First-Trimester Sequential Screening for Preeclampsia Using Angiogenic Factors: Study Protocol for a Prospective, Multicenter, Real Clinical Setting Study.

Abstract

Introduction:

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.

Methods and Analysis:

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.

Ethics and Dissemination:

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).

Clinical Trial Registration:

ClinicalTrials.gov, identifier: NCT04767438.

• Authors: Cristina Trilla, Cristina Luna, Silvia De León Socorro, Leire Rodriguez, Aina Ruiz-Romero, Josefina Mora Brugués, Taysa Benítez Delgado, Marta Fabre, Alicia Martin Martínez, Sara Ruiz-Martinez, Elisa Llurba, Daniel Oros
• Journal: Frontiers in cardiovascular medicine (Front Cardiovasc Med) Vol. 9 Pg. 931943 ( 2022) ISSN: 2297-055X [Print] Switzerland
• PMID: 35958398 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Trilla, Luna, De León Socorro, Rodriguez, Ruiz-Romero, Mora Brugués, Benítez Delgado, Fabre, Martin Martínez, Ruiz-Martinez, Llurba and Oros.