Allergic disease and neurodevelopment

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The publication of the recent 'game-changer' by Sapone and colleagues* (full-text) defining a spectrum of gluten-related disorders outside of just coeliac disease got me thinking again about allergy, its definition and relationship to lots of different things.

Allergy has been discussed previously on this blog and in particular, how the tangled mess that is allergy and intolerance might link into some cases of autism spectrum conditions. The net result of that post was to say that based on the cumulative evidence so far, classical allergy, as defined by the presence of type 1 immediate IgE hypersensitivity, is probably not going to be one of the more important mechanism in relation to autism in general. I say this acknowledging that IgE-mediated allergy is nevertheless present in cases of autism; as per the ethos on this blog, autism is seemingly not protective of other comorbidity.

Another interesting paper hit my radar recently by Meldrum and colleagues**. Interesting because it suggests that allergic disease in early infancy might correlate with certain findings in relation to neurodevelopment. I was fortunate to receive a full-text copy of the paper and there are a quite a few interesting findings to note.

The summary:

• Four hundred and twenty term infants from mothers with confirmed allergic disease made up the initial study population as part of a larger randomised trial looking at the effects of high dose DHA-enriched fish oil supplements compared with a placebo oil.
• A 12-month immunology assessment was undertaken consisting of skin prick testing to a range of different allergens alongside parental questionnaires and clinical assessment by a paediatric immunologist. Various operational criteria were used to determine atopic diseases such as eczema, asthma and allergic rhinoconjunctivitis.
• An 18-month neurodevelopmental assessment was undertaken consisting of 3 schedules: (i) the Bayley Scales of Infant Toddler Development (BSID-III), (ii) the Achenbach Child Behaviour Checklist (CBCL) and (iii) the Macarthur-Bates Communicative Development Inventory (MCDI). The CBCL in particular looks for signs of various developmental conditions including ADHD and pervasive developmental issues.
• Taking into account various confounding variables including whether fish oil supplementation might have had any bearing on results, various mixed data were available based on the tests and testing occasions. So out of 323 infants, around 40% (129/323) presented with confirmed eczema and 13% with an IgE-mediated food allergy (44/323). These rates are high because mum's allergic history deemed offspring allergy risk to be elevated.
• When comparing those with any allergic disease vs. no allergic disease on the various neurodevelopmental measures undertaken at 18 months, composite scores of motor behaviour on the the BSID-III were negatively associated with allergic disease present at 12 months (p=0.003) remaining significant even after adjustment for confounders (p=0.016). More specifically, those with eczema showed significantly lower gross motor skill scores compared with no eczema to be present (adjusted, p=0.001). There were other interesting trends but nothing that really reached statistical significance. When it came to correlation between allergy status and the DSM-orientated scores on the CBCL, nothing turned up as significantly different although there was some link suggested between non IgE-mediated food allergies and internalising/externalising behaviours.

As per the author discussions, the key point to this work was the suggested link between allergic disease and composite motor skill scores and the possibility of a neuro-immune interaction. I know to some this might seem like a coincidental relationship given the multitude of other factors which might also show association. To others however this might make perfect sense; that the immune system and various neurological systems might actually 'talk' to, or 'modify', each other through biological mechanisms such as inflammation and even more psychological aspects such as stress. I think about the report of fever affecting the presentation of some cases of autism and the proposed association between inflammation and alexithymia (definition here) as possible examples of this complicated relationship in an area which is crying out for more study.

I finish this post with an ode to the Irish Rover and it's crew including Barney McGee, Johnny McGirr and the skipper Mick McCann (RIP poor old dog). Farewell also to Niall Quinn and the great service he has done to the city of Sunderland particularly to local children's hospital services - "Go raibh maith agat".

* Sapone A. et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Medicine. February 2012.
DOI: 10.1186/1741-7015-10-13

** Meldrum SJ. et al. Allergic disease in the first year of life is associated with differences in subsequent neurodevelopment and behaviour. Early Human Development. 2012
DOI: 10.1016/j.earlhumdev.2011.12.032