SMFM Fetal Anomalies Consult Series #4: Genitourinary Anomalies

Introduction

The fetal genitourinary system includes the fetal kidneys, ureters, bladder, and internal and external genitalia. The standard ultrasound examination of the fetal genitourinary system after the first trimester of pregnancy includes visualization of the fetal kidneys and bladder (Figures 1, A and B, and 2). The renal pelvis should be assessed for dilation in an axial view of the anteroposterior diameter in the second and third trimesters of pregnancy (Figure 1, C). The fetal genitalia should be examined in multiple gestations, as this can aid in the determination of chorionicity, or when medically indicated as when a patient is at risk of an X-linked genetic disorder (Figure 3). In addition, measurement of the amniotic fluid volume should be performed (Figure 4), as it provides a functional assessment of the fetal kidneys, which produce amniotic fluid after 16 to 17 weeks of gestation. Renal pathology can therefore result in both increased and decreased amniotic fluid volume.

When indicated, a detailed ultrasound examination (76811) may include an examination of the adrenal glands and interrogation of the renal arteries (Figure 5). Examination of the fetal genitalia is also included.1

Abnormalities of the genitourinary system are among the most common fetal structural malformations. Such anomalies range from mild (eg, mild urinary tract dilation) to severe life-threatening anomalies (eg, bilateral renal agenesis).

Because the kidneys are responsible for the production of amniotic fluid, serious renal abnormalities that impair the production or excretion of urine (eg, urinary tract obstruction) can result in severe oligohydramnios, which can lead to pulmonary hypoplasia and can be life-threatening. The fetal bladder and renal pelvis are relatively easily visualized, and therefore, renal abnormalities are usually readily detected. Those abnormalities that are more difficult to identify, such as unilateral renal agenesis or a pelvic kidney, are less likely to be life-threatening or harmful to the fetus.

Most renal anomalies are isolated, and as a general rule, the risk of underlying aneuploidy or genetic syndromes is low. The exception is polycystic kidneys, which can be associated with autosomal recessive or dominant disorders. Other genetic syndromes can be characterized by various forms of multicystic or polycystic kidneys. Therefore, cystic kidney disease should prompt careful assessment to look for other anomalies and inherited diseases.

This Consult reviews the ultrasonographic diagnosis, genetic evaluation, and potential treatment and outcome of the following genitourinary abnormalities:

1 Adrenal neuroblastoma

2 Autosomal recessive polycystic kidney disease

3 Bladder outlet obstruction

4 Duplicated collecting system

5 Ectopic ureterocele

6 Hydroureter

7 Hypospadias 

8 Multicystic dysplastic kidney

9 Ovarian cyst

10 Pelvic kidney

11 Renal agenesis

12 Renal pelvic dilation

13 Urinoma

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Coding

When coding for fetal genitourinary anomalies, the Society for Maternal-Fetal Medicine Coding Committee recommends utilizing the International Classification of Diseases, Tenth Revision, code series O35.8XX.

ACKNOWLEDGMENTS

The authors wish to acknowledge Mary E. Norton, MD; Jeffrey A. Kuller, MD; and Angie C. Jelin, MD, for providing a review of the genetics content and Joseph Wax, MD, for providing a general review of this Consult.

REFERENCE

1. AIUM practice parameter for the performance of detailed second- and third-trimester diagnostic obstetric ultrasound examinations. J Ultrasound Med 2019;38:3093–100.

Adrenal neuroblastoma

Society for Maternal-Fetal Medicine (SMFM); Jeffrey Sperling, MD

Introduction

The fetal adrenal glands can be seen by ultrasonography by the end of the first trimester of pregnancy.1 They appear as pyramidal hypoechoic structures superior to the hyperechoic kidney. During the second trimester of pregnancy, corticomedullary differentiation can be observed with a hypoechoic cortex and hyperechoic medulla. The size of the gland increases throughout gestation but remains smaller than the kidney. During the third trimester of pregnancy, the appearance of the fetal adrenal glands is similar to that of the neonatal adrenal glands.1

Neuroblastomas account for 50% of fetal adrenal masses.2,3 They are more common in White infants and slightly more common in males than in females.2 Neuroblastomas originate in the neural crest cells of the sympathetic nervous system. Although most cases arise from the adrenal gland, they can also occur in the posterior mediastinum.2

Definition

The term neuroblastoma refers to a spectrum of neuroblastic tumors (eg, neuroblastomas, ganglioneuroblastomas, and ganglioneuromas) that arise from sympathetic ganglion cells.2 Although neuroblastomas are malignant tumors, and some can metastasize, the prognosis is excellent, and many cases regress spontaneously.4

Ultrasound Findings

Adrenal neuroblastoma generally appears as a well-encapsulated cystic or solid mass adjacent to but separate from the kidney and other retroperitoneal structures (Figure).3 Assessment of the contralateral adrenal gland to rule out normal but prominent adrenal glands is recommended. Findings on color Doppler interrogation are variably reported and include peripheral flow, no flow, or internal vascularization of the hyperechogenic aspects of the mass.3,5 A single feeding artery is not typically present and would suggest the more common subdiaphragmatic bronchopulmonary sequestration (BPS).6

Associated Abnormalities

Postnatally, neuroblastoma has been associated with LiFraumeni syndrome, Hirschsprung disease, and neurofibromatosis type 1, but these associations have not been reported in prenatal cases. If a neuroblastoma markedly enlarges and compresses the gastrointestinal tract, polyhydramnios may develop.7 Elevated catecholamines have been reported and may cause maternal symptoms, such as tachycardia, hypertension, nausea, and vomiting.8 In addition, catecholamine release has been associated with fetal cardiomyopathy, tachycardia, and hydrops.9 Rarely, fetal neuroblastomas may metastasize to the liver.10

Differential Diagnosis

The differential diagnosis of a mass in this region includes adrenal cysts11 (isolated or associated with multicystic dysplastic kidneys or Beckwith-Wiedemann syndrome), adrenal hemorrhage,12 subdiaphragmatic BPS,13 hepatic tumors, and adrenogenital syndrome (secondary to congenital adrenal hyperplasia).14 Hemorrhage in adrenal cysts associated with Beckwith-Wiedemann syndrome has been reported, in which case the appearance is that of a complex mass.15

Genetic Evaluation

Fetal neuroblastoma is typically a sporadic finding. If no further abnormalities are noted on ultrasound and the family history is unremarkable, no genetic evaluation beyond standard aneuploidy screening is typically recommended.

Pregnancy and Delivery Management

Hydrops fetalis, polyhydramnios, or both may develop in rare circumstances, typically with large lesions or in the setting of metastatic disease; therefore, serial ultrasound examinations should be performed. Serial ultrasound assessment can help rule out adrenal hemorrhage, which can evolve.4,16 A consultation with pediatric oncology, neonatology, and surgery should be obtained to plan and coordinate prenatal and postnatal management. In general, a pregnancy termination is an option that should be offered to patients when a major fetal anomaly is detected.

However, in most cases of neuroblastoma, the prognosis is favorable, and the outcome is good. Shared patient decision-making requires a thorough evaluation and multidisciplinary counseling regarding prognosis. If pregnancy termination is pursued, histologic evaluation can confirm the diagnosis.

In most cases, vaginal delivery is appropriate, and cesarean delivery should be reserved for the usual obstetrical indications. Cesarean delivery has been suggested as potentially preferable for very large cystic adrenal masses to prevent rupture or soft tissue dystocia. Adrenal cyst aspiration before delivery is controversial because this may cause bleeding, malignancy seeding, preterm labor, or infection. Delivery in a tertiary care center is recommended with consideration of early delivery if there is evidence of fetal compromise. The postnatal investigation, including ultrasound, magnetic resonance imaging, or other imaging modalities, is recommended. Expectant management, needle biopsy, or surgical exploration may be needed based on the results of the above imaging, final diagnosis, and neonatal condition.

Prognosis

In general, the prognosis is good, and neuroblastomas may even resolve in utero or shortly after birth.3,13 Survival rates of infants with the low-stage disease are excellent, even for those with metastatic disease.17 Cases of spontaneous involution have been reported.18 The recurrence risk of this lesion is unknown but likely low.

Summary

Fetal adrenal neuroblastomas, derived from neural crest cells, are the most frequently diagnosed extracranial solid tumor of childhood. These rare tumors are associated with an excellent postnatal prognosis. Close surveillance with serial ultrasound examinations evaluating for signs of hydrops fetalis and polyhydramnios is recommended. Antenatal consultation with pediatric oncology, neonatology, and surgery is advised.

REFERENCES

1. Norton ME. Callen’s Ultrasonography in Obstetrics and Gynecology EBook. Elsevier Health Sciences; 2016.

2. Goodman MT, Gurney J, Smith M, Olshan A. Sympathetic nervous system tumors. Cancer incidence and survival among children and adolescents: United States SEER Program. 1975;1995:65–72.

3. Sauvat F, Sarnacki S, Brisse H, et al. The outcome of suprarenal localized masses diagnosed during the perinatal period: a retrospective multicenter study. Cancer: Interdisciplinary International Journal of the American Cancer Society. 2002;94(9):2474–80.

4. Fisher JPH, Tweddle DA. Neonatal neuroblastoma. Seminars in fetal & neonatal medicine 2012 Aug;17(4):207–15.

5. Schwärzler P, Bernard JP, Senat MV, Ville Y. Prenatal diagnosis of fetal adrenal masses: differentiation between hemorrhage and solid tumor by color Doppler sonography. Ultrasound in Obstetrics and Gynecology: The Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 1999;13(5):351–5.

6. Curtis MR, Mooney DP, Vaccaro TJ, et al. Prenatal ultrasound characterization of the suprarenal mass: the distinction between neuroblastoma and subdiaphragmatic extra lobar pulmonary sequestration. Journal of Ultrasound in Medicine 1997;16(2):75–83.

7. Cho JY, Lee YH. Fetal tumors: prenatal ultrasonographic findings and clinical characteristics. Ultrasonography 2014;33(4):240.

8. Jennings RW, LaQuaglia MP, Leong K, Hendren WH, Adzick NS. Fetal neuroblastoma: prenatal diagnosis and natural history. Journal of Pediatric Surgery 1993;28(9):1168–74.

9. Inoue T, Ito Y, Nakamura T, Matsuoka K, Sago H. Catecholamine-secreting neuroblastoma leads to hydrops fetalis. Journal of Perinatology 2014;34:405–7.

10. Desai G, Filly RA, Rand L. Prenatal detection of extra-adrenal neuroblastoma with hepatic metastases. J Ultrasound Med 2009;28(8): 1085–90.

11. Patti G, Fiocca G, Latini T, Celli E, Bellussi A, Nazzicone P. Prenatal diagnosis of bilateral adrenal cysts. The Journal of Urology 1993;150(4): 1189–91.

12. Strouse P, Bowerman RA, Schlesinger AE. Antenatal sonographic findings of fetal adrenal hemorrhage. Journal of Clinical Ultrasound 1995;23(7):442–6.

13. Rubenstein S, Benacerraf B, Retik A, Mandell J. Fetal suprarenal masses: sonographic appearance and differential diagnosis. Ultrasound in Obstetrics & Gynecology 1995;5(3):164–7.

14. Maki E, Oh K, Rogers S, Sohaey R. Imaging and differential diagnosis of suprarenal masses in the fetus. J Ultrasound Med 2014;33(5):895–904.

15. Gocmen R, Basaran C, Karcaaltincaba M, et al. Bilateral hemorrhagic adrenal cysts in an incomplete form of Beckwith-Wiedemann syndrome: MRI and prenatal US findings. Abdominal Imaging 2005;30(6):786–9.

16. Birkemeier KL. Imaging of solid congenital abdominal masses: a review of the literature and practical approach to image interpretation. Pediatr Radiol 2020 Dec;50(13):1907–20.

17. London W, Castleberry R, Matthay K, et al. Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children’s Oncology Group. Journal of Clinical Oncology 2005;23(27): 6459–65.

18. Holgersen LO, Subramanian S, Kirpekar M, Mootabar H, Marcus JR. Spontaneous resolution of antenatally diagnosed adrenal masses. Journal of Pediatric Surgery 1996;31(1):153–5.

Autosomal recessive polycystic kidney disease

Society for Maternal-Fetal Medicine (SMFM); Kate Swanson, MD

Introduction

Autosomal recessive polycystic kidney disease (ARPKD) is a rare genetic disorder with an estimated incidence of 1 in 20,000 live births.1 Although there is variability in presentation and new advances changing the life expectancy of affected individuals, it remains a disease with high morbidity and mortality, particularly when diagnosed prenatally.

Definition

Individuals affected with ARPKD typically have biallelic pathogenic variants in the PKHD1 gene on chromosome 6p21. These variants affect the production of fibrocystin, a protein found in the primary cilium or basal body complex of epithelial cells in the renal tubules and hepatic bile ducts.2 These variations result in the elongation and dilation of the collecting ducts, formation of microcystins, and diffuse enlargement of the kidneys.3 As a result, affected individuals develop end-stage renal disease and hepatobiliary disease.

Ultrasound Findings

There is wide variability in the prenatal presentation of ARPKD. In some cases, enlarged hyperechoic kidneys with poor corticomedullary differentiation can be identified in the second trimester of pregnancy. Frequently, the kidneys are quite enlarged, ranging from 4 to 15 standard deviations above normal in size. In addition, oligohydramnios or hydramnios are frequently present in ARPKD. In more subtle cases, mild enlargement and a hyperechoic cortical rim may be the only findings. In the third trimester of pregnancy, larger cysts >3 mm in size may develop. These cysts can be bilateral or unilateral. In some cases, no abnormality is identified prenatally (Figure).4

Associated Abnormalities

Aside from oligohydramnios or hydramnios and the resultant pulmonary hypoplasia, which can sometimes be suspected with ultrasonography, additional ultrasonographic anomalies are uncommon. Although hepatic fibrosis and biliary dysgenesis are common in affected patients, these findings are rarely identified prenatally.4,5

Differential Diagnosis

Bardet-Biedl syndrome is another ciliopathy that can present prenatally with enlarged cystic kidneys. Postaxial polydactyly is common in individuals with Bardet-Biedl syndrome and can help differentiate it from ARPKD. In addition, the renal parenchyma is typically more homogenous in individuals with Bardet-Biedl syndrome.6 Meckel-Gruber syndrome is another rare autosomal recessive condition that can present with enlarged cystic kidneys; the cysts often appear earlier than in ARPKD. Postaxial polydactyly and central nervous system malformations are common with Meckel-Gruber syndrome.5

Genetic Evaluation

Prenatal diagnostic testing should be offered when ARPKD is suspected. In addition, chromosomal microarray analysis can be offered when the prenatal diagnosis is performed, particularly in the presence of additional ultrasound findings, although it will not detect single-gene disorders, including ARPKD. Molecular genetic testing on tissue obtained by chorionic villus sampling or amniocentesis can be used to identify pathogenic variants in the PKHD1 gene. The presence of two pathogenic variants in this gene confirms the diagnosis of ARPKD. However, even in cases with strong histopathologic and clinical support for the diagnosis, variant detection rates range from 80% to 85%.7,8 If there are additional anomalies, consanguinity, or a family history of a specific condition, gene panel testing or exome sequencing is sometimes useful.

Pregnancy and Delivery Management

Given the poor prognosis of individuals with prenatally identified ARPKD, particularly in the setting of early oligohydramnios or hydramnios, patients with an affected fetus should be offered pregnancy termination. Parents who choose to continue their pregnancy should be offered comfort care for the neonate at the time of delivery. During pregnancy, serial ultrasound examinations can be useful to assess kidney size and amniotic fluid volume.9 Parents who desire full resuscitation should deliver at a center with a level IV neonatal intensive care unit. Because massive enlargement of the kidneys can result in an abdominal circumference that may preclude a vaginal delivery at term, cesarean delivery may be necessary.10

Prognosis

There exists marked variability in the presentation and prognosis of ARPKD. Prenatally diagnosed ARPKD is associated with poorer outcomes than ARPKD identified in the neonatal period or childhood. Those with oligohydramnios or hydramnios identified on prenatal ultrasound are at considerable risk of pulmonary hypoplasia and have an approximately 30% mortality rate within the first year of life.11 In addition, it is reported that the genotype may have some association with phenotype and that individuals with truncating variants are more likely to have poor outcomes than those with missense variants.3

Individuals who survive beyond the first month of life have a better prognosis, with reported survival rates at 10 years as high as 82%. However, these patients typically require dialysis and renal transplantation and frequently develop hypertension, hepatic fibrosis, and portal hypertension.12

Summary

ARPKD is infrequently diagnosed on prenatal ultrasound. However, when it is identified, it is associated with significant morbidity and mortality. As an autosomal recessive disease with variable expressivity, parents and siblings of patients with affected pregnancies should be evaluated and counseled on their risks of also having an affected pregnancy.

REFERENCES

1. Wilson PD. Polycystic kidney disease. N Engl J Med 2004;350:151–64.

2. Ward CJ, Yuan D, Masyuk TV, et al. Cellular and subcellular localization of the ARPKD protein; fibrocystin is expressed on primary cilia. Hum Mol Genet 2003;12:2703–10.

3. Denamur E, Delezoide AL, Alberti C, et al. Genotype-phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease. Kidney Int 2010;77:350–8.

4. Avni FE, Garel L, Cassart M, et al. Perinatal assessment of hereditary cystic renal diseases: the contribution of sonography. Pediatr Radiol 2006;36:405–14.

5. Erger F, Brüchle NO, Gembruch U, Zerres K. Prenatal ultrasound, genotype, and outcome in a large cohort of prenatally affected patients with autosomal-recessive polycystic kidney disease and other hereditary cystic kidney diseases. Arch Gynecol Obstet 2017;295:897–906.

6. Mary L, Chennen K, Stoetzel C, et al. Bardet-Biedl syndrome: antenatal presentation of forty-five fetuses with biallelic pathogenic variants in known Bardet-Biedl syndrome genes. Clin Genet 2019;95:384–97.

7. Bergmann C, Senderek J, Schneider F, et al. PKHD1 mutations in families requesting prenatal diagnosis for autosomal recessive polycystic kidney disease (ARPKD). Hum Mutat 2004;23:487–95.

8. Guay-Woodford LM, Desmond RA. Autosomal recessive polycystic kidney disease: the clinical experience in North America. Pediatrics 2003;111:1072–80.

9. Guay-Woodford LM, Bissler JJ, Braun MC, et al. Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference. J Pediatr 2014;165:611–7.

10. Dukic L, Schaffelder R, Schaible T, Sütterlin M, Siemer J. [Massive increase of fetal abdominal circumference due to hereditary polycystic kidney disease]. Z Geburtshilfe Neonatol 2010;214:119–22.

11. Sweeney WE, Avner ED. Polycystic kidney disease, autosomal recessive. Seattle, WA: University of Washington; 2021.

12. Bergmann C, Senderek J, Windelen E, et al. Clinical consequences of PKHD1 mutations in 164 patients with autosomal-recessive polycystic kidney disease (ARPKD). Kidney Int 2005;67:829–48.

Bladder outlet obstruction

Society for Maternal-Fetal Medicine (SMFM); Anne Mardy, MD

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.1e3 After the first trimester of pregnancy, there is no single definition of megacystis, with many different definitions found in the literature.4 One study defined the normal sagittal length as the gestational age in weeks minus 5 mm (95% upper or lower confidence interval [CI]¼7); megacystis was defined as greater than the upper limit of the 95% CI for the gestational age.5 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.

Associated Abnormalities

Most cases (78%) of LUTO are isolated.6 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 as 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.6

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-microcolony syndrome (thin-walled bladder without dilated posterior urethra; normal or increased amniotic fluid).6,7 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 was resolved during the pregnancy.6

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 a reflex to CMA if these test results are expected. 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 proper 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.7 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.8 After the first vesicocentesis, a subsequent ultrasound examination can determine whether the bladder refills. The absence of a bladder refill usually indicates severe renal dysfunction, and no further vesicocenteses are recommended.7

A staging system for LUTO with recommended fetal therapies has been established.7 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.9 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.10

Parents who desire full resuscitation should deliver at a center with a level IV neonatal intensive care unit (NICU). In general, the 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.11,12 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.13 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 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 the intervention, the prognosis is often poor, with high rates of pulmonary hypoplasia, end-stage renal disease, and bladder dysfunction.

REFERENCES

1. Sebire NJ, Von Kaisenberg C, Rubio C, Snijders RJ, Nicolaides KH. Fetal megacystis at 10-14 weeks of gestation. Ultrasound Obstet Gynecol 1996;8:387–90.

2. Liao AW, Sebire NJ, Geerts L, Cicero S, Nicolaides KH. Megacystis at 10-14 weeks of gestation: chromosomal defects and outcome according to bladder length. Ultrasound Obstet Gynecol 2003;21:338–41.

3. Kagan KO, Staboulidou I, Syngelaki A, Cruz J, Nicolaides KH. The 11- 13-week scan: diagnosis and outcome of holoprosencephaly, exomphalos, and megacystis. Ultrasound Obstet Gynecol 2010;36:10–4.

4. Taghavi K, Sharpe C, Stringer MD. Fetal megacystis: a systematic review. J Pediatr Urol 2017;13:7–15.

5. Maizels M, Alpert SA, Houston JT, Sabbagha RE, Parilla BV, MacGregor SN. Fetal bladder sagittal length: a simple monitor to assess normal and enlarged fetal bladder size, and forecast clinical outcome. J Urol 2004;172:1995–9.

6. Malin G, Tonks AM, Morris RK, Gardosi J, Kilby MD. Congenital lower urinary tract obstruction: a population-based epidemiological study. BJOG 2012;119:1455–64.

7. Ruano R, Dunn T, Braun MC, Angelo JR, Safdar A. Lower urinary tract obstruction: fetal intervention based on prenatal staging. Pediatr Nephrol 2017;32:1871–8.

8. Abdennadher W, Chalouhi G, Dreux S, et al. Fetal urine biochemistry at 13-23 weeks of gestation in lower urinary tract obstruction: criteria for inutero treatment. Ultrasound Obstet Gynecol 2015;46:306–11.

9. Morris RK, Malin GL, Quinlan-Jones E, et al. Percutaneous vesicoamniotic shunting versus conservative management for fetal lower urinary tract obstruction (PLUTO): a randomized trial. Lancet 2013;382: 1496–506.

10. Haeri S, Simon DH, Pillutla K. Serial amnioinfusions for fetal pulmonary palliation in fetuses with renal failure. J Matern Fetal Neonatal Med 2017;30:174–6.

11. Kilbride HW, Yeast J, Thibeault DW. Defining limits of survival: lethal pulmonary hypoplasia after mid-trimester premature rupture of membranes. Am J Obstet Gynecol 1996;175:675–81. 

12. Nakayama DK, Harrison MR, de Lorimier AA. Prognosis of posterior urethral valves presenting at birth. J Pediatr Surg 1986;21:43–5.

13. Morris RK, Kilby MD. Long-term renal and neurodevelopmental outcome in infants with LUTO, with and without fetal intervention. Early Hum Dev 2011;87:607–10.

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