Ghazvini Saman, Uthaman Saji, Synan Lilly, Lin Eugene C, Sarkar Soumik, Santillan Mark K, Santillan Donna A, Bardhan Rizia
Department of Chemical and Biological Engineering Iowa State University Ames Iowa USA.
Nanovaccine Institute Iowa State University Ames Iowa USA.
Bioeng Transl Med. 2023 Aug 31;9(1):e10595. doi: 10.1002/btm2.10595. eCollection 2024 Jan.
Preeclampsia is a life-threatening pregnancy disorder. Current clinical assays cannot predict the onset of preeclampsia until the late 2nd trimester, which often leads to poor maternal and neonatal outcomes. Here we show that Raman spectroscopy combined with machine learning in pregnant patient plasma enables rapid, highly sensitive maternal metabolome screening that predicts preeclampsia as early as the 1st trimester with >82% accuracy. We identified 12, 15 and 17 statistically significant metabolites in the 1st, 2nd and 3rd trimesters, respectively. Metabolic pathway analysis shows multiple pathways corresponding to amino acids, fatty acids, retinol, and sugars are enriched in the preeclamptic cohort relative to a healthy pregnancy. Leveraging Pearson's correlation analysis, we show with Raman Spectroscopy that metabolites are associated with several clinical factors, including patients' body mass index, gestational age at delivery, history of preeclampsia, and severity of preeclampsia. We also show that protein quantification alone of proinflammatory cytokines and clinically relevant angiogenic markers are inadequate in identifying at-risk patients. Our findings demonstrate that Raman spectroscopy is a powerful tool that may complement current clinical assays in early diagnosis and in the prognosis of the severity of preeclampsia to ultimately enable comprehensive prenatal care for all patients.
子痫前期是一种危及生命的妊娠疾病。目前的临床检测方法直到孕中期晚期才能预测子痫前期的发病,这往往导致母婴不良结局。在此,我们表明,将拉曼光谱与机器学习相结合用于孕妇血浆检测,能够实现快速、高度灵敏的母体代谢组筛查,早在孕早期就能预测子痫前期,准确率超过82%。我们分别在孕早期、孕中期和孕晚期鉴定出12种、15种和17种具有统计学意义的代谢物。代谢途径分析表明,与健康妊娠相比,子痫前期队列中与氨基酸、脂肪酸、视黄醇和糖类相对应的多种途径富集。利用皮尔逊相关分析,我们通过拉曼光谱表明,代谢物与几个临床因素相关,包括患者的体重指数、分娩时的孕周、子痫前期病史以及子痫前期的严重程度。我们还表明,仅对促炎细胞因子和临床相关血管生成标志物进行蛋白质定量不足以识别高危患者。我们的研究结果表明,拉曼光谱是一种强大的工具,可在子痫前期的早期诊断和严重程度预后方面补充当前的临床检测方法,最终为所有患者提供全面的产前护理。