Bente Mertz Nørgård

Background and aim Paternal use of analgesics during the time of conception and adverse birth outcomes are poorly studied. We investigated the association between paternal exposure to non‐steroid anti‐inflammatory drugs and opioids within 3 months before the date of conception and the risk of adverse birth outcomes (preterm birth, small for gestational age, low Apgar score, and major congenital malformations). Methods We used nationwide data from the Danish health registers. We included information on all singleton live births, and their fathers and mothers from 1997 to 2018. We created two exposed cohorts, children with preconception paternal exposure to (1) non‐steroid anti‐inflammatory drugs and (2) opioids. The unexposed cohort was children without preconception paternal exposure to non‐steroid anti‐inflammatory drugs or opioids, and we performed a sub‐analysis against paternal use of acetaminophen (paracetamol). We used logistic regression models to estimate the odds ratios of adverse birth outcomes including 95% confidence intervals. Results We identified 1,260,934 children, 45,667 children with paternal exposure to non‐steroid anti‐inflammatory drugs, 10,086 children with paternal exposure to opioids, and 1,205,181 unexposed children. The adjusted odds ratio for preterm birth was 1.08 (95% confidence interval, 1.03–1.13) after paternal exposure to non‐steroid anti‐inflammatory drugs and 1.21 (95% confidence interval, 1.08–1.35) after paternal exposure to opioids. The adjusted odds ratio for small for gestational age was 1.09 (95% confidence interval, 1.03–1.17) after paternal exposure to non‐steroid anti‐inflammatory drugs, and 1.03 (95% confidence interval, 0.88–1.21) after paternal exposure to opioids. We found null‐associations for a low Apgar score and major congenital malformations. Estimates were attenuated when compared against paternal paracetamol exposure. Conclusions Overall, we found null‐associations across the comparisons made. Weak associations were found for paternal exposure to non‐steroid anti‐inflammatory drugs or opioids and preterm birth and small for gestational age, but not with low Apgar score or major congenital malformation. All associations were attenuated when compared against an active comparator of paternal paracetamol exposure. The effect sizes were small and less likely to be of clinical relevance.

INTRODUCTION: Patients with inflammatory bowel diseases (IBD) commonly require analgesic medications to treat pain, which may be associated with complications. We examined trends of analgesic use according to age at IBD onset. METHODS: This nationwide cohort study included adults diagnosed with IBD between 1996 and 2021 in Denmark. Patients were stratified according to their age at IBD onset: 18–39 years (young adult), 40–59 years (adult), and older than 60 years (older adult). We examined the proportion of patients who received prescriptions for analgesic medications within 1 year after IBD diagnosis: strong opioids, tramadol, codeine, nonsteroidal anti-inflammatory drugs, and paracetamol. Multivariable logistic regression analysis was performed to examine the association between age at IBD onset and strong opioid prescriptions and the composite of strong opioid/tramadol/codeine prescriptions. RESULTS: We identified 54,216 adults with IBD. Among them, 25,184 (46.5%) were young adults, 16,106 (29.7%) were adults, and 12,926 (23.8%) were older adults at IBD onset. Older adults most commonly received analgesic prescriptions of every class. Between 1996 and 2021, strong opioid, tramadol, and codeine prescriptions were stable, while paracetamol prescriptions increased and nonsteroidal anti-inflammatory drug prescriptions decreased. After multivariable logistic regression analysis, older adults had higher adjusted odds of receiving strong opioid prescriptions (adjusted odds ratio 1.95, 95% confidence interval 1.77–2.15) and the composite of strong opioid/tramadol/codeine prescriptions (adjusted odds ratio 1.93, 95% confidence interval 1.81–2.06) within 1 year after IBD diagnosis compared with adults. DISCUSSION: In this nationwide cohort, older adults most commonly received analgesic prescriptions within 1 year after IBD diagnosis. Additional research is needed to examine the etiology and sequelae of increased analgesic prescribing to this demographic.

Summary Objective In patients with elderly (≥60 years) onset inflammatory bowel disease (IBD), we studied initiation of medications, drug persistency and surgeries. Design A nationwide cohort study based on Danish registries, comprising incident IBD patients ≥18 years from 1995 to 2020 ( N = 69,039). Patients were divided into elderly ( N = 19,187) and adult onset ( N = 49,852). Outcomes were initiation of thiopurines, 5‐ASA, biologics and corticosteroids within 1 and 5 years after diagnosis, and for those who initiated medications, we estimated drug persistency. Surgeries were examined within 1 and 5 years. We used regression models controlling for covariates. Results In elderly patients, the adjusted hazard ratios (aHR) for initiating thiopurines, 5‐ASA and biologics within 1 year were 0.44 (95% CI 0.42–0.47), 0.77 (95% CI 0.75–0.79) and 0.29 (95% CI 0.26–0.31) respectively. The results were similar within 5 years. In elderly patients, drug persistency for thiopurines, 5‐ASA and biologics was not impaired within 5 years. The aHR of stopping steroids within 1 and 5 years were 0.80 (95% CI 0.76–0.84) and 0.77 (95% CI 0.74–0.80) respectively. The risk of surgeries was increased in the elderly patients (in ulcerative colitis, within 5 years, aHR 1.39 [95% CI 1.27–1.52], and in Crohn's disease 1.13 [95% CI 1.04–1.23]). Conclusion We found significantly low chance of initiation of IBD medications in elderly patients, the reason may not be due to mild disease course. In elderly patients, drug persistency was comparable to adults. Clinicians should carefully consider whether they underuse IBD‐specific medications in elderly patients, and special attention should be applied to timely discontinuation of corticosteroids.