The study, published Monday in the journal JAMA Pediatrics, links the use of acid-suppressive medications and antibiotics during infancy with the subsequent development of allergic diseases, including asthma, in childhood.
“These medications are given frequently. In our study, we found that about 8% of all children received a prescription for acid-suppressive therapy,” said Dr. Edward Mitre, an associate professor in the Department of Microbiology and Immunology at the Uniformed Services University in Bethesda, Maryland, who was lead author of the study.
Mitre, a father of three, thought of his own son while conducting the study. When the boy was a newborn, a pediatrician once recommended that the baby take an acid-suppressive medication because he often cried when he was laid down a certain way, Mitre said.
Acid-suppressive medications are typically prescribed or available over the counter to help reduce problems related to gastric acidity, like acid reflux or ulcers, and commonly known versions of these drugs incude ranitidineand lansoprazole.
“These medications are usually given to infants who regurgitate food and appear fussy. For most infants, though, regurgitation of food is not a disease. Rather, it’s a developmentally normal process,” Mitre said.
“There are some infants with severe gastroesophageal reflux, who have disease from this and who warrant medical therapy, but it is probable that the vast majority do not,” he said. “So we feel this study is important because it suggests that antibiotics and acid-suppressive medications should be used only in situations of clear clinical benefit, since we see this association with increased risk of allergies.”
In the United States, food allergies affect about 5% of children and 4% of adults, and allergic rhinitis or hay fever affects about 8% of adults and children, according to the National Institutes of Health.
In the United Kingdom, food allergies and intolerances affect about 8% of children and 2% of adults, according to the Food Standards Agency.
As for asthma, globally, about 235 million people have the condition, which is the most common chronic disease among children, according to the World Health Organization.
In the US, the number of people with asthma has soared by more than 60% since the early 1980s, according to the WHO.
Antibiotics tied to greater than two-fold asthma risk
The new study included data on 792,130 children, born between October 2001 and September 2013, whose medical records were within the US Department of Defense’s TRICARE Military Health System.
Using the system’s database, the researchers took a close look at which children were prescribed outpatient acid-suppressive medications — histamine-2 receptor antagonists also known as H2 blockers, or proton pump inhibitors — or antibiotics, such as penicillin, at any time within their first six months of life.
After examining the medication prescriptions, the researchers looked at which children in the data were diagnosed with an allergic disease, such as a food allergy or asthma, from 6 months of age and older.
The researchers found that an increased risk of every allergic disease they assessed, except seafood allergy, was tied to having received H2 blockers or proton pump inhibitors during infancy.
“This includes food allergy, anaphylaxis, asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, urticaria — which is hives — contact dermatitis, medication allergy and a class of other allergies,” Mitre said.
The dosage of the medications also played a role in that association. Infants prescribed more than 60 days of proton pump inhibitors had a 52% greater risk of being diagnosed with food allergy in childhood than those prescribed 60 days or less, the researchers found.
The researchers also found that antibiotic prescriptions during infancy were significantly associated with an increased risk of allergic diseases, but there appeared to be no dose-dependent risk. Regardless of dose, antibiotics prescribed during infancy were associated with a greater than two-fold risk of asthma in childhood, the researchers found.
The findings were “very interesting” to Dr. Bradley Becker, a professor of allergy and immunology in the Department of Pediatrics at the Saint Louis University School of Medicine and a fellow of the American Academy of Allergy, Asthma and Immunology, who was not involved in the study.
“The most important thing is that these medications — the acid-suppressors and the antibiotics — not only affected food allergy but also affected other allergies, such as asthma and skin problems like contact dermatitis or eczema, as well as other respiratory allergies like nasal and eye allergies, and even affected drug allergy development,” Becker said.
“I think it’s really important for pediatricians and other doctors to only give the acid-suppressant medicines and antibiotics for clear indications for which they would improve a child’s health,” he added.
The study had some limitations, including that the findings showed only associations and not causal relationships.
For instance, acid-suppressive medications or antibiotics could have been prescribed to infants because they had allergy symptoms that were misdiagnosed.
“That’s called reverse causality, and that is definitely a limitation of this study … but we do not think that counted for the majority of the associations we saw,” Mitre said.
“We saw increased rates of a number of allergic diseases in which it’s hard to make an argument of reverse causation,” he said. “We saw increased rates of anaphylaxis, of hives and of medication allergy, and no one would generally give an H2 receptor blocker for those clinical presentations.”
More research is needed to confirm causality, to determine whether similar findings would emerge in a different database of children and to determine the mechanism behind the relationship between over-prescribing certain medications and the emergence of allergies.
Yet that relationship is not new to scientific literature.
“There has been evidence over the last several years that the microbiome — that’s the bacteria that normally live in the gut and other places like the respiratory tract and the skin — are important in modulating our immune system, especially in young children,” Becker said.
Medications, especially acid suppressors and antibiotics, can alter the bacteria present in the ecosystem, possibly leading to the development of food and other allergies, he added.
What’s your microbiome got to do with it?
The new study adds to the “mounting evidence” showing a possible relationship between acid-suppressive medications and antibiotics in children who go on to develop a wide variety of allergies, said Dr. Sarena Sawlani, medical director of Chicago Allergy & Asthma and a member of the American Academy of Allergy, Asthma and Immunology, who was not involved in the study.
There are several hypotheses about why there could be a relationship, she added.
“These medications might alter the natural bacteria and flora in our intestinal system. It may be enough of a shift in our gut microbiome that it alters our immune system and goes on to confuse our immune system into triggering allergic pathways,” Sawlani said.
“While we are still far from elucidating exactly how this shift in the natural gut bacteria is affecting our immune system in certain individuals, this study should bolster the ongoing efforts to better understand the mechanism of this unique process,” she said.
For now, “we would need prospective trials with a randomized design before we would draw any definitive conclusions,” she added. “It is too early to recommend any specific changes to the way pediatricians are using these medications.”