Clinical manifestations and initial management of infants with bladder exstrophy

INTRODUCTION — Bladder exstrophy is a complex congenital anomaly involving the musculoskeletal system and the urinary, reproductive, and intestinal tracts. It is one of three disorders within the exstrophy-epispadias complex.

The diagnosis, clinical features, and initial management of bladder exstrophy are reviewed here. The surgical management and postoperative care of children with bladder exstrophy are discussed separately. (See "Surgical management and postoperative outcome of children with bladder exstrophy".)

EXSTROPHY-EPISPADIAS COMPLEX — The exstrophy-epispadias complex encompasses the following congenital anomalies, including bladder exstrophy.

●Epispadias, the least severe defect of the group, is characterized by failure of the urethra to close normally, and, as a result, the inner lining of the urethra lays flat and exposed on the dorsal (top) surface of the penis. Patients with bladder exstrophy will also have epispadias. However, isolated epispadias is less common than is classical bladder exstrophy and is diagnosed in 1 in 200,000 to 400,000 live births.

●Bladder exstrophy is classically characterized by an open, inside-out bladder (the inner surface exposed) on the surface of the lower abdominal wall and an open exposed dorsal urethra (picture 1 and figure 1 and picture 2 and picture 3). Bladder exstrophy usually involves several organ systems in the body, including the urinary tract, reproductive tract, digestive system, muscles and skin of the lower abdominal wall, and muscles and bones of the pelvis.

●Cloacal exstrophy, the most severe defect, is classically characterized by exstrophy of the urinary bladder and large intestine (hindgut) through an abdominal wall defect, anal atresia, hypoplasia of the colon, omphalocele, and anomalous genitalia (picture 4). In some cases, there may also be hypoplasia of the small intestine. The pelvic bone abnormalities are typically more pronounced in cloacal exstrophy relative to bladder exstrophy. The vertebral column (backbone) and spinal cord are also often abnormally developed. Individuals with cloacal exstrophy require evaluation and management by orthopedic and neurosurgery specialists. There may also be associated abnormalities of one or both kidneys such as impaired development, abnormal function or position, or absence of a kidney. (See "Body stalk anomaly and cloacal exstrophy: Prenatal diagnosis and management".)

PATHOGENESIS — The pathogenesis of bladder exstrophy appears to be due to an embryologic defect in abdominal wall development. The most universally accepted theory proposed by Marshall and Muecke is that lower abdominal wall development is disrupted by the overdevelopment of the cloacal membrane, which prevents medial migration of the mesenchymal tissue toward the midline [1]. The subsequent rupture of the cloacal membrane results in herniation of the lower abdominal components to the surface of the lower abdominal wall and the characteristic features of the exstrophy-epispadias complex. (See 'Exstrophy-epispadias complex' above.)

EPIDEMIOLOGY — The reported incidence of bladder exstrophy ranges from 3 to 5 per 100,000 live births (ie, 1 per 20,000 to 33,000 live births) [2-4]. It occurs more often in males than females [2,4,5] and is more frequent in firstborn children as well as in White infants compared with Black or Hispanic infants [6]. There appears to be a genetic predisposition as the risk of bladder exstrophy increases in offspring of affected individuals to 1 in 70 live births, approximately a 500-fold greater incidence than the general population [5,7].

CLINICAL FEATURES

Classic exstrophy — Patients with classic bladder exstrophy typically have a constellation of findings that affect the bladder, abdominal wall, pelvic bones, anus, and genitalia (picture 1 and figure 1 and picture 2 and picture 3). In the majority of cases, bladder exstrophy is an isolated anomaly to the bladder and pelvis without other associated malformations [4,8].

These include the following:

●Open bladder plate and exposed urethra through its entire length – The triangular defect caused by the premature rupture of the abnormal cloacal membrane contains the exstrophied bladder and exposed urethra.

●Low-set umbilicus – The umbilicus lies just above the apex of the defect (at the uppermost extent of the exposed bladder) in a more caudal position than normal.

●Diastasis of the symphysis pubis – Diastasis of the symphysis pubis is caused by outward malrotation of the pelvic bones, more specifically, the innominate bones (ilium, ischium, and pubis) that form the acetabulum. This results in the widening or separation of the pubic bones from the anterior midline (image 1). Other findings include an increased distance between the hips and outward rotation of the acetabula and lower limbs [9]. In one study, computed tomography (CT) demonstrated greater external rotation of both the iliac wing angle and sacroiliac joint angle in children with bladder exstrophy compared with age- and sex-matched controls [10]. Other findings included a greater mean pubic diastasis (4.2 versus 0.6 cm) and an increase in inferior rotation in patients with bladder exstrophy compared with controls. These deformities, if not corrected, may result in an abnormal gait in affected children. Infants with classic bladder exstrophy are also at risk for hip dysplasia [11]. (See "Developmental dysplasia of the hip: Clinical features and diagnosis".)

●Anteriorly displaced anus – The perineum is short and broad with displacement of the anus anteriorly, directly behind the urogenital diaphragm, which demarcates the posterior limit of the triangular fascial defect [12]. The anterior anal displacement and associated abnormalities in the pelvic floor musculature may predispose patients with bladder exstrophy to fecal incontinence and rectal prolapse and are important considerations for surgical correction. However, surgical reconstruction of this component of the anatomical defects present in bladder exstrophy is usually unnecessary.

●Inguinal hernia – Inguinal hernias are common in patients with bladder exstrophy [4,13].

●Genitalia anomalies – Although genitalia defects occur in both males and females, defects are generally more severe and complex in affected males.

•Males – In affected males, clinical features include epispadias with the urethral opening along the dorsal (top) surface aspect of the penis, dorsal (upward) curvature with absent dorsal foreskin, and an open prostate gland, which does not encircle the urethra but lies posterior to it (figure 1 and picture 2). The penis is shortened because of marked deficiency of anterior corpora cavernosa tissue and the diastasis of the symphysis pubis (figure 2). Magnetic resonance imaging (MRI) demonstrates altered infantile prostate anatomy with prostates that are almost twice as wide, greater in anteroposterior dimension, and shorter in craniocaudal dimension patients with bladder exstrophy compared with normal patients [14]. In addition, both neonatal and adult male patients with bladder exstrophy have a shorter anterior corporal (erectile body/tissue) length compared with normal controls [15,16].

•Females – Affected females have epispadias with a bifid clitoris and small, laterally displaced labia minora (picture 1).The vagina, which is of otherwise normal caliber, is shortened to one-half of the length seen in normal controls [17]. However, a note of caution as this report was based on only five girls with bladder exstrophy and, if confirmed, the implications of these findings are not clear. In the sexually active mature female, vaginal dilation may occasionally be required to allow satisfactory sexual intercourse. The fallopian tubes and ovaries are generally normal. Female patients may be predisposed to the development of uterine prolapse, which may require corrective surgery [18].

Variants — Variants of the classic bladder include the following:

●Superior vesical fissure – These patients have the typical muscular and skeletal defects of classic bladder exstrophy, but only the upper (cephalad) portion of the bladder is affected. The urethra may be intact.

●Pseudoexstrophy – These patients have the typical muscular and skeletal defects of classic bladder exstrophy but do not have any urinary tract abnormality (ie, intact normal urinary system).

●Duplicate exstrophy – These patients have a duplicated lower urinary tract, which includes one closed system and one open system with an exposed bladder and urethra on the surface of the lower abdominal wall, anterior to the inner closed bladder.

●Covered exstrophy – These patients have the typical muscular and skeletal defects of classic bladder exstrophy with only a skin covering over the bladder and urethra.

Other congenital anomalies — Other anomalies outside of the exstrophy complex include kidney abnormalities, vertebral and joint abnormalities, and cardiac defects (eg, persistent foramen ovale, patent ductus arteriosus, and atrial and ventricular defects) [8].

DIAGNOSIS — Often, the diagnosis of bladder exstrophy is made by prenatal ultrasound and, in some cases, may be confirmed by MRI. In the event that a prenatal diagnosis is not made, the diagnosis should be clinically apparent and recognizable at birth in the delivery room. A report from a multiinstitutional database found marked increases in prenatal diagnosis of bladder exstrophy and OEIS syndrome (omphalocele-exstrophy-imperforate anus-spinal defect) over a 20-year study period, with doubling of the prenatal diagnosis of bladder exstrophy [19].

Prenatal ultrasound — In a review of 40 prenatal ultrasound examinations performed in 25 pregnancies in which the offspring had classic bladder exstrophy, the following findings were consistent with the prenatal diagnosis of bladder exstrophy (image 2) [20]:

●Absence of bladder filling

●Low-set umbilicus

●Pubic bone diastasis

●Diminutive genitalia

●Lower abdominal mass that increases in size as the pregnancy progresses and as the intraabdominal viscera increase in size

Delivery room — If a prenatal diagnosis is not made, the diagnosis of bladder exstrophy should be clinically recognizable at delivery. A careful physical examination will differentiate bladder exstrophy from other congenital anomalies that involve abdominal wall defects, such as omphalocele, gastroschisis, and cloacal exstrophy.

INITIAL MANAGEMENT

Prenatal care — Following the prenatal diagnosis of bladder exstrophy, prenatal care includes the following:

●Education and counseling of the parents/caregivers – This includes reviewing the diagnosis of bladder exstrophy and its implications, touring the neonatal intensive care unit, meeting the pediatric urologic care team, and allowing the expectant parent(s)/caregivers the opportunity to interact with other families with a child with bladder exstrophy.

●Preparation for delivery – In many tertiary centers, one option for planning initial surgical management is an induced vaginal delivery that is scheduled in late gestation with coordination with an on-site pediatric urology service. This approach facilitates bladder closure within 72 hours of life. (See "Surgical management and postoperative outcome of children with bladder exstrophy", section on 'Surgical approaches'.)

Delivery room and nursery care — After delivery of an infant with bladder exstrophy, the following measures are used, with the main focus of limiting trauma to the mucosa of the exposed open bladder.

●Umbilical cord ‒ After initial routine plastic clamp occlusion of the umbilical cord at delivery, the clamp is exchanged for soft cloth umbilical "tape" or silk ligature to limit trauma to the exposed inner surface of the bladder.

●Bladder coverage ‒ The bladder is covered with a nonadherent film of plastic wrap or a transparent adhesive dressing (picture 5). We prefer using transparent adhesive dressing because it adheres to the intact skin immediately (surrounding the exposed bladder), provides protection of the bladder by covering without sticking to the surfaces of the bladder and urethra, and prevents diaper abrasion. It also allows egress of urine along the scrotum in boys and the genitalia in girls and prevents irritation to the exposed bladder and urethra from abrasive diapers.

●Bladder irrigation ‒ The bladder may be irrigated intermittently with sterile saline during diaper changes, although this is not absolutely necessary. The bladder may be submersed in water for a tub bath. We cleanse the exposed bladder and urethra with mild soap and water, followed by a water-only "rinse," particularly for infants who will not have immediate repair.

●Referral ‒For a newborn who presents at delivery without a prior antenatal diagnosis, pediatric urology, orthopedics, anesthesia, and social services should be consulted during the newborn period.

●No need for prophylactic antibiotics ‒ Broad-spectrum antibiotics are generally not necessary prior to initial reconstructive surgery.

Preoperative evaluation — The preoperative evaluation includes a thorough physical examination, blood tests, and imaging studies.

●Physical examination ‒ Important features of the initial physical examination, which may impact further management decisions, include:

•Size of the bladder plate – The size of the bladder plate may affect the timing of surgical closure. Patients with a small bladder plate may have delayed reconstruction to allow further growth of the bladder to facilitate successful bladder closure. However, other factors, such as surgeon and institutional preference, affect timing of initial surgery (within 48 to 72 hours after birth versus 6 to 12 weeks of life). (See "Surgical management and postoperative outcome of children with bladder exstrophy", section on 'Neonatal iliac osteotomy and pelvic immobilitzation'.)

•Position of the testes – As for any newborn male infant, the examination should identify the position of the testes to exclude cryptorchidism. In males with bladder exstrophy, the testes may appear to be undescended in their course from the widened pubic tubercles to the flat, wide scrotum. However, most males with bladder exstrophy do not have cryptorchidism and do not require orchiopexy. (See "Undescended testes (cryptorchidism) in children: Clinical features and evaluation", section on 'Clinical features'.)

•Presence of an inguinal hernia – If present, an inguinal hernia may be repaired at the time of surgical closure of the bladder.

•Periumbilical anatomy (eg, presence of omphalocele) – The presence of an omphalocele suggests a diagnosis of cloacal exstrophy. However, omphalocele (protruding, covered intraabdominal organs) may occasionally be associated with bladder exstrophy. (See "Body stalk anomaly and cloacal exstrophy: Prenatal diagnosis and management", section on 'Cloacal exstrophy'.)

•Position of the anus – The anus is usually displaced anteriorly, which may have important clinical implications for urinary and fecal continence, pelvic organ prolapse, and surgical reconstruction. However, surgical revision of the anus is generally uncommon.

•Degree of pubic symphysis diastasis and malleability of the pelvis – The need for pelvic osteotomy at the time of bladder closure depends on the severity of these two features. (See "Surgical management and postoperative outcome of children with bladder exstrophy", section on 'Neonatal iliac osteotomy and pelvic immobilitzation'.)

●Laboratory studies ‒ The laboratory evaluation includes a complete blood count, serum electrolytes, and kidney function tests. Blood urea nitrogen and creatinine at birth are reflective of maternal kidney functions, and subsequent tests are useful in determining whether or not there is any kidney impairment. In general, patients with bladder exstrophy have normal kidneys and kidney function. (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Serum creatinine'.)

●Imaging ‒ Imaging studies performed within the first two days of life prior to complete primary repair include:

•Renal ultrasound to screen for any congenital anomaly of the kidney or urinary tract. Patients with classic bladder exstrophy typically have two normal kidneys in normal (orthotopic) position. (See "Overview of congenital anomalies of the kidney and urinary tract (CAKUT)".)

•Abdominal plain film to measure the degree of pubic diastasis. This is best performed with a radiopaque ruler that is visible on the radiograph, placed on the front of the upper thighs of the baby or on the lower abdominal wall but not to obscure the pubic bones.

•Pelvic MRI may be helpful to assess the bony and soft tissue anatomy of the pelvis [21]. (See "Surgical management and postoperative outcome of children with bladder exstrophy".)

SUMMARY AND RECOMMENDATIONS

●Definition ‒ Bladder exstrophy is a complex congenital anomaly within the exstrophy-epispadias complex, a spectrum that involves the musculoskeletal system and the urinary, genital, and intestinal tracts. The other two conditions within this complex are epispadias and cloacal exstrophy. (See 'Exstrophy-epispadias complex' above.)

●Pathogenesis ‒ The pathogenesis of bladder exstrophy appears to be due to an embryologic defect in abdominal wall development due to the in utero rupture of an overdeveloped cloacal membrane that results in herniation of lower abdominal components, including the open, exposed urinary bladder, onto the lower abdominal wall surface. (See 'Pathogenesis' above.)

●Epidemiology ‒ The incidence of bladder exstrophy is approximately 1 per 30,000 to 50,000 live births. It occurs more frequently in males, firstborn children, and White infants. The incidence increases in offspring of affected individuals to a rate of 1 in 70 live births. (See 'Epidemiology' above.)

●Clinical features ‒ The clinical features of classic bladder exstrophy are an open bladder and exposure of the urethra on the surface of the lower abdomen and top (dorsum) of the penis, respectively; low-set umbilicus; diastasis of the symphysis pubis; anteriorly displaced anus; inguinal hernia; and genitalia defects, which are generally more severe and complex in male than in female patients (picture 1 and figure 1 and picture 2 and picture 3 and image 1). (See 'Classic exstrophy' above.)

●Diagnosis ‒ The diagnosis of bladder exstrophy is often made by prenatal ultrasound (image 2), or, if a prenatal diagnosis is not made, the diagnosis is apparent on physical examination immediately at birth. (See 'Diagnosis' above.)

●Initial management ‒ The initial management for bladder exstrophy includes the following:

•Prenatal care – When the diagnosis is made prenatally, prenatal care includes education and counseling for the family/caregivers and scheduled delivery in late gestation at a tertiary center with an available on-site pediatric urology service, which can coordinate perioperative evaluation and surgical repair following the scheduled delivery. (See 'Prenatal care' above.)

•Care in the delivery room ‒ After delivery, it is important to limit trauma to the mucosa of the exposed open bladder and urethra. Measures include (see 'Delivery room and nursery care' above):

-Replacement of the plastic clamp routinely used to occlude the umbilical cord with a soft silk ligature or umbilical tape.

-Covering the bladder with transparent adhesive dressing that adheres to the intact skin immediately surrounding the exposed bladder and urethra to protect against diaper abrasion or, if this is unavailable, soft plastic wrap. (See 'Delivery room and nursery care' above.)

•Referral ‒ For the neonate who was not diagnosed prenatally, pediatric urology, orthopedics, anesthesia, and social services should be consulted in the newborn period.

•Perioperative evaluation includes a complete physical evaluation, laboratory testing (ie, complete blood count and serum electrolytes), and imaging (ie, renal ultrasound, abdominal plain film, and, possibly, pelvic MRI). (See 'Preoperative evaluation' above.)

●Surgical management ‒ The surgical and postoperative management of bladder exstrophy is discussed separately. (See "Surgical management and postoperative outcome of children with bladder exstrophy".)