Abstract
Background
The risk of morbidity and mortality related to paediatric-onset inflammatory bowel disease (PIBD) and its treatment is a major concern to both patients and clinicians, especially when this may affect early adult life. We aimed to determine whether PIBD patients are at increased risk of ischaemic heart disease (IHD), stroke, cancer and death in a nationwide population-based study using administrative health data research methodology.
Methods
All children diagnosed with PIBD in Scotland 1981–2017 were identified within the Scottish Morbidity Record inpatient and day-case dataset (SMR01). PIBD cases were defined as any inpatient International Classification of Diseases (ICD) coding for Crohn’s disease (CD; 555/K50) or ulcerative colitis (UC; 556/K51) until age 16; 10% of cases were individually validated. A nested case-control study (1:3 ratio) matched for sex, age, postcode sector and deprivation quintile within the Scottish population was performed. Data-linkage was applied to SMR01, SMR06 (Scottish Cancer Registry) and NRS deaths datasets to identify any diagnosis of IHD, acute stroke, cancer or mortality. Cancer diagnoses were classified into potential disease related (small bowel, colonic, rectal, anal, hepatobiliary) or treatment related (lymphoma, leukaemia, myeloma, PTLD) cancers. Hazard ratios (HR) were calculated for each outcome using mixed effects Cox regression and the potential effect of sex, year of diagnosis and age at diagnosis were explored.
Results
The study population comprised 2484 children with PIBD and 7451 matched controls. Median age of PIBD diagnosis was 12 years (IQR 10–14) and age at end of follow-up 24 years (IQR 17–33) with 141,605 total person-years follow-up. Validation identified 242/261 true positive cases (positive predictive value 93%). 2 cases (0.08%) and 7 controls (0.09%) had an admission for IHD during follow-up (p = 0.845); 6 cases (0.24%) and 5 controls (0.07%) were admitted for stroke (p = 0.024). PIBD cases had a significantly higher risk of any cancer diagnosis (62 cases: 97 controls) HR 1.97 (p < 0.001), including a 31.9 times higher risk of disease-related cancers (p < 0.001) and a 6 times higher risk of treatment-related cancers (p = 0.011). The effect of PIBD on cancer risk was higher in males, but not related to year or age. PIBD cases had a greater risk of mortality (60 cases: 51 controls) HR 3.61 (p < 0.001). The specific mortality risk from infection was 21.4 times higher in PIBD cases (p = 0.004); the risk of suicide was 2.4 times higher but not statistically significant (p = 0.085). The effect of PIBD on mortality risk was not modified by sex, year or age.
Conclusion
Cancer and mortality are meaningful, serious early adult life adverse sequelae of PIBD however IHD and stroke occur infrequently.
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