Autism risk and interpregnancy interval

Pregnancy issues and adverse birth factors 'associated' with the development of autism in offspring is a topic which has cropped up more than once on this blog, as autism research strives to identify as many possible 'risk' factors potentially linked to symptom onset. Lots of different birth-related variables have been analysed and put forward as potential candidates related to risk (see this post) ranging from birth weight (see here) to birth order (see here) and even season of conception/birth (see here).

Let me out... @ Wikipedia  

That's not to say however that anything concrete in terms of generalised offspring risk of autism has emerged from these various lines of research inquiry. Indeed, as per the study by Schieve and colleagues* (which I've already blogged about) hinted, many of these factors may be contributory but not necessarily 'causative' of autism when looked at on a population scale. This bearing in mind that I've not introduced the various 'exposure' events during pregnancy which have also been linked to offspring autism risk (e.g. the emerging valproate story) and the idea that population risk does not necessarily always translate into personal circumstances and risk.

Another factor which has seen some research action is the idea that having children in close temporal succession to one and another - a short interpregnancy interval - might also elevate the risk of the second child presenting with autism. The paper by Cheslack-Postava and colleagues** (full-text) hinted at this effect as per their conclusion: "children born after shorter intervals between pregnancies are at increased risk of developing autism". I note that Dr Emily Deans over at Evolutionary Psychiatry carried some discussion on this paper too (see here).

The more recent paper by Nina Gunnes and colleagues*** adds to the literature on this topic; indeed coming to pretty much the same conclusion: "interpregnancy intervals shorter than 1 year were associated with increased risk of autistic disorder in the second-born child". Based on yet more analysis out of Norway (although I am unsure whether this was a MoBa study or not), researchers looked at the records of several thousand sibling pairs in order to identify the length of the interpregnancy interval (IPI) and whether autism was mentioned in the records of second-born children. Their conclusion about short IPI and an elevated risk of autism in second-born children seemed to be particularly pertinent to those children born 9 months after their sibling compared with those born 3 years or later after their sibling.

A few points are worthy of mention. The very discerning readers out there might have already spotted a couple of familiar names attached to the Gunnes paper authorship in the form of Mady Hornig and Ian Lipkin (see this quite recent post).

I note also the authors suggest that a "depletion of micronutrients" might have something to do with the explanation for the short IPI-autism association, which carries hints of the late David Barker's hypothesis (see here) and is pretty much in line with what Dr Deans previously mentioned. Indeed, to reiterate her discussion about baby 'sucking out' whatever nutrients it needs from its host (i.e. mum) I can remember similar words being told when my/our brood were due for an appearance. With all the current fascination on things like folic acid and autism (see here and here), one might very easily say that there is a possible link to be had there, bearing in mind Gunnes and colleagues did not assay for or report on maternal or offspring folic acid levels at any point during their study.

If also I had to play devil's advocate on such 'association' research I might point out that looking at the IPI alone and knowing relatively little about the family or offspring in terms of their lives is still methodologically problematic. We don't for example know about any medical or psychiatric familial history which might also be an important modifier of offspring risk. I assume the authors already controlled for whether sibling number one had a formal diagnosis of autism (as per the autism recurrence data previously discussed), but did they for example, ask about the potential presence of sub-clinical signs and symptoms associated with something like the broader autism phenotype for example? Were they also able to comment on any additional siblings after child number two and the elevated risk or not for them presenting on the autism spectrum either alone or as a function of IPI?

Then there's the volume of research suggesting that a short IPI might also increase the risk of reduced birth weight**** or the risk of preterm birth***** which I assume have been controlled for, but still one wonders about their impact on the presentation of offspring autism and any wider links (see here). I might also draw readers' attention to an interesting correspondence from Downs & Jonas****** (full-text) with regards to research suggesting a link between short IPI and risk of offspring schizophrenia. In short(!), one has to be careful of making too much of such association data at the current time.

That being said, I don't want to take anything away from the Gunnes study and results. It was a well-powered study and they got what they got. Their data also add to the various other information suggesting that when it comes to having children, mums (and dads) are advised to give themselves a bit of breather between kids.

Some music to finish. How about Robbie & Kylie?

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* Schieve LA. et al. Have secular changes in perinatal risk factors contributed to the recent autism prevalence increase? Development and application of a mathematical assessment model. Ann Epidemiol. 2011 Dec;21(12):930-45.

** Cheslack-Postava K. et al. Closely spaced pregnancies are associated with increased odds of autism in California sibling births. Pediatrics. 2011 Feb;127(2):246-53.

*** Gunnes N. et al. Interpregnancy Interval and Risk of Autistic Disorder. Epidemiology. 2013 Sep 16.

**** Smits LJ. et al. The association between interpregnancy interval and birth weight: what is the role of maternal polyunsaturated fatty acid status? BMC Pregnancy Childbirth. 2013 Jan 25;13:23.

***** De Franco EA. et al. A short interpregnancy interval is a risk factor for preterm birth and its recurrence. Am J Obstet Gynecol. 2007 Sep;197(3):264.e1-6.

****** Downs JM. & Jonas S. Short inter-pregnancy interval and schizophrenia: overestimating the risk. Br J Psychiatry. 2012; 200: 160.

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Gunnes N, Surén P, Bresnahan M, Hornig M, Lie KK, Lipkin WI, Magnus P, Nilsen RM, Reichborn-Kjennerud T, Schjølberg S, Susser ES, Oyen AS, & Stoltenberg C (2013). Interpregnancy Interval and Risk of Autistic Disorder. Epidemiology (Cambridge, Mass.) PMID: 24045716