Digestive Diseases and Sciences

, Volume 60, Issue 9, pp 2750–2761 | Cite as

Inflammatory Bowel Disease Increases Risk of Adverse Pregnancy Outcomes: A Meta-Analysis

  • Aoibhlinn O’TooleEmail author
  • Ogochukwu Nwanne
  • Tracy Tomlinson
Original Article



Inflammatory bowel disease may place women at greater risk of adverse pregnancy outcomes.


To examine the association between inflammatory bowel disease and adverse pregnancy outcomes: preterm birth, small for gestational age (SGA) birth weight, congenital anomalies, and stillbirth.


We searched PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and for studies published from January 1980 through February 2014 and reference lists of relevant studies. We reviewed 1748 citations and identified studies evaluating outcomes of pregnancies complicated by inflammatory bowel disease. Selected studies evaluated one or more of the outcomes of interest, were in English, and gave sufficient details to perform meta-analysis. Three investigators independently reviewed articles for inclusion; discordant decisions were resolved by team review and consensus. Twenty-three studies that included 15,007 women with inflammatory bowel disease (5449 Crohn’s, 6559 ulcerative colitis) and 4,614,271 controls met selection criteria. Random-effects analytical methods were used to generate pooled odds ratios.


We found an increased odds of the outcomes studied among women with inflammatory bowel disease compared with non-diseased controls: 1.85 for preterm birth (22 studies; 95 % confidence interval [CI] 1.67–2.05), 1.36 for SGA birth weight (13 studies; 95 % CI 1.16–1.60), 1.57 for stillbirth (10 studies; 95 % CI 1.03–2.38), and 1.29 for congenital anomalies (11 studies; 95 % CI 1.05–1.58). The latter result, however, may be unreliable secondary to publication bias.


Inflammatory bowel disease may increase the odds of adverse pregnancy outcomes.


Pregnancy Ulcerative colitis Crohn’s disease Congenital anomalies Preterm birth Stillbirth 


Conflict of interest



  1. 1.
    Shivananda S, Lennard-Jones J, Logan R, et al. Incidence of inflammatory bowel disease across Europe: is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD). Gut. 1996;39:690–697.PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Mountifield R, Bampton P, Prosser R, Muller K, Andrews JM. Fear and fertility in inflammatory bowel disease: a mismatch of perception and reality affects family planning decisions. Inflamm Bowel Dis. 2009;15:720–725.CrossRefPubMedGoogle Scholar
  3. 3.
    Cornish J, Tan E, Teare J, et al. A meta-analysis on the influence of inflammatory bowel disease on pregnancy. Gut. 2007;56:830–837.PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Coelho J, Beaugerie L, Colombel JF, et al. Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME Study. Gut. 2011;60:198–203.CrossRefPubMedGoogle Scholar
  5. 5.
    Nielsen OH, Loftus EV Jr, Jess T. Safety of TNF-alpha inhibitors during IBD pregnancy: a systematic review. BMC Med. 2013;11:174.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Abhyankar A, Ham M, Moss AC. Meta-analysis: the impact of disease activity at conception on disease activity during pregnancy in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2013;38:460–466.PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Wang ML, Dorer DJ, Fleming MP, Catlin EA. Clinical outcomes of near-term infants. Pediatrics. 2004;114:372–376.CrossRefPubMedGoogle Scholar
  8. 8.
    van Baar AL, Vermaas J, Knots E, de Kleine MJ, Soons P. Functioning at school age of moderately preterm children born at 32 to 36 weeks’ gestational age. Pediatrics. 2009;124:251–257.CrossRefPubMedGoogle Scholar
  9. 9.
    Larzilliere I, Beau P. Chronic inflammatory bowel disease and pregnancy. Case control study. Gastroenterol Clin Biol. 1998;22:1056–1060.PubMedGoogle Scholar
  10. 10.
    Moser MA, Okun NB, Mayes DC, Bailey RJ. Crohn’s disease, pregnancy, and birth weight. Am J Gastroenterol. 2000;95:1021–1026.CrossRefPubMedGoogle Scholar
  11. 11.
    Bengtson MB, Slberg IC, Aamodt G, et al. Relationships between inflammatory bowel disease and perinatal factors: both maternal and paternal disease are related to preterm birth of offspring. Inflamm Bowel Dis. 2010;16:847–855.CrossRefPubMedGoogle Scholar
  12. 12.
    Juni P, Altman DG, Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ. 2001;323:42–46.PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Egger M, Schneider M, Smith GD. Spurious precision? Meta-analysis of observational studies. BMJ. 1998;316:140–144.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Baird DD, Narendranathan M, Sandler RS. Increased risk of preterm birth for women with inflammatory bowel disease. Gastroenterology. 1990;99:987–994.PubMedGoogle Scholar
  15. 15.
    Ban L, Tata LJ, Fiaschi L, Card T. Limited risks of major congenital anomalies in children of mothers with IBD and effects of medications. Gastroenterology. 2014;146:76–84.CrossRefPubMedGoogle Scholar
  16. 16.
    Bortoli A, Pedersen N, Duricova D, et al. Pregnancy outcome in inflammatory bowel disease: prospective European case-control ECCO-EpiCom study, 2003–2006. Aliment Pharmacol Ther. 2011;34:724–734.CrossRefPubMedGoogle Scholar
  17. 17.
    Bush MC, Patel S, Lapinski RH, Stone JL. Perinatal outcomes in inflammatory bowel disease. J Matern Fetal Neonatal Med. 2004;15:237–241.CrossRefPubMedGoogle Scholar
  18. 18.
    Cleary BJ, Kallen B. Early pregnancy azathioprine use and pregnancy outcomes. Birth Defects Res A Clin Mol Teratol. 2009;85:647–654.CrossRefPubMedGoogle Scholar
  19. 19.
    Dominitz JA, Young JC, Boyko EJ. Outcomes of infants born to mothers with inflammatory bowel disease: a population-based cohort study. Am J Gastroenterol. 2002;97:641–648.CrossRefPubMedGoogle Scholar
  20. 20.
    Elbaz G, Fich A, Levy A, Holcberg G, Sheiner E. Inflammatory bowel disease and preterm delivery. Int J Gynaecol Obstet. 2005;90:193–197.CrossRefPubMedGoogle Scholar
  21. 21.
    Fedorkow DM, Persaud D, Nimrod CA. Inflammatory bowel disease: a controlled study of late pregnancy outcome. Am J Obstet Gynecol. 1989;160:998–1001.CrossRefPubMedGoogle Scholar
  22. 22.
    Fonager K, Sorensen HT, Olsen J, Dahlerup JF, Rasmussen SN. Pregnancy outcome for women with Crohn’s disease: a follow-up study based on linkage between national registries. Am J Gastroenterol. 1998;93:2426–2430.CrossRefPubMedGoogle Scholar
  23. 23.
    Kornfeld D, Cnattingius S, Ekbom A. Pregnancy outcomes in women with inflammatory bowel disease—a population-based cohort study. Am J Obstet Gynecol. 1997;177:942–946.CrossRefPubMedGoogle Scholar
  24. 24.
    Langagergaard V, Pedersen L, Gislum M, Norgard B, Sorensen HT. Birth outcome in women treated with azathioprine or mercaptopurine during pregnancy: a Danish nationwide cohort study. Aliment Pharmacol Ther. 2007;25:73–81.CrossRefPubMedGoogle Scholar
  25. 25.
    Lin HC, Chiu CJ, Chen SF, Lou HY, Chiu WT, Chen YH. Ulcerative colitis and pregnancy outcomes in an asian population. Am J Gastroenterol. 2010;105:387–394.CrossRefPubMedGoogle Scholar
  26. 26.
    Ludvigsson JF, Ludvigsson J. Inflammatory bowel disease in mother or father and neonatal outcome. Acta Paediatr. 2002;91:145–151.CrossRefPubMedGoogle Scholar
  27. 27.
    Mahadevan U. Gastrointestinal medications in pregnancy. Best Pract Res Clin Gastroenterol. 2007;21:849–877.CrossRefPubMedGoogle Scholar
  28. 28.
    Mayberry JF, Weterman IT. European survey of fertility and pregnancy in women with Crohn’s disease: a case control study by European collaborative group. Gut. 1986;27:821–825.PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Nguyen GC, Boudreau H, Harris ML, Maxwell CV. Outcomes of obstetric hospitalizations among women with inflammatory bowel disease in the United States. Clin Gastroenterol Hepatol. 2009;7:329–334.CrossRefPubMedGoogle Scholar
  30. 30.
    Norgard B, Fonager K, Sorensen HT, Olsen J. Birth outcomes of women with ulcerative colitis: a nationwide Danish cohort study. Am J Gastroenterol. 2000;95:3165–3170.CrossRefPubMedGoogle Scholar
  31. 31.
    Norgard B, Fonager K, Pedersen L, Jacobsen BA, Sorensen HT. Birth outcome in women exposed to 5-aminosalicylic acid during pregnancy: a Danish cohort study. Gut. 2003;52:243–247.PubMedCentralCrossRefPubMedGoogle Scholar
  32. 32.
    Oron G, Yogev Y, Shkolnik S, et al. Inflammatory bowel disease: risk factors for adverse pregnancy outcome and the impact of maternal weight gain. J Matern Fetal Neonatal Med. 2012;25:2256–2260.CrossRefPubMedGoogle Scholar
  33. 33.
    Porter RJ, Stirrat GM. The effects of inflammatory bowel disease on pregnancy: a case-controlled retrospective analysis. Br J Obstet Gynaecol. 1986;93:1124–1131.CrossRefPubMedGoogle Scholar
  34. 34.
    Raatikainen K, Mustonen J, Pajala MO, Heikkinen M, Heinonen S. The effects of pre- and post-pregnancy inflammatory bowel disease diagnosis on birth outcomes. Aliment Pharmacol Ther. 2011;33:333–339.CrossRefPubMedGoogle Scholar
  35. 35.
    Stephansson O, Larsson H, Pedersen L, et al. Crohn’s disease is a risk factor for preterm birth. Clin Gastroenterol Hepatol. 2010;8:509–515.CrossRefPubMedGoogle Scholar
  36. 36.
    Stephansson O, Larsson H, Pedersen L, et al. Congenital abnormalities and other birth outcomes in children born to women with ulcerative colitis in Denmark and Sweden. Inflamm Bowel Dis. 2011;17:795–801.CrossRefPubMedGoogle Scholar
  37. 37.
    Romero R, Espinoza J, Kusanovic JP, et al. The preterm parturition syndrome. BJOG. 2006;113:17–42.CrossRefPubMedGoogle Scholar
  38. 38.
    Pinar H, Goldenberg RL, Koch MA, et al. Placental findings in singleton stillbirths. Obstet Gynecol. 2014;123:325–336.PubMedCentralCrossRefPubMedGoogle Scholar
  39. 39.
    Goldenberg RL, McClure EM, Saleem S, Reddy UM. Infection-related stillbirths. Lancet. 2010;375:1482–1490.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Aoibhlinn O’Toole
    • 1
    Email author
  • Ogochukwu Nwanne
    • 2
  • Tracy Tomlinson
    • 3
  1. 1.Department of GastroenterologyBeth Israel Deaconess Medical CenterBostonUSA
  2. 2.Institute of Human VirologyPent HouseGarki, AbujaNigeria
  3. 3.Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Women’s HealthSaint Louis University School of MedicineSt. LouisUSA

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