Almqvist C, Garden F, Xuan W, Mihrshahi S, Leeder SR, Oddy W et al.. Omega-3 and omega-6 fatty acid exposure from early life does not affect atopy and asthma at age 5 years. J Allergy Clin Immunol 119, 1438-1444
The Childhood Asthma Prevention Study was a randomized controlled trial conducted in children with a family history of asthma in whom omega-3 fatty acid supplementation and restriction of dietary omega-6 fatty acids did not prevent asthma, eczema, or atopy at age 5 years.
We sought to examine the relation of all measures of omega-3 and omega-6 polyunsaturated fatty acids with outcomes at age 5 years in the whole birth cohort, regardless of randomization group.
Plasma fatty acids were measured at 18 months, 3 years, and 5 years. Compliance with the fatty acid supplements was estimated every 6 months. Dietary intake was assessed at 18 months by means of weighed-food record and at 3 years by means of food-frequency questionnaire. At age 5 years, 516 children were examined for wheeze and eczema (questionnaire) and atopy (skin prick tests, n = 488). Multiple logistic regression was used to evaluate associations between exposures and outcomes.
Plasma levels of omega-3 or omega-6 fatty acids were not associated with wheeze, eczema, or atopy at age 5 years (P = .11-.96). Overall, fatty acid exposure, measured as plasma levels, dietary intake, and compliance with supplements, was not associated with any respiratory or allergic outcomes (P = .35-.59).
This observational analysis of the cohort, using the full range of observed variation in omega-3 and omega-6 fatty acid exposure, supports the negative findings of the randomized controlled trial.
Modification of dietary polyunsaturated fatty acids in early childhood is not helpful in preventing atopy and asthma.
"Several studies have shown an association between offspring asthma and low socio-economic status50,51, high maternal BMI52,53, maternal smoking during pregnancy14,54, maternal asthma55,56, maternal intake of paracetamol57,58, exposure to antibiotics 59, maternal stress during pregnancy 60, maternal intake of vitamin D 61, vitamin E22,62, folic acid63,64, and omega-3 polyunsaturated fatty acids65,66 during pregnancy and mode of delivery 67–69. Twin studies, however, indicate that some of these exposures are rather confounders, since twins share maternal factors but can still differ in size and incidence of asthma/atopic disease 35 (Fig. 1A). "
[Show abstract][Hide abstract] ABSTRACT: Early genetic and environmental factors have been discussed as potential causes for the high prevalence of asthma and allergic disease in the western world, and knowledge on fetal growth and its consequence on future health and disease development is emerging.
This review article is an attempt to summarize research on fetal growth and risk of asthma and allergic disease. Current knowledge and novel findings will be reviewed and open research questions identified, to give basic scientists, immunologists and clinicians an overview of an emerging research field.
PubMed-search on pre-defined terms and cross-references.
Several studies have shown a correlation between low birth weight and/or gestational age and asthma and high birth weight and/or gestational age and atopy. The exact mechanism is not yet clear but both environmental and genetic factors seem to contribute to fetal growth. Some of these factors are confounders that can be adjusted for, and twin studies have been very helpful in this context. Suggested mechanisms behind fetal growth are often linked to the feto-maternal circulation, including the development of placenta and umbilical cord. However, the causal link between fetal growth restriction and subsequent asthma and allergic disease remains unexplained. New research regarding the catch-up growth following growth restriction has posited an alternative theory that diseases later on in life result from rapid catch-up growth rather than intrauterine growth restriction per se. Several studies have found a correlation between a rapid weight gain after birth and development of asthma or wheezing in childhood.
Asthma and allergic disease are multifactorial. Several mechanisms seem to influence their development. Additional studies are needed before we fully understand the causal links between fetal growth and development of asthma and allergic diseases.
"Maternal fish oil supplementation in pregnancy has been shown to alter neonatal T-cell cytokine production  and to reduce asthma risk in the offspring . However, supplementation of infants with fish oil seems not to reduce allergic sensitisation or asthma  , although studies of asthma-related outcomes in older children are equivocal  . As allergic sensitisation occurs early in life, exposures at this time are most likely to influence immune development. "
[Show abstract][Hide abstract] ABSTRACT: Variation in exposure to polyunsaturated fatty acids (PUFAs) might influence the development of atopy, asthma, and wheeze. This study aimed to determine whether differences in PUFA concentrations in maternal plasma phosphatidylcholine are associated with the risk of childhood wheeze or atopy. For 865 term-born children, we measured phosphatidylcholine fatty acid composition in maternal plasma collected at 34 weeks' gestation. Wheezing was classified using questionnaires at 6, 12, 24, and 36 months and 6 years. At age of 6 years, the children underwent skin prick testing, fractional exhaled nitric oxide (FENO) measurement, and spirometry. Maternal n-6 fatty acids and the ratio of n-3 to n-6 fatty acids were not associated with childhood wheeze. However, higher maternal eicosapentaenoic acid, docosahexaenoic acid, and total n-3 fatty acids were associated with reduced risk of non-atopic persistent/late wheeze (RR 0.57, 0.67 and 0.69, resp. P = 0.01, 0.015, and 0.021, resp.). Maternal arachidonic acid was positively associated with FENO (P = 0.024). A higher ratio of linoleic acid to its unsaturated metabolic products was associated with reduced risk of skin sensitisation (RR 0.82, P = 0.013). These associations provide some support for the hypothesis that variation in exposure to n-6 and n-3 fatty acids during pregnancy influences the risk of childhood wheeze and atopy.
"On the other hand, a study on 706 infants in Australia demonstrated that high-dose omega-3 PUFAs supplementation of 900 mg/day in pregnancy did not reduce the overall incidence of immunoglobulin E (IgE) associated food allergy in the first 12 months of life, although omega-3 PUFAs supplementation lowered the incidence of atopic eczema and egg sensitization . Fish oil supplementation during infancy or childhood has also shown to result in higher omega-3 PUFAs status in infants or children and that fish oil provision may be associated with immunologic changes in the blood [35–43]. However, it is not clear whether these are of clinical significance and if these changes persist as other factors come into play. "
[Show abstract][Hide abstract] ABSTRACT: Maternal nutrition has critical effects on the developing structures and functions of the fetus. Malnutrition during pregnancy can result in low birth weight and small for gestational age babies, increase risk for infection, and impact the immune system. Long-chain polyunsaturated fatty acids (PUFAs) have been reported to have immunomodulatory effects. Decreased consumption of omega-6 PUFAs, in favor of more anti-inflammatory omega-3 PUFAs in modern diets, has demonstrated the potential protective role of omega-3 PUFAs in allergic and respiratory diseases. In this paper, we examine the role of PUFAs consumption during pregnancy and early childhood and its influence on allergy and respiratory diseases. PUFAs act via several mechanisms to modulate immune function. Omega-3 PUFAs may alter the T helper (Th) cell balance by inhibiting cytokine production which in turn inhibits immunoglobulin E synthesis and Th type 2 cell differentiation. PUFAs may further modify cellular membrane, induce eicosanoid metabolism, and alter gene expression. These studies indicate the benefits of omega-3 PUFAs supplementation. Nevertheless, further investigations are warranted to assess the long-term effects of omega-3 PUFAs in preventing other immune-mediated diseases, as well as its effects on the later immunodefense and health status during early growth and development.
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