Pogliani Laura, Falvella Felicia S, Cattaneo Dario, Pileri Paola, Moscatiello Anna F, Cheli Stefania, Baldelli Sara, Fabiano Valentina, Cetin Irene, Clementi Emilio, Zuccotti Gianvincenzo
*Department of Pediatrics, ASST Fatebenefratelli-Sacco, L. Sacco University Hospital, Milan; †Unit of Clinical Pharmacology, ASST Fatebenefratelli-Sacco, L. Sacco University Hospital, Milan; ‡Department of Gynecology and Obstetrics, ASST Fatebenefratelli-Sacco, L. Sacco Hospital, University Hospital, Milan; §Department of Pediatrics, ASST Fatebenefratelli-Sacco, Ospedale dei Bambini V. Buzzi, Milan; ¶Clinical Pharmacology Unit, Consiglio Nazionale delle Ricerche Institute of Neuroscience, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Università degli Studi di Milano, Milan; and ‖E. Medea Scientific Institute, Bosisio Parini, Italy.
Ther Drug Monit. 2017 Apr;39(2):197-201. doi: 10.1097/FTD.0000000000000370.
An involvement of selective serotonin reuptake inhibitors (SSRIs) in increasing the risk of malformations, neonatal withdrawal syndrome, has been suggested recently. Here, we aimed to investigate the contribution of individual pharmacogenetics of SSRI on infants' outcome. We also estimated the umbilical/maternal plasma SSRI concentration ratio in the pregnant women still on SSRI therapy at the time of delivery.
Thirty-four pregnant women, referred to our hospital from January 2011 to July 2015, who were given SSRIs in the third trimester, and related children, were considered. The umbilical/maternal plasma SSRI concentration ratio was estimated in 15 mothers still on SSRI therapy at the time of delivery. For patients with pharmacokinetic analyses, blood samples were collected for pharmacogenetic analyses.
Nineteen newborns presented clinical signs possibly related to drug toxicity. A high umbilical/maternal plasma ratio of SSRI was observed in 10 of the 15 evaluated newborns. Five mothers were intermediate metabolizers and 1 a poor metabolizer for the major CYP enzyme involved in pharmacokinetic pathway.
Individualized psychopharmacologic treatment that takes into account the mother's exposure to SSRI concentrations and eventually her genetic background may become the standard of care to maximize drug benefit and minimize risks to the newborn.
最近有人提出，选择性5-羟色胺再摄取抑制剂（SSRI）会增加胎儿畸形、新生儿戒断综合征的风险。在此，我们旨在研究SSRI的个体药物遗传学对婴儿结局的影响。我们还估算了在分娩时仍接受SSRI治疗的孕妇的脐血/母体血浆SSRI浓度比。
研究对象为2011年1月至2015年7月转诊至我院的34名孕妇及其相关子女，这些孕妇在孕晚期使用了SSRI。对15名在分娩时仍接受SSRI治疗的母亲估算了脐血/母体血浆SSRI浓度比。对于进行药代动力学分析的患者，采集血样进行药物遗传学分析。
19名新生儿出现了可能与药物毒性相关的临床症状。在15名接受评估的新生儿中，有10名的脐血/母体血浆SSRI比例较高。5名母亲是参与药代动力学途径的主要CYP酶的中间代谢者，1名是慢代谢者。
考虑母亲接触的SSRI浓度以及最终其遗传背景的个体化精神药理学治疗，可能会成为将药物益处最大化并将对新生儿的风险最小化的标准治疗方法。
