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Fetal Lower Urinary Tract Obstruction (LUTO)

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Last update: 
August 30, 2009
Authors: 
Albert P. Sarno
Authors: 
Michael W. Bebbington
Authors: 
R. Douglas Wilson
Authors: 
Mark Paul Johnson

Key Points

- The fetal genitourinary tract should be evaluated routinely when sonographic assessment is performed in the second or third trimester
- Serial vesicocentesis (x3) should be performed and renal parenchyma evaluated for evidence of cystic dysplasia to assess fetal renal function when LUTO is identified
- Vesicoamniotic shunt placement should be considered in LUTO in male fetuses who demonstrate a normal karyotype, absence of renal dysplasia by sonographic assessment, urinary electrolyte and protein levels below established abnormal cutoff threshold values and oligo/anhydramnios

Introduction

Lower urinary tract obstruction (LUTO) is a heterogeneous condition with a quite variable natural history. Though early studies suggested a perinatal mortality in excess of 50% with a significant proportion of survivors suffering long-standing pulmonary and renal morbidity, 1 recent case-series have demonstrated in excess of 90% survival in fetuses properly selected for in utero therapy by vesicoamniotic shunting. 2

  1. 1. Nakayama DK, Harrison MR, deLorimier AA: Prognosis of posterior urethral valves presenting at birth. J Pediatr Surg 1986;21:43-48.
  2. 2. Biard JM, Johnson MP, Carr MC, et al. Long-term outcomes in children treated by prenatal shunting for lower urinary tract obstruction. Obstet Gynecol 2005;106(3):503-8.

Diagnosis/definition

Fetal LUTO is a heterogeneous group of disorders characterized by proximal urethral obstruction, enlarged bladder, bilateral hydronephrosis with pyelocaliectasis, and oligo/anhydramnios. In the male fetus, posterior urethral valves, urethral atresia, and Prune Belly syndrome variant (urethral hypoplasia) are the most common causes. In the female fetus, LUTO is almost always associated with cloacal developmental abnormalities.

Epidemiology

The incidence of posterior urethral valves has been reported to be between 1 in 5000 and 1 in 25,000 births.1 This range of incidence is due to the wide spectrum of severity seen in LUTO that includes fetal disease characterized by oligohydramnios, renal dysplasia and pulmonary hypoplasia to the serendipitous identification of asymptomatic bladder outlet obstruction in adult males undergoing unrelated cystoscopic evaluation.

  1. 1. Atwell JD. Posterior urethral valves in the British Isles: a multicenter BAPS review. J Pediatr Surg 1983; 18:70-74.

Genetics

Embryology:
Posterior urethral valves are embryologically derived from mullerian duct remnants or remnants of the cloacal membrane between the 7th and 11th week of gestation.1 Persistence of these valves in male fetuses can result in proximal urethral dilatation, hypertrophy and distention of the bladder, hydroureters and hydronephrosis.
LUTO due to posterior urethral valves or urethral atresia is a sporadic condition, with no increased risk of recurrence greater than the general population. Familial recurrence has been reported, however. The megacystis-microcolon-hypoperistalsis syndrome, which occurs more frequently in females, is a rare cause of bladder outlet obstruction that may be difficult to distinguish prenatally from other etiologies of LUTO. The distinction is important to establish postnatally however, due to autosomal recessive genetic transmission with a 25% recurrence risk.

  1. 1. Dewan PA, Zappala SM, Ransley PG, et al. Endoscopic reappraisal of the morphology of congenital obstruction of the posterior urethra. Br J Urol 1992; 70:439-444.

Pathophysiology

There are no known teratogenic agents associated with the occurrence of LUTO. The basic pathophysiology of LUTO includes bladder outlet obstruction due to several possible etiologies including posterior urethral valves (most common), urethral atresia and Prune Belly syndrome variant in males, and cloacal developmental abnormalities in female fetuses.1 The triad of abdominal muscular deficiency, obstructive uropathy, and failure of testicular descent is well described; however, there remains no consensus regarding the etiology and developmental pathogenesis of this group of findings. The contributions of urinary extravasation or bladder distention to the development of the “prune belly” phenomenon remain controversial. Nevertheless, the resultant effect of LUTO is marked distention of the fetal bladder, hydroureters, hydronephrosis and the subsequent development of oligo/anhydramnios, pulmonary hypoplasia and renal fibrocystic dysplasia. Animal models support this pathophysiology.2

  1. 1. Johnson MP. Fetal obstructive uropathy. In Harrison MR, Evans MJ, Adzick NS, Holzgreve W, eds. The Unborn Patient: The Art and Science of Fetal Therapy. Philadelphia: W.B.Saunders, 2001:259-286.
  2. 2. Harrison MR, Ross NA, Noall R, deLorimier AA: Correction of urogenital hydronephrosis in utero. The: Fetal urethral obstruction produces hydronephrosis and pulmonary hypoplasia in fetal lambs. J Pediatr Surg 1983;18:247-256.

Classification

A classification scheme for PUV has been described.1 2 In Type I PUV, sail-like valve leaflets arise from the crista-urethralis distal to the verumontanum and may cover/obstruct the lower half of the urethra or may completely obstruct the urethra. Type II valves are non-obstructing folds of the superficial muscle and mucosa that extend from the verumontanum to the bladder neck. Type III valves usually cause a diaphragm-like obstruction at the level of the verumontanum, but can be seen at the level of the anterior urethra distal to the external urethral sphincter.

  1. 1. Young HH, Frantz WA. Congenital obstruction of the posterior urethra. J Urol 1919;3289-365.
  2. 2. Hendren WH. Posterior urethral valves in boys: a broad clinical spectrum. J Urol 1971;106:298-307.

Risk factors/associations

No known risk factors.

Complications

Pregnancies complicated by LUTO (with or without shunt placement) generally deliver at 34-35 weeks gestation due to preterm, premature rupture of membranes.1

  1. 1. Johnson MP. Fetal obstructive uropathy. In Harrison MR, Evans MJ, Adzick NS, Holzgreve W, eds. The Unborn Patient: The Art and Science of Fetal Therapy. Philadelphia: W.B.Saunders, 2001:259-286.

Pregnancy considerations

Screening:
Sonographic detection is currently used as a screening tool for LUTO.
Ultrasound:
Findings: The sonographic as well as ultrafast fetal MRI findings in LUTO are variable due to the wide spectrum of disease. However, pathologic obstruction common to all cases of LUTO results in a distended fetal bladder with or without a “keyhole” dilatation of the posterior urethra, hydroureters and hydronephrosis. (Figure 1) The fetal bladder after drainage by vesicocentesis for either urethral atresia or complete obstructing posterior urethral valves demonstrates a symmetrically round and very thick walled appearance.10 Evaluation of the renal parenchyma may show normal appearing cortex, echogenic cortex due to parenchymal compression or, in advanced cases, the finding of cystic renal dysplasia. (Figure 2) Hydronephrosis may be absent if renal dysplasia has occurred, with subsequent cessation of fetal urine production. Extensive and long-standing obstruction may cause extravasation of urine, resulting in a perinephric urinoma due to rupture of the renal cortex, or urinary ascites due to rupture of the fetal bladder. 11,12 This “safety valve” rupture phenomenon has been postulated to transiently prevent further renal compromise, however, renal outcomes remain highly variable. Long-standing oligo/anhydramnios may cause additional fetal deformations including clubfeet and Potter facies (the latter generally identifiable only at birth).
Amniotic fluid: The amniotic fluid volume depends on the gestational age of the fetus and the degree of lower urinary tract obstruction. Prior to 16 weeks gestation, normal amniotic fluid volume may be seen since amniotic fluid is primarily a transudate of fluid from the fetal skin tissues and placental membranes. Following this gestational age, amniotic fluid volume begins to reflect fetal renal production of urine and fetal swallowing.13 Partial obstruction of the lower urinary tract may result in normal to low normal amniotic fluid volume, while with complete obstruction, oligohydramnios or frank anhydramnios is generally established by 18-20 weeks gestation.
Placenta: Normal appearance by ultrasound and ultrafast fetal MRI imaging.
Biometry/measurement data: Normal fetal biometric parameters. In the presence of urinary ascites or severely hydronephrotic kidneys, an enlarged fetal abdominal circumference may be documented.
When detectable: LUTO may be identified as early as 12-14 weeks of gestation with modern high frequency ultrasound transducers. However, many of these cases will spontaneously resolve by 15 weeks of gestational age. Complete lower urinary tract obstruction should be identifiable in all cases by 18-20 weeks gestation.
Pitfalls: Bilateral ureteropelvic junction (UPJ) obstruction or ureterovesical obstruction/reflux (the latter including findings of hydroureters) may be mistaken for LUTO. The key to prenatal differentiation includes the appearance of the distended fetal bladder and severity of amniotic fluid volume compromise. Renal dysplasia should only be strongly suspected in the presence of renal cortical cysts. Echogenicity may be due to compression of renal parenchyma due to increased intrarenal pressure and not represent true fibrocystic dysplasia. Urinary electrolytes and protein levels obtained by serial fetal vesicocentesis should be used in conjunction with sonographic criteria to determine if renal dysplasia is present.14
Differential diagnosis: The differential diagnosis of LUTO includes all causes of bilateral hydronephrosis (Table 1). The sex of the fetus will be helpful in determining the differential diagnosis. The presence of male external genitalia with LUTO suggests the diagnosis of urethral obstruction with posterior urethral valves and urethral atresia being most frequent. Female genitalia and urethral atresia may be associated with a cloacal developmental abnormality, caudal regression syndrome or megacystis-microcolon-hypoperistalsis syndrome. Sonographic features of the latter condition, a rare and generally lethal condition affecting primarily female fetuses, include small bowel dilatation and polyhydramnios in the third trimester. Rarely, an intravesical ectopic ureterocele can result in complete bladder outlet obstruction. (Figure 3)
Where else to look: A careful sonographic evaluation for associated structural malformations is required. Due to the often-concurrent oligo/anhydramnios, transabdominal amnioinfusion may be required to develop an acoustic window allowing detailed assessment of the fetus. Sonographic markers of fetal aneuploidy should be evaluated since approximately 10% of fetuses with LUTO will be found to be aneuploid (Trisomies 21, 18 and 13).15 The fetal heart, spine, brain and the appearance of the extremities should be evaluated for signs of an underlying genetic syndrome or abnormal developmental sequence.

Pregnancy Management

Principles

Due to the heterogeneity of LUTO, counseling of the patient and family can be quite problematic. Obtaining and reviewing all the appropriate data is essential prior to providing a diagnosis and planning further management. In the karyotypically normal male fetus with LUTO due to urethral obstruction with no other structural malformations, the family may be counseled that the fetus is likely to face a 50% or greater perinatal mortality and substantial pulmonary and renal morbidity if conservative management is employed. In the presence of anhydramnios before 20 weeks, outcome is almost universally lethal. Pulmonary hypoplasia is the leading cause of neonatal mortality in LUTO. Intrauterine fetal demise is also possible due to anhydramnios and associated cord compromise. Spontaneous preterm delivery occurs frequently.
Pregnancy termination should be offered due to the substantial morbidity and mortality associated with LUTO dependent on gestational age at evaluation. Perinatal autopsy should be recommended for confirmation of the diagnosis and to determine the source of urinary obstruction. Induction of labor with misoprostol rather than dilatation and extraction may provide an intact fetus for better pathologic study.

Prevention

Primary prevention is not currently feasible, however epidemiologic evidence suggests that folic acid deficiency may predispose the fetus to malformations in several organ systems, including the genitourinary tract.1 Periconceptional folic acid therapy may reduce the risk of genitourinary anomalies, but is undetermined at this time and will require prospective study.

  1. 1. Gordon TE. Leeth EA, Nowinski CJ, et al. Geographic and temporal analysis of folate-sensitive fetal malformations. J Soc Gynecol Investig 2003; 10:298-301.

Work-up

A thorough and comprehensive sonographic assessment is required to exclude associated structural malformations. Fetal echocardiography should be a component of this assessment. Ultrafast fetal MRI is also a reasonable consideration, particularly to image the fetal central nervous system. A fetal karyotype is essential. If oligo/anhydramnios precludes amniocentesis, a fetal karyotype may be obtained by transabdominal chorionic villous sampling or cordocentesis. Fluorescence in-situ hybridization (FISH) analysis can provide rapid screening for major autosomal aneuploidies (Trisomy 21, 18, 13) and sex chromosome aneuploidies from both amniocytes and chorionic villi with 48-72 hours with complete, banded karyotypes available in 7-10 days. Cordocentesis can provide a complete banded karyotype within 72 hours, but is not any longer necessary.
Serial vesicocenteses (a total of at least 3) are performed at 48-72 hour intervals to assess the status of fetal renal function by quantitation of urinary components including Na, Cl, Osmolality, Ca, total protein and beta 2-microglobulin. The use of multiple fetal urine aspirations to document change in tonicity has helped to select fetuses that will benefit from in utero therapy.1 (Table 2). If available, antenatal consultation with a pediatric urologist is recommended.

  1. 1. 14. Johnson MP, Corsi P, Bradfield W, et al. Sequential fetal urine electrolytes provides greater precision in the evaluation of fetal obstructive uropathy. Am J Obstet Gynecol; 173:59-65.

Therapy

Fetal intervention in selected fetuses is indicated to restore amniotic fluid volume and prevent neonatal death due to pulmonary hypoplasia.1 The benefit to preservation of renal function is less clear. Criteria for placement of a vesicoamniotic shunt include a male fetus with LUTO due to urethral obstruction, normal karyotype and lack of other associated malformations, oligo/anhydramnios, lack of renal cystic dysplasia by ultrasound in conjunction with fetal urinary electrolytes and protein levels below threshold values. Amnioinfusion with Ringers lactate may be necessary to re-establish reasonable amniotic fluid volume for proper shunt placement. Technical aspects of shunt placement are well described and will not be discussed here.2 Thorough counseling of the patient prior to the procedure is necessary to discuss the risk, expected benefits and alternatives to vesicoamniotic shunt placement. Vesicoamniotic shunt placement is not recommended if these criteria cannot be satisfied. At present, shunt intervention is not recommended if amniotic fluid volume is maintained in normal to low normal AFI range. In conservatively managed cases with only partial obstruction and in which late onset oligohydramnios or renal dysplasia is suspected, the decision to promote preterm delivery should be carefully based on a balance of the risks and benefits of ex utero therapy versus the potential morbidity and mortality associated with prematurity. Shunt intervention for female fetuses with LUTO is not recommended since previous attempts at in utero shunt therapy have not been shown to improve outcome due to the often-associated complex developmental abnormalities of the cloaca and the changing composition and character of the fluid in the cloaca as pregnancy progresses.

  1. 1. Johnson MP. Fetal obstructive uropathy. In Harrison MR, Evans MJ, Adzick NS, Holzgreve W, eds. The Unborn Patient: The Art and Science of Fetal Therapy. Philadelphia: W.B.Saunders, 2001:259-286.
  2. 2. Johnson MP. Fetal obstructive uropathy. In Harrison MR, Evans MJ, Adzick NS, Holzgreve W, eds. The Unborn Patient: The Art and Science of Fetal Therapy. Philadelphia: W.B.Saunders, 2001:259-286.

Antepartum testing

Ultrasound monitoring is suggested weekly following shunt placement to assess shunt position, bladder size, kidney appearance and amniotic fluid volume. Up to 40% of shunts become displaced and may require replacement if oligohydramnios recurs in the midgestation.1 Following confirmation of successful shunt position over the next three weeks, the patient may be assessed every two weeks. In patients with partial obstructions not undergoing shunt placement, amniotic fluid volume and assessment of renal parenchyma for evidence of cystic dysplasia should be performed every 1-2 weeks.

  1. 1. Johnson MP. Fetal obstructive uropathy. In Harrison MR, Evans MJ, Adzick NS, Holzgreve W, eds. The Unborn Patient: The Art and Science of Fetal Therapy. Philadelphia: W.B.Saunders, 2001:259-286.

Delivery

Route of delivery is dictated by obstetrical indications. A neonatologist should be present for delivery if viability is felt to be possible. Decision regarding fetal monitoring and surgical delivery for a non-reassuring fetal heart rate tracing should be discussed prior to onset of labor.

Post-partum/breastfeeding

Neonatology management:
Resuscitation: Because pulmonary function may be compromised by pulmonary hypoplasia, bladder distension, renal enlargement or urinary ascites, preparations for assisted ventilation at delivery by a skilled practitioner are mandatory.
Transport/testing/confirmation/nursery management: Transport to a tertiary level center capable of further diagnostic and therapeutic intervention and pediatric urologic specialty care is warranted unless survival is not expected or aggressive management is not requested by the parents. Further management in the nursery includes appropriate respiratory support and nutrition. Fluid and protein intake should be monitored carefully until urethral patency and renal function have been determined. Serum electrolytes, BUN and creatinine may be reasonable markers of renal function, but they are inaccurate in the first 48-72 hours of life, reflecting transition from placental to newborn renal clearance. Abdominal ultrasound for assessment of the neonatal genitourinary tract, voiding cystourethrogram and nuclear renal scan will also be helpful in further evaluating the neonate.1

Surgery:
Preoperative assessment/operative indications/types of procedures: Surgical intervention is indicated when there is evidence of obstruction that threatens renal function. Minimally invasive decompression by transurethral or suprapubic catheter placement may be employed as a temporizing measure until definitive surgical repair can be performed. Posterior urethral valves and obstructing ureterocele may be amenable to cystoscopic therapy, though further surgical intervention may be necessary in the newborn period or early in infancy.
Long-term outcome of prenatal intervention: Unfortunately, there have been no randomized trials or large multicenter studies to address outcome of children with prenatal intervention for LUTO. However, a recent study was designed to focus on the long-term outcomes of children with LUTO due primarily specific urethral obstructions and treated with antenatal vesicoamniotic shunt placement.2 In this group of children selected for in utero intervention by established criteria, survival at one year was 91% with two neonatal deaths occurring due to pulmonary insufficiency (hypoplasia). Posterior urethral valves and prune-belly syndrome were the most common final postnatal diagnosis (39% each). At a median follow-up age of 5.8 years, 44% of the entire group demonstrated acceptable renal function (creatinine clearance >70 ml/min) while an additional 22% demonstrated mild renal insufficiency (creatinine clearance <70 ml/min) not requiring renal replacement. Persistent respiratory problems were present in 44% of children (asthma and recurrent pulmonary infections most common), musculoskeletal problems in 50% and frequent urinary tract infections in 50%. Spontaneous voiding was experienced by 61% of the group. Interestingly, health-related quality of life assessed by both children and parents did not differ from a healthy child population.

Maternal postpartum:
Future pregnancy preconceptional counseling: Because the condition is sporadic, future pregnancies are at low risk for recurrence. However, reasonable surveillence includes a screening sonographic evaluation at 15-16 weeks, comprehensive fetal anatomic survey at 20-22 weeks and mid-third trimester evaluation of amniotic fluid volume and renal architecture if bladder enlargement and/or hydronephrosis are present.

  1. 1. Bianchi DW, Crombleholme TM, D’Alton ME. Fetology: Diagnosis and Management of the Fetal Patient. New York: McGraw-Hill, 2000:593-606.
  2. 2. Biard JM, Johnson MP, Carr MC, et al. Long-term outcomes in children treated by prenatal shunting for lower urinary tract obstruction. Obstet Gynecol 2005;106(3):503-8.

Future

Future developments will include efforts to further refine the approach to intervention in LUTO, with development of techniques to decrease the greatest technical complication of shunt displacement and migration. One technique currently under evaluation is the cystoscopic disruption of posterior urethral valves.1 In this approach, microcystoscopy is performed and the proximal urethra directly visualized. If valves can be confirmed, then laser ablation or mechanical disruption may be technically possible. This approach has been used investigatively with mixed results, but may hold promise for the future by relieving the obstruction without the need for a diverting catheter. Perhaps more importantly, it may allow for a more normal physiologic state of bladder cycling with storage and voiding, which has been suggested to play an important role in long-term bladder function.

  1. 1. Johnson MP. Fetal obstructive uropathy. In Harrison MR, Evans MJ, Adzick NS, Holzgreve W, eds. The Unborn Patient: The Art and Science of Fetal Therapy. Philadelphia: W.B.Saunders, 2001:259-286.

Tables

Figures

Algorithms