In the last eleven months, Pediatrics has published three
commentaries highly critical of the position held by the American Academy
of Pediatrics (AAP) in regard to infant male circumcision.[1-3] The
content of the commentaries is redundant and the opinions expressed are
based on a selective bibliography and other like-minded opinion pieces.
While opinions can fuel productive debate, the policies and
recommendations that result from debate should be evidence-based. That
should mean based on all the evidence.
The 1999 Task Force Report:
I agree with the commentators that the 1999 AAP Task Force on
Circumcision report had deficiencies. The report ignored some
evidence,[4,5] included methodologically weak references,[6] and took
positions inconsistent with other policy statements of the AAP and other
national organizations.
Neonatal anesthesia: In 1987 the AAP recommended that when
administering anesthetic agents to newborns “the decision to withhold such
medication should be based on the same medical criteria used for older
patients.”[7] Older children or adults are circumcised under general
anesthetic supplemented with a caudal or penile block for post-operative
pain relief.[8] Based on this AAP Policy, newborns should be circumcised
using general anesthesia. However, the risks of general anesthesia are
greater for a newborn and not warranted for an elective procedure. The
Australasian Association of Paediatric Surgeons recommends delaying
circumcision until general anesthesia is a safer option.[9]
Some have argued that the newborn period is the optimal time to
circumcise. While topical and local anesthetics reduce the pain of the
procedure, the rise in cortisol from baseline levels with these agents
indicates that the procedure is still quite stressful and painful. Two
studies have attempted to perform circumcisions in adults using EMLA
alone. Both were abandoned early because of the clear lack of
efficacy.[10,11] The financial “savings” of performing a circumcision on a
newborn is offset ethically by providing an inadequate anesthetic.
Restraints: Most infant circumcisions are performed using a
restraining mechanism. The most common method uses four-point restraints.
This procedure violates the Joint Commission on Hospital Accreditation and
Federal guidelines on restraints.[12,13] While the guidelines have an
exception to protect pediatric surgical sites, this would apply to the
post-operative period. Waiting until the child was old enough to tolerate
general anesthetic would avoid this conflict. Circumcision is not
performed in older infants because they cannot easily be strapped down and
are very vocal. Parents and ancillary staff would also strongly object.
There is little evidence that the benefits of circumcision would be
diminished if the operation was delayed until puberty. Doing so would
greatly reduce the incidence of complications, since penis would be mature
size, the foreskin would be not be torn away from the glans, and the
procedure would be less painful given that full anesthesia and
postoperative analgesia would be available.
Female circumcision: The AAP “opposes all forms” of female genital
mutilation.[14] This includes forms that are less invasive and less
harmful than male circumcision. The parallels between male and female
circumcision on a cultural level are multiple and not coincidental.[15-18]
Evidence is accumulating that female genital alterations may result in
medical benefits, such as the significant shortening of the second stage
of labor[19] and a reduction in the risk for HIV infection.[20]
Consequently, the AAP may need to readdress their position on female
cutting, or bring their position on male cutting into line. This is not to
suggest that I advocate female circumcision, but rather to highlight the
gender discrepancies.
Breastfeeding: The AAP acknowledges that breastfeeding reduces the
risk of urinary tract infections in infants,[21] yet the Task Force failed
to acknowledge the evidence that circumcision interferes with early
breastfeeding.[22] This may explain why male infants are more likely to
have higher bilirubin levels than female infants.[23]
Informed consent: The AAP Committee on Bioethics issued a statement
regarding informed consent, parental permission, and assent in pediatric
practice in 1995.[24] Because newborns do not have the capacity to give
informed consent, proxy consent is sought from parents or guardians. In
the 1995 statement, the Committee stated that proxy consent can only be
given in situations of medical necessity, such as disease, trauma, or
deformity. The healthy newborn male has a foreskin that is without
disease, trauma, or deformity. The Task Force concluded that circumcision
was not medically necessary. Therefore, as a matter of simple logic, proxy
consent is not valid. The 1995 statement goes on to say that for non-
essential treatments that can be deferred without loss of efficacy they
should wait until the child’s consent can be obtained (around 14 years of
age). Clearly, male circumcision fits this description. Instead, the Task
Force left the choice up to the parents, thus abandoning the obligation of
the physicians to protect their patients from unnecessary procedures. This
recommendation runs contrary to well-established bioethical and legal
principles and certainly out of step with an evolved human rights
culture.[18,25] For example, the International Covenant on Civil and
Political Rights, ratified by the US Senate on June 22, 1992, provides
every American, even minors, with a right to security of person and the
freedom from cruel, inhumane, or degrading treatment.[26]
To be consistent with other AAP policies, either the policy on
circumcision needs to be altered in a manner reflecting their other
policies, or the other policies need to be revised and explicitly mention
newborn circumcision as an exception.
Complication rate: Finally, the Task Force report stated that the
complication rate was between 0.2% and 0.6%. The first figure was from a
typographical error in the abstract of a study that had a complication
rate of 2%.[27] The second figure was from a letter to the editor that was
never subjected to peer review.[28] In studies based on actual chart
reviews (not merely databases), the immediate complication rate is 3.2% to
6.8%.[4,29] By underreporting the complication rate by 10-fold, the Task
Force did those physicians providing care of newborns a disservice.
Going to source materials:
Each of the recent commentaries cites the “marked decrease” of a variety
of conditions provided by infant circumcision without providing any
evidence other than each other’s opinion pieces. This is not acceptable.
Penile inflammation: Only three populations of children have been
studied regarding the risk of penile inflammation related to circumcision
status, none found a “marked decrease” in circumcised boys.[30-32] Two
found that circumcised boys under three years of age were at greater
risk.[31,32] This topic has not been well-studied in adults.
Phimosis: The incidence of pathologic phimosis in noncircumcised boys
is 0.6% by a boy’s fifteenth birthday and rarely occurs in the first five
years of life.[33] The most common cause is balanitis xerotica obliterans
(BXO). The incidence of preputial stenosis in which the glans of the penis
cannot be extruded as the result of a narrow circumcision scar is about
0.3% to 1.7%.[5,34,35] There are only four populations in which the risk
of phimosis was compared by circumcision status. None found a
statistically significant difference.[5,30,31,36]
Paraphimosis: The incidence of paraphimosis is unknown and rare (0.3%
of males referred for non-retractile foreskins).[37] In children it is
nearly always iatrogenic, and simple reduction is sufficient to prevent
recurrence.[38] The incidence of pseudoparaphimosis from a retained
PlastiBell is between 0.27% and 1% in circumcisions using a
PlastiBell.[27,39] The risk of paraphimosis appears to be lower than this,
but there are no comparison data.
Dermatosis: There is only one study that compared the rate of penile
dermatosis in adult males based on circumcision status.[40] These were
British men referred to a dermatologist. The study suffers from an obvious
referral bias and a control group with a 47.8% circumcision rate in a
country with a 21% circumcision rate.[41]
New information since the 1999 Task Force report:
Urinary tract infections (UTIs): Recent studies on UTIs should change the
way we think about them. The advent of prenatal ultrasound has revealed
that males have a propensity for prenatal urinary tract anomalies,
primarily vesicouretaral reflux (VUR).[42-45] Most VUR resolves
spontaneously;[46,47] however, some males with more severe prenatal VUR
have associated kidney damage.[44] In the era prior to routine prenatal
ultrasounds, VUR would be diagnosed accompanying a UTI, and the renal
damage would be wrongly attributed to the UTI. The whole paradigm of VUR
as a factor in renal scarring has been called into question,[48-50] and
boys with VUR are more likely to see spontaneous resolution than girls
with VUR.[44,47,51] There is no evidence of an association between
circumcision status and VUR.[52,53]
With the advent of nuclear renal imaging, the clinical signs of
pyelonephritis are not as directly associated with renal damage as
previously thought.[54,55] There is no link between renal damage and
circumcision status.[53,56] Evidence has also accumulated that infection
is rarely a cause of end-stage renal disease.[57-61] In follow-up studies,
children with UTIs, renal scarring, and primary, uncomplicated VUR did not
develop hypertension.[62,63] Finally, one study found that these
infections can be successfully treated with oral antibiotics.[64] The
connection between urinary tract infections in noncircumcised boys and
subsequent serious renal sequelae, if it indeed exists at all, has never
been proven. A meta-analysis of the association of circumcision and UTI
found that the risk of having a foreskin is lower than previously
advertised,[65] placing it in a range that could be explained all or in
part by confounding factors.[66] Female infants have a higher rate of
UTIs, which are treated with appropriate antibiotics instead of surgery.
Community-acquired Staphylococcus aureus (CA-MRSA): It was first
documented in 1966 that circumcised infants were more prone to
staphylococcal infections.[67] This was confirmed by two additional
studies.[68,69] Recently, this has taken an interesting twist with several
reports of outbreaks of CA-MRSA in newborn nurseries. These infections are
almost exclusively in boys with the lesions primarily in the pubic
area.[70] Circumcised infants are at 12 times the risk for CA-MRSA.[71]
Sexual function: Until the last few years the impact of circumcision
on sexual function had not been studied. While it was known that the
ridged band of the prepuce contained nearly all of the fine touch
neuroreceptors in the penis and this structure was completely removed by
circumcision,[72,73] the impact on physiology was unknown. There have been
several small studies that have surveyed men who were circumcised as
adults for medical indications to determine the difference in sexual
issues following the surgery.[74-77] While surgery was intended to correct
their medical problem, a substantial number of these men failed to improve
or worsened sexually. There were reports of increases in erectile
dysfunction, loss of sensitivity, and problems with intromission following
the procedure. These studies suffered from small sample sizes, poor
response rates, using subjective measures, and short follow-up periods.
Three studies have used objective measures of the penis. One study
was underpowered and found no differences.[78] One study of 125 men
referred to urology, both with and without erectile dysfunction, measuring
fine-pressure thresholds on three locations found noncircumcised men were
more sensitive, but the differences were no longer statistically
significant when adjusted for age, diabetes mellitus, and
hypertension.[79] In a study of 159 men taken from the general population
without diabetes or erectile dysfunction, fine-pressure thresholds were
measured on 11 to 17 locations on the penis. The circumcision scar was the
most sensitive portion of the circumcised penis, whereas the most
sensitive portion of the intact penis was the portion removed by
circumcision, and the glans of the intact penis was more sensitive than
the glans of the circumcised penis.[80]
Penile cancer: There have been two new case-controlled studies of the
risk factors associated with penile cancer.[81,82] Both found that having
phimosis, rather than just having a foreskin, was the principal risk
factor. This is consistent with growing evidence of a link between BXO and
penile cancer.[83-85] Slightly more than half of the penile cancers are
attributed to human papillomavirus (HPV), so BXO may account for the rest.
Of course removing tissue decreases the ability to develop cancer in that
tissue thereby giving the appearance of a decreased incidence of cancer or
disease. For example, if every boy had his left testicle removed at birth,
the rate of testicular cancer would be expected to decrease by more than
half.
Cervical cancer: A new study found a trend toward a greater risk of
cervical cancer in women with noncircumcised male partners, but the
results were not statistically significant.[86] Placed within the context
of the previously published studies, the AAP would be justified in
dismissing this topic again. Hopefully, the HPV vaccine will make
discussions of penile and cervical cancer as irrelevant as blood-letting
for fevers.
HPV: There are several new studies on the correlation of circumcision
status and HPV infections. Several have problems with sampling bias, small
numbers, and misclassification bias. When incorporated into a meta-
analysis, there is no statistically significant association.[87] The only
new study in the United States found no difference in risk.[88]
Sexually transmitted diseases (STDs): A meta-analysis found syphilis
and chancroid to be more common in noncircumcised men, primarily in
Africa. They found no statistically significant difference in
seropositivity for herpes simplex virus type 2 (HSV2).[89] Two subsequent
studies of HSV2 have confirmed this.[90,91] Another meta-analysis suggests
that circumcised men are at greater risk for sexually transmitted
urethritis.[92] The commentaries published recently in Pediatrics make
much of the recent New Zealand study suggesting that noncircumcised men
are at greater overall risk for STDs.[93] The commentators failed to
review the literature. If they had, they would have found the eleven
studies that have failed to confirm this finding and actually indicate
that circumcised men are at overall greater risk for acquiring an
STD.[90,94-103] More importantly, recently completed randomized controlled
trials (RCTs) from Africa are expected to report that other than clinical
genital ulcerative disease, circumcision had no significant impact on
syphilis, herpes simplex virus type 2 serology, gonorrhea, or
chlamydia.[104] The reality ignored by the previous commentaries is that
these STDs are avoidable by observing prudence in sexual contacts and
behavior and easily curable with antibiotics. Permanently altering the
genitals is out of all proportion to the danger posed by these infections.
HIV: Three RCTs in Africa were recently halted prior to their
completion because they found African men with foreskins were at greater
risk of contracting HIV infection.[105-107] Although these were RCTs,
they have serious problems. It was impossible to blind the subjects, so
the study could have expectation bias. The study began when subjects
randomized to the circumcision arm were circumcised, but the treatment arm
was instructed to abstain from sexual contact while the circumcision
healed whereas the men in the control arm continued to be sexually active,
thus introducing a lead-time bias that would only be amplified by early
termination of the trial. Early termination is more likely to result in an
overestimate of the treatment effect.[108,109] The studies also suffered
from attrition bias, length bias (no long-term follow-up is planned), and
selection bias (only men interested in circumcision were included). There
were ethical concerns regarding the trials,[110,111] and the subjects may
have been financially coerced by being offered a free circumcision, money
equivalent to two-weeks worth of employment, unlimited access to free
condoms, and free health care for 21 to 24 months.
Instituting a circumcision program will not benefit Africa, let alone
the United States. A “safe” circumcision is not readily available in
Africa. One African study found a 20.2% complication rate with 3.1% having
had part of the glans amputated.[112] Another study found that boys
circumcised before they became sexually active had greater risk for
HIV.[113] Circumcisions performed outside the medical system in Africa
could result in more deaths than the procedure has been speculated to
prevent.
Being circumcised may give men the mistaken message that they no longer
need to use condoms or practice safe sex. This could lead to an increase
in HIV infection. More importantly, the resources used to circumcise will
not be available for other less expensive, more effective prevention
strategies. For example, for the cost of one circumcision in Africa, 3,500
condoms can be purchased. While some outside of Africa consider the
results of the RCTs compelling, public health officials in Africa
recognize that circumcision is less effective and more expensive than
what is currently available and would take resources away from these
effective measures.[18]
Applying the results to infants in United States is even more problematic.
These studies were done on adults. To date there is no evidence that
infant circumcision prevents HIV infection. Infants and children are at
very low risk for sexually transmitted HIV and by the time today’s
newborns begin having sexual contact a vaccine or more effective anti-
retrovirals may be available. The United States has a much lower rate of
HIV than in countries in Africa. The strain of HIV infecting people in
Africa is different than the strain found in the U.S. Most of the HIV
infections in the United States are in men having sex with men (MSM),
while presumably the African epidemic is among men having sex with women
(MSW). In the United States it is claimed that the cases of HIV from MSW
accounts for only 15% of the cases.
The sexual mixing patterns in the United States, in general, are
different from Africa and may be responsible for driving the epidemic in
Africa.[114] When the various factors that account for the spread of HIV
infection, behavior components are responsible for more than 85% of the
risk. Consequently, the focus of preventions should be on the behavioral
factors.[115]
One of the major deficiencies in advocating circumcision as a
preventive for HIV infection is the lack of biological plausibility.
Circumcision proponents have repeatedly claimed that the inner lining of
the foreskin is more susceptible to abrasion, that the subpreputial space
acts as a breeding ground for sexually transmitted viruses, and that the
inner foreskin is rich in Langerhans cells, which are responsible for
transmission of HIV.[116] There is no scientific evidence that the inner
lining of the foreskin is more susceptible to abrasion, as the only study
to address this issue found a trend toward circumcised men having more
penile abrasions.[117] As mentioned above, the incidence of the two
sexually transmitted viruses, HPV and HSV2, are not affected by
circumcision status. The role of Langerhans cells in the transmission of
HIV has been called into question by a recent study that found that
langerin, a C-type lectin specifically expressed by Langerhans cells,
interferes with HIV transmission and inhibited T-cell infection. It was
only when the Langerhans cells were overwhelmed by a high viral count that
infection occurred. If Langerhans cells were not present, infection rates
would be higher.[118] Aggressive treatment of STDs in Africa has been
shown to be more effective and less expensive than circumcision.[119]
The United States has an incidence of HIV that is several-fold higher
than the incidence in Europe and Japan but many times lower than that seen
in Sub-Saharan Africa. We also have the distinction of having the highest
rates of circumcision among Western nations. Among ethnic groups in the
U.S., blacks have the highest rates of heterosexually transmitted HIV and
have circumcision rates similar to white non-Hispanics. Hispanics have the
lowest rate of circumcision and a rate of HIV infection between that of
blacks and white non-Hispanics. The US situation can be interpreted in one
of two ways. The first is that the circumcision experiment has already
been performed in the U.S. and failed to impact the spread of HIV. The
second, which is less likely, is that without a highly circumcised
population the HIV infection rate would be much greater. Regardless of the
interpretation, a couple of things remain clear. Our effort to contain the
epidemic has been woefully ineffective, and the positive impact of further
increasing the rate of circumcision would be miniscule. Although there is
no reason to believe that the results of the RCTs would apply to the US
population, with our current rate of heterosexually transmitted HIV, the
number needed to treat would be 4500 to prevent one case of HIV.[120] If
the cost per neonatal circumcision is $200,[121] then it would cost
$900,000 to prevent one case of HIV. This $900,000 could buy 36 million
condoms. Our resources would be far better spent adequately implementing
the interventions we already have.
For the individual male, if the $200 is not spent on a neonatal
circumcision and allowed to grow at 5% per annum, by 14 years of age $396
would be available. By 18 years this would be $481, and by 21 years this
would amount to $557. Foregoing circumcision in the newborn period would
allow the boy to keep his anatomy intact and make 15,840, 19,250, or
22,290 condoms available to him, respectively. Better still, if we educate
the boy properly and he follows a course of abstinence followed by
fidelity, he gets to keep his foreskin and the resources become available
elsewhere.
When compared to other HIV preventives, circumcision is much less
effective and much more expensive than education, condom use, abstinence,
fidelity, and aggressive surveillance and treatment of STDs. Comparing the
effectiveness of condoms to circumcision in preventing HIV is analogous to
comparing the effectiveness of oral contraceptives to the rhythm method in
preventing pregnancy.[122] At the very best circumcision may delay
infection, but it does not eliminate the risk.[18] Instead of imposing
circumcision on the infant without his consent, give him a choice when he
becomes sexually active: take these 15,840+ condoms and use them every
time you have sex, or we will cut off the pleasure center of your
genitals. With this trade-off, not many teenagers will elect the surgical
option.
There is a further danger that promoting circumcision will undercut
the efforts to promote condom use. This will happen in three ways. First,
with the most sensitive portion of the penis removed, condom use in a
circumcised man reduces his pleasure even further. This makes him less
likely to use one consistently. Second, condoms are more likely to slip
off the circumcised penis.[123] Third, it will be nearly impossible to
sell the idea that you still need to use a condom every time you have sex
even if you are circumcised. If consistent condom use is about 99%
effective, what added value is there to being circumcised? The only value
in being circumcised is if you want to engage in high-risk behavior
without a condom. This disinhibition will only increase the risk of
disease transmission.
When all of the costs and health outcomes related to infant
circumcision are combined in a cost-utility analysis, it was impossible,
even with assumptions most favorable to circumcision, including a 60%
reduction in HIV risk, to manipulate the numbers to make the practice
preserve health or save money. If the African numbers apply to the U.S.
(there is no evidence to support this assumption) it would cost between $1
million and $11 million to avert one case of heterosexually transmitted
HIV. Neonatal circumcision resulted in lifetime costs of $828.42 per
person and a reduction in health of 15.30 quality-adjusted life-years per
1000 males.[121]
Summary:
The United States is addicted to circumcision, much in the way the
star-bellied Sneetches loved their stars.[124] Over the past 150 years,
circumcision has become so entrenched in our culture as a social norm,
that rational discussions of the topic are rare.[125] It is not clear
whether the foreskin is amputated from blind adherence to tradition or a
fear of nonconformity coupled with a complete discounting of the
foreskin’s contribution to the sexual pleasure of the male and his
partner. As a scientific organization, I hope that the AAP would consider
newborn circumcision on its scientific merits and in the light of current
standards of medical ethics and human rights, thereby creating a policy
that reflects these principles and that is consistent with its other
policies. We should not be in the business of being culture brokers, as
some circumcision proponents have suggested,[126] nor capitulate to
political pressures; rather we should stand for what is in the best
interests of our patients. Welcoming a newborn into the world by cutting
off part of his penis is not in his best interest.
References:
1. Schoen EJ. Ignoring evidence of circumcision benefits. Pediatrics.
2006; 118: 385-387.
2. Flynn P, Havens P, Brady M, et al. Male circumcision for
prevention of HIV and other sexually transmitted diseases. Pediatrics.
2007; 119: 821-822.
3. Dickerman JD. Circumcision in the time of HIV: when is there
enough evidence to revise the Academy of Pediatric’ policy on
circumcision? Pediatrics. 2007; 119: 1006-1007.
4. O'Brien TR, Calle EE, Poole WK. Incidence of neonatal circumcision
in Atlanta, 1985-1986. South Med J. 1995; 88: 411-415.
5. Van Howe RS. Variability in penile appearance and penile findings:
a prospective study. Br J Urol. 1997; 80: 776-782.
6. Masters W, Johnson V. Human Sexual Response. Boston, Mass: Little
Brown & Co; 1966.
7. Poland RL, Roberts RJ, Guitierrez-Mazorra JF, Fonkalsrud EW.
Committee on Fetus and Newborn, Committee on Drugs, Section on
Anesthesiology, Section on Surgery. Neonatal Anesthesia. Pediatrics. 1987;
80: 446.
8. Holthusen H, Eichwede F, Stevens M, Willnow U, Lipfert P. Pre-
emptive analgesia: comparison of preoperative with postoperative caudal
block on postoperative pain in children. Br J Anaesth. 1994; 73: 440-442.
9. Leditschke JF. Australasian Association of Paediatric Surgeons.
Guidelines for circumcision. Hersion, Queensland, Australia; April 1996.
10. Siddique NI, D’Alossio JG, Dmochowski RM. A comparative study of
topical eutetic mixture of local anesthetics (EMLA) cream and dorsal nerve
block for circumcision in adults [abstract]. Reg Anesth. 1997; 22(2S): 94.
11. Laffon M, Gouchet A, Quenum M, Haillot O, Mercier C, Huguet M.
Eutectic mixture of local anesthetics in adult urology patients: an
observational trial. Reg Anesth Pain Med. 1998; 23: 502-505.
12. Joint Commission Perspectives. Official Joint Commission
Newsletter 20. 1999; 16(1).
13. 42 C.F.R. §482.13(f) (Centers for Medicare & Medicaid
Services, Department of Health and Human Services. Condition of
Participation: Patients’ Rights. Standard: Seclusion and Restraint for
Behavior Management).
14. Committee on Bioethics. Female genital mutilation. Pediatrics.
1998; 102: 153-156.
15. Lightfoot-Klein H. Similarities in attitudes and misconceptions
about male and female sexual mutilations. In Denniston GC, Milos MF,
editors. Sexual mutilations a human tragedy. New York: Plenum Press; 1997:
131-135.
16. Bell K. Genital cutting and western discourses on sexuality. Med
Anthropol Q. 2005; 19: 125-148.
17. Hellsten SK. Rationalising circumcision: from tradition to
fashion, from public health to individual freedom — critical notes on
cultural persistence of the practice of genital mutilation. J Med Ethics.
2004; 30: 248-253.
18. Myers A, Myers J. Male circumcision — the new hope? S Afr Med J.
2007; 97: 338-341.
19. Essén B, Sjöberg N-O, Gudmundsson S, Östergren P-O, Lindqvist PG.
No association between female circumcision and prolonged labour: a case
control study of immigrant women giving birth in Sweden. Eur J Obstet
Gynecol Reprod Biol. 2005; 121: 182-185.
20. Stallings RY, Karugendo E. Female circumcision and HIV infection
in Tanzania: for better or for worse?[abstract] Third International AIDS
Society Conference on HIV Pathogenesis and Treatment. Rio de Janeiro, July
25-27, 2005.
21. American Academy of Pediatrics Work Group on Breastfeeding.
Breastfeeding and the use of human milk. Pediatrics. 1997; 100: 1035-1039.
22. Howard CR, Howard FM, Weitzman ML. Acetaminophen analgesia in
neonatal circumcision: the effect on pain. Pediatrics. 1994; 93: 641-646.
23. Newman TB, Xiong B, Gonzales VM, Escobar GJ. Prediction and
prevention of extreme neonatal hyperbilirubinemia in a mature health
maintenance organization. Arch Pediatr Adolesc Med. 2000; 154; 1140-1147.
24. Committee on Bioethics. Informed consent, parental permission,
and assent in pediatric practice. Pediatrics. 1995; 95: 314-317.
25. Svoboda JS, Van Howe RS, Dwyer JG. Informed consent for neonatal
circumcision: an ethical and legal conundrum. J Contemp Health Law Policy.
2000; 17: 61-133.
26. International Covenant on Civil and Political Rights, GA res.
2200A (XXI), 21 UN GAOR Supp. (No. 16) at 52, UN Doc. A/6316 (1966), 999
UNTS 171, entered into force March 23, 1976.
27. Gee WF, Ansell JS. Neonatal circumcision: a ten-year overview:
with comparison of the Gomco clamp and the Plastibell device. Pediatrics.
1976; 58: 824-827.
28. Harkavy KL. The circumcision debate. Pediatrics. 1987; 79: 649-
650.
29. Moreno CA, Realini JP. Infant circumcision in an outpatient
setting. Tex Med. 1989; 85: 37-40.
30. Herzog LW, Alvarez SR. The frequency of foreskin problems in
uncircumcised children. Am J Dis Child. 1986; 140: 254-256.
31. Fergusson DM, Lawton JM, Shannon FT. Neonatal circumcision and
penile problems: an 8-year longitudinal study. Pediatrics. 1988; 81: 537-
541.
32. Van Howe RS. Neonatal circumcision and penile inflammation in
young boys. Clin Pediatr (Phila). 2007; 46: 329-333.
33. Shankar KR, Rickwood AMK. The incidence of phimosis in boys. BJU
Int. 1999; 84: 101-102.
34. Kaweblum YA, Press S, Kogan L, Levine M, Kaweblum M. Circumcision
using the Mogen clamp. Clin Pediatr (Phila). 1984; 23: 679-682.
35. Stenram A, Malmfors G, Okmian L. Circumcision for
phimosis–indications and results. Acta Paediatr Scand. 1986; 75: 321-323.
36. Metcalf TJ, Osborn LM, Mariani EM. Circumcision. A study of
current practices. Clin Pediatr (Phila). 1983; 22: 575-579.
37. Saxena AK, Schaarschmidt K, Reich A, Willital GH. Non-retractile
foreskin: a single center 13-year experience. Int Surg. 2000; 85: 180-183.
38. Rickwood AM. The unkindest cut of all? J Ir Coll Physicians
Surgeons. 1992; 21(3): 179-181.
39. Rubenstein MM, Bason WM. Complication of circumcision done with a
plastic bell clamp. Am J Dis Child. 1968; 116: 381-382.
40. Mallon E, Hawkins D, Dinneen M, et al. Circumcision and genital
dermatoses. Arch Dermatol. 2000; 136: 350-354.
41. Johnson AM, Wadsworth J, Wellings K, Field J, Bradshaw S. Sexual
Attitudes and Lifestyles. Oxford: Blackwell Scientific; 1994.
42. Herndon CDA, McKenna PH, Kolon TF, Gonzales ET, Baker LA, Docimo
SG. A multicenter outcomes analysis of patients with neonatal reflux
presenting with prenatal hydronephrosis. J Urol. 1999; 162: 1203-1208.
43. Anderson PAM, Rickwood AMK. Features of primary vesicoureteric
reflux detected by prenatal sonography. Br J Urol. 1991; 67: 267-271.
44. Yeung CK, Godley ML, Dhillon HK, Gordon I, Duffy PG, Ransley PG.
The characteristics of primary vesico-ureteric reflux in male and female
infants with pre-natal hydronephrosis. Br J Urol. 1997; 80: 319-327.
45. Tsai JD, Huang FY, Tsai TC. Asymptomatic vesicoureteral reflux
detected by neonatal ultrasonographic screening. Pediatr Nephrol. 1998;
12: 206-209.
46. Steele BT, Robitalle P, Demaria J, Grignon A. Follow-up
evaluation of prenatally recognized vesicoureteric reflux. J Pediatr.
1989; 115: 95-96.
47. Wennerstrom M, Hansson S, Jodal U, Stokland E. Disappearance of
vesicoureteral reflux in children. Arch Pediatr Adolesc Med. 1998; 152:
879-883.
48. Linshaw MA. Controversies in childhood urinary tract infections.
World J Urol. 1999; 17: 383-395.
49. Garin EH, Campos A, Homsy Y. Primary vesicoureteral reflux:
review of current concepts. Pediatr Nephrol. 1998; 12: 249-256.
50. Ortigas AP, Cunningham AS. Three facts to know before you order a
VCUG. Cont Pediatr. 1997; 14(9): 69, 73-74, 79.
51. Sillén U, Bachelard M, Hansson S, Hjälmås K, Jodal U, Hanson E.
Resolution rate in infantile dilating vesicoureteral reflux diagnosed
after UTI [Abstract 109]. Pediatrics. 1998; 102: 869.
52. Mueller ER, Steinhardt G, Naseer S. The incidence of
genitourinary abnormalities in circumcised and uncircumcised boys
presenting with an initial urinary tract infection by 6 months of age
[Abstract 121]. Pediatrics. 1997; 100: 580.
53. Heldrich FJ, Barone MA, Spiegler E. UTI: diagnosis and evaluation
in symptomatic pediatric patients. Clin Pediatr (Phila). 2000; 39: 461-
472.
54. Majd M, Rushton HG, Jantausch B, Wiedermann BL. Relationship
among vesicoureteral reflux, P-fimbriated Escherichia coli, and acute
pyelonephritis in children with febrile urinary tract infection. J
Pediatr. 1991; 119: 578-585.
55. Rushton HG. The evaluation of acute pyelonephritis and renal
scarring with technetium 99m-dimercaptosuccinic acid renal scintigraphy:
evolving concepts and future directions. Pediatr Nephrol. 1997; 11: 108-
120.
56. Landau D, Turner ME, Brennan J, Majd M. The value of urinalysis
in differentiating acute pyelonephritis from lower urinary tract infection
in febrile infants. Pediatr Infect Dis J. 1994; 13: 777-781.
57. Sreenarasimhaiah S, Hellerstein S. Urinary tract infections per
se do not cause end-stage kidney disease. Pediatr Nephrol. 1998; 12: 210-
213.
58. Helin I, Winberg J. Chronic renal failure in Swedish children.
Acta Paediatr Scand. 1980; 69: 607-611.
59. Esbjörner E, Berg U, Hansson S. Epidemiology of chronic renal
failure in children: a report from Sweden 1986-1994. Swedish Pediatric
Nephrology Association. Pediatr Nephrol. 1997; 11: 438-442.
60. Esbjörner E, Aronson S, Berg U, Jodal U, Linne T. Children with
chronic renal failure in Sweden 1978-1985. Pediatr Nephrol. 1990; 4: 249-
252.
61. Wennerström M, Hansson S, Jodal U, Stokland E. Primary and
acquired renal scarring in boys and girls with urinary tract infection. J
Pediatr. 2000; 136: 30-34.
62. Wolfish NM, Delbrouck NF, Shanon A, Matzinger MA, Stenstrom R,
McLaine PN. Prevalence of hypertension in children with primary
vesicoureteral reflux. J Pediatr. 1993; 123: 559-563.
63. Wennerström M, Hansson S, Hedner T, Himmelmann A, Jodal U.
Ambulatory blood pressure 16-26 years after the first urinary tract
infection in childhood. J Hypertens. 2000; 18: 485-491.
64. Hoberman A, Wald ER, Hickey RW, et al. Oral versus initial
intravenous therapy for urinary tract infections in young febrile
children. Pediatrics. 1999; 104: 79-86.
65. Singh-Grewal D, Macdessi J, Craig J. Circumcision for the
prevention of urinary tract infection in boys: A systematic review of
randomized trials and observational studies. Arch Dis Child. 2005; 90: 838
-838.
66. Van Howe RS. Effect of confounding in the association between
circumcision status and urinary tract infection. J Infect. 2005; 51: 59-
68.
67. Thompson DJ, Gezon HM, Rogers KD, Yee RB, Hatch TF. Excess risk
of staphylococcal infection and disease in newborn males. Am J Epidemiol.
1966; 84: 314-328.
68. Enzenauer RW, Dotson CR, Leonard T, Reuben L, Bass JW, Brown J
III. Male predominance in persistent staphylococcal colonization and
infection of the newborn. Hawaii Med J. 1985; 44: 389-390, 392, 394-396.
69. Rush J, Fiorino-Chiovitti R, Kaufman K, Mitchell A. A randomized
controlled trial of a nursery ritual: wearing cover gowns to care for
healthy newborns. Birth. 1990; 17: 25-30.
70. Van Howe RS, Robson WLM, The possible role of circumcision in
newborn outbreaks of community-aassociated methicillin-resistant
Staphylococcus aureus. Clin Pediatr (Phila). 2007; 46: 356-359.
71. Nguyen DM, Bancroft E, Mascola L, Guevara R, Yasuda L. Risk
factors for neonatal methicillin-resistant Staphylococcus aureus infection
in a well-infant nursery. Infect Control Hosp Epidemiol. 2007; 28: 406-
411.
72. Taylor JR, Lockwood AP, Taylor AJ. The prepuce: specialized
mucosa of the penis and its loss to circumcision. Br J Urol. 1996; 77: 291
-295.
73. Cold CJ, Taylor J. The prepuce. BJU Int. 1999; 83 (suppl 1): 34-
44.
74. Fink KS, Carson CC, DeVellis RF. Adult circumcision outcomes
study: effect on erectile function, penile sensitivity, sexual activity
and satisfaction. J Urol. 2002; 167: 2113-2116.
75. Coursey JW, Morey AF, McAninch JW, et al. Erectile function after
anterior urethroplasty. J Urol. 2001; 166: 2273-2276.
76. Collins S, Upshaw J, Rutchik S, Ohannessian C, Ortenberg J,
Albertsen P. Effects of circumcision on male sexual function: debunking a
myth? J Urol. 2002; 167: 2111-2112.
77. Shen Z, Chen S, Zhu C, Wan Q, Chen Z. [Erectile function
evaluation after adult circumcision] Zhonghua Nan Ke Xue. 2004; 10: 18-19.
78. Payne K, Thaler L, Kukkonen T, Carrier S, Binik Y. Sensation and
sexual arousal in circumcised and uncircumcised men. J Sex Med. 2007; Epub
ahead of print.
79. Bleustein CB, Fogarty JD, Eckholdt H, Arezzo JC, Melman A. Effect
of neonatal circumcision on penile neurologic sensation. Urology. 2005;
65: 773-777.
80. Sorrells ML, Snyder JL, Reiss MD, et al. Fine-touch pressure
thresholds in the adult penis. BJU Int. 2007; 99: 864-869.
81. Tseng HF, Morgenstern H, Mack T, Peters RK. Risk factors for
penile cancer: results of a population-based case-control study in Los
Angeles County (United States). Cancer Causes Control. 2001; 12: 267-277.
82. Daling JR, Madeleine MM, Johnson LG, et al. Penile cancer:
Importance of circumcision, human papillomavirus and smoking in in situ
and invasive disease. Int J Cancer. 2005; 116: 606-616.
83. Pietrzak P, Hadway P, Corbishley CM, Watkin NA. Is the
association between balanitis xerotica obliterans and penile carcinoma
underestimated? BJU Int. 2006; 98: 74-76.
84. Velazquez EF, Cubilla AL. Lichen sclerosus in 68 patients with
squamous cell carcinoma of the penis: frequent atypias and correlation
with special carcinoma variants suggests a precancerous role. Am J Surg
Pathol. 2003; 27: 1448-1453.
85. Powell J, Robson A, Cranston D, Wojnarowska F, Turner R. High
incidence of lichen sclerosus in patients with squamous cell carcinoma of
the penis. Br J Dermatol. 2000; 145: 85-89.
86. Castellsagué X, Bosch FX, Muñoz N, et al. Male circumcision,
penile human papillomavirus infection, and cervical cancer in female
partners. N Engl J Med. 2002; 346: 1105-1112.
87. Van Howe RS. Human papillomavirus and circumcision: A meta-
analysis. J Infect. 2007; 54: 490-496.
88. Weaver BA, Feng Q, Holmes KK, et al. Evaluation of genital sites
and sampling techniques for detection of human papillomavirus DNA in men.
J Infect Dis. 2004; 189: 677-685.
89. Weiss HA, Thomas SL, Munabi SK, Hayes RJ. Male circumcision and
risk of syphilis, chancroid, and genital herpes: a systematic review and
meta-analysis. Sex Transm Infect. 2006; 82: 101-110.
90. Dickson N, van Roode T, Paul C. Herpes simplex virus type 2
status at age 26 is not related to early circumcision in a birth cohort.
Sex Transm Dis. 2005; 32: 517-519.
91. Xu F, Markowitz LE, Sternberg MR, Aral SO. Prevalence of
circumcision and herpes simplex type 2 infection in men in the United
States: the National Health and Nutrition Examination Survey (NHANES),
1999-2004. Sex Transm Dis. 2007; Epub ahead of print.
92. Van Howe RS. Genital ulcer disease and sexually transmitted
urethritis and circumcision: a meta-analysis. Int J STD AIDS. In press.
93. Fergusson DM, Boden JM, Horwood LJ. Circumcision status and risk
of sexually transmitted infection in young adult males: an analysis of a
longitudinal birth cohort. Pediatrics. 2006; 118: 1971-1977.
94. Aynaud O, Piron D, Bijaoui G, Casanova JM. Developmental factors
of urethral human papillomavirus lesions: correlation with circumcision.
BJU Int. 1999; 84: 57-60.
95. Dave SS, Fenton KA, Mercer CH, Erens B, Wellings K, Johnson AM.
Male circumcision in Britain: findings from a national probability sample
survey. Sex Transm Infect. 2003; 79: 499-500.
96. Diseker RA 3rd, Peterman TA, Kamb ML, et al. Circumcision and STD
in the United States: cross sectional and cohort analyses. Sex Transm
Infect. 2000; 76: 474-479.
97. Laumann EO, Masi CM, Zuckerman EW. Circumcision in the United
States: prevalence, prophylactic effects, and sexual practice. JAMA. 1997;
277: 1052-1057.
98. Parker SW, Stewart AJ, Wren MN, Gollow MM, Straton JA.
Circumcision and sexually transmissible disease. Med J Aust. 1983; 2: 288-
290.
99. Schrek R, Lenowitz H. Etiologic factors in carcinoma of penis.
Cancer Research. 1947; 7: 180-187.
100. Richters J, Smith AMA, de Visser RO, Grulich AE, Rissel CE.
Circumcision in Australia: prevalence and effects on sexual health. Int J
STD AIDS. 2006; 17: 547-554.
101. Seed J, Allen S, Mertens T, et al. Male circumcision, sexually
transmitted disease, and risk of HIV. J Acquir Immune Defic Syndr Hum
Retrovirol. 1995; 8: 83-90.
102. Taylor PK, Rodin P. Herpes genitalis and circumcision. Br J
Vener Dis. 1975; 51: 274-277.
103. Urassa M, Todd J, Boerma JT, Hayes R, Isingo R. Male
circumcision and susceptibility to HIV infection among men in Tanzania.
AIDS. 1997; 11: 73-80.
104. Auvert B, Bailey R, Gray R. Results of the South African trial,
the Kenyan trial, and the Rakai Trial. Centers for Disease Control and
Prevention Consultation on Public Health Issues Regarding Male
Circumcision in the United States for the Prevention of HIV Infection and
Other Health Consequences. Atlanta, Georgia. April 26, 2007.
105. Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R,
Puren A. Randomized, controlled intervention trial of male circumcision
for reduction of HIV infection risk: The ANRS 1265 Trial. PLoS Med. 2005;
2(11): e298.
106. Bailey RC, Moses S, et al. Male circumcision for HIV prevention
in young men in Kisumu, Kenya: a randomised controlled trial. Lancet.
2007; 369: 643-656.
107. Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV
prevention in men in Rakai, Uganda: a randomised trial. Lancet. 2007; 369:
657-666.
108. Mills E, Siegfried N. Cautious optimism for new HIV/AIDS
prevention strategies. Lancet. 2006; 368: 1236.
109. Montori VM, Devereaux PJ, Adhikari NK, et al. Randomized trial
stopped early for benefit: a systematic review. JAMA. 2005; 294: 2203-
2209.
110. Van Howe RS, Svoboda JS, Hodges FM. HIV infection and
circumcision: cutting through the hyperbole. J R Soc Health. 2005; 125:
259-265.
111. Siegfried N. Does male circumcision prevent HIV infection? PLoS
Med. 2005; 2(11): e393.
112. Okeke LI, Asinobi AA, Ikuerowo OS. Epidemiology of complications
of male circumcision in Ibadan, Nigeri. BMC Urol. 2006; 6: 21.
113. Brewer DD, Potterat JJ, Roberts JM Jr, Brody S. Male and female
circumcision associted with prevalent HIV infection in virgins and
adolescents in Kenya, Lesotho, and Tanzania. Ann Epidemiol. 2007; 17: 217-
226.
114. Chin J. The AIDS Pandemic: The Collision of Epidemiology with
Political Correctness. Oxford: Radcliffe Publishing; 2007.
115. Donovan B, Ross MW. Preventing HIV: determinants of sexual
behaviour. Lancet. 2000; 355: 1897-1901.
116. Schoen EJ, Wiswell TE, Moses S. New policy on circumcision —
cause for concern. Pediatrics. 2000; 105: 620-623.
117. Bailey RC, Neema S, Othieno R. Sexual behaviours and other HIV
risk factors in circumcised and uncircumcised men in Uganda. J Acquir
Immune Defic Syndr Hum Retrovirol. 1999; 22: 294-301.
118. de Witte L, Nabatov A, Pion M, et al. Langerin as a natural
barrier to HIV-1 transmission by Langerhans cells. Nat Med. 2007; advance
online publication. doi:10.1038/nm1541.
119. Gilson L, Mkanje R, Grosskurth H, et al. Cost-effectiveness of
improved treatment services for sexually transmitted diseases in
preventing HIV-1 infection in Mwanza Region, Tanzania. Lancet. 1997; 350:
1805-1809.
120. Van Howe RS. A cost-utility analysis of neonatal circumcision.
Med Decis Making. 2004; 24: 584-601.
121. Schoen EJ, Colby CJ, To TT. Cost analysis of neonatal
circumcision a large health maintenance organization. J Urol. 2006; 175:
1111-1115.
122. Garenne M. Male circumcision and HIV control in Africa. PLoS Med
2006; 3: e78.
123. Richters J, Gerofi J, Donovan B. Why do condoms break or slip
off in use? An exploratory study. Int J STD AIDS. 1995; 6: 11-18.
124. Geisel TS. The sneetches and other stories. New York, NY: Random
House; 1961.
125. Waldeck SE. Using male circumcision to understand social norms
as multipliers. U Cinn L Rev. 2003; 72: 455-526.
126. Moses S, Bailey RC, Ronald AR. Male circumcision: assessment of
health benefits and risks. Sex Transm Inf. 1998: 74: 368-373.
Conflict of Interest:
None declared
eLetters: ![[Read eLetters]](/icons/misc/sectionDOWN.gif){kind=icon}
