title: Safety of TNF-α inhibitors during IBD pregnancy: a systematic review.
abstract: BACKGROUND
  Tumor necrosis factor (TNF)-α inhibitors are increasingly being used in inflammatory bowel disease (IBD). Because this chronic intestinal disorder often affects women of fertile age, it is essential to assess the effect of biologics on pregnancy outcome.
  
  
  METHODS
  We performed a systematic review of the English-language literature to investigate if treatment with TNF-α blockers during pregnancy in women with IBD increases the risk of spontaneous abortions, preterm delivery, stillbirth, low birth weight, congenital malformations, or risk of infections in the offspring. Of 552 articles and abstracts reviewed, 58 articles or abstracts with unique content were identified and included in this systematic review. However, most presentations were case reports or case series supplied by a limited number of observational studies. No randomized controlled studies were available.
  
  
  RESULTS
  TNF-α inhibitors do not seem to affect either outcome of pregnancy in mothers with IBD, or the outcome in the offspring (congenital malformations and immunosuppression). Further, recent data have not identified any increased risk of infections in the first year of life in the offspring of mothers who received biologics, even in combination with immunomodulators (thiopurines).
  
  
  CONCLUSIONS
  From the present systematic review, no association was found between administration of TNF inhibitors for IBD during pregnancy and adverse pregnancy outcome or congenital abnormalities. Further, no increased relative risk of infections has been reported in the first year of life in offspring of mothers who received biologics. Biologics should be discontinued during pregnancy solely if the IBD is in remission using the same stopping criteria as for patients with IBD in general, as uncontrolled activity of IBD may expose the mother and child to a risk greater than those only potentially coming from the use of TNF-α inhibitors. In such cases, inoculation of the offspring with live vaccines is contraindicated until the biologic agent is no longer detectable in the child's circulation.
authors.affiliation: Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark. ohn@dadlnet.dk
authors.forename: Ole Haagen
authors.initials: OH
authors.lastname: Nielsen
authors.forename: Edward V
authors.initials: EV
authors.lastname: Loftus
authors.forename: Tine
authors.initials: T
authors.lastname: Jess
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000453:epidemiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000453:epidemiology; D011256:Pregnancy Outcome / Q000453:epidemiology; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000175:diagnosis* / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha
references.citation: J Intern Med. 2011 Jul;270(1):15-28
references.pmid: 21241384
references.citation: J Rheumatol. 2009 Mar;36(3):635-41
references.pmid: 19132789
references.citation: Rev Med Chir Soc Med Nat Iasi. 2007 Jul-Sep;111(3):613-9
references.pmid: 18293689
references.citation: J Rheumatol. 2009 Mar;36(3):465-6
references.pmid: 19286856
references.citation: Inflamm Bowel Dis. 2010 May;16(5):881-95
references.pmid: 19885906
references.citation: Gut. 2007 Jun;56(6):830-7
references.pmid: 17185356
references.citation: Dig Liver Dis. 2006 Jun;38(6):439-40
references.pmid: 16563889
references.citation: Inflamm Bowel Dis. 2010 Oct;16(10):1641-2
references.pmid: 20186946
references.citation: Rev Esp Enferm Dig. 2012 Feb;104(2):59-64
references.pmid: 22372798
references.citation: Inflamm Bowel Dis. 2010 Oct;16(10):1634-6
references.pmid: 20027647
references.citation: Aliment Pharmacol Ther. 2011 May;33(9):1053-8
references.pmid: 21366638
references.citation: Am J Gastroenterol. 2004 Dec;99(12):2385-92
references.pmid: 15571587
references.citation: J Clin Gastroenterol. 2009 Aug;43(7):613-6
references.pmid: 19142167
references.citation: BMJ. 2008 Jul 03;337:a427
references.pmid: 18599468
references.citation: Clin Gastroenterol Hepatol. 2009 Sep;7(9):944-7
references.pmid: 19410016
references.citation: Am J Gastroenterol. 2012 Sep;107(9):1409-22
references.pmid: 22890223
references.citation: Gastroenterol Clin North Am. 2002 Mar;31(1):265-73, xii
references.pmid: 12122737
references.citation: N Engl J Med. 2010 Apr 15;362(15):1383-95
references.pmid: 20393175
references.citation: Gut. 2009 Apr;58(4):608
references.pmid: 19299393
references.citation: Am J Gastroenterol. 2001 Jul;96(7):2274-5
references.pmid: 11467677
references.citation: Eur J Gastroenterol Hepatol. 2010 Oct;22(10):1260-4
references.pmid: 20671559
references.citation: Gastroenterology. 2006 Jul;131(1):283-311
references.pmid: 16831611
references.citation: J Rheumatol. 2009 Sep;36(9):2122; author reply 2123
references.pmid: 19738224
references.citation: Hum Exp Toxicol. 2000 Apr;19(4):226-8
references.pmid: 10918512
references.citation: J Crohns Colitis. 2011 Jun;5(3):262
references.pmid: 21575893
references.citation: Scand J Gastroenterol. 1984 Sep;19(6):724-32
references.pmid: 6515312
references.citation: Clin J Gastroenterol. 2010 Aug;3(4):179-81
references.pmid: 26190243
references.citation: Inflamm Bowel Dis. 2011 Sep;17(9):1846-54
references.pmid: 21830263
references.citation: Inflamm Bowel Dis. 2011 Mar;17(3):868-9
references.pmid: 20564533
references.citation: Nat Rev Gastroenterol Hepatol. 2013 Mar;10(3):130-1
references.pmid: 23247511
references.citation: Inflamm Bowel Dis. 2008 Mar;14(3):435-6
references.pmid: 18050300
references.citation: J Crohns Colitis. 2010 Nov;4(5):603-5
references.pmid: 21122568
references.citation: Clin Gastroenterol Hepatol. 2013 Mar;11(3):286-92; quiz e24
references.pmid: 23200982
references.citation: Am J Gastroenterol. 2009 Jan;104(1):228-33
references.pmid: 19098873
references.citation: Am J Gastroenterol. 1998 Dec;93(12):2426-30
references.pmid: 9860403
references.citation: J Gastroenterol Hepatol. 2007 Apr;22(4):542-9
references.pmid: 17376049
references.citation: Aliment Pharmacol Ther. 2009 Oct 15;30(8):854-63
references.pmid: 19764940
references.citation: Orphanet J Rare Dis. 2011 Aug 16;6:56
references.pmid: 21846383
references.citation: Inflamm Bowel Dis. 2009 Sep;15(9):1410-6
references.pmid: 19462435
references.citation: Scand J Gastroenterol. 2010 Nov;45(11):1302-6
references.pmid: 20602569
references.citation: Am J Gastroenterol. 2011 Feb;106(2):214-23; quiz 224
references.pmid: 21157441
references.citation: Clin Gastroenterol Hepatol. 2006 Oct;4(10):1255-8
references.pmid: 17045211
references.citation: Dig Dis Sci. 2006 Nov;51(11):2045-7
references.pmid: 17009112
references.citation: J Gastroenterol Hepatol. 2003 Apr;18(4):465-6
references.pmid: 12653902
references.citation: Pharmacotherapy. 2005 Sep;25(9):1181-92
references.pmid: 16164393
references.citation: Clin Gastroenterol Hepatol. 2010 May;8(5):475-6
references.pmid: 20005982
references.citation: Rheumatology (Oxford). 2007 Apr;46(4):695-8
references.pmid: 17158212
references.citation: Curr Pharm Biotechnol. 2011 May;12(5):765-73
references.pmid: 21342120
references.citation: Arthritis Rheum. 2009 May 15;61(5):587-92
references.pmid: 19404999
references.citation: Gut. 2005 Jun;54(6):890
references.pmid: 15888806
references.citation: Aliment Pharmacol Ther. 2008 May;27(10):885-94
references.pmid: 18284649
references.citation: Clin Gastroenterol Hepatol. 2013 Mar;11(3):318-21
references.pmid: 23103819
references.citation: World J Gastroenterol. 2013 May 7;19(17):2591-602
references.pmid: 23674866
references.citation: Expert Opin Drug Saf. 2010 May;9(3):421-9
references.pmid: 20367495
references.citation: JAMA. 2000 Apr 19;283(15):2008-12
references.pmid: 10789670
references.citation: Inflamm Bowel Dis. 2006 Aug;12(8):827-8
references.pmid: 16917239
references.citation: Am J Gastroenterol. 2013 Mar;108(3):433-40
references.pmid: 23318480
references.citation: World J Gastroenterol. 2008 May 21;14(19):3085-7
references.pmid: 18494064
references.citation: J Crohns Colitis. 2010 Dec;4(6):687-9
references.pmid: 21122583
references.citation: Aliment Pharmacol Ther. 2005 Mar 15;21(6):733-8
references.pmid: 15771759
references.citation: Rev Gastroenterol Disord. 2004 Fall;4(4):196-210
references.pmid: 15580154
references.citation: Gastroenterology. 2001 Nov;121(5):1088-94
references.pmid: 11677200
references.citation: J Crohns Colitis. 2012 Apr;6(3):358-61
references.pmid: 22405174
references.citation: J Crohns Colitis. 2011 Aug;5(4):317-23
references.pmid: 21683301
references.citation: Scand J Gastroenterol. 1983 Sep;18(6):735-42
references.pmid: 6669937