ORIGINAL ARTICLE The Effect of Disease Activity on Birth Outcomes in a Nationwide Cohort of Women with Moderate to Severe Inflammatory Bowel Disease Heidi Kammerlander, MD,* Jan Nielsen, PhD,* Jens Kjeldsen, MD, PhD, † Torben Knudsen, MD, DMSc, ‡ Sonia Friedman, MD,* ,§ and Bente Nørgård, MD, PhD, DMSc* ,§ Background: Active inflammatory bowel disease (IBD) during conception and pregnancy may increase the risk of adverse birth outcomes. Former studies have examined heterogeneous groups of women with varying degrees of IBD severity. We aimed to examine the effect of active IBD on birth outcomes in a more homogeneous group of women with a moderate to severe disease course. Since in Denmark, moderate to severe IBD is an indication for use of anti-tumor necrosis factor-a therapy, we examined all women who used anti-tumor necrosis factor therapy during pregnancy. Methods: We identified a nationwide cohort of 219 singleton pregnancies in women treated with anti-tumor necrosis factor-a therapy during pregnancy (2005–2014). Pregnancies with clinical disease activity (65.8%) constituted the exposed cohort and pregnancies without disease activity constituted the unexposed (34.2%). Disease activity scores were supported by levels of fecal calprotectin. Outcomes included low birth weight, preterm birth, and congenital anomalies. Results: In women with IBD, disease activity was associated with adjusted odds ratio of low birth weight and preterm birth; 2.05 (95% confidence interval, 0.37–11.35) and 2.64 (95% confidence interval, 0.85–8.17), respectively. In those with clinical moderate to severe disease activity, the odds ratio for preterm birth was 3.60 (95% confidence interval, 1.14–11.36). In women with ulcerative colitis and disease activity, 19.5% had a child with low birth weight and 29.3% gave birth preterm. Conclusion: In women with moderate to severe IBD, 66% experienced disease activity during pregnancy. In those with the highest degree of disease activity, the risk of preterm birth was increased 3 to 4 folds. The proportion of adverse birth outcomes was high, particularly among women with ulcerative colitis and disease activity. (Inflamm Bowel Dis 2017;23:1011–1018) Key Words: inflammatory bowel disease, birth outcomes, clinical epidemiology, anti-TNF-a therapy T he majority of patients with inflammatory bowel disease (IBD) are diagnosed during the ages of 15 to 35 years, coinciding with the peak years of fertility and pregnancy, 1 and therefore questions regarding reproductive outcomes are relevant. Recent studies have suggested that disease activity in pregnant women with IBD is associated with adverse birth outcomes but the results have been conflicting. 2–6 In studies of IBD and birth outcomes, it is often difficult to separate out the effects of disease activity, medication use, and IBD severity. 7 Most recent studies on birth outcomes in women with IBD have included women with varying degrees of disease severity and immunosuppressive medications, thereby making the interpretations difficult. 8–12 Although it is relevant to study women who are not on immunosuppressive medications or who do not have moderate or severe disease, it is also highly relevant to study those with a more severe disease course. Although these more severely diseased patients are just a subset of the women with IBD in general, they are the patients who require the most care. To examine this group of women with IBD who are more likely to do poorly during pregnancy, we studied a cohort of Danish women with moderate to severe IBD who had all been treated at some time during pregnancy with anti-tumor necrosis factor alpha (anti-TNF-a) therapy. In Denmark, anti-TNF-a ther- apy is given to patients with IBD who have moderate to severe disease; this is according to the European Crohn’s and Colitis Organisation guidelines and to the Danish national guidelines. 13–15 Using these criteria, we were able to identify Received for publication January 5, 2017; Accepted February 10, 2017. From the *Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; † Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark; ‡ Department of Medical Gastroen- terology, Hospital of Southwest Jutland, Esbjerg, Denmark; and § Crohn’s and Colitis Center, Brigham and Women’s Hospital, Boston, Massachusetts and Harvard Med- ical School, Boston, Massachusetts. Supported by the region of Southern Denmark (Region Syddanmarks, PhD pulje 2013 [2] journal nr: 13/25954 and 13/27667), by the Hospital of Southwest Jutland, and by the University of Southern Denmark. The authors have no conflicts of interest to disclose. Address correspondence to: Heidi Kammerlander, MD, Center for Clinical Epidemiology, Odense University Hospital, Kløvervænget 30, Entrance 216, 5000 Odense C, Denmark (e-mail: heidi.kammerlander@rsyd.dk). Copyright © 2017 Crohn’s & Colitis Foundation DOI 10.1097/MIB.0000000000001102 Published online 24 March 2017. Inflamm Bowel Dis  Volume 23, Number 6, June 2017 www.ibdjournal.org | 1011 Copyright © 2017 Crohn’s & Colitis Foundation. Unauthorized reproduction of this article is prohibited. Downloaded from https://academic.oup.com/ibdjournal/article-abstract/23/6/1011/4561128 by guest on 30 May 2020