Fetal Lower Urinary Tract Obstruction Research Articles

Fetal Lower Urinary Tract Obstruction - Current Diagnostic and Therapeutic Strategies and Future Directions.

Fetal lower urinary tract obstruction (LUTO) is a rare congenital anomaly in which the bladder cannot empty properly. The clinical presentation is variable. On the severe end of the spectrum the amniotic fluid index can be sufficiently low resulting in fetal lung development that is incompatible with life outside the womb. The pressure in the urinary tract system can also result in severe damage to the kidney, resulting in renal failure in utero or in the first couple years of life. Therefore, much work has been done to determine which fetuses need intervention in utero to allow for survival outside of the womb and avoidance of end stage renal disease. Multiple therapies have been developed to relieve the obstruction in utero with the mainstay being vesicoamniotic shunting and posterior urethral valve ablation. While much has been investigated to determine which fetuses would benefit from fetal intervention, the current indications are not without their flaws. This review describes the current indications and their shortcomings, as well as new experimental methods of determining need for intervention. Additionally, this review describes the milestone animal studies that established the challenges of current fetal interventions and the utility of an experimental valved shunt in sheep over the last 20 years. Our understanding of LUTO and which fetuses benefit from in utero intervention has grown over the last 20 years. However, traditional markers have proven to be less predictive than previously thought, opening the door to exciting new advances. Vesicoamniotic shunting, while lifesaving, does not preserve bladder function and frequently dislodges. Animal studies over the last 20 years have established the utility of a valved shunt to maintain bladder function. Current advances are working to create such a shunt that can be percutaneously deployed and have greater adherence to the bladder wall to avoid dislodgement.

Fetal lower urinary tract obstruction: international Delphi consensus on management and core outcomes set.

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). 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. 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. 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.

Fetal lower urinary tract obstruction caused by sacrococcygeal teratoma: A case report

Background: Fetal lower urinary tract obstruction (LUTO) is a rare occurrence that is usually associatedwith major morbidity and mortality after birth. It has an incidence of 2.2 in 10000 pregnancies. In males,the most common cause is persistent posterior urethral valves (50-60%). Other causes include urethralatresia with a poor prognosis. Most fetuses that survive to term with LUTO need dialysis or renaltransplant.Case presentation: A 35-year-old gravida 3 presented for routine antenatal follow-up. Her antenatalfollow-up remained normal until she underwent a growth scan at 33 weeks. Ultrasound revealed a fetuswithin normal growth centiles, but the renal system had features of obstruction. Renal calyces weredilated with hyperechoic renal parenchyma. The bladder was also markedly distended and had athickened wall, and a keyhole sign was present. There was a multicystic lesion in the sacral regionwithout blood flow on Doppler imaging. There was oligohydramnios. She had fetal vesicocentesis, whichrevealed normal kidney function. She had serial fetal vesicocentesis, and renal ultrasound showedimprovement in the corticomedullary differentiation of the kidney. At 38 weeks, the patient underwent acesarean delivery. Imaging studies showed a sacrococcygeal teratoma that was causing pressure on therenal system. This was excised, and the patient was allowed to return home on physiotherapy. Renalfunction test after delivery remained normal.Conclusion: Fetal lower urinary tract obstruction in males is mostly managed using the placement ofvesicoamniotic shunts or stents. In male fetuses with posterior urethral valves, ablation is performed inutero using cystoscopy. In this case report, LUTO was managed by serial vesicocentesis, whichpreserved renal function. In low-resource settings where surgery is not available, serial vesicocentesiscan be performed to relieve obstruction.

1093 Management and Core Outcomes Set of Fetal Lower Urinary Tract Obstruction: Delphi Consensus

1093 Management and Core Outcomes Set of Fetal Lower Urinary Tract Obstruction: Delphi Consensus

Outcomes of fetal lower urinary tract obstruction based ontiming of oligohydramnios onset.

Fetal Lower Urinary Tract Obstruction (LUTO) is associated with oligohydramnios and significant fetal morbidity, resulting in poor lung development and perinatal death. However, oligohydramnios may develop at different gestational periods, and the impact of timing on fetal outcomes remains unknown. Our objective was to characterize the impact onset of oligohydramnios had on prenatal outcomes. This study is a retrospective cohort study of all patients with a prenatal diagnosis of LUTO at our tertiary referral center from 2014 to 2023. All patients underwent detailed ultrasonography and interdisciplinary counseling and were subsequently delivered at our institution. Data were obtained from electronic medical records and complete extraction was required for final inclusion. During the study time period, 93 patients met inclusion criteria of which 68 (73.1%) developed oligohydramnios during their pregnancy. 63 (93%) of these pregnancies resulted in livebirths with 28 (41.1%) perinatal deaths. Onset of oligohydramnios was earlier in pregnancies with perinatal death (23 vs. 28weeks, p=0.004) and associated with pulmonary hypoplasia. Our data show the impact of oligohydramnios timing in pregnancy on pulmonary hypoplasia and ultimately perinatal death. This allows for detailed patient counseling on the impact oligohydramnios may have on pregnancies by the gestational age of onset.

Development and validation of a novel fetal vesico-amniotic shunt, the vortex shunt.

Fetal lower urinary tract obstruction (LUTO) is a severe malformation associated with an up to 80% mortality risk as well as significant renal and pulmonary morbidity in survivors. Fetal vesico-amniotic shunts (VAS) bypass the bladder obstruction, improve amniotic fluid volume and enhance in-utero pulmonary development. VAS has been shown to reduce respiratory morbidity and mortality in the neonatal period without proven benefit on long-term renal and bladder function. Clinically available shunts are associated with an up to 80% dislodgement rate, leading to repeat invasive procedures which increase fetal and maternal risks. We developed a novel "Vortex" shunt, which incorporates enhanced fixation to reduce dislodgement, a one-way valve to optimize in-utero bladder function, and enhanced sonographic echogenicity that optimizes the accurate deployment. Following the validation of these characteristics in initial benchtop experiments we have moved to feasibility studies in the fetal lamb model. We hope that the Vortex shunt may ultimately facilitate shunt deployment, reduce dislodgement risk, improve neonatal morbidity and mortality, and decrease the significant healthcare expenditures associated with long-term morbidity in LUTO survivors. In this manuscript, we review the natural history of LUTO, the risks and benefits of clinically available fetal shunts, and our development and early validation experiments.

The utility of gene sequencing in identifying an underlying genetic disorder in prenatally suspected lower urinary tract obstruction.

Fetal megacystis generally presents as suspected lower urinary tract obstruction (LUTO), which is associated with severe perinatal morbidity. Genetic etiologies underlying LUTO or a LUTO-like initial presentation are poorly understood. Our objectives are to describe single gene etiologies in fetuses initially ascertained to have suspected LUTO and to elucidate genotype-phenotype correlations. A retrospective case series of suspected fetal LUTO positive for a molecular diagnosis was collected from five centers in the Fetal Sequencing Consortium. Demographics, sonograms, genetic testing including variant classification, and delivery outcomes were abstracted. Seven cases of initially prenatally suspected LUTO-positive for a molecular diagnosis were identified. In no case was the final diagnosis established as urethral obstruction that is, LUTO. All variants were classified as likely pathogenic or pathogenic. Smooth muscle deficiencies involving the bladder wall and interfering with bladder emptying were identified in five cases: MYOCD (2), ACTG2 (2), and MYH11 (1). Other genitourinary and/or non-genitourinary malformations were seen in two cases involving KMT2D (1) and BBS10 (1). Our series illustrates the value of molecular diagnostics in the workup of fetuses who present with prenatally suspected LUTO but who may have a non-LUTO explanation for their prenatal ultrasound findings.

Fetal bladder morphology as a predictor of outcome in fetal lower urinary tract obstruction.

We evaluate survival of fetuses with severe Lower Urinary Tract Obstruction (LUTO) based on bladder morphology. We hypothesize that fetuses with a "floppy" appearing bladder on initial prenatal ultrasound will have worse infant outcomes than fetuses with full/rounded bladders. We retrospectively reviewed all cases of LUTO evaluated in our fetal center between January 2013 and December 2021. Ultrasonographic assessment, renal biochemistry, and bladder refilling contributed to a "favorable" or "unfavorable" evaluation. Bladder morphology on initial ultrasound was classified as "floppy" or "full/rounded." Vesicoamniotic shunting was offered for favorably evaluated fetuses. Baseline demographics, ultrasound parameters, prenatal evaluations of fetal renal function, and infant outcomes were collected. Fetuses diagnosed with severe LUTO were included in analysis using descriptive statistics. The primary outcome measured was survival at 6months of life. 104 LUTO patients were evaluated; 24 were included in analysis. Infant survival rate at 6months was 60% for rounded bladders and 0% for floppy bladders (p=0.003). Bladder refill adequacy was lower in fetuses with floppy bladders compared with rounded bladders (p value<0.00001). We propose that bladder morphology in fetuses with severe LUTO may be a prognostication factor for predicting infant outcomes and provides a valuable, noninvasive assessment tool.

Fetal bladder morphology may predict neonatal outcomes in fetal lower urinary tract obstruction (LUTO)

Objectives: To evaluate postnatal survival outcomes of severe LUTO-affected fetuses based on fetal bladder shape. We hypothesize that fetuses with a “floppy” appearing bladder on initial prenatal ultrasound will have worse neonatal outcomes than fetuses with full/rounded bladders. Study Design: We performed a retrospective case review of all cases of LUTO that were evaluated for fetal intervention in a single large fetal center between January 2013 and December 2021. Fetuses were given a “favorable” or “unfavorable” evaluation based on comprehensive ultrasound, renal biochemistry testing, and bladder refill testing. Favorable evaluations were offered fetal intervention with vesicoamniotic shunt placement. Baseline demographics, ultrasound parameters, prenatal renal function testing, and neonatal outcomes were collected. Those with a diagnosis of severe LUTO were included in analysis. Descriptive statistics were used to analyze candidate data. Primary outcome was survival at 6 months of life. Results: Of the 104 LUTO patients evaluated, 24 were included in analysis. Details of prenatal evaluations are shown in Table 1a; six-month survival among groups based on fetal bladder morphology are shown in Table 1b. Postnatal survival at six months in patients with rounded bladders was 60% overall. Fetuses with floppy bladders showed a 0% six-month overall survival, which was significantly lower (p=0.002) as compared with the full/rounded bladder group. Conclusions: We propose that analysis of bladder shape in fetuses with severe LUTO may be an important prognostication factor for predicting neonatal outcomes. This simple, non-invasive assessment may inform clinical decision-making regarding further testing or fetal intervention.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Urine Biochemistry of a Human Fetus with Urinary Tract Obstruction – A Case Report

Introduction Fetal lower urinary tract obstruction (LUTO) can be mild or severe with oligohydramnios, renal dysplasia and pulmonary hypoplasia. Fetal urine biochemical markers correlate with fetal prognosis and, if favorable, surgical intervention is feasible. Methods We report a patient in her 18th gestational week whose fetus was diagnosed with LUTO and underwent fetal urine sampling for calcium, sodium, chloride, beta2-microglobulin and total protein of the routine LUTO panel, with the addition of creatinine, glucose, phosphate, urea, ammonia, albumin, and NGAL. Results Although the routine fetal urine biochemistry seemed to be favorably trending favorably, sodium, beta2-microglobulin, glucose, and urea did not decrease to the reference ranges, and ammonia and creatinine were lower than the reference ranges. Ultrasound demonstrated no improvement of the obstruction. Conclusions This case highlights the need to acquire further experience with biochemical fetal urine markers in order to better manage LUTO.

Definition, diagnosis and management of fetal lower urinary tract obstruction: consensus of the ERKNet CAKUT-Obstructive Uropathy Work Group.

Fetal lower urinary tract obstruction (LUTO) is associated with high mortality and postnatal morbidity caused by lung hypoplasia and impaired kidney function. Specific diagnostic features that can guide clinical approach and decisions are lacking; thus, the European Reference Network for Rare Kidney Diseases established a work group to develop recommendations regarding the clinical definition, diagnosis and management of prenatally detected LUTO. The work group recommends the use of antero-posterior diameter of renal pelvis as the most reliable parameter for suspecting obstructive uropathies and for suspecting prenatal LUTO in the presence of fetal megacystis. Regarding prenatal and postnatal prognosis of fetuses with LUTO, the risk of fetal and neonatal death depends on the presence of oligohydramnios or anhydramnios before 20 weeks' gestation, whereas the risk of kidney replacement therapy cannot be reliably foreseen before birth. Parents of fetuses with LUTO must be referred to a tertiary obstetric centre with multidisciplinary expertise in prenatal and postnatal management of obstructive uropathies, and vesico-amniotic shunt placement should be offered in selected instances, as it increases perinatal survival of fetuses with LUTO.

Development and in-vitro characterization of a novel fetal vesicoamniotic shunt - The Vortex shunt.

To develop and test a novel vesicoamniotic shunt (VAS) to treat fetal lower urinary tract obstruction (LUTO), decrease dislodgement and optimize shunt deployment in-vitro. Vesicoamniotic shunt design objectives included: (1) robust and atraumatic fixation elements, (2) kink resistant conduit to adjust to fetal movement and growth, (3) one-way pressure valve to facilitate bladder cycling, and (4) echogenic deployment visualization aids. The force to dislodge the novel Vortex shunt was compared with existing commercially available shunts in a bench-top porcine bladder model. Sonographic echogenicity was evaluated with ultrasound-guided deployment, and the shunt valve pressure measured. A prototype novel Vortex shunt was developed using braided nitinol "umbrella-type" ends with a kink-resistant stem incorporating an internal one-way valve. The peak force required to dislodge the Vortex shunt was significantly higher than commercially available shunts (p<0.01). Shunt deployment in the bench-top model was easily confirmed with ultrasound guidance and the brisk decompression of the inflated porcine bladder thereafter. In-vitro valve gauge pressure testing mirrored bladder pressures in human LUTO cases. In-vitro testing shows that the Vortex shunt may improve deployment, sonographic visualization, kink resistance, and dynamic size adjustment. Validation in preclinical animal models are warranted and currently underway.

Vesico-amniotic shunt insertion prior to the completion of 16 weeks results in improved preservation of renal function in surviving fetuses with isolated severe lower urinary tract obstruction (LUTO)

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.

Fetal therapy of LUTO (lower urinary tract obstruction) – a follow-up observational study

Purpose 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. Material and methods 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 Somatex® intrauterine shunt system. MC was defined as an increased longitudinal measurement of the bladder >15 mm. The median follow-up time after birth was 18 months. Results Eight 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. Conclusion Overall, 5 of 9 LUTO fetuses (55%) undergoing VAS with the Somatex® intrauterine shunt system showed long-term survival beyond the neonatal period of 28 d (5/9; 55%) with varying morbidity.

Bladder outlet obstruction

Bladder outlet obstruction

Two Cases of Fetal Lower Urinary Tract Obstruction (LUTO) with Similar Presentations Before But Contrasting Outcomes After Fetoscopic Laser Fulguration of Posterior Urethral Valves

Two Cases of Fetal Lower Urinary Tract Obstruction (LUTO) with Similar Presentations Before But Contrasting Outcomes After Fetoscopic Laser Fulguration of Posterior Urethral Valves

Fetal lower urinary tract obstruction: a current overview of intrauterine diagnosis and treatment.

The aim of this review article is to provide apractical and concise overview of diagnosis and management of pregnancy with fetal lower urinary tract obstruction. Review of literature and current studies. Proper diagnosis and management of isolated fetal lower urinary tract obstruction with oligohydramnios allows appropriate implementation of intrauterine treatment in indicated cases. The treatment is aprevention of pulmonary hypoplasia and also improves renal function; this finally contributes to the improvement of overall perinatal morbidity and mortality.

Novel scoring system for determining fetal candidacy for prenatal intervention for severe congenital lower urinary tract obstruction

ObjectivesTo evaluate a novel scoring system that combines several prenatal parameters for selecting ideal candidates for fetal intervention, and for predicting postnatal survival in patients with severe fetal lower urinary tract obstruction (LUTO). MethodsWe retrospectively reviewed all cases of severe LUTO evaluated for fetal intervention in a single large fetal center between January 2013 and December 2017. A scoring system for determining fetal candidacy for intervention was retrospectively developed based on postnatal outcomes. The proposed scoring system included fetal urinary biochemistry, renal ultrasound parameters, initial bladder volume, and degree of bladder refill. Relevant demographic characteristics, ultrasound reports and laboratory results were reviewed. Receiver operating characteristic (ROC) curves were used to select the cut-off values for initial bladder volume and degree of bladder refill and to evaluate the performance of the scoring system in predicting postnatal death. ResultsOf the 79 LUTO patients evaluated, 31 were eligible for the study. The overall 6-month postnatal survival was 64.5 % (20/31). A scoring system (0−8) was suggested with 2 points for unfavorable biochemistry, 4 points for ultrasound evidence of dysplastic kidneys, 1 point for inadequate initial bladder volume and 1 point for inadequate bladder refill. Scores>3 (N = 7) were associated with 0 % 6-month survival. The ROC curve for predicting postnatal mortality showed area under curve (AUC) of 0.82 (95 % CI 0.65−0.99). Subgroup analysis within subjects who underwent fetal intervention (N = 22) also confirmed the significance of the distribution of the scoring system between groups who survived and those who did not after adjustment for GA at delivery (p = 0.01). ConclusionWe propose a novel scoring system for antenatal evaluation of patients with severe LUTO which may be useful in selecting those candidates most appropriate for intervention and in counseling parents about predicted postnatal outcome.

Urethroplasty with balloon catheterization in fetal lower urinary tract obstruction: observational study of 10 fetuses.

To present the preliminary outcomes of fetal urethroplasty using a coronary angioplasty balloon catheter in lower urinary tract obstruction (LUTO). We included 10 consecutive male fetuses diagnosed with LUTO caused by presumed isolated posterior urethral valves (PUVs), who underwent urethroplasty with a balloon catheter in our center between 2015 and 2018. During urethroplasty, the fetal urethra was dilated using a balloon catheter (diameter, 0.014 inches; balloon size, 2 × 9 mm) inserted under ultrasonographic guidance via an 18-gauge needle introduced into the fetal bladder. Mean gestational age at the time of urethroplasty was 17.8 (range, 16.5-20.4) weeks. All fetuses survived the procedure without any complications and there was no case of preterm prelabor rupture of the membranes. The procedure was successful in 5/10 (50%) fetuses, while in the other five (50%), we were unable to insert the balloon catheter into the urethra. In the five successfully treated cases, mean gestational age at delivery was 38 (range, 36-40) weeks and presence of PUVs was confirmed after birth. All five neonates micturated spontaneously and presented with normal urine output after birth. During the follow-up period, the parameters of kidney function were within normal limits in two neonates, whereas signs of impaired renal function were seen in another two. The other was diagnosed with renal insufficiency and required kidney transplant with bladder sparing at 2 years of age. Urethroplasty with a balloon catheter is a new prenatal treatment option for fetuses with PUVs. By restoring fetal micturition, the procedure can preserve normal urinary bladder and kidney function. Although data on its efficacy and potential to differentiate the etiology of LUTO are sparse, a significant advantage of this method is its safety for the fetus and the mother. Even if the neonates develop renal insufficiency, they may be eligible for kidney transplant with connection to their own bladder, without the need for urostomy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Interventions for Fetal Lower Urinary Tract Obstruction

Interventions for Fetal Lower Urinary Tract Obstruction