Trilla Cristina, Luna Cristina, De León Socorro Silvia, Rodriguez Leire, Ruiz-Romero Aina, Mora Brugués Josefina, Benítez Delgado Taysa, Fabre Marta, Martin Martínez Alicia, Ruiz-Martinez Sara, Llurba Elisa, Oros Daniel
Obstetrics and Gynecology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Red RICORS "Primary Care Interventions to Prevent Maternal and Child Chronic Diseases of Perinatal and Developmental Origin", RD21/0012/0001, Instituto de Salud Carlos III, Madrid, Spain.
Front Cardiovasc Med. 2022 Jul 26;9:931943. doi: 10.3389/fcvm.2022.931943. eCollection 2022.
The incidence of preeclampsia (PE) is about 2-8%, making it one of the leading causes of perinatal morbidity and maternal mortality in the world. Early prophylactic low dose administration (150 mg) of acetylsalicylic acid is associated with a significant reduction in the incidence of early-onset PE, intrauterine growth restriction (IUGR), and neonatal mean stay in the intensive care unit (ICU). Universal implementation of a first-trimester screening system including angiogenic and antiangiogenic markers [the Placental Growth Factor (PlGF) and/or soluble fms-like Tyrosine Kinase-1 (sFlt-1)] has shown a prediction rate of 90% for early-onset PE but entails a high financial cost. The aim of this study is to determine the predictive and preventive capacity of a universal PE first-trimester two-step sequential screening model, determining the PlGF only in patients previously classified as intermediate risk by means of a multivariate model based on resources already used in the standard pregnancy control, in a real clinical setting. We hypothesize that this screening model will achieve similar diagnostic performance as the universal determination of PlGF but at a lower economic cost.
This is a prospective, multicentric, cohort study in a real-world clinical setting. Every singleton pregnancy will be recruited at the routine first pregnancy visit. In a first step, the first-trimester risk of PE will be calculated using a multivariate Gaussian distribution model, based on medical history, mean blood pressure, Pregnancy-Associated Plasma Protein A (PAPP-A), and Uterine Artery Doppler Pulsatility Index (UTPI). Patients will be classified into three risk groups for PE: (1) risk ≥ 1/50, high-risk with no further testing (blinded PlGF); (2) risk between 1/51 and 1/500, medium-risk requiring further testing; and (3) risk ≤ 1/501, low-risk with no further testing. In a second step, the PlGF will only be determined in those patients classified as intermediate risk after this first step, and then reclassified into high- or low-risk groups. Prophylactic administration of aspirin (150 mg/day) will be prescribed only in high risk patients. As a secondary objective, sFlt-1 values will be blindly determined in patients with high and intermediate risk to assess its potential performance in the screening for PE.
The study will be conducted in accordance with the principles of Good Clinical Practice. This study is approved by the Aragon Research Ethics Committee (CEICA) on 3 July 2020 (15/2020).
ClinicalTrials.gov, identifier: NCT04767438.
子痫前期（PE）的发病率约为2%-8%，是全球围产期发病率和孕产妇死亡率的主要原因之一。早期预防性低剂量（150mg）服用乙酰水杨酸与早发型PE、宫内生长受限（IUGR）的发病率显著降低以及新生儿在重症监护病房（ICU）的平均住院时间缩短有关。普遍实施包括血管生成和抗血管生成标志物[胎盘生长因子（PlGF）和/或可溶性fms样酪氨酸激酶-1（sFlt-1）]的孕早期筛查系统，早发型PE的预测率为90%，但成本高昂。本研究的目的是在实际临床环境中，确定一种通用的孕早期两步序贯PE筛查模型的预测和预防能力，该模型仅对先前通过基于标准孕期检查中已使用资源的多变量模型分类为中度风险的患者测定PlGF。我们假设这种筛查模型将实现与普遍测定PlGF相似的诊断性能，但成本更低。
这是一项在实际临床环境中的前瞻性、多中心队列研究。每例单胎妊娠将在首次常规产检时招募。第一步，基于病史、平均血压、妊娠相关血浆蛋白A（PAPP-A）和子宫动脉多普勒搏动指数（UTPI），使用多变量高斯分布模型计算孕早期PE风险。患者将被分为PE的三个风险组：（1）风险≥1/50，高风险，无需进一步检测（PlGF检测结果保密）；（2）风险在1/51至1/500之间，中度风险，需要进一步检测；（3）风险≤1/501，低风险，无需进一步检测。第二步，仅对第一步分类为中度风险的患者测定PlGF，然后重新分类为高风险或低风险组。仅对高风险患者开具阿司匹林（150mg/天）预防性用药。作为次要目标，将对高风险和中度风险患者的sFlt-1值进行保密测定，以评估其在PE筛查中的潜在性能。
本研究将按照良好临床实践原则进行。本研究于2020年7月3日获得阿拉贡研究伦理委员会（CEICA）批准（15/2020）。
ClinicalTrials.gov，标识符：NCT04767438。
