Caesarean section births and autism risk?

It was a familiar story. Big media headlines such as: Caesarean sections 'may increase risk of autism' appearing all over, but when it came to finding the study behind the headlines, the publishing journal seemed to be trailing a little way behind. We've been in a similar situation before.

"As the flames rose to her Roman nose"

Anyhow, the paper by Eileen Curran and colleagues [1] (open-access) has finally made it to the research table and hence is fodder for today's ramblings with the suggestion that the way we make our grand entrance into the world might correlate with some heightened risk for autism spectrum disorder (ASD).

I have to say that I was initially quite interested in the Curran findings for quite a few reasons. Primary among them is some curiosity I have about the gut microbiota in relation to quite a few states and diagnoses (see here) and how our mode of entry into the world can seemingly impact on our first exposure to the bacterial passengers which eventually call us home. It is perhaps one of the lesser known observations, that the voyage down our dear mothers birth canal is also a great meet-and-greet opportunity for baby and bacteria. For those who don't get to experience such wonders, there is a suggestion that different types of bacteria might make friends which are then 'programmed' to be accepted by our developing immune systems [2] with onwards possible significance for future health and wellbeing. That being said, there is still a way to go to understanding such a relationship more thoroughly despite some intriguing results specifically with autism and the gut microbiome in mind (see here). I might also add that some of the authors on the Curran paper seemingly have some interest in the whole gut bacteria - behaviour relationship as per another recent paper [3].

The Curran paper is a systematic review of the literature which looked at: "mode of delivery on autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD)". They concluded that: "Thirteen studies reported an adjusted estimate for CS-ASD [Caesarean section-ASD], producing a pooled odds ratio (OR) of 1.23 (95% CI: 1.07, 1.40)". Said studies were analysed up to February 2014. The population attributable fraction calculated by authors implied that: "5.36% of cases of ASD may be attributable to delivery by CS assuming the observed association is causal".

The lead author is rightly cautious about their findings, as per some other comment in the media: “Parents should be reassured that the overall risk of a child developing ASD (Autism Spectrum Disorder) is very small and that Caesarean section is largely a very safe procedure and when medically indicated, it can be lifesaving,”. I wouldn't disagree with those sentiments allowing for the fact that (a) a fair proportion of deliveries these days are by C-section, and (b) not every child diagnosed with autism is delivered via C-section.

That being said, there does seem to be more to do in this area of science. Subsequent studies published after the cut-off point set by Curran have reported C-sections as a 'risk factor' for autism. The paper by Salhia and colleagues [4] for example, looking at the epidemiology of autism in [some] Arab Gulf countries found as much, alongside some other quite frequently reported variables potentially influencing autism risk (e.g. advanced maternal and paternal age).

I'm going to drop in a few additional papers and then I'm done. Chien and colleagues [5] also talked about C-sections as a risk factor for autism but with the added twist that the use of a general anaesthetic during said procedure might be implicated in any relationship. You might scoff at the suggestion that anaesthetic has anything to do with autism but before you do, perhaps have a read through the paper by DiMaggio and colleagues [6] first and slightly more speculatively, the paper by Johnson and colleagues [7]. The study by Chudal and colleagues [8] - mentioned by Curren et al - looking at various perinatal factors in the context of bipolar disorder is also worthwhile introducing bearing in mind that interest in such comorbidity is increasing in the context of some autism (see here). As with many other variables 'correlated' to autism risk, to shut the door on any association with comorbidity outside of just the diagnosis of autism is foolhardy.

Irrespective of your opinion about whether C-sections might be linked to autism risk and the other possible reasoning behind said suggestion [9], the Curran paper joins a growing list of variables potentially associated with autism. Systematic reviews and meta-analyses are consolidating quite a bit of this data, although as always the heterogeneity covered under the label of autism and the important issue of comorbidity need to be kept in mind. As with the growing idea that many small genetic issues might cumulatively be linked to [some] autism further compounded by more recent data [10] (see here for some media), so one might assume that multiple small contributions from the 'environment' might likewise also influence offspring risk of autism too. Determining how and when these genetic and environmental variables come together seems to be to be the next logical step...

Music to close: The Specials and Ghost Town. Have a spooky day!

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[1] Curran EA. et al. Research Review: Birth by Caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Journal of Child Psychology and Psychiatry. 2014. October 27.

[2] Weng M. & Walker WA. The role of gut microbiota in programming the immune phenotype. J Dev Orig Health Dis. 2013 Jun;4(3):203-14.

[3] Stilling RM. et al. Friends with social benefits: host-microbe interactions as a driver of brain evolution and development? Front. Cell. Infect. Microbiol. 2014. October 29.

[4] Salhia HO. et al. Systemic review of the epidemiology of autism in Arab Gulf countries. Neurosciences (Riyadh). 2014 Oct;19(4):291-6.

[5] Chien LN. et al. Risk of Autism Associated With General Anesthesia During Cesarean Delivery: A Population-Based Birth-Cohort Analysis. J Autism Dev Disord. 2014 Sep 26.

[6] 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.

[7] Johnson B. et al. Fibromyalgia, autism, and opioid addiction as natural and induced disorders of the endogenous opioid hormonal system. Discov Med. 2014 Oct;18(99):209-20.

[8] Chudal R. et al. Perinatal factors and the risk of bipolar disorder in Finland. J Affect Disord. 2014 Feb;155:75-80.

[9] Gialloreti LE. et al. Are caesarean sections, induced labor and oxytocin regulation linked to Autism Spectrum Disorders? Med Hypotheses. 2014 Jun;82(6):713-8.

[10] Iossifov I. et al. The contribution of de novo coding mutations to autism spectrum disorder Nature. 2014. October 29.

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Curran EA, O'Neill SM, Cryan JF, Kenny LC, Dinan TG, Khashan AS, & Kearney PM (2014). Research Review: Birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Journal of child psychology and psychiatry, and allied disciplines PMID: 25348074