10158954440868JAMA PediatrJAMA PediatrJAMA pediatrics2168-62032168-621124820907457879710.1001/jamapediatrics.2013.5414HHSPA722375ArticleRates of Adverse Events Associated with Male Circumcision in U.S. Medical Settings, 2001 – 2010El BcheraouiCharbelPhD123ZhangXinjianPhD2CooperChristopher S.MD4RoseCharles E.PhD2KilmarxPeter H.MD2ChenRobert T.MD MA2Epidemic Intelligence Service, Division of Applied Sciences, Scientific Education and Professional Development Program, Office of Surveillance, Epidemiology and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, GADivision of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GAInstitute for Health Metrics and Evaluation, University of Washington, Seattle, WADivision of Pediatric Urology, the University of Iowa, Iowa City, IAPlease address all correspondence to: Charbel El Bcheraoui, 2301 Fifth Ave., Suite 600, Seattle, WA 98121 USA, phone: 404-639-3311, charbel@uw.edu12920157201422920151687625634Importance

Over 1.4 million male circumcisions are performed annually in U.S. medical settings. However, population-based estimates of male circumcision associated adverse events are lacking.

Objectives

To estimate the incidence rate of male circumcision associated adverse events, and assess whether adverse event rates differed by age at circumcision.

Design

We selected 41 possible male circumcision adverse events based on literature review and medical billing codes. We estimated a likely risk window for incidence calculation for each male circumcision adverse event based on pathogenesis. We used 2001 – 2010 data from SDIhealth, a large administrative claims dataset, to conduct a retrospective cohort study.

Setting

SDIhealth provided administrative claims data from inpatient and outpatient U.S. medical settings.

Main outcome measures

For each adverse event, we calculated incidence per million male circumcisions. We compared incidence risk ratio and incidence rate difference for: a) circumcised vs. uncircumcised newborn males, and b) males circumcised at ≤1 year, 1–9 years, or ≥10 years of age. An adverse event was considered probably related to male circumcision if the incidence risk ratio significantly exceeded one at p<0.05 or occurred only in circumcised males.

Results

Records were available for 1,400,920 circumcised males, 93.3% as newborns. Of the 41 possible male circumcision adverse events, 16 (39%) were probable. Incidence of total male circumcision adverse event was slightly less than half percent. Rates of potentially serious male circumcision adverse events ranged from 0.76 per million male circumcision (95% CI: 0.10 – 5.43) for stricture of male genital organs to 703.23 per million male circumcision (95% CI: 659.22 – 750.18) for repair of incomplete circumcision. Compared to males circumcised at ≤1 year of age, the incidence was approximately 20- and 10-fold greater for males circumcised between 1 – 9 years and those ≥10 years of age, respectively.

Conclusions and Relevance

male circumcision had a relatively low incidence of adverse events overall, especially if the procedure was performed during the first year of life, but rose 10–20 fold when performed after infancy.

adverse eventsmale circumcision
Introduction

The American Academy of Pediatrics (AAP) updated its guidance on male circumcision (MC) in 2012 to state “the procedure’s benefits justify access to this procedure for families who choose it.”1 Whether MC should be considered an important public health intervention in the United States and other developed countries based on results of three randomized controlled trials24 showing its HIV protective effect has been debated.58 A key aspect of this debate is the rate of adverse events (AE), especially serious ones, attributable to MC, both for males circumcised as infants, and those undergoing voluntary circumcision as adults/adolescents.

Several studies have reported on MC AE, from mild to severe, ranging from 0.0008% to 3.6% in infants and from 0.9% to 8.8% in adults.921 However, most of these studies22 were based on relatively small samples, one clinical site or state, cross-sectional data or non-representative cohorts. While the Weiss review 22 and one case series describing the experience of one pediatric urologist conducting Gomco circumcision in 150 neonates and infants23 suggested generally higher rates of AE with older age at MC, to our knowledge, none have compared rates of AE across all age groups at MC from neonatal to adults in the same study. To provide stakeholders with better population-based information on the risk of MC AE, we use a large administrative claims dataset to 1) estimate the incidence rate of AE associated with MC via comparison of incidence risk ratio (IRR) and incidence rate difference (IRD) of AE between circumcised and uncircumcised newborn males, and 2) compare the IRR and IRD of AE associated with MC across age groups (≤1 year, 1 – 9 years, and ≥10 years).

Methods

SDIhealth (Plymouth Meeting, PA) consolidates U.S. electronic healthcare reimbursement claims. SDIhealth data include International Classification of Diseases, 9th revision (ICD-9) and Current Procedural Terminology (CPT) codes, and are available about two months after clinical visits. SDIhealth creates a unique anonymous identifier for each patient, enabling individuals to be followed longitudinally.

The Charge Data Master (CDM) is SDIhealth’s inpatient dataset. It gathers data from a 20% convenience sample of all inpatient encounters of short-stay, acute care, and non-federal hospitals from 48 states and Washington DC, representing ~120 million unique hospitalized patients. CDM hospitals are located in all U.S. regions (25% East, 12% North, 45% South, 16% West, and data on regions is unspecified for 2%). Of these hospitals, 85% are urban, 36% are teaching, with a wide variability of bed-size (median size 200–299 beds). Of patients seen at these hospitals, about 10% of patients are covered by Medicaid, 30% by Medicare, and the remainder covered by Third Party payers. CDM data is formed by two datasets: CDM1 (~80% of CDM) is available since 2001 and updated monthly; only the month of diagnosis or procedure is provided, with date of discharge defaulted to the first day of the discharge month. CDM2 (~20% of CDM), is available since 2005 and updated weekly; unlike CDM1, the exact discharge date of a diagnosis or a procedure is available. SDIhealth also collects data from >870,000 unique outpatient medical providers with the exact discharge date of diagnoses and procedures. For this study, we used CDM data available through February 2010.

Possible MC AE for this analysis were first identified from a review of a) PubMed using the search terms “circumcision” and “adverse events,” and b) the ICD-9 and the CPT manuals for conditions that are not necessarily due to, but could be related to MC. Our search yielded 41 possible MC AE that we classified into ten clinical syndromic groups (eTable 1).

For each of the 41 possible MC AE, one of the co-authors who is a board-certified pediatric urologist (CSC), a priori defined the likely risk window in days based on pathogenesis (eTable 1). The possible AE were further classified by CSC as potentially serious (italicized in eTable 1) or not, based on clinical judgment, and assuming a worst case scenario.

We edited the CDM MC dataset by a) removing circumcised males who had a MC date prior to their birth date, and b) reclassified newborn males who did not have a MC record but had a MC-specific AE (CPT: 54162 and 54163) as circumcised.

We performed a retrospective cohort study using log binomial regression modeling (SAS 9.2) to ascertain the risk associated with MC. We first calculated the incidence of each AE over its risk window, per million circumcised (and separately for uncircumcised) newborn males using discharge date of circumcision (or birth for uncircumcised) for the beginning of the risk window. We then calculated the IRR, IRD, and their respective 95% confidence interval (CI) between the circumcised and uncircumcised groups. 24

To minimize potential confusion on causal relationships in this exploratory study, the AE and person time outside the risk window in circumcised persons were deleted from analysis (instead of included in medical procedure-unexposed group as done in another risk window safety study).25 An AE was considered probably related to MC if the IRR significantly exceeded one at p<0.05 or occurred only in circumcised newborn males. Multiple comparisons were not adjusted in our analysis because almost all the significant associations found were at p<0.001, which is less than any typically used correction factor (e.g., Bonferroni). To estimate the total incidence of AE associated with MC, we calculated the IRD between incidences of probable AE in circumcised vs. uncircumcised newborns, using unduplicated counts of males who had one or more AE in each group divided by the number of circumcised and uncircumcised newborns, respectively. For some syndromic groups, the risk window was not equal for all AE. To obtain the total for the syndromic group in this case, all conditions were followed for the longest risk window in the group. IRR and 95% CI were then generated.

We assessed if rates of probable MC AE differed in the following three age groups: males circumcised before one year of age (reference group), between one and nine years of age, and at age ten years or older. The age groups’ cut-off points separated infants from children prior to puberty and older males. We used the same statistical approach as above to calculate incidence per million male circumcisions (PMMC), IRR, IRD, and 95% CI.

To better detect rare MC AE, we first conducted the analysis using all available data including CDM1, CDM2, and outpatient datasets. Due to CDM1 day of discharge being defaulted to the first day of the month, all AE risk windows <28 days were reset to 28 days, the shortest risk window that could possibly be tracked, and the closest to a complete month, in this analysis (Tables 2 and 3). We then conducted a second analysis maximizing specificity of date by using only CDM2 and outpatient, the two datasets with exact dates for each procedure needed for exact risk window analysis (eResults, eTable2, eTable 3. This research was determined to be exempt from institutional review board evaluation because it entailed secondary analysis of administrative data procured from SDI Health (http://sdihealth.com/portal/site/imshealth) without personal identifiable human subjects. SDI Health originally collected this data from processing of US health care insurance reimbursement claims.

Results

During 2001–2010, 1,400,920 MC reimbursement claims for males of all ages were submitted from U.S. hospital settings and available to SDIhealth (CDM1, CDM2, outpatient data). Forty seven males (0.0033%) had a MC dated prior to their birth date and these records were removed from analysis. Also, of all newborn males, 346 (0.015%) had a MC-specific AE but did not have a MC record. These were reclassified as circumcised newborn males.

Comparison of MC AE incidence between circumcised and uncircumcised newborn males (<xref ref-type="table" rid="T2">Table 2</xref>)

Data was available for a total of 2,339,760 newborn male births. Among these, 1,306,812 (55.8%) were linked to a circumcision record. Of the initial 41 possible MC AE, 16 (39%) met the criteria for probable MC AE (underlined in Table 2). Six probable MC AE occurred only in circumcised but not uncircumcised newborns [Amputation of penis, partial; Replantation of penis; Lysis or excision of penile post-circumcision adhesions; Repair incomplete circumcision; Stricture of male genital organ; and Suture of artery]. Among the 16 probable AE, ten were also classified as potentially serious.

There were 4,924 newborns, 4,059 circumcised and 865 uncircumcised, with one or more probable AE. In total, there were 5,385 and 1,100 AE recorded among circumcised and uncircumcised newborns, respectively. Of the 4,924 total, 4,523 (91.8%) were cared for in a hospital setting and 401 in outpatient setting. The estimated incidence of probable AE associated with MC was less than one percent, either crude [4.059/1,306,812 = 0.31% (95% CI = 0.30 – 0.32)] or adjusting for the background rate [(4,059/1,306,812) - (865/1,032,948) = 0.23% (95%CI = 0.21 – 0.24)].

The IRD for potential serious probable AE ranged from a low of 0.76 persons with Stricture of male genital organ PMMC (95%CI: 0.10 – 5.43) to a high of 703.23 persons with repair of incomplete circumcision PMMC (95%CI: 659.22 – 750.18). The most common probable MC AE was Division of penile adhesions [199.69 PMMC (95%CI: 153.92 – 245.66)].

Nine AE were significantly less likely to occur in circumcised compared to uncircumcised infants at p<0.05.

Circumcised newborn males had a higher risk for Wounds, Correctional procedures, Inflammations, and Bleedings compared to uncircumcised ones, but a lower risk for Surgical procedures, Penile disorders and gangrene, Pneumothorax and Infections.

Among the extremely rare but serious AE occurring only among circumcised newborns (but once or none among uncircumcised), we found no cases of Complete amputation of penis, three cases of Partial amputation of penis four cases of Replantation of penis,16 cases of Suture of artery, and one case of Stricture of male genital organs.

Comparison of MC AE by age group (Table 3)

Of the 1,400,920 circumcised males, 1,335,180 (95.3%) male infants were circumcised during infancy. Another 28,197 (2.0%) males were circumcised between age one and nine years, and 37,543 (2.7%) males were circumcised at age ≥10 years [8590 (22.9%) of whom were 10 – 18 years old]. Incidence of probable AE varied by age group: 0.40% (95% CI 0.39 – 0.41) among males circumcised during infancy; 9.06% (95% CI 8.73 – 9.40) among males circumcised between age one and nine years, and 5.31% (95% CI 5.09 – 5.55) among males circumcised at age ≥ten years; or approximately 20- and 10-fold higher for the older age groups compared to infants, respectively.

Except for the comparisons in which no AE cases occurred in one or both of the older age groups, the IRR of each of the other studied AE comparisons significantly exceeded one and IRD exceeded 100 PMMC (except for Suture of artery) when MC was performed after the first year of life. The highest IRR among males circumcised between one and nine years of age was found for Division of penile adhesions (IRR = 67.64; 95% CI: = 61.98 – 73.81). The highest IRR among males circumcised at age ≥ 10 years was found for Other inflammatory disorders of penis (IRR = 112.06; 95% CI: = 93.88 – 133.75). While these are not explicitly defied in the ICD-9 manual, they can be skin condition such as infection, cellulitis, abscess, boil, carbuncle, or cavernitis.

Discussion

We studied the AE outcomes after ~1.4 million MC in the United States, about 10 fold larger than the largest prior studies.910 Using a broad definition of 41 possible MC AE to search a large medical administrative database, then restricting to the 16 probable MC AE with significantly elevated rates in pre-defined risk windows or occurring only in circumcised persons, we estimate the incidence of AE associated with newborn male circumcision in medical settings adjusted for the background rate to be less than half percent (0.30% for the more specific CDM2 dataset). Overall, the most common probable MC AE were related to correctional procedures at ~2000 PMMC and bleeding at ~1000 PMMC. Our findings were largely similar irrespective of whether the month-specific or date-specific datasets were used and consistent with the earlier U.S. studies given differences in methodology9, 10.

Our findings also suggest that many AE such as penile reconstruction, pneumothorax and infections occur less frequently in circumcised males, perhaps due to a “healthy baby” bias – those newborns who undergo MC are more likely to be healthier (and without such disorders) compared to their uncircumcised counterparts. This type of selection bias is commonly seen in non-randomized observational studies of outcomes after medical procedures26, 27 and results in the observed lower rate of AE among circumcised males.

We found the incidence of MC AE was 10 – 20-fold higher when performed at older age groups compared to infancy. These findings are consistent with earlier studies22, 23 and may provide for the first time, a direct measure of the relative difference in AE rate by age at MC. Recent data on MC AE from a clinical trial in Kenya that included males 12 years of age or older, reported similar high rates of AE for this age group28. Interestingly, in a study on infant MC AE from Kenya, an increased risk for AE was found if MC was performed in the second month of life compared to the first one29. The indications for MC in older age groups in the U.S. may be more medical in nature (e.g., infections, adhesions) than the cultural/religious basis in most routine healthy newborns, however; future studies will need to carefully adjust for this potential source of confounding.

The incidence of amputations was highest among males circumcised at ten years of age or older: 0.17% (95% CI: 0.13 – 0.21%). In total, the absolute number of amputations in our database was 71. Most penile amputations captured in our dataset (45 out of 71) are recorded using ICD-9 code 643.0 which does not differentiate complete from partial penile amputation. Of the 71 recorded amputations, three were coded as complete — one among males circumcised in infancy, and two among males circumcised at ten years of age or older. Wiswell reported the absence of total penile amputations over five years in a study of MC AE among newborns from U.S. Army hospital settings9. Consistent with these findings, our data captured less than one total penile amputation PMMC, suggesting the possibility that most penile amputations recorded using ICD-9 code and captured in our dataset are likely to be partial. Without access to primary medical records, we can only speculate that the four patients that had penile amputation in the uncircumcised population likely were miscoded, were circumcised at non-medical settings, or patients undergoing operative intervention for severe genital anomalies. It’s noteworthy that other studies have reported on the success of treatment, including replantation, in the case of penile amputations.30, 31 We could not study deaths potentially related to MC as deaths in general are not captured in healthcare reimbursement claims databases like SDIhealth. In an earlier review, Wiswell reported three deaths due to male circumcision during the period 1954 – 1989 [~0.08 deaths from neonatal MC in the United States per year].9

Our study has several potential limitations. First, most of our data (~80%) assigns a discharge date of the first day of the month for the medical record. Hence, in the case where the AE has a risk window of < 28 days and falls in the same month of the MC it will be counted even if it occurs outside of the risk window. Also, in the case where an AE has a risk window of < 28 days and is encountered during the month following MC, it will be missed. The first scenario tends to over count some AE while the second tends to undercount some others. However, limiting our analysis to data with exact discharge date, our findings remained almost unchanged (eResults, eTable 2, eTable 3). At the same time, some of the males circumcised within the last year of our data, might have encountered an AE within a risk window outside of the available data. This might have decreased our overall rate of AE by a small fraction. Secondly, if an AE occurred on the same day of MC, it is impossible to determine whether the AE occurred before or after MC. Indeed, certain AE can also be an indication for MC. Hence, our reported rate might be inflated in case some AE were diagnosed on the same day as, or before MC.

A third limitation is that our data may not be generalized to the entire U.S. population as it came from a convenience sample. However,, the very large volume of administrative SDIhealth data used in this study (~20% of U.S. hospital discharges and >870,000 unique outpatient medical providers) strengthens our findings. A recent publication showed the trends in neonatal MC in SDIhealth data were virtually identical to that of two nationally representative datasets32 also further support its validity- at least for newborn males.

A fourth limitation of our data was that it was collected for billing purposes only. If a circumcision or an AE was not covered by a third party payer, it would be missing from this analysis. Also, some circumcisions might occur in non-medical settings, such as religious MC, but a resulting AE might require medical intervention, and hence be captured as occurring among uncircumcised newborns. Indeed, some uncircumcised newborn males in our data had a MC-specific AE. However, these did not exceed 0.01% of all newborns and the incidence of AE in our analysis was in the range of those from previous U. S. publications. 910 Therefore, while the true rate may be lower or higher than our estimates, billing records should capture the vast majority of MC procedures.

Finally, MC can occur concurrently with other operative procedures for anesthesia-convenience reasons. The AE that might result from these cases might be confounded by other health conditions of the patient. Future studies overcoming these limitations and examining other databases to confirm our findings are needed to better estimate specific AE rates attributable only to MC.

Conclusions

Our data suggest the rate of AE associated with newborn circumcision is less than half percent. Importantly, the incidence of AE increased substantially when MC occurred after the first year of life. Given the current debate about whether MC should be delayed from infancy to adulthood for autonomy reasons33, our results are timely and can help physicians counsel parents about circumcising their sons.

Supplementary MaterialAcknowledgements

The authors wish to thank:

Farid Khan MPH, Laurel Edelman BS, and Joel Greenspan, MD, of SDI Health, for answering our inquiries about the data

Kris Greiner BA from the Division of Pediatric Urology, The University of Iowa, for formatting the manuscript to adhere with JAMA Pediatrics’ style

Sanjyot Shinde, PhD, Deborah Gust, PhD, and Charles LeBaron, MD, Division of HIV/AIDS Prevention, CDC, for their valuable assistance in reviewing and providing valuable comments for this manuscript.

The corresponding author, Dr. Charbel El Bcheraoui, confirms that written permission has been obtained from all persons named in the Acknowledgment section.

Funding/Support: This study was funded by the Centers for Disease Control and Prevention.

The authors have no financial relationships relevant to this article to disclose.

The authors have no conflicts of interest to disclose.

Disclaimer: Although the Centers for Disease Control and Prevention played a role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, as well as preparation, review, and approval of the manuscript, the findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Charbel El Bcheraoui and Xinjian Zhang had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Charbel El Bcheraoui: Dr. El Bcheraoui assisted in conceptualizing this study, developed the analysis plan for this study, conducted the data analysis, drafted the original manuscript and approved the final manuscript as submitted.

Xinjian Zhang: Dr. Zhang assisted in developing the analysis methods, provided statistical analysis, and approved the final manuscript as submitted.

Christopher S. Cooper: Dr. Cooper assisted in conceptualizing this study, estimated risk windows to be used for adverse events analysis, acquisition, analysis, or interpretation of data, and approved the final manuscript as submitted.

Charles E. Rose: Dr. Rose assisted in developing the analysis methods, provided statistical analysis, and approved the final manuscript as submitted.

Peter H. Kilmarx: Dr. Kilmarx assisted in conceptualizing this study, provided guidance in data analysis and approved the final manuscript as submitted.

Robert T. Chen: Dr. Chen assisted in conceptualizing this study, provided guidance in data analysis, manuscript development, and approved the final manuscript as submitted.

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Counts, incidence rates, incidence risk ratio, and incidence rate difference of adverse events between circumcised and uncircumcised newborn males. Charge Data Master 1 (CDM1), CDM2, and outpatient data, Unites States 2001 – 2010

Adverse eventsa(Italicized = Potentially serious;Underlined = probablyassociated with malecircumcision)Count among uncircumcisednewborns (Incidence permillion uncircumcisednewborn; 95% CI) N =1,032,948Count among circumcisednewborns (Incidence permillion circumcised newborn;95% CI) N = 1,306,812P valueIncidence RiskRatio (95% CI)Incidence RateDifference (95% CI)
Amputationsb4 (3.87; 1.45 – 10.31)3 (2.29; 0.74 – 7.11)0.50.59 (0.13 – 2.64)−1.58(−6.18 – 3.02)
   Amputation of penisb4 (3.87; 1.45 – 10.31)0 (0)N.A.N.A.N.A.
   Amputation of penis, partialb0 (0)3 (2.29; 0.74 – 7.11)N.A.N.A.3 (2.29; 0.74 – 7.11)
Woundsb32 (30.97; 21.90 – 43.80)89 (68.10; 55.32 – 83.83)<0.0012.19 (1.46 – 3.29)37.12(19.37 – 54.88)
   Open wound of penis without mention of complicationb29 (28.07; 19.51 – 40.40)83 (63.51; 51.21 – 78.75)<0.0012.26 (1.48 – 3.45)35.44(18.38 – 52.50)
   Open wound of penis, complicatedb3 (2.90; 0.93 – 9.00)6 (4.59; 2.06 – 10.21)0.51.58 (0.39 – 6.32)1.68(−3.24 – 6.62)
Correctional procedurese644 (623.45; 577.13 – 673.50)3281 (2510.69; 2426.33 – 2597.97)<0.0014.02 (3.70 – 4.38)1887.23(1778.85 – 1985.62)
   Suture of laceration of penisb43 (41.62; 30.87 – 56.12)293 (224.21; 199.95 – 251.40)<0.0015.38 (3.91 – 7.41)182.58(154.06 – 211.11)
   Suture of laceration of penise55 (53.24; 40.88 – 69.35)299 (228.80; 204.28 – 256.25)<0.0014.29 (3.22 – 5.72)175.56(146.05 – 205.06)
   Reconstruction of penisd64 (61.95; 48.49 – 79.15)15 (11.47; 6.91 – 19.03)<0.0010.18 (0.10 – 0.32)−50.48(−66.03 – −34.23)
   Reconstruction of penise77 (74.54; 59.62 – 93.19)30 (22.95; 16.05 – 32.83)<0.0010.30 (0.20 – 0.46)−51.59(−70.15 – −23.02)
   Replantation of penisb0 (0)4 (3.06; 1.14 – 8.15)N.A.
   Replantation of penise1 (0.96; −0.13 – 6.87)4 (3.06; 1.14 – 8.15)0.33.16 (0.35 – 28.28)2.09(−1.46 – 5.64)
   Other repairs of penisd181 (175.22; 151.47 – 202.70)354 (270.88; 244.09 – 300.62)<0.0011.54 (1.29 – 1.84)95.66(57.61 – 133.71)
   Other repairs of penise277 (268.16; 238.37 – 301.67)715 (547.13; 508.47 – 588.73)<0.0012.04 (1.77 – 2.34)278.97(227.93 – 330.00)
   Division of penile adhesionse234 (226.53; 199.29 – 257.49)557 (426.22; 392.26 – 463.12)<0.0011.88 (1.61 – 2.19)199.69(153.92 – 245.66)
   Lysis or excision of penile post-circumcision adhesionse0 (0)757 (579.27; 539.45 – 622.02)N.A.N.A.757 (579.27; 539.45 – 622.02)
   Repair incomplete circumcisione0 (0)919 (703.23; 659.22 – 750.18)N.A.N.A.919 (703.23; 659.22 – 750.18)
Surgical procedurese224 (216.85; 190.24 – 247.19)52 (39.79; 30.32 – 52.21)<0.0010.18 (0.13 – 0.240−177.06(−207.65 – −146.68)
   Incision of penisb186 (180.06; 155.96 – 207.89)21 (16.07; 10.47 – 24.64)<0.0010.08 (0.05 – 0.14)−163.99(−190.77 – −137.22)
   Incision of penise202 (195.55; 170.36 – 224.46)35 (26.78; 19.22 – 37.30)<0.0010.13 (0.09 – 0.19)−168.77(−197.16 – −140.39)
   Other operations on penise22 (21.29; 14.02 – 32.34)17 (13.00; 8.08 – 20.92)0.10.61 (0.32 – 1.15)−8.29(−19.13 – 2.54)
Disordersb1062 (1028.12; 968.14 – 1091.82)799 (611.41; 570.46 – 655.29)<0.0010.59 (0.54 – 0.65)−416.71(−491.65 – −341.77)
   Vascular disorders of penisb11 (10.64; 5.89 – 19.22)70 (53.56; 42.37 – 67.70)<0.0015.03 (2.66 – 9.49)42.92(28.88 – 56.95)
   Other specified disorders of penisb934 (904.20; 849.06 – 964.06)638 (488.21; 451.76 – 527.59)<0.0010.59 (0.53 – 0.65)−415.99(−485.24 – −346.76)
   Unspecified disorders of penisb87 (84.224; 68.26 – 103.91)78 (59.68; 47.80 – 74.51)0.020.70 (0.52 – 0.96)−24.54(−46.64 – 2.43)
   Gangrene, death and decay of body tissue, often occurring in a limb, caused by insufficient blood supply and usually following injury or diseaseb30 (29.04; 20.30 – 41.53)13 (9.94; 5.77 – 17.13)0.0010.34 (0.17 – 0.65)−19.09(−30.81 – −7.38)
Pneumothoraxb263 (254.61; 225.62 – 287.31)120 (91.82; 76.78 – 109.81)<0.0010.36 (0.29 – 0.44)−162.78(−197.66 – −127.91)
   Spontaneous tension pneumothoraxb144 (139.40; 118.40 – 164.13)66 (50.50; 39.67 – 64.28)<0.0010.36 (0.27 – 0.48)−88.90(−114.73 – −63.08)
   Iatrogenic pneumothoraxb119 (115.20; 96.25 – 137.87)54 (41.32; 31.64 – 53.95)<0.0010.35 (0.26 – 0.49)−73.88(−97.33 – 50.43)
Infectionsb842 (815.14; 761.92 – 872.07)834 (638.19; 596.33 – 682.99)<0.0010.78 (0.71 – 0.86)−176.95(−246.98 – −106.92)
   Meningitis of unspecified cause: non-pyogenic meningitisb2 (1.93; 0.48 – 7.74)2 (1.53; 0.38 – 6.11)0.990.79 (0.11 – 5.61)−0.41(−3.82 – 3.01)
   Meningitis of unspecified cause: meningitis unspecifiedb415 (401.76; 364.91 – 442.32)399 (305.32; 276.79 – 336.79)<0.0010.76 (0.66 – 0.87)−96.44(−145.34 – −47.54)
   Methicillin resistant pneumonia due to staphylococcus aureusb9 (8.71; 4.53 – 16.74)5 (3.82; 1.59 – 9.19)0.10.43 (0.14 – 1.31)−4.98(−11.49 – 1.72)
   Cellulites, unspecified siteb160 (154.89; 132.66 – 180.85)207 (158.40; 138.22 – 181.51)0.81.02 (0.83 – 1.25)3.50(−28.77 – 35.78)
   Bacteremiab252 (243.96; 215.62 – 276.01)203 (155.34; 135.37 – 178.24)<0.0010.63 (0.52 – 0.76)−88.62(−125.55 – −51.69)
   Staphylococcal scalded skin syndrome/Ritter’s diseaseb4 (3.87; 1.45 – 10.31)18 (13.77; 8.67 – 21.86)0.023.55 (1.20 – 10.50)9.90(2.49 – 17.31)
Inflammationsb313 (303.01; 271.24 – 338.50)616 (471.37; 435.59 – 510.10)<0.0011.55 (1.35 – 1.78)168.36(118.24 – 218.47)
   Other inflammatory disorders of penis/Cellulites penisb42 (40.66; 30.04 – 55.01)142 (108.66; 99.21 – 136.35)<0.0012.67 (1.89 – 3.77)68.00(46.31 – 89.69)
   Edema of penisb108 (104.55; 86.58 – 126.25)289 (221.14; 197.06 – 248.17)<0.0012.11 (1.69 – 2.63)116.59(84.36 – 148.82)
   Other inflammatory disorders of male genitalsb17 (16.45; 10.23 – 26.47)35 (26.78; 19.22 – 37.30)0.091.62 (0.91 – 2.90)10.33(−1.0 – 22.15)
   Edema of male genital organsb146 (141.34; 120.18 – 166.23)150 (114.78; 97.80 – 134.70)0.070.81 (0.64 – 1.01)−26.56(−55.94 – 2.82)
Stricturesc73 (70.67; 56.18 – 88.89)104 (79.58; 65.66 – 96.44)0.41.12 (0.83 – 1.51)8.91(−13.37 – 31.19)
   Postoperative urethral stricturec1 (0.96; −0.13 – 6.87)8 (6.12; 3.06 – 12.24)0.086.32 (0.79 – 50.55)5.15(0.51 – 9.80)
   Urethral stricture, unspecifiedc72 (69.70; 55.32 – 87.81)95 (72.69; 59.45 – 88.88)0.781.04 (0.76 – 1.41)2.99(−18.75 – 24.74)
   Stricture of male genital organsc0 (0)1 (0.76; 0.10 – 5.43)N.A.0.76 (0.10 – 5.43)
Bleedingb462 (447.26; 408.29 – 489.95)1889 (1445.50; 1381.80 – 1512.13)<0.0013.23 (2.91 – 3.57)998.24(921.39 – 1075.09)
   Unspecified hemorrhage of newbornb44 (42.59; 31.69 – 57.23)37 (28.31; 20.51 – 39.07)0.060.66 (0.42 – 1.02)−14.28(−29.82 – 1.26)
   Intra-operative bleedingb350 (338.83; 305.13 – 376.25)1614 (1235.06; 1176.29 – 1296.77)<0.0013.73 (3.31 – 4.19)896.23(826.33 – 966.13)
   Hemorrhage controlb26 (25.17; 17.13 – 36.96)173 (132.38; 114.05 – 153.65)<0.0015.25 (3.48 – 7.94)107.21(85.24 – 129.18)
Suture of arteryb0 (0)16 (12.24; 7.50 – 19.98)N.A.12.24 (7.50 – 19.98)
   Suture of veinb32 (30.97; 21.90 – 43.80)30 (22.95; 16.05 – 32.83)0.20.74 (0.45 – 1.21)−8.02(−21.59 – 5.94)
   Suture of vesselb10 (9.68; 5.20 – 17.99)19 (14.53; 9.27 – 22.79)0.291.50 (0.69 – 3.22)4.86(−4.01 – 13.73)

The total count for a group of adverse events was obtained by adding counts of all individual; potentially serious AE are Italicized

Risk window defined for 28 days post-circumcision or post-birth for circumcised males and uncircumcised males respectively

Risk window defined for 180 days post-circumcision or post-birth for circumcised males and uncircumcised males respectively

Risk window defined for 365 days post-circumcision or post-birth for circumcised males and uncircumcised males respectively

Risk window defined for 1200 days post-circumcision or post-birth for circumcised males and uncircumcised males respectively

Note: Adverse events that were not encountered in this analysis, i.e. had a count of zero, were not presented to reduce the length of the table. These are: complete amputation of penis, repair and plastic operation on penis, incision and drainage of penis.

CI: confidence interval

N.A.: not applicable

Counts, incidence rates and incidence risk ratio of adverse events between males circumcised at 3 different age groups. Charge Data Master 1 (CDM1), CDM2, and outpatient data, Unites States 2001 – 2010

Adverse events(Italicized = Potentiallyserious)Age at circumcisionCount among circumcised males(Incidence per million circumcisions; 95% CI)Incidence Risk Ratios (95%CI)Incidence Rate Difference(95% CI)
Amputationsa< 1 year old8(5.99;3.00–11.99)Reference groupReference group
1 – 9 years old0N.A.N.A.
≥ 10 years old63(1678.07; 1311.17 – 2147.64)81.29(33.44 – 197.58)420.94(212.12 – 629.75)
Amputation of penisa< 1 year old0 (0)Reference groupReference group
1 – 9 years old0 (0)N.A.N.A.
≥ 10 years old45 (1198.62; 895.09 – 1605.08)N.A.45 (1198.62; 895.09 – 1605.08)
   Amputation of penis, partiala< 1 year old7(5.24;2.50 – 11.00)Reference groupReference group
1 – 9 years old0N.A.N.A.
≥ 10 years old16(426.18; 261.12 – 695.58)81.29(33.44 – 197.58)420.94(212.12 – 629.75)
Amputation of penis, completea< 1 year old1 (0.75; 2.50 – 11.01)Reference groupReference group
1 – 9 years old0 (0)N.A.N.A.
≥ 10 years old2 (53.27; 26.11 – 69.55)71.03 (6.44 – 783.35)52.52(−21.32–126.37)
Woundsa< 1 year old87 (65.25; 52.88 – 80.50)Reference groupReference group
1 – 9 years old11 (390.11; 216.06 – 704.34)5.97 (3.19 – 11.19))324.95(94.05 – 555.86)
≥ 10 years old113 (3009.88; 2503.77 – 3618.28)46.12 (34.88 – 60.99))2944.7(2390.4 – 3499.0)
Open wound of penis w/out mention of complicationsa< 1 year old87 (65.25; 52.88 – 80.50)Reference groupReference group
1 – 9 years old11 (390.11; 216.06 – 704.34)5.97 (3.19 – 11.19)324.95(94.05 – 555.86)
≥ 10 years old113 (3009.88; 2503.77 – 3618.28)46.12 (34.88 – 60.99)2944.7(2390.4 – 3499.0)
Correctional proceduresd< 1 year old4018(3009.3;2917.8 – 3103.7)Reference groupReference group
1 – 9 years old2947 (104515;101004 – 108147)34.73(33.17 – 36.37)101505(97933 – 105077)
≥ 10 years old1219 (32469;30725 – 34313)10.79(10.13 – 11.49)29460(27665 – 31255)
Suture of laceration of penisa< 1 year old314 (235.49; 210.84 – 263.03)Reference groupReference group
1 – 9 years old25 (886.61; 599.20 – 1311.90)3.76 (2.50 – 5.65)651.44(303.07 – 999.82)
≥ 10 years old55 (1464.98; 1124.97 – 1907.76)6.22 (4.67 – 8.28)1229.8(842.05 – 1617.6)
Suture of laceration of penisd< 1 year old322 (241.49; 216.51 – 269.36)Reference groupReference group
1 – 9 years old27 (957.74; 656.78 – 1396.03)3.96 (2.67 – 5.870716.38(354.41 – 1078.4)
≥ 10 years old61 (1624.80; 1264.45 – 2087.84)6.72 (5.11 – 8.84)1383.6(975.37 – 1791.9)
   Replantation of penisa< 1 year old4(3.00;1.12 – 7.98)Reference groupReference group
1 – 9 years old0N.A.N.A.
≥ 10 years old0N.A.N.A.
Replantation of penisd< 1 year old4(3.00;1.12 – 7.98)Reference groupReference group
1 – 9 years old0N.A.N.A.
≥ 10 years old0N.A.N.A.
Other repair of penisc< 1 year old841 (630.74; 589.53 – 674.83)Reference groupReference group
1 – 9 years old468 (16598.00; 15171.34 – 18157.74)26.31 (23.51 – 29.44)15968(14476 – 17459)
≥ 10 years old394 (10495.00; 9512.83 – 11577.76)16.63 (14.76 – 18.74)9864.8(8833.1 – 10896)
Other repair of penisd< 1 year old1213 (909.74; 859.98 – 962.38)Reference groupReference group
1 – 9 years old471 (16704.00; 15273.04 – 18268.81)18.36 (16.51 – 20.40)15795(14299 – 17292)
≥ 10 years old399 (16628; 9639.56 – 11717.37)11.68 (10.43 – 13.07)9719.3(8680.8 – 10758)
Division of penile adhesionsd< 1 year old841 (630.74; 589.53 – 674.83)Reference groupReference group
1 – 9 years old1203 (42664.00; 40369.23 – 45089.44)67.64 (61.98 – 73.81)42034(39675 – 44394)
≥ 10 years old489 (13025.00; 11927.20 – 14223.97)20.65 (18.48 – 23.07)12395(11247 – 13543)
Lysis or excision of penile post-circumcision adhesionsd< 1 year old685 (513.74; 476.68 – 553.68)Reference groupReference group
1 – 9 years old369 (13086.00; 11825.03 – 14482.52)25.47 (22.45 – 28.89)12573(11246 – 13901)
≥ 10 years old116 (3089.79; 2576.43 – 3705.43)6.01 (4.94 – 7.32)2576.8(2014.0 – 3139.5)
Repair incomplete circumcisiond< 1 year old953 (714.74; 670.79 – 761.57)Reference groupReference group
1 – 9 years old877 (31103.00; 29140.98 – 33196.26)43.51 (39.73 – 47.65)30389(28362 – 32416)
≥ 10 years old154 (4101.96; 3503.81 – 4802.22)5.73 (4.84 – 6.80)3388.2(2740.1 – 4036.3)
Disordersa< 1 year old17 (12.73; 7.92 –20.48)Reference groupReference group
1 – 9 years old0N.A.N.A.
≥ 10 years old9 (239.73; 124.74 – 460.70)18.83 (8.39 – 42.24)226.99 (70.27 – 383.71)
Vascular disorders of Penisa< 1 year old17 (12.73; 7.92 –20.48)Reference groupReference group
1 – 9 years old0N.A.N.A.
≥ 10 years old9 (239.73; 124.74 – 460.70)18.83 (8.39 – 42.24)226.99 (70.27 – 383.71)
Infectionsa< 1 year old18 (13.48; 8.49 –21.40)Reference groupReference group
1 – 9 years old0N.A.N.A.
≥ 10 years old0N.A.N.A.
Staphylococcal scalded skin syndrome / Ritter’s diseasea< 1 year old18 (13.48; 8.49 –21.40)Reference groupReference group
1 – 9 years old0N.A.N.A.
≥ 10 years old0N.A.N.A.
Inflammationsa< 1 year old470 (352.01;321.59 – 385.31)Reference groupReference group
1 – 9 years old191 (6773.77;5880.97 – 7802.11)16.45 (13.93 – 19.43)6421.8(5463.8 – 7379.7)
≥ 10 years old673 (17926.11;16632.98 – 19319.78)83.05 (74.11 – 93.07)17574(16232 – 18917)
Other inflammatory disorders of penis / cellulites penisa< 1 year old161 (120.74; 103.46 – 140.91)Reference groupReference group
1 – 9 years old111 (3936.58; 3269.54 – 4739.72)32.60 (25.60 – 41.50)3816.0(3084.9 – 4547.1)
≥ 10 years old508 (13531.00; 12411.52 – 14751.77)112.06 (93.88 – 133.75)13411(12242 – 14579)
Edema of penisa< 1 year old309 (231.74; 207.29 – 259.07)Reference groupReference group
1 – 9 years old80 (2837.18; 2279.58 – 3531.17)12.24 (9.57 – 15.65)2605.8(1984.4 – 3227.1)
≥ 10 years old165 (4394.96; 3774.28 – 5117.70)18.96 (15.70 – 22.90)4163.5(3493.9 – 4833.2)
Stricturesb< 1 year old1(0.75;0.11 – 5.32)Reference groupReference group
1 – 9 years old0N.A.N.A.
≥ 10 years old1(26.64;3.75 – 189.09)35.56(2.22 – 568.60)25.89(−26.34 – 78.11)
Stricture of male genital organsb< 1 year old1(0.75;0.11 – 5.32)Reference groupReference group
1 – 9 years old0N.A.N.A.
≥ 10 years old1(26.64;3.75 – 189.09)35.56(2.22–568.60)25.89(−26.34 – 78.11)
Bleedinga< 1 year old1998(1496.4;1432.3 – 1563.5)Reference groupReference group
1 – 9 years old279(9894.7;8804.3 – 11120)6.61(5.84 – 7.49)8398.2(7241.1 – 9555.4)
≥ 10 years old332(8843.2; 7945.1 – 9842.8)5.91(5.26 – 6.63)7346.8(6397.5 – 8296.1)
Intra-operative bleedinga< 1 year old1779 (1334.23; 1273.69 – 1397.65)Reference groupReference group
1 – 9 years old249 (8830.72; 7803.55 – 9993.10)6.61 (5.80 – 7.55)7498.3(6404.6 – 8592.1)
≥ 10 years old304 (8097.38; 7239.73 – 9056.62)6.06 (5.37 – 6.85)6765.0(5856.3 – 7673.7)
Hemorrhage controla< 1 year old200 (149.99; 130.58 – 172.29)Reference groupReference group
1 – 9 years old27 (957.54; 656.78 – 1396.03)6.38 (4.27 – 9.53)807.76(446.14 – 1169.4)
≥ 10 years old27 (719.17; 714.17 – 1360.00)4.79 (3.20 – 7.16)569.38(297.41 – 841.35)
Suture of arterya< 1 year old19(14.23; 9.08 – 22.31)Reference groupReference group
1 – 9 years old3(106.39;34.32 – 329.86)7.48(2.21 – 25.26)92.16(−28.40 – 212.72)
≥ 10 years old1(26.64;3.75 – 189.09)1.87(0.25 – 13.98)12.41(−40.19 – 65.00)

Risk window defined for 28 days post-circumcision

Risk window defined for 180 days post-circumcision

Risk window defined for 365 days post-circumcision

Risk window defined for 1200 days post-circumcision

Note: Adverse events that were not encountered in this analysis, i.e. had a count of zero, were not presented to reduce the length of the table. These are: repair and plastic operation on penis.

CI: confidence interval

N.A.: not applicable