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'Circumcision pain' unlikely to cause autism

  • Kaiser Permanente Moanalua Medical Center
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‘Circumcision pain’ unlikely to cause
Claims by Frisch and Simonsen
that ‘circumcision
pain’ increases risk of autism spectrum disorder are
flawed. They dredged Danish medical records of
342,877 boys aged 0–10 years looking for an adverse
effect of circumcision. Marginal significance was
apparent for autism spectrum disorder at age
0–4 years for 28 Muslim boys circumcised before
the age of 2 years. Since HR was 1.54 (95% CI,
1.03–2.31), the circumcision effect involved approxi-
mately 10 boys. In 0–4-year-old circumcised non-
Muslim boys they noted six autism spectrum disorder
diagnoses and three hyperkinetic disorder diagnoses.
Of 337 Muslim boys aged 0–10 years with autism
spectrum disorder, only 10.9% were ‘circumcised’,
89.1% being ‘intact’, which is improbable and under-
mines their findings.
The authors cite a survey that found pain was high
in 4% of infants during six weeks post-circumcision.
Since the Danish study was about pain why didn’t
Frisch and Simonsen examine other painful condi-
tions? Urinary tract infections are associated with
excruciating pain, are common and very much
higher in uncircumcised male infants and boys.
the authors’ pain hypothesis were correct, then
autism spectrum disorder should be associated with
urinary tract infections and therefore being
Anaesthetics are neurotoxic to the developing
brain. Systemic use in children aged under 3 years is
associated with later cognitive impairment.
unnecessary general anaesthesia, not pain, have con-
tributed to autism spectrum disorder?
They cite a study correlating autism spectrum dis-
order and circumcision prevalence post-1995, but fail
to state that this was actually a study of paracetamol
usage, circumcisions being merely a proxy.
‘hypothesis generating exploratory analysis’ was
prompted by the difference in paracetamol metabol-
ism in immature brains that might produce neuronal
damage in susceptible infants.
Most likely, both autism spectrum disorder diag-
nosis and early circumcision reflect parental
Competing interests: None declared
1. Frisch M and Simonsen J. Ritual circumcision and risk
of autism spectrum disorder in 0- to 9-year old boys:
national cohort study in Denmark. J R Soc Med 2015;
Epub ahead of print Jan 8, 2015:doi:10.1177/
2. Morris BJ and Wiswell TE. Circumcision and lifetime
risk of urinary tract infections: A systematic review and
meta-analysis. J Urol 2013; 189: 2118–2124.
3. Ing C, DiMaggio C, Whitehouse A, Hegarty MK,
Brady J, von Ungern-Sternberg BS, et al. Long-term
differences in language and cognitive function after
childhood exposure to anesthesia. Pediatrics 2012;
130: e476–e85.
4. Bauer AZ and Kriebel D. Prenatal and perinatal anal-
gesic exposure and autism: an ecological link. Environ
Health 2013; 12: 41.
Brian J Morris
School of Medical Sciences, University of Sydney, Sydney,
New South Wales, Australia
Thomas E Wiswell
Center for Neonatal Care, Florida Hospital, Orlando, FL, USA
Circumcision-autism link needs
thorough evaluation: Response to
Morris and Wiswell
Morris and Wiswell express concern over small num-
bers of circumcised boys with autism spectrum dis-
order (ASD) and hyperkinetic disorder in non-
Muslim families, apparently unaware of the fact
that our findings were statistically significant despite
the limited statistical power of these analyses, not
because of it. Also, without substantiation, our critics
consider the overall proportion of boys in Muslim
families who were ritually circumcised by Danish
doctors (10.9%) ‘improbable’, although no one
knows the exact proportions of ritual circumcisions
Journal of the Royal Society of Medicine; 2015, Vol. 108(8) 297–298
DOI: 10.1177/0141076815590404
by guest on August 12, 2015jrs.sagepub.comDownloaded from
... In the autism study, criticisms 16 24 We calculated that ASD in their general population was 4986/342,877×100 = 1.45%. In the circumcised group we calculated ASD prevalence to be 55/(2903 + 444) × 100 = 1.64%. ...
... Critics pointed out that only 11% of Muslim boys in the study were recorded as being circumcised, that a significant association with ASD diagnosis was found in boys under the age of 4 years, but association was not significant in boys aged 5-9 years, which was relevant to alternative explanations. 16 Medications for post-NMC analgesia, specifically acetaminophen, found in 1994 to be effective for managing post-NMC pain, 52 led the AAP to recommend acetaminophen in 1999. 7 Supporting acetaminophen rather than NMC being responsible for ASD, Bauer and Kriebel found the association of NMC with ASD was "considerably weaker" prior to 1995. ...
... 22 Acetaminophen breakdown by sulfation is the primary metabolic route in children, and is very much lower in neonates, and even more so in ASD. 22 Bauer criticized the Danish ASD study for falsely suggesting that her group's findings applied to NMC. 53 And she explained why older boys in the Danish study (born before the 1999 guidelines 7 ) showed only a weak association of circumcision with ASD, whereas those born after 1999 showed a stronger association, 16,53 thus supporting the acetaminophen hypothesis. ...
Full-text available
Objective: To conduct the first systematic review critically examining evidence on whether early male circumcision has short- and long-term adverse psychological effects. Methods: We searched PubMed, EMBASE, SCOPUS, Cochrane Library, and Google Scholar. Results: Twenty-four studies with original data met the inclusion criteria. These comprised 11,173 total males, 4340 circumcised in infancy and 6908 uncircumcised. Nineteen were rated 1+, 2++ or 2+, and 5 were rated 2- by SIGN criteria. Neonatal circumcision, particularly without anesthetic, increased vaccination pain response, but had little effect on breastfeeding or cognitive ability. Studies reporting associations with sudden infant death syndrome, autism, alexithymia and impaired sexual function and pleasure had design flaws and were rated 2-. Sexual arousal, touch, pain, and warmth thresholds measured by quantitative sensory testing were not diminished in neonatally circumcised men. Neonatal circumcision was not associated with empathy in men, contradicting the hypothesis that procedural pain causes central nervous system changes. After correcting all associations with socioaffective processing parameters for multiple testing only higher sociosexual desire, dyadic sexual libido/drive, and stress remained significant. The relatively greater sexual activity found in circumcised men might reflect reduced sexual activity in uncircumcised men overall owing to pain and psychological aversion in those with foreskin-related medical conditions (reverse causality). Most studies employed case-control designs with limited follow-up. Studies beyond childhood were prone to confounding. Conclusion: The highest quality evidence suggest that neonatal and later circumcision has limited or no short-term or long-term adverse psychological effects.
... Relatively little research has investigated pain-related responses to circumcision in infants (Dixon et al., 1984;Fergusson et al., 2007;Gattari et al., 2013;Gunnar et al., 1981Gunnar et al., , 1995Marshall et al., 1980Marshall et al., , 1982Mondzelewski et al., 2016;Page, 2004;Svoboda and Van Howe, 2013;Taddio et al., 1997aTaddio et al., , 1997bTalbert et al., 1976;Williamson et al., 1986;Williamson and Williamson, 1983), and only a handful of studies have generated evidence regarding potential long-term effects lasting into adulthood (Bauer and Kriebel, 2013;Bollinger and Van Howe, 2011;Frisch and Simonsen, 2015a;Ullmann et al., 2017). The small number of studies that have investigated long-term effects have been argued to exhibit methodological flaws and limitations (Boyle, 2017;Morris et al., 2012;Morris and Wiswell, 2015) leading to calls for further research in this area Frisch and Simonsen, 2015b). ...
... More recently, two large-sample studies suggested a positive correlation between circumcision and autism spectrum disorder (ASD; Bauer and Kriebel, 2013;Frisch and Simonsen, 2015a). Although the causal implications of this research has been questioned (Morris et al., 2012;Morris and Wiswell, 2015), these studies suggest that early-circumcision might have an impact on adult psychosocial functioning. It has been extensively debated whether circumcision affects sexual outcome variables, including sensation and satisfaction (e.g., Bossio et al., 2014;Boyle, 2015;Earp, 2016;Morris and Krieger, 2015), with research in this area often conflating studies of newborn versus adult circumcision. ...
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Background Neonatal male circumcision is a painful skin-breaking procedure that may affect infant physiological and behavioral stress responses as well as mother-infant interaction. Due to the plasticity of the developing nociceptive system, neonatal pain might carry long-term consequences on adult behavior. In this study, we examined whether infant male circumcision is associated with long-term psychological effects on adult socio-affective processing. Methods We recruited 408 men circumcised within the first month of life and 211 non-circumcised men and measured socio-affective behaviors and stress via a battery of validated psychometric scales. Results Early-circumcised men reported lower attachment security and lower emotional stability while no differences in empathy or trust were found. Early circumcision was also associated with stronger sexual drive and less restricted socio-sexuality along with higher perceived stress and sensation seeking. Limitations This is a cross-sectional study relying on self-reported measures from a US population. Conclusions Our findings resonate with the existing literature suggesting links between altered emotional processing in circumcised men and neonatal stress. Consistent with longitudinal studies on infant attachment, early circumcision might have an impact on adult socio-affective traits or behavior.
... Critics exposed numerous flaws in the study, pointing out that the number of cases was small, statistical significance was marginal, association was stronger in Muslim boys which might suggest a need for consideration of genetic or cultural influences, association with ASD of painful conditions more prevalent in uncircumcised boys (such as cystitis) was not examined, association with ASD diagnosis was found in boys under the age of 4 years, but not in boys aged 5-9 years, which is relevant to alternative explanations such as neuronal damage caused by analgesic usage on immature brains. 94 General anesthesia, sometimes advocated for infant MC, 95 is neurotoxic and associated with later cognitive impairment. 96 It has generally been disavowed in favor of local anesthesia. ...
... 158 Amongst these were 2 fine-touch receptors, but no genital corpuscles that have been invoked as the nerve endings responsible for erogenous sensations. 143 To arrive at "20 000," 212 would need to be multiplied by 94 160 Those measurements showed that foreskin size is highly variable, very much more so than penis length. 161 Darwin noted, "An organ, when rendered useless, may well be variable, for its variations cannot be checked by natural selection." ...
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Objective: To systematically evaluate evidence against male circumcision (MC). Methods: We searched PubMed, Google Scholar, EMBASE and Cochrane databases. Results: Database searches retrieved 297 publications for inclusion. Bibliographies of these yielded 101 more. After evaluation we found: Claims that MC carries high risk were contradicted by low frequency of adverse events that were virtually all minor and easily treated with complete resolution. Claims that MC causes psychological harm were contradicted by studies finding no such harm. Claims that MC impairs sexual function and pleasure were contradicted by high-quality studies finding no adverse effect. Claims disputing the medical benefits of MC were contradicted by a large body of high-quality evidence indicating protection against a wide range of infections, dermatological conditions, and genital cancers in males and the female sexual partners of men. Risk-benefit analyses reported that benefits exceed risks by 100-200 to 1. To maximize benefits and minimize risks, the evidence supported early infant MC rather than arguments that the procedure should be delayed until males are old enough to decide for themselves. Claims that MC of minors is unethical were contradicted by balanced evaluations of ethical issues supporting the rights of children to be provided with low-risk, high-benefit interventions such as MC for better health. Expert evaluations of case-law supported the legality of MC of minors. Other data demonstrated that early infant MC is cost-saving to health systems. Conclusions: Arguments opposing MC are supported mostly by low-quality evidence and opinion, and are contradicted by strong scientific evidence.
... He fails to mention that the aap responded at the time, arguing convincingly that a cultural bias against imc is more likely to exist in Europe than cultural bias favouring imc in the usa, since the usa comprises similar proportions of men who are circumcised and uncircumcised and both options are considered culturally acceptable (Task, 2013). The lead author of the European article, Morten Frisch, is a vocal imc critic whose research reflects this bias (Morris et al., 2012c;Morris and Krieger, 2013;Morris and Wiswell, 2015). ...
... Adler cites a study by Frisch and Simonsen of 0-9 year olds that reported an association of mc with autism spectrum disorder in a very small proportion of subjects (Frisch and Simonsen, 2015). Those findings were disputed in published critiques (Anonymous, 2015;Morris and Wiswell, 2015) that Adler failed to cite. In another Danish study ASD prevalence in uncircumcised boys was 7.2%, leading the authors to suggest that the study by Frisch and Simonsen suffered from confounding (Sneppen and Thorup, 2016). ...
Full-text available
We evaluate Peter Adler's challenge to the Centers for Disease Control and Prevention (cdc) draft recommendations on male circumcision (this issue, see pp. 237-262). The CDC advocates elective male circumcision (mc) to improve public health in the usa based on strong scientific evidence. In marked contrast to the cdc, Adler's criticisms depend on speculative claims and obfuscation of the scientific data. Adler's central argument that circumcision in infancy should be delayed to allow a boy to make up his own mind as an adult fails to appreciate that circumcision later in life is a more complex operation, entails higher risk, is more likely to involve general anaesthesia and presents financial, psychological and organisational barriers. These limitations are avoided by circumcision early in infancy, when it is convenient, safe, quick, low risk, usually involves local anaesthesia and provides benefits immediately. Benefits of male circumcision include: protection against: urinary tract infections that are ten times higher in uncircumcised infants; inflammatory skin conditions; other foreskin problems; sexually transmitted infections and genital cancers in the male and his female sexual partners. Circumcision during infancy is also associated with faster healing and improved cosmetic outcomes. Circumcision does not impair sexual function or pleasure. Some authorities regard the failure to offer circumcision as unethical, just as it would be unethical to fail to encourage paediatric vaccination. Since the benefits vastly outweigh the risks, each intervention is in the best interests of the child. In conclusion, Adler's criticisms of the cdc's evidence-based male circumcision policy are flawed scientifically, ethically and legally, and should be dismissed as endangering public health and individual well-being.
... 142 The percentage of circumcised males in those studies was approximately tenfold higher than their recent study. Problems with statistical analyses, inclusion criteria, and other issues in each study were identified by the present authors [143][144][145] and others. [146][147][148][149] Additionally, those earlier studies used the same algorithm to control for ethnicity but, as we have shown in this article, that algorithm failed. ...
... Thus, an alternative explanation for the association observed between circumcision and ASD is that acetaminophen provided coincident or following the procedure may increase the risk of ASD. Others have previously made this same observation [11,12]. ...
Full-text available
Some evidence from the literature suggests that postnatal acetaminophen exposure may be associated with increased risk of autism spectrum disorder (ASD). Using a data set obtained from a previous study that was derived from an Internet-based survey among parents on 1515 children from the US, an adjusted odds ratio (aOR) and gender-specific aORs for doses of postnatal acetaminophen provided before age two were calculated against the outcome of ASD. Separately, parental uncertainty on the number of doses of acetaminophen provided was analyzed. A population attributable fraction (PAF) associated with postnatal acetaminophen exposure before age two for ASD among males was also estimated. Postnatal acetaminophen exposure, measured in doses before age two, was found to be associated with ASD among male children (aOR 1.023, CI 1.005–1.043, p = 0.020*), and parental uncertainty on the number of doses of acetaminophen provided before age two was also found to be associated with ASD. Using this data set, the PAF associated with postnatal acetaminophen was estimated to be about 40% of the risk of ASD among male children in the US. These results suggest the possibility that postnatal acetaminophen may be a significant contributor to the risk of ASD among males in the US.
... That report has been criticized. 41,46,47 Sneppen and Thorup, in particular, found ASD prevalence was 7.2% in uncircumcised Danish boys and suggested Frisch's study suffered from confounding. 41 ...
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Frisch and Earp, opponents of male circumcision, have criticized draft recommendations from the CDC that advocate counseling men and parents of newborn boys in the United States about the benefits and risks of male circumcision. We provide a rebuttal to Frisch and Earp's criticisms and contend that the recommendations are entirely appropriate and merit consideration for policy development.
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We critically evaluate arguments in a recent Journal of Law, Medicine & Ethics article by Svoboda, Adler, and Van Howe disputing the 2012 affirmative infant male circumcision policy recommendations of the American Academy of Pediatrics. We provide detailed evidence in explaining why the extensive claims by these opponents are not supported by the current strong scientific evidence. We furthermore show why their legal and ethical arguments are contradicted by a reasonable interpretation of current U.S. and international law and ethics. After all considerations are taken into account it would be logical to conclude that failure to recommend male circumcision early in infancy may be viewed as akin to failure to recommend childhood vaccination to parents. In each case, parental consent is required and the intervention is not compulsory. Our evaluation leads us to dismiss the arguments by Svoboda et al. Instead, based on the evidence, infant male circumcision is both ethical and lawful.
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Based on converging observations in animal, clinical and ecological studies, we hypothesised a possible impact of ritual circumcision on the subsequent risk of autism spectrum disorder (ASD) in young boys. National, register-based cohort study. Denmark. A total of 342,877 boys born between 1994 and 2003 and followed in the age span 0-9 years between 1994 and 2013. Information about cohort members' ritual circumcisions, confounders and ASD outcomes, as well as two supplementary outcomes, hyperkinetic disorder and asthma, was obtained from national registers. Hazard ratios (HRs) with 95% confidence intervals (CIs) associated with foreskin status were obtained using Cox proportional hazards regression analyses. With a total of 4986 ASD cases, our study showed that regardless of cultural background circumcised boys were more likely than intact boys to develop ASD before age 10 years (HR = 1.46; 95% CI: 1.11-1.93). Risk was particularly high for infantile autism before age five years (HR = 2.06; 95% CI: 1.36-3.13). Circumcised boys in non-Muslim families were also more likely to develop hyperkinetic disorder (HR = 1.81; 95% CI: 1.11-2.96). Associations with asthma were consistently inconspicuous (HR = 0.96; 95% CI: 0.84-1.10). We confirmed our hypothesis that boys who undergo ritual circumcision may run a greater risk of developing ASD. This finding, and the unexpected observation of an increased risk of hyperactivity disorder among circumcised boys in non-Muslim families, need attention, particularly because data limitations most likely rendered our HR estimates conservative. Considering the widespread practice of non-therapeutic circumcision in infancy and childhood around the world, confirmatory studies should be given priority. © The Royal Society of Medicine.
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Background Autism and Autism Spectrum Disorder (ASD) are complex neurodevelopmental disorders. Susceptibility is believed to be the interaction of genetic heritability and environmental factors. The synchronous rises in autism/ASD prevalence and paracetamol (acetaminophen) use, as well as biologic plausibility have led to the hypothesis that paracetamol exposure may increase autism/ASD risk. Methods To explore the relationship of antenatal paracetamol exposure to ASD, population weighted average autism prevalence rates and paracetamol usage rates were compared. To explore the relationship of early neonatal paracetamol exposure to autism/ASD, population weighted average male autism prevalence rates for all available countries and U.S. states were compared to male circumcision rates – a procedure for which paracetamol has been widely prescribed since the mid-1990s. Prevalence studies were extracted from the U.S. Centers for Disease Control and Prevention Summary of Autism/ASD Prevalence Studies database. Maternal paracetamol usage and circumcision rates were identified by searches on Pub Med. Results Using all available country-level data (n = 8) for the period 1984 to 2005, prenatal use of paracetamol was correlated with autism/ASD prevalence (r = 0.80). For studies including boys born after 1995, there was a strong correlation between country-level (n = 9) autism/ASD prevalence in males and a country’s circumcision rate (r = 0.98). A very similar pattern was seen among U.S. states and when comparing the 3 main racial/ethnic groups in the U.S. The country-level correlation between autism/ASD prevalence in males and paracetamol was considerably weaker before 1995 when the drug became widely used during circumcision. Conclusions This ecological analysis identified country-level correlations between indicators of prenatal and perinatal paracetamol exposure and autism/ASD. State level correlation was also identified for the indicator of perinatal paracetamol exposure and autism/ASD. Like all ecological analyses, these data cannot provide strong evidence of causality. However, biologic plausibility is provided by a growing body of experimental and clinical evidence linking paracetamol metabolism to pathways shown to be important in autism and related developmental abnormalities. Taken together, these ecological findings and mechanistic evidence suggest the need for formal study of the role of paracetamol in autism.
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Purpose: Urinary tract infection is common in infant males who are uncircumcised and can lead to renal parenchymal disease of the still growing pediatric kidney. Although the rate of urinary tract infection is highest in the first year of life, the cumulative incidence during the rest of the lifetime is under-recognized, but is expected to be nontrivial. Thus, any intervention that might prevent urinary tract infection would be expected to reduce suffering and medical costs. Materials and methods: We conducted a meta-analysis of 22 studies examining the single risk factor of lack of circumcision, then determined the prevalence and relative risk of urinary tract infection in different age groups (0 to 1, 1 to 16 and older than 16 years). From these data we estimated the lifetime prevalence. Results: For age 0 to 1 year the relative risk was 9.91 (95% CI 7.49-13.1), for age 1 to 16 years RR was 6.56 (95% CI 3.26-13.2) and for older than 16 years it was 3.41-fold (95% CI 0.916-12.7) higher in uncircumcised males. We then calculated that 32.1% (95% CI 15.6-49.8) of uncircumcised males experience a urinary tract infection in their lifetime compared with 8.8% (95% CI 4.15-13.2) of circumcised males (RR 3.65, 95% CI 1.15-11.8). The number needed to treat was 4.29 (95% CI 2.20-27.2). Conclusions: The single risk factor of lack of circumcision confers a 23.3% chance of urinary tract infection during the lifetime. This greatly exceeds the prevalence of circumcision complications (1.5%), which are mostly minor. The potential seriousness of urinary tract infection supports circumcision as a desirable preventive health intervention in infant males.
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Over the past decade, the safety of anesthetic agents in children has been questioned after the discovery that immature animals exposed to anesthesia display apoptotic neurodegeneration and long-term cognitive deficiencies. We examined the association between exposure to anesthesia in children under age 3 and outcomes in language, cognitive function, motor skills, and behavior at age 10. We performed an analysis of the Western Australian Pregnancy Cohort (Raine) Study, which includes 2868 children born from 1989 to 1992. Of 2608 children assessed, 321 were exposed to anesthesia before age 3, and 2287 were unexposed. On average, exposed children had lower scores than their unexposed peers in receptive and expressive language (Clinical Evaluation of Language Fundamentals: Receptive [CELF-R] and Expressive [CELF-E]) and cognition (Colored Progressive Matrices [CPM]). After adjustment for demographic characteristics, exposure to anesthesia was associated with increased risk of disability in language (CELF-R: adjusted risk ratio [aRR], 1.87; 95% confidence interval [CI], 1.20-2.93, CELF-E: aRR, 1.72; 95% CI, 1.12-2.64), and cognition (CPM: aRR, 1.69; 95% CI, 1.13-2.53). An increased aRR for disability in language and cognition persisted even with a single exposure to anesthesia (CELF-R aRR, 2.41; 95% CI, 1.40-4.17, and CPM aRR, 1.73; 95% CI, 1.04-2.88). Our results indicate that the association between anesthesia and neuropsychological outcome may be confined to specific domains. Children in our cohort exposed to anesthesia before age 3 had a higher relative risk of language and abstract reasoning deficits at age 10 than unexposed children.