Offspring exposed to maternal CD early in life had a markedly increased risk for developing CD compared with those exposed to parental CD later in life.

Sun-Ho Lee, MD, PhD
Mount Sinai Hospital, Canada

Offspring of parents with Crohn’s disease have a 6-8-fold higher risk for incident CD compared with the general population. In particular, pregnancy and the first year postpartum seem to be critical for the development and maturation of both the gut microbiome and immune responses. Therefore, Sun-Ho Lee, MD, PhD, of Mount Sinai Hospital and his team tried to explore whether exposure to parental CD diagnosis during this period compared with exposure later in life is associated with an increased risk for CD. Particularly, they assessed whether early life exposure to CD impacts the offspring’s gut inflammation, intestinal permeability, and gut microbiome.

The researchers analyzed data from 1,252 offspring of patients with CD who were recruited in the Crohn´s Colitis Canada GEM Project, a large prospective cohort study following healthy, first-degree relatives of patients with CD to identify genetic, environmental, and microbial determinants of CD. “We specifically concentrated on the offspring cohort and looked when parents received their CD diagnosis,” Dr. Lee explained. Therefore, they classified offspring into “perinatally exposed” and “exposed later in life” to parental CD diagnosis. In total, 586 patients with a parental CD diagnosis in the perinatal period (pregnancy and first year postpartum) could be identified and were compared with offspring that had parents with a CD diagnosis after the perinatal period (N=666). The only difference between the cohorts was the country of recruitment.

After a 5-year period, 2% of the early-exposure cohort compared with only 0.5% of the late cohort had a diagnosis of CD. This translated in a hazard ratio of 4.73, even after adjustment for age. “You see a dose effect regarding the exposure to mother’s CD diagnosis. The earlier you are exposed, the higher seems to be the effect size,” Dr. Lee says. Patients with an exposure to a parent’s CD diagnosis during the perinatal period had an increase in intestinal permeability and an altered fecal bacterial composition.

The authors conclude that environmental exposure to a parent with CD during the perinatal period may have a lingering impact on offspring’s gut barrier function and gut microbiome development and thus elevates the risk for CD development.

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