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Association found between atopic disease and early exposure to antibiotics

A population-based birth cohort study of Canadian neonates and their parents has found evidence in support of the association between early antibiotic exposure and increased risk of atopic disease, but also found that prenatal maternal exposure to dogs and acetaminophen were protective against allergic disease.

That is according to a paper published in the Journal of Developmental Origins of Health and Disease (Dec. 2016; 7(6):655-671).

The so-called hygiene hypothesis—the idea that a reduction in early microbial or allergen exposure can contribute to atopic disease—has been a concern for some time, said Dr. Michael Cyr, an associate clinical professor in the Division of Clinical Immunology & Allergy at McMaster University in Hamilton, and a staff physician at Hamilton Health Sciences.

“Antibiotics can alter the infant’s microbial environment, and the concern that such exposure was a risk for the development of atopy and allergic diseases was already there, and really fits the hygiene hypothesis. So, when we saw [antibiotic exposure] was associated with increased atopy, that was not surprising but it was nice to see it confirm what we thought,” Dr. Cyr added.

Different skin types call for different approaches

“I was interested in looking at core blood markers to see if they could predict which kids would go on to develop allergy,” said Dr. Cyr. He said that the project started as a small undertaking but the opportunity arose to collaborate with a much larger project, the family Atherosclerosis Monitoring in early life (FAMILY) birth cohort study. “They were looking at early life predictors of cardiovascular disease and obesity, and nutrition.”

Dr. Cyr and his team were able to add questions related to allergy and allergy-related environmental exposures during pregnancy to the FAMILY questionnaires, which were already asking about diet and other exposures, he said. The collaboration also provided Dr. Cyr with access to some samples of cord blood, and some allergic skin prick test results.

The nice thing about collaborating with the FAMILY cohort was that this was a generalized cohort,” said Dr. Cyr. “This wasn’t a high-risk, allergic cohort—it was just the general population. So, that was really quite attractive to us, too.”

Pets may provide protective exposure

Overall, the study population included 901 babies, 857 mothers, and 530 fathers. Questionnaires were completed during the antenatal period and at one year after birth, and those questionnaires and skin prick testing were used to evaluate the end points of atopy and allergic disease.

At one year, 24.5% of participating children had atopy, 17.5% had food allergy, 4.8% had cow’s milk allergy, 18.6% had wheezing, and 16% had eczema.

Multivariate analysis revealed an association between infant antibiotic exposure and increased atopy (odds ratio (Or): 2.04, 95% confidence interval (CI): 1.45–2.88].

Also, tying into the hygiene hypothesis, the investigators also found a protective effect from prenatal maternal exposure to dogs (Or: 0.60, 95% CI: 0.42–0.84). “It fits very nicely with the hygiene hypothesis and the going theory of increased microbial exposure that could be related to dog ownership,” Dr. Cyr said.

When Dr. Cyr started practicing as an allergist, there was a prevalent idea that individuals who wanted to avoid developing allergies should avoid pets, he said. “That turns out to probably not be entirely correct.”

While this cohort did show a protective effect from having a dog in the home, the evidence is not strong enough to recommend acquiring a dog for protective purposes. Instead, it simply suggests there is no cause to remove a pet from a home if no one in the home is currently allergic to it.

A more surprising finding that Dr. Cyr and his team identified was that in this cohort, prenatal exposure to acetaminophen was also associated with decreased risk of atopy (Or: 0.68, 95% CI: 0.51–0.92).

“I wasn’t surprised to see that there was an association, but what we were surprised to see was the direction of the association,” said Dr. Cyr. Many prior studies had raised concerns about a possible association between acetaminophen use and increased risk of wheezing and asthma in children, he said. However, being association studies, the direction of causation was unclear.

Contrary to this, Dr. Cyr and his team found a protective effect from infant acetaminophen use. “In our study, it looked like it decreased the risk of allergic disease and decreased atopy.”

Continuing to contribute data to CHILD study

“If you have the hygiene hypothesis in mind, our data might suggest that exposure in early life to microbial infections would lead to these kids having fever and being treated with acetaminophen, and that is why we are seeing a protective effect.” Essentially, use of acetaminophen did not itself lower or increase the risk of allergic disease, it was merely reflective of greater infection exposure.

The FAMILY cohort is still being followed, and Dr. Cyr said that it would be valuable to look at the atopy and allergy data from that cohort prospectively over the next several years. As well, the team has contributed to some of the immunology and allergy questions for the Canadian Healthy Infant Longitudinal Development (CHILD) cohort study, which is ongoing.

Previously published in the Dec. 2016 edition of The Chronicle of Skin & Allergy.

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