From the Division of Neonatology (K.S.E., S.W.).
and Division of Paediatric Pharmacology and Pharmacometrics (A.A., M.P.).
Hypertension. 2018 Jun;71(6):1178-1184. doi: 10.1161/HYPERTENSIONAHA.117.10314. Epub 2018 Apr 23.
Preeclampsia has been shown to be associated with changes in cerebral structure and cognitive function later in life. Nf (neurofilaments) are specific scaffolding proteins of neurons, and their quantification in serum has been proposed as a biomarker for neuroaxonal injury. We performed a prospective, longitudinal, single-center study at the University Hospital of Basel to determine serum Nf concentrations in pregnant women with singleton pregnancies and with high risk of preeclampsia or with early signs of preeclampsia. Enrollment started at 21 weeks of gestation, followed up with multiple visits until delivery. Sixty out of 197 women developed preeclampsia (30.5%). NfL (Nf light chain) was measured with a highly sensitive single molecule array (Simoa) assay, in addition to the established preeclampsia markers sFlt-1 (soluble fms-like tyrosine kinase-1) and PlGF (placental growth factor). The most important independent predictors of NfL were maternal age, number of pregnancies, and proteinuria. NfL levels increased during pregnancy and were significantly higher in women developing preeclampsia. The discriminatory accuracy of NfL, PlGF, and sFlt-1 in receiver operating characteristic curves analysis (area under the curve) of the overall group was 0.68, 0.81, and 0.84, respectively, and in women older than 36 years 0.7, 0.62, and 0.79, respectively. We conclude that increased axonal injury serum marker NfL predicts preeclampsia particularly in older women, with an accuracy similar to the established angiogenic factors. NfL may serve as an early indicator of preeclampsia-induced changes in cerebral structure and may help to stratify disease management.
子痫前期与大脑结构和认知功能的改变有关。神经丝（NF）是神经元特有的支架蛋白，其在血清中的定量已被提出作为神经轴突损伤的生物标志物。我们在巴塞尔大学医院进行了一项前瞻性、纵向、单中心研究，以确定患有单胎妊娠且有子痫前期高危或有早期子痫前期迹象的孕妇的血清 NF 浓度。招募工作从 21 孕周开始，随后进行多次随访直到分娩。197 名女性中有 60 名（30.5%）发展为子痫前期。除了已建立的子痫前期标志物 sFlt-1（可溶性 fms 样酪氨酸激酶-1）和 PlGF（胎盘生长因子）外，还使用高灵敏度的单分子阵列（Simoa）测定法测量了 NF-L（NF 轻链）。NF-L 的最重要独立预测因子是母亲年龄、妊娠次数和蛋白尿。NF-L 水平在怀孕期间增加，在发生子痫前期的女性中显着更高。在整个组的受试者工作特征曲线分析（曲线下面积）中，NF-L、PlGF 和 sFlt-1 的鉴别准确性分别为 0.68、0.81 和 0.84，而在年龄大于 36 岁的女性中分别为 0.7、0.62 和 0.79。我们得出结论，增加的轴突损伤血清标志物 NF-L 特别在年龄较大的女性中预测子痫前期，其准确性与已建立的血管生成因子相似。NF-L 可能作为子痫前期引起的大脑结构变化的早期指标，并有助于分层疾病管理。
