三期末使用对乙酰氨基酚后产前动脉导管闭合或胎儿肾功能损害的风险可忽略：德国胚胎毒性队列评估。

Negligible risk of prenatal ductus arteriosus closure or fetal renal impairment after third-trimester paracetamol use: evaluation of the German Embryotox cohort.

机构信息

Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Klinische Pharmakologie und Toxikologie, Pharmakovigilanz- und Beratungszentrum für Embryonaltoxikologie, Berlin, Germany.

Department of Mathematics, Beuth Hochschule für Technik-University of Applied Sciences, Berlin, Germany.

出版信息

BJOG. 2019 Dec;126(13):1560-1567. doi: 10.1111/1471-0528.15872. Epub 2019 Aug 7.

DOI:10.1111/1471-0528.15872

PMID:31310697

Abstract

OBJECTIVE

Risk of fetotoxicity after paracetamol exposure in the third trimester.

DESIGN

Observational cohort study and retrospective case assessment.

SETTING

Germany, 2008-2017.

POPULATION

Pregnant women exposed to paracetamol.

METHODS

Prospectively enrolled third-trimester pregnancies that had been exposed to paracetamol (604) were compared with pregnancies exposed to paracetamol in the first and/or second trimester only (1192). Exclusion criteria were exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) in the second or third trimester. Additionally, the Embryotox 'adverse drug reaction in pregnancy' database was screened for cases of fetotoxicity.

MAIN OUTCOME MEASURES

The prenatal study end points focused on narrowing or closure of ductus arteriosus Botalli, late fetal death, and oligohydramnios. The postnatal end points included patent ductus arteriosus (PDA), primary pulmonary hypertension (PPHT), and impaired renal function.

RESULTS

In both cohorts, no fetus with intrauterine narrowing or closure of the ductus arteriosus Botalli was reported (0/604 versus 0/1192). Oligohydramnios was diagnosed at a similar frequency in both cohorts: 1.3% (8/604) versus 1.6% (19/1192). There was one stillbirth in the study cohort (1/604, 0.2%) and four stillbirths in the comparison cohort (4/1192, 0.3%). The rates of PDA in neonates were similar: 0.7% (4/615) versus 0.7% (9/1212). PPHT as well as serious postnatal renal disorders were reported once in each cohort. In 12 out of 96 retrospective cases, there were indicators for study end points; however, co-exposure to NSAIDs or complex situations weaken the assumption of paracetamol toxicity.

CONCLUSIONS

Fetal cardiovascular or renal toxicity of maternal third-trimester paracetamol use appears to be negligible.

TWEETABLE ABSTRACT

Paracetamol use in the third trimester does not seem to be associated with a relevant risk of fetotoxicity.

摘要

目的

评估第三孕期扑热息痛暴露后的胎儿毒性风险。

设计

观察性队列研究和回顾性病例评估。

地点

德国，2008 年至 2017 年。

人群

暴露于扑热息痛的孕妇。

方法

前瞻性纳入第三孕期暴露于扑热息痛的妊娠（604 例），并与仅在第一或第二孕期暴露于扑热息痛的妊娠（1192 例）进行比较。排除标准为在第二或第三孕期暴露于非甾体抗炎药（NSAIDs）。此外，还对 Embryotox“妊娠不良药物反应”数据库进行了筛查，以确定胎儿毒性病例。

主要观察指标

产前研究终点主要集中在缩窄或闭锁动脉导管 Botalli、晚期胎儿死亡和羊水过少。产后终点包括动脉导管未闭（PDA）、原发性肺动脉高压（PPHT）和肾功能受损。

结果

在两个队列中，均未报告胎儿宫内动脉导管 Botalli 缩窄或闭锁（0/604 与 0/1192）。两个队列的羊水过少发生率相似：1.3%（8/604）与 1.6%（19/1192）。研究队列中有一例死产（1/604，0.2%），对照组有四例死产（4/1192，0.3%）。新生儿 PDA 的发生率相似：0.7%（4/615）与 0.7%（9/1212）。每个队列均报告了一例 PPHT 以及严重的产后肾脏疾病。在 96 例回顾性病例中，有 12 例存在研究终点的指标；然而，同时暴露于 NSAIDs 或复杂情况削弱了扑热息痛毒性的假设。