Acid suppression in infancy and antibiotic use are associated with celiac disease

Acid suppression in infancy and antibiotic use are associated with celiac disease

Celiac disease (CD) is an immune-mediated enteropathy that arises due to persistent gluten intolerance in genetically susceptible individuals. Between 1975 and 2000, the prevalence of celiac disease increased fivefold in the United States.

Improved recognition of heterogeneous presentation, better screening, and increased disease awareness may be responsible for the increased diagnosis of this disease. Other factors also likely contribute to the pathogenesis of CD; However, why some at-risk people develop the disease remains unclear.

Learn: Acid suppression and antibiotics given in infancy are associated with celiac disease.Photo credit: George Rudy / Shutterstock.com

Possible risk factors for CD

Along with gluten exposure and genetic susceptibility, changes in the gut microbiome and intestinal permeability impact the way the immune system encounters antigens. Previous studies have reported that gastrointestinal infections and antibiotic exposure are associated with an increased risk of developing celiac disease.

Acid-suppressing medications such as histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) are the two most common antibiotics prescribed to pediatric patients. To this end, a dose-response relationship was observed in patients in which more courses of antibiotics increased the risk of developing celiac disease.

In addition, pH change affecting the gut microbiome and degradation of food antigens may also be associated with CD pathogenesis. Exposure to H2RA and PPIs in the first year of life may also lead to early onset of celiac disease due to changes in the intestinal mucosal barrier and gut microbiota.

A new study published in The Journal of Pediatrics determined whether exposure to H2RAs, PPIs, and other antibiotics after the first six months of life was associated with childhood celiac disease diagnosis.

About the study

The current retrospective study utilized the TRICARE Military Health System (MHS) database. The study included children who had a birth record in the database between October 1, 2001 and September 30, 2013, as well as those enrolled in TRICARE within 35 days of birth.

Children with incomplete demographic or enrollment data, a stay of more than seven days at first birth, and an outcome of interest within the first six months of life were ineligible for the study.

Classification of medications was based on the American Hospitalformulary Service (AHFS) classification system. Information on the name of the medication, the number of days it was prescribed, and the patient's age were collected from each eligible prescription and then the duration of the prescription was evaluated.

CD outcome was defined using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code 579.0. Birth by cesarean section and preterm birth were additional variables extracted using ICD-9-CM codes. In addition, information on each child's inpatient and outpatient medical visits was retrieved from the MHS database.

The hazard ratio (HR) of CD development based on H2RAs, PPIs, and other antibiotic exposures after the first six months of life was also calculated.

Study participants were divided into groups based on the average days they were prescribed medication. Groups included those who received no medication and received PPIs or H2RAs for one to 60 days or more than 60 days.

For antibiotics, low exposure was defined as antibiotic use for up to 10 days, while high exposure was defined as antibiotic use for more than ten days. The effects of exposure to multiple combinations of antibiotics were also assessed.

Study results

A total of 968,524 children were included in the study. 472,564 were female, 37,145 were premature, and 256,262 were born by cesarean section. 181,166 children were prescribed an antibiotic, 18,911 a PPI and 79,319 an H2RA. A total of 1,704 children were diagnosed with celiac disease, with a median age of diagnosis of 3.5 years.

Exposure to PPIs, H2RAs, and antibiotics was associated with an increased risk of developing celiac disease. However, neither the type of delivery nor preterm birth were associated with this increased risk.

Long-term prescription of acid-suppressing medications was associated with a higher risk of developing celiac disease. Furthermore, HR was higher for PPI and H2RA prescription durations longer than 60 days compared to less than 60 days. Multiple drug classes increased the HR for CD development with each additional drug class.

Conclusions

PPIs, H2RAs, and antibiotic prescriptions during the first six months of life can increase the risk of developing celiac disease. This risk increases even further with multi-category prescriptions and when these drugs are prescribed for a longer period of time.

The study results highlight preventive factors such as: B. the responsible use of medications that can help reduce the occurrence of celiac disease. However, further research is needed to understand how early infant exposure, antigen presentation, protein degradation and microbiome may lead to the development of celiac disease.

restrictions

The study has certain limitations. First, the early symptoms and indications for prescribing medication were unknown. Second, the study did not include infants younger than six months.

Analysis of patients' HLA genotypes and celiac disease risk was not performed. In addition, age at introduction of solid foods or gluten and breastfeeding status could not be assessed.

The current study did not include patients diagnosed with celiac disease in adulthood or adolescence, nor those diagnosed several years after taking the drug. In addition, the study only examined outpatient prescriptions.

Reference:

• Boechler, M., Susi, A., Hisle-Gorman, E., et al. (2022). Säureunterdrückung und im Säuglingsalter verabreichte Antibiotika stehen im Zusammenhang mit Zöliakie. Das Journal of Pediatrics. doi:10.1016/j.jpeds.2022.10.013.

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