The effect of prenatal supplementation with omega 3 long chain poly- fatty acids unsaturated (n-3 LCPUFA) on childhood allergic disease at six years of age

Abstract

There is general consensus that the remarkable increase in allergic disease over the last 30-40 years is due to environmental influences including lifestyle and diet. Due to a number of factors associated with an industrialised world, the gross imbalance of n-6 (omega 6) and n-3 (omega 3) polyunsaturated fatty acids (PUFA) in our diet is no longer concordant with our genetically determined biology. Data from clinical and animal studies suggest that dietary n-3 LCPUFA in early life may influence immune system development and immune cell function reducing inflammatory responses, however clinically beneficial effects are more conflicting. I conducted a systematic review of the literature including observational studies of increased maternal dietary intake of n-3 PUFA and RCT evidence of prenatal n-3 LCPUFA supplementation on outcomes of allergic disease in the offspring. Whilst limitations of cohort studies are well recognised, the concordance between outcomes from both study designs is noteworthy and suggestive of benefits. The paucity of RCT evidence beyond early childhood however, makes it difficult to draw any strong conclusions regarding the effect prenatal n-3 LCPUFA supplementation. The six year allergy follow up study was a double blind randomised controlled trial designed to investigate the effect of supplementation of women with a fetus at high risk of atopy with 900mg of n-3 LCPUFA or a blended vegetable oil (with no n-3 LCPUFA) on outcomes of allergic disease in the offspring. 668 families were invited to take part in an allergy assessment to determine the incidence of allergic disease symptoms (eczema, wheeze or allergic rhinitis) and sensitisation to determine food and aeroallergen sensitisation. 603 children (90.2% of eligible cohort) completed an allergy assessment at six years of age. Results show that n-3 LCPUFA supplementation in pregnancy does not reduce the overall incidence of IgE-mediated allergic disease at six years of age, 116/367 (31.48%) vs106/336 (31.46%) control, aRR 1.04 (0.82, 1.33), p=0.73. However, secondary outcomes suggest that the intervention reduces the incidence of ‘sensitisation to house dust mite’ and parent reported ‘hayfever ever’, 49/367 (13.42%) vs 68/336 (20.30%), aRR 0.67 (0.44, 1.00), p=0.0495; 81/367 (22.05%) vs 98/336 (29.05%), aRR: 0.77 (0.59, 1.01), p=0.055 respectively. This cohort of children with high hereditary risk of allergy also completed assessment of allergic disease and sensitisation at 1 and 3 years of age. A longitudinal analysis was performed on 1, 3 and 6 year data indicating that there was not enough evidence to conclude that the relative risk of sensitisation (n-3 LCPUFA vs control) changed over time or was associated with any outcomes of allergic disease or sensitisation across all years. There are plausible mechanisms by which increasing maternal dietary n-3 LCPUFA intake may modulate the fetal immune system and subsequent development of allergic disease in infants at risk of atopic disease. Although my results did not show a reduction in overall IgE associated disease at 6 years or impact on longitudinal outcomes (1, 3 and 6 years), they are consistent with previous studies and suggestive of benefits of prenatal n-3 LCPUFA supplementation on certain aspects of allergic disease, namely sensitisation. My results support the necessity to further investigate these outcomes and their relationship to the clinical expression of disease.