In uteroexposure to thiopurines/anti-TNF agents and long-term health outcomes during childhood and adolescence in Denmark

Background Data on long-term health outcomes of children exposedin uteroto thiopurines and anti-TNF medications are lacking. Aims To examine the association betweenin uteroexposure to thiopurines and anti-TNF medications and child health outcomes of site-specific groups of infections, a composite endpoint including psychiatric diagnoses/autism spectrum disorder (ASD)/attention deficit hyperactivity disorder (ADHD), and malignancies during childhood/adolescence. Methods A nationwide cohort study based on Danish health registries included 1 311 009 live born children during 1995 through 2015. Outcomes were based on hospital diagnoses (in-patients/out-patients/emergency department contacts). Results In total, 1048 children were exposedin uteroto thiopurines and 1 309 961 were unexposed. The adjusted hazard ratios (HRs) for site-specific groups of infections in the first 3 years of life were close to unity. The adjusted HR of psychiatric diagnoses/ASD/ADHD was 1.11 (95% CI 0.81-1.52). The HR of malignancies was not calculated (only two events among the exposed). In total, 493 children were exposedin uteroto anti-TNF medications and 728 055 were unexposed. Within the first year of life, the adjusted HR of respiratory, urological/gynaecological infections and other infections were 1.34 (95% CI 1.03-1.74), 2.36 (95% CI 1.15-4.81) and 1.61 (95% CI 1.21-2.13), respectively. We found no increased risk of other adverse outcomes. Conclusions Afterin uteroexposure to thiopurines, we found no increased risk of infections, psychiatric diagnoses/ASD/ADHD, or malignancies during childhood/adolescence. Afterin uteroexposure to anti-TNF medications, the risk of respiratory, urological/gynaecological infections and other infections was increased during the first year of life.