Asthma and other wheezing disorders is one of the main causes for health care utilization in childhood with an increasing prevalence in westernized countries in recent decades. Concomitantly, the use of vegetable oils and grain feeding of livestock has resulted in an increase in the intake of n-6 polyunsaturated fatty acids (PUFA) and a decrease in n-3 PUFA, especially the long chain PUFA (LCPUFA) eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA) particularly found in fish and this has been hypothesized to be a potential cause of childhood asthma. LCPUFA influence immune regulation and some observational studies have reported an association between n-3 LCPUFA deprived diet during pregnancy and increased risk of asthma and related disorders in the offspring. Randomized controlled trials (RCTs) of n-3 LCPUFA supplementation to pregnant women have generally been under-powered and shown ambiguous results. We recently conducted a double-blind RCT of n-3 LCPUFA supplementation during third trimester of pregnancy in an unselected group of 743 pregnant Danish women from the COPSAC2010 cohort showing that n-3 LCPUFA supplementation in pregnancy was associated with reduced risk of asthma in the offspring (Bisgaard et al. NEJM 2016). Specifically, the preventive effect of supplementation was highest in children of mothers with intake and blood-levels of EPA+DHA prior to the intervention and with FADS gene risk variants (minor allele at rs1535). A similar tendency was seen for allergic rhinitis.
Variants in the maternal fatty acid desaturase (FADS) gene region (rs1535 and closely correlated SNPs) have been reported to be associated with EPA and DHA levels during pregnancy. Child genotype has been shown to have smaller but independent effect on cord blood levels of EPA and DHA. This gene variation therefore provide an opportunity to study genetically the hypothesis that prenatal n-3 LCPUFA levels affect the risk of asthma in the offspring. This would support that supplementation with n-3 LCPUFA during pregnancy could prevent asthma in the offspring and therefore could have large importance for asthma prevention.