Australian researchers tested whether greater exposure to egg and peanut before birth and during breastfeeding could help shape food tolerance before infants begin eating these allergens themselves.
Study: Trial of a Maternal Diet Rich in Eggs and Peanuts to Reduce Infant Allergy. Image Credit: Zhuravlev Andrey / Shutterstock
A large randomized trial published in the New England Journal of Medicine found that increasing maternal consumption of eggs and peanuts during pregnancy and breastfeeding did not significantly reduce the risk of egg or peanut allergy in infants at 1 year of age who had a strong family history of allergic disease.
Background
The authors reported in their previous work that egg-specific immune responses can be established by 4 months in some susceptible infants. These responses were unaltered by the early introduction of egg into the infant's solid-foods diet at approximately 4 to 6 months, as recommended by current guidelines aimed at preventing food allergies.
The authors suggested that tolerance may need to begin developing earlier, during pregnancy and lactation, when tolerance pathways appear to be initiated.
The fetal immune system is exposed to maternal antigens during pregnancy, including through the ingestion of food allergens from amniotic fluid. Breast milk likely provides another route of exposure to food allergens after birth, and has been reported to induce tolerance in animal studies.
Limited evidence in literature
Yet evidence that changing maternal diet prevents food allergy has been limited. A 2018 meta-analysis found that avoiding allergenic foods during pregnancy or lactation did not reduce the risk of allergic disease in children. It was unclear whether the amount of maternal allergen consumption and the frequency and dose of fetal and infant exposure influence allergy risk.
One large observational study found that higher maternal consumption of peanuts and tree nuts during pregnancy was associated with a lower risk of peanut and tree nut allergies in children. In infant solid-food diets, higher consumption of peanut and egg has been associated with a lower prevalence of these food allergies than lower consumption. Higher maternal egg intake was associated with higher egg protein concentration in breast milk.
The PrEggNut trial tested whether high maternal consumption of eggs and peanuts during pregnancy and lactation could prevent food allergy in infants.
Study characteristics
The investigators planned to recruit 2,136 women who were less than 23 weeks pregnant, had a singleton pregnancy, and planned to breastfeed for at least 4 months. The fetus also had to have at least two biological family members with medically diagnosed allergic disease, such as asthma, eczema, allergic rhinitis, or IgE-mediated food allergy. Women with egg or peanut allergy were excluded because they could not safely follow the intervention.
The sample size was based on an estimated 16% egg or peanut allergy in this high-risk population. They designed the study to capture a 30% reduction in allergy compared to low intake.
The 23-week initiation point marks when fetal immune cells become responsive to allergens, while the period up to four months after birth appears important for primary food-allergy prevention.
The study was conducted in Adelaide, Melbourne, Perth, and Sydney, Australia. It enrolled 2,137 pregnant women, of whom 1,070 women were randomly assigned to a high egg–peanut diet and 1,067 to a standard diet.
The high-intake diet included at least 6 eggs and 60 peanuts per week, in any form, from enrollment until 4 months after delivery during lactation, or until breastfeeding ended if it stopped earlier. Those in the standard-diet group were asked to consume no more than 3 eggs and 30 peanuts per week. The investigators considered this consistent with current best practice because guidelines do not recommend maternal avoidance of common food allergens during pregnancy or lactation, and the amounts also reflected typical Australian intake.
Randomization was stratified by city and birth order. Monthly surveys were used to monitor adherence. Outcome assessors, the trial statistician, investigators, and the serious-adverse-event committee were unaware of group assignments, while participants and intervention staff knew the assigned diet because the intervention involved whole foods.
After the intervention, both groups received Australasian guidance on infant feeding and allergy prevention, with solid foods recommended around 6 months of age and peanut butter and cooked egg introduced during the first year.
The primary outcome was IgE-mediated egg or peanut allergy at 1 year of age. Infant assessment occurred at a median age of 12.9 months.
Infants underwent skin-prick testing for egg white and peanut. Those with positive tests but no history or test results strongly suggestive of clinical allergy underwent in-hospital oral food challenges.
Secondary outcomes included egg allergy, peanut allergy, sensitization to each allergen, and medically diagnosed eczema at 4 and 12 months.
In both groups, 88% continued to lactate until 4 months. The participants showed moderate adherence to the assigned diet. Among participants with known adherence status, 64.4% in the high-intake group met the egg target, and 66.6% met the peanut target, across 75% or more of the monthly surveys.
In the standard-diet group, these figures were 72.7% for eggs and 79.7% for peanuts. Both groups differed markedly in the actual weekly consumption of eggs and peanuts.
Maternal intake did not significantly reduce peanut or egg allergy
IgE-mediated egg or peanut allergy occurred in 83 of 1,066 infants (7.8%) in the high egg–peanut group and 89 of 1,064 infants (8.4%) in the standard-diet group, with no statistically significant difference in the combined risk of egg or peanut allergy.
When the analysis was restricted to women who breastfed for 4 months with adequate adherence to the assigned diet, the null finding remained unchanged, with allergy rates of 5.6% and 6.8% in the respective groups.
Other analyses supported these results, with little evidence that the intervention effect differed according to birth order, household intake of eggs and peanuts, or socioeconomic status.
The individual allergy outcomes were similar between groups, including IgE-mediated egg allergy and peanut allergy, infant egg or peanut sensitization, and medically diagnosed eczema at 4 and 12 months.
No apparent differences were found in maternal or infant safety outcomes. Serious adverse events occurred in 3.6% of the high-intake group and 3.8% of the standard-diet group. Infant anaphylaxis to egg or peanut occurred in 0.5% and 0.9%, respectively.
Limitations
One limitation was that the actual prevalence of egg or peanut allergy was only about 8%, rather than the anticipated 16%. According to the authors, this might have reduced the study's ability to detect a preventive effect. The authors note that the confidence interval does not completely exclude a clinically important 30% reduction in risk.
The lower-than-expected allergy prevalence may reflect changes in infant feeding after the 2016 Australian allergy-prevention guidelines. The authors noted that their 16% estimate came from data collected before the guideline update and cited another Australian study in which direct provision of the guidelines promoted introduction of egg and peanut at around 6 months and reduced allergy prevalence.
Future studies should account for the reduced incidence of these allergies, linked to changes in infant feeding practices in some countries, when determining sample sizes.
The authors concluded that higher maternal intake of eggs and peanuts during pregnancy and lactation did not reduce or increase the risk of IgE-mediated egg or peanut allergy in infants. They also pointed to separate evidence supporting timely introduction of egg and peanut directly into the infant diet.
Study: Multiple dietary patterns linked to slower biological aging