Multicentre study and systematic review: Allopurinol exposure during pregnancy

Author:

Crouwel Femke1ORCID,Simsek Melek1,de Boer Marjon A.2,van Asseldonk Dirk P.3,Bhalla Abha4,Weusthuis Angelique L. M.5,Gilissen Lennard P. L.6,Verburg Robert J.7,Mares Wout G. N.8,Jharap Bindia9,Kuijvenhoven Johan P.10,Oldenburg Bas11,Buiter Hans J. C.12,Julsgaard Mette1314ORCID,de Boer Nanne K.1

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 Gynaecology Vrije Universiteit Amsterdam, Amsterdam Reproduction & Development Research Institute Amsterdam The Netherlands

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

4. Department of Gastroenterology and Hepatology HagaZiekenhuis Den Haag The Netherlands

5. Department of Gastroenterology and Hepatology Deventer Ziekenhuis Deventer The Netherlands

6. Department of Gastroenterology and Hepatology Catharina Hospital Eindhoven Eindhoven The Netherlands

7. Department of Gastroenterology and Hepatology Haaglanden Medisch Centrum Den Haag The Netherlands

8. Department of Gastroenterology and Hepatology Ziekenhuis Gelderse Vallei Ede The Netherlands

9. Department of Gastroenterology and Hepatology Meander Medisch Centrum Amersfoort The Netherlands

10. Department of Gastroenterology and Hepatology Spaarne Gasthuis Haarlem The Netherlands

11. Department of Gastroenterology and Hepatology UMC Utrecht Utrecht The Netherlands

12. Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centre Vrije Universiteit Amsterdam Amsterdam The Netherlands

13. Department of Hepatology and Gastroenterology Aarhus University Hospital Aarhus Denmark

14. Institute of Clinical Medicine, Health Aarhus University Denmark

Abstract

SummaryBackgroundData about the safety of allopurinol in pregnant women are sparsely reported.AimsTo investigate the risk of adverse pregnancy outcome and congenital abnormalities after in utero exposure to allopurinol in inflammatory bowel disease (IBD) pregnancies and in general.MethodsWe collected safety data of patients with IBD who were treated with allopurinol during pregnancy between January 2013 and March 2022. Additionally, we performed a systematic review about the teratogenic potential of allopurinol.ResultsWe collected data from 42 allopurinol‐exposed pregnancies, including one twin pregnancy; in all women, allopurinol was combined with a thiopurine. Six pregnancies (14.3%) resulted in miscarriage and one in stillbirth at 32 weeks. A congenital anomaly was observed in one newborn (coarctation of the aorta discovered postpartum). Three pregnancies, including the twin pregnancy, ended in moderate preterm delivery and one in very preterm delivery. Five neonates (15.2%) were small for gestational age. From our literature search, we identified an additional 102 allopurinol‐exposed pregnancies resulting in 129 live births, including 36 infants from our cohort. Ten infants (7.8%) were born with a congenital anomaly. Two (1.6%) had a comparable pattern of multiple anomalies. The systematic review sub‐analysis including only infants born to mothers with IBD (n = 76) revealed that 2.6% of infants had congenital anomalies after in utero exposure to a low dose of allopurinol.ConclusionsOverall, the teratogenicity of allopurinol remains inconclusive. Children conceived by mothers treated for IBD with allopurinol/thiopurine co‐therapy do not seem to have an increased risk of congenital anomalies.

Publisher

Wiley

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