Prediction of preeclampsia using circulationg levels of Galectin-1 and HSD17B1 in the first trimester

• Project/Area Number: 17K11247
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Jichi Medical University
• Principal Investigator: Ohkuchi Akihide 自治医科大学, 医学部, 教授 (10306136)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: preeclampsia / HSD17B1 / placental growth factor / prediction / galectin 1 / preterm preeclampsia / blood pressure / multivariable analysis / 妊娠高血圧腎症 / 妊娠初期 / 発症予知 / バイオマーカー / 胎盤蛋白質 / 臨床

Outline of Final Research Achievements

The Data of hydroxysteroid (17-β) dehydrogenase 1 (HSD17B1) measured using commercially available enzyme-linked immuno sorbent assay ELISA were unstable. The levels of placental protein 13 (PP-13) in the first trimester in women with singleton pregnancy using commercially available ELISA could not predict the occurrence of preeclampsia (PE). Using 800 women in the first trimester, we measured galectin 1 (Gal-1), and placental growth factor (PlGF). High levels of Gal-1 in women with singleton pregnancy using commercially available ELISA predicted the occurrence of PE. The combination of PlGF (Elecsys PlGF, Roche), blood pressure levels, and a past history of PE/gestational hypertension (GH) yielded sensitivity of 60% at 10% of false positive rate for predicting preterm PE, suggesting that the measurement of serum PlGF levels in the first trimester in real practice will become a very important laboratory test for predicting and preventing preterm PE.

Academic Significance and Societal Importance of the Research Achievements

本研究では、早産期発症PEは10例以上発症したため、単変量（PlGF、血圧レベル）、多変量（PlGF、血圧レベル、PE/GH既往の組み合わせ）で予知可能かを検討した。現在、妊娠16週以前からの低用量アスピリン投与のターゲットが早産期発症PEであり、今後は、妊娠初期での早産期発症PE発症予知・予防研究が主体となってくると予想される。その意味で、わずか3つの組み合わせではあるが、血圧レベル、血清PlGF、および既往PE/GHの組み合わせによって、疑陽性率10％で十分に臨床的に意味のある感度（60％）が得られたことから、妊娠初期のPlGF測定はPE予知において重要な位置づけになっていくと予想される。

Research Products

• [Journal Article] Temporary hypertension and white coat hypertension in the first trimester as risk factors for preeclampsia (2019)
  • Author(s): Ohkuchi A, Hirashima C, Arai R, Takahashi K, Suzuki H, Ogoyama M, Nagayama S, Takahashi H, Baba Y, Usui R, Shirasuna K, Matsubara S
  • Journal Title: Hypertens Res Volume: 42 Issue: 12 Pages: 2002-2012
  • DOI: 10.1038/s41440-019-0307-6
  • Peer Reviewed
• [Presentation] 妊娠高血圧腎症のハイリスクとしての妊娠初期のtemporary hypertension (2019)
  • Author(s): 平嶋 周子, 大口 昭英, 高橋 佳代, 鈴木 寛正, 小古山 学, 永山 志穂, 高橋 宏典, 薄井 里英, 桑田 知之, 松原 茂樹
  • Organizer: 日本妊娠高血圧学会