Impact of prenatal and postnatal maternal IBD status on offspring's risk of IBD: a population-based cohort study.

OBJECTIVE: In utero exposure to maternal inflammation may impact immune system development and subsequent risk of disease. We investigated whether a maternal diagnosis of IBD before childbirth is linked to a higher risk of IBD in offspring compared with a diagnosis after childbirth. Further, we analysed paternal IBD status for comparison. DESIGN: Using Danish health registers, we identified all individuals born in Denmark between 1997 and 2022 and their legal parents, as well as their IBD status. Cox proportional hazards regression analyses adjusted for calendar period and mode of delivery were used to estimate offspring IBD risk by maternal and paternal IBD status before and after childbirth. RESULTS: Of 1 290 358 children, 10 041 (0.8%) had mothers with IBD diagnosis before childbirth and 9985 (0.8%) had mothers with IBD diagnosis after childbirth. Over 18 370 420 person-years, 3537 individuals were diagnosed with IBD. Offspring of mothers with IBD before childbirth had an adjusted HR of IBD of 6.27 (95% CI 5.21, 7.54) compared with those without maternal IBD, while offspring of mothers with IBD after childbirth had an adjusted HR of 3.88 (95% CI 3.27, 4.60). Corresponding adjusted HRs were 5.26 (95% CI 4.22, 6.56) among offspring with paternal IBD before childbirth and 3.73 (95% CI 3.10, 4.50) for paternal IBD after childbirth. CONCLUSION: Offspring had a greater risk of IBD when either parent was diagnosed before childbirth rather than later, emphasising genetic predisposition and environmental risk factors rather than maternal inflammation in utero as risk factors for IBD.

Epidemiology of Elderly-Onset IBD: A Nationwide Population-based Cohort Study.

BACKGROUND AND AIMS: We examined the incidence and natural history of patients with very elderly-onset (herein, referred to as very late-onset) inflammatory bowel diseases (IBD) (age ≥70y at diagnosis), compared with patients diagnosed between ages 60-69y in Denmark. METHODS: In the Danish National Patient Register, between 1980-2018, we identified all individuals ≥60y with newly diagnosed Crohn's disease (CD) and ulcerative colitis (UC) and examined trends in incidence, cumulative risk of hospitalization, treatment patterns, IBD-related surgery, serious infection, cancer and cardiovascular and venous thromboembolic risks among very late-onset (70-79y or 80+ years) vs. late-onset (60-69y) IBD, using non-parametric competing risk analysis treating death as competing risk. RESULTS: We identified 3,459 patients with onset of CD at age ≥60y (47% ≥70y) and 10,774 patients with onset of UC aged ≥60y (51% ≥70y). Over the last three decades, incidence changes for very late-onset and late-onset IBD have followed the same patterns. Also, both for CD and UC, cumulative incidence of IBD-related hospitalization and corticosteroid use was comparable in very late-onset vs. late-onset patients. However, the burden of disease-modifying therapy, either immunomodulator or TNF antagonist use, and major IBD-related surgery was significantly lower in patients with very late-onset than in late-onset IBD. On the other hand, 5-year risk of serious infections and cardiovascular events was higher in patients with very late-onset IBD. CONCLUSION: This nationwide cohort study shows that patients diagnosed with very late-onset (≥70y) IBD have a higher relative burden of disease- and aging-related complications, with limited use of steroid-sparing strategies and surgery, compared with late-onset IBD.

Medication-Wide Study: Exploring Medication Use 10 Years Before a Diagnosis of Inflammatory Bowel Disease.

INTRODUCTION: There is growing interest in the prediagnostic phase of inflammatory bowel disease (IBD) and in the overlap of IBD with other diseases. We described and compared use of any prescription medication between individuals with and without IBD in a 10-year period preceding diagnosis. METHODS: Based on cross-linked nationwide registers, we identified 29,219 individuals diagnosed with IBD in Denmark between 2005 and 2018 and matched to 292,190 IBD-free individuals. The primary outcome was use of any prescription medication in years 1-10 before IBD diagnosis/matching date. Participants were considered as medication users if they redeemed ≥1 prescription for any medication in the World Health Organization Anatomical Therapeutic Chemical (ATC) main groups or subgroups before diagnosis/matching. RESULTS: The IBD population had a universally increased use of medications compared with the matched population before IBD diagnosis. At 10 years before diagnosis, the proportion of users was 1.1-fold to 1.8-fold higher in the IBD population in 12 of 14 ATC main groups of medication ( P -value < 0.0001). This applied across age, sex, and IBD subtypes, although it was the most pronounced for Crohn's disease (CD). Two years before diagnosis, the IBD population had a steep increase in medication use for several organ systems. When analyzing therapeutic subgroups of medication, the CD population exhibited 2.7, 2.3, 1.9, and 1.9 times more users of immunosuppressants, antianemic preparations, analgesics, and psycholeptics, respectively, than the matched population 10 years before diagnosis ( P -value < 0.0001). DISCUSSION: Our findings demonstrate universally increased medication use years before IBD, especially CD, diagnosis and indicates multiorgan involvement in IBD.

Fasting serum levels of ferritin are associated with impaired pancreatic beta cell function and decreased insulin sensitivity: a population-based study.

AIMS/HYPOTHESIS: Elevated serum ferritin levels are associated with an increased risk of type 2 diabetes, but the nature of this association remains elusive. The aim of this study was to test the hypothesis that an elevated fasting serum ferritin level is associated with an increased risk of type 2 diabetes due to its association with impaired beta cell function and decreased insulin sensitivity. METHODS: We investigated 6,392 individuals from the Danish general population. Surrogate measures of beta cell function and insulin sensitivity were calculated for approximately 6,100 individuals based on OGTT examinations. RESULTS: The ORs for type 2 diabetes were 4.2 (95% CI 2.4, 7.2) for the highest vs the lowest quintile of serum ferritin, and 17 (95% CI 8.9, 33) for serum ferritin levels ≥97.5th percentile vs <20th percentile. Elevated serum ferritin levels were associated with elevated plasma glucose levels at 0, 30 and 120 min (p < 0.001), elevated serum insulin levels at 0 and 120 min (p = 0.02 and p < 0.001), decreased beta cell function estimated as the insulinogenic index and corrected insulin response (p < 0.001), and decreased insulin sensitivity estimated by the Matsuda index of insulin sensitivity and HOMA-IR (p < 0.001). Whereas the association with impaired beta cell function was present in both men and women, the association with decreased insulin sensitivity was observed among men and older women but not among younger women. CONCLUSIONS/INTERPRETATION: Elevated fasting serum ferritin levels are associated with surrogate measures of both impaired beta cell function and decreased insulin sensitivity. Menopause seems to modify the association with insulin sensitivity.