Intest Res.  2016 Apr;14(2):139-145. 10.5217/ir.2016.14.2.139.

Pregnancy outcome in women with inflammatory bowel disease treated with anti-tumor necrosis factor and/or thiopurine therapy: a multicenter study from Japan

• Komoto S
• Motoya S
• Nishiwaki
• Matsui T
• Kunisaki R
• Matsuoka K
• Yoshimura
• Kagaya T
• Naganuma M
• Hida N
• Watanabe M
• Hibi T
• Suzuki Y
• Miura S
• Hokari R
• Japanese study group for pregnant women with IBD

• KMID: 2425286
• DOI: http://doi.org/10.5217/ir.2016.14.2.139

Abstract

BACKGROUND/AIMS
Anti-tumor necrosis factor drugs (anti-TNF) and thiopurines are important treatment options in patients with inflammatory bowel disease (IBD), including during pregnancy. However, there are limited data on the benefit/risk profile of anti-TNF and thiopurines during pregnancy in Asia. The aim of this study was to analyze pregnancy outcomes of female Japanese IBD patients treated with anti-TNF and/or thiopurines.
METHODS
This cross-sectional study assessed pregnancy outcomes in 72 women with IBD. Pregnancy outcomes were compared among 31 pregnancies without exposure to infliximab (IFX), adalimumab (ADA), or thiopurines; 24 pregnancies with exposure to anti-TNF treatment (23 IFX, 1 ADA); 7 pregnancies with exposure to thiopurines alone; and 10 pregnancies with exposure to both IFX and thiopurines.
RESULTS
Thirty-five of the 41 pregnancies (85.3%) that were exposed to anti-TNF treatment and/or thiopurines resulted in live births after a median gestational period of 38 weeks. Of the 35 live births, 3 involved premature deliveries; 7, low birth weight; and 1, a congenital abnormality. There were 6 spontaneous abortions in pregnancies that were exposed to anti-TNF treatment (17.7%). Pregnancy outcomes among the 4 groups were similar, except for the rate of spontaneous abortions (P =0.037).
CONCLUSIONS
Exposure to anti-TNF treatment or thiopurines during pregnancy was not related to a higher incidence of adverse pregnancy outcomes in Japanese IBD patients except for spontaneous abortion.

Keyword

Inflammatory bowel diseases; Anti tumor necrosis factor-alpha; Thiopurines; Pregnancy outcome

MeSH Terms

Adalimumab
Abortion, Spontaneous
Asia
Asian Continental Ancestry Group
Congenital Abnormalities
Cross-Sectional Studies
Female
Humans
Incidence
Infliximab
Infant, Low Birth Weight
Infant, Newborn
Inflammatory Bowel Diseases*
Japan*
Live Birth
Necrosis*
Pregnancy
Pregnancy Outcome*
Pregnancy*

Reference

1. Nielsen OH, Loftus EV Jr, Jess T. Safety of TNF-α inhibitors during IBD pregnancy: a systematic review. BMC Med. 2013; 11:174. DOI: 10.1186/1741-7015-11-174. PMID: 23902720.

2. Schnitzler F, Fidder H, Ferrante M, et al. Outcome of pregnancy in women with inflammatory bowel disease treated with antitumor necrosis factor therapy. Inflamm Bowel Dis. 2011; 17:1846–1854. PMID: 21830263.

3. 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. PMID: 21115547.

4. Akbari M, Shah S, Velayos FS, Mahadevan U, Cheifetz AS. Systematic review and meta-analysis on the effects of thiopurines on birth outcomes from female and male patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013; 19:15–22. PMID: 22434610.

5. Mahadevan U, Sandborn WJ, Li DK, Hakimian S, Kane S, Corley DA. Pregnancy outcomes in women with inflammatory bowel disease: a large community-based study from Northern California. Gastroenterology. 2007; 133:1106–1112. PMID: 17764676.

6. Ziadeh S, Yahaya A. Pregnancy outcome at age 40 and older. Arch Gynecol Obstet. 2001; 265:30–33. PMID: 11327090.

7. Bush MC, Patel S, Lapinski RH, Stone JL. Perinatal outcomes in inflammatory bowel disease. J Matern Fetal Neonatal Med. 2004; 15:237–241. PMID: 15280131.

8. Fedorkow DM, Persaud D, Nimrod CA. Inflammatory bowel disease: a controlled study of late pregnancy outcome. Am J Obstet Gynecol. 1989; 160:998–1001. PMID: 2712128.

9. Morales M, Berney T, Jenny A, Morel P, Extermann P. Crohn's disease as a risk factor for the outcome of pregnancy. Hepatogastroenterology. 2000; 47:1595–1598. PMID: 11149010.

10. Nørgård B, Hundborg HH, Jacobsen BA, Nielsen GL, Fonager K. Disease activity in pregnant women with Crohn's disease and birth outcomes: a regional Danish cohort study. Am J Gastroenterol. 2007; 102:1947–1954. PMID: 17573787.

11. Reddy D, Murphy SJ, Kane SV, Present DH, Kornbluth AA. Relapses of inflammatory bowel disease during pregnancy: inhospital management and birth outcomes. Am J Gastroenterol. 2008; 103:1203–1209. PMID: 18422816.

12. 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. PMID: 23855477.

13. 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. PMID: 17185356.

14. Naganuma M, Kunisaki R, Yoshimura N, et al. Conception and pregnancy outcome in women with inflammatory bowel disease: a multicentre study from Japan. J Crohns Colitis. 2011; 5:317–323. PMID: 21683301.

15. Johnson D, Jones K, Jimenez J, Mirrasoul N, Salas E, Chambers C. Pregnancy outcomes in women exposed to adalimumab: an update on the autoimmune diseases in Pregnancy Project. Am J Gastroenterol. 2009; 104:S410.

16. Mozaffari S, Abdolghaffari AH, Nikfar S, Abdollahi M. Pregnancy outcomes in women with inflammatory bowel disease following exposure to thiopurines and antitumor necrosis factor drugs: a systematic review with meta-analysis. Hum Exp Toxicol. 2015; 34:445–459. PMID: 25378092.

17. Verstappen SM, King Y, Watson KD, Symmons DP, Hyrich KL. BSRBR Control Centre Consortium. BSR Biologics Register. Anti-TNF therapies and pregnancy: outcome of 130 pregnancies in the British Society for Rheumatology Biologics Register. Ann Rheum Dis. 2011; 70:823–826. PMID: 21362710.

18. Fotiadou C, Lazaridou E, Sotiriou E, Ioannides D. Spontaneous abortion during ustekinumab therapy. J Dermatol Case Rep. 2012; 6:105–107. PMID: 23329988.