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

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Abstract

Background

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

Aim

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.

Methods

We searched PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov 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.

Results

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.

Conclusion

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

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References

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  5. Nielsen OH, Loftus EV Jr, Jess T. Safety of TNF-alpha inhibitors during IBD pregnancy: a systematic review. BMC Med. 2013;11:174.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Wang ML, Dorer DJ, Fleming MP, Catlin EA. Clinical outcomes of near-term infants. Pediatrics. 2004;114:372–376.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  9. Larzilliere I, Beau P. Chronic inflammatory bowel disease and pregnancy. Case control study. Gastroenterol Clin Biol. 1998;22:1056–1060.

    CAS  PubMed  Google Scholar 

  10. Moser MA, Okun NB, Mayes DC, Bailey RJ. Crohn’s disease, pregnancy, and birth weight. Am J Gastroenterol. 2000;95:1021–1026.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  12. Juni P, Altman DG, Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ. 2001;323:42–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Egger M, Schneider M, Smith GD. Spurious precision? Meta-analysis of observational studies. BMJ. 1998;316:140–144.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Baird DD, Narendranathan M, Sandler RS. Increased risk of preterm birth for women with inflammatory bowel disease. Gastroenterology. 1990;99:987–994.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  17. Bush MC, Patel S, Lapinski RH, Stone JL. Perinatal outcomes in inflammatory bowel disease. J Matern Fetal Neonatal Med. 2004;15:237–241.

    Article  CAS  PubMed  Google Scholar 

  18. Cleary BJ, Kallen B. Early pregnancy azathioprine use and pregnancy outcomes. Birth Defects Res A Clin Mol Teratol. 2009;85:647–654.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  26. Ludvigsson JF, Ludvigsson J. Inflammatory bowel disease in mother or father and neonatal outcome. Acta Paediatr. 2002;91:145–151.

    Article  CAS  PubMed  Google Scholar 

  27. Mahadevan U. Gastrointestinal medications in pregnancy. Best Pract Res Clin Gastroenterol. 2007;21:849–877.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  37. Romero R, Espinoza J, Kusanovic JP, et al. The preterm parturition syndrome. BJOG. 2006;113:17–42.

    Article  CAS  PubMed  Google Scholar 

  38. Pinar H, Goldenberg RL, Koch MA, et al. Placental findings in singleton stillbirths. Obstet Gynecol. 2014;123:325–336.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Goldenberg RL, McClure EM, Saleem S, Reddy UM. Infection-related stillbirths. Lancet. 2010;375:1482–1490.

    Article  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215, USA

    Aoibhlinn O’Toole

  2. Institute of Human Virology, Pent House, Maina Court, Plot 252, Herbert Macaulay Way, Central Business District, P.O. Box 9396, Garki, Abuja, Nigeria

    Ogochukwu Nwanne

  3. Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Women’s Health, Saint Louis University School of Medicine, 6420 Clayton Road, Suite 6520, St. Louis, MO, 63117, USA

    Tracy Tomlinson

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  1. Aoibhlinn O’Toole
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Correspondence to Aoibhlinn O’Toole.

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O’Toole, A., Nwanne, O. & Tomlinson, T. Inflammatory Bowel Disease Increases Risk of Adverse Pregnancy Outcomes: A Meta-Analysis. Dig Dis Sci 60, 2750–2761 (2015). https://doi.org/10.1007/s10620-015-3677-x

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  • DOI: https://doi.org/10.1007/s10620-015-3677-x

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