Pre- and perinatal exposures associated with developing pediatric-onset immune-mediated inflammatory disease: A Danish nation-wide cohort study

Objectives: We aimed to identify pre- and perinatal risk factors for developing pediatric-onset immune-mediated inflammatory (pIMID). Methods: This nation-wide, cohort study included all children born in Denmark from 1994 to 2014 identified from the Danish Medical Birth registry. Individuals were followed through 2014 and cross-linked to the continuously updated national socioeconomic and healthcare registers to obtain data on pre- and perinatal exposures (maternal age, educational level, smoking, maternal IMID, parity, mode of conception and delivery, plurality, child's sex, and birth season). The primary outcome was a pIMID diagnosis (inflammatory bowel disease, autoimmune hepatitis, primary sclerosing cholangitis, juvenile idiopathic arthritis, or systemic lupus erythematosus) before 18 years of age. Risk estimates were calculated using Cox proportional hazards model and presented by hazard ratios (HR) with 95% confidence intervals (95%CI). Results: We included 1,350,353 children with a follow-up time of 14,158,433 person-years. Among these, 2,728 were diagnosed with a pIMID. We found a higher risk of pIMID in children born to women with a preconception IMID diagnosis (HR: 3.5 [95%CI: 2.7–4.6]), children born by Caesarean section (HR: 1.2 [95%CI: 1.0–1.3]), and among females (1.5 [95%CI: 1.4–1.6]) than among children without these characteristics. Plural pregnancies were associated with a lower risk of pIMID than single pregnancies (HR: 0.7 [95%CI: 0.6–0.9]). Conclusions: Our results indicate a high genetic burden in pIMID but also identifies intervenable risk factors, such as Cesarean section. Physicians should, keep this in mind when caring for high-risk populations and pregnant women previously diagnosed with an IMID.