Overview of Prenatal Diagnosis: Cincinnati Fetal Center

The three major causes of LUTO are urethral atresia (complete obstruction with no communication from bladder neck through urethra), posterior urethral valves (flap of tissue in proximal urethra), and mid-urethral hypoplasia (significant tapering and narrowing that becomes progressive obstruction as pelvic anatomy matures).

In complete urethral obstruction, progressive oligohydramnios leads to anhydramnios, causing physical deformations (joint contractures, ear flattening, Potter's phenotype), pulmonary hypoplasia due to inability to expand and contract chest, and severe hydronephrosis with progressive renal fibrocystic dysplasia resulting in renal failure after birth.

The stepwise approach to identifying fetuses for possible shunt therapy involves: (1) high-resolution ultrasound to evaluate anatomy and rule out associated anomalies like myelomeningocele and cardiac disease, (2) karyotype confirmation to rule out chromosomal abnormalities and confirm male sex, and (3) renal function evaluation by serial bladder drainage.

Amnioinfusion is sometimes necessary when sonographic evaluation is difficult due to oligohydramnios, to expand the amniotic fluid space and restore the fluid interface for better ultrasound imaging.

Female fetuses with large bladder-like structures usually have cloacal abnormalities and do not benefit from shunting because it is a completely different process and underlying pathophysiology.

Renal function evaluation involves draining the bladder completely on several occasions and analyzing sodium, chloride, calcium, osmolarity, total proteins, and beta-2 microglobulin as reflections of proximal tubular injury and possible direct injury to the glomerular apparatus.

Characteristic early LUTO ultrasound findings include large fluid-filled bladder with markedly thickened and echogenic walls due to smooth muscle hypertrophy and hyperplasia from pressure, dilated kidneys with increased echogenicity, and dilation of the intrarenal collecting system.

Increased renal echogenicity is evidence of compression of the renal parenchyma rather than a poor prognostic sign per se; following serial bladder drainages and allowing kidneys to drain, re-expansion of parenchyma occurs with more normal echogenicity.

The pathophysiology of hydronephrosis involves the collecting system (like a balloon) expanding within the kidney (like a sponge in a glass fishbowl), compressing the parenchyma against the serosa, impairing delicate vasculature, resulting in cell death, progressive fibrosis, and eventually cystic dysplasia.

The presence of discrete cortical cysts indicates irreversible kidney damage and means the kidney is not amenable to any kind of in utero therapy because of the severity of underlying injury.

Obstructing ureteroceles from ectopic insertion of a duplicated collecting system upper pole can cause bladder outlet obstruction and obstructive uropathy, and these are amenable to therapy.

Patent urachus (a tract from the dome of the bladder to the umbilical cord insertion) can open back up with early obstruction and high bladder pressure, draining urine into the amniotic fluid space, which is one underlying etiology for obstructive uropathy with normal amniotic fluid volume.

In megacystis-microcolon-hypoperistalsis syndrome (more common in females but seen in at least six dozen male cases), there is a neurologic defect in bladder and ureteral muscles preventing bladder contraction and emptying, with massively distended bladder but normal amniotic fluid; most do not survive more than a few years.

In megacystis-microcolon-hypoperistalsis syndrome, after bladder drainage the bladder wall remains very thin because it does not develop the hyperplasia or thickening typically seen in complete obstruction, and amniotic fluid flows into the amniotic cavity through a completely patent urethra.

With new technology, particularly FISH, vesicocentesis can be used to screen and confirm male karyotype and rule out major aneuploidies when amniocentesis is difficult due to anhydramnios or severe oligohydramnios.

Good prognostic urinary values for potential survival with successful shunt placement are: sodium <100, chloride <90, osmolarity <210, calcium <8, beta-2 microglobulin <6, and total protein <20 (units not specified in transcript).

Values above the cutoff thresholds indicate significant underlying renal injury and fibrotic changes; histologic examination of fetuses with values not much higher than these levels showed pretty significant fibrotic injury to the kidneys.

The first urine specimen from bladder tap is not predictive or reliable because it has been exposed to degradation products and osmotic gradients that change electrolyte composition; serial taps are necessary.

The second bladder tap (2 days after first) samples urine that was in the ureters and intrarenal collecting system; the third tap (2 days after second) samples freshly produced urine by the kidney and has much higher predictive value for detecting significant underlying injury.

Improving urinary values across serial taps (e.g., sodium initially poor but dropping after second and third taps) indicates an excellent candidate with reasonably good prognosis with successful shunting; worsening values indicate ongoing irreversible damage that shunting won't benefit.

After complete bladder drainage and refill, urethral atresia cases show symmetric, very thick, universal bladder wall thickening with a typical keyhole; posterior urethral valve cases show elongated bladder shape with more proximal than distal thickening; mid-urethral hypoplasia (prune belly/triad) cases show a 'snowman appearance' with typical keyhole but unusual three-part bladder shape.

In mid-urethral hypoplasia cases, histologic study showed typical hypertrophy and thickening in the lower bladder wall, but significant smooth muscle deficiency and abnormal composition in the upper bladder (more like a hernia sac), with abnormal smooth muscle from proximal ureters to renal pelvis and severe abnormalities in the bladder dome.

All urinary electrolyte cutoff thresholds are based on urine analyzed between 18 to 22 weeks of gestation and cannot be reliably used before 18 weeks or after 22 weeks without adjustment.

For fetuses at 17 weeks, the cutoff value would be extrapolated to be a bit higher; for 24 or 26 week fetuses, cutoff thresholds would be extrapolated to be much lower due to maturation and increasing kidney function with advancing gestational age.

There is no good data that allows prediction of renal injury at gestational ages of 26 or 28 weeks using the established electrolyte cutoffs.

The primary goal of fetal bladder shunting is to prevent pulmonary hypoplasia secondary to oligohydramnios; secondary goals are preservation of renal function and bladder function.

The Rocket shunt is a double-tailed silastic pigtail catheter inserted with coils in different directions; theoretically the flat end outside the baby's abdomen cannot be grabbed and pulled out, and the other end is inside the bladder.

Shunt procedures are done as outpatient with IV remifentanyl and if necessary propofol, local anesthetic, antibiotic, a dose of indomethacin, and possibly nifedipine immediately afterwards; the mother usually goes home a couple of hours later.

Amnioinfusion before shunt placement is the most important step because without good fluid volume around the fetus, the external end of the shunt (the trickiest part of the procedure) cannot be deposited properly.

Shunt placement inferior to the bladder is preferred; the higher the shunt placement, the greater the risk that when the bladder deflates, some holes in the shunt will be in the peritoneal cavity, potentially causing urine leakage and fetal urinary ascites.

Difficulties in fetal therapy trials include: rare conditions, many undetected prenatally, many parents choosing termination when faced with outcome realities, delay in accepting new therapy reflecting clinician and patient bias based on small heterogeneous observational studies, and loss of clinical equipoise.

In the Canadian population, when parents look at the outcome studies showing that only 40-50% have normal renal function and one-third need dialysis or transplant, many parents opt for termination of pregnancy rather than shunting.

Some LUTO cases can resolve spontaneously, as demonstrated by a case where a baby diagnosed at 14 weeks with anhydramnios at 17 weeks was observed peeing and filling its sac at 19 weeks, with recollection of amniotic fluid by 23 weeks with no intervention.

Spontaneous bladder decompression can occur through asymmetrical hydronephrosis or urinary ascites from bladder rupture; spontaneous rupture is unusual but very commonly happens after bladder drainage and always resolves after a few days.

Megacystis-microcolon-hypoperistalsis syndrome presents with very large bladder in a female fetus with normal amniotic fluid volume; these are cases where shunting is not advocated.

Massively enlarged bladder secondary to cloacal dysgenesis is a case where there is no role whatsoever for intervention.