OBJECTIVE: To reach a Delphi-generated international expert consensus on the diagnosis, prognostic, management, and core outcome set (COS) of fetal Lower Urinary Tract Obstruction (LUTO).
METHODS: A three-round Delphi procedure was conducted among an international panel of LUTO experts. The panel was provided with a list of literature review-generated parameters for the diagnosis, prognostic, management, and outcomes. A parallel procedure was conducted along with patient groups during the development of COS.
RESULTS: A total of 160 experts were approached, of whom 99 completed the first round and 80 (80/99, 80.8%) completed all three rounds. In the first trimester, an objective measurement of longitudinal bladder diameter (with ≥7 mm being abnormal) should be used to suspect LUTO. In the second trimester, imaging parameters of LUTO could include: a) an enlarged bladder, b) a keyhole sign, c) bladder wall thickening, d) bilateral hydro (uretero) nephrosis, and e) male sex. There was a lack of consensus on the current prognostic scoring literature. However, experts agreed on the value of amniotic fluid volume (< 24 weeks) to predict survival and that the value of fetal intervention is to improve neonatal survival. While experts endorsed the role of sonographic parameters of renal dysplasia, at least one vesicocentesis, and urine biochemistry for prognosis and counseling, these items did not reach a consensus for determining fetal intervention candidacy. On the other hand, imaging parameters suggestive of LUTO, absence of life-limiting structural or genetic anomalies, gestational age of ≥16 weeks, and oligohydramnios defined as deepest vertical pocket (DVP) <2 cm should be used as candidacy criteria for fetal intervention based on experts\' consensus. If a bladder refill was evaluated, it should be assessed subjectively. Vesicoamniotic shunt should be the first line of fetal intervention. In the presence of suspected fetal renal failure, serial amnioinfusion should only be offered as an experimental procedure under research protocols. The core outcome set for future studies was agreed upon.
CONCLUSIONS: International consensus on the diagnosis, prognosis, and management of fetal LUTO, as well as the Core Outcome Set, should inform clinical care and research to optimize perinatal outcomes. This article is protected by copyright. All rights reserved.

OBJECTIVE: Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a well described clinical condition, but reports are focused on microcolon and intestinal hypoperistalsis, while data on bladder management are scant. Aim of the study is to present urological concerns in MMIHS.
METHODS: Retrospective evaluation of clinical data on urological management of MMIHS patients treated in the last 10 years.
RESULTS: Six patients were enrolled (3 male, 3 female). Three girls had prenatal diagnosis of megacystis (1 vesicoamniotic shunt was placed). All patients had genetic diagnosis: 5 had ACTG2 gene mutations and 1 MYH11 mutation. All patients were addressed to our attention for urinary symptoms, such as urinary retention, urinary tract infections, acute renal injury. Two patients presented frequent stoma prolapses. All children underwent a complete urological evaluation, and then started a bladder management protocol (clean intermittent catheterization, via urethra or cystostomy-tube placement), with improvement of urinary infections, upper urinary tract dilation and stoma prolapses, if present. All patients had good renal function at last follow-up.
CONCLUSIONS: We believe that MMIHS patients must be addressed soon and before onset of symptoms for a multidisciplinary evaluation, including an early assessment by a pediatric urologist expert in functional disorder, to preserve renal function at its best.

BACKGROUND: 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.
METHODS: 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.
CONCLUSIONS: 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.

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.
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.
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.
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.

Fetal megacystis is a sonographic sign, defined in first trimester as a longitudinal bladder length (LBD)>7 mm. Different causes may be associated with megacystis and outcomes vary with many factors. There are no international guidelines on how to manage megacystis cases, and invasive testing is controversial when no other abnormalities are found. The main objective of this study is to compare etiologies, management and outcomes of fetuses with first trimester megacystis, specifically between groups of LBD≤15 mm and >15 mm. This is a retrospective cohort study of megacystis cases managed in a Prenatal Diagnosis Center, between January 2009 and September 2020. Descriptive and bivariate analysis were performed. We studied 43 fetuses: 67.4% with LBD≤15 mm and 32.6% with LBD>15 mm. We found an association between LBD and isolated Low Urinary Tract Obstruction (LUTO) (3.4% vs 64.3%; p<0.001) and with isolated megacystis (44.8% vs 0.0%; p = 0.001). No differences were seen regarding the presence of aneuploidies (31.0% vs 14.3%; p = 0.213). Invasive testing was performed in 93.0% of cases. Overall, we report 41.9% of live births, 39.5% of pregnancy termination and 18.6% of intrauterine fetal demise. We found a higher rate of live births in fetuses with LBD≤15 mm (55.2% vs 14.3%; p = 0.011). For a mean follow-up time of 20.6 months, we report one neonatal death and one case of renal insufficiency. In conclusion, isolated LUTO is more frequent if LBD>15 mm whereas isolated megacystis is more frequently found if LBD≤15 mm. If LBD≤15 mm, live birth rates and long-term outcomes seem to be enhanced.

We present a case of antenatally detected fetal megacystis caused by an obstructing posterior urethral polyp. Antenatal and postnatal ultrasounds showed bladder wall thickening and bilateral hydroureteronephrosis, most marked antenatally. A working diagnosis of posterior urethral valves was therefore made. However, further postnatal assessment with a micturating cystourethrogram (MCUG) combined with a retrograde urethrogram identified a pedunculated urethral polyp as the cause. The addition of a retrograde urethrogram as an adjunct to the MCUG in the diagnosis of posterior urethral polyp has not previously been reported, and in this case provided diagnostic confidence of this rare condition, allowing for definitive surgical planning.

Smooth muscle disorders affecting both the intestine and the bladder have been known for a decade. However, the recent discovery of genes associated with these dysfunctions has led to the description of several clinical phenotypes. We performed a systematic review of all published cases involving seven genes with pathogenic variants, ACTG2, MYH11, FLNA, MYLK, RAD21, MYL9 and LMOD1, and included 28 articles describing 112 patients and 5 pregnancies terminated before birth. The most commonly described mutations involved ACTG2 (75/112, 67% of patients), MYH11 (14%) and FLNA (13%). Twenty-seven patients (28%) died at a median age of 14.5 months. Among the 76 patients for whom this information was available, 10 (13%) had isolated chronic intestinal pseudo-obstruction (CIPO), 17 (22%) had isolated megacystis, and 48 (63%) had combined CIPO and megacystis. The respective proportions of these phenotypes were 9%, 20% and 71% among the 56 patients with ACTG2 mutations, 20%, 20% and 60% among the 10 patients with MYH11 mutations and 50%, 50% and 0% among the 7 patients with FLNA mutations.

(1) Background: The aim of this study was to compare perinatal outcomes and complication rates of vesicoamniotic shunting (VAS) before 17 + 0 weeks in isolated LUTO (lower urinary tract obstruction) with the Somatex® intrauterine shunt vs. the Harrison fetal bladder shunt. (2) Methods: This is a retrospective cohort study in two tertiary fetal medicine centers. From 2004−2014, the Harrison fetal bladder shunt was used, and from late 2014−2017, the Somatex shunt. Obstetrics and pediatric charts were reviewed for complications, course of pregnancy, perinatal outcome, and postnatal renal function. (3) Results: Twenty-four fetuses underwent VAS with a Harrison (H) shunt and 33 fetuses with a Somatex (S) shunt. Live birth rates and survival to last follow-up were significantly higher in the Somatex group, at 84.8% and 81.8%, respectively, vs. 50% and 33.3% in the Harrison group (p = 0.007 and p < 0.001). The dislocation rate in the Somatex group (36.4%) was significantly lower than in the Harrison group (87.5%) (p < 0.001). The median time to dislocation was significantly different, at 20.6 days (H) vs. 73.9 days (S) (p = 0.002), as was gestational age at dislocation (17 (H) vs. 25 (S) weeks, p < 0.001). Renal function was normal in early childhood in 51% (S) vs. 29% (H) (p = 0.11). (4) Conclusions: VAS before 17 + 0 weeks gestational age with a Somatex shunt improves perinatal survival significantly and might even have a positive effect on renal function, probably due to the lower dislocation rates. A normal amount of amniotic fluid in the third trimester was the best predictor of normal renal function in early childhood.

The purpose of this retrospective cohort study was to compare the outcome of human fetuses with isolated severe lower urinary tract obstructions (LUTO) that were first treated before the completion of 16 weeks of gestation to fetuses first treated later in gestation.
Vesicoamniotic shunt insertion (VAS) was performed in 63 subsequent fetuses with LUTO between 12 + 5 and 30 + 3 weeks. The fetuses were analyzed in three groups: Group-I-fetuses underwent their first intervention until the completion of 16 weeks, Group-II-fetuses were first treated between 16 + 1 and 24 + 0 weeks and Group-III-fetuses beyond 24 + 1 weeks. Renal and pulmonary outcome parameters and complicating factors were assessed.
- All mothers tolerated the procedures well. Overall fetal survival was 47 of 63 (75%). The mean age at delivery of survivors was 35 weeks. 68% of Group-I-fetuses, 77% of group-II-fetuses, and 100% of group-III-fetuses survived beyond postnatal hospital discharge. Amongst the survivors the chance for normal renal function was higher for group I with 79% (15/19) compared to first fetal intervention after the completion of 16 weeks with 32% (9/28, p = 0.003, OR = 7.9 [2.0, 30.8] 95% CI). Clinically relevant pulmonary hypoplasia was observed in 11% of Group-I-, 27% of Group-II-, and 20% of Group-III-fetuses.
Early intervention in fetal LUTO before the completion of 16 weeks may achieve a higher rate of normal renal and pulmonary function in survivors than treatment beyond that point in time. This observation is important for the future management of this challenging patient population.

OBJECTIVE: Chronic intestinal pseudo-obstruction (CIPO) is a clinically heterogeneous syndrome characterized by compromised peristalsis and intestinal obstruction. Variants of actin gamma 2 (ACTG2), a protein crucial for correct enteric muscle contraction, have been found in CIPO patients. The aim of this study is to examine the clinical features and ACTG2 variants in Korean patients with CIPO.
METHODS: From January 1995 to August 2020, 12 patients diagnosed with CIPO were included and genetic analysis testing of ACTG2 was performed.
RESULTS: Heterozygous ACTG2 missense variants were found in 6 patients (50.0%). The p.Arg257Cys variant was found in 3 patients, and p.Arg63Gln and p.Arg178His variants were found in 1 patient each. A novel variant, p.Ile193Phe, was found in 1 patient. Three patients were diagnosed at birth, 2 at the age of 1 year, and 1 at 3 years of age. Abnormal prenatal genitourinary ultrasonographic findings were found in all 6 patients; microcolon was found in 4 patients (66.7%), and megacystis in all 6 patients. The pathology showed abnormal ganglion cells as well as myopathic findings. All patients are dependent on total parenteral nutrition and are to date alive.
CONCLUSIONS: ACTG2 variants are commonly found in Korean patients with CIPO. In CIPO patients with megacystis and abnormal prenatal ultrasonography, genetic testing of ACTG2 should be considered. Molecular diagnosis of CIPO is more important than pathologic diagnosis.