Systematic review of complications arising from male circumcision

Abstract Background Neonatal male circumcision is the most common procedure performed on paediatric patients (Simpson et al., 2014) and one of the most common surgical procedures in the world (American Academy of Pediatrics, 2012). Methods A search was conducted for articles about complications arising from male circumcision surgeries by entering the term ‘male circumcision’ into PubMed on June 16, 2020. Six thousand six hundred forty‐one articles published from 1945 to 2020 were found. Seventy‐eight articles were ultimately selected for the systematic review. Results The 78 articles selected from the literature search were entered into one of three tables. The first table includes 15 articles pertaining to chart reviews and cohort studies and report complication rates. The second table reports specific complications from 51 case reports and case series, and the third table is a summary from 12 articles regarding physician questionnaires and society recommendations. Additionally, the 78 articles were used to compile a list of 47 specific complications arising from male circumcision surgeries. Conclusions Complications from neonatal male circumcisions are common and healthcare providers need to be better informed of the potential complications of the surgery so that they can more effectively counsel their patients about potential risks, likelihood of complications and what can be done to prevent them. While experienced providers who practice in sterile settings have better outcomes with fewer complications, encouraging parents to take into account who is performing their son's circumcision, what was their training, how clean is their practice and how much experience they have and reminding them they have the option to decline the procedure entirely allow the parents to get a more complete picture and play an essential role in the decision‐making process.


| INTRODUCTION
Neonatal male circumcision is the most common procedure performed on paediatric patients 1 and one of the most common surgical procedures in the world. 2 About 30% of all men are circumcised worldwide. 3 In recent years, the rate of neonatal circumcision has been dropping in the United States, but it still varies among certain populations. 2 Despite the prevalence of this procedure, there are a number of ethical and moral debates surrounding the practice of male circumcision, 4 especially regarding whether a neonate can give consent for his own circumcision. In June 2012, an appellate court in Germany ruled that nontherapeutic circumcision of boys is irreversible bodily harm that violates the child's right to autonomy and selfdetermination and that the procedure should be delayed until an age where the boy can consent for himself. 5,6 The discussion around male circumcision is often emotionally charged and intense, with some even comparing the practice to female genital mutilation.
Historically, male circumcision has been practiced since ancient times. There are reports of male circumcision on Egyptian mummies and in the biblical covenants recorded in the Old Testament. 1 In the United States, male circumcision began to be widely practiced in the Victorian era as a means of deterring masturbation and improving genital cleanliness. 7,8 In modern times, male circumcision is performed at various ages by many potential providers, in many areas of the world, as part of cultural, religious and/or medical practices. Those of Jewish and Muslim faith consider male circumcision an indispensable element to their religion. 6 Jewish people circumcise their boys on the eighth day of life. 9 Muslim people circumcise their boys before puberty, generally between 4 and 13 years of age. 9,10 Parents commonly hear about the reported health benefits of male circumcision such as decreased rate of viral sexually transmitted infections, including HIV and HPV, among heterosexual males. However, spread of HIV and some other STIs is dependent on multiple risk factors, including unprotected sexual intercourse, intravenous drug use, unscreened blood donations and vertical transmission during gestation or childbirth. Massive circumcision efforts have begun in Africa to voluntarily circumcise males in order to try to limit the spread of HIV. 11 The data regarding this are not well reported and does not provide resounding support to the idea that male circumcision prevents spread of HIV. Additionally, while male circumcision may be useful in protecting against the incidence of male urinary tract infections, 12 bacterial colonization is still present after circumcision, so genital hygiene is regarded as more effective in preventing UTIs rather than circumcision surgeries. 13 In certain instances where hygiene is poor, circumcision may be implemented to prevent urinary tract infections.
In the United States, parents are generally not informed how circumcisions are performed. Those that take place in the medical setting are done with the use of the Gomco, Mogen or Plastibell clamps.
Additionally, 'free-hand circumcision' is also practiced. Each instrument and technique has its own risks and benefits. Local anaesthesia is supposed to be administered for neonatal circumcisions, and general anaesthesia must be administered for circumcisions past the neonatal period. 14 Circumcisions should ideally be done in sterile medical settings by trained and experienced providers due to the nature of this operation.
In some situations, male circumcision surgeries are necessary for medical reasons. Pathologic phimosis and recurrent balanitis are generally accepted medical indications for circumcision. 10 Physiologic phimosis is present in almost all neonates, and the prepuce is eventually retractable in 99% of males by age 16. 15,16 If a prepubescent patient presents with tight but otherwise normal foreskin, watching and waiting until after puberty should be considered. 15 A dorsal slit or circumcision surgery will eliminate the pathologic phimosis if it is bothersome to the patient, or the patient is postpubescent.
As with any surgical procedure, complications after a male circumcision surgery are possible. Some of these complications are minor and easily treated such as bleeding (in patients without a bleeding disorder) and infection; others, however, require additional surgery to correct the complication such as trapped penis and unsatisfactory cosmetic results. Some complications are irreversible such as decreased sexual sensation and death. Psychological issues have been reported to arise in children after operations, including circumcisions. 17 The purpose of this research is to compile a recent and comprehensive list of complications that can arise from circumcision surgeries, in hopes that medical providers and parents will be able to make more informed decisions as to whether they will have their sons circumcised. The aim of the present study is to systematically review the studies on complications arising from male circumcisions published during the past two decades.

| METHODS
A search was conducted for articles written regarding complications arising from male circumcision surgeries. The term 'male circumcision' was entered into PubMed on June 16, 2020, and 6641 articles published from 1945 to 2020 were found. The search was then narrowed to include only articles from 2000 to 2020, which contained 4464 papers. These papers were analysed to look for full-text articles referring to specific complications arising from male circumcision surgeries, in English, Italian, Spanish, French, Portuguese or German languages. One hundred thirty-four articles fit these criteria. These articles were read and ultimately 78 of them were used to compile a list of 47 specific complications arising from male circumcision surgeries. The article selection process is shown using the PRISMA flow diagram.
The 78 articles used to compile the list of 47 specific complications arising from male circumcision surgeries were entered into one of three tables. The first table organizes the articles that are chart reviews and cohort studies and gives estimates of the incidence of complications, the second table organizes the articles that are case reports and case series with the specific complications experienced, and the third table organizes the articles that are literature searches, physician questionnaires and society recommendations. Table 4 contains the list of 47 specific complications arising from male circumcision surgeries.

| RESULTS
Seventy-eight articles selected from the literature search were used to conduct the systematic review and build the above-mentioned three tables as well as the comprehensive list of complications, contained in Table 4. Table 1 shows the 15 out of the 78 articles that were chart reviews and cohort studies. These followed a group of males that were circumcised and then saw how many of them developed complications from the circumcision operations. The studies were conducted mostly in the Middle East or United States, and the sample sizes ranged from as few as 25 patients 50 to nearly 1.5 million infants. 69 The complication rates ranged from less than 0.1% for meatal stenosis 69 to almost 23% for bleeding in the context of a genetic condition: haemophilia, sickle cell trait and factor VII deficiency. 52 The most common complication reported in most studies was haemorrhage/bleeding (outside of a genetic deficiency). Other complications reported included preputial stenosis, meatal stenosis, insufficient foreskin removal/redundant foreskin, long foreskin obstructing urine flow, early sloughing of foreskin tissue, device displacement, infection (minor and major), oedema, phimosis (referring to pathological phimosis), penile hematoma, bleeding in the context of a genetic condition (haemophilia, sickle cell trait and factor VII deficiency), skin bridges (penile skin adhesion), trapped/ buried/concealed/inconspicuous penis, nonhealing wound, scrotal injuries and meatitis.

Extensive penile skin defects/avulsion
Penile resurfacing using a reverse bilateral anterior scrotal artery flap 18 Penile injuries from proximal migration of the Plastibell circumcision ring 19 Circumcision mishaps in Nigerian children 20 2. Infection (minor and major) Newborn male circumcision 21 Infectious complications of circumcision and their prevention 22 Examination of short and long term complications of thermocautery, plastic clamping, and surgical circumcision techniques 23 A longitudinal population analysis of cumulative risks of circumcision 24 Acute ischemia of the glans penis after circumcision treated with hyperbaric therapy and pentoxifylline: Case report and revision of the literature 25 Canadian Pediatrics Society position statement on newborn circumcision: A riskbenefit analysis revisited 26 Complications of circumcision 27 Complications following circumcision: Presentations to the emergency department 28 Circumcision mishaps in Nigerian children 20 Rates of complications after newborn circumcision in a well-baby nursery, special care nursery, and neonatal intensive care unit 29 Male circumcision from an infectiological point of view 6 Circumcision: Postoperative complications that required reoperation 30 Reconstruction of the penile skin loss due to 'radical' circumcision with a full thickness skin graft 31 Serious complications in male infant circumcisions in Scandinavia indicate that this always be performed as a hospital-based procedure 32

Necrosis
Nontherapeutic circumcision of minors as an ethically problematic form of iatrogenic injury 4 Delayed glans necrosis after circumcision: Role of testosterone in salvaging glans 35 Complications of circumcision 27 Penile injuries from proximal migration of the Plastibell circumcision ring 19 Ischemia of the glans penis following circumcision: Case report and revision of the Sickle cell trait and haemophilia: A rare association 46 A newborn with simmering bleeding after circumcision 47 Déficit congénital en facteur VII révélé par une hémorragie post circoncision 48 Circumcision in males with bleeding disorders 49 Risk of bleeding and inhibitor development after circumcision of previously untreated or minimally treated severe hemophilia A children 50 A single centre experience in circumcision of haemophilia patients: Izmir protocol 51 To circumcise or not to circumcise? Circumcision in patients with bleeding disorders 52 Neonatal circumcision in severe haemophilia: A survey of paediatric haematologists at United States Hemophilia Treatment Centers 53 A rare but important adverse event associated with adult voluntary medical male circumcision: Prolonged bleeding 54 9. Oedema Evaluation of male circumcision: Retrospective analysis of one hundred and ninetyeight patients 45 Serious complications in male infant circumcisions in Scandinavia indicate that this always be performed as a hospital-based procedure 32 10. Keloids Keloid formation after pediatric male genital surgeries: An uncommon and difficult problem to manage 55 A rare presentation of penile keloids after traditional circumcision: Case report 56 Keloid formation after circumcision and its treatment 57 11. Phimosis (referring to pathological phimosis) Nontherapeutic circumcision of minors as an ethically problematic form of iatrogenic injury 4 Secondary phimosis after circumcision 58 Acquired phimosis after plastibell circumcision: A preventable consequence 59 Complications of circumcision 27 Revisions after unsatisfactory adult circumcisions 60 Dermatological complications of circumcision: Lesson learned from cases in a pediatric dermatology practice 61 12. Sudden infant death syndrome Neonatal circumcision and prematurity are associated with sudden infant death syndrome (SIDS) 62 13. Haemorrhage/bleeding (outside of a genetic deficiency) Circumcision bleeding complications: Neonatal intensive care infants compared to those in the normal newborn nursery 63 Circumcision: Postoperative complications that required reoperation 30 Immediate complications of elective newborn circumcision 64 A longitudinal population analysis of cumulative risks of circumcision 24 Evaluation of male circumcision: Retrospective analysis of one hundred and ninetyeight patients 45 Acute ischemia of the glans penis after circumcision treated with hyperbaric therapy and pentoxifylline: Case report and revision of the literature 25 Canadian Pediatrics Society position statement on newborn circumcision: A riskbenefit analysis revisited 26 Neonatal circumcision: New recommendations & implications for practice 1 Vitamin K deficiency bleeding and early infant male circumcision in Africa 65 Complications of circumcision 27 Bleeding complications after ritual circumcision: About six children 42 Complications following circumcision: Presentations to the emergency department 28 Surgically correctable morbidity from male circumcision: Indications for specialist surgical care in Lagos 43 Circumcision mishaps in Nigerian children 20 Rates of complications after newborn circumcision in a well-baby nursery, special care nursery, and neonatal intensive care unit 29 Bleeding at circumcision: Patient or operator issue 66 Male circumcision from an infectiological point of view 6 Examination of short and long term complications of thermocautery, plastic clamping, and surgical circumcision techniques 23 Serious complications in male infant circumcisions in Scandinavia indicate that this always be performed as a hospital-based procedure 32 (Continues) Complication Description

Nonhealing wound A longitudinal population analysis of cumulative risks of circumcision 24
Revisions after unsatisfactory adult circumcisions 60 Serious complications in male infant circumcisions in Scandinavia indicate that this always be performed as a hospital-based procedure 32 15. Scrotal injuries Examination of short and long term complications of thermocautery, plastic clamping, and surgical circumcision techniques 23 Scrotal injuries during neonatal circumcision 67

Preputial stenosis
Circumcision: Postoperative complications that required reoperation 30 17. Meatal stenosis Complication of newborn circumcision: Meatal stenosis or meatal web 68 Does circumcision increase meatal stenosis risk?-A systematic review and metaanalysis 69 Nontherapeutic circumcision of minors as an ethically problematic form of iatrogenic injury 4 Circumcision: Postoperative complications that required reoperation 30 Are mechanical and chemical trauma the reason of meatal stenosis after newborn circumcision 70 Canadian Pediatrics Society position statement on newborn circumcision: A riskbenefit analysis revisited 26 Neonatal circumcision: New recommendations & implications for practice 1 Complications of neonatal circumcision requiring surgical intervention in a developing country 40 Complications of circumcision 27 Incidence of asymptomatic meatal stenosis in children following neonatal circumcision 71 Surgically correctable morbidity from male circumcision: Indications for specialist surgical care in Lagos 43 Rates of complications after newborn circumcision in a well-baby nursery, special care nursery, and neonatal intensive care unit 29 Meatal stenosis in boys following circumcision for lichen sclerosus (balanitis xerotica obliterans) 72 18. Cicatrix Combination treatment for cicatrix after neonatal circumcision: An office-based solution to a challenging problem 73 Revisions after unsatisfactory adult circumcisions 60 Rates of complications after newborn circumcision in a well-baby nursery, special care nursery, and neonatal intensive care unit 29 19. Meatitis Examination of short and long term complications of thermocautery, plastic clamping, and surgical circumcision techniques 23 Nontherapeutic circumcision of minors as an ethically problematic form of iatrogenic injury 4 Complications of circumcision 27 Male circumcision from an infectiological point of view 6 20. Trapped/buried/concealed/inconspicuous penis Examination of short and long term complications of thermocautery, plastic clamping, and surgical circumcision techniques 23 Nontherapeutic circumcision of minors as an ethically problematic form of iatrogenic injury 4 Dermatological complications of circumcision: Lesson learned from cases in a pediatric dermatology practice 61 Complications of neonatal circumcision requiring surgical intervention in a developing country 40 Inconspicuous penis 74 Complications of circumcision 27 Reconstruction of the penile skin loss due to 'radical' circumcision with a full thickness skin graft 31 Buried and trapped penis: A case report 75 Surgically correctable morbidity from male circumcision: Indications for specialist surgical care in Lagos 43 The relationship between obesity and complications after neonatal circumcision 76 Buried penis after newborn circumcision 77 Rates of complications after newborn circumcision in a well-baby nursery, special care nursery, and neonatal intensive care unit 29 The inconspicuous penis in children 78 (Continues)   46. Excessive skin removal Rates of complications after newborn circumcision in a well-baby nursery, special care nursery, and neonatal intensive care unit 29 Serious complications in male infant circumcisions in Scandinavia indicate that this always be performed as a hospital-based procedure 32 47. Injury to urethra Rates of complications after newborn circumcision in a well-baby nursery, special care nursery, and neonatal intensive care unit 29 Serious complications in male infant circumcisions in Scandinavia indicate that this always be performed as a hospital-based procedure 32 have multiple instruments at the ready that they are trained and comfortable in using? Will they pick the technique of circumcision that best fits the baby's anatomy?

| DISCUSSION
Given the results of this study, it is clear that physicians must be prepared to counsel parents who are unsure of the decision to circumcise their sons or not, taking into account the vast number of complications that could arise as a result. The medical professionals must put aside their own personal beliefs and experiences in order to listen to the patient and parents' experiences, concerns and hesitations. Some families may come in with a decision already made about wanting to get the procedure done, and because parents may have a number of religious or cultural reasons for wanting their infant circumcised, it is vital that providers be able to participate in a balanced discussion that also takes into account the various types of complications and their potential severity. But it is also likely that a family will come into the office unsure of what to do. The physician must step up and counsel them. It is not ethical to push onto a patient or his family a procedure that they are unsure or uninformed about. Other families will have already decided to not circumcise their sons. Their decisions must be respected.
It is equally important that physicians discuss with their patients and parents ways of addressing common issues that could develop in natural male anatomy without the use of surgical intervention, for example, genital hygiene and presence of phimosis in a prepubescent male. Phimosis is present in almost all neonates, and the prepuce is eventually retractable in 99% of males by age 16. 15,16 If a prepubescent patient presents with tight but otherwise normal foreskin, watching and waiting until after puberty should be considered. 15 Male circumcision is not without its risks and complications, and all families, regardless of hesitations or not, must be informed of these potential adverse effects. In any scenario, a well-researched and experienced physician who can offer guidance and counselling will provide patients and their families comfort and guidance through this irreversible decision.

CONFLICT OF INTEREST
No interests to declare.

AUTHOR CONTRIBUTIONS
Stanca Iris Iacob did the background research and wrote the text.
Lauren Sardi gave guidance as to what topic could be covered in a systematic review, guided the initial phase of background research and helped with editing the text. Richard S. Feinn had the idea of creating the tables, helped format them and incorporated them into the text.