according to the findings of a large population-based study.
It remains unclear whether the risk reflects infections in themselves or the use of antibiotic therapy, wrote Charles N. Bernstein, MD, of the University of Manitoba, Winnipeg, and associates. Infections did not appear to be a proxy for immunodeficiency disorders, which were similarly infrequent among cases and controls, they noted. Limiting antibiotic usage, while desirable, would be difficult to do for infections as serious as many in the study. Hence, they suggested research to determine “exactly what antibiotic intake does to infant gut microflora or intestinal or systemic immune responses,” and whether giving probiotics or prebiotics after antibiotic therapy helps attenuate the risk of inflammatory bowel disease (IBD) and other autoimmune disorders. The findings were published in Gastroenterology.
IBD is probably multifactorial, but specific causal factors remain unclear. Based on mounting evidence for the role of gut dysbiosis, the researchers explored whether IBD is associated with higher rates of infections and other critical events during the neonatal period and the first year of life by comparing 825 patients with IBD and 5,999 controls matched by age, sex, and area of residence. The data source was the University of Manitoba IBD Epidemiology Database, which includes all Manitobans diagnosed with IBD from 1984 to 2010. The researchers also compared patients with 1,740 unaffected siblings.
Gastrointestinal infections, gastrointestinal disease, and abdominal pain during the first year of life did not predict subsequent IBD. Maternal IBD was the strongest risk factor (odds ratio, 4.5; 95% confidence interval, 3.1-6.7). Among neonatal events, the only significant risk factor was being in the highest versus the lowest socioeconomic quintile (OR, 1.35; 95% CI, 1.01-1.79). This association persisted during the first year of life.
Infections during the first year of life were a significant risk factor for IBD before age 10 (OR, 3.1; 95% CI, 1.1-8.8) and age 20 years (OR, 1.6; 95% CI, 1.2-2.2) in the population-based analysis. In contrast, patients and their unaffected siblings had similar rates of infection during early life. The study may have missed differences in exposures between these groups, or perhaps patients lack certain protective genes possessed by healthy siblings, the researchers wrote.
Numbers of antibiotic prescriptions during the first year and the first decade of life did not significantly differ between 33 cases and 270 controls with available data. However, there was a trend toward more antibiotics prescribed to patients versus controls.
“Together with our past reports that neither cesarean section birth nor antenatal or perinatal maternal use of antibiotics predict ultimate development of IBD, it seems that neonatal changes to the microbiome are subsumed by those occurring in the first year of life,” the investigators concluded. They recommended studying the infant gut microbiome before and for several months after infections and antibiotic exposure to determine which shifts in microbiota predict IBD onset.
The Manitoba Centre for Health Policy provided access to the Population Health Research Data Repository. Dr. Bernstein is supported by the Bingham Chair in Gastroenterology. He reported ties to AbbVie Canada, Ferring Canada, Janssen Canada, Shire Canada, Takeda Canada, Pfizer Canada, Napo Pharmaceuticals, 4D Pharma, and Mylan.
SOURCE: Bernstein CN et al. Gastroenterology. 2019 Feb 14. doi: 10.1053/j.gastro.2019.02.004.