abnormalities.