M Chaparro1, A Verreth2, T Lobaton3, E Gravito-Soares4, M Julsgaard5, E Savarino6, F Magro7, Avni I Biron8, P Lopez-Serrano9, M J Casanova1, M Gompertz10, S Vitor11, M Arroyo12, D Pugliese13, Y Zabana14, R Vicente15, M Aguas16, Bar-Gil A Shitrit17, A Gutierrez18, G A Doherty19, L Fernandez-Salazar20, Martínez J Cadilla21, J M Huguet22, A OʼToole23, E Stasi24, Manceñido N Marcos25, A Villoria26, K Karmiris27, J F Rahier28, C Rodriguez29, Diz-Lois M Palomares30, G Fiorino31, J M Benitez32, M Principi33, T Naftali34, C Taxonera35, G Mantzaris36, L Sebkova37, B Iade38, D Lissner39, Ferrer I Bradley40, Lopez-San A Roman41, I Marin-Jimenez42, O Merino43, M Sierra44, M Van Domselaar45, F Caprioli46, I Guerra47, P Peixe48, M Piqueras49, I Rodriguez-Lago50, Y Ber51, K van Hoeve52, P Torres3, M Gravito-Soares4, D Rudbeck-Resdal5, O Bartolo6, A Peixoto7, G Martin8, A Armuzzi13, A Garre1, M G Donday1, Martín F J de Carpi53, J P Gisbert1. 1. Gastroenterology Units Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain. 2. Department of Gastroenterology and Department of Pediatric Gastroenterology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. 3. Hospital Universitari Germans Trias i Pujol and CIBEREHD, Badalona, Spain. 4. Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. 5. Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. 6. University of Padua, Padua, Italy. 7. Centro Hospitalar São João, Porto, Portugal. 8. Gastroenterology Devision, Rabin Medical Center, Petach Tikva, Israel. 9. Hospital Universitario Fundación Alcorcón, Alcorcón, Spain. 10. Hospital Clinic and CIBEREHD, Barcelona, Spain. 11. Hospital de Santa Maria - Centro Hospitalar Lisboa Norte, Lisboa, Portugal. 12. Hospital Clinico Universitario Lozano Blesa, IIS Aragon, CIBEREHD, Zaragoza, Spain. 13. IBD Unit, Presidio Columbus, Fondazione Policlinico Gemelli Università Cattolica, Roma, Italy. 14. Hospital Universitari Mutua de Terrassa and CIBEREHD, Terrassa, Spain. 15. Hospital Universitario Miguel Servet, Zaragoza, Spain. 16. Hospital Universitario La Fe and CIBEREHD, Valencia, Spain. 17. Shaare Zedek Medical Center, Jerusalem, Israel. 18. Hospital General Universitario de Alicante and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Alicante, Spain. 19. St. Vincents University Hospital, Dublin, Ireland. 20. Hospital Clinico Universitario de Valladolid, Valladolid, Spain. 21. Hospital Universitario Alvaro Cunqueiro, Vigo, Spain. 22. Hospital General Universitario de Valencia, Valencia, Spain. 23. Beaumont Hospital, Dublin, Ireland. 24. IRCCS Saverio de Bellis, Castellana Grotte, Italy. 25. Hospital Universitario Infanta Sofia, Madrid, Spain. 26. Hospital Universitari Parc Taulí.Institut d'Investigació i Innovació Parc Taulí. Departament de Medicina, Universitat Autònoma de Barcelona.CIBERehd, Instituto de Salud Carlos III, Sabadell, Spain. 27. Venizeleio General Hospital, Heraklion, Greece. 28. CHU UCL Namur, Yvoir, Belgium. 29. Complejo Universitario de Navarra, Pamplona, Spain. 30. Hospital Universitario A Coruña, Coruña, Spain. 31. IBD Center, Humanitas Clinical and Research Institute, Rozzano, Milan, Italy and Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy. 32. Hospital Universitario Reina Sofia and IMIBIC, Córdoba, Spain. 33. Azienda Policlinico Ospedaliero-Universitaria di Bari, Bari, Italy. 34. Meir Hospital Kfar saba Tel Aviv University, Tel Aviv, Israel. 35. Hospital Clínico San Carlos and IdISSC, Madrid, Spain. 36. Evangelismos, Ophthalmiatreion Athinon and Polyclinic Hospitals, Athens, Greece. 37. Azienda Ospedaliera "Pugliese-Ciaccio", Catanzaro, Italy. 38. Hospital de Clinicas, Montevideo, Uruguay. 39. Universitatsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. 40. Hospital de Manises, Manises, Spain. 41. Hospital Ramón y Cajal, Madrid, Spain. 42. Hospital General Universitario Gregorio Marañón and IiSGM, Madrid, Spain. 43. Hospital Universitario de Cruces, Baracaldo, Spain. 44. Complejo Universitario de León, León, Spain. 45. Hospital de Torrejón, Torrejón de Ardoz, Spain. 46. Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano AND Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. 47. Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain. 48. Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal. 49. Consorci Sanitari de Terrasa, Terrasa, Spain. 50. Hospital de Galdakao, Vizcaya, Spain. 51. Hospital San Jorge, Huesca, Spain. 52. Department of Paediatrics, University Hospitals Leuven, KU Leuven, Leuven, Belgium. 53. Hospital Sant Joan de Deu, Barcelona, Spain.
Abstract
OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.
OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.
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Authors: Christopher Andrew Lamb; Nicholas A Kennedy; Tim Raine; Philip Anthony Hendy; Philip J Smith; Jimmy K Limdi; Bu'Hussain Hayee; Miranda C E Lomer; Gareth C Parkes; Christian Selinger; Kevin J Barrett; R Justin Davies; Cathy Bennett; Stuart Gittens; Malcolm G Dunlop; Omar Faiz; Aileen Fraser; Vikki Garrick; Paul D Johnston; Miles Parkes; Jeremy Sanderson; Helen Terry; Daniel R Gaya; Tariq H Iqbal; Stuart A Taylor; Melissa Smith; Matthew Brookes; Richard Hansen; A Barney Hawthorne Journal: Gut Date: 2019-09-27 Impact factor: 23.059