Journal of Pediatric Urology (2023) 19, 66e74
Review Article
Department of Urology, Faculty
of Medicine, Universitas
Indonesia, Cipto
Mangunkusumo Hospital, Jalan
Diponegoro No. 71, Jakarta
10430, Indonesia
* Correspondence to: I.
Wahyudi, Department of
Urology, Faculty of Medicine,
Universitas Indonesia, Cipto
Mangunkusumo Hospital, Jalan
Diponegoro No. 71, Jakarta,
10430, Indonesia, Fax: þ6221
3145592
irf.wahyudi2011@gmail.com
(I. Wahyudi)
Keywords:
Antenatal hydronephrosis;
Circumcision; Obstructive
hydronephrosis; Posterior ure-
thral valve; Urinary tract
infection; Vesicoureteral reflux
Received 11 September 2022
Revised 22 October 2022
Accepted 26 October 2022
Available online 28 October
2022
https://doi.org/10.1016/j.jpurol.2022.10.029
1477-5131/ª 2022 The Author(s). Published by Elsevier Ltd on behalf of Journal of Pediatric Urology Company. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Circumcision reduces urinary tract
infection in children with antenatal
hydronephrosis: Systematic review and
meta-analysis
Irfan Wahyudi *, Putu Angga Risky Raharja,
Gerhard Reinaldi Situmorang, Arry Rodjani
Summary
Introduction
Urinary tract infection (UTI) is more prevalent in
boys with antenatal hydronephrosis (ANH). Circum-
cision is known to lessen the risk of UTI. This study
was performed to examine the associations between
circumcision and UTI among patients with ANH.
Methods
The Preferred Reporting Items for Systematic Re-
views and Meta-Analyses standards were followed
for conducting this systematic review and meta-
analysis. PubMed, ScienceDirect, EMBASE, and
Cochrane Library databases were searched through
August 4th, 2022 to identify eligible studies. The risk
of bias was measured using the Newcastle-Ottawa
Scale (NOS). Review manager 5.4 was used for all
analysis.
Introduction
In 1%e2% of all pregnancies, antenatal hydro-
nephrosis (ANH) is a frequently diagnosed con-
dition [1]. The rate of detection is rising due to
the extensive use of prenatal ultrasonography
[2]. ANH reflects a spectrum of potential eti-
ologies, including transient or physiologic
hydronephrosis, vesicoureteral reflux (VUR),
ureteropelvic junction obstruction (UPJO),
ureterovesical junction obstruction (UVJO),
posterior urethral valve (PUV), and other con-
ditions [1]. Early diagnosis during the antenatal
period permits early postnatal monitoring for
complications such as urinary tract infection
(UTI), hypertension, growth failure, and even
renal failure [2].
Identifiable factors linked with UTI in ANH
patients remain under investigation [3].
Several studies found that hydronephrosis
grade, VUR, gender, circumcision status, and
Results
A total of 21 studies involving 8,968 patients with
ANH were included in the meta-analysis. The in-
cidences of UTI were 18.1% in the uncircumcised
group and 4.9% in the circumcised group. From
analysis, circumcision had significant protective ef-
fect against UTI with pooled OR of 0.28 (95% CI
0.23e0.32). The significant protective effects were
also found in subgroup analysis of hydronephrosis
etiology, including vesicoureteral reflux (pooled OR
of 0.24; 95% CI 0.17e0.32), obstructive hydro-
nephrosis (pooled OR of 0.34; 95% CI 0.21e0.53), and
posterior urethral valve (pooled OR of 0.28; 95% CI
0.16e0.52).
Conclusion
Our meta-analysis showed that circumcision was
associated with a decreased incidence of UTI in
children with ANH. This benefit was consistent irre-
spective of the underlying cause of hydronephrosis.
prophylactic antibiotic use were linked with
the incidence of UTI in hydronephrosis pa-
tients [4e10]. This is evidence that boys with
hydronephrosis are more prone to getting UTI
[11,12]. Ellison et al. stated that the incidence
of UTI among boys with ANH (12%) was
significantly higher compared to healthy
boys (1%) [12].
In boys with hydronephrosis, circumcision is
known to minimize the risk of UTI [13]. The
American Academy of Pediatrics’ (AAP)
consensus statement on male circumcision also
recommends circumcision for boys with uro-
logical anomalies to reduce UTI incidence [14].
A meta-analysis investigating the correlations
between circumcision and UTI in boys with ANH
has not been published. Consequently, we
performed a systematic review and meta-
analysis to review the available evidence
regarding potential associations between
circumcision and UTI in children with ANH.
Circumcision reduces UTI in children with ANH
Material and methods
Literature search
This study was conducted in accordance with the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) guidelines. Through August 4th, 2022, systematic
searches were performed using PubMed, ScienceDirect,
EMBASE, and Cochrane Library databases to identify rele-
vant literature evaluating associations between circumci-
sion and the incidence of UTI in children with ANH. The
subsequent subject terms and keywords were used:
(“circumcision” or “circumcised” or “uncircumcised”) and
(“UTI” or “urinary tract infection” or “urinary infection” or
“bacteriuria” or “bacteremia” or “pyuria”) and (“hydro-
nephrosis” or “renal dilatation” or “renal dilation” or
“vesico-ureteral reflux” or “vesicoureteral reflux” or “VUR”
or “ureteropelvic junction obstruction” or “UPJO” or
“ureterovesical junction obstruction” or “UVJO” or “meg-
aureter” or “dilated ureter” or “posterior urethral valve” or
“PUV”. This study conducted a search using the most
pertinent keywords for each database. In addition, manual
searches using references from related papers were also
undertaken. This study’s protocol has been registered.
Inclusion and exclusion criteria
The population is comprised of male children with ANH
history or subsequent postnatal diagnosis. This study
included patients with reflux (VUR), obstructive hydro-
nephrosis (UPJO and UVJO), PUV, and unspecified hydro-
nephrosis. The outcome of the eligible studies must have
included any UTI associated with circumcision status. The
following inclusion criteria were necessary for studies to
qualify: (1) a prospective, retrospective, or randomized
trial evaluating the associations between circumcision sta-
tus and UTI in ANH patients; (2) English language; and (3)
comparability of UTI incidence between case and control
groups in order to calculate odds ratios (OR). These were
the exclusion criteria for the study: (1) qualitative studies,
case reports, commentary, editorials, systematic reviews,
and meta-analyses; and (2) unavailability of full text. The
dates of publication were not restricted. When two studies
of the same population were found, only the one with the
bigger sample size was used.
Quality assessment and data extraction
Two independent investigators conducted data extraction
and quality assessment. Disagreement was addressed by
discussion and, if necessary, the assistance of other in-
vestigators. The risk of bias was evaluated using the
Newcastle-Ottawa Scale (NOS) [15]. We identified three
domains for assessing bias, including: (1) selection, (2)
comparability, and (3) outcome. Based on the scores in
each domain, the total methodological quality was derived.
Information on the author, publication year, population
characteristics, UTI definition, circumcision classification,
and circumcision incidence from eligible studies was
collected.
67
Statistical analysis
Associations between circumcision status and the incidence
of urinary tract infections were evaluated using OR and 95%
confidence interval (CI). A chi-square-based Q test was
conducted to examine the heterogeneity of the eligible
studies. The presence of heterogeneity was established if
the P value was less than 0.10. The fixed-effects model was
employed for the calculation of pooled ORs for homoge-
neous studies (p value of Q test >0.10). In instances of
heterogeneity, the random-effects model was utilized. If at
least two studies were available, sub-analyses based on the
etiology of hydronephrosis were conducted. The publica-
tion bias was assessed with Begg’s funnel plot. Review
manager 5.4. (Revman Cochrane, London, UK) was utilized
to perform statistical analyses.
Results
Literature search and study characteristics
There were 682 articles identified from the first literature
search. There were 488 articles remaining after the
removal of duplicates. After further title and abstract re-
view, 411 articles were excluded. Then, the eligibility of
the full texts of the remaining 77 articles was evaluated.
Finally, we found 21 studies that met the criteria for in-
clusion in the meta-analysis [3,4,8,12,16e32]. Fig. 1 de-
picts the eligibility process in this meta-analysis. The
characteristics of the studies considered in the quantitative
synthesis are presented in Table 1. Table 2 shows that,
based on the NOS scale, 9 studies (43%) were judged to be
of high quality.
Circumcision status and UTI in patients with ANH
All studies were included in the quantitative synthesis. This
resulted in 21 studies, with a total of 8,968 patients with
ANH, and 4,272 (47.6%) were circumcised. The overall
incidence of UTI in this population was 11.8% (1,060/8,968).
The incidence of UTI was 3.7 times higher in the uncir-
cumcised group (18.1%; 851/4,696) compared to the
circumcised group (4.9%; 209/4,272). From the meta-
analysis, circumcision had a significant protective effect
against UTI in patients with ANH with a pooled OR of 0.28
(95% CI 0.23e0.32) as shown in Fig. 2. This dataset exhibi-
ted no substantial heterogeneity, as evidenced by the I2 of
6% and p value of the Q test of 0.38. Fig. 2 shows that there
was no publication bias because there was no asymmetry in
the funnel plot.
Circumcision status and UTI in patients with VUR
There were nine studies involving 1,408 patients with VUR.
The overall incidence of UTI in this population was 28%
(395/1,408) and 12.9% (67/521) of circumcised males
developed UTI compared to 37% (328/887) of uncircumcised
males. Circumcision also had a significant protective effect
against UTI in patients with VUR with a pooled OR of 0.24
(95% CI 0.17e0.32) as shown in Fig. 3. Sub-analysis of VUR
68
Fig. 1 Flow chart of eligible study selection.
grade showed that patients with high grade VUR (grade
4e5) also benefited from circumcision (pooled OR of 0.10;
95% CI 0.05e0.21). Sub-analysis for low grade VUR (grade
1e3) was not possible since there was only one study
included [22]. However, a protective effect was also
observed in low grade VUR based on that study. The dataset
was homogenous with an I2 of 16% and p value of Q test of
0.30. There was no publication bias among eligible studies
based on the funnel plot.
Circumcision status and UTI in patients with
obstructive ANH
We also performed sub-analysis in patients with
obstructive ANH, including UPJO and primary non-refluxing
megaureter. In the four studies with obstructive ANH, there
were 823 patients, and 402 (48.8%) were circumcised. The
overall incidence of UTI in this population was 14% (115/
I. Wahyudi et al.
823) and 6.7% (27/402) of circumcised males developed UTI
compared to 20.9% (88/421) of uncircumcised males. As
shown in Fig. 4, circumcision was significantly protective
against developing UTI in obstructive hydronephrosis pa-
tients with a pooled OR of 0.34 (95% CI 0.21e0.53). Eligible
studies showed no heterogeneity (I2 Z 0%; p value of Q
test Z 0.63). The funnel plot revealed no significant pub-
lication bias.
Circumcision status and UTI in patients with PUV
In the three studies with UTI rates in patients with PUV,
there were 316 males, and 115 (36.4%) were circumcised.
The overall incidence of UTI in this population was 34.5%
(109/316) and 15.7% (18/115) of circumcised males devel-
oped UTI compared to 45.3% (91/201) of uncircumcised
males. Circumcision was significantly protective against
developing UTI in PUV males with a pooled OR of 0.28 (95%
 Circumcision reduces UTI in children with ANH
Table 1 Characteristics of individual studies included in the meta-analysis.
No Study Country Designs Population Hydronephrosis UTI Definition Circumcision UTI/Total UTI/Total
Definition Classification Circumcised Uncircumcised
1 Herndon et al., United States Retrospective Children VUR Not stated Medical records 7/36 10/19
1999 [16]
2 Farhat et al., Canada Cohort, Infants Primary VUR Positive urine Not stated 1/7 6/17
2000 [17] 1993e1998 culture collected
with catheter
3 Kwak et al., Korea Cohort, Boys after anti- Primary VUR Recurrent UTI Performed 2/27 11/50
2004 [18] 1985e1993 reflux surgery (positive culture in during study
midstream urine
specimen) after
surgery
4 Mukherjee United Retrospective Boys (1e18 years) PUV Possible febrile UTI Performed 8/27 51/78
et al., 2009 [19] Kingdom treated with during study
antibiotics or proven
from culture results
5 Roth et al., United States Retrospective Children UPJO & Symptomatic Medical records 0/41 2/24
2009 [20] obstructive infection with
megaureter positive urine culture
6 Alsaywid et al., Australia Cohort, Boys High-grade Not stated Performed 5/74 62/137
2010 [21] 1995e2006 (birth-8.8 years) primary VUR during study
7 Gücük et al., Turkey Randomized Boys (<3 years) Low-grade VUR Symptomatic UTI with Performed 0/45 9/46
2013 [22] trial positive urine culture during study
8 Sencan et al., United States Prospective, Children Antenatal Signs and/or Not stated 5/480 10/128
2014 [23] 1998e2010 hydronephrosis symptoms with
positive urine culture
9 Zareba et al., Canada Retrospective Infants Antenatal Symptomatic with Medical records 4/76 23/149
2014 [8] hydronephrosis positive culture from
a catheterized urine
specimen
10 Braga et al., Canada Cohort, Infants (birth-18 Antenatal Positive urine culture Not stated 5/95 35/166
2015 [4] 2010e2013 months) hydronephrosis from catheter
specimen associated
with fever
11 Evans et al., United Kingdom Retrospective Children Primary VUR Positive urine culture Not stated 6/27 17/25
2015 [24] (<16 years) accompanied with
fever
12 Hidas et al., United States Retrospective Children (0e Primary VUR Infection Medical records 1/23 6/42
2015 [25] 130 months) characterized by
fever, positive
urinalysis, and
culture
(continued on next page)

69
 70
Table 1 (continued )
No Study Country Designs Population Hydronephrosis UTI Definition Circumcision UTI/Total UTI/Total
Definition Classification Circumcised Uncircumcised
13 Braga et al., Canada Cohort, Infants Primary non- Fever, pyuria, and Not stated 4/21 21/51
2016 [26] a 2008e2015 (birth-21 months) refluxing positive urine culture
megaureter
14 Zee et al., 2016 United States Retrospective Infants (<2 years) Antenatal Positive urine culture Medical records 1/116 4/31
[3] hydronephrosis based on laboratory
testing
15 Ellison et al., United States Retrospective, Boys Antenatal Database records of Database records 146/2386 514/3174
2018 [12] claims database hydronephrosis UTI diagnosis
16 Varda et al., United States Retrospective Infants Antenatal Symptoms and Medical records 0/185 2/77
2018 [27] (<3 months) hydronephrosis microbiology results
17 Chan et al., United States Retrospective Children UPJO undergoing Symptoms with Medical records 2/80 4/25
2021 [28] (<18 years) robot-assisted positive urine culture
laparoscopic and positive urinalysis
pyeloplasty
18 Holzman et al., United States Cohort, Infants Primary VUR Symptomatic/febrile Examinations 1/24 17/81
2021 [29] 2014e2020 (<1 year) infection with pyuria
and positive culture
19 Holzman et al., United States Cohort, Infants Antenatal Pyuria with positive Registry data 7/89 27/90
2021 [30] a 2008e2020 hydronephrosis urine culture
with
concomitant
dilated ureter
20 Chamberlin United States Retrospective Infants Antenatal Symptoms with Registry data 3/364 12/244
et al., 2022 [31] (<2 years) hydronephrosis positive urine culture
21 Harper et al., France Randomized trial Boys PUV Fever with evidence Performed 1/49 8/42
2022 [32] of pyuria and culture- during study
proven infection from
catheterization or
suprapubic aspiration
a
These studies will be identified with (2) in the forest plot since there was similar first author name.

I. Wahyudi et al.
Circumcision reduces UTI in children with ANH 71

Table 2 Summary of quality assessment scores using Newcastle Ottawa Scale.

No Study Selection Comparability Outcome Methodological
(max. 4 stars) (max. 2 stars) (max. 3 stars) quality (high 7 stars)
1 Herndon et al., 1999 [16] ** * ** Low
2 Farhat et al., 2000 [17] *** * ** Low
3 Kwak et al., 2004 [18] *** ** ** High
4 Mukherjee et al., 2009 [19] ** * ** Low
5 Roth et al., 2009 [20] *** * ** Low
6 Alsaywid et al., 2010 [21] *** ** *** High
7 Gücük et al., 2013 [22] *** * ** Low
8 Sencan et al., 2014 [23] *** * ** Low
9 Zareba et al., 2014 [8] **** ** *** High
10 Braga et al., 2015 [4] *** ** *** High
11 Evans et al., 2015 [24] *** * ** Low
12 Hidas et al., 2015 [25] *** * ** Low
13 Braga et al., 2016 [26] a *** ** ** High
14 Zee et al., 2016 [3] **** ** ** High
15 Ellison et al., 2018 [12] ** * *** Low
16 Varda et al., 2018 [27] *** * *** High
17 Chan et al., 2021 [28] ** * *** Low
18 Holzman et al., 2021 [29] *** ** *** High
19 Holzman et al., 2021 [30] a *** * ** Low
20 Chamberlin et al., 2022 [31] ** * *** Low
21 Harper et al., 2022 [32] **** * ** High
*, **, *** corresponds to number of stars of each scale.
a
These studies will be identified with (2) in the forest plot since there was similar first author name.

CI 0.16e0.52), as shown in Fig. 5. Due to a lack of data,
further sub-analysis of VUR status among PUV populations
was not feasible. Harper et al. discovered that 55.2% of PUV
patients had high-grade VUR (grades III-V) [32]. There was
no significant variability between eligible studies (I2 Z 23%;
p value of Q test Z 0.27). In addition, no asymmetry was
observed in the resulting funnel plot.
Discussion
Our analysis indicates that UTI incidence in ANH patients
was higher among uncircumcised boys (18.1%) compared to
circumcised boys (4.9%). Circumcision is found to have a
significant protective effect in such a population. Further
sub-analysis found that the significant protective effect of
circumcision was consistent regardless of the etiology of
hydronephrosis (VUR, obstructive ANH, and PUV).
Circumcision appears to be a successful, very straight-
forward, and inexpensive treatment for patients with ANH.
The mechanism by which circumcision reduces UTI is most
likely due to a reduction in bacterial contamination [19].
Uropathogens can adhere to the preputial mucosal surface
in uncircumcised males, enhancing colonization around the
meatus [22,33]. After circumcision, pathogenic periurethral
bacterial flora will be replaced by non-uropathogenic spe-
cies [22]. In the first few months of infancy, boys with ANH
have the highest risk of developing UTI [24]. Circumcision
should be considered as soon as possible. However, the
decision to perform circumcision must be individualized for

Fig. 2 Forest and funnel plots for showing pooled estimates of UTI rates according to circumcision status in patients with ANH.
72
Fig. 3 Forest and funnel plots for showing pooled estimates of UTI rates according to circumcision status in patients with VUR.
each patient since not all UTI result in renal scarring. In
addition to possible unneeded complications, circumcision
may also cause discomfort and affect the appearance of the
genitalia.
Most VUR patients who required reimplantation had a
breakthrough UTI [16]. In addition, antibiotic prophylaxis
does not appear to prevent UTI in many children [21]. Our
data revealed that circumcision reduces UTI in children
with VUR, especially those with high-grade VUR. It seems
logical that circumcision could lessen the necessity for
surgical intervention and assist the resolution of reflux by
extending observation time [16]. However, the impact of
circumcision performed during anti-reflux surgery on the
subsequent incidence of UTI is still inconclusive [18,22].
Our analysis showed a lower incidence of UTI among
patients with obstructive ANH compared to VUR and PUV.
Several studies also discovered similar findings [12,20].
However, circumcision also significantly reduced the risk of
UTI in such population. Chan et al. found that boys with
UPJO who had robot-assisted laparoscopic pyeloplasty had
a significantly fewer UTI after the surgery if they had been
circumcised [28]. Braga et al. also discovered that cir-
cumcisedmales with a primary non-refluxing megaureter
had a substantially lower febrile UTI rate [26].
In PUV patients, our study demonstrated that circumci-
sion also reduces UTI considerably. Mukherjee et al.
discovered that although circumcision reduced the inci-
dence of UTI, it did not improve renal outcome [19]. Only
after circumcision is performed does it provide protection.
If the procedure is delayed, the preventive impact is
Fig. 4 Forest and funnel plots for showing pooled estimates of UTI rates according to circumcision status in patients with
obstructive ANH.
I. Wahyudi et al.
diminished, and pyelonephritis and subsequent kidney
scarring may have already occurred [19]. Therefore, early
circumcision in PUV is advantageous because it leads to
improvement in renal outcome over the long term.
Our analysis contained various potential biases. We
decided to include all prenatal hydronephrosis patients,
including those with VUR, UPJO, isolated hydronephrosis,
non-refluxing megaureter, and PUV. Some of the in-
dividuals, however, were diagnosed postnatally. Several
studies also failed to identify or discuss the cause of
hydronephrosis. In addition, there were studies that did not
specify how they defined UTI and circumcision status.
There was heterogeneity in the definition of UTI between
studies, with the possibility of phimosis and inadequate
urine collection methods. In addition, we did not differ-
entiate between febrile and non-febrile UTI, which may
have affected the outcomes. Most of the studies also did
not mention the hydronephrosis severity and timing of
circumcision. There is a need for further study to define the
relationship between circumcision and UTI, stratified by
the severity of hydronephrosis and circumcision timing.
This meta-analysis is, to our knowledge, the only study
to evaluate the relationship between circumcision and UTI
among children with ANH. Our findings may improve coun-
seling regarding the risks and advantages of circumcision
from the patient’s perspective. Nevertheless, this meta-
analysis had a number of limitations. The majority of
studies were retrospective studies with poor quality. There
was a possibility of inclusion bias among included studies.
More high-quality RCTs are needed for future meta-
Circumcision reduces UTI in children with ANH
Fig. 5 Forest and funnel plots for showing pooled estimates of UTI rates according to circumcision status in patients with PUV.
analysis. In addition, there was limited number of studies
that were eligible for subgroup analyses of hydronephrosis
etiology. Other UTI risk factors, such as the severity of
hydronephrosis and the use of prophylactic antibiotics,
were not controlled. In this meta-analysis, only English-
language studies were assessed for inclusion. This may have
excluded studies conducted in languages other than
English.
Conclusions
Our meta-analysis revealed that circumcision was associ-
ated with a lower incidence of UTI in children with ANH.
This associated advantage was consistent with several eti-
ologies of hydronephrosis, including VUR, obstructive ANH,
and PUV. These findings will assist in counseling the risks
and advantages of circumcision from the patient’s
perspective.
Funding
This study was supported by Universitas Indonesia with
Publikasi Terindeks Internasional (PUTI) Q2 Grant [Grant
Number NKB-1235/UN2.RST/HKP.05.00/2022].
Conflict of interest
None.
Acknowledgements
None.
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