Early-Life Antibiotic Exposure and Childhood Food Allergy: A Systematic Review

To identify studies investigating the association between antibiotic exposure and food allergy.

Articles that evaluated an association between antibiotics and food allergy in children (0–18 years of age) were included.

An extensive systematic literature search of online databases was done to identify the association childhood food allergy and early-life antibiotic exposure in children 0–18 years old. In the search, food allergy was defined only as symptoms related to ingestion of a food with a positive test for skin or serum-specific IgE, or diagnosis of food allergy by a physician.

Of 1058 articles initially identified, only 2 prospective and 4 retrospective studies met entry criteria. Of those, 1 prospective and 3 retrospective studies found a significant association between early-life antibiotic exposure and food allergy. Two of those 4 studies also found an association between the number of courses of antibiotics and food allergy. Two studies found the strongest association was with broad-spectrum antibiotic use. Because food allergy is associated with other IgE–mediated diseases, 3 studies adjusted for other atopic conditions of which in 2 studies the association between antibiotic use and food allergy remained unchanged. In the third, only the association between antibiotic use and nonmilk allergy was no longer significant. The studies differed in design, methods, and even definition of food allergy. At least one might not have been powered adequately to detect an association.

There is some (but inconsistent) evidence to support the hypothesis that early life antibiotic use is associated with childhood food allergy. Whether the association is causal or merely correlation and factors that may affect the association are unknown.

In a way, this study prompts more questions than it answers. The fact that only 6/1058 articles met entry criteria indicates the need for more well-designed, prospective studies. If the association holds up in large studies, identification of specific factors (demographic factors, number and duration of courses of antibiotics, age of exposure, etc) that increase risk may be possible. The association between antibiotic use early in life and food allergy is probably multifactorial. Of course, antibiotics affect the diversity of the microbiome. Do different antibiotics affect different individuals’ microbiomes to different extents? In addition to increasing risk of food allergy, to what degree do antibiotics increase risk for other atopic diseases?

We try hard to not prescribe antibiotics without evidence of a bacterial infection. This study supports that effort, especially in babies. But in which babies with otitis do you wait to see if there is spontaneous resolution or treat immediately? For those of us on the front lines of patient care, these are difficult questions for which there are no easy answers. It is clear however that we need to be judicious in our use of antibiotics and use shared decision making with the parents of our patients.