Neonatal Circumcision in Boys With Posterior Urethral Valves

Abstract

Source: Harper L, Blanc T, Peycelon M, et al. Circumcision and risk of febrile urinary tract infection in boys with posterior urethral valves: result of the CIRCUP randomized trial. Eur Urol. 2022;81(1):64-72; doi:10.1016/j.eururo.2021.08.024Investigators from multiple institutions in France conducted a randomized controlled trial to assess the effect of circumcision on the risk of febrile urinary tract infection (fUTI) in infant boys with posterior urethral valves (PUV). Participants were male neonates 1-28 days old with PUV diagnosed by voiding cystogram, who were enrolled between 2012 and 2017 at 13 pediatric urology centers. Study patients were randomized to circumcision and antibiotic prophylaxis (CATB), or antibiotic prophylaxis alone (ATB) treatment groups. Circumcision was performed at the time of valve resection under general anesthesia. Antibiotic prophylaxis consisted of cefaclor 10 mg/kg/day for 1 month, followed by cotrimoxazole (15 mg/kg/day) until participants were 2 years old. A technetium-99m dimercaptosuccinic acid (DMSA) scan was performed when patients were 1-2 months and 2 years of age to evaluate renal damage. Study children were followed for 2 years. The primary outcome was fUTI, defined as culture-proven infection (≥103 bacteria/mL in catheterized specimens and ≥104 bacteria/mL for urine specimens obtained by suprapubic aspiration) with pyuria, in the presence of fever (>38.5° C) and signs of inflammation (leukocytosis, elevated C-reactive protein, and/or procalcitonin). The risk of fUTI in the 2 treatment groups was assessed using Kaplan-Meier analysis, and Cox regression was used to compare the risks. Adherence to antibiotic prophylaxis was assessed throughout the 2-year follow-up period and compared between groups. Evidence of increased renal damage between the initial and follow-up DMSA scans was determined and compared in those with and without fUTI with a chi-square test.Data were analyzed on 91 boys, including 49 randomized to CATB and 42 to the ATB group; the mean age at enrollment was 4.3 ± 5.0 and 7.1 ± 6.7 days, respectively, and mean age at valve resection was 5.2 ± 5.4 and 9.4 ± 11.6 days, respectively. A total of 64 (70%) children completed the entire 2-year follow-up period (33 in the CATB group and 31 in the ATB group). Overall, the risk of fUTI was 20% in the ATB group and 3% in those randomized to circumcision (hazard ratio [HR], 10.3; 95% CI, 1.3, 82.5). Adherence to the antibiotic prophylaxis regimen declined in participants during the study period but was not significantly different between treatment groups. At the time of the initial DMSA scan, 63% of children had abnormalities identified, and deterioration on DMSA scans was noted on 18% at follow-up, including 33% of those with a history of fUTI and 16% without fUTI (P = 0.29).The authors conclude circumcision decreased the risk of fUTI in boys born with PUV.Dr Sanchez-Kazi has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The prevalence of fUTI is highest during the newborn period in boys with PUV.1 fUTI increases the risk of renal scarring, which can lead to chronic kidney disease. (See AAP Grand Rounds. 2019;42(5):53.)2 The current investigators evaluated whether circumcision reduces the risk of fUTI in boys with PUV. Although the results showed that CATB lowered the risk of fUTI, there was no difference between groups in the degree of kidney scarring as shown on the DMSA scans. Although it may be possible that this lack of significant change is explained by a lower number of participants, high attrition rate, variability in the radiographic interpretation of the DMSAs, short period of follow-up, or the inherent abnormal kidney parenchyma in boys with PUV due to possible dysplasia. However, the most likely explanation is that despite a substantial effect size (the rate of worsening DMSA scans was >2 times higher in those with fUTI than those without), there was insufficient power to detect a statistically significant difference in the outcomes.As stated in the accompanying editorial, circumcision reduced the occurrence of fUTI, but it did not decrease morbidity or mortality related to kidney scars.3 Steroid cream is currently used to manage phimosis in uncircumcised infants with fUTI.4 Will a retractable foreskin have the same advantage in infants with PUV?4 In boys with PUV however, neurogenic bladder and hydronephrosis are additional factors that significantly increase the probability of fUTI.1 In the most recent AAP Policy Statement on Circumcision in boys with a normal urinary tract, the committee left the decision-making to parents.5 The Canadian Urological Association also recommends early parental discussion of circumcision in the presence of an abnormal urinary tract including PUV, since the risk of fUTI is highest within the first 3 months of life.1,6 The results of the current study hopefully will contribute to more knowledgeable parental decision making.Neonatal circumcision in boys with posterior urethral valve decreases the risk of fUTI.