Preeclampsia (PE) affects from 2 to 8% of pregnant women. Recent studies show that prevention is the best strategy to improve perinatal outcomes. Therefore, the development of new strategies for preeclampsia screening becomes essential in order to determine the individual risk for each patient, and thus, to identify those who would be candidates for receiving prophylactic treatment with low-dose aspirin from the first trimester of pregnancy. The aim of our study is to determine prospectively, during clinical practice, the predictive and preventive capacity of a model of preeclampsia sequential screening in the first trimester of pregnancy.

This is a prospective, multicentre, cohort study, with the collaboration of Hospital de la Santa Creu i Sant Pau (Barcelona), Hospital Universitario de Cruces (Bilbao), Hospital Son Llàtzer (Mallorca) and Hospital Clínico Universitario Lozano Blesa (Zaragoza). Women with a singleton pregnancy attending to the 12-week ultrasound scan at one of the maternity hospitals participating in the study between March 1st 2021 and 30th October 2021 will be recruited. Patients who accept to participate in the study will be classified into three risk groups (low-risk, moderate-risk and high risk) based on medical history, Mean Arterial Pressure (MAP), Pregnancy-Associated Plasma Protein A (PAPP-A) and Uterine Artery Pulsatility Index (UTPI). Placental Growth Factor (PlGF) will only be determined in those patients classified as intermediate risk after this first step and then reclassified in high and low-risk patients depending on its values. The number of first-trimester scans performed by these hospitals is approximately 8200 patients annually. Due to PE prevalence in our environment is around 3% of the total population, a total of 246 cases of PE are to be expected. Therefore, based on similar previous experiences, we could assume that 80% of the patients will accept to participate in the study, meaning a total sample of 6560 pregnant women.

All the data required to carry out this study, including those derived from sonographies and blood tests, will be collected during the normal pregnancy control, without further appointments. A blood test will be requested in all pregnant women in the first appointment of pregnancy control between 9 and 13 weeks, to determine risk of chromosomal disorders according to the national protocol and it will be used this same sample to analyze angiogenic factors without requiring new blood extractions. In the first-trimester scan, the mean uterine arteries pulsatility index will be determined, as well as mean arterial pressure. In this visit, the patient will be asked about her medical history. We will offer the patients the inclusion to our study in that moment; those who agree to participate in the study will sign the informed consent. In the participants, the initial risk of PE will be calculated using maternal medical history, MAP, UTPI and PAPP-A (already used in aneuploidies screening), using the software validated to each laboratory. Patients will be classified into 3 groups:

• Low risk of PE (<1/500)
• Intermediate risk of PE (between 1/50 and 1/500)
• High risk of PE (>1/50) In those patients classified as intermediate and high-risk, PlGF and s-Flt-1 will be determined from the blood samples kept in biobanks of each hospital according to the current legislation. SFlt-1 results will be analyzed at the end of the study in order to decrease the cost because there will not be used to make clinical decisions. PlGF in high-risk patients will not be considered either to reclassify those patients. In both cases, the diagnostic efficiency will be analyzed at the end of the study.

Patients in the intermediate-risk group (1/50-1/500) will be reclassified after adding PlGF levels in the predictive algorithm in 2 groups: Low risk of PE (<1/160) and High risk of PE (>1/160).

To the patients classified as high risk at any of the steps, will be offered prophylactic treatment with AcetylSalicylic acid (ASA) (150mg/24h) until 36 weeks of pregnancy, if there is not a contraindication. All data from eligible patients will be analyzed. A bivariant statistical analysis will be performed in order to assess the relationship between dependent variables (diagnose of PE and/or IUGR) and the other variables included in this study

Inclusion Criteria:

• Singleton pregnancies;
• Gestational age less than 14 weeks, estimated according to Crown-Rump Length (CRL);
• Blood sample between 8 and 14 weeks of pregnancy;
• Patients who accept to participate in the study and sign the informed consent

Exclusion Criteria:

• Fetus with chromosomal disorders, major congenital malformations or congenital infections diagnosed in the first-trimester ultrasound;
• Multiple pregnancies;
• Non-acceptance of participation in the study.

Every singleton pregnancy attending during the period study