Dathe Katarina, Benndorf Carolin, Bergner Simone, Schaefer Christof
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Clinical Pharmacology and Toxicology, Embryotox Center of Clinical Teratology and Drug Safety in Pregnancy, Augustenburger Platz 1, 13353 Berlin, Germany.
Federal Institute for Drugs and Medical Devices, Pharmacovigilance Division, Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany.
Pharmaceuticals (Basel). 2024 Nov 26;17(12):1592. doi: 10.3390/ph17121592.
Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used during pregnancy. Due to their fetotoxicity, NSAIDs are contraindicated during the third trimester. There is ongoing controversy about the extent to which NSAIDs may cause cardiovascular and renal impairment in the fetus earlier in the second trimester. Paracetamol, used as an effective treatment for closure of patent ductus arteriosus (PDA) after birth, is suspected to cause similar but unwanted effects during the third trimester of pregnancy. Three major pharmacovigilance databases (VigilanceCentral, EudraVigilance, and VigiBase) were searched for Individual Case Safety Reports (ICSRs; = 1288) on fetotoxic effects that have been shown to result from NSAID exposure in late pregnancy. In 219/1288 cases, an NSAID and/or paracetamol was taken after the first trimester, and the ICSR was not related to other reported risk factors. Out of these 219 ICSRs, 48 were exposed to NSAIDs in the second but not the third trimester or to paracetamol in the third trimester. Causality assessment was "probable or likely" in four NSAID reports and none of the paracetamol reports. The scarcity of adverse drug reactions (ADRs) in our study and in the literature, despite decades of pharmaceutical marketing and worldwide use of paracetamol as an analgesic of choice in the third trimester and the absence of formal contraindications against NSAIDs in the second trimester, speaks against a substantial cardiovascular and nephrotoxic risk of temporary use of NSAIDs in the second trimester or paracetamol in the third trimester. NSAIDs continue to be contraindicated in the third trimester.
对乙酰氨基酚和非甾体抗炎药（NSAIDs）在孕期经常被使用。由于其对胎儿的毒性，NSAIDs在孕晚期是禁忌的。关于NSAIDs在孕中期早期对胎儿造成心血管和肾脏损害的程度，目前仍存在争议。对乙酰氨基酚在出生后用作治疗动脉导管未闭（PDA）的有效药物，有人怀疑它在孕期第三个月会产生类似但不良的影响。检索了三个主要的药物警戒数据库（VigilanceCentral、EudraVigilance和VigiBase），以查找关于孕晚期接触NSAIDs导致胎儿毒性作用的个体病例安全报告（ICSRs；n = 1288）。在1288例病例中，有219例在孕早期后服用了NSAID和/或对乙酰氨基酚，且该ICSR与其他报告的风险因素无关。在这219份ICSR中，有48例在孕中期而非孕晚期接触了NSAIDs，或在孕晚期接触了对乙酰氨基酚。在4份NSAID报告中因果关系评估为“可能或很可能”，而对乙酰氨基酚报告中无一例如此。尽管经过数十年的药品营销以及全球范围内在孕晚期将对乙酰氨基酚作为首选镇痛药使用，且在孕中期没有对NSAIDs的正式禁忌，但我们的研究和文献中药物不良反应（ADR）较少，这表明在孕中期临时使用NSAIDs或在孕晚期使用对乙酰氨基酚不存在实质性的心血管和肾毒性风险。NSAIDs在孕晚期仍然是禁忌的。
