Shared risk factors for COVID-19 and preeclampsia in the first trimester: An observational study

Coronavirus disease 2019; First trimester; PreeclampsiaCoronavirus 2019; Primer trimestre; PreeclàmpsiaCoronavirus 2019; Primer trimestre; PreeclampsiaIntroduction: The association between preeclampsia and coronavirus disease 2019 (COVID-19) is under study. Previous publications have hypothesized the existence of shared risk factors for both conditions or a deficient trophoblastic invasion as possible explanations for this association. The primary aim of this study was to examine baseline risk factors measured in the first-trimester combined screening for preeclampsia in pregnant women with COVID-19 compared with the general population. A secondary aim of this study was to compare risk factors among patients with mild and severe COVID-19. Material and methods: This was an observational retrospective study conducted at Vall d'Hebron Hospital Campus (Catalonia, Spain). Study patients were 231 pregnant women undergoing the first-trimester screening for preeclampsia and positive for severe acute respiratory syndrome coronavirus 2 between February 2020 and September 2021. The reference cohort were 13 033 women of the general population from six centers across Catalonia from May 2019 to June 2021. Based on the need for hospitalization, patients were classified in two groups: mild and severe COVID-19. First-trimester screening for preeclampsia included maternal history, mean arterial blood pressure, mean uterine artery pulsatility index (UtAPI), placental growth factor (PlGF), and pregnancy-associated plasma protein-A (PAPP-A). Results: The proportion of cases at high risk for preeclampsia was significantly higher among the COVID-19 group compared with the general population (19.0% and 13.2%, respectively; p = 0.012). When analyzing risk factors for preeclampsia individually, women with COVID-19 had higher median body mass index (25.2 vs 24.5, p = 0.041), higher UtAPI multiple of the median (MoM) (1.08 vs 1.00, p < 0.001), higher incidence of chronic hypertension (2.8% vs 0.9%, p = 0.015), and there were fewer smokers (5.7% vs 11.6%, p = 0.007). The MoMs of PlGF and PAPP-A did not differ significantly between both groups (0.96 vs 0.97, p = 0.760 and 1.00 vs 1.01, p = 0.432; respectively). Conclusions: In patients with COVID-19, there was a higher proportion of women at high risk for preeclampsia at the first-trimester screening than in the general population, mainly because of maternal risk factors, rather than placental signs of a deficient trophoblastic invasion

Clinical effectiveness of routine first-trimester combined screening for pre-eclampsia in Spain with the addition of placental growth factor

Aspirin; Placental growth factor; Pre-eclampsiaAspirina; Factor de crecimiento placentario; PreeclampsiaAspirina; Factor de creixement placentari; PreeclampsiaIntroduction Pre-eclampsia affects 2%–8% of pregnancies and is one of the leading causes of maternal and perinatal morbidity and mortality. First-trimester screening using an algorithm that combines maternal characteristics, mean arterial blood pressure, uterine artery pulsatility index and biomarkers (pregnancy-associated plasma protein-A and placental growth factor) is the method that achieves a greater diagnostic accuracy. It has been shown that daily salicylic acid administration before 16 weeks in women at a high risk for pre-eclampsia can reduce the incidence of preterm pre-eclampsia. However, no previous studies have evaluated the impact of routine first-trimester combined screening for pre-eclampsia with placental growth factor after being implemented in the clinical practice. Material and methods This was a multicenter cohort study conducted in eight different maternities across Spain. Participants in the reference group were prospectively recruited between October 2015 and September 2017. Participants in the study group were retrospectively recruited between March 2019 and May 2021. Pre-eclampsia risk was calculated between 11+0 and 13+6 weeks using the Gaussian algorithm combining maternal characteristics, mean arterial pressure, uterine arteries pulsatility index, pregnancy-associated plasma protein-A and placental growth factor. Patients with a risk greater than 1/170 were prescribed daily salicylic acid 150 mg until 36 weeks. Patients in the reference group did not receive salicylic acid during gestation. Results A significant reduction was observed in preterm pre-eclampsia (OR 0.47; 95% CI: 0.30–0.73), early-onset (<34 weeks) pre-eclampsia (OR 0.35; 95% CI: 0.16–0.77), preterm small for gestational age newborn (OR 0.57; 95% CI: 0.40–0.82), spontaneous preterm birth (OR 0.72; 95% CI: 0.57–0.90), and admission to intensive care unit (OR 0.55; 95% CI: 0.37–0.81). A greater treatment adherence resulted in a significant reduction in adverse outcomes. Conclusions Routine first-trimester screening for pre-eclampsia with placental growth factor leads to a reduction in preterm pre-eclampsia and other pregnancy complications. Aspirin treatment compliance has a great impact on the effectiveness of this screening program

The Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) Trial to Avoid Adverse Perinatal Outcomes: Protocol for a Multicenter, Open-Label, Randomized Controlled Trial

Angiogenic factors; Fetal growth restriction; Small for gestational ageFactores angiogénicos; Restricción del crecimiento fetal; Pequeño para la edad gestacionalFactors angiogènics; Restricció del creixement fetal; Petit per a l'edat gestacionalBackground: Fetal smallness affects 10% of pregnancies. Small fetuses are at a higher risk of adverse outcomes. Their management using estimated fetal weight and feto-maternal Doppler has a high sensitivity for adverse outcomes; however, more than 60% of fetuses are electively delivered at 37 to 38 weeks. On the other hand, classification using angiogenic factors seems to have a lower false-positive rate. Here, we present a protocol for the Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) trial, which compares the use of angiogenic factors and Doppler to manage small fetuses at term. Objective: The primary objective is to demonstrate that classification based on angiogenic factors is not inferior to estimated fetal weight and Doppler at detecting fetuses at risk of adverse perinatal outcomes. Methods: This is a multicenter, open-label, randomized controlled trial conducted in 20 hospitals across Spain. A total of 1030 singleton pregnancies with an estimated fetal weight ≤10th percentile at 36+0 to 37+6 weeks+days will be recruited and randomly allocated to either the control or the intervention group. In the control group, standard Doppler-based management will be used. In the intervention group, cases with a soluble fms-like tyrosine kinase to placental growth factor ratio ≥38 will be classified as having fetal growth restriction; otherwise, they will be classified as being small for gestational age. In both arms, the fetal growth restriction group will be delivered at ≥37 weeks and the small for gestational age group at ≥40 weeks. We will assess differences between the groups by calculating the relative risk, the absolute difference between incidences, and their 95% CIs. Results: Recruitment for this study started on September 28, 2020. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences in early 2023. Conclusions: The angiogenic factor-based protocol may reduce the number of pregnancies classified as having fetal growth restriction without worsening perinatal outcomes. Moreover, reducing the number of unnecessary labor inductions would reduce costs and the risks derived from possible iatrogenic complications. Additionally, fewer inductions would lower the rate of early-term neonates, thus improving neonatal outcomes and potentially reducing long-term infant morbidities

Angiogenic factors for planning fetal surveillance in fetal growth restriction and small-for-gestational-age fetuses : A prospective observational study

The aim of this study was to assess the added value of the soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio for adjusting the periodicity of ultrasound examinations in early-onset fetal growth restriction (FGR) and small for gestational age (SGA). A prospective, observational study. Tertiary referral hospital. One hundred and thirty-four single pregnancies with ultrasonographic estimated fetal weight (EFW) below the 10th centile between 20 +0 and 31 +6 weeks of gestation with antegrade umbilical artery flow. The time from Doppler and sFlt-1/PlGF assessment to delivery was recorded and classified into four ranges: 85 required an elective delivery before 1 week. sFlt-1/PlGF values in early-onset SGA and FGR are predictive of the time to delivery and could be used for planning fetal surveillance, by reducing the frequency of ultrasound in cases with sFlt-1/PlGF 85. sFlt-1/PlGF values in early-onset SGA/FGR could be used in addition to Doppler for planning fetal surveillance. sFlt-1/PlGF values in early-onset SGA/FGR could be used in addition to Doppler for planning fetal surveillance. Linked article : This article is commented on by Cecilia Villalaín, pp. 1878 in this issue. To view this minicommentary visi

First-trimester screening for pre-eclampsia and small for gestational age : A comparison of the gaussian and Fetal Medicine Foundation algorithms

Pre-eclampsia (PE) and small for gestational age (SGA) can be predicted from the first trimester. The most widely used algorithm worldwide is the Fetal Medicine Foundation (FMF) algorithm. The recently described Gaussian algorithm has reported excellent results although it is unlikely to be externally validated. Therefore, as an alternative approach, we compared the predictive accuracy for PE and SGA of the Gaussian and FMF algorithms. Secondary analysis of a prospective cohort study was conducted at Vall d'Hebron University Hospital (Barcelona) with 2641 singleton pregnancies. The areas under the curve for the predictive performance for early-onset and preterm PE and early-onset and preterm SGA were calculated with the Gaussian and FMF algorithms and subsequently compared. The FMF and Gaussian algorithms showed a similar predictive performance for most outcomes and marker combinations. Nevertheless, significant differences for early-onset PE prediction favored the Gaussian algorithm in the following combinations: mean arterial blood pressure (MAP) with pregnancy-associated plasma protein A, MAP with placental growth factor, and MAP alone. The first-trimester Gaussian and FMF algorithms have similar performances for PE and SGA prediction when applied with all markers within a routine care setting in a Spanish population, adding evidence to the external validity of the FMF algorithm. The first-trimester Gaussian and Fetal Medicine Foundation algorithms have similar predictive performances for pre-eclampsia and small-for-gestational-age fetuses

Confirmation of preeclampsia-like syndrome induced by severe COVID-19 : An Observational Study

Since the outbreak of the COVID-19 pandemic, some studies have reported an increased preeclampsia (PE) incidence in pregnant women with SARS-CoV-2 infection. Several explanations for this association have been proposed, including a preeclampsia-like syndrome induced by severe COVID-19. This syndrome was described in a small case series and has not been confirmed in larger studies and its impact in perinatal outcomes has not been studied. The aim of this study was to confirm the preeclampsia-like syndrome due to COVID-19 and to investigate its implications in pregnancy outcomes and prognosis. This was a prospective, observational study conducted in a tertiary referral hospital. Inclusion criteria were pregnant women admitted to the Intensive Care Unit for severe pneumonia due to COVID-19. They were classified in three groups based on clinical and laboratory findings: PE, PE-like syndrome, and women without PE features. The three cohorts were analyzed and compared at three different times: before, during and after severe pneumonia. The main outcomes were incidence of adverse perinatal outcomes and signs and symptoms of PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes and increased angiogenic factors (soluble fms-like tyrosine kinase-1 to placental growth factor ratio [sFlt-1/PlGF]). A total of 106 women were admitted to Intensive Care Unit due to severe pneumonia and 68 were included in the study. Of those, 53 (50.0%) did not meet the diagnostic criteria for PE and remained pregnant after pneumonia (non-PE), seven (6.6%) met the diagnostic criteria for PE, had abnormal (>38) sFlt-1/PlGF (PE) and delivered during severe pneumonia, and eight (7.5%) met the diagnostic criteria for PE, had normal (≤38) sFlt-1/PlGF (PE-like) and did not deliver during pneumonia. Despite not having delivered, most PE-related features improved after severe pneumonia in women with PE-like syndrome. Women with PE had significantly poorer outcomes than women with PE-like syndrome or without PE. More than 50% of women with severe COVID-19 and diagnostic criteria for PE may not be PE but a PE-like syndrome, which may affect up to 7.5% of women with severe COVID-19. PE-like syndrome might have similar perinatal outcomes to those of normotensive women with severe pneumonia due to COVID-19. For these reasons, PE-like syndrome should be excluded by using sFlt-1/PlGF in future research and before making clinical decisions

First-trimester screening for pre-eclampsia and small for gestational age: A comparison of the gaussian and Fetal Medicine Foundation algorithms

Preeclampsia d'inici precoç; Primer trimestreEarly-onset pre-eclampsia; First trimesterPreeclampsia de inicio precoz; Primer trimestreObjective Pre-eclampsia (PE) and small for gestational age (SGA) can be predicted from the first trimester. The most widely used algorithm worldwide is the Fetal Medicine Foundation (FMF) algorithm. The recently described Gaussian algorithm has reported excellent results although it is unlikely to be externally validated. Therefore, as an alternative approach, we compared the predictive accuracy for PE and SGA of the Gaussian and FMF algorithms. Methods Secondary analysis of a prospective cohort study was conducted at Vall d'Hebron University Hospital (Barcelona) with 2641 singleton pregnancies. The areas under the curve for the predictive performance for early-onset and preterm PE and early-onset and preterm SGA were calculated with the Gaussian and FMF algorithms and subsequently compared. Results The FMF and Gaussian algorithms showed a similar predictive performance for most outcomes and marker combinations. Nevertheless, significant differences for early-onset PE prediction favored the Gaussian algorithm in the following combinations: mean arterial blood pressure (MAP) with pregnancy-associated plasma protein A, MAP with placental growth factor, and MAP alone. Conclusions The first-trimester Gaussian and FMF algorithms have similar performances for PE and SGA prediction when applied with all markers within a routine care setting in a Spanish population, adding evidence to the external validity of the FMF algorithm

Confirmation of preeclampsia-like syndrome induced by severe COVID-19: an observational study

COVID-19; Preeclampsia; PregnancyCOVID-19; Preeclampsia; EmbarazoCOVID-19; Preeclampsia; EmbaràsBACKGROUND Since the outbreak of the COVID-19 pandemic, some studies have reported an increased preeclampsia incidence in pregnant women with SARS-CoV-2 infection. Several explanations for this association have been proposed, including a preeclampsia-like syndrome induced by severe COVID-19. This syndrome was described in a small case series and has not been confirmed in larger studies, and its effect on perinatal outcomes has not been studied. OBJECTIVE This study aimed to confirm the preeclampsia-like syndrome because of COVID-19 and to investigate its implications on pregnancy outcomes and prognosis. STUDY DESIGN This was a prospective, observational study conducted in a tertiary referral hospital. The inclusion criteria were pregnant women admitted to the intensive care unit for severe pneumonia because of COVID-19. They were classified into 3 groups based on clinical and laboratory findings: preeclampsia, preeclampsia-like syndrome, and women without preeclampsia features. The 3 cohorts were analyzed and compared at 3 different times: before, during, and after severe pneumonia. The main outcomes were incidence of adverse perinatal outcomes and signs and symptoms of PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, and increased angiogenic factors (soluble fms-like tyrosine kinase 1–to–placental growth factor ratio). RESULTS A total of 106 women were admitted to the intensive care unit because of severe pneumonia, and 68 women were included in the study. Of those, 53 (50.0%) did not meet the diagnostic criteria for preeclampsia and remained pregnant after pneumonia (non-preeclampsia); 7 (6.6%) met the diagnostic criteria for preeclampsia, had abnormal (>38) soluble fms-like tyrosine kinase 1–to–placental growth factor ratio (preeclampsia), and delivered during severe pneumonia, and 8 (7.5%) met the diagnostic criteria for preeclampsia, had normal (≤38) soluble fms-like tyrosine kinase 1–to–placental growth factor ratio (preeclampsia like), and did not deliver during pneumonia. Despite not having delivered, most preeclampsia-related features improved after severe pneumonia in women with preeclampsia-like syndrome. Women with preeclampsia had significantly poorer outcomes than women with preeclampsia-like syndrome or without preeclampsia. CONCLUSION More than 50% of women with severe COVID-19 and diagnostic criteria for preeclampsia may not be preeclampsia but a preeclampsia-like syndrome, which may affect up to 7.5% of women with severe COVID-19. Preeclampsia-like syndrome might have similar perinatal outcomes to those of normotensive women with severe pneumonia because of COVID-19. For these reasons, preeclampsia-like syndrome should be excluded by using soluble fms-like tyrosine kinase 1–to–placental growth factor ratio in future research and before making clinical decisions

Clinical effectiveness of routine first-trimester combined screening for pre-eclampsia in Spain with the addition of placental growth factor

Pre-eclampsia affects 2%-8% of pregnancies and is one of the leading causes of maternal and perinatal morbidity and mortality. First-trimester screening using an algorithm that combines maternal characteristics, mean arterial blood pressure, uterine artery pulsatility index and biomarkers (pregnancy-associated plasma protein-A and placental growth factor) is the method that achieves a greater diagnostic accuracy. It has been shown that daily salicylic acid administration before 16 weeks in women at a high risk for pre-eclampsia can reduce the incidence of preterm pre-eclampsia. However, no previous studies have evaluated the impact of routine first-trimester combined screening for pre-eclampsia with placental growth factor after being implemented in the clinical practice. This was a multicenter cohort study conducted in eight different maternities across Spain. Participants in the reference group were prospectively recruited between October 2015 and September 2017. Participants in the study group were retrospectively recruited between March 2019 and May 2021. Pre-eclampsia risk was calculated between 11 +0 and 13 +6 weeks using the Gaussian algorithm combining maternal characteristics, mean arterial pressure, uterine arteries pulsatility index, pregnancy-associated plasma protein-A and placental growth factor. Patients with a risk greater than 1/170 were prescribed daily salicylic acid 150 mg until 36 weeks. Patients in the reference group did not receive salicylic acid during gestation. A significant reduction was observed in preterm pre-eclampsia (OR 0.47; 95% CI: 0.30-0.73), early-onset (<34 weeks) pre-eclampsia (OR 0.35; 95% CI: 0.16-0.77), preterm small for gestational age newborn (OR 0.57; 95% CI: 0.40-0.82), spontaneous preterm birth (OR 0.72; 95% CI: 0.57-0.90), and admission to intensive care unit (OR 0.55; 95% CI: 0.37-0.81). A greater treatment adherence resulted in a significant reduction in adverse outcomes. Routine first-trimester screening for pre-eclampsia with placental growth factor leads to a reduction in preterm pre-eclampsia and other pregnancy complications. Aspirin treatment compliance has a great impact on the effectiveness of this screening program. Routine first-trimester combined screening for pre-eclampsia in Spain with the addition of placental growth factor resulted in a significant reduction of pre-eclampsia and other pregnancy complications

Cribado secuencial de preeclampsia

La preeclàmpsia és una malaltia pròpia de l'embaràs que afecta aproximadament un 2-4% de les gestacions, i representa una de les principals causes de morbimortalitat tant materna com fetal. El seu origen s'atribueix a múltiples factors, tot i que es reconeix el paper significatiu de la placentació anòmala en el desenvolupament. Tot i que hi ha mesures preventives disponibles, no s'ha identificat un tractament curatiu, llevat de la finalització electiva de l'embaràs. Això no obstant, la terminació prematura de l'embaràs comporta un augment considerable en els riscos de morbimortalitat neonatal i a llarg termini per al nounat. A més, s'ha observat que les dones que han experimentat preeclàmpsia presenten una morbiditat més gran al llarg de les seves vides. A causa d'aquestes raons, la prevenció d'aquesta malaltia adquireix una importància cabdal. Durant l'última dècada, s'han emprat diverses estratègies per identificar les pacients amb més risc de desenvolupar preeclàmpsia. Actualment, hi ha sofisticats programes de cribratge durant el primer trimestre d'embaràs, els quals permeten identificar fins a un 90% de les pacients que desenvoluparan la malaltia, amb una taxa de falsos positius del 10-15%. En aquesta població de risc, s'ha demostrat que l'administració d'àcid acetilsalicílic en dosis baixes redueix el risc de desenvolupar preeclàmpsia en un 60-80%. Tot i això, és important destacar que l'administració de fàrmacs comporta riscos, especialment en embarassades. En aquesta població, s'hi ha associat l'ús d'àcid acetilsalicílic amb efectes secundaris com el despreniment de placenta normoinserida i complicacions hemorràgiques peripart. Per tant, resulta crucial que l'exposició a fàrmacs durant l'embaràs es faci utilitzant la dosi més baixa i durant el menor temps possible. L'objectiu d'aquesta tesi doctoral és avaluar la validesa dun programa de cribratge de preeclàmpsia realitzat en dues etapes. En primer lloc, es busca determinar l'eficàcia de l'algorisme de cribratge del primer trimestre, basat en un enfocament gaussià, a la nostra població mitjançant la seva implementació i la comparació de la seva taxa de detecció amb l'algorisme proposat per la Fetal Medicine Foundation. En segon lloc, s'investiga la possibilitat d'identificar els falsos positius del cribratge utilitzant marcadors del segon trimestre, com ara el sFlt-1/PlGF o l'índex de pulsatilitat mitjà de les artèries uterines. Per a les pacients identificades com a baix risc en aquesta segona etapa, s'avalua la seguretat de suspendre el tractament preventiu amb àcid acetilsalicílic. Els resultats obtinguts als estudis presentats en aquesta tesi demostren la validesa interna de l'algorisme de cribratge, l'efectivitat de l'estratègia de cribratge seqüencial i la seguretat de la suspensió en segon trimestre de l'àcid acetilsalicílic per prevenir la preeclàmpsia i altres complicacions de l'embaràs.La preeclampsia es una enfermedad propia del embarazo que afecta a aproximadamente un 2-4% de las gestaciones, y representa una de las principales causas de morbimortalidad tanto materna como fetal. Su origen se atribuye a múltiples factores, aunque se reconoce el papel significativo de la placentación anómala en su desarrollo. Aunque existen medidas preventivas disponibles, no se ha identificado un tratamiento curativo, a excepción de la finalización electiva del embarazo. No obstante, la terminación prematura del embarazo conlleva un aumento considerable en los riesgos de morbimortalidad neonatal y a largo plazo para el recién nacido. Además, se ha observado que las mujeres que han experimentado preeclampsia presentan una mayor morbilidad a lo largo de sus vidas. Debido a estas razones, la prevención de esta enfermedad adquiere una importancia primordial. Durante la última década, se han empleado diversas estrategias con el fin de identificar a las pacientes con mayor riesgo de desarrollar preeclampsia. En la actualidad, se cuenta con sofisticados programas de cribado durante el primer trimestre de embarazo, los cuales permiten identificar hasta un 90% de las pacientes que desarrollarán la enfermedad, con una tasa de falsos positivos del 10-15%. En esta población de riesgo, se ha demostrado que la administración de ácido acetilsalicílico en dosis bajas reduce el riesgo de desarrollar preeclampsia en un 60-80%. Sin embargo, es importante destacar que la administración de fármacos conlleva riesgos, especialmente en embarazadas. En esta población, se ha asociado el uso de ácido acetilsalicílico con efectos secundarios como el desprendimiento de placenta normoinserta y complicaciones hemorrágicas periparto. Por tanto, resulta crucial que la exposición a fármacos durante el embarazo se realice utilizando la dosis más baja y durante el menor tiempo posible. El objetivo de esta tesis doctoral es evaluar la validez de un programa de cribado de preeclampsia realizado en dos etapas. En primer lugar, se busca determinar la eficacia del algoritmo de cribado del primer trimestre, basado en un enfoque gaussiano, en nuestra población mediante su implementación y la comparación de su tasa de detección con el algoritmo propuesto por la Fetal Medicine Foundation. En segundo lugar, se investiga la posibilidad de identificar los falsos positivos del cribado utilizando marcadores del segundo trimestre, como el sFlt-1/PlGF o el índice de pulsatilidad medio de las arterias uterinas. Para las pacientes identificadas como bajo riesgo en esta segunda etapa, se evalúa la seguridad de suspender el tratamiento preventivo con ácido acetilsalicílico. Los resultados obtenidos en los estudios presentados en esta tesis demuestran la validez interna del algoritmo de cribado, la efectividad de la estrategia de cribado secuencial y la seguridad de la suspensión en segundo trimestre del ácido acetilsalicílico para prevenir la preeclampsia y otras complicaciones del embarazo.Preeclampsia is a gestation-related disease that affects between 2% and 4% of pregnancies, and represents one of the main causes of both maternal and fetal morbidity and mortality. Its origin is attributed to multiple factors, although the significant role of abnormal placentation in its development is recognized. Although preventive measures are available, no curative treatment has been identified, except for elective termination of pregnancy. However, the premature termination of pregnancy carries a considerable increase in the risks of neonatal and long-term morbidity and mortality for the newborn. In addition, it has been observed that women who have experienced preeclampsia have increased morbidity throughout their lives. Due to these reasons, the prevention of this disease assumes paramount importance. Over the last decade, various strategies have been used to identify patients at increased risk of developing preeclampsia. Currently, there are sophisticated screening programs during the first trimester of pregnancy, which make it possible to identify up to 90% of the patients who will develop the disease, with a false positive rate of 10-15%. In this at-risk population, low-dose aspirin has been shown to reduce the risk of developing preeclampsia by 60-80%. However, it is important to note that drug administration carries risks, especially in pregnant women. In this population, the use of acetylsalicylic acid has been associated with side effects such as placental abruption and peripartum bleeding complications. Therefore, it is crucial that drug exposure during pregnancy is carried out using the lowest dose and for the shortest duration possible. The objective of this doctoral thesis is to evaluate the validity of a preeclampsia screening program carried out in two stages. First, we seek to determine the efficacy of the first trimester screening algorithm, based on a Gaussian approach, in our population by implementing it and comparing its detection rate with the algorithm proposed by the Fetal Medicine Foundation. Second, the possibility of identifying false positives from screening using second trimester markers such as sFlt-1/PlGF or mean uterine artery pulsatility index is investigated. For patients identified as low risk in this second stage, the safety of discontinuing preventive treatment with acetylsalicylic acid is evaluated. The results obtained in the studies presented in this thesis demonstrate the internal validity of the screening algorithm, the effectiveness of the sequential screening strategy, and the safety of suspending aspirin in the second trimester to prevent preeclampsia and other pregnancy complications