The results of some recent studies highlight the potential for maternal diet to benefit the development of oral tolerance in the infant during lactation.
Current government advice is to exclusively breastfeed infants for the first 6 months of life if possible1 and that there is no reason for women who are breastfeeding their babies to avoid eggs or other allergenic foods unless they themselves are allergic to them2. It is known that maternal antigens to potential food allergens, such as eggs, can pass into breast milk and it has been suggested that infants might be sensitised to foods by exposure to these antigens in their mother’s milk. Until recently, there has only been limited evidence to support this suggestion and the authors of a Cochrane review on the subject in 2012 concluded that there was insufficient evidence to recommend antigen avoidance diets during breastfeeding to reduce the risk of subsequent infant allergies but observed that further research in this area was required3.
In 2018, as part of the SACN (Scientific Advisory Committee on Nutrition) review of infant feeding4, various separate pieces of work were commissioned to inform their decision-making process. This included a systematic review and meta-analysis of evidence regarding early exposure to food antigens and development of allergic responses, immune tolerance, and autoimmune disease in the infant5. The systematic review concluded that there was only limited data, derived predominantly from observational studies, for the effects of maternal diet in either pregnancy or lactation on subsequent food allergic disease in childhood.
Findings from some recent studies support the hypothesis that mothers who eat eggs when breastfeeding may help protect their babies against future egg allergy.
The first study6, carried out in mice at Boston Children’s Hospital, found that lactating mothers sensitised to egg protein (ovalbumin) passed IgG4 antibodies on to their offspring, allowing them to tolerate the food.
Through a series of experiments in a mouse model, which had similar features to human food allergy, the research team showed that pregnant and breastfeeding mice exposed through the skin barrier to ovalbumin transferred protective IgG4 antibodies to their babies through their breastmilk. The antibodies caused the babies to produce allergen-specific regulatory T immune cells, also known as Treg cells, which appears to have enabled them to tolerate the allergenic food. The babies from sensitised mothers who were then subjected to skin sensitisation and oral challenge to ovalbumin showed a much smaller allergic response to the allergen.
Breastmilk appeared to protect against food allergy even when it was fed to unrelated offspring who had not experienced in utero exposure to maternal IgG4 antibodies. Furthermore, when mothers had not been sensitised, but were supplemented with ovalbumin-specific IgG4 antibodies whilst breastfeeding, the babies were also protected.
Even after the mothers' antibody disappeared from the babies’ circulation, the babies showed no allergic response to skin or oral challenges with ovalbumin, suggesting a long-lasting effect. The researchers also examined mice born to allergen-exposed mothers nursed from mothers that had never consumed allergenic foods. They still saw protection from the in utero exposure, but the protection was better when the mice were also exposed through breastfeeding. The researchers commented that combining both in utero and breastfeeding exposure gave optimal induction of food tolerance.
Human breast milk was also protective in mice whose immune systems were tailored to respond to human antibodies, suggesting that the mouse findings may translate to human infants.
The second study7, a randomised controlled trial (RCT) undertaken at the University of Western Australia, investigated how maternal dietary egg ingestion during early breastfeeding influences egg protein (ovalbumin) levels detected in human breastmilk and whether this influences sensitivity or tolerance to egg protein in the infant.
Women were allocated to a dietary group for the first six weeks of lactation: high-egg diet (> 4 eggs per week), low-egg diet (one-three eggs per week) or an egg-free diet. Breastmilk samples were collected at 2, 4 and 6 weeks of lactation for the measurement of ovalbumin. Blood levels of egg-specific immunoglobulin E (a measure of sensitisation to egg) and immunoglobulin G4 (IgG4) (an indication of protection against allergy and tolerance to egg) were measured in the infants at 6 weeks as well as before introducing egg in solids at 16 weeks.
Average maternal egg consumption correlated with breastmilk ovalbumin concentration; for each additional egg ingested each week, there was an average 25% increase in ovalbumin concentration. Ovalbumin concentrations were significantly higher in the breastmilk of the 'high-egg' group compared with the 'egg-free' group. Blood levels of egg-specific IgG4 in the infants were positively related to maternal egg consumption, with an average 22% increase in infant egg-specific IgG4 per additional egg consumed each week.
The researchers concluded that increased maternal egg consumption is associated with increased breast milk ovalbumin, and with markers of immune tolerance in infants. However, an interesting observation in this trial was that ovalbumin was also present in the breast milk of two thirds of the mothers in the egg-free intervention group, which the authors speculate may have occurred via accidental or environmental exposure to household egg intake. Furthermore, a quarter of mothers in the high‐egg intervention group had no detectable ovalbumin in their breast milk. The authors observe that this suggests that maternal egg intake is not a reliable predictor of egg ovalbumin in breast milk and that in further research, milk ovalbumin levels should be measured.
Therefore, in a subsequent, small, proof of concept, study from this research group8, they measured ovalbumin levels in breast milk at 3 and 6 months in a cohort of women at high allergic risk, who were control participants from a larger RCT (the Infant Fish Oil Supplementation Study). Data was available for 88 children. In this cohort from 2011 the median age of introduction of eggs was high -11 months – and interestingly at 1 year there was no statistically significant difference in the prevalence of IgE-mediated egg allergy between children exposed to breast milk ovalbumin and those whose mothers’ milk had no ovalbumin present at 3 and/or 6 months. However, at age 2.5 years, the study showed that there was a more than four-fold reduction in IgE-mediated egg allergy among the children exposed to ovalbumin in breast milk at 3 and 6 months as compared to those children whose mothers had no detectable ovalbumin in their milk at either 3 or 6 months.
The authors conclude that this small preliminary study suggests that the presence of ovalbumin in breast milk is associated with a decreased risk of subsequent egg allergy in children. They also conclude from this and their earlier study that the heterogeneity in the presence of egg ovalbumin in breast milk may be a contributing factor to the lack of good reproducible evidence for the prevention of childhood egg allergy through maternal egg consumption whilst breastfeeding.
Sources
1 NHS Choices http://www.nhs.uk/Conditions/pregnancy-and-baby/pages/why-breastfeed.as…
2 NHS Choices http://www.nhs.uk/conditions/pregnancy-and-baby/pages/lifestyle-breastf…
3 Kramer and Kakuma (2012) Maternal dietary antigen avoidance during pregnancy or lactation, or both, for preventing or treating atopic disease in the child. Cochrane Database Syst Rev.(link is external) 2012 Sep 12;9:CD000133. doi: 10.1002/14651858.CD000133.pub3.
4 Scientific Advisory Committee on Nutrition (2018) Feeding in the First Year of Life https://assets.publishing.service.gov.uk/government/uploads/system/uplo…
5 Garcia-Larsen V et al. (2018) Diet during pregnancy and infancy and risk of allergic or autoimmune disease: A systematic review and meta-analysis. https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed…
6 Ohsaki A et al. (2017) Maternal IgG immune complexes induce food allergen–specific tolerance in offspring doi: 10.1084/jem.20171163 http://jem.rupress.org/content/early/2017/11/17/jem.20171163
7 Metcalfe JR et al. (2016) Clin Exp Allergy.(external link) 2016 Dec;46(12):1605-1613. doi: 10.1111/cea.12806. Epub 2016 Oct 7.
8 Verhasselt V et al. (2019) Ovalbumin in breast milk is associated with a decreased risk of IgE‐mediated egg allergy in children. https://onlinelibrary.wiley.com/doi/full/10.1111/all.14142