Journal of Crohn's and Colitis, 2015, 371–372 doi:10.1093/ecco-jcc/jjv048 Advanced Access publication March 13, 2015 Editorial
Editorial Managing Pregnant Patients with Inflammatory Bowel Disease: A Difficult Compromise patients discontinuing the treatment while in remission.5 Nevertheless, in a rare case of relapse in such a situation, a short course of corticosteroids could be an alternative to resumption of anti-TNF treatment. This approach would be of low risk in terms of immediate neonatal outcomes, but, based on the new data provided by Leung et al.,1 may result in an increased risk of gestational diabetes with adverse effects on the child’s health in the long term.6 In this light, prospective studies evaluating complications of maternal corticosteroid use during pregnancy with specific stratification according to dose, timing and duration of the treatment are much needed. In conclusion, the management of a pregnant IBD patient remains a difficult compromise between the consistently proven harmful impact of active disease and the potential adverse effects, thus far not fully recognized, of the medication on pregnancy outcomes. Properly designed prospective studies looking at both maternal and neonatal outcomes and prospective long-term follow-up registries are indispensable to discussion of the pros and cons of using the drugs concerned during pregnancy. In the meantime, meticulous reevaluation of old drugs considered low-risk using new relevant outcomes represents one of the possible ways of improving care in this specific setting. Zuzana Zelinkova1,2, Janneke C. van der Woude3 IBD Centre, Thalion, Bratislava, Slovakia 2Insitute of Medical Biology, Genetics and Clinical Genetics, Medical Faculty of Comenius University, Bratislava, Slovakia 3Department of Gastroenterology & Hepatology, Erasmus Medical Center, Rotterdam, the Netherlands Corresponding author: Zuzana Zelinkova, MD, PhD, IBD Centre, Thalion, Tomasikova 50/C, 831 04 Bratislava, Slovakia. Tel. +421 2 57108511; fax +421 2 57108520; Email: [email protected] 1
Conflict of interest statement None declared. http://ecco-jcc.oxfordjournals.org/lookup/suppl/ doi:10.1093/ecco-jcc/jjv048/-/DC1
References 1. Leung Y, Kaplan G, Coward S, et al. Inflammatory bowel disease patients are at higher risk of gestational diabetes. J Crohns Colitis 2015. 2. Herbst AL, Ulfelder H, Poskanzer DC. Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med 1971;284:878–81. 3. Hviid A, Molgaard-Nielsen D. Corticosteroid use during pregnancy and risk of orofacial clefts. CMAJ 2011;183:796–804.
Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected]
371
Downloaded from http://ecco-jcc.oxfordjournals.org/ by guest on March 22, 2016
In the March issue of JCC, in the paper entitled ‘Inflammatory bowel disease patients are at higher risk of gestational diabetes’, Leung et al.1 analysed pregnancy outcomes of 116 inflammatory bowel disease (IBD) patients matched by age at conception with 381 pregnant women without IBD. In this Canadian cohort, after accounting for age and smoking status, IBD patients were independently at higher risk of gestational diabetes (odds ratio [OR] = 4.3; 95% CI 1.2–16.3; p = 0.03), preterm birth (OR = 19.7; 95% CI 2.2–173.9; p = 0.007) and C-section mode of delivery (OR = 2.7; 95% CI 1.6–4.6; p = 0.0002). Disease activity, overall use of IBD medication and specific use of thiopurines or biologicals were not associated with adverse pregnancy outcomes; however, the use of systemic corticosteroids among IBD patients slightly increased the risk of gestational diabetes (OR = 4.5; 95% CI 1.2–16.8; p = 0.03). In the subanalysis, the risk of gestational diabetes was significantly increased only among IBD patients using systemic corticosteroids, although a trend was present also in IBD patients without this treatment. Unfortunately, the retrospective design of the study precludes better identification of IBD patients at risk of steroid-induced gestational diabetes; more specifically, no dose- or timing-depending effects of corticosteroids could have been analysed in this cohort. Nevertheless, this study teaches us a valuable lesson on the quality of data we base our strategies upon to manage IBD during pregnancy. First, it points out the issue, thus far underestimated, of maternal complications other than IBD flare. Traditionally, the main primary outcomes used to assess specific drug safety for maternal use during pregnancy are neonatal outcomes such as birth weight, gestational age, Apgar score, neonatal ICU admissions, congenital abnormalities and mode of delivery. Data on the long-term outcomes of children exposed to a particular drug in utero are scarce and mainly limited to a few years of postnatal follow-up. These limited outcomes are the only data we have now in hand to counsel our patients, although we know that negative effects of in utero exposure to some agents may become apparent only in the later phases of the offspring’s life.2 The second important point this study raises is a new view on the safety of old drugs with an extensive track record of use during pregnancy across a whole spectrum of maternal autoimmune disorders.3 With this track record, systemic corticosteroids are considered lowrisk during pregnancy, which makes them preferred therapies in cases of severe disease flare during pregnancy.4 With the current understanding of the pharmacokinetics of anti-tumour necrosis factor biologicals (anti-TNFs), these agents are discontinued during the second trimester of the pregnancy in order to limit placental transfer. This approach seems not to increase the risk of relapse during pregnancy in IBD
372 4. van der Woude CJ, Ardizzone S, Bengtson MB, et al. The Second European Evidenced-Based Consensus on Reproduction and Pregnancy in Inflammatory Bowel Disease. J Crohns Colitis 2015, in press, doi:10.1093/ecco-jcc/jju006. 5. Zelinkova Z, van der Ent C, Bruin KF, et al. Effects of discontinuing antitumor necrosis factor therapy during pregnancy on the course of inflam-
Z. Zelinkova and J. C. van der Woude matory bowel disease and neonatal exposure. Clin Gastroenterol Hepatol 2013;11:318–21. 6. Malcolm J. Through the looking glass: gestational diabetes as a predictor of maternal and offspring long-term health. Diabetes Metab Res Rev 2012;28:307–11.
Downloaded from http://ecco-jcc.oxfordjournals.org/ by guest on March 22, 2016
Editorial Managing Pregnant Patients with Inflammatory Bowel Disease: A Difficult Compromise patients discontinuing the treatment while in remission.5 Nevertheless, in a rare case of relapse in such a situation, a short course of corticosteroids could be an alternative to resumption of anti-TNF treatment. This approach would be of low risk in terms of immediate neonatal outcomes, but, based on the new data provided by Leung et al.,1 may result in an increased risk of gestational diabetes with adverse effects on the child’s health in the long term.6 In this light, prospective studies evaluating complications of maternal corticosteroid use during pregnancy with specific stratification according to dose, timing and duration of the treatment are much needed. In conclusion, the management of a pregnant IBD patient remains a difficult compromise between the consistently proven harmful impact of active disease and the potential adverse effects, thus far not fully recognized, of the medication on pregnancy outcomes. Properly designed prospective studies looking at both maternal and neonatal outcomes and prospective long-term follow-up registries are indispensable to discussion of the pros and cons of using the drugs concerned during pregnancy. In the meantime, meticulous reevaluation of old drugs considered low-risk using new relevant outcomes represents one of the possible ways of improving care in this specific setting. Zuzana Zelinkova1,2, Janneke C. van der Woude3 IBD Centre, Thalion, Bratislava, Slovakia 2Insitute of Medical Biology, Genetics and Clinical Genetics, Medical Faculty of Comenius University, Bratislava, Slovakia 3Department of Gastroenterology & Hepatology, Erasmus Medical Center, Rotterdam, the Netherlands Corresponding author: Zuzana Zelinkova, MD, PhD, IBD Centre, Thalion, Tomasikova 50/C, 831 04 Bratislava, Slovakia. Tel. +421 2 57108511; fax +421 2 57108520; Email: [email protected] 1
Conflict of interest statement None declared. http://ecco-jcc.oxfordjournals.org/lookup/suppl/ doi:10.1093/ecco-jcc/jjv048/-/DC1
References 1. Leung Y, Kaplan G, Coward S, et al. Inflammatory bowel disease patients are at higher risk of gestational diabetes. J Crohns Colitis 2015. 2. Herbst AL, Ulfelder H, Poskanzer DC. Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med 1971;284:878–81. 3. Hviid A, Molgaard-Nielsen D. Corticosteroid use during pregnancy and risk of orofacial clefts. CMAJ 2011;183:796–804.
Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected]
371
Downloaded from http://ecco-jcc.oxfordjournals.org/ by guest on March 22, 2016
In the March issue of JCC, in the paper entitled ‘Inflammatory bowel disease patients are at higher risk of gestational diabetes’, Leung et al.1 analysed pregnancy outcomes of 116 inflammatory bowel disease (IBD) patients matched by age at conception with 381 pregnant women without IBD. In this Canadian cohort, after accounting for age and smoking status, IBD patients were independently at higher risk of gestational diabetes (odds ratio [OR] = 4.3; 95% CI 1.2–16.3; p = 0.03), preterm birth (OR = 19.7; 95% CI 2.2–173.9; p = 0.007) and C-section mode of delivery (OR = 2.7; 95% CI 1.6–4.6; p = 0.0002). Disease activity, overall use of IBD medication and specific use of thiopurines or biologicals were not associated with adverse pregnancy outcomes; however, the use of systemic corticosteroids among IBD patients slightly increased the risk of gestational diabetes (OR = 4.5; 95% CI 1.2–16.8; p = 0.03). In the subanalysis, the risk of gestational diabetes was significantly increased only among IBD patients using systemic corticosteroids, although a trend was present also in IBD patients without this treatment. Unfortunately, the retrospective design of the study precludes better identification of IBD patients at risk of steroid-induced gestational diabetes; more specifically, no dose- or timing-depending effects of corticosteroids could have been analysed in this cohort. Nevertheless, this study teaches us a valuable lesson on the quality of data we base our strategies upon to manage IBD during pregnancy. First, it points out the issue, thus far underestimated, of maternal complications other than IBD flare. Traditionally, the main primary outcomes used to assess specific drug safety for maternal use during pregnancy are neonatal outcomes such as birth weight, gestational age, Apgar score, neonatal ICU admissions, congenital abnormalities and mode of delivery. Data on the long-term outcomes of children exposed to a particular drug in utero are scarce and mainly limited to a few years of postnatal follow-up. These limited outcomes are the only data we have now in hand to counsel our patients, although we know that negative effects of in utero exposure to some agents may become apparent only in the later phases of the offspring’s life.2 The second important point this study raises is a new view on the safety of old drugs with an extensive track record of use during pregnancy across a whole spectrum of maternal autoimmune disorders.3 With this track record, systemic corticosteroids are considered lowrisk during pregnancy, which makes them preferred therapies in cases of severe disease flare during pregnancy.4 With the current understanding of the pharmacokinetics of anti-tumour necrosis factor biologicals (anti-TNFs), these agents are discontinued during the second trimester of the pregnancy in order to limit placental transfer. This approach seems not to increase the risk of relapse during pregnancy in IBD
372 4. van der Woude CJ, Ardizzone S, Bengtson MB, et al. The Second European Evidenced-Based Consensus on Reproduction and Pregnancy in Inflammatory Bowel Disease. J Crohns Colitis 2015, in press, doi:10.1093/ecco-jcc/jju006. 5. Zelinkova Z, van der Ent C, Bruin KF, et al. Effects of discontinuing antitumor necrosis factor therapy during pregnancy on the course of inflam-
Z. Zelinkova and J. C. van der Woude matory bowel disease and neonatal exposure. Clin Gastroenterol Hepatol 2013;11:318–21. 6. Malcolm J. Through the looking glass: gestational diabetes as a predictor of maternal and offspring long-term health. Diabetes Metab Res Rev 2012;28:307–11.
Downloaded from http://ecco-jcc.oxfordjournals.org/ by guest on March 22, 2016
