Genetic, environmental and lifestyle factors influence the risk for food sensitization and food allergies during the first thousand days of life, according to a literature review published in Annals of Allergy, Asthma & Immunology.

Erin C. Davis, PhD, postdoctoral fellow in the department of pediatrics’ division of allergy and immunology at the University of Rochester School of Medicine and Dentistry and the Center for Food Allergy at Golisano Children’s Hospital, University of Rochester Medical Center, in Rochester, N.Y., based their findings on a PubMed search of articles in English on food allergy (FA) and food sensitization (FS), prioritizing studies published after 2015.

The review explored the genetic risks for food allergy, links between atopic dermatitis (AD) and food allergy, dietary allergen exposures in early life, maternal antigen consumption during pregnancy and lactation, breastfeeding and formula feeding, introduction to solid foods, lifestyle and environmental exposures, the gut microbiome and metabolome in food allergy and potential early immune biomarkers of food allergy.

Genetic risks for food allergy include the number of parents or siblings with a history of allergic disease, although the researchers caution that some of this association may be due to the family’s practice of prolonged avoidance or late introduction of the allergen.

Specifically, researchers have found connections between the major histocompatibility complex genes, which encode the human leukocyte antigen complex, and FA development including sensitization to peanut, cow’s milk and egg.

The review also found that approximately one of every three children with AD are prone to immediate-type IgE-mediated FA. One hypothesis suggests the impaired skin barrier that patients with AD experience allows epicutaneous sensitization to foods before oral ingestion.

Noting that infants may be exposed to allergens early in life, the researchers said that the mechanisms behind sensitization or tolerance likely vary based on how that exposure occurred.

For example, the researchers said, infants may be exposed to allergens in utero or through human milk or infant formula before they begin solid foods. Environmental or household exposures to allergens are plausible as well.

However, the researchers found scarce and contradictory findings about the relationship between maternal intake of allergenic foods and infant FA risks, even though major food allergens have been detected in amniotic fluid and human milk. The American Academy of Pediatrics does not recommend maternal dietary restrictions to prevent atopic disease.

Studies that have evaluated the protective effect of breastfeeding against FA have been mixed, the researchers continued. Human milk includes immunomodulatory components that shape the early life microbiome and immune system, but variations between women influence the risk for disease.

Early introduction to solid foods appears to have a significant impact, as the researchers cited the Learning Early About Peanut trial, which demonstrated how the early and sustained intake of peanut could be protective against peanut allergy. Also, the Enquiring About Tolerance Study found a 67% lower risk for FA with early introduction when children are aged 1 to 3 years.

The growing adoption of a Westernized lifestyle that limits less industrialized exposures to microbial influences may contribute to increasing rates of FA and FS as part of the hygiene hypothesis, the researchers further found.

For instance, larger family sizes are related to lower incidences of AD and hay fever. Exposure to pets and vaginal delivery also are associated with lower risks for allergic diseases. Farming lifestyles can be protective as well.

Such early exposures to diverse populations of microorganisms may train the immune system to mount tolerogenic responses during exposures later in life to environmental or food allergens, the researchers said.

The gut microbiome, meanwhile, also is a factor mediating the association between increases in the prevalence of allergic disease and industrialization. There may be an association between FA and FS development and less mature microbiomes, the researchers said, although studies have provided limited data.

Finally, the researchers found studies demonstrating associations between a differential infant immune profile and FS and FA. The loss of immune cell populations and potential hyper-responsive profiles could increase risks for aberrant responses including sensitization, the researchers said.

Multiple factors drive disease pathogenesis, including genetics as well as maternal and infant allergen exposure, human milk composition and other environmental factors, the researchers concluded, with tolerance or sensitization likely depending on the route of first exposures and possibly genetic risk.

Further, the researchers called for additional observational studies and clinical trials that span from early pregnancy through childhood so novel biomarkers and risk factors for predicting susceptibility for FS and FA could be uncovered.