Aliment Pharmacol Ther. 2024 Aug;60(4):503-518. doi: 10.1111/apt.18126.Epub 2024 Jul 10.

Femke Crouwel ¹, Melek Simsek ¹, Marjon A de Boer ², Dirk P van Asseldonk ³, Abha Bhalla ⁴, Angelique L M Weusthuis ⁵, Lennard P L Gilissen ⁶, Robert J Verburg ⁷, Wout G N Mares ⁸, Bindia Jharap ⁹, Johan P Kuijvenhoven ¹⁰, Bas Oldenburg ¹¹, Hans J C Buiter ¹², Mette Julsgaard ^13 14, Nanne K de Boer ¹

Author information

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

²Department of Obstetrics and Gynaecology, Vrije Universiteit Amsterdam, Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands.

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

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

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

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

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

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

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

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

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

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

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

¹⁴Institute of Clinical Medicine, Health, Aarhus University, Denmark.

Abstract

Background: Data about the safety of allopurinol in pregnant women are sparsely reported.

Aims: To 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.

Methods: We 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.

Results: We 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.

Conclusions: Overall, 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.