USF Fetal Therapy Center
USF Health - College of Medicine

Fetal Lower Urinary Tract Obstruction:
Information For Healthcare Professionals

Fetal urinary tract obstruction (UTO) is defined as partial or complete obstruction of any portion of the urinary tract from the kidney to the urethra. The definition excludes conditions that result in dilatation of the urinary tract secondary to neurogenic etiologies. The term includes atresia, stenosis, stricture or occlusion of one or both ureters, the bladder neck, the urethra or urethral meatus, dilatation of one or both ureters, hydronephrosis, hydroureter, hypoplastic ureter, megaloureter, obstruction of the ureteropelvic junction (UPJ), the ureterovesical (UV) junction, or the vesicourethral (VU) junction, posterior urethral valves, anterior urethral valves and urethral valves, type not specified.

Fetoscopy

Incidence

This sporadic condition occurs in approximately 1:5000-8000 male fetuses with the most common cause being posterior valves. In females urethral atresia accounts for the majority of cases. Untreated, LUTO may lead to hydronephrosis, renal dysplasia, and perinatal death. Prenatally diagnosed cases of posterior urethral valves have a 30-50% mortality. If oligohydramnios is present at the time of prenatal diagnosis, the mortality is as high as 77 %. Death is attributed to pulmonary hypoplasia and renal dysplasia. To avert these complications, percutaneous vesico-amniotic shunts or open fetal vesicostomy have been previously performed in utero to treat these conditions.

Diagnosis

The differential diagnosis is best addressed by noting the presence or absence of a key-hole sign. If a key-hole sign is present, the fetus may be affected by PUV or urethral atresia. If a key-hole sign is absent, the fetus may be affected by prune-belly syndrome, VUR, neurogenic bladder, megacystis-microcolon, or cloacal dysgenesis. Dilated ureters may result from VUR or UVJ obstruction and may not be distinguished with ultrasound alone. A poor correlation exists between pyelectasis, hydronephrosis and obstruction. Indeed, grade IV-V VUR and prune-belly syndrome may al present with marked hydronephrosis, whereas PUV or urethral atresia may not.

Assessment of fetuses with obstructive uropathy for in utero therapy

  1. Ultrasound criteria for therapy. In utero therapy is usually limited to fetuses with bladder outlet obstruction, with two exceptions: bilateral UPJ obstruction, or ureteral obstruction secondary to an ectopic ureter without megacystis. Fetuses with unilateral UPJ obstruction are not typically considered candidates for in utero therapy, regardless of the magnitude of the obstruction or renal findings. In these patients, the risk/benefit ratio of in utero intervention favors expectant management, even if this means loss of the ipsilateral renal unit. There is no consensus as to whether patients with bilateral UPJ obstruction may be offered treatment, with derivation of one or both obstructed pelves. As mentioned, obstructive ureteroceles may cause unilateral or bilateral ureteral obstruction without megacystis. These cases may be amenable to in utero therapy via the fetal bladder, although with more far more difficulty than when megacystis is present.
  2. Ultrasound prognostic factors. The assessment of fetuses with presumed obstructive uropathy begins with a thorough ultrasound examination. Ultrasound may assist in determining the level of dilatation, the differential diagnosis, presence or absence of hydronephrosis or renal cystic dysplasia, and to rule out possible associated congenital anomalies. Genuine bladder outlet obstruction may be suspected by the presence of a key-hole sign. Hydroureters from obstruction may be suspected if a dilated UVJ is absent, but may not be ruled out if the UVJ is dilated (secondary dilatation). Hydronephrosis, renal cysts and hyperechogenicity have been assessed as prognostic factors of renal cystic dysplasia (Mahony, 1984).
  3. Fetal gender. Sonographic assessment of the fetal gender is paramount, as different conditions affect males, females, or both. Sonographic identification of the fetal gender may be hindered by the presence of oligohydramnios and distortions of the fetal anatomy from massive megacystis among other factors.
  4. Associated anomalies. Associated congenital anomalies may be present in approximately 17-30% of fetuses with obstructive uropathy. Because of their frequence and clinical significance, the search for associated anomalies should not be overlooked despite the presence of impressive urinary tract abnormalities.
  5. Chromosomal abnormalities. The incidence of karyotypic abnormalities in fetuses with sonographic findings suggestive of obstructive uropathy is 8- 23%. Karyotype analysis is thus part of the basic assessment of these fetuses. If megacystis and oligohydramnios are both present, it is frequently easier to obtain fetal urine than amniotic fluid or fetal blood. Successful chromosomal analysis can be achieved from fetal urine in up to 95% of cases, and in 65% of fluorescent in situ hybridization (FISH) studies. Because of the high incidence of chromosomal abnormalities, therapy should be withheld until results of the chromosome analysis become available.
  6. Fetal urinary markers of renal function. Fetal renal function may be assessed by analysis of fetal urinary parameters via vesicocentesis. Renal damage from obstructive uropathy is associated with salt-wasting. Fetal urinary sodium decreases normally with gestational age, consistent with increased renal maturation. Several urinary parameters have been assessed as predictors of renal cystic dysplasia including sodium, calcium, total protein, microalbumin, phosphate, N-acetyl-beta-D-glucosaminidase, osmolality, and B-2-microglobulin. Patients are considered candidates for in utero therapy if fetal urinary parameters are below the threshold for renal cystic dysplasia. If the values are above threshold, therapy should not be offered. The diagnostic indices of the most commonly used abnormal fetal urinary parameters (Johnson, 1994)
    1. Sodium >100 mEq/dl
    2. Chloride >90 mEq/dl
    3. Calcium >8 mEq/dl
    4. Beta-2-microglobulin >10 mg/L
    5. Osmolality >210 mOsm/L
    6. Total protein >20 mg/dL
  7. Single or repeated vesicocentesis. Stagnant fetal urine within the fetal bladder is apt to become concentrated with time due to preferential loss of water through the bladder wall. As a result, "old" fetal urine is less likely to reflect the actual fetal renal function at the time of the vesicocentesis. If an initial vesicocentesis yields urinary values below the threshold for renal cystic dysplasia, no further vesicocenteses are necessary. However, if the values are above threshold, a second vesicocentesis within 48 hours is recommended. Some authors recommend a third vesicocentesis if the second sample still yields values above threshold.
  8. Complications of vesicocentesis. There is a paucity of literature on the complications of vesicocentesis. Iatrogenic vesicoperitoneal fistula has been reported, with subsequent fetal urinary ascites. Premature rupture of membranes, chorioamnionitis, miscarriage and fetal death may also occur. The frequency of these complications is additive as repeated procedures are performed.
  9. Umbilical cord sampling. Fetal renal function status may also be assessed from fetal serum via cordocentesis. Potential advantages of this approach over fetal vesicocentesis include performance of a single procedure and faster karyotype results. Disadvantages include potential increased risk of fetal demise, increased degree of technical difficulty and decreased access.
    Beta 2-microglobulin and creatinine are both serum markers of renal function in children and adults. In contrast to creatinine, beta 2-microglobulin does not cross the placenta to a significant extent. Fetal beta 2-microglobulin values remain unchanged or decrease with advancing gestation. Thus, increased serum beta 2-microglobulin values correlate with decreased renal function. Different threshold values have been proposed. A beta 2-microglobulin above 5.6 mg/L has been associated with a sensitivity of 80.0%, specificity of 98.6%, a positive predictive value of 88.9%, and a negative predictive value of 97.1% for the prediction of renal cystic dysplasia. Unilateral renal damage is also associated with elevated beta 2-microglobulin values, suggesting that the contralateral kidney is unable to fully compensate the unilateral loss of renal function in utero. Thus, cordocentesis should not be used to differentiate unilateral from bilateral renal damage.
  10. Results of the work-up algorithm. The application of selection criteria on patients with fetal UTO for possible in utero therapy results in a significant attrition rate. Disqualification from therapy may result both from "too healthy" or "too sick" conditions. Examples of "too healthy" conditions include normal amniotic fluid volume or suggestion of non-obstructive dilatation of the urinary tract. Examples of "too sick" conditions include sonographic evidence of renal cystic dysplasia, abnormal fetal urinary parameters, abnormal karyotype, or the presence of associated major congenital anomalies. Of 90 patients referred to our institution from October 1996 to October 2003, more than half were disqualified from therapy from single or overlapping conditions. Approximately 19% were classified as being "too healthy" and approximately 33% being "too sick."

Treatment of Fetal UTO

VESICOAMNIOTIC SHUNTING

Percutaneous ultrasound-guided vesicoamniotic shunting (VAS) of fetuses with LOU began in the early 1980's. The goal of therapy is to avert development of pulmonary hypoplasia from the attendant oligohydramnios as well as to preserve renal function. Fetal vesicostomy via open fetal surgery was at one time proposed, as a way to avoid the limitations of VAS, but did not gain acceptance and is thus only of historical interest. VAS should currently be offered only to patients without sonographic or biochemical evidence consistent with renal cystic dysplasia, normal karyotype, and lack of associated major congenital anomalies.

FETAL CYSTOSCOPY

In 1995, we proposed the use of endoscopy to assess the fetal bladder for both diagnostic and surgical purposes. The technique can be performed with submillimetric or standard diagnostic or operative fetoscopy endoscopes. Fetal cystoscopy allows a whole new set of diagnostic and therapeutic procedures not possible with any other approach.

LASER ABLATION URETERAL VALVES

Fetal cystoscopy may disclose ureteral valves unsuspected in a fetus with fetal UTO. Ureteral valves result from failure of a thin membrane between the bladder and ureter to disappear by the 37th day of gestation. Rarely, the valve is complete, allowing some urine to flow into the bladder. If the ipsilateral kidney is dysplastic, this may lead to above threshold values for fetal urinary values during vesicocentesis even though the contralateral kidney may be unaffected, as mentioned above. Because of this, fetal therapy may still be warranted in these cases despite urinary markers above-threshold values. Ablation of ureteral valves is easily accomplished with the YAG laser.

LYSIS OF OBSTRUCTIVE URETEROCELE

Ureteroceles resulting in bladder outlet obstruction may be diagnosed on ultrasound by the presence of megacystis, hydroureter(s), and a membrane-like structure within the bladder. In the absence of oligohydramnios, therapy is not indicated, as this suggests that the obstruction is not complete. Treatment is indicated to prevent renal damage and pulmonary hypoplasia in cases associated with progressive development of oligohydramnios. Fetal cystoscopy allows identification of the ureterocele within the bladder. The urethra is typically dilated as a result of the obstruction. Treatment is accomplished by performing a linear lysis of the wall of the ureterocele from within the fetal bladder with a contact YAG laser fiber. The incision must involve a significant longitudinal length, to avoid resealing. As a result of the lysis, the ureterocele collapses and urethral patency is restored.

LASER ABLATION OF POSTERIOR URETHRAL VALVES

In normal fetuses, the urethra is not dilated, appearing as a small hole within the bladder. A non-dilated urethra may also be found in patients with Prune Belly Syndrome in which, despite massive megacystis, urethral dilatation is not typically present. In patients with a true urethral obstruction, endoscopy will show a variable dilatation of the urethra at the level of the bladder neck. Ablation of posterior valves is accomplished with the YAG laser and contact laser fiber.

Specific complications of endoscopic ablation of posterior urethral valves.

  1. Iatrogenic ascites. Leakage of fluid around the trocar into the fetal abdomen may occur during surgery. This complication may also occur with standard VAS, although it is probably more likely with cystoscopy, because of the larger trocar diameter and from vesicoinfusion to improve visualization. Unless fetal bradycardia develops, we do not recommend removing the ascites after leaving the bladder, as this may result in iatrogenic gastroschisis.
  2. Urethrorectal fistula. This complication results from thermal damage beyond the posterior wall of the urethra into the perirectal space. To avoid this complication, only 5-10 Watts of energy in short bursts should be used while ablating the valves.

Referrals

Please contact us to fax the Fetal Bladder Evaluation/Screening Form to your office. For further information, feel free to contact us.

Phone Toll Free: 1-877-FETAL-77
Phone: 813-259-8513
Fax: 813-259-0839
Email: sdzabel@tgh.org 

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