Definition Ambiguous genitalia is a term used to describe the clinical situation when examination of the external genitalia does not allow a clear gender assignment. Those conditions where chromosomal sex and phenotypic sex do not correspond are called disorders of sexual development.
Epidemiology The condition occurs in 1 in 5000 live births.
Embryology The term ambiguous genitalia can be used for those disorders with abnormally formed genitalia (severe penile hypospadias) to complete sex reversal (Smith-Lemli-Opitz syndrome). The most common etiology of isolated ambiguous genitalia is congenital adrenal hyperplasia (CAH), with masculinization of the female fetus (90% of cases). Other congenital abnormalities are present in up to 40% of infants with genital malformations. Additional etiologies of ambiguous genitalia, especially with associated malformations, are chromosomal abnormalities (trisomies 13 and 18, and triploidy) and over 50 genetic syndromes/associations, including Smith-Lemli Opitz syndrome, velocardiofacial syndrome, Prader-Willi syndrome, VACTERL (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, limb abnormalities) association, CHARGE (coloboma, heart defect, atresia choanae, retarded growth, genital anomaly, ear abnormality) association, Fraser syndrome, and Cornelia de Lange syndrome.
Inheritance Patterns Congenital adrenal hyperplasia is autosomal recessive. Recurrence risks for other conditions are dependent on their specific inheritance patterns.
Teratogens Isotretinoin is teratogenic.
Prognosis Prognosis depends on the degree of genital malformation and the underlying etiology. The psychological and social implications of gender assignment in these infants require a multidisciplinary team approach.
Short phallus/clitoromegaly
Bifid scrotum/fused labia
Abnormal phallic shape
Undescended testes in the third trimester
Abnormal urinary stream
Associated congenital anomalies
Urogenital
Extragenital
Discrepancy between the external and internal fetal gender
Presence or absence of the uterus
The presence of a uterus results in an increased distance between the bladder and rectum.
Uncertain appearance of external genitalia should prompt a more detailed assessment.
Clitoris versus penis
Labia versus scrotum
Late second- or third-trimester evaluation can look for testicular descent or the uterus.
Testicular descent is first noted at 25 weeks’ gestation.
Testicular descent occurs in 62% of cases between 28 and 30 weeks’ gestation; 93% of fetuses at 32 weeks’ gestation have descended testes.
Visualization of the testes distinguishes XY and XX disorders of sexual development.
The presence of a uterus results in an increased distance between the bladder and rectum compared to normal male fetuses.
The term uterus measures 32 ± 5 mm in length and 20 mm transversely.
Congenital adrenal hyperplasia
Hypertrophied adrenal glands
In the transverse plane, adrenals are enlarged and are circular rather than triangular.
They are first detected at 22 weeks’ gestation.
Hypospadias
Usually, hypospadias occurs (50%) on the distal penis (first degree).
With second-degree hypospadias (30%), the urethral opening is along the penile shaft.
In third-degree hypospadias (20%), the urethral opening is at the penoscrotal junction.
Third-degree hypospadias can be detected sonographically by the “tulip sign.”
There is persistent angulation of the penile shaft due to chordee.
Bifid scrotum may be an associated finding.
Most often, hypospadias is an isolated finding.
First- and second-degree hypospadias are usually not detected prenatally, except when the external genitalia are carefully inspected in the context of other anomalies.
Color Doppler can be used to distinguish the downward urinary stream of hypospadias.
Three-dimensional (3-D) sonography can assist in the evaluation of the external genitalia.
Micropenis is a normally formed penis that is less than 2.5 standard deviations below the mean.
Investigations and Consultations Required A complete ultrasound examination should be performed to determine whether this is an isolated abnormality. Fetal echocardiography should be done, as cardiac defects are associated with a number of the possible etiologic conditions. A careful history is essential to assess for congenital abnormalities in the parents or previous children. The history also should include information regarding consanguinity and any potential teratogen exposure. A fetal karyotype and microarray should be obtained. Consultation with a medical geneticist is essential to determine appropriate molecular testing, including for congenital adrenal hyperplasia, the most common cause for ambiguous genitalia in a female fetus. Other consultations obtained are based on the presumptive diagnosis and the need for neonatal, medical, or surgical therapy.
Fetal Intervention None is indicated. In cases of congenital adrenal hyperplasia, prevention of virilization of a female fetus using high-dose maternally administered corticosteroids has been studied. This therapy has no role once virilization has occurred but would be considered in an at-risk family for a subsequent pregnancy. This approach is controversial, as it is not entirely successful, carries substantial risks, and involves treating unaffected fetuses.
Monitoring Follow-up ultrasonographic examinations later in gestation may be performed to assess the maturation of the external genitalia and to reassess for associated anomalies that would affect the final diagnosis.
Pregnancy Termination Issues Unless a precise diagnosis has been established prenatally, the method of termination should provide an intact fetus for a complete morphologic and radiologic examination.
Delivery The complex nature of these multiple-malformation conditions requires that delivery and neonatal management occur in a tertiary center. Even if a diagnosis of congenital adrenal hyperplasia is made, the need for a multidisciplinary team for management makes delivery at a tertiary center mandatory.
Resuscitation There are no special issues for delivery room management. If other associated anomalies exist, then management may need to be directed toward their related issues. Assignment of gender should be deferred until complete evaluation at a tertiary center.
Transport Referral to a tertiary perinatal center with multiple pediatric and surgical subspecialists is always indicated.
Testing and confirmation Careful physical examination and evaluation for associated congenital anomalies are essential. The initial laboratory evaluation should include chromosome analysis and assessment of gonadal and adrenal steroids. Additional laboratory values to be obtained include molecular genetic studies for the SRY gene (regulator of male sex determination); serum 17-OH progesterone measurement; serum DHEA (dehydroepiandrosterone), 17-hydroxyprenenolone, and 11-deoxycortisol levels; corticotropin (ACTH); and serial serum and urine electrolytes. Abdominal and pelvic ultrasounds are performed to determine the presence of gonads, a uterus, or a vagina. Cystoscopy/vaginoscopy may be necessary to better delineate the anatomy.
Nursery management Evaluation should begin immediately at the time of birth as CAH due to 21-hydroxylase deficiency (salt wasting) may be life threatening if not diagnosed and treated. In the presence of electrolyte abnormalities suggestive of salt-wasting CAH, treatment with hydrocortisone is initiated pending the results of adrenal testing. If clinical symptoms of adrenal insufficiency develop, such as hypoglycemia, hyponatremia, hypovolemia, hyperkalemia, or vomiting and diarrhea, intravenous fluid therapy should be instituted immediately with dextrose and normal saline solution to restore electrolyte imbalance. Assignment of gender requires counseling with a multidisciplinary team consisting of individuals from pediatric genetics, endocrinology, surgery, urology, and neonatology specialties, in addition to professional counseling and psychosocial support for the family. Referral to a pediatric tertiary center that specializes in disorders of sexual development, is highly recommended.
Definition Bladder exstrophy is a failure of closure of the bladder, lower urinary tract, overlying symphysis pubis, rectus muscles, and skin. It is part of the exstrophy-epispadias complex that includes epispadias, exstrophy of the bladder, and cloacal exstrophy.
Epidemiology Occurrence is 1 per 10,000 to 50,000 births (M2:Fl).
Embryology Bladder exstrophy is theorized to result from a disorder in the development of the cloacal membrane, preventing medial migration of mesenchyme, and early rupture of the membrane. The most commonly associated malformations involve the upper urinary tract (ureteropelvic junction [UPJ] obstruction, horseshoe kidney, ectopic kidney). Approximately 7% of patients will have a spinal abnormality, such as spina bifida occulta, scoliosis, or hemivertebrae.
Inheritance Patterns Most cases are likely the result of multifactorial inheritance, with a recurrence risk of approximately 1%. There are rare case reports of families that appear to have autosomal recessive or X-linked inheritance.
Teratogens None are known.
Screening Maternal serum α-fetoprotein is elevated in most cases of bladder exstrophy.
Prognosis Surgical correction is complicated, but approximately 80% of patients will eventually have continence; it is much lower with closure failures. With current surgical techniques, the majority of patients will have full continence, adequate sexual function, and normal psychosocial outcomes.
Absent fetal bladder
Normal amniotic fluid volume
Normal fetal kidneys
Lower abdominal cauliflower mass (posterior wall of the bladder)
Low umbilical cord insertion
Laterally splayed iliac crests
Ambiguous genitalia
Female: widely separated labia
Male: complete epispadias
This may occur as an isolated congenital anomaly or as part of cloacal exstrophy or OEIS (omphalocele, exstrophy of the bladder, imperforate anus, and spinal defects, usually a meningomyelocele).
In exstrophy, a persistent cloacal membrane prevents normal midline fusion. As a result, there is a shortened lower abdominal wall and a low cord insertion.
Three-dimensional sonography can be utilized to better assess the lower abdominal mass and genitalia in cases of suspected bladder exstrophy.
Investigations and Consultations Required Associated abnormalities other than of the spine or kidneys are rare in bladder exstrophy. In patients planning to continue the pregnancy, fetal echocardiography may be appropriate to exclude cardiac defects before deciding on the site for delivery. A pediatric urologist should be consulted to discuss management with the family. Although chromosome abnormalities are not associated with bladder exstrophy, confirmation of fetal sex may be useful in defining prognosis for surgical repair.
Monitoring No alteration in standard obstetric care is indicated.
Pregnancy Course No obstetric complications are associated with this disorder.
Pregnancy Termination Issues An intact fetus should be delivered to allow confirmation of the sonographic diagnosis.
Delivery There is no evidence that cesarean delivery improves prognosis. Delivery at a tertiary center is not required. It is more important that the infant be transferred to an institution with individuals experienced in the repair of this rare condition.
Resuscitation Respiratory difficulty is not expected with this lesion.
Transport Referral to a tertiary center with a pediatric urologist experienced in the repair of exstrophy is essential for early surgical intervention.
Testing and Confirmation The bladder and lower urinary tract are open anteriorly from the urethral meatus to the umbilicus. There is wide separation of the pubic symphysis and rectus muscles. In males, the scrotum is broad with frequent undescended testes and a short broad penis without canalization. In females, the clitoris and labia are widely separated, with occasional vaginal stenosis. Upper tract anomalies are typically not associated with this lesion.
Nursery Management The exposed viscera should be covered with plastic film (Saran™ Wrap) to limit heat and evaporative water loss and contamination. Administration of antibiotics should be considered to reduce the risk of infection.
Preoperative Assessment Complete physical examination; laboratory testing, including electrolytes and complete blood cell count; abdominal flat plate; renal ultrasound; and pelvic magnetic resonance imaging (MRI) should be performed.
Types of Procedures Two surgical approaches are currently used to correct bladder exstrophy: modern staged repair of bladder exstrophy (MSRE) and complete primary repair of bladder exstrophy (CPRE). In both, the bladder and posterior urethra are reapproximated to form a new bladder.
Surgical Results/Prognosis The prognosis is dependent on any associated renal anomalies, but there is a survival rate of more than 90%. Secondary surgical procedures are frequently required to achieve urinary continence and functioning genitalia. Possible short-term surgical complications include wound dehiscence and infection. Urinary continence, the primary goal of successful repair, is achieved in more than 70% of patients. Long-term follow-up is required to monitor bladder, renal, and sexual function and to address psychological issues that may result from poor body image.
Definition Cloacal exstrophy is an extensive lower abdominal wall defect that combines exstrophy of the bladder with intervening intestinal epithelium, imperforate anus, and wide separation of the anterior pubic arch.
Epidemiology Occurrence is 1 in 200,000 births. The sex ratio has been reported to be twice as common in males in some studies and more common in females in other studies. The incidence figures vary widely and likely reflect ascertainment biases, especially because of the high rate of pregnancy termination when detected prenatally. If stillborn and terminated fetuses are included, the incidence is more likely to be in the range of 1 in 30,000 pregnancies.
Embryology Exstrophies are theorized to result from a disorder in the development of the cloacal membrane, preventing medial migration of mesenchyme, and early rupture of the membrane. Cloacal exstrophy occurs if the rupture occurs before the urorectal septum divides the gastrointestinal from the genitourinary tracts. The bladder and lower urinary tract are open anteriorly from the urethral meatus to the umbilicus. There is wide separation of the pubic symphysis and rectus muscles. In males, the scrotum is broad with undescended testes, and there is a short, broad penis without canalization. In females, the clitoris and labia are widely separated with occasional vaginal stenosis. The upper urinary tract is malformed in approximately one-third of cases, with the common abnormalities being UPJ obstruction, horseshoe kidney, and ectopic kidney. In females, the uterus is frequently bicornuate, and the vagina is duplex, ending blindly near the bladder mucosa. Ninety percent of patients with cloacal exstrophy have an omphalocele or other gastrointestinal abnormalities, and nearly all have significant neurospinal abnormalities, including neural tube defects, vertebral anomalies, spinal myelodysplasia, and tethered cord. One form of the disorder is known as the OEIS complex.
Inheritance Patterns Inheritance is likely multifactorial. The overall risk of recurrence for disorders in the exstrophy-epispadias complex is approximately 1%. Only rare affected siblings have been described.
Teratogens None are known.
Screening Maternal serum α-fetoprotein is elevated in most cases.
Prognosis Surgical correction is complicated and requires a multidisciplinary team. Neonatal mortality in cloacal exstrophy is low in centers with experience in managing complex birth defects. Urinary and fecal continence are established in approximately 50% of cases. There are no data on sexual function and few on the quality of life. Intelligence in survivors is normal.
Absent fetal bladder
Abnormally shaped cloaca in pelvis
Midline infraumbilical septated cyst (cloacal membrane)
Omphalocele
Neural tube defect
Ambiguous genitalia
Pubic diastasis
Didelphic uterus
Single umbilical artery
Clubfeet
Renal anomalies
Hydronephrosis
Pelvic kidney
Unilateral renal agenesis
Horseshoe kidney
Crossed renal ectopy
Kyphoscoliosis
Urinary ascites
Ventriculomegaly
First trimester
Increased nuchal translucency
Megacystis
Visualization of normal external genitalia excludes cloacal exstrophy.
If an evaluation of the lower pelvis detects an anal canal and rectum, cloacal exstrophy is excluded.
The most common differential diagnosis is hydrocolpos with a distended, sometimes septated, vagina and lower urinary tract obstruction (LUTO).
Investigations and Consultations Required Chromosomal studies, including microarray, and fetal echocardiography should be performed to exclude other malformations. Consultation with a pediatric urologist should be obtained.
Fetal Intervention None is indicated.
Monitoring Serial ultrasonographic studies should be done to monitor the urinary tract and possible associated anomalies.
Pregnancy Course No specific obstetric complications should be anticipated.
Pregnancy Termination Issues An intact fetus may be necessary to confirm the diagnosis and to exclude genetic syndromes that may have cloacal abnormalities as a component of the disorder.
Delivery In cases with an associated omphalocele or neural tube defect, delivery may be complicated. In general, no specific delivery issues are anticipated.
Resuscitation Saline-soaked sterile dressings are applied to protect the exposed bowel and bladder mucosa and, if present, the accompanying omphalocele from surface contamination and trauma. Limitation of evaporative heat and water loss can be achieved by encasing the lower body in a sterile plastic bag (bowel bag).
Transport Transfer by an experienced neonatal transport team to a tertiary center with pediatric surgical subspecialists and diagnostic capabilities is indicated on an emergency basis.
Testing and Confirmation The assessment and determination of the exact spectrum and aberrant anatomy in these conditions require a coordinated multidisciplinary approach, often using the full range of imaging and endoscopic techniques. In cloacal exstrophy, there is a high association with cardiac, skeletal, and neurologic anomalies, necessitating diagnostic imaging of these organ systems as well. Chromosomal analysis for genetic gender identification is essential if it has not been obtained prenatally.
Nursery Management Initial management is directed toward providing fluid and electrolyte support and decompression of both the urinary and the intestinal systems, as indicated. The choice and staging of surgical procedures for palliation or correction will vary with the results of the diagnostic evaluation. Provision of social and emotional support and counseling for the parents is important in facilitating their adaptation to the long-term demands for the care of their child. Multiple surgeries will be required for complete management of all the abnormalities.
Preoperative Assessment The major areas that require preoperative evaluation are the upper urinary tract anomalies, central nervous system abnormalities, musculoskeletal deformities, and gender. Ultrasonography is used to evaluate the spinal cord and genitourinary tract. Magnetic resonance imaging may be useful in assessing abdominal and central nervous system malformations.
Operative Indications All children with this anomaly require bladder reconstruction and omphalocele repair. If a myelomeningocele is present, repair will be needed. Diastasis of the pubic bones must also be repaired. The goal of reconstruction is to help the patient achieve adequate bowel and urinary control and satisfactory sexual function.
Surgical Results/Prognosis In the absence of lethal renal abnormalities, an excellent survival rate between 80% and 100% is expected.
Definition A duplex collecting system is a single kidney that is drained by two pyelocaliceal systems. A ureterocele is a cystic dilatation of the terminal part of the ureter in the bladder.
Epidemiology A duplex collecting system is present in 1 in 125 in autopsy series, and antenatally, the incidence has been reported to be between 1:70 and 1:500 (M1:F2). Ureteroceles are found in 1 in 5000 neonates (M1:F3-5).
Embryology A duplex collecting system may drain into a single ureter, a bifid ureter, or two separate ureters. When there are two ureters,
The lower pole drains cranially and laterally into the trigone.
The cranial position results in a shorter intramural tunnel and higher likelihood of reflux.
The upper pole drains medially and caudally.
It usually ends in a ureterocele; it may also end in the urethra or vagina.
The upper pole may be dysplastic.
This may be confused with a suprarenal mass (i.e., a neuroblastoma).
Weigert-Meyers law: The upper pole obstructs and the lower refluxes.
Approximately 10% to 20% of cases are bilateral. Renal dysplasia in a duplex kidney may be due to faulty embryogenesis or to obstruction. The faulty embryogenesis theory appears more likely based on embryologic and pathologic studies. Displacement of the orifices laterally or caudally results in abnormalities of the associated kidney segment. The further the ureter is displaced, the greater the abnormality will be; severe displacement results in renal dysplasia. Of duplex collecting systems, 70% have other congenital anomalies: Vesicoureteral reflux (VUR) is the most common abnormality. And, 80%-90% of ureteroceles are associated with a duplicated collecting system.
Inheritance Patterns Inheritance is sporadic in most cases. Rare families having dominant inheritance have been reported.
Teratogens None are known.
Prognosis The overall prognosis is excellent. The need for surgical intervention will depend on the degree of hydronephrosis and whether an obstructing ureterocele is present.
Two separate renal collecting systems
Increased renal length
Upper-/lower-pole hydronephrosis
Cyst-like structure in the upper pole (i.e., second renal pelvis)
Ureterocele
Hydroureter
UPJ obstruction (4%)
Renal dysplasia of the upper pole
Of ureteroceles, 90% are associated with a duplex, two-ureter system.
A ureterocele that is totally within the bladder is intravesical (“Foley catheter sign”).
A ureterocele partially within the bladder neck or urethra is ectopic.
Of ectopic ureteroceles, 80%-90% are associated with a duplex kidney.
Bilateral ureteroceles may occur.
Hydronephrosis
Polycystic kidneys
Solitary renal cysts
Ureteropelvic junction obstruction
Investigations and Consultations Required In general, because this is an isolated anomaly, no other investigations are required. If the diagnosis is unclear, especially in the presence of significant hydronephrosis, detailed sonographic assessment is necessary to exclude other abnormalities. Pediatric urologic consultation should be obtained.
Fetal Intervention In general, no intervention is necessary, as these fetuses do well.
Monitoring No change in obstetric care is indicated. Serial ultrasonographic examinations monthly may be helpful in monitoring the kidneys for the degree of hydronephrosis and evidence of pathology in the contralateral kidney, as well as the rare case that develops oligohydramnios due to an obstructing ureterocele.
Pregnancy Course No obstetric complications should be expected.
Pregnancy Termination Issues In general, these cases do not usually result in pregnancy termination, but if that is chosen, an intact fetus, appropriate for confirming the anatomic findings on autopsy, is warranted.
Delivery In cases with significant obstruction, there may be a need for immediate neonatal evaluation to establish a diagnosis. Delivery in those cases should be in a tertiary center.
Resuscitation In the absence of other conditions, resuscitative efforts are usually not required.
Transport In cases of an isolated duplex collecting system diagnosed antenatally, transfer to a tertiary center is not necessary. The evaluation can be performed as an outpatient at 1-2 weeks of age. In infants with suspected associated renal anomalies, hydroureter, bladder abnormalities, evidence of obstructive uropathy, or presence of a ureterocele, transfer to a tertiary center is indicated for evaluation and management.
Testing and confirmation Ultrasonography of the kidneys and bladder or voiding cystourethrogram (VCUG) are diagnostic. Timing of these studies is dependent on the severity of the associated congenital anomalies of the kidney and urinary tract, including obstructive uropathy, presence of a ureterocele, and VUR.
Nursery Management Depending on the severity of associated renal abnormalities and the presence of associated VUR or obstructive uropathy, antibiotic prophylaxis with amoxicillin (12-25 mg/kg orally daily) is recommended. While infants with an isolated duplex collecting system may be safely evaluated at an age older than 7 days, earlier evaluation in the immediate newborn period may help ease parental anxiety and concern. Follow-up with pediatric urology is indicated.
Definition Infantile polycystic kidney disease/autosomal recessive polycystic kidney disease (ARPKD) is an autosomal recessive genetic disorder characterized by nonobstructive fusiform dilations of the renal collecting ducts, resulting in symmetric renal enlargement and renal failure. All patients have some degree of congenital hepatic fibrosis as well.
Epidemiology Occurrence is 1 in 20,000 births (M1:F1).
Embryology Autosomal recessive polycystic kidney disease causes both renal and hepatic disease. ARPKD is caused by numerous mutations in PKHD1 (polycystic kidney and hepatic disease 1). In general, the combination of mutations determines phenotypic presentation (i.e., the extent of renal and liver involvement), but there are no precise genotype-phenotype correlations. There is significant variation in the expression of ARPKD, resulting in renal manifestations occurring prenatally and neonatally, in infancy, and as a juvenile. There may be variable expression of ARPKD in one family.
Inheritance Patterns There is autosomal recessive inheritance. The gene for infantile polycystic kidney disease has been localized to chromosome 6p, and genetic diagnosis is available in involved families. In de novo cases, testing for a panel of causative genes is possible.
Teratogens None are known.
Prognosis The perinatal mortality rate is approximately 30% to 40% and is correlated with the presence of oligohydramnios prenatally. There is a 90% one-year survival rate. In survivors, the major morbidities are hypertension, renal failure requiring transplantation, and portal hypertension.
Kidneys retain reniform shape.
Renal size is above the 95th centile.
There are no detectable renal cysts.
There is loss of corticomedullary differentiation.
Kidneys are diffusely echogenic.
Fetal bladder is absent.
There is intrauterine growth restriction.
The numerous tiny cysts are below the resolution of ultrasound equipment.
The interface produced by the innumerable small cysts results in the increased echogenicity.
Fetal kidneys are considered hyperechoic when they are more echogenic than adjacent spleen or liver.
The earlier the presentation is, the worse the prognosis.
It is first detected in the early second trimester.
The kidneys may have a normal size and architectural pattern in the second trimester.
Once the sonologist has made a presumptive diagnosis of ARPKD, serial ultrasound examinations every 2 to 3 weeks should be performed to assess renal size and amniotic fluid volume.
Enlarged echogenic kidneys in a fetus are not diagnostic for polycystic kidney disease.
Kidney size in ARPKD does not correlate with renal function.
While ultrasound can diagnose severe prenatal disease, it cannot identify less-severe clinical types.
Meckel-Gruber syndrome (look for polydactyly and encephalocele): Renal cysts in this condition are usually visible.
Benign glomerulosclerosis: There are large echogenic kidneys, but pyramids are echopenic and the amniotic fluid is normal or mildly increased.
Adult polycystic kidney disease (autosomal dominant): There are large kidneys that may not be symmetrically enlarged. The kidneys are echogenic; cysts usually are seen in the fetus. A positive family history may be obtained.
Trisomy 13: The kidneys may be slightly enlarged and are echogenic with or without cysts. Numerous other pathologic findings, such as holoprosencephaly, will be present.
Beckwith-Wiedemann syndrome and Perlman syndrome: With both of these syndromes, the kidneys can be large and echogenic, but there is also macrosomia, and amniotic fluid volumes are normal. In the case of Beckwith-Wiedemann syndrome, omphalocele and macroglossia are often present.
Fetal cytomegalovirus (CMV) infection typically infects the kidneys, resulting in increased renal echogenicity and oligohydramnios.
Investigations and Consultations Required If there is no family history of ARPKD, the following investigations are appropriate:
Chromosomal evaluation to include microarray.
Fetal echocardiography to exclude other conditions that present with polycystic kidneys (trisomy 13 and Meckel-Gruber syndrome).
Viral studies to exclude fetal CMV.
Consultation with a pediatric nephrologist should be arranged to develop a management plan and to discuss the implications of this diagnosis with the family.
Monitoring Serial ultrasound examinations to monitor amniotic fluid volume and fetal abdominal circumference should be performed.
Pregnancy Course Most cases will develop oligohydramnios by the third trimester. Early-onset oligohydramnios is a poor prognostic sign. Intrauterine growth restriction is also common but does not affect prognosis.
Pregnancy Termination Issues A precise pathologic diagnosis is essential for counseling the family regarding the risk of recurrence. Unless the family is known to be at risk because of a previously affected pregnancy, an intact fetus should be delivered for complete external and internal examination.
Delivery Unless a precise diagnosis has been established prenatally, delivery should occur at a tertiary center, where an immediate evaluation can be performed to establish a diagnosis and to determine prognosis. Dystocia from extremely large abdominal circumference may be an indication for elective cesarean section in rare cases.
Resuscitation If a lethal prognosis is certain because of past family history or the prenatal diagnosis of early-onset oligohydramnios, a decision to withhold resuscitation is appropriate. If limited renal function is possible, but not certain, initial support is indicated until the infant can be evaluated and the prognosis can be determined. Infants may present with respiratory distress at delivery, either from pulmonary hypoplasia as a result of long-standing oligohydramnios or from severe abdominal distension due to renal enlargement. Severely affected infants may present with clinical features of Potter’s syndrome, including pulmonary hypoplasia, positional limb deformities, and facial dysmorphism secondary to oligohydramnios.
Transport Transport is indicated for full confirmation of the diagnosis and prognosis if an infant demonstrates survival potential initially.
Testing and Confirmation Ninety percent of patients with infantile polycystic kidney disease present with bilateral abdominal masses at birth. Careful, staged evaluation of renal function and structure by urine production, urinalysis, blood and urine chemistries, and ultrasonography is indicated. Subsequent procedures may be necessary to define renal function and survival potential.
Nursery Management Provide mechanical ventilation as necessary to maintain adequate gas exchange. Supportive care consists of management of hypertension; electrolyte imbalance, specifically hyponatremia requiring fluid restriction; and nutritional support. In severe cases, neonates with end-stage renal disease may require dialysis for survival. A multidisciplinary team consisting of neonatologists, nephrologists, hepatologists, and geneticists is required for the ongoing care of the infant.
Prognosis Currently, there is no cure for ARPKD. Long-term survival is dependent on the degree of renal and hepatic involvement. The mortality rate is 30% and is greatest in neonates who present with severe pulmonary hypoplasia and renal disease from the time of birth.
4.6 LOWER URINARY TRACT OBSTRUCTION (POSTERIOR URETHRAL VALVES, URETHRAL ATRESIA, URETHRAL STENOSIS)
Definition In general, the disorders designated as lower urinary tract obstruction (LUTO) have a blockage at the level of the urethra. In the case of posterior urethral valves (PUVs), the prostatic urethra is obstructed.
Epidemiology The incidence of LUTO is 2.2 per 10,000 live births. PUV occurs only in males, with an incidence of 1 in 4000 to 1 in 7500 infants. At least 60% of LUTO are on the basis of PUVs.
Embryology Posterior urethral valves are structures that normally develop in the prostatic urethra between 6 and 8 weeks of gestation. Hypertrophy of these valves causes proximal urethral distention, a thick-walled distended bladder, reflux, and hydronephrosis. Chromosome abnormalities, including trisomies 21, 13, and 18, have been reported in up to 20% of cases. Urethral atresia or stenosis is much more commonly associated with chromosome abnormalities, especially trisomies 13 and 18.
Inheritance Patterns Inheritance is sporadic. There are rare reports of familial recurrence.
Teratogens None are known.
Prognosis The prognosis is dependent on renal function. The overall mortality rate for antenatally diagnosed cases is 50%, but the mortality rate is 95% for those cases with oligohydramnios. Fifty percent of neonatal survivors develop chronic renal failure.
Male fetus
Distended bladder
Thickened bladder wall in a contracted state
Bilateral pyelocaliectasis
Dilated prostatic urethra (“keyhole” sign)
Hydroureter
Urinoma
Urinary ascites
Renal cortical cysts
Increased renal echogenicity
Oligohydramnios
Fetal bladder outlet obstruction has been diagnosed at 11 weeks’ gestation.
Dilatation of the proximal urethra anterior to the bladder is a characteristic sonographic finding with severe lower tract obstruction.
Spontaneous remission of fetal urinary tract obstruction from PUVs may occur due to rupture of the urethral valves.
The triad of increased renal echogenicity, cortical cysts, and oligohydramnios is highly predictive of renal damage.
Cortical cysts correlate with interstitial fibrosis and a decreased number of glomeruli.
Cortical cysts predict dysplasia. However, the absence of cortical cysts does not exclude dysplasia.
Increased renal echogenicity is a subjective assessment and is less predictive of renal dysplasia than cortical cysts.
Bladder wall thickness changes with the degree of bladder distention.
Thickness is best assessed when the bladder is contracted.
In the presence of early (18-24 weeks’ gestation) oligohydramnios, there is a high risk of pulmonary hypoplasia; normal amniotic fluid does not guarantee normal postnatal renal function.
Urethral obstruction with a massively enlarged bladder or urinary ascites may result in a “prune-belly” abdomen (i.e., abdominal muscle deficiency).
Urinary ascites is first detected at 23 weeks’ gestation.
Urine extravasation into the peritoneal cavity occurs too late to protect fetal renal function.
The detection rate of PUVs is 50% at 18-22 weeks’ gestation and 80% at 28 weeks’ gestation.
The most common diagnosis in false-positive cases of PUVs is severe VUR.
Of cases suspected of having PUVs, 5% actually have severe reflux.
Megacystis-microcolon-intestinal hypoperistalsis syndrome
The bladder wall is not thickened.
Ureters are generally not dilated.
Amniotic fluid volume is most commonly normal.
Investigations and Consultations Required Chromosome abnormalities are found in up to 20% of cases. Therefore, fetal karyotyping and microarray are essential. Fetal echocardiography should be performed to exclude associated heart defects, although these are uncommon associated anomalies. Pediatric urologic consultation is recommended to plan postnatal management. Consultation with pediatric nephrology may be beneficial, especially when in utero intervention is being entertained, to provide parents information on the long-term consequences of chronic renal insufficiency.
Fetal Intervention LUTO has long been proposed as a diagnosis for which in utero fetal intervention may be helpful and is achievable. The main goal of fetal intervention for LUTO is to prevent pulmonary hypoplasia due to anhydramnios during the canalicular phase of lung development (16-24 weeks’ gestation). For this reason, LUTO fetuses with normal amniotic fluid volume are not candidates for in utero intervention. A secondary, and more elusive, goal is the preservation of renal function. The majority of survivors of LUTO have some degree of renal insufficiency, and the need for dialysis is frequent. Renal transplant is complicated by a high incidence of failure to thrive among survivors.
Ultrasound has not been proven to be useful in predicting long-term renal function in survivors. Although cortical thinning, echogenicity, and cyst formation are indicative of renal dysplasia and a poor prognosis, their absence is not indicative of a good outcome. Serial vesicocentesis to assess for the preservation of renal concentrating capacity can better discriminate patients with “good prognosis” from “bad prognosis” after 20 weeks’ gestation. This information may be useful when considering in utero intervention.
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