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Bladder outlet obstruction

Published:September 07, 2021DOI:https://doi.org/10.1016/j.ajog.2021.06.039

      Introduction

      Fetal bladder outlet obstruction (or lower urinary tract obstruction [LUTO]) is most commonly caused by posterior urethral valves and urethral atresia and can lead to abnormal renal development and pulmonary hypoplasia. It is associated with a high rate of perinatal morbidity and mortality.

      Definition

      Prenatally detected LUTO occurs because of a blockage in the lower urinary tract (the bladder outlet) of the developing fetus and leads to megacystis, a thickened bladder wall, and bilateral hydronephrosis with or without cystic dysplasia of the renal parenchyma.

      Ultrasound Findings

      In the first trimester of pregnancy, megacystis, or an enlarged bladder, is commonly defined as a sagittal length >7 mm.
      • Sebire N.J.
      • Von Kaisenberg C.
      • Rubio C.
      • Snijders R.J.
      • Nicolaides K.H.
      Fetal megacystis at 10-14 weeks of gestation.
      • Liao A.W.
      • Sebire N.J.
      • Geerts L.
      • Cicero S.
      • Nicolaides K.H.
      Megacystis at 10-14 weeks of gestation: chromosomal defects and outcome according to bladder length.
      • Kagan K.O.
      • Staboulidou I.
      • Syngelaki A.
      • Cruz J.
      • Nicolaides K.H.
      The 11-13-week scan: diagnosis and outcome of holoprosencephaly, exomphalos and megacystis.
      After the first trimester of pregnancy, there is no single definition of megacystis, with many different definitions found in the literature.
      • Taghavi K.
      • Sharpe C.
      • Stringer M.D.
      Fetal megacystis: a systematic review.
      One study defined the normal sagittal length as the gestational age in weeks minus 5 mm (±95% upper or lower confidence interval [CI]=7); megacystis was defined as greater than the upper limit of the 95% CI for the gestational age.
      • Maizels M.
      • Alpert S.A.
      • Houston J.T.
      • Sabbagha R.E.
      • Parilla B.V.
      • MacGregor S.N.
      Fetal bladder sagittal length: a simple monitor to assess normal and enlarged fetal bladder size, and forecast clinical outcome.
      A thickened bladder wall is defined as one that measures >3 mm. Hydronephrosis is defined as dilation of the renal pelvis, as measured in the anteroposterior diameter, of ≥4 mm in the second trimester of pregnancy and ≥7 mm in the third trimester of pregnancy (Figure 1). A dilated posterior urethra, also known as the “keyhole” sign, is commonly associated with posterior urethral valves (Figure 2). In addition, ureteral dilation may be seen because of the reflux from high bladder pressure. The kidneys may develop cystic dysplasia or become echogenic and atrophied.
      Figure thumbnail gr1
      Figure 1Marked bladder dilation with dilation of the renal pelves
      Dilation of renal pelvis consistent with bladder outlet obstruction.
      LK, left kidney; RK, right kidney.
      Society for Maternal-Fetal Medicine. SMFM Fetal Anomalies Consult Series #4. Am J Obstet Gynecol 2021.
      Figure thumbnail gr2
      Figure 2Markedly dilated bladder
      The asterisk indicates a distended proximal urethra, giving the characteristic keyhole appearance of the proximal urethral valves. Oligohydramnios is present.
      Society for Maternal-Fetal Medicine. SMFM Fetal Anomalies Consult Series #4. Am J Obstet Gynecol 2021.

      Associated Abnormalities

      Most cases (78%) of LUTO are isolated.
      • Malin G.
      • Tonks A.M.
      • Morris R.K.
      • Gardosi J.
      • Kilby M.D.
      Congenital lower urinary tract obstruction: a population-based epidemiological study.
      LUTO is often associated with oligohydramnios, possibly leading to clubbed feet or pulmonary hypoplasia. Urinary ascites and perinephric urinomas can occur as a result of bladder or kidney rupture.

      Differential Diagnosis

      The most common etiology of LUTO is posterior urethral valves (63%), which are congenital membranes in the posterior urethra that act as valves to block micturition. Classic features include megacystis, thickened bladder wall, dilated posterior urethra (“keyhole” sign), bilateral hydronephrosis or cortical cysts, and oligohydramnios. Urethral atresia is the second most common etiology of LUTO (10%) and may have the same appearance of a greatly enlarged bladder, although without a dilated urethra or keyhole appearance. Unlike posterior urethral valves, which occur only in males, urethral atresia can occur in both male and female fetuses.
      • Malin G.
      • Tonks A.M.
      • Morris R.K.
      • Gardosi J.
      • Kilby M.D.
      Congenital lower urinary tract obstruction: a population-based epidemiological study.
      Other conditions in the differential diagnosis of a dilated bladder include Prune-Belly syndrome (the triad of lax or absent abdominal musculature; a thin-walled, dilated bladder; and cryptorchidism), aneuploidy (most commonly trisomy 13,18, or 21), megacystis-megaureter syndrome (severe vesicoureteral reflux), and megacystis-microcolon syndrome (thin-walled bladder without dilated posterior urethra; normal or increased amniotic fluid).
      • Malin G.
      • Tonks A.M.
      • Morris R.K.
      • Gardosi J.
      • Kilby M.D.
      Congenital lower urinary tract obstruction: a population-based epidemiological study.
      ,
      • Ruano R.
      • Dunn T.
      • Braun M.C.
      • Angelo J.R.
      • Safdar A.
      Lower urinary tract obstruction: fetal intervention based on prenatal staging.
      In a female fetus, a dilated vagina caused by a septal anomaly can mimic a dilated bladder. A persistent cloaca (convergence of bladder, rectum, and vagina with a single perineal opening) should also be considered. A large case series found that 26.9% of prenatal diagnoses of LUTO were falsely positive. The most common final postnatal diagnoses in these cases were vesicoureteral reflux (24.5%), cloacal dystrophy (18.9%), and hydronephrosis (11.3%). In 5 cases, the obstruction resolved during the pregnancy.
      • Malin G.
      • Tonks A.M.
      • Morris R.K.
      • Gardosi J.
      • Kilby M.D.
      Congenital lower urinary tract obstruction: a population-based epidemiological study.

      Genetic Evaluation

      Diagnostic testing with amniocentesis or chorionic villus sampling and chromosomal microarray analysis (CMA) should be offered when bladder outlet obstruction is detected. If a dilated bladder and severe oligohydramnios make amniocentesis not feasible, testing can be done by placental biopsy or on fluid obtained by vesicocentesis. If ultrasound findings or screening test results suggest a common aneuploidy, it is reasonable to initially perform karyotype analysis or fluorescence in situ hybridization, with reflex to CMA if these test results are normal. If there are additional anomalies, consanguinity, or a family history of a specific condition, gene panel testing or exome sequencing is sometimes useful because CMA does not detect single-gene (Mendelian) disorders. If exome sequencing is pursued, appropriate pretest and posttest genetic counseling by a provider experienced in the complexities of genomic sequencing is recommended. After appropriate counseling, cell-free DNA screening is an option for patients who decline diagnostic evaluation particularly if a common aneuploidy is suspected.

      Pregnancy and Delivery Management

      Given the poor prognosis associated with LUTO, pregnancy termination should be offered. Shared patient decision-making requires a thorough evaluation and multidisciplinary counseling regarding prognosis. For patients who continue their pregnancy, serial vesicocenteses have been suggested to assess fetal renal function to help determine whether fetal intervention should be pursued, although there is controversy regarding their benefit as prognostic markers.
      • Ruano R.
      • Dunn T.
      • Braun M.C.
      • Angelo J.R.
      • Safdar A.
      Lower urinary tract obstruction: fetal intervention based on prenatal staging.
      Fluid from the bladder is completely removed two or three times sequentially to measure urinary electrolytes and the degree of bladder refilling. Normal values for fetal urine are as follows: sodium<100 mg/dL, chloride<90 mg/dL, osmolarity<200 mOsm/L, calcium<8 mg/dL, total protein<20 mg/dL, and beta-2-microglobulin<4 mg/dL.
      • Abdennadher W.
      • Chalouhi G.
      • Dreux S.
      • et al.
      Fetal urine biochemistry at 13-23 weeks of gestation in lower urinary tract obstruction: criteria for in-utero treatment.
      After the first vesicocentesis, a subsequent ultrasound examination can determine whether the bladder refills. The absence of bladder refill usually indicates severe renal dysfunction, and no further vesicocenteses are recommended.
      • Ruano R.
      • Dunn T.
      • Braun M.C.
      • Angelo J.R.
      • Safdar A.
      Lower urinary tract obstruction: fetal intervention based on prenatal staging.
      A staging system for LUTO with recommended fetal therapies has been established.
      • Ruano R.
      • Dunn T.
      • Braun M.C.
      • Angelo J.R.
      • Safdar A.
      Lower urinary tract obstruction: fetal intervention based on prenatal staging.
      Possible fetal interventions include cystoscopy, vesicoamniotic shunt, or amnioinfusion. Cystoscopy can allow for both diagnosis and therapy by guidewire passage through the urethra or laser ablation of posterior urethral valves. In the PLUTO (Percutaneous vesicoamniotic shunting for fetal Lower Urinary Tract Obstruction) trial, a vesicoamniotic shunt did not increase survival to 28 days compared with conservative management in an intention-to-treat analysis but did increase survival based on actual treatment. Morbidity and mortality were very high in both groups, and there was a high rate of shunt complications.
      • Morris R.K.
      • Malin G.L.
      • Quinlan-Jones E.
      • et al.
      Percutaneous vesicoamniotic shunting versus conservative management for fetal lower urinary tract obstruction (PLUTO): a randomised trial.
      Serial amnioinfusions have been proposed as an option to allow survival in severe cases by reducing the risk of pulmonary hypoplasia, although data are limited, and further research is needed to determine the appropriate role for this intervention.
      • Haeri S.
      • Simon D.H.
      • Pillutla K.
      Serial amnioinfusions for fetal pulmonary palliation in fetuses with renal failure.
      Parents who desire full resuscitation should deliver at a center with a level IV neonatal intensive care unit (NICU). In general, mode of delivery should be based on usual obstetrical indications and parents’ preferences regarding resuscitation in severe cases. Planned preterm delivery to shunt the bladder has not been demonstrated to be of benefit.

      Prognosis

      LUTO is associated with high fetal and perinatal morbidity and mortality. The worst prognosis is seen in the presence of early, severe, prolonged oligohydramnios with associated pulmonary hypoplasia.
      • Kilbride H.W.
      • Yeast J.
      • Thibeault D.W.
      Defining limits of survival: lethal pulmonary hypoplasia after midtrimester premature rupture of membranes.
      ,
      • Nakayama D.K.
      • Harrison M.R.
      • de Lorimier A.A.
      Prognosis of posterior urethral valves presenting at birth.
      Other poor prognostic features include renal parenchymal abnormalities and abnormal fetal urinalysis. A significant percentage of patients with posterior urethral valves will develop end-stage renal disease and require dialysis and transplantation.
      • Morris R.K.
      • Kilby M.D.
      Long-term renal and neurodevelopmental outcome in infants with LUTO, with and without fetal intervention.
      These patients require a prolonged NICU stay, often require a gastrotomy tube for several years, and are prone to infections and mechanical dialysis failures. In addition, posterior urethral valves may cause damage to the bladder, and the child may require clean intermittent catheterization or bladder surgeries to achieve continence after birth and throughout life.

      Summary

      Fetal LUTO is characterized by an enlarged bladder, thickened bladder wall, and hydronephrosis. It is most commonly caused by posterior urethral valves. Fetal LUTO can lead to abnormal renal development and pulmonary hypoplasia and is associated with a high perinatal morbidity and mortality rate. Vesicocentesis and genetic testing should be offered to evaluate for the possibility of fetal intervention, although the optimal intervention and outcomes are unclear. Interventions that have been reported include cystoscopy with or without ablation of the valve, vesicoamniotic shunting, or amnioinfusion. Despite intervention, the prognosis is often poor, with high rates of pulmonary hypoplasia, end-stage renal disease, and bladder dysfunction.

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