Multicentre study and systematic review: Allopurinol exposure during pregnancy

Femke Crouwel; Melek Simsek; Marjon A de Boer; Dirk P van Asseldonk; Abha Bhalla; Angelique L M Weusthuis; Lennard P L Gilissen; Robert J Verburg; Wout G N Mares; Bindia Jharap; Johan P Kuijvenhoven; Bas Oldenburg; Hans J C Buiter; Mette Julsgaard; Nanne K de Boer

doi:10.1111/apt.18126

Multicentre study and systematic review: Allopurinol exposure during pregnancy

Femke Crouwel, Melek Simsek, Marjon A de Boer, Dirk P van Asseldonk, Abha Bhalla, Angelique L M Weusthuis, Lennard P L Gilissen, Robert J Verburg, Wout G N Mares, Bindia Jharap, Johan P Kuijvenhoven, Bas Oldenburg, Hans J C Buiter, Mette Julsgaard, Nanne K de Boer

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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.

Original language	English
Pages (from-to)	503-518
Number of pages	16
Journal	Alimentary Pharmacology & Therapeutics
Volume	60
Issue number	4
Early online date	10 Jul 2024
DOIs	https://doi.org/10.1111/apt.18126
Publication status	Published - Aug 2024

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Aliment Pharmacol Ther - 2024 - Crouwel - Multicentre study and systematic review Allopurinol exposure during pregnancyFinal published version, 0.98 MBLicence: CC BY-NC-ND

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Crouwel, F., Simsek, M., de Boer, M. A., van Asseldonk, D. P., Bhalla, A., Weusthuis, A. L. M., Gilissen, L. P. L., Verburg, R. J., Mares, W. G. N., Jharap, B., Kuijvenhoven, J. P., Oldenburg, B., Buiter, H. J. C., Julsgaard, M., & de Boer, N. K. (2024). Multicentre study and systematic review: Allopurinol exposure during pregnancy. Alimentary Pharmacology & Therapeutics, 60(4), 503-518. https://doi.org/10.1111/apt.18126

@article{41dc52a2fa3844b294ff389b60bdab05,

title = "Multicentre study and systematic review: Allopurinol exposure during pregnancy",

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.",

author = "Femke Crouwel and Melek Simsek and {de Boer}, {Marjon A} and {van Asseldonk}, {Dirk P} and Abha Bhalla and Weusthuis, {Angelique L M} and Gilissen, {Lennard P L} and Verburg, {Robert J} and Mares, {Wout G N} and Bindia Jharap and Kuijvenhoven, {Johan P} and Bas Oldenburg and Buiter, {Hans J C} and Mette Julsgaard and {de Boer}, {Nanne K}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.",

year = "2024",

month = aug,

doi = "10.1111/apt.18126",

language = "English",

volume = "60",

pages = "503--518",

journal = "Alimentary Pharmacology & Therapeutics",

issn = "0269-2813",

publisher = "Wiley-Blackwell",

number = "4",

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Crouwel, F, Simsek, M, de Boer, MA, van Asseldonk, DP, Bhalla, A, Weusthuis, ALM, Gilissen, LPL, Verburg, RJ, Mares, WGN, Jharap, B, Kuijvenhoven, JP, Oldenburg, B, Buiter, HJC, Julsgaard, M & de Boer, NK 2024, 'Multicentre study and systematic review: Allopurinol exposure during pregnancy', Alimentary Pharmacology & Therapeutics, vol. 60, no. 4, pp. 503-518. https://doi.org/10.1111/apt.18126

TY - JOUR

T1 - Multicentre study and systematic review

T2 - Allopurinol exposure during pregnancy

AU - Crouwel, Femke

AU - Simsek, Melek

AU - de Boer, Marjon A

AU - van Asseldonk, Dirk P

AU - Bhalla, Abha

AU - Weusthuis, Angelique L M

AU - Gilissen, Lennard P L

AU - Verburg, Robert J

AU - Mares, Wout G N

AU - Jharap, Bindia

AU - Kuijvenhoven, Johan P

AU - Oldenburg, Bas

AU - Buiter, Hans J C

AU - Julsgaard, Mette

AU - de Boer, Nanne K

PY - 2024/8

Y1 - 2024/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85198123786&partnerID=8YFLogxK

U2 - 10.1111/apt.18126

DO - 10.1111/apt.18126

M3 - Article

C2 - 38984819

SN - 0269-2813

VL - 60

SP - 503

EP - 518

JO - Alimentary Pharmacology & Therapeutics

JF - Alimentary Pharmacology & Therapeutics

IS - 4

ER -

Multicentre study and systematic review: Allopurinol exposure during pregnancy

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