Pediatric Urology

Clinical Manifestations and Management

of Prune-belly Syndrome in a Large
Contemporary Pediatric Population
Natan E. Seidel, Angela M. Arlen, Edwin A. Smith, and Andrew J. Kirsch
OBJECTIVE
METHODS

RESULTS

CONCLUSION

To review the clinical manifestations and operative management of a large contemporary pediatric cohort of patients with prune-belly syndrome (PBS).
PBS patients aged <21 years followed up in our pediatric urology clinic were identied by the
International Classication of Diseases, Ninth Revision code (756.71). Demographics, concomitant
diagnoses, surgical history, imaging studies, and renal or bladder function were evaluated.
Data were available for 46 pediatric patients (44 boys and 2 girls). Mean age was 7.6
4.7 years
(range, 0.9-20 years). Average length of clinical follow-up was 6.8
5 years. Forty-ve children
(97.8%) had hydroureteronephrosis, and 36 of them (78.3%) had vesicoureteral reux. Five
patients (10.9%) had signicant pulmonary insufciency, and 2 patients (4.3%) were oxygen
dependent. Eighteen children (39.1%) had other congenital malformations, including cardiac in
4 patients (8.7%) and musculoskeletal anomalies in 10 patients (21.7%). Orchidopexy was the
most common surgery, with all boys aged 3 years having undergone the procedure. Twenty-two
patients (47.8%) had a history of ureteral surgery, 22 (47.8%) had bladder surgery, 11 (23.9%)
had renal surgery, and 6 (13%) had urethral procedures. Nineteen patients (41.3%) underwent
abdominoplasty. Eighteen children (39.1%) had documented chronic kidney disease, and 8
children (17.4%) underwent renal transplantation. Average age at transplantation was 5.1

2.9 years. The mean nadir creatinine level for patients with end-stage renal disease was 1.4 mg/dL
compared with 0.4 mg/dL for those not requiring transplantation (P <.001).
Children with PBS have signicant comorbidities and require frequent operative intervention,
with disease heterogeneity necessitating an individualized management approach. Early end-stage
renal disease is prevalent, with approximately 15% of children requiring kidney
transplantation. UROLOGY -: -e-, 2014.
2014 Elsevier Inc.

rune-belly syndrome (PBS) is a rare multisystem

disease characterized by a deciency of abdominal
wall musculature, bilateral intra-abdominal testes,
and urinary tract abnormalities including megacystis,
hydroureteronephrosis, and renal dysplasia. PBS predominantly affects boys, with a contemporary incidence
of 3.6-3.8 per 100,000 live male births in the United
States.1,2 Females represent <5% of PBS cases and
present with abdominal wall deciency and urinary tract
dysmorphism without any gonadal anomaly. There is
wide variability in disease severity, and patients may also
experience concomitant cardiopulmonary, gastrointestinal, and/or musculoskeletal anomalies.3,4 Patients

Financial Disclosure: The authors declare that they have no relevant nancial interests.
Ethical approval approved under the Childrens Healthcare of Atlanta IRB 14-034.
From the Department of Pediatric Urology, Childrens Healthcare of Atlanta and
Emory University School of Medicine, Atlanta, GA
Address correspondence to: Andrew J. Kirsch, M.D., Department of Pediatric
Urology, Childrens Healthcare of Atlanta and Emory University School of Medicine,
5445 Meridian Mark Rd, Suite 420 Atlanta, GA 30342. E-mail: akirschmd@gmail.
com
Submitted: August 13, 2014, accepted (with revisions): September 23, 2014

2014 Elsevier Inc.

All Rights Reserved

often undergo multiple reconstructive procedures

throughout childhood including bilateral orchidopexy,
individually tailored urinary tract reconstruction, and
abdominoplasty.3,5
Optimal long-term management remains controversial,
but initial intervention is directed at cardiopulmonary
stabilization and bladder drainage. Historically, instrumentation of the urinary tract, including clean intermittent catheterization (CIC) and urodynamic studies, has
been discouraged in PBS because of an anticipated high
rate of urinary tract infection (UTI) and its sequelae.6
The use of continuous antibiotic prophylaxis and the
desire to prevent urinary stasis have changed this paradigm in recent years. As with many complex congenital
anomalies, meaningful PBS outcomes research is limited
by the rarity of the condition. As a result, there is a
paucity of recently published data describing outcomes of
children with PBS. We evaluated the clinical manifestations, operative and medical management, and longterm urologic outcomes of the largest contemporary
cohort of children with PBS.
http://dx.doi.org/10.1016/j.urology.2014.09.029
0090-4295/14

METHODS
Institutional review board approval was obtained. We identied a total of 46 patients diagnosed with PBS ranging in age
from 0.9 to 20 years (mean, 7.6
4.7 years). Children diagnosed with PBS, currently followed up in our outpatient pediatric urology clinic were identied by the International
Classication of Diseases, Ninth Revision code (756.71). The
electronic medical records of all pediatric patients with clinically conrmed PBS were retrospectively reviewed. Patient
demographics, concomitant diagnoses, respiratory status, imaging studies, and renal or bladder function were evaluated. All
surgical interventions and current bladder management were
also assessed. Patients aged >21 years and those not seen in the
previous 36 months were excluded from study. Statistical
analysis was performed using SAS 9.3 (SAS Institute, Cary,
NC), with P <.05 representing statistical signicance.

RESULTS
Patient Demographics
Fifty-seven patients with clinically conrmed PBS were
identied in our outpatient clinic system; detailed clinical
data were available on 46 pediatric patients (44 boys and
2 girls) who met all inclusion criteria. Mean age was 7.6

4.7 years (range, 0.9-20 years). Average length of
clinical follow-up was 6.8
5 years. Nineteen patients
(41.3%) were Caucasian, 18 (39.1%) African American,
3 (6.5%) Hispanic, 1 (2.2%) Asian, and 5 (10.9%) were
of mixed ethnicity.
Urologic Diagnoses
Forty-ve patients (97.8%) had bilateral hydroureteronephrosis, and 36 (78.3%) had a history of vesicoureteral reux (VUR); 34 cases were bilateral, and 2
cases were unilateral. The majority of patients (78.3%)
had at least 1 documented UTI, and 15 patients (32.6%)
had a history of febrile UTI. Of the 42 patients
aged 3 years, 14 of them (33.3%) experienced incontinence beyond expected for age and/or developmental
stage.
Comorbidities
Twenty-one children (45.7%) had other congenital
malformations, including cardiac anomalies in 4 (8.7%)
and musculoskeletal anomalies in 10 (21.7%). Eleven
patients (23.9%) had associated gastrointestinal diagnoses; an additional 13 children (28.3%) experienced
constipation. Five patients (10.9%) had signicant pulmonary insufciency, and 2 of them (4.3%) were oxygen
dependent. Three children (6.5%) had documented
psychiatric disorders including oppositional deant disorder, anxiety, and adjustment disorder. Urologic diagnoses and comorbidities are detailed in Table 1.
Urologic Surgeries
All children required surgical intervention (Table 2).
The most prevalent surgery was open or laparoscopic
orchidopexy, with 40 of 41 male patients having undergone bilateral orchidopexy by at least 3 years of age. A
2

Table 1. Urologic diagnoses and comorbidities in children

with prune-belly syndrome
N (%)
Sex
Male
Female
Age (y)
Mean age
Mean age at last follow-up
Urologic diagnoses
VUR
Nonfebrile UTI
Febrile UTI
Hydroureteronephrosis
Incontinence (children aged 3 y)
Other congenital malformations
Yes
Cardiac anomalies
Musculoskeletal anomalies
Spinal deformity
Club foot
Gastrointestinal anomalies
Pulmonary insufciency
Oxygen dependent
No

44 (95.7)
2 (4.3)
7.6
6.3
36
36
15
45
14

(78.3)
(78.3)
(32.6)
(97.8)
(33.3)

21
4
10
5
5
11
5
2
25

(45.7)
(8.7)
(21.7)
(10.9)
(10.9)
(23.9)
(10.9)
(4.3)
(54.3)

VUR, vesicoureteral reux; UTI, urinary tract infection.

Table 2. Urologic surgical procedures performed in children with prune-belly syndrome

N (%)
Urethral surgery
Urethral dilation
Urethrotomy
Bladder surgery
Vesicostomy
Appendicovesicostomy
Reduction cystoplasty
Tumor resection
Casale procedure
Cystostomy
Cystolithotomy
Testicular surgery
Renal surgery
Nephrectomy
Transplant
Nephrostomy
Ureteral surgery
Reimplantation
Ureterectomy
Pyeloplasty

6
5
1
22
5
16
4
1
1
1
1
41
11
8
8
1
22
19
7
3

(13.0)
(10.9)
(2.2)
(47.8)
(10.9)
(34.8)
(8.7)
(2.2)
(2.2)
(2.2)
(2.2)
(93.2)
(23.9)
(17.4)
(17.4)
(2.2)
(47.8)
(41.3)
(15.2)
(6.5)

single male patient (2.3%) had unilateral cryptorchidism

and subsequently underwent unilateral orchidopexy.
Twenty-two patients (47.8%) had a history of ureteral
surgery, 19 of whom (41.3%) underwent ureteral reimplantation. Twenty-two patients (47.8%) underwent
bladder procedures, including vesicostomy in 5 (10.9%)
and appendicovesicostomy in 16 (34.8%) patients.
Eleven patients (23.9%) had renal surgery, including
transplantation in 8 of them (17.4%). Six patients (13%)
underwent urethral surgery, with the most common procedure being serial urethral dilation (n 5, 10.9%).
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Nineteen patients (41.3%) underwent an abdominoplasty. Seventeen children underwent a modied

Monfort abdominoplasty; a single patient each underwent
an Ehrlich and Firlit abdominal wall reconstruction.
Mean age at abdominoplasty was 3.9
1.4 years. Seven
children underwent appendicovesicostomy concomitantly with abdominoplasty, and 3 children underwent a
Mitrofanoff catheterizable channel separate from their
abdominal wall reconstruction. Patients underwent a
mean of 2.3
2.6 procedures per year, with 1.1
1.5
general anesthetics per year.
Bladder Management
Twenty-four patients (52.2%) managed their bladder with
CIC, 16 (34.7%) via a continent catheterizable channel
and 8 (17.4%) per urethra due to incomplete bladder
emptying with or without recurrent UTIs. All patients on a
CIC regimen remain on prophylactic antibiotics and undergo annual surveillance renal bladder ultrasound. Fourteen patients (30.4%) underwent videourodynamics.
Indications for urodynamic (UDS) testing included preoperative planning in 11 patients (78.6%), recurrent infections in 2 (14.3%), and stomal leakage in 1 patient
(7.1%). All UDS studies demonstrated normal to supranormal capacity in patients without vesicostomy (mean,
2.4
1.4 times capacity for estimated bladder capacity for
age) and normal bladder compliance (mean, 63
50 mL/
cm H2O) with a mean postvoid residual of 63.1%. UDS
indications and ndings are detailed in Table 3.
Chronic Renal Disease
Eighteen patients (39.1%) had documented chronic
kidney disease, and 8 children (17.4%) underwent renal
transplantation. Average age at transplantation was 5.1

2.9 years, with 87.5% graft survival at a mean of 4.6

2.4 years after renal transplant. A single patient (12.5%)
experienced graft failure 7 years after transplantation and
is currently on hemodialysis. The mean nadir creatinine
level in infancy for patients with end-stage renal disease
(ESRD) was 1.4 mg/dL (range, 0.6-3.0 mg/dL) compared
with 0.4 mg/dL for those not requiring transplantation
(P <.001). Two transplanted children (25%) required
vesicostomy in infancy, and 5 of them (62.5%) currently
performed CIC via appendicovesicostomy because of poor
bladder drainage. Appendicovesicostomy was performed
before transplantation in all cases. All 8 children requiring
transplantation had bilateral hydroureteronephrosis and
VUR; 2 children (25%) also had recurrent febrile UTIs
despite continuous antibiotic prophylaxis and adequate
bladder drainage. Of the 8 children requiring transplantation, 3 had undergone prior abdominoplasty. No
complications secondary to abdominal wall reconstruction
were reported at the time of transplantation.

COMMENT
Optimal management of children with PBS remains
challenging, and treatment is further confounded by the
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rarity and broad spectrum of severity of the syndrome.

The initial postnatal course is dictated by the severity of
comorbidities; up to 75% of children with PBS have
concomitant diagnoses with prematurity being the most
common.1,3,7,8 Perinatal mortality rates range between
10% and 25% and are primarily related to the degree of
pulmonary hypoplasia and prematurity. The incidence of
concomitant cardiac (8.7%) and pulmonary (10.9%) diagnoses in our PBS cohort was considerably lower than
that reported in the literature (25% and 58%, respectively).1,3 This is likely secondary, at least in part, to our
patient cohort being derived from an outpatient setting.
Mortality is signicantly higher in neonates with prematurity and severe cardiopulmonary abnormalities; children
not seen in our clinic were excluded from the study. The
incidence of musculoskeletal anomalies (21.7%),
including scoliosis and club feet, as well as gastrointestinal
associations (23.9%), were consistent with those seen in
the literature.
The bladder is often hypotonic, with high compliance
and low-pressure VUR in approximately 75% of patients.9 Although competent at storage, PBS bladders
often demonstrate incomplete emptying and poor detrusor contraction.6 Initial urologic management is therefore
directed at bladder drainage and renal preservation.
Circumcision and prophylactic antibiotics are often recommended to decrease the incidence of UTI. Urinary
diversion may be necessary as a temporary measure in
children with acute renal failure, urinary sepsis, or bladder
outlet obstruction from urethral atresia with limited
patency of the urachus. When temporary urinary diversion is indicated, a cutaneous vesicostomy is the procedure of choice.10 In our series, 10.9% of children
underwent vesicostomy, which is consistent with the rate
recently reported by Routh et al1 using the Kids Inpatient
Database. Despite measures to combat urinary stasis and
reduce infection risk, the majority of children (78.3%) in
our cohort had a history of UTI, with approximately onethird experiencing pyelonephritis.
Bilateral intra-abdominal testes are a dening feature of
PBS and thought to be secondary to mechanical
obstruction from an enlarged bladder and dilated upper
urinary tract. This hypothesis is anecdotally supported by
a unique patient in our series who was born with a unilateral intra-abdominal testicle. The normally descended
testicle was ipsilateral to a prenatal shunt that was inadvertently placed into a dilated ureter rather than the
bladder. Traditional single-stage orchidopexy and singlestage vs 2-stage Fowler-Stephens orchidopexy are options and can be performed via an open or laparoscopic
approach depending on surgeon preference. Orchidopexy
can also be performed concomitantly with other surgical
procedures, such as appendicovesicostomy and abdominoplasty,6,11 which may be particularly benecial in
children with compromised respiratory status to limit the
number of general anesthetics. Children with PBS
frequently require numerous surgical procedures; our patients underwent a mean of >2 procedures per year,
3

Table 3. Indications and ndings of urodynamic testing obtained in children with prune-belly syndrome
Indication

Capacity

Compliance
mL/cm H2O

PVR,
mL (%)

Preoperative planning

2.9

27

522 (50)

Prolapsing vesicostomy,
preoperative planning

0.5

44

110 (100)

Preoperative planning

5.5

110

1850 (100)

Preop planning,
vesicostomy

0.8

26

139 (100)

2.7

28

Preoperative planning,
hx of VUR
Preoperative planning

5.2

204

710 (91)

7
8

Preoperative planning
Preoperative planning

2
3.2

39
90

440 (92)
200 (42)

Recurrent febrile UTIs

1.1

20

50 (14)

10 Preoperative planning

2.7

111

11
12
13
14

1.3
1.5
1.9
2.5

32
41
84
26

2.4
1.4

63
50

Preoperative planning
Recurrent febrile UTIs
Preoperative planning
Stomal leakage
Mean

435
200
342
150

(100)
(73)
(100)
(22)

63.1
38.9

Additional Findings

Management

Bilateral VUR

Appendicovesicostomy
and reimplant
Unable to ll due to Vesicostomy takedown and
appendicovesicostomy
prolapsing
vesicostomy,
did not void
per urethra
Appendicovesicostomy
and reduction cystoplasty
Left VUR, did not
Vesicostomy takedown,
void per urethra
left reimplant, and
appendicovesicostomy
No VUR
Abdominoplasty without
concomitant procedures
Abdominoplasty without
concomitant procedures
Appendicovesicostomy
Abdominoplasty without
concomitant procedures
VUR into transplant Increase frequency of CIC
kidney
per appendicovesicostomy
Bilateral VUR
Abdominoplasty and
bilateral reimplant
Appendicovesicostomy
Bilateral VUR
CIC per urethra
Appendicovesicostomy
Increase frequency of CIC
per appendicovesicostomy

CIC, clean intermittent catheterization; PVR, postvoid residual; other abbreviations as in Table 1.
Capacity multiplied by normal estimated bladder capacity for age using the formula (age 2)  30 mL. Postvoid residual recorded as
volume as well as percentage of individual bladder capacity.

averaging 1 general anesthetic procedure per year. It

should be emphasized, however, that in the absence of
any overriding medical issue, orchidopexy should be
performed as described by the current American Urological Association guideline.12 To this end, although 7
children
undergoing
abdominoplasty
underwent
concomitant appendicovesicostomy and 6 children underwent ureteral reimplantation, the majority underwent
orchidopexy before major urinary tract or abdominal
reconstruction. The need for appendicovesicostomy and/
or ureteroneocystostomy was based on preoperative UDS
ndings; all children with persistent VUR at the time of
abdominoplasty underwent concomitant ureteral
reimplantation.
Timing of urinary tract reconstruction and abdominoplasty remains a source of debate. Early simultaneous
correction of PBS anomalies with individualized urinary
tract reconstruction, orchidopexy, and abdominoplasty
has been described.5 Preservation of renal function is
paramount as children with incomplete bladder emptying
and/or recurrent UTIs with VUR may require CIC,
appendicovesicostomy, and/or antireux surgery.
Abdominal wall reconstruction has also been shown to
improve bladder emptying independent of genitourinary
reconstruction.13 It has been our practice to offer
4

abdominoplasty before entering school, with the mean

age at surgery being just <4 years. Three children in our
series underwent renal transplantation after abdominoplasty without complication; no abdominoplasties were
performed after transplant. Although not all children
undergo UDS testing at our institution, it is often performed preoperatively to determine the need for additional procedures such as appendicovesicostomy and/or
ureteral reimplantation. Durable cosmetic results after
abdominal wall reconstruction have been reported with
long-term follow-up.14 Anecdotally, abdominoplasty and
urinary tract reconstruction have a positive effect on both
parental and patients quality of life and is the source of
ongoing study at our institution.
Renal dysplasia is common in PBS, and approximately
40%-50% of patients will ultimately require renal
replacement therapy.15 Presence of 1 normal kidney on
ultrasound and a nadir serum creatinine level of <0.7 mg/
dL during the rst year of life are predictive of satisfactory
long-term renal function.16 Not surprisingly, children in
our cohort requiring transplantation had a signicantly
higher nadir serum creatinine level in infancy than those
not requiring renal replacement therapy, and all but 1
child had a nadir serum creatinine level of 0.7 mg/dL
suggestive of congenital renal dysplasia. Furthermore, all
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these patients had VUR that may have contributed to

their declining renal function. In addition, 7 of 8 transplanted patients had incomplete bladder drainage necessitating vesicostomy (n 2) or appendicovesicostomy
(n 5).
Patients undergoing renal transplantation were similar
in age (5.1
2.9 years) to that reported in the literature
(5.8
2.1 years).17 One-year and 5-year graft survival
rates are lower for children with lower urinary tract
dysfunction including PBS, with a 5-year 67% survival
rate,17,18 highlighting a serious concern as children with
PBS were transplanted at an average age of <6 years.
Seven of 8 children in our series had good graft function
at a mean of 4.5 years after transplantation. Early ESRD,
as seen in our patient population, is thought to be secondary to renal dysplasia, whereas later progression to
ESRD is often attributed to parenchymal damage from
repeated infections and high pressures generated from
incomplete emptying.19 VUR and incomplete bladder
drainage, despite antibiotic prophylaxis and vesicostomy
or CIC, may have also contributed to renal failure in
patients who required a renal transplant.
Our study has several limitations that warrant
acknowledgment aside from its retrospective and
descriptive nature, which subject it to the aws inherent
with such study design. Comorbidities and surgeries were
assessed; however, complications and the role of reconstruction in prevention of renal deterioration were not
evaluated in the present study. Patients were identied in
the outpatient clinic setting; those who did not survive
the neonatal period were therefore not included, and the
known high-perinatal mortality of PBS was not addressed
in the present study. The incidence of concomitant
congenital anomalies in our series may be articially low,
given that children who did not survive the neonatal
period were excluded from study. UDS testing was performed predominantly for preoperative planning purposes, and ndings may therefore not be reective of the
PBS population as a whole. Furthermore, both surgeon
and family preference inuence both the timing of
abdominoplasty and type of urinary tract reconstruction
performed. Despite these limitations, our study represents
the largest contemporary single-institution series of children with PBS, emphasizing the continued need for
numerous surgical interventions in this unique patient
population.

CONCLUSION
Children with PBS require multiple procedures to correct
associated urologic anomalies and address comorbidities

UROLOGY

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with testicular, bladder, and ureteral surgeries performed

most frequently. Despite early diagnosis, active renal and
bladder radiographic surveillance, use of CIC, and prophylactic antibiotics, early ESRD is prevalent, with
approximately 15% of children requiring kidney transplantation. Signicant disease heterogeneity necessitates
an individualized management approach.
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