Peanut Allergy Prevention Should Be Starting During Mother Pregnancy

Recently, UK Department of Health has circulated advice aimed at reducing the development of peanut allergy. The advice, based on an expert-committee report, is that pregnant women “may wish” to avoid eating peanuts or foods containing peanut products if they or the father or siblings of the unborn child are atopic. The same advice is given for the lactation period.

Peanut allergy is important because it is a common cause of anaphylaxis, and fatal reactions occur. Its prevalence has increased substantially, with one in 200 4-year-olds having this form of allergy. The allergy is strongly associated with atopy (in 96%) and with clinical allergic disease (in 96% overall, with asthma in 76%, atopic eczema in 60%, and rhinitis in 73%). There seems to be decline in the age of onset and an inverse correlation between this age and year of birth. Onset occurs before the age of 3 years in 55% of people with peanut allergy, and in the first year of life in 17%.

The increase is probably related to the recent doubling or trebling in the prevalence of allergic asthma, rhinitis, and eczema in certain, mainly “westernized”, populations. Peanut butter is now recommended as a weaning food in the UK. The observation that peanut allergy was occurring almost exclusively in atopic individuals, and that babies and young children were particularly affected, led to the suggestion that early introduction of peanuts into an at-risk atopic population may be a causal factor in the allergy, and that young atopic children should avoid peanuts.

Other observations have been interpreted as suggesting even earlier sensitization, either in utero or through breast milk. The Southampton group found that 80% of individuals with peanut allergy reacted to their first known exposure to peanut-containing food, and a study from France found that 8% of babies up to age 4 months had IgE antibody to peanut allergens. Another suggestion is that sensitization might occur topically, through the application of creams containing arachis (peanut) oil for eczema. However, there is no evidence that the oil in these preparations contains peanut protein.

Factors influencing the fetomaternal interface are incompletely understood. The Th1 and Th2 subsets of CD4 T cells are important in determining the response to antigen. The normal response to antigens (eg, infectious agents) is a Th1 (interferton-?) response, whereas in an allergic individual exposure to an allergen leads to a Th2 (interleukin-4) response with IgE production and the inflammatory processes seen in allergic disease. The fetal immune response is skewed to Th2, but infection in early life is the main immune stimulus, and it helps restore the balance between Th1 and Th2 responses.

In immunologically naive rat pups inhalation or ingestion of an allergen leads to transient low-level IgE production (tolerance), but the response is influenced by genetic factors, so that in some strains IgE production persists. The response is also influenced by environmental factors—expected Th2 responses could be suppressed by concomitant exposure to infection, or enhanced by concomitant exposure to air pollutants.

There is epidemiological evidence that, in genetically susceptible infants, early exposure to allergens (eg, house- dust mite, pollens, animal dander), induces a Th2- dominant response. Enhancing factors include concomitant exposure to cigarette smoke. By contrast, infection protects against the development of allergy. The decline in infection rate and increased use of antibiotics in developed countries may predispose to the persistence of a Th2-dominant phenotype in the infant, so that early exposure to allergen tends to induce an allergic response. There seems to be an early “window of opportunity” before the Th1-dominant state is reached, when allergen exposure is more likely to lead to a proallergic Th2 rather than a Th1 response. The low prevalence of peanut allergy in countries such as Indonesia, where groundnut (peanut) is part of the staple diet, may be due to the presence of coexisting factors that protect against allergy.The lifestyle there is not westernized, the population is poor, and infection is endemic.

Is there evidence of sensitization in utero or via breast- milk? In pregnant rats, food proteins can be detected in serum and amniotic fluid. In human beings, food proteins (egg and milk) are detectable in maternal serum, but there is no evidence of transfer to the fetal circulation. Maternal IgE cannot cross the placenta. There is anecdotal evidence of transfer of allergen in breast milk, with reports of amelioration or exacerbation of infant allergy by exclusion or reintroduction, respectively, of egg or cow’s milk in the maternal diet. Cow’s milk and egg proteins, in nanogram amounts, have been detected in breast milk after ingestion, but whether such concentrations will sensitize the infant for IgE production is not known. Data suggesting that exposure to allergen may begin in utero include the detection of allergen- specific T cells in cord and fetal blood.

Allergen-avoidance measures in the newborn, which included breastfeeding but no restriction of maternal diet, have reduced the incidence of allergic disease due to foods or inhaled allergens. However, there is a lack of convincing evidence from prospective studies that manipulation of the maternal diet during pregnancy has a lasting effect on the development of food allergy. Although temporary reductions before the age 2 years have been reported, such studies are difficult and require recognition of many influences. One study showed that maternal dietary restriction during lactation combined with other allergen-avoidance measures reduced the incidence of total allergy. Retrospective analysis of peanut intake during pregnancy also shows no convincing link, probably because such analyses are insufficiently sensitive.

Early exposure to allergen is almost certainly important in the development of peanut allergy, but it is difficult to know how early this sensitization occurs. As pointed out in the report on peanut allergy, there is no evidence of sensitization to peanut allergen in utero. Indirect data suggest that lactation is a more likely route of primary sensitization, but this point remains to be established. Prospective studies of peanut avoidance in pregnancy and lactation, without confounding variables, are required, so that these public-health measures can be soundly based.