Monday, 12 January 2015

Ritual circumcision and risk of autism

A quote to begin: "We confirmed our hypothesis that boys who undergo ritual circumcision may run a greater risk of developing ASD [autism spectrum disorder]."
"Objetos dispersos" de Xulio Formoso 2008

That was the rather surprising finding reported by Morten Frisch & Jacob Simonsen [1] (open-access) following their register-based cohort study based in Denmark. Some of the media following this paper can be seen here.

I'll be honest with you and say that my brow furrowed somewhat upon first reading about this paper. Of all the correlations associated with 'risk of autism' this has to be one of the more unusual (aside that is from meat consumption perhaps). That brow furrowing however softened as I read the study and realised that (a) the source data for the 'correlation' relied on one of those ever-so interesting Scandinavian population databases that have suggested quite a few important factors might be linked to autism (see here and see here), and (b) the authors make mention of the accumulating data looking at certain types of pain relief - yes, you paracetamol - as potentially being something requiring further investigation with regards to autism and other neurodevelopmental risks (see here).

Anyhow, the Frisch/Simonsen paper is open-access but as always, a few pointers...

  • The rationale for the study seems to stem from "recent animal findings linking a single painful injury to lifelong deficits in stress response" and data from the paper by Bauer & Kriebel [2] (open-access) suggesting "that with each 10% increase in a population’s neonatal circumcision rate, the estimated prevalence of ASD increased significantly by 2.01 per 1000 boys."
  • Based on a cohort of over 340,000 boys born and 'tagged' in the Danish healthcare system between 1994 and 2003, the authors located just over 5000 boys "diagnosed with ASD before their 10th birthday". Ritual circumcision - that is circumcision with a specific religious significance - is coded in Denmark, whether carried out in a state hospital or at a private clinic (subsidised by the state healthcare system). Sources of those codings were tracked. Out of a total of 3347 circumcisions (in the entire cohort) the authors found 57 boys with ASD included in that category. 
  • Results: after various statistical procedures and correction for confounding variables including cultural background and birth and perinatal characteristics, the authors concluded: "Ritual circumcision among Danish boys is linked to an overall 46–62% increase in ASD risk in the first 10 years of life". Further: "More strikingly, risk was 80–83% increased in the first 0–4 years of life, an increase that was restricted to infantile autism." At the same time, there was no significant link between circumcision and "risk of hyperkinetic disorder" nor risk of asthma.
  • The authors offer some 'significant' discussion about the limitations of their findings including the possibility that circumcision rates were under-estimated: "Muslim authorities in Denmark explained to the National Board of Health that Muslim circumcisions are often made by private practitioners in their clinics or in the boys’ homes." They also go on quite a bit in the paper and in the media reports on the paper about how the early life pain/stress of circumcision somehow might translate into an increased risk for autism. I'd tend to agree however with an external commentator talking about the study who said: "I have some issues with the premise in that their speculations regarding early pain as a cause of autism are, to say the least, highly speculative."

These are interesting findings albeit observational. Correlation is not the same as causation is also a term which should be reiterated when it comes to such data but there are some potentially important gems of information included in the Frisch/Bauer study. Capitalising on the idea that modern circumcision (the practice itself being around for quite a while) normally involves the use of pain relief following surgical anaesthetic, I want to emphasise something the authors said about this: "Unfortunately, we had no data available on analgesics or possible local anaesthetics used during ritual circumcisions in our cohort, so we were unable to address the paracetamol hypothesis directly."

I'm not necessarily saying that there is a connection between anaesthetics and autism, even though other data has hinted that there may be more to see [3]. On the strength of that study by DiMaggio and colleagues for example, and their suggestion of an increasing risk of "developmental or behavioral disorders" it would be interesting to see how many more times anaesthesia was used in the circumcised autism group vs. other groupings and whether 'the dose [really does] make(s) the poison'.

I've already mentioned pain relief as being something already on the autism/neurodevelopmental research radar insofar as the growing interest into how something like prenatal paracetamol (acetaminophen) exposure might 'correlate' with various offspring outcomes. Although stepping onto even more contentious autism research ground, the idea that post-vaccination paracetamol use is potentially linked to cases of autism [4] offers something of a template for further study in this area.

I'm a little unsure how to end this post bearing in mind my blogging caveats about not giving anything that looks, sounds or smells like medical or clinical advice. I appreciate that this study might not be particularly well received by religious groups who undertake ritual circumcision, or to others, might just seem like a bit of daft 'correlation is not causation' autism research. I'd however be minded to suggest that there could be more research to see and do in this area when brows are a little less furrowed...

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[1] Frisch M. & Simonsen J. Ritual circumcision and risk of autism spectrum disorder in 0- to 9-year-old boys: national cohort study in Denmark. JRSM. 2015. 8 January.

[2] Bauer AZ. & Kriebel D. Prenatal and perinatal analgesic exposure and autism: an ecological link. Environ Health. 2013 May 9;12:41.

[3] DiMaggio C. et al. Early childhood exposure to anesthesia and risk of developmental and behavioral disorders in a sibling birth cohort. Anesth Analg. 2011 Nov;113(5):1143-51.

[4] Schultz ST. et al. Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: the results of a parent survey. Autism. 2008 May;12(3):293-307.

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ResearchBlogging.org Frisch, M., & Simonsen, J. (2015). Ritual circumcision and risk of autism spectrum disorder in 0- to 9-year-old boys: national cohort study in Denmark Journal of the Royal Society of Medicine DOI: 10.1177/0141076814565942