Infection during pregnancy and offspring autism risk

The paper by Lee and colleagues [1] forms the starting material for today's blog post looking at hospitalisation for infection during pregnancy as potentially being a risk factor for receipt of a subsequent diagnosis for autism in offspring.

"Chaos is what killed the dinosaurs, darling"

Based on data derived from one of those very useful Scandinavian health registries, authors observed "approximately a 30% increase in ASD [autism spectrum disorder] risk associated with any inpatient diagnosis of infection". The strength of this finding is based on the large sample covered for analysis (N=2,371,403) including "24,414 ASD cases". The authors note that their findings "adds to the growing body of evidence, encompassing both animal and human studies, that supports possible immune-mediated mechanisms underlying the etiology of ASD".

Of course we've kinda been here before in research terms. The body of peer-reviewed evidence suggestive of maternal immune activation being potentially linked to offspring autism risk (see here and see here) is growing, specifically with inflammatory processes in mind (see here). And that risk does not seem to just end at a diagnosis of autism neither (see here).

I was quite interested in another observation made by Lee et al when looking at autism with and without learning disability (LD). They note: "In a subsample analysis, infections were associated with greater risk of ASD with intellectual disability than for ASD without intellectual disability". This kinda ties in with the findings from Langridge and colleagues [2] (open-access here) who similarly reported: "In the multivariate analysis no maternal conditions or perinatal factors were associated with an increased risk of ASD without ID [intellectual disability]". I can't readily offer any explanation for these findings aside from reiterating the words of Prof. Gillberg on autism plus [3]: "It is high time that the comorbidities, sometimes even more important than the autism, came back on the diagnostic agenda" as being important.

I have just a few more points to made about the Lee findings and then I'm done. First is the stress on 'infections requiring hospitalisation' in the current paper as potentially being important. I think back to the Atladóttir findings [4] talking about: "little evidence that various types of mild common infectious diseases or febrile episodes during pregnancy were associated with ASD/infantile autism" suggesting that infection severity (or individual response to infection) might be an important variable. The same author in another paper [5]  also reported: "admission to hospital due to maternal viral infection in the first trimester and maternal bacterial infection in the second trimester were found to be associated with diagnosis of ASDs in the offspring" reiterating that "requiring hospitalisation" link.

The paper by Zerbo and colleagues [6] (discussed in a previous post) also adds something with their findings of no general association between infant outcome and maternal influenza during pregnancy but perhaps more to see when it comes to maternal fever during pregnancy. Their observations of antipyretic (fever reducing) use potentially augmenting offspring autism / developmental delay risk adds another layer of complexity, bearing in mind certain antipyretics have themselves come under the 'risk spotlight' (see here).

What readers can perhaps take from this post is that there is a complicated relationship emerging between what happens during the nine months that made us and subsequent child and adult outcomes. In amongst the various factors which might influence child outcomes, our relationship with infection - be it viral, bacterial or parasitic - whilst in-utero might have a role to play in development and seems important to at least some autism. This bearing in mind that post-natal infection might also be an area in need of continued investigation (see here) save any cries of autism universally coming about as a result of issues during the prenatal period.

Oh, and that this area also extends outside of autism too...

Music. The Cardigans and My Favourite Game.

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[1] Lee BK. et al. Maternal hospitalization with infection during pregnancy and risk of autism spectrum disorders. Brain Behav Immun. 2014 Sep 10. pii: S0889-1591(14)00452-8.

[2] Langridge AT. et al. Maternal conditions and perinatal characteristics associated with autism spectrum disorder and intellectual disability. PLoS One. 2013;8(1):e50963.

[3] Gillberg C. Fernell E. Autism Plus Versus Autism Pure. J Autism Dev Disord. 2014 Jun 24.

[4] Atladóttir HÓ. et al. Autism after infection, febrile episodes, and antibiotic use during pregnancy: an exploratory study. Pediatrics. 2012 Dec;130(6):e1447-54.

[5] Atladóttir HÓ. et al. Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. J Autism Dev Disord. 2010 Dec;40(12):1423-30.

[6] Zerbo O. et al. Is maternal influenza or fever during pregnancy associated with autism or developmental delays? Results from the CHARGE (CHildhood Autism Risks from Genetics and Environment) study. J Autism Dev Disord. 2013 Jan;43(1):25-33.

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Lee BK, Magnusson C, Gardner RM, Blomström S, Newschaffer CJ, Burstyn I, Karlsson H, & Dalman C (2014). Maternal hospitalization with infection during pregnancy and risk of autism spectrum disorders. Brain, behavior, and immunity PMID: 25218900