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Re: The effect of introducing fish may be confounded by eczema before the age of 6 months

Alm et al. reported an interesting article stating that introducing fish before 9 months of age having beneficial effect on eczema in infancy.

However, as we know, atopic dermatitis usually develops in the first several months after birth.(1) Parents might delay the introduction of fish when they saw their babies suffering from eczema. Thus, those infants with eczema might receive fish later in comparison with healthy infants. The causal relationship might be reversed when using questionnaire result at age of 1 year as the outcome measurement.

The definition of a confounding factor is: first, it should be a risk factor to the outcome; second, it has effect on the exposure distribution; third, it should not be an intermediate factor. Eczema before 6 months of age is a risk factor for eczema at one year old. It very possibly has effect on the timing of introducing fish. It is obviously not an intermediate factor between introducing fish and eczema at one year old. So, it is very possibly a significant confounding factor in this cohort.

Because a questionnaire has been obtained at the age of 6 months, I would suggest the authors to control eczema before 6 months old using stratified analysis or a multiple logistic regression model.

References:

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Re: Reasons supporting that a protective effect of early fish introduction is real

Sir,

We understand the concerns of doctors Lin and Fu about reverse causation regarding the protective effect of fish on eczema at one year of age. We cannot, of course, be sure that reverse causation does not contribute to our results, but there are reasons that speak in favour of a real effect.

Firstly, we found no correlation between time of onset of the eczema and age at introduction of fish.

Secondly, when excluding infants with food-induced eczema, there was still a protective effect, as was the case when excluding infants with food allergy.

Thirdly, when excluding infants with onset of eczema before 4 months of age, there was still a protective effect in infants with later onset of eczema. Also, the protective effect was equal between infants with and without atopic heredity.

Furthermore, we are not the only group that has reported such effects. In the BAMSE study (1), Kull et al. found that fish consumption during the first year of life was protective against allergic disease at 4 years. In a Norwegian study (1), Øien et al. found that fish reduced the risk of having allergic disease at 2 years. Both studies excluded children with disease before one year of age to avoid reverse causation.

We are at this moment analysing the data from our follow-up when the children are 4.5 years old, and will hopefully be able to address the question further.

References:

1. Kull I, Bergström A, Lilja G, Pershagen G, Wickman M. Fish consumption during the first year of life and development of allergic diseases during childhood. Allergy. 2006;61:1009-15.

2. Øien T, Storrø O, Johnsen R. Fish and cod liver oil consumption during pregnancy and the first year of life and allergic diseases at 2 years of age. A prospective birth cohort study. XXVII Congress of the European Academy of Allergology and Clinical Immunology, Barcelona. [Abstract]. 2008.

Yours sincerely,

Bernt Alm MD PhD, Nils Åberg MD PhD, Laslo Erdes MD, Per Möllborg MD, Rolf Pettersson MD, Gunnar Norvenius MD PhD, Emma Goksör MD, and Göran Wennergren MD PhD.