{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T18:06:05Z","timestamp":1767204365582,"version":"build-2238731810"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Crohn's disease is a chronic disease, which commonly affects women during their reproductive years. Poorly treated Crohn's disease is associated with adverse pregnancy outcomes. Biologics, a group of therapeutic drugs targeting inflammatory mediators including anti-TNF, anti-integrins and anti-interleukins, are increasingly used in pregnant women with Crohn's disease, exposing both the women and their fetuses to treatment-related complications. At present, it is unclear which biologics are more superior. This study performed a systematic review and meta-analysis to assess the risk of adverse pregnancy outcomes in women with Crohn's disease after exposure to biologics. Bibliographic databases were searched from inception to May 2021. The outcomes of interest were preterm delivery, low birth weight, spontaneous abortion, and congenital abnormalities. A total of 11 studies comprised of 1,875 pregnancies among women with Crohn's disease were included. Of these, 1,162 received biologics and 713 received non-biologic therapy. During the remission phase of the disease, the use of biological therapy increased the risk of adverse pregnancy outcomes, of which anti-integrins were associated with a higher incidence of adverse pregnancy outcomes than anti-TNF and anti-interleukins.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Systematic Review Registration:<\/jats:bold>\n                    <jats:ext-link>http:\/\/www.crd.york.ac.uk\/PROSPERO<\/jats:ext-link>\n                    , identifier: CRD42020191275.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2021.753088","type":"journal-article","created":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T01:31:40Z","timestamp":1635125500000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["RETRACTED: Adverse Pregnancy Outcomes Following Exposure to Biologics in Women With Crohn's Disease: A Systematic Review and Meta-Analysis"],"prefix":"10.3389","volume":"8","author":[{"given":"Han","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengdie","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1159\/000083874","article-title":"Pregnancy and Crohn's disease","volume":"71","author":"Mottet","year":"2005","journal-title":"Digestion."},{"key":"B2","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1053\/j.gastro.2015.12.003","article-title":"The Toronto Consensus Statements for the management of inflammatory bowel disease in pregnancy","volume":"150","author":"Nguyen","year":"2016","journal-title":"Gastroenterology."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1038\/ajg.2016.254","article-title":"The effects of active IBD during pregnancy in the era of novel IBD therapies","volume":"111","author":"de Lima-Karagiannis","year":"2016","journal-title":"Am J Gastroenterol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1053\/j.gastro.2007.07.019","article-title":"Pregnancy outcomes in women with inflammatory bowel disease: a large community-based study from Northern California","volume":"133","author":"Mahadevan","year":"2007","journal-title":"Gastroenterology."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1111\/j.1572-0241.2000.01852.x","article-title":"Crohn's disease, pregnancy, and birth weight","volume":"95","author":"Moser","year":"2000","journal-title":"Am J Gastroenterol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1111\/j.1572-0241.2007.01355.x","article-title":"Disease activity in pregnant women with Crohn's disease and birth outcomes: a regional Danish cohort study","volume":"102","author":"N\u00f8rg\u00e5rd","year":"2007","journal-title":"Am J Gastroenterol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1186\/1741-7015-11-174","article-title":"Safety of TNF-\u03b1 inhibitors during IBD pregnancy: a systematic review","volume":"11","author":"Nielsen","year":"2013","journal-title":"BMC Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/j.cgh.2010.02.014","article-title":"Crohn's disease is a risk factor for preterm birth","volume":"8","author":"Stephansson","year":"2010","journal-title":"Clin Gastroenterol Hepatol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.bpobgyn.2015.03.003","article-title":"Autoimmune connective tissue diseases","volume":"29","author":"\u00d8stensen","year":"2015","journal-title":"Best Pract Res Clin Obstet Gynaecol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1002\/acr.22516","article-title":"Proceedings from the American College of Rheumatology Reproductive Health Summit: the management of fertility, pregnancy, and lactation in women with autoimmune and systemic inflammatory diseases","volume":"67","author":"Kavanaugh","year":"2015","journal-title":"Arthritis Care Res (Hoboken)."},{"key":"B11","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1002\/ibd.20839","article-title":"Fear and fertility in inflammatory bowel disease: a mismatch of perception and reality affects family planning decisions","volume":"15","author":"Mountifield","year":"2009","journal-title":"Inflamm Bowel Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1002\/ibd.20082","article-title":"Voluntary childlessness is increased in women with inflammatory bowel disease","volume":"13","author":"Marri","year":"2007","journal-title":"Inflamm Bowel Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/s10654-010-9491-z","article-title":"Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses","volume":"25","author":"Stang","year":"2010","journal-title":"Eur J Epidemiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"DerSimonian","year":"1986","journal-title":"Control Clin Trials."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1001\/jama.283.15.2008","article-title":"Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group","volume":"283","author":"Stroup","year":"2000","journal-title":"JAMA."},{"key":"B16","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003","journal-title":"BMJ."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1916","DOI":"10.1097\/MIB.0000000000001234","article-title":"Anti-TNF-\u03b1 use during the third trimester of pregnancy in women with moderate-severe inflammatory bowel disease and the risk of preterm birth and low birth weight","volume":"23","author":"Kammerlander","year":"2017","journal-title":"Inflamm Bowel Dis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.cgh.2012.10.024","article-title":"Effects of discontinuing anti-tumor necrosis factor therapy during pregnancy on the course of inflammatory bowel disease and neonatal exposure","volume":"11","author":"Zelinkova","year":"2013","journal-title":"Clin Gastroenterol Hepatol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.1038\/s41395-018-0202-9","article-title":"Pregnancy outcomes reported during the 13-year TREAT registry: a descriptive report","volume":"113","author":"Lichtenstein","year":"2018","journal-title":"Am J Gastroenterol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1111\/apt.16192","article-title":"Safety of ustekinumab or vedolizumab in pregnant inflammatory bowel disease patients: a multicentre cohort study","volume":"53","author":"Wils","year":"2021","journal-title":"Aliment Pharmacol Ther."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2385","DOI":"10.1111\/j.1572-0241.2004.30186.x","article-title":"Outcome of pregnancy in women receiving infliximab for the treatment of Crohn's disease and rheumatoid arthritis","volume":"99","author":"Katz","year":"2004","journal-title":"Am J Gastroenterol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1002\/ibd.21583","article-title":"Outcome of pregnancy in women with inflammatory bowel disease treated with antitumor necrosis factor therapy","volume":"17","author":"Schnitzler","year":"2011","journal-title":"Inflamm Bowel Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1111\/bcp.12642","article-title":"Pregnancy outcome after TNF-\u03b1 inhibitor therapy during the first trimester: a prospective multicentre cohort study","volume":"80","author":"Weber-Schoendorfer","year":"2015","journal-title":"Br J Clin Pharmacol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1002\/art.40508","article-title":"Pregnancy outcomes after exposure to certolizumab pegol: updated results from a pharmacovigilance safety database","volume":"70","author":"Clowse","year":"2018","journal-title":"Arthritis Rheumatol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1111\/apt.15539","article-title":"Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti-TNF or conventional therapy: results of the European CONCEIVE study","volume":"51","author":"Moens","year":"2020","journal-title":"Aliment Pharmacol Ther."},{"key":"B26","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1038\/ajg.2012.430","article-title":"Safety of thiopurines and anti-TNF-\u03b1 drugs during pregnancy in patients with inflammatory bowel disease","volume":"108","author":"Casanova","year":"2013","journal-title":"Am J Gastroenterol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1136\/gutjnl-2015-309321","article-title":"Tailored anti-TNF therapy during pregnancy in patients with IBD: maternal and fetal safety","volume":"65","author":"de Lima","year":"2016","journal-title":"Gut."},{"key":"B28","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.biopha.2006.06.022","article-title":"Do anti-tumor necrosis factors induce response and remission in patients with acute refractory Crohn's disease? A systematic meta-analysis of controlled clinical trials","volume":"61","author":"Rahimi","year":"2007","journal-title":"Biomed Pharmacother."},{"key":"B29","doi-asserted-by":"publisher","first-page":"3684","DOI":"10.2174\/138161210794079236","article-title":"Efficacy and tolerability of immunoregulators and antibiotics in fistulizing Crohn's disease: a systematic review and meta-analysis of placebo-controlled trials","volume":"16","author":"Nikfar","year":"2010","journal-title":"Curr Pharm Des."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2737","DOI":"10.1111\/j.1572-0241.2007.01508.x","article-title":"Health-related quality of life during natalizumab maintenance therapy for Crohn's disease","volume":"102","author":"Feagan","year":"2007","journal-title":"Am J Gastroenterol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"3132","DOI":"10.1111\/j.1572-0241.2008.02175.x","article-title":"Effects of adalimumab maintenance therapy on health-related quality of life of patients with Crohn's disease: patient-reported outcomes of the CHARM trial","volume":"103","author":"Loftus","year":"2008","journal-title":"Am J Gastroenterol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1007\/s10620-007-0006-z","article-title":"On the benefit of probiotics in the management of pouchitis in patients underwent ileal pouch anal anastomosis: a meta-analysis of controlled clinical trials","volume":"53","author":"Elahi","year":"2008","journal-title":"Dig Dis Sci."},{"key":"B33","first-page":"273","article-title":"Off-label uses and side effects of infliximab","volume":"3","author":"Scheinfeld","year":"2004","journal-title":"J Drugs Dermatol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1097\/00054725-200105000-00011","article-title":"Inflammatory bowel disease and pregnancy","volume":"7","author":"Katz","year":"2001","journal-title":"Inflamm Bowel Dis."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1097\/MIB.0000000000001102","article-title":"The effect of disease activity on birth outcomes in a nationwide cohort of women with moderate to severe inflammatory bowel disease","volume":"23","author":"Kammerlander","year":"2017","journal-title":"Inflamm Bowel Dis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2750","DOI":"10.1007\/s10620-015-3677-x","article-title":"Inflammatory bowel disease increases risk of adverse pregnancy outcomes: a meta-analysis","volume":"60","author":"O'Toole","year":"2015","journal-title":"Dig Dis Sci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"a427","DOI":"10.1136\/bmj.39566.681458.BE","article-title":"Inflammatory bowel disease in pregnancy","volume":"337","author":"Ferguson","year":"2008","journal-title":"Bmj."},{"key":"B38","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1111\/j.1572-0241.2002.05543.x","article-title":"Outcomes of infants born to mothers with inflammatory bowel disease: a population-based cohort study","volume":"97","author":"Dominitz","year":"2002","journal-title":"Am J Gastroenterol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1586\/eci.10.35","article-title":"Inflammatory bowel disease and pregnancy: an update","volume":"6","author":"Kwan","year":"2010","journal-title":"Expert Rev Clin Immunol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1111\/apt.12833","article-title":"Factors associated with pregnancy outcome in anti-TNF treated women with inflammatory bowel disease","volume":"40","author":"Seirafi","year":"2014","journal-title":"Aliment Pharmacol Ther."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1097\/MIB.0000000000000060","article-title":"Birth outcomes in women with inflammatory bowel disease: effects of disease activity and drug exposure","volume":"20","author":"Br\u00f6ms","year":"2014","journal-title":"Inflamm Bowel Dis."},{"key":"B42","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1038\/nature06005","article-title":"Unravelling the pathogenesis of inflammatory bowel disease","volume":"448","author":"Xavier","year":"2007","journal-title":"Nature."},{"key":"B43","doi-asserted-by":"crossref","first-page":"S449","DOI":"10.14309\/00000434-200809001-01150","article-title":"Natalizumab use during pregnancy","volume":"103","author":"Nazareth","year":"2008","journal-title":"Am J Gastroenterol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1097\/AOG.0000000000000978","article-title":"Care of the pregnant patient with inflammatory bowel disease","volume":"126","author":"Mahadevan","year":"2015","journal-title":"Obstet Gynecol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1111\/apt.13960","article-title":"Vedolizumab exposure in pregnancy: outcomes from clinical studies in inflammatory bowel disease","volume":"45","author":"Mahadevan","year":"2017","journal-title":"Aliment Pharmacol Ther."},{"key":"B46","doi-asserted-by":"publisher","first-page":"CD008794","DOI":"10.1002\/14651858.CD008794.pub2","article-title":"Adverse effects of biologics: a network meta-analysis and Cochrane overview","volume":"2011","author":"Singh","year":"2011","journal-title":"Cochrane Database Syst Rev."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1946","DOI":"10.1056\/NEJMoa1602773","article-title":"Ustekinumab as induction and maintenance therapy for Crohn's disease","volume":"375","author":"Feagan","year":"2016","journal-title":"N Engl J Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.fertnstert.2003.06.007","article-title":"A new role for natural killer cells, interleukin (IL)-12, and IL-18 in repeated implantation failure after in vitro fertilization","volume":"81","author":"L\u00e9d\u00e9e-Bataille","year":"2004","journal-title":"Fertil Steril."},{"key":"B49","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1080\/17474124.2018.1496820","article-title":"Pregnant women with inflammatory bowel disease: the effects of biologicals on pregnancy, outcome of infants, and the developing immune system","volume":"12","author":"Wieringa","year":"2018","journal-title":"Expert Rev Gastroenterol Hepatol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1093\/aje\/kwq028","article-title":"Umbilical cord serum cytokine levels and risks of small-for-gestational-age and preterm birth","volume":"171","author":"Neta","year":"2010","journal-title":"Am J Epidemiol."}],"updated-by":[{"DOI":"10.3389\/fmed.2022.915112","type":"retraction","label":"Retraction","source":"retraction-watch","updated":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T00:00:00Z","timestamp":1650499200000},"record-id":"37122"},{"DOI":"10.3389\/fmed.2022.915112","type":"retraction","label":"Retraction","source":"publisher","updated":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T00:00:00Z","timestamp":1650499200000}}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.753088\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T09:32:54Z","timestamp":1712136774000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.753088\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,25]]},"references-count":50,"alternative-id":["10.3389\/fmed.2021.753088"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2021.753088","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,25]]},"article-number":"753088"}}