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In utero exposure to thiopurines/anti‐TNF agents and long‐term health outcomes during childhood and adolescence in Denmark
Author(s) -
Nørgård Bente Mertz,
Nielsen Jan,
Friedman Sonia
Publication year - 2020
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.15956
Subject(s) - medicine , in utero , hazard ratio , pediatrics , cohort study , cohort , autism spectrum disorder , pregnancy , psychiatry , autism , confidence interval , fetus , genetics , biology
Summary Background Data on long‐term health outcomes of children exposed in utero to thiopurines and anti‐TNF medications are lacking. Aims To examine the association between in utero exposure to thiopurines and anti‐TNF medications and child health outcomes of site‐specific groups of infections, using 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 exposed in utero to 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 exposed in utero to 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 After in utero exposure to thiopurines, we found no increased risk of infections, psychiatric diagnoses/ASD/ADHD, or malignancies during childhood/adolescence. After in utero exposure to anti‐TNF medications, the risk of respiratory, urological/gynaecological infections and other infections was increased during the first year of life.