Joseph Meserve1, Jiyu Luo2, Wenhong Zhu3, Nina Veeravalli4, Gretchen Bandoli5, Christina D Chambers5, Abha G Singh6, Brigid S Boland1, William J Sandborn1, Uma Mahadevan7, Siddharth Singh8. 1. Division of Gastroenterology, University of California San Diego, La Jolla, California. 2. Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California; OptumLabs Visiting Fellow, Eden Prairie, Minnesota. 3. OptumLabs Visiting Fellow, Eden Prairie, Minnesota; Altman Clinical and Translational Research Institute, University of California San Diego, La Jolla, California. 4. OptumLabs, Eden Prairie, Minnesota. 5. Department of Pediatrics and Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California. 6. Division of Rheumatology, Allergy and Immunology, University of California San Diego, La Jolla, California. 7. Division of Gastroenterology, University of California San Francisco, San Francisco, California. 8. Division of Gastroenterology, University of California San Diego, La Jolla, California; OptumLabs Visiting Fellow, Eden Prairie, Minnesota; Division of Biomedical Informatics, University of California San Diego, La Jolla, California. Electronic address: sis040@ucsd.edu.
Abstract
BACKGROUND & AIMS: We conducted a retrospective cohort study to inform the safety of exposure to immunosuppressive and/or biologic agents around conception in expectant fathers with immune-mediated inflammatory diseases (IMIDs) on birth outcomes. METHODS: Using a deidentified administrative claims database (OptumLabs Data Warehouse), we identified 7453 expectant fathers with IMIDs (inflammatory bowel diseases, rheumatoid arthritis, psoriasis/psoriatic arthritis, and ankylosing spondylitis) linked to newborns with periconception medication exposure between 38 and 60 weeks before the newborn birth date (34-58 weeks prior for preterm newborns) and neonatal follow-up for 3 months after the birth date. Through logistic regression adjusting for paternal age and race (and, in a subset, for maternal age, race, presence of IMIDs, and nonsingleton births), we compared the risk of major congenital malformations (primary outcome) and preterm birth and low birth weight in fathers exposed to thiopurines (n = 461), methotrexate (n = 171), tumor necrosis factor (TNF) α antagonists (n = 1082), or non-TNF-targeting biologic agents (n = 132) vs fathers not exposed to any of these medications (n = 5607). RESULTS: As compared to unexposed fathers (3.4% prevalence of major congenital malformations), exposure to thiopurines (relative risk [RR], 1.12; 95% confidence interval [CI], 0.66-1.76), methotrexate (RR, 0.67; 95% CI, 0.21-1.55), TNF-α antagonists (RR, 1.14; 95% CI, 0.81-1.57), and non-TNF-targeting biologic agents (RR, 1.75; 95% CI, 0.80-3.24) was not associated with increased risk of major congenital malformations. No association was observed between paternal medication exposure and risk of preterm birth or low birth weight. Results were stable on subanalyses of linked father-mother-newborn triads. CONCLUSIONS: In a large cohort study of 7453 expectant fathers with IMIDs, exposure to immunosuppressive or biologic agents around conception was not associated with increased risk of adverse birth outcomes.
BACKGROUND & AIMS: We conducted a retrospective cohort study to inform the safety of exposure to immunosuppressive and/or biologic agents around conception in expectant fathers with immune-mediated inflammatory diseases (IMIDs) on birth outcomes. METHODS: Using a deidentified administrative claims database (OptumLabs Data Warehouse), we identified 7453 expectant fathers with IMIDs (inflammatory bowel diseases, rheumatoid arthritis, psoriasis/psoriatic arthritis, and ankylosing spondylitis) linked to newborns with periconception medication exposure between 38 and 60 weeks before the newborn birth date (34-58 weeks prior for preterm newborns) and neonatal follow-up for 3 months after the birth date. Through logistic regression adjusting for paternal age and race (and, in a subset, for maternal age, race, presence of IMIDs, and nonsingleton births), we compared the risk of major congenital malformations (primary outcome) and preterm birth and low birth weight in fathers exposed to thiopurines (n = 461), methotrexate (n = 171), tumor necrosis factor (TNF) α antagonists (n = 1082), or non-TNF-targeting biologic agents (n = 132) vs fathers not exposed to any of these medications (n = 5607). RESULTS: As compared to unexposed fathers (3.4% prevalence of major congenital malformations), exposure to thiopurines (relative risk [RR], 1.12; 95% confidence interval [CI], 0.66-1.76), methotrexate (RR, 0.67; 95% CI, 0.21-1.55), TNF-α antagonists (RR, 1.14; 95% CI, 0.81-1.57), and non-TNF-targeting biologic agents (RR, 1.75; 95% CI, 0.80-3.24) was not associated with increased risk of major congenital malformations. No association was observed between paternal medication exposure and risk of preterm birth or low birth weight. Results were stable on subanalyses of linked father-mother-newborn triads. CONCLUSIONS: In a large cohort study of 7453 expectant fathers with IMIDs, exposure to immunosuppressive or biologic agents around conception was not associated with increased risk of adverse birth outcomes.