An overview of the literature on congenital lower urinary tract obstruction and introduction to the PLUTO trial: Percutaneous shunting in lower urinary tract obstruction

Congenital lower urinary tract obstruction (LUTO) comprises a heterogeneous group of pathologies causing obstruction to the urethra, the most common being posterior urethral valves. Such pathology is often associated with high perinatal mortality and varying degrees of perinatal and infant morbidity. A high proportion of LUTO may be visualised during routine second trimester (and first trimester) ultrasound giving rise to the possibility of determining individual fetal prognosis and treatments such as vesico-amniotic shunting, with a view to altering pathogenesis. The aims of the percutaneous shunting in low urinary tract obstruction (PLUTO) trial are to determine the effectiveness of these treatments and accuracy of the investigations with the primary outcome measures being perinatal mortality and postnatal renal function.     

Fetal surgery for severe lower urinary tract obstruction

Fetal interventions have been proposed for treatment of severe lower urinary tract obstruction (LUTO), as this condition is associated with high rates of perinatal mortality and postnatal renal impairment. The rationale for in utero treatment for those cases is based on the possibility of relieving the obstruction, improving the amniotic fluid volume, and preventing renal and bladder damage. Candidates for fetal intervention should be rigorously selected based on the confirmation of severe LUTO (dilated bladder and bilateral hydronephrosis), oligohydramnios or anyhydramnios and 'favorable' fetal urinalysis (dependent on gestational age). Nowadays there are two different therapeutic options with specific technical approaches. Vesico-amniotic shunting is an easier procedure, but with a higher frequency of related complications. Fetal cystoscopy can be used for diagnostic purpose and for treatment of posterior urethral valves, with suggestive advantage of allowing a more physiological release of the obstruction. According to the literature, estimated survival rates and postnatal normal renal function frequencies are approximately 40 and 50% after vesico-amniotic shunting and 75 and 65% after fetal cystoscopy, respectively.     

Diagnosis and outcome of fetal lower urinary tract obstruction in the northern region of England

OBJECTIVE: We reviewed the prenatal and postnatal management of fetal lower urinary tract obstruction (LUTO) in a large geographically defined population. METHODS: The records of 113 cases of LUTO seen over a 14-year period were examined. The predictive accuracy of prenatal findings for chronic renal failure (CRF) and a comparison of prenatal-suspected and non-suspected cases were made. RESULTS: The incidence of LUTO was 2.2 in 10 000 births. During the study period, prenatal detection improved from 33 to 62%. Sensitivity of prenatal ultrasound detection of renal dysplasia and fetal urinary sodium, calcium, and beta2-microglobulin for CRF or renal dysplasia on autopsy were 59, 33, 66, and 63% respectively. Compared to undetected cases, those detected prenatally had higher mortality and a higher rate of CRF at 24 months (17% vs 57%, p < 0.01). CONCLUSION: Our observations confirm the poor prognosis associated with fetal LUTO. The value of serial fetal urine biochemistry, other prenatal predictors of postnatal renal function, and the benefits of vesicoamniotic shunting require larger series and longer follow-up.     

Serial amnioinfusions for fetal pulmonary palliation in fetuses with renal failure

Fetal lower urinary tract obstruction (LUTO) encompasses a heterogeneous group of congenital pathologies and generally results in oligohydramnios. Fetal intervention (e.g. vesicoamniotic shunting, fetal cystoscopy) has traditionally been reserved for cases with a favorable renal profile, while those with unfavorable renal function have been offered termination or expectant management with the latter leading to high incidence of marked pulmonary hypoplasia, neonatal morbidity and mortality. Here, we describe two cases, which were not candidates for traditional intervention based on abnormal fetal renal function, who elected to proceed with serial amnioinfusions for fetal pulmonary palliation to attenuate the risk of pulmonary hypoplasia.     

Effectiveness of percutaneous vesico-amniotic shunting in congenital lower urinary tract obstruction: divergence in prior beliefs among specialist groups

Objective

To explore the prior beliefs regarding the effectiveness of percutaneous vesico-amniotic shunting in congenital lower urinary tract obstruction among different clinical specialist groups involved in caring for this condition.

Study design

Questionnaire survey of experts in the field based on principles of Bayesian elicitation of prior beliefs. The sample was 59 consultants in three specialties. Of these, 37 (63%) were subspecialty trained fetal medicine practitioners, 16 (27%) were paediatric nephrologists and 6 (10%) were paediatric urologists. The questionnaire elicited experts’ opinions as to: control arm perinatal mortality, effect of vesico-amniotic shunting on perinatal mortality, current clinical practice and the level of evidence required to change current practice.

Results

The response rates were 28% for fetal medicine specialists, 29% for paediatric nephrolgists and 10% for paediatric urologists. The median belief for fetal medicine specialists was a 10% (inter-quartile range, IQR 0-20%) reduction in perinatal mortality with shunting and a mean control arm perinatal mortality of 61%. For paediatric nephrologists the results were 5% (IQR −10 to 15%) and 18% and for paediatric urologists 10% (IQR 0-15%) and 17%. Fetal medicine specialists had the most optimistic beliefs regarding effect of shunting on perinatal mortality. Thirty-eight experts (68%) indicated that vesico-amniotic shunting would most likely reduce morbidity associated with renal dysfunction.

Conclusion

The prior beliefs show a divergence of opinion among specialists. This establishes clinical equipoise, which should be resolved with a randomised trial.     

PLUTO trial protocol: percutaneous shunting for lower urinary tract obstruction randomised controlled trial

OBJECTIVES: The primary objective is to determine whether intrauterine vesicoamniotic shunting for fetal bladder outflow obstruction, compared with conservative, noninterventional care, improves prenatal and perinatal mortality and renal function. The secondary objectives are to determine if shunting for fetal bladder outflow obstruction improves perinatal morbidity, to determine if improvement in outcomes is related to prognostic assessment at diagnosis and, if possible, derive a prognostic risk index and to determine the safety and long-term efficacy of shunting. DESIGN: A multicentre randomised controlled trial (RCT). SETTING: Fetal medicine units. POPULATION: Pregnant women with singleton, male fetus with isolated lower urinary tract obstruction (LUTO). METHODS: Following ultrasound diagnosis of LUTO in a male fetus and exclusion of other structural and chromosomal anomalies, participation in the trial will be discussed with the mother and written information given. Consent for participation in the trial will be taken and the mother randomised via the internet to either insertion of a vesicoamniotic shunt or expectant management. During pregnancy, both groups will be followed with regular ultrasound scans looking at viability, renal measurements and amniotic fluid volume. Following delivery, babies will be followed up by paediatric nephrologists/urologists at 4-6 weeks, 12 months and 3 and 5 years to assess renal function via serum creatinine, renal ultrasound and need for dialysis/transplant. MAIN OUTCOME MEASURES: The main outcome measures will be perinatal mortality rates and renal function at 4-6 weeks and 12 months measured via serum creatinine, renal ultrasound and need for dialysis/transplant. FUNDING: Wellbeing of Women. ESTIMATED COMPLETION DATE: September 2010. TRIAL ALGORITHM: [flowchart: see text].     

Fetoscopic transuterine release of posterior urethral valves: a new technique

Fetal urinary tract obstruction with oligohydramnios produces pulmonary hypoplasia and renal dysplasia. Decompression of the obstructed urinary tract may restore amniotic fluid and allow lung growth, but transabdominal catheter shunt decompression is often inadequate and does not allow for cycling of the bladder, while open procedures cause significant maternal morbidity. Disruption of the anatomic obstruction, usually posterior urethral valves in a male fetus, would be ideal but has proven technically difficult. Here we describe a new technique of percutaneous fetal cystoscopy and disruption of posterior urethral valves, and the case report of our first application of this technique. We pre-sent a case of a 17-week male fetus with posterior urethral valves which underwent fetal cystoscopy for mechanical disruption of posterior urethral valves. This minimally invasive approach to disruption of posterior urethral valves in a fetus is a novel method for decompressing the urinary tract. The technique offers a minimal degree of maternal morbidity and, if instituted early enough, can restore amniotic fluid volume, avert fatal pulmonary hypoplasia and may preserve renal function.     

Discordant lower urinary tract obstruction in early twin gestations: management and outcome

OBJECTIVE: To report our experience with the management of twin pregnancies discordant for lower urinary tract obstruction. METHODS: Cases of twin pregnancies discordant for lower urinary tract obstruction were identified from our fetal medicine database. Information on ultrasonographic findings, antenatal course, pregnancy complications, and perinatal outcome was obtained by reviewing medical records or contacting the referring obstetricians. RESULTS: Five twin pregnancies discordant for lower urinary tract obstruction were diagnosed between 11 and 15 weeks of gestation. There were 3 dichorionic and 2 monochorionic pregnancies (1 diamniotic and 1 monoamniotic). The dichorionic pregnancies were managed conservatively, resulting in a pregnancy loss of both twins in 1 case, a single fetal death at 29 weeks in 1 case, and an early neonatal death due to lung hypoplasia of the affected twin in 1 case. On the other hand, both monochorionic twin pregnancies were managed with serial vesicocenteses. In both cases, the prenatal course was complicated, 1 by premature rupture of the membranes and the other by cord entanglement, requiring delivery at 29 and 31 weeks, respectively. Among the 4 continuing pregnancies with complete perinatal outcome, none of the affected twins survived, and the structurally normal twins were delivered between 29 and 36 weeks and discharged from the hospital in good condition. CONCLUSION: Twin pregnancies discordant for lower urinary tract obstruction are at high risk of perinatal death and premature delivery. Prenatal intervention seems not to be associated with an improved perinatal outcome of the affected twin, but it may be beneficial in selected cases to attain viability of the unaffected twin.     

Antenatal ultrasound to predict postnatal renal function in congenital lower urinary tract obstruction: systematic review of test accuracy

Background  Congenital urinary tract obstruction can lead to perinatal mortality and morbidity. Assessing antenatal ultrasound features may help identify fetuses likely to suffer complications.
Objective  To evaluate the accuracy of antenatal ultrasound in the prediction of postnatal renal function in cases of congenital lower urinary tract obstruction (LUTO).
Search strategy  We conducted electronic searches in MEDLINE, EMBASE, the Cochrane Library, MEDION, SIGLE, SCISEARCH Index of scientific and technical proceedings, National Research Register (database inception – 2008) and Medical Conferences register and searched reference lists.
Selection criteria  Two reviewers independently selected articles in which the accuracy of fetal ultrasound features were evaluated to predict postnatal renal function with no language restrictions.
Data collection and analysis  Data were extracted on study characteristics, quality and results to construct 2 × 2 tables. Likelihood ratios for positive (LR+) and negative (LR−) test results, sensitivity and specificity were generated for the different ultrasound parameters and reference standards.
Main results  Thirteen articles that met the selection criteria, including 215 women and 33 2 × 2 tables. Meta-analysis was performed using clinically similar subgroups to minimise clinical heterogeneity. The ultrasound parameter that showed the best predictive value for postnatal renal function in survivors was renal cortical appearance, sensitivity 0.57 (95% CI 0.37–0.76) and specificity 0.84 (95% CI 0.71–0.94), area under the curve 0.78.
Conclusion  Measurement of amniotic fluid volume and the appearance of the renal cortex at diagnosis of LUTO show promising predictive accuracy for poor postnatal renal function.     

In utero therapy for lower urinary tract obstruction.

Lower urinary tract obstruction has a significant impact on neonatal and child health. Pulmonary hyperplasia and renal impairment could be direct or indirect consequences of this condition leading to significant morbidity and mortality. Evaluation of fetuses with suspected lower urinary tract obstruction is performed not only to confirm the diagnosis but also to assess renal prognosis. Ultrasound examination and urinary analysis aid in the evaluation of these fetuses. The decision to perform fetal intervention in these cases is a difficult one. Vesico-amniotic fetal shunting, open fetal surgery and more recently endoscopic fetal surgery for this condition are available as possible modalities of fetal intervention. Case selection for fetal intervention is extremely important in order to both avoid unnecessary intervention in those unlikely to survive, and also to avoid procedure related complications in fetuses likely to do well without intervention. Vesico-amniotic shunting has the advantage of bypassing the obstruction, however it is often associated with complications. Open fetal surgery is not usually recommended because of the complications and high fetal loss rate. Endoscopic surgery to visualise and treat the cause of lower urinary tract obstruction has been tried. Fetal endoscopic surgery is in its infancy and endoscopic procedures are limited to a few groups. This current review addresses evaluation, case selection and therapeutic options for lower urinary tract obstruction in utero. It also discusses the limited data against which the efficacy of the various options can be assessed. The current state of fetal intervention is detailed in the present review.     

Sequential invasive assessment of fetal renal function and the intrauterine treatment of fetal obstructive uropathies

Persistent fetal lower urinary tract obstruction carries a very poor prognosis secondary to damaged renal capacity and oligohydramnios, with its related pulmonary hypoplasia. Several attempts in the past several years to divert urinary flow via an intrauterine shunt have generally been disappointing, primarily because of poor patient selection. In this study we report our experiences with aggressive decompression of megacystis in 11 patients, the value in selected cases of sequential evaluations of fetal urine biochemistry, and the success of intrauterine bladder shunting procedures in appropriately chosen patients. Our data suggest that a single fetal urine determination may be insufficient to declare irreversible damage. Following decompression, improvement in urine biochemistry or its lack may be more likely representative of ultimate outcome. Decompression by either needle aspiration or intrauterine shunting is warranted in carefully selected cases and can save fetuses that are otherwise very likely doomed.     

Secondary infertility as a late complication of vesico-amniotic shunt therapy

OBJECTIVE: Vesico-amniotic shunting can be used for the treatment of fetal obstructive uropathy. However, the procedure is associated with a significant risk of complications. We report a case of a complicated vesico-amniotic placement, where a vesico-amniotic shunt ultimately resulted in, fortunately reversible, infertility. CASE: A 36-year-old multigravida was referred to our center at 13 weeks' gestation for the evaluation of fetal lower urinary obstruction. A vesico-amniotic shunt placement requiring several attempts was performed. A few weeks later premature rupture of the membranes occurred. At the request of the parents, the pregnancy was terminated at 22 weeks'gestation. The patient visited us again for secondary infertility, which turned out to be caused by a shunt left behind in the uterus, acting as an IUD. After hysteroscopic removal, she soon became pregnant again. CONCLUSION: This case illustrates the importance of careful documentation relating to each and every operation, of all materials used and what was retained in the patient. At delivery, obstetric staff should be completely aware of the prenatal treatment procedures performed, to ensure that no foreign objects are left by oversight, inside the patient's body.     

Lung development in diamniotic twins discordant for complete urinary tract obstruction.

OBJECTIVES: To investigate the effect of anhydramnios on the lung development of 1 twin in the presence of a normal amniotic fluid volume in its diamniotic co-twin. METHODS: Three sets of diamniotic twins, discordant for complete urinary tract obstruction and anhydramnios, were followed prospectively with regular ultrasound scans and after delivery. RESULTS: All 3 twins with complete urinary tract obstruction and anhydramnios died within 2 days after birth, with confirmed severe pulmonary hypoplasia. In every case the twin with a normal amount of surrounding amniotic fluid had a normal postnatal outcome. CONCLUSIONS: The observation that a normal amniotic fluid volume in one sac does not protect the anhydramniotic twin from pulmonary hypoplasia has important implications for the aetiology of the condition and for the possibility of therapeutic septostomy. These results are discussed in relation to previous human and animal studies.     

Fetal interventions for obstructive uropathy

Obstructive uropathy is a significant source of morbidity and mortality in the neonate and infant, despite advances in postnatal management. Diagnosis is typically made early in the second trimester on the basis of sonographic measurements. In utero therapy holds promise for improved outcomes by preventing progressive urinary tract damage and permitting drainage of urine into the amniotic space to minimize the pulmonary sequelae of oligohydramnios. Multiple studies with animal models have showed the benefits of midgestational intervention, but large prospective, randomized studies have not yet been performed to confirm these findings in humans. Standardization of the diagnostic evaluation allows for refined patient selection, resulting in improved postnatal outcomes after fetal vesicoamniotic shunting. Research into the role of specific growth factors and immunoproteins in renal development and function may further improve patient selection and outcome. This article reviews diagnosis, technique, and outcomes for fetal treatment of obstructive uropathy.     

Fetal urinary tract obstruction: is active intervention before delivery indicated?

Obstruction of the urinary tract was diagnosed by ultrasound in four fetuses at 16-30 weeks: three of these diagnoses were confirmed after delivery; the fourth fetus had multicystic kidneys with hydroureter and hydronephrosis but no obstruction. The fetus with obstruction diagnosed at 16 weeks was terminated: it had lung hypoplasia with the prune-belly syndrome. The other two fetuses with obstruction were diagnosed at 25 and 34 weeks; the urinary tracts of both were drained for 5-14 days with reduction of distension. Both were born alive but that diagnosed at 25 weeks died of lung hypoplasia, the other survived, required nephrectomy and at the age of 3 is small but developing normally. Fetal urinary tract obstruction may prevent normal development of the lungs, be associated with other anomalies which cannot be diagnosed before delivery and retard infant development in survivors. Drainage of the dilated urinary tract does not harm the fetus or mother but has not been shown to improve neonatal survival or infant development.     

Vesicoamniotic shunting using a double-basket catheter appears effective in treating fetal bladder outlet obstruction

BACKGROUND: To estimate the effect of vesicoamniotic shunting using a double-basket catheter on treating fetal bladder outlet obstruction. METHODS: A retrospective study involving 8 prenatally diagnosed bladder outlet obstruction cases that underwent vesicoamniotic shunt placement using a double-basket catheter from 1998 to 2004. Patients were followed-up for prenatal and neonatal outcome analyses. RESULTS: Vesicoamniotic shunting was performed in 8 fetuses aged between 13.7 and 25.4 weeks' gestation (mean+/-SD, 19.7+/-3.5 weeks). Final diagnoses included 5 posterior urethral valves, 1 cloacal anomaly, 1 urethral stenosis, and 1 unknown. There were no maternal complications associated with the procedures. One woman diagnosed as having a fetus with posterior urethral valves decided to terminate her pregnancy and one fetus died in uterus spontaneously. Six women delivered live babies, and one baby required postnatal ventilatory support. Postnatal follow-up ranged from 3 to 60 months. Of the 6 newborns, 4 survived with normal renal function, 1 had renal insufficiency, and 1 died of renal failure at 3 months of age. CONCLUSIONS: Vesicoamniotic shunt placement using a double-basket catheter may be effective in improving perinatal and neonatal outcomes through long-term decompression of the fetal urinary tract in carefully selected cases.     

Fetal urinary tract obstruction: is active intervention before delivery indicated?

Summary. Obstruction of the urinary tract was diagnosed by ultrasound in four fetuses at 16—30 weeks: three of these diagnoses were confirmed after delivery; the fourth fetus had multicystic kidneys with hydroureter and hydronephrosis but no obstruction. The fetus with obstruction diagnosed at 16 weeks was terminated: it had lung hypoplasia with the prune-belly syndrome. The other two fetuses with obstruction were diagnosed at 25 and 34 weeks; the urinary tracts of both were drained for 5–14 days with reduction of distension. Both were born alive but that diagnosed at 25 weeks died of lung hypoplasia, the other survived, required nephrectomy and at the age of 3 is small but developing normally. Fetal urinary tract obstruction may prevent normal development of the lungs, be associated with other anomalies which cannot be diagnosed before delivery and retard infant development in survivors. Drainage of the dilated urinary tract does not harm the fetus or mother but has not been shown to improve neonatal survival or infant development.     

Endovaginal sonographic diagnosis of the fetal urinary tract anomalies in early pregnancy

Transvaginal sonography has enhanced the ability to follow fetal development and detect pathologies in early gestation. Examination of the fetal urinary tract is an integral part of routine sonographic examinations in the second trimester of pregnancy and one of the major benefits of prenatal sonography is to allow early diagnosis of relatively common urinary tract malformations. Detailed evaluation of the fetal urinary tract and identification of anomalies were considered to be difficult before the 18th week of gestation prior to the use of transvaginal sonography. Using the transvaginal route, a detailed evaluation of the kidneys is possible around 12 weeks and structural anomalies of the urinary tract are being detected at an ever-increasing rate. Transvaginal sonography, owing to its proximity to the maternal pelvic organs, allows an earlier determination of the normal fetal urinary system and more accurate diagnosis and identification of fetal urinary anomalies as compared with transabdominal ultrasound. Received: 22 May 2000 / Accepted: 21 August 2000     

Fetal pulmonary hypoplasia, anuria, and oligohydramnios: clinicopathologic observations and review of the literature

The pathology of the lungs was studied in infants dying perinatally with urinary tract malformations. Fetal pulmonary hypoplasia was found in association with anuria and oligohydramnios; however, when renal function was present, pulmonary hypoplasia was absent. Pulmonary hypoplasia appears not to be related genetically or teratologically to the various urinary tract malformations but rather to be secondary to fetal anuria and oligohydramnios. The presence of minimal amounts of amniotic fluid is probably necessary for normal development of the fetal lung.     

Diagnostik der pränatalen Nierenfunktion

The evaluation of prenatal kidney function by fetal urinalysis for electrolytes, osmolality, proteins, amino acids, urea, creatinine and glucose is reviewed. Interpretation of the data requires knowledge of the normal urine values in healthy fetuses and due consideration for gestational age and maternal and fetal factors. Up to now there is no general consensus in the literature on the normal fetal urine composition. In cases with ultrasonographically detectable oligohydramnios and urinary tract obstruction fetal urinalysis has been proposed as a means of predicting postnatal kidney function. However, the present methods lack sensitivity and specificity, which makes an accurate prognosis in the individual case very difficult.