Exposure to Thioguanine During 117 Pregnancies in Women With Inflammatory Bowel Disease

Author:

Crouwel Femke1ORCID,Simsek Melek1,de Boer Marjon A2,Mulder Chris J J1,van Andel Emma M3,Creemers Rob H4ORCID,van Asseldonk Dirk P3,van Bodegraven Ad A14,Horjus Carmen S5,Visschedijk Marijn C6,Weusthuis Angelique L M7,Seinen Margien L8,Jharap Bindia9,van Schaik Fiona D M10,Ahmad Ishfaq11,Boekema Paul J12,Tack Greetje J13,Wormmeester Louktje14,Lutgens Maurice W M D15,van Boeckel Petra G A16,Gilissen Lennard P L17,Kerkhof Marjon18,Russel Maurice G V M19,Hoentjen Frank2021,Bartelink Maartje E7,Kuijvenhoven Johan P22,Maljaars Jeroen W J23,van Dop Willemijn A20,Wonders Janneke24,van der Voorn Michael M P J A24,Buiter Hans J C25,de Boer Nanne K1

Affiliation:

1. Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam , Amsterdam , The Netherlands

2. Department of Obstetrics and Gyneacology, Amsterdam Reproduction & Development Research Institute, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam , Amsterdam , The Netherlands

3. Department of Gastroenterology and Hepatology, Noordwest Ziekenhuisgroep , Alkmaar , The Netherlands

4. Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine [Co-MIK], Zuyderland Medical Centre , Heerlen-Sittard-Geleen , The Netherlands

5. Department of Gastroenterology and Hepatology, Rijnstate Hospital , Arnhem , The Netherlands

6. Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen , Groningen , The Netherlands

7. Department of Gastroenterology and Hepatology, Deventer Hospital , Deventer , The Netherlands

8. Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis , Amsterdam , The Netherlands

9. Department of Gastroenterology and Hepatology, Meander Medical Centre , Amersfoort , The Netherlands

10. Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht University , Utrecht , The Netherlands

11. Department of Gastroenterology and Hepatology, Streekziekenhuis Koningin Beatrix , Winterswijk , The Netherlands

12. Department of Gastroenterology and Hepatology, Máxima Medical Centre , Veldhoven , The Netherlands

13. Department of Gastroenterology and Hepatology, Medical Centre Leeuwarden , Leeuwarden , The Netherlands

14. Department of Gastroenterology and Hepatology, Treant Zorggroep , Emmen-Hoogeveen-Stadskanaal , The Netherlands

15. Department of Gastroenterology and Hepatology, Elisabeth-TweeSteden Hospital , Tilburg , The Netherlands

16. Department of Gastroenterology and Hepatology, Sint Antonius Hospital , Nieuwegein , The Netherlands

17. Department of Gastroenterology and Hepatology, Catharina Hospital , Eindhoven , The Netherlands

18. Department of Gastroenterology and Hepatology, Groene Hart Hospital , Gouda , The Netherlands

19. Department of Gastroenterology and Hepatology, Medical Spectrum Twente , Enschede , The Netherlands

20. Department of Gastroenterology, Radboud University Medical Center , Nijmegen , The Netherlands

21. Division of Gastroenterology, Department of Medicine, University of Alberta , Edmonton, AB , Canada

22. Department of Gastroenterology and Hepatology, Spaarne Gasthuis , Haarlem and Hoofddorp , The Netherlands

23. Department of Gastroenterology and Hepatology, Leiden University Medical Center , Leiden , The Netherlands

24. Department of Gastroenterology and Hepatology, HagaZiekenhuis , Den Haag , The Netherlands

25. Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centre , Amsterdam , The Netherlands

Abstract

Abstract Background Safety of thioguanine in pregnant patients with inflammatory bowel disease [IBD] is sparsely recorded. This study was aimed to document the safety of thioguanine during pregnancy and birth. Methods In this multicentre case series, IBD patients treated with thioguanine during pregnancy were included. Data regarding disease and medication history, pregnancy course, obstetric complications, and neonatal outcomes were collected. Results Data on 117 thioguanine-exposed pregnancies in 99 women were collected. Most [78%] had Crohn’s disease and the mean age at delivery was 31 years. In 18 pregnancies [15%], IBD flared. Obstetric and infectious complications were seen in 15% [n = 17] and 7% [n = 8] of pregnancies, respectively. Ten pregnancies [8.5%] resulted in a first trimester miscarriage, one in a stillbirth at 22 weeks of gestational age and one in an induced abortion due to trisomy 21. In total, 109 neonates were born from 101 singleton pregnancies and four twin pregnancies. One child was born with a congenital abnormality [cleft palate]. In the singleton pregnancies, 10 children were born prematurely and 10 were born small for gestational age. Screening for myelosuppresion was performed in 16 neonates [14.7%]; two had anaemia in umbilical cord blood. All outcomes were comparable to either the general Dutch population or to data from three Dutch cohort studies on the use of conventional thiopurines in pregnant IBD patients. Conclusion In this large case series, the use of thioguanine during pregnancy is not associated in excess with adverse maternal or neonatal outcomes.

Funder

Teva Nederland

Publisher

Oxford University Press (OUP)

Subject

Gastroenterology,General Medicine

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