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多中心研究和系统评价:妊娠期别嘌醇暴露。

Multicentre study and systematic review: Allopurinol exposure during pregnancy.

机构信息

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

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

出版信息

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

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.

摘要

背景

关于别嘌醇在孕妇中的安全性数据报道甚少。

目的

调查炎症性肠病(IBD)妊娠和一般妊娠中母体暴露于别嘌醇后不良妊娠结局和先天性异常的风险。

方法

我们收集了 2013 年 1 月至 2022 年 3 月期间接受别嘌醇治疗的 IBD 患者的安全性数据。此外,我们还对别嘌醇的致畸潜力进行了系统评价。

结果

我们共收集了 42 例别嘌醇暴露妊娠的数据,其中包括 1 例双胞胎妊娠;所有女性均同时接受了硫唑嘌呤治疗。6 例(14.3%)妊娠发生流产,1 例妊娠于 32 周时发生死胎。1 例新生儿(产后发现主动脉缩窄)存在先天性异常。3 例妊娠(包括双胞胎妊娠)足月分娩,1 例早产。5 例新生儿(15.2%)为小于胎龄儿。通过文献检索,我们还发现了另外 102 例别嘌醇暴露妊娠,共 129 例活产儿,其中包括我们队列中的 36 例。10 例婴儿(7.8%)出生时存在先天性异常。2 例(1.6%)存在类似的多发畸形模式。系统评价的亚分析仅纳入了母亲患有 IBD 的婴儿(n=76),结果显示,母体暴露于低剂量别嘌醇后,2.6%的婴儿存在先天性异常。

结论

总体而言,别嘌醇的致畸性仍不确定。母亲在治疗 IBD 时接受别嘌醇/硫唑嘌呤联合治疗所生育的儿童似乎没有增加先天性异常的风险。

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