Sequential screening for preeclampsia

Erika Bonacina

Manel Mendoza Cobaleda

Maternal-Fetal Medicine

SEQUENTIAL SCREENING FOR PREECLAMPSIA Preeclampsia (PE) is a pregnancy disease that can have serious repercussions for the health of the mother and the baby. Currently, there is no curative treatment beyond elective termination of pregnancy, which can be very premature. Screening programs have been developed in the first trimester of pregnancy that can identify women with a high risk of developing PE. In this population, it has been shown that the administration of acetylsalicylic acid (ASA) at low doses reduces their risk. However, ASA has been associated with several adverse effects in pregnant women. In addition, due to the low prevalence of PE, of 100 patients considered at high risk, only 3 will actually develop PE, while the other 97 will be treated with ASA “uselessly”. This thesis has proposed to investigate the possibility of performing a sequential screening for preeclampsia, which allows identifying patients at risk in the first trimester, and then identifying among them the false positives during the second trimester, in order to suspend the medication without increasing the risk of PE. The study has been carried out in two stages: - VALIDATION OF THE SCREENING ALGORITHM. It consists of 2 studies: o the first has proposed to investigate the detection capacity of the Gaussian-type preeclampsia screening algorithm (algorithm created at our Center, the Vall d'Hebron Hospital, jointly with the Dexeus Hospital), comparing it with the Fetal Medicine Foundation algorithm (the most used internationally, and with more internal and external validation studies). Published in the journal International Journal of Gynecology and Obstetrics, Impact Factor (JCR 2021): 4,447 (Q1). o the second one has set out to find out if the application of such an algorithm to our population has allowed to reduce complications related to PE. Published in the journal International Journal of Gynecology and Obstetrics, Impact Factor (JCR 2021): 4.447 (Q1). - IDENTIFICATION OF FALSE POSITIONS using 2 techniques: o The third study is a randomized clinical trial (StopPRE) that has set out to identify false positives by studying placental angiogenic factors (sFlt-1/PlGF). A normal sFlt-1/PlGF ratio has been shown to have a very high negative predictive value to rule out PE in the second trimester of pregnancy. For this reason, the hypothesis of the clinical trial was that patients with a normal sFlt-1/PlGF ratio would not develop preterm PE and, therefore, were false positives of the first trimester PE screening. Published in the journal JAMA. Impact factor (JCR 2021): 157.375 (D1) o The fourth study is a subanalysis of the aforementioned clinical trial, which proposed to identify false positives using the Doppler study of the uterine arteries, since a normal value of this assessment has been associated with a high negative predictive value to rule out PE. Published in the journal BJOG. Impact factor: 5.8 (Q1). The study was under review in the journal when the thesis was published. All these studies have given positive results, demonstrating that the algorithm is applicable and effective in our population. In addition, it has been seen that the suspension of ASA decreases the hemorrhagic complications associated with ASA in pregnant women.

The predictive capacity of the Gaussian algorithm for the screening of preeclampsia (PE) first trimester is comparable to that of the most used algorithm, that of the Fetal Medicine Foundation. Su routine application in our population has demonstrated its usefulness in prevention of preterm PE and maternal admission to the intensive care unit in a clinical context real, reducing the incidence of preterm preeclampsia by 45% and the maternal income by ICU for preeclampsia in 43%. These studies have made it possible to internally validate the algorithm, favoring its implementation in clinical practice in more than 30 maternity hospitals Spanish today. In addition, this thesis demonstrates that it is possible to safely suspend treatment with AAS, in patients with a low risk of PE at 24-28 weeks, identified by means of the sFlt- 1/PlGF ≤38 or normal uterine artery Doppler. This novel evidence could be integrated into the management protocols of high-risk PE screening patients in the first trimester of pregnancy, reducing the risk of bleeding complications, iatrogenic interventions and complications related to placental insufficiency a term, as well as maternal anxiety, treatment costs and the number of visits and ultrasounds It is also possible to carry out cost-effectiveness studies to evaluate the impact economic of the early suspension of AAS in pregnant women, which could help a establish more cost-effective health policies.

Preeclampsia (PE); Pregnancy Disease; Maternal Health; Baby Health; Curative Treatment; Elective Termination of Pregnancy; Premature Birth; First Trimester Screening Programs; High Risk Identification; Acetylsalicylic Acid (ASA); Low-Dose ASA; Risk Reduction; Adverse Effects; Low Prevalence; False Positives; Sequential Screening; Second Trimester Identification; Medication Suspension; Screening Algorithm Validation; Gaussian-Type Preeclampsia Screening Algorithm; Vall d'Hebron Hospital; Dexeus Hospital; Fetal Medicine Foundation Algorithm; Detection Capacity; Complications Reduction; Randomized Clinical Trial (StopPRE); Placental Angiogenic Factors; sFlt-1/PlGF Ratio; Negative Predictive Value; Preterm PE; Doppler Study of Uterine Arteries; Hemorrhagic Complications; Algorithm Effectiveness.