Impact of prenatal and postnatal maternal IBD status on offspring's risk of IBD: a population-based cohort study
Linéa Bonfils1, Gry Poulsen2, Manasi Agrawal2,3
1Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark lineab@dcm.aau.dk.
Insights
Parental inflammatory bowel disease (IBD) diagnosed before childbirth significantly increases offspring IBD risk. This highlights genetic and early environmental factors over in utero inflammation for IBD development.
Area of Science:
- Gastroenterology
- Immunology
- Genetics
Background:
- Maternal inflammation in utero may influence immune development and disease susceptibility.
- Inflammatory bowel disease (IBD) encompasses Crohn's disease and ulcerative colitis, chronic conditions affecting the digestive tract.
Purpose of the Study:
- To determine if maternal IBD diagnosis before childbirth elevates offspring IBD risk compared to diagnosis after childbirth.
- To compare paternal IBD status's impact on offspring IBD risk.
Main Methods:
- Utilized Danish health registers to identify children born between 1997-2022 and their parents' IBD status.
- Employed Cox proportional hazards regression, adjusting for calendar period and delivery mode, to assess IBD risk in offspring based on parental IBD diagnosis timing.
Main Results:
- Offspring of mothers with IBD before childbirth had a 6.27-fold increased IBD risk (aHR).
- Offspring of mothers with IBD after childbirth had a 3.88-fold increased IBD risk (aHR).
- Paternal IBD before childbirth showed a 5.26-fold increased risk (aHR), and after childbirth a 3.73-fold risk (aHR).
Conclusions:
- Parental IBD diagnosis before childbirth is associated with a substantially greater offspring IBD risk.
- Findings suggest genetic predisposition and early environmental factors are more significant contributors to IBD risk than in utero inflammation.
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.
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