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Perinatal period is crucial for the risk of developing CD

Presented by
Prof. Sun-Ho Lee, Mount Sinai Hospital, Canada
Medical Writer
Susanne Kammerer
ECCO 2023
Babies that are exposed to parental’s Crohn’s disease (CD) within the first year of life have a more than 4-fold increased risk of developing CD compared with those exposed to parental’s CD from year 1 onwards. Early exposure to a mother’s CD is associated with an even 6-fold risk.

Studies have shown that the perinatal period is critical for the development and maturation of both the gut microbiome as well as immune responses [1,2]. Newborns of women with CD have altered stool microbiome composition and immune cell function [2]. Furthermore, the offspring of parents with CD have a 6-8-fold risk of incident CD compared with the general population [1]. Therefore, Prof. Sun-Ho Lee (Mount Sinai Hospital, Canada) and his team tried to explore whether exposure to parental CD diagnosis during this vulnerable period compared with exposure later in life is associated with an increased risk of CD [3]. Particularly, they assessed whether early life exposure to a parent’s CD diagnosis impacts the offspring’s gut inflammation markers, intestinal permeability, and gut microbiome.

Data was analysed 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 had their CD diagnosis,” Dr Lee explained. Accordingly, participants were classified as “perinatally exposed” (i.e. during pregnancy and the first year postpartum; n=586) or “exposed later in life” (n=666) to parental CD diagnosis. The only difference between the cohorts was the country of recruitment.

After 5 years, 2% of the early-exposure cohort compared with only 0.5% of the late-exposure cohort had a diagnosis of CD. This translated into a hazard ratio (HR) of 4.7 (95% CI 1.28–17.46), even after adjustment for age (see Figure). “You see a dose effect regarding the exposure to a mother’s CD diagnosis: the earlier you are exposed, the higher seems to be the effect size,” Dr Lee said. This effect was not observed in the fathers. Exposure to a mother’s CD who was diagnosed more than a year before birth was associated with an HR of 6.3. This effect was not observed in the fathers. Participants exposed to their parents’ CD diagnosis during the perinatal period had an increased intestinal permeability and altered faecal bacterial composition.

Figure: Higher survival probability in offspring exposed to Parent’s CD after perinatal period [3]

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

  1. Moller FT, et al. Am J Gastroenterol. 2015;110:564–71.
  2. Torres J, et al. Gut. 2020;69:42–51.
  3. Lee SH, et al. Peri-natal exposure to parental Crohn’s disease is associated with impaired gut barrier, microbiome composition differences and increased risk of Crohn’s disease. OP29, ECCO 2023, 1–4 March, Copenhagen, Denmark.

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