Bartho Lucy A, Keenan Emerson, Walker Susan P, MacDonald Teresa M, Nijagal Brunda, Tong Stephen, Kaitu'u-Lino Tu'uhevaha J
Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg 3084, Victoria, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, Australia.
Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg 3084, Victoria, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, Australia.
EBioMedicine. 2023 Aug;94:104704. doi: 10.1016/j.ebiom.2023.104704. Epub 2023 Jul 6.
Lipids serve as multifunctional metabolites that have important implications for the pregnant mother and developing fetus. Abnormalities in lipids have emerged as potential risk factors for pregnancy diseases, such as preeclampsia and fetal growth restriction. The aim of this study was to assess the potential of lipid metabolites for detection of late-onset preeclampsia and fetal growth restriction.
We used a case-cohort of 144 maternal plasma samples at 36 weeks' gestation from patients before the diagnosis of late-onset preeclampsia (n = 22), delivery of a fetal growth restricted infant (n = 55, defined as <5th birthweight centile), gestation-matched controls (n = 72). We performed liquid chromatography-tandem mass spectrometry (LC-QQQ) -based targeted lipidomics to identify 421 lipids, and fitted logistic regression models for each lipid, correcting for maternal age, BMI, smoking, and gestational diabetes.
Phosphatidylinositol 32:1 (AUC = 0.81) and cholesterol ester 17:1 (AUC = 0.71) best predicted the risk of developing preeclampsia or delivering a fetal growth restricted infant, respectively. Five times repeated five-fold cross validation demonstrated the lipids alone did not out-perform existing protein biomarkers, soluble tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) for the prediction of preeclampsia or fetal growth restriction. However, lipids combined with sFlt-1 and PlGF measurements improved disease prediction.
This study successfully identified 421 lipids in maternal plasma collected at 36 weeks' gestation from participants who later developed preeclampsia or delivered a fetal growth restricted infant. Our results suggest the predictive capacity of lipid measurements for gestational disorders holds the potential to improve non-invasive assessment of maternal and fetal health.
This study was funded by a grant from National Health and Medical Research Council.
脂质作为多功能代谢产物,对妊娠母亲和发育中的胎儿具有重要意义。脂质异常已成为妊娠疾病(如先兆子痫和胎儿生长受限)的潜在危险因素。本研究的目的是评估脂质代谢产物检测晚发型先兆子痫和胎儿生长受限的潜力。
我们使用了一个病例队列,包含144例孕36周时的孕妇血浆样本,这些样本来自晚发型先兆子痫诊断前的患者(n = 22)、分娩胎儿生长受限婴儿的患者(n = 55,定义为出生体重低于第5百分位数)、孕周匹配的对照组(n = 72)。我们采用基于液相色谱 - 串联质谱(LC - QQQ)的靶向脂质组学方法来鉴定421种脂质,并针对每种脂质拟合逻辑回归模型,对产妇年龄、体重指数、吸烟情况和妊娠糖尿病进行校正。
磷脂酰肌醇32:1(AUC = 0.81)和胆固醇酯17:1(AUC = 0.71)分别最能预测先兆子痫的发生风险或分娩胎儿生长受限婴儿的风险。五次重复的五折交叉验证表明,仅脂质在预测先兆子痫或胎儿生长受限时,表现不如现有的蛋白质生物标志物可溶性酪氨酸激酶 - 1(sFlt - 1)和胎盘生长因子(PlGF)。然而,脂质与sFlt - 1和PlGF测量值相结合可改善疾病预测。
本研究成功鉴定了孕36周时从后来发生先兆子痫或分娩胎儿生长受限婴儿的参与者中采集的孕妇血浆中的421种脂质。我们的结果表明,脂质测量对妊娠疾病的预测能力有潜力改善对母婴健康的非侵入性评估。
本研究由澳大利亚国家卫生与医学研究委员会的一项拨款资助。