Dad's obesity and risk of offspring autism

In this post I'm talking about the paper by Pål Surén and colleagues [1] (open-access here) and their suggestion that "paternal obesity is an independent risk factor for ASDs [autism spectrum disorders] in children". I do so not with the intent of stigmatising parents and specifically parents with weight issues, which tend to be present for many more reasons than just food and exercise (see here), but merely to highlight how parental physical health may show some relationship to offspring cognitive and developmental progress. Indeed, the findings from Surén et al are to viewed in the context of some other related research in this area (see here).

By the water @ Renoir @ Wikipedia 

Quite a nice summary of the Surén work can be found here and here. The basics are: MoBa (see here), questioning parents particularly fathers about their physical health while their partner was pregnant, following up offspring and their subsequent development - specifically whether they had received a diagnosis of "autistic disorder", Asperger syndrome or pervasive developmental disorder not otherwise specified (PDD-NOS).

The results: well, the rate of autism reported (0.45%) was interesting. Certainly compared to other prevalence estimates we've been hearing about recently, quite a different figure was noted altogether (see here) allowing for age differences in case ascertainment. Then to the primary findings: "The risk of autistic disorder was 0.27% (25 of 9267) in children of obese fathers and 0.14% (59 of 41 603) in children of fathers with normal weight (BMI <25), generating an adjusted OR of 1.73 (95% CI: 1.07–2.82)". And with regards to Asperger syndrome: "The risk was 0.38% (18 of 4761) in children of obese fathers and 0.18% (42 of 22 736) in children of normal-weight fathers, and the adjusted OR was 2.01 (95% CI: 1.13–3.57)". Ergo, potentially double the risk of offspring autism when fathers were categorised as overweight or obese based on body mass index (BMI).

It goes without saying that the suggestion of a link between paternal weight and offspring risk of autism is by no means proved by this latest research. Think correlation not being the same as causation as one reason why we should not just accept the results of this work at face value irrespective of how enthusiastic researchers might be about their data and what they were able to control for as potential interfering variables. That also BMI has it's 'issues' when it comes to defining healthy weight is another reason for caution where muscle mass for example, is not accounted for in such a simplistic formula.

But all that doesn't mean the results are not interesting...

In recent times I've noticed quite a bit more research looking at the potential role of father's health and wellbeing on offspring development treading in the footsteps of how ageing might play a role. Take for example the recent opinion piece in Nature titled 'Sins of the father' which introduces another side to the Surén results: the science of epigenetics. The paper by Lambrot and colleagues [2] is as good an example as any on how a father's nutritional status with folate in mind, might impact on offspring health. I'm not asking you to take this as fact; merely that the focus on maternal nutrition and offspring outcome might not be the only important variable in any relationship.

Harking back to another paper by the Surén research group (including Drs Hornig and Lipkin) [3] reveals nutrition to be something that the authors had probably thought about with the current results in mind. On that occasion, the focus was on the elevated risk of autism in cases of a short inter-pregnancy interval (see here) and mention of a "depletion of micronutrients" as a possible factor. Shadows indeed of the work of the late David Barker and his foetal programming hypothesis.

I do believe there are more investigation to be done building on the Surén results. I've already made mention of folate in the father-offspring relationship given the link between the folate cycle and the availability of methyl groups for the process of DNA methylation, an important epigenetic process. One might also wonder about the body of work looking at more traditional genetic issues in the genes involved in that cycle such as everyone's favourite Scrabble gene and enzyme:  Methylenetetrahydrofolate reductase (MTHFR) and its growing links with some autism (see here). Could issues with MTHFR present in fathers confer susceptibility to offspring autism, or weight issues pertinent to an elevated risk via epigenetic mechanisms? That being said, I'm sure that any relationship is going to be complicated and not necessarily relevant to every child diagnosed with an autism spectrum condition.

Music to close. In memory of author Sue Townsend and her Adrian Mole series of books... Profoundly in Love with Pandora.

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[1] Surén P. et al. Parental Obesity and Risk of Autism Spectrum Disorder. Pediatrics. 2014. April 7.

[2] Lambrot R. et al. Low paternal dietary folate alters the mouse sperm epigenome and is associated with negative pregnancy outcomes. Nature Comms. 2013; 4: 2889.

[3] Gunnes N. et al. Interpregnancy interval and risk of autistic disorder. Epidemiology. 2013 Nov;24(6):906-12.

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Suren, P., Gunnes, N., Roth, C., Bresnahan, M., Hornig, M., Hirtz, D., Lie, K., Lipkin, W., Magnus, P., Reichborn-Kjennerud, T., Schjolberg, S., Susser, E., Oyen, A., Smith, G., & Stoltenberg, C. (2014). Parental Obesity and Risk of Autism Spectrum Disorder PEDIATRICS DOI: 10.1542/peds.2013-3664