Antibiotic and acid suppressant exposure during the perinatal period was linked to the development of eosinophilic esophagitis (EoE) later in life, a Danish cohort study found.
Infants with any antibiotic use had a 40% greater risk of developing EoE later in childhood compared to matched controls without such exposure (adjusted OR 1.4, 95% CI 1.1-1.7), while maternal use in pregnancy was associated with a 50% increased risk of the child developing EoE (adjusted OR 1.5, 95% CI 1.2-1.9), reported Elizabeth Jensen, MPH, PhD, of Wake Forest University School of Medicine in Winston-Salem, North Carolina, and coauthors.
Moreover, infant use of acid suppression was also associated with an increased risk of EoE development (adjusted OR 15.9, 95% CI 9.1-27.7), according to the case-control study published in JAMA Pediatrics.
“Several potential mechanisms may explain our findings. Antibiotics and acid suppressants have been suggested to increase the risk of allergic sensitization, and several reports have linked maternal and infant antibiotic use to the development of other (non-EoE) atopic diseases,” Jensen and colleagues wrote. “Still, it can be difficult to disentangle the temporality of these associations.”
“Contextualizing our results for acid suppressants is somewhat more difficult,” they cautioned. “Prematurity increases the likelihood of prophylactic acid suppressant use. When examining the magnitude of risk associated with acid suppressants, we observed the highest magnitude of association among preterm infants. Therefore, prophylactic acid suppressant use might contribute to increased EoE risk.”
The study nevertheless suggests environmental triggers for the rapidly increasing chronic condition, in which eosinophils build up in the epithelial lining of the esophagus, leading to inflammation and often severe difficulty swallowing. “Although studies have elucidated possible genetic susceptibility markers for EoE, heritability of EoE is relatively low compared with other immune-mediated conditions,” the researchers wrote.
While not proving causation, “there’s clearly a correlation between early antibiotic use and atopic diseases like eosinophilic esophagitis,” John Russo, MD, of Nationwide Children’s Hospital in Columbus, Ohio, told MedPage Today. “We need to be judicious in our use of antibiotics especially early in life.”
Rajitha Venkatesh, MD, MPH, also of Nationwide Children’s Hospital, noted that “early life has been demonstrated to be the period for colonization of the gut where any changes could have lasting consequences to diversity and relative abundance features in the microbiome.”
And Vincent Mukkada, MD, of Cincinnati Children’s Hospital, said he and his colleagues routinely bring up the possibility of maternal exposure in the clinic.
“It’s become standard practice to say — ‘Let’s talk about your pregnancy. Were there any issues during pregnancy? What type of delivery was it? Was the baby born full term?'” said Mukkada. “That sometimes catches people by surprise when you’re asking about a 12-year-old, but it may well have some relevance, and I think it helps fill in the picture for us.”
Russo, Venkatesh, and Mukkada were not involved in the research.
For their study, Jensen and colleagues relied on a registry of 1.4 million children born from 1997 to 2018, and prescription data from the Danish National Prescription Registry.
Final study analysis included 392 patients with EoE matched by birth year and sex to 3,637 controls. The average patient age was 11 years old, and about a third were female.
EoE cases were seen more frequently among children who were delivered via c-section, born preterm, and admitted to neonatal intensive care unit, the researchers noted.
The association between infant and maternal antibiotic use and increased EoE risk was found to be dose-dependent. For example, infants recorded as having three or more antibiotic prescriptions saw their risk for developing EoE rise by 80% (adjusted OR 1.8, 95% CI 1.3-2.5).
Penicillins and β-lactam antibacterials were the most commonly prescribed class of antibiotics during participant pregnancies. The period of time with the highest risk of developing EoE was found to be the third trimester of pregnancy up to age 6 months for a child.
Study authors added that the association between acid suppressant use in infancy and EoE was stronger for those born preterm (adjusted OR 27.5, 95% CI 8.2- 92.4) compared with at-term counterparts (adjusted OR 13.9, 95% CI 7.3-26.5).
Race and ethnicity were not recorded as part of the patient registry used for the study. Other potential limitations to the study include a small case set, missing information regarding the specific use of prescribed antibiotics, and that medication use was measured through the filling of prescriptions, rather than confirmation of administration.
This research study was supported by funding from the National Institutes of Allergy and Infectious Diseases.
Jensen reported receiving grants from the National Institutes of Health, the Duke Endowment, Kate B. Reynolds Trust, and TARGET-RWE; and consulting fees from Regeneron and Jazz.
Russo and Venkatesh are co-directors of the Eosinophilic GI Disorders Program at Nationwide Children’s Hospital and reported no disclosures.
Mukkada reported relationships with Takeda/Shire, Regeneron, Sanofi, Allakos, and Alladapt Immunotherapeutics.
Source Reference: Jensen ET, et al “Maternal and infant antibiotic and acid suppressant use and risk of eosinophilic esophagitis” JAMA Pediatr 2023; DOI:10.1001/jamapediatrics.2023.4609.