Saint-Lary Laura, Beau Anna-Belle, Sommet Agnès, Leroy Valériane, Loane Maria, Cavero-Carbonell Clara, Garne Ester, Hoareau Jonathan, Bielenska Anna Latos, Monier Isabelle, Nelen Vera, Neville Amanda J, O'Mahony Mary, Perthus Isabelle, Pierini Anna, Rissmann Anke, Rouget Florence, Sichitiu Joanna, Tucker David, Dolk Helen, Damase-Michel Christine
Inserm U1295, Team SPHERE, CERPOP, Université Paul Sabatier Toulouse 3, 37 Allées Jules Guesde, 31000, Toulouse, France.
Service de Pharmacologie Clinique, CHU de Toulouse, Université de Toulouse, Toulouse, France.
Eur J Clin Pharmacol. 2025 May;81(5):697-709. doi: 10.1007/s00228-025-03814-w. Epub 2025 Feb 26.
Antiretroviral drugs are recommended during pregnancy to achieve HIV viral suppression and reduce mother-to-child transmission. Congenital anomaly signals were reported after fetal exposure to antiretroviral drugs in several studies warranting further investigation. We aimed to evaluate the risk of congenital anomalies after fetal exposure to antiretroviral drugs using the European congenital anomaly registry data.
A case/non-case study was performed, using the EUROmediCAT central database. All the congenital anomalies, exposed to any antiretroviral drugs, were included from 1995 to 2019. We explored each signal identified from the literature for associations between congenital anomalies and specific antiretroviral exposures. We compared antiretroviral exposure between the signal anomalies (cases) and all other malformed registrations (controls). Reporting odds ratio (ROR) and their 95% confidence intervals were estimated and adjusted for registry and maternal age.
Between 1995 and 2019, 173 cases of congenital anomalies were observed after any exposure to antiretroviral drugs. The signal previously identified in the literature between congenital heart defects and exposure to zidovudine was confirmed in the main analysis (aROR 3.66 [1.63-8.23]). Other signals identified in the literature were not confirmed, although two cases of hypospadias and two cases of limb defects were reported after zidovudine and atazanavir exposure, respectively. The signal detection analysis did not reveal any new signal after applying the Bonferroni correction.
Our study does not reveal new signals but confirms the previously identified signal between congenital heart defects and fetal exposure to zidovudine. The physio-pathological hypothesis induced by zidovudine exposure should be explored in future studies.
推荐在孕期使用抗逆转录病毒药物以实现HIV病毒抑制并减少母婴传播。多项研究报告了胎儿暴露于抗逆转录病毒药物后出现先天性异常信号，这值得进一步调查。我们旨在利用欧洲先天性异常登记数据评估胎儿暴露于抗逆转录病毒药物后出现先天性异常的风险。
使用EUROmediCAT中央数据库进行病例/非病例研究。纳入1995年至2019年期间所有暴露于任何抗逆转录病毒药物的先天性异常病例。我们探究了文献中确定的每个信号，以寻找先天性异常与特定抗逆转录病毒药物暴露之间的关联。我们比较了信号异常（病例）与所有其他畸形登记（对照）之间的抗逆转录病毒药物暴露情况。估计报告比值比（ROR）及其95%置信区间，并针对登记处和母亲年龄进行调整。
1995年至2019年期间，观察到173例在暴露于任何抗逆转录病毒药物后出现的先天性异常病例。主要分析证实了文献中先前确定的先天性心脏缺陷与齐多夫定暴露之间的信号（调整后ROR 3.66 [1.63 - 8.23]）。文献中确定的其他信号未得到证实，尽管分别报告了2例在齐多夫定暴露后出现的尿道下裂病例和2例在阿扎那韦暴露后出现的肢体缺陷病例。应用Bonferroni校正后，信号检测分析未发现任何新信号。
我们的研究未发现新信号，但证实了先前确定的先天性心脏缺陷与胎儿暴露于齐多夫定之间的信号。未来研究应探索齐多夫定暴露引发的生理病理假说。
