Risk assessment of the use of anti-anxiety and hypnotic drug during pregnancy on placental trophoblastic functions

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07149
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Hokkaido University
• Principal Investigator: Furugen Ayako 北海道大学, 薬学研究院, 助教 (90767261)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 胎盤 / Trophoblast / 抗不安・睡眠薬 / Benzodiazepine

Outline of Final Research Achievements

In this study, we focused on benzodiazepine (BZ) receptor agonists and their transfer to placental trophoblast. We evaluated the effects of BZs on transporter function, hormone secretion, and differentiation. Differences in the accumulation of 17 types of BZs were observed in vitro. Our findings indicated that BZs had no effect on P-gp function. Moreover, the validity of hormone secretion and differentiation potential was evaluated as indices using valproic acid, a drug with reported risks for use during pregnancy. Using this evaluation system, we found that clobazam did not affect hormone secretion or the differentiation potential of trophoblasts. Furthermore, using human placental samples, we evaluated the relationship between differentiation-related genes and neonatal/placental parameters. A positive correlation was found between MFSD2A and the parameters. Further investigation will contribute to understanding the use of anxiolytic and sleep medications during pregnancy.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

本研究では、胎盤の多彩な生理機能に着目し、抗不安・睡眠薬の1つであるBenzodiazepine (BZ) 受容体作動薬の影響を包括的かつ多面的に評価した。一般的に、妊娠期の女性を対象とした臨床試験はハードルが高く、胎児へのリスク評価や回避に関わる基礎情報は重要であると考えられる。また、近年、周産期メンタルヘルスケアの重要性が着目されており、精神科系薬剤のリスク評価ならびに薬剤選択に関わる情報構築が望まれる。今後も更なる研究を進めるとともに、新規の睡眠薬に関する検討を行うことで、抗不安・睡眠薬の妊娠期の安全性に関する情報の構築、ならびに児のリスク低減に向けた方策の提案に繋げたい。