789 Inflamm Bowel Dis • Volume 25, Number 4, April 2019 ORIGINAL RESEARCH ARTICLE—CLINICAL Safety of Anti-TNF-Alpha Therapy During Pregnancy on Long- term Outcome of Exposed Children: A Controlled, Multicenter Observation Dana Duricova, MD, PhD,* Eva Dvorakova, PharmD,* Ondrej Hradsky, MD, PhD, † Katarina Mitrova, MD, PhD,* ,† Marianna Durilova, MD, PhD, ‡ Jana Kozeluhova, MD, PhD, § Pavel Kohout, MD, PhD, ¶ Kristyna Zarubova, MD, † Jiri Bronsky, MD, PhD, † Nora Hradska, MD, ‖ Eva Bronska, MD,** Miroslava Adamcova, MD,** Nadezda Machkova, MD,* Veronika Hruba, MD,* Martin Bortlik, MD, PhD,* ,††,‡‡ Martin Lukas, MD,* Karin Malickova, MD,* and Milan Lukas, MD, PhD* Background: Evidence of the impact of in utero exposure to anti–tumor necrosis factor (TNF)–alpha on long-term childhood development is limited. The aim was to assess the impact of in utero exposure to anti-TNF-alpha due to mothers’ infammatory bowel disease (IBD) on long- term postnatal development of exposed children. Methods: We included consecutive children (≥12 months of age) born to mothers with IBD (2007–2016) treated with anti-TNF-alpha during pregnancy in 3 centers in the Czech Republic. A control group was comprised of unexposed children of non-IBD mothers undergoing mandatory check-ups at general pediatricians’ offces. Data on perinatal period, psychomotor development, vaccination, infections, antibiotics, and allergy were collected by treating pediatricians using a predefned questionnaire. Results: Seventy-two exposed and 69 unexposed children were included (median age, 35 and 50 months, respectively). Exposed children had growth and psychomotor development similar to controls. There was no signifcant difference in infectious complications within the frst year of life (23.9% vs 17.4%; P = 0.36) or during the whole follow-up between exposed infants and controls (P = 0.32). Concomitant immunosup- pressants during pregnancy and anti-TNF-alpha levels in cord blood were not associated with elevated infection rate within the frst year of life (P > 0.05). Over 95% of exposed children had adequate serologic response to vaccination, except for haemophilus and mumps vaccines. Clinically manifested allergy was similar between the groups (P = 0.98). Conclusions: Anti-TNF-alpha exposure in utero does not seem to have a negative impact on postnatal development of children with regard to infectious complications, allergy, growth, or psychomotor development when compared with unexposed children of non-IBD women. Key Words: anti-TNF-alpha, children, infections, vaccination, inflammatory bowel disease INTRODUCTION Infammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic infamma- tory bowel disorder diagnosed mainly at a young, reproductive age. 1 Thus, a clinically signifcant proportion of female patients conceive after the onset of the disease and are exposed during their pregnancy to IBD-related medication including biologic therapy. Therefore, a knowledge of safety for the treatment Received for publications August 1, 2018; Editorial Decision August 23, 2018. From the *IBD Clinical and Research Center, ISCARE IVF, a.s., Prague, Czech Republic; † Department of Pediatrics and ‡ Department of Pediatric Surgery, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic; § Department of Internal Medicine, University Hospital Plzeň, Plzeň, Czech Republic; ¶ Department of Internal Medicine, Thomayer University Hospital, Prague, Czech Republic; ‖ Private practice, Litovel, Czech Republic; ** Private practice, Prague, Czech Republic; †† Department of Internal Medicine, First Faculty of Medicine, Charles University and Military University Hospital, Prague, Czech Republic; ‡‡ Institute of Pharmacology, First Faculty of Medicine, Charles University, Prague, Czech Republic © 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Conficts of interest: Dana Duricova: speaker for AbbVie and Takeda; attendance of advisory board for Janssen. Eva Dvorakova: none to declare. Ondrej Hradsky: lectures/ congress fees/consultancy: MSD, AbbVie, Nutrica, Nestlé, Ferring, Falk. Katarina Mitrova: speaker for AbbVie. Marianna Durilova: none to declare. Jana Kozeluhova: none to declare. Pavel Kohout: lecture fees from MSD, Abbvie; consultancy: Janssen. Kristyna Zarubova: consultancy for Nestlé, Nutricia. Jiri Bronsky: lectures/congress fees/con- sultancy: AbbVie, MSD, Nutricia, Nestle, Biocodex, Akacia, Walmark. Nora Hradska: none to declare. Eva Bronska: congress fees from Pfzer. Miroslava Adamcova: none to declare. Nadezda Machkova: speaker for AbbVie and Takeda. Veronika Hruba: speaker for Janssen. Martin Bortlik: consultant or speaker for Abbvie, Janssen, Pfzer, Takeda, Biogen, and Egis. Martin Lukas: none to declare. Karin Malickova: consultant and speaker for Takeda Celltrion. Milan Lukas: consultant or speaker for Janssen, MSD, Pfzer, Takeda Celltrion, and Egis. Supported by: This study was supported by the IBD-COMFORT Foundation. Address correspondence to: Dana Duricova, MD, PhD, IBD Clinical and Research Centre, ISCARE IVF, Jankovcova 1569/2c, Prague 7, 170 00, Czech Republic (dana. duricova@seznam.cz). doi: 10.1093/ibd/izy294 Published online 20 September 2018 Downloaded from https://academic.oup.com/ibdjournal/article/25/4/789/5104315 by guest on 18 June 2022