Preeclampsia is a major cause of health problems for both pregnant women and unborn babies worldwide. However, the underlying causes of preeclampsia are not fully understood, leading to limited effective treatments. The goal of this study is to enhance our knowledge of its causes, devise prevention strategies, and develop treatments.We performed a systematic literature search. Six models regarding the pathogenesis of preeclampsia are discussed in this review.This review focuses on the latest advancements in understanding preeclampsia's origins. Preeclampsia is a complex condition caused by various factors, processes, and pathways. Reduced blood flow and oxygen to the uterus and placenta, heightened inflammatory reactions, immune imbalances, altered genetic changes, imbalanced blood vessel growth factors, and disrupted gut bacteria may contribute to its development.Preeclampsia is thought to result from the interplay of these factors.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

An electrical analogue model of an artery that terminates into a vascular bed is presented. The model consists of an uniform transmission line that represents the artery and a load impedance that represents the vascular bed. The transmission line parameters are based on a well-established first-order approximation of the Navier-Stokes equations for fluid flow in distensible tubes. The model can be used to predict the incident and reflected components of both the arterial pressure and flow waveforms. In addition, it can predict the vessel diameter change and the mean blood velocity waveforms. In this study, the model was applied to the uterine artery so that the characteristics of the utero-placental circulation can be related to Doppler ultrasound recordings. It was found that the presence of the dicrotic notch in the uterine artery time-velocity waveform is the result of wave reflection and that a persistent notch past 20 weeks' gestation may be indicative of an abnormally high placental bed resistance. It is shown that the simulation results are consistent with the known physiological data and the clinically recorded uterine Doppler waveforms.

Two prospective multicenter studies demonstrated that a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio cutoff of ≤38 can rule out preeclampsia within 1 week with a negative predictive value (NPV) of 99.3% (PROGNOSIS) and 98.6% (PROGNOSIS Asia). We report a subanalysis of the Japanese cohort from the PROGNOSIS Asia study. Pregnant women with suspected preeclampsia between gestational weeks 18 + 0 days and 36 + 6 days were enrolled at eight Japanese sites. Primary objectives: Assess the performance of the Elecsys® sFlt-1/PlGF ratio cutoff ≤38 to rule out preeclampsia within 1 week and of the cutoff >38 to rule in preeclampsia within 4 weeks. Key secondary objectives: Prediction of maternal and fetal adverse outcomes (MAOs/FAOs) and their relationship with duration of pregnancy. Of 192 women enrolled, 180 (93.8%)/175 (91.1%) were evaluable for primary/combined endpoint analyses. Overall preeclampsia prevalence was 13.3%. A sFlt-1/PlGF ratio of ≤38 provided an NPV of 100% (95% confidence interval [CI], 97.5–100) for ruling out preeclampsia within 1 week, and a ratio of >38 provided a positive predictive value of 32.4% (95% CI, 18.0–49.8) for ruling in preeclampsia within 4 weeks. The area under the curve for the prediction of preeclampsia/maternal/fetal adverse outcomes within 1 week was 94.2% (95% CI, 89.3–97.8). After adjusting for gestational age and final preeclampsia status, Cox regression indicated a 2.8-fold greater risk of imminent delivery for women with a sFlt-1/PlGF ratio >38 versus ≤38. This subanalysis of Japanese women with suspicion of preeclampsia showed high predictive value for a Elecsys sFlt-1/PlGF ratio cutoff of 38 for short-term prediction of preeclampsia.

Preeclampsia (PE), a multisystem disorder in pregnancy, is one of the leading causes of perinatal morbidity and mortality that poses financial and physical burdens worldwide. Preterm PE with delivery at <37 weeks of gestation is associated with a higher risk of adverse maternal and perinatal outcomes than term PE with delivery at ≥37 weeks of gestation. A myriad of first trimester screening models have been developed to identifying women at risk of preterm PE. In fact, the Fetal Medicine Foundation (FMF) first trimester prediction model has undergone successful internal and external validation. The FMF triple test enables the estimation of patient-specific risks, using Bayes theorem to combine maternal characteristics and medical history together with measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor. Establishing a quality control process for regular monitoring and to ensure data standardization, reliability, and accuracy is key to maintaining optimal screening performance. The rate of preterm PE can be reduced by 62% by using the FMF prediction model, followed by the administration of low-dose aspirin. Recent evidence has also demonstrated that metformin has the potential for preventing PE in patients at high-risk of the disorder. In this article, we will summarize the existing literature on the different screening methods, different components of risk assessment, therapeutic interventions, and clinical implementation of the first trimester screening and prevention program for PE with specific considerations for Chinese mainland.

\n Low-dose aspirin has been used during pregnancy, most commonly to prevent or delay the onset of preeclampsia. The American College of Obstetricians and Gynecologists issued the\n Hypertension in Pregnancy Task Force Report\n recommending daily low-dose aspirin beginning in the late first trimester for women with a history of early-onset preeclampsia and preterm delivery at less than 34 0/7 weeks of gestation, or for women with more than one prior pregnancy complicated by preeclampsia. The U.S. Preventive Services Task Force published a similar guideline, although the list of indications for low-dose aspirin use was more expansive. Daily low-dose aspirin use in pregnancy is considered safe and is associated with a low likelihood of serious maternal, or fetal complications, or both, related to use. The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine support the U.S. Preventive Services Task Force guideline criteria for prevention of preeclampsia. Low-dose aspirin (81 mg/day) prophylaxis is recommended in women at high risk of preeclampsia and should be initiated between 12 weeks and 28 weeks of gestation (optimally before 16 weeks) and continued daily until delivery. Low-dose aspirin prophylaxis should be considered for women with more than one of several moderate risk factors for preeclampsia. Women at risk of preeclampsia are defined based on the presence of one or more high-risk factors (history of preeclampsia, multifetal gestation, renal disease, autoimmune disease, type 1 or type 2 diabetes, and chronic hypertension) or more than one of several moderate-risk factors (first pregnancy, maternal age of 35 years or older, a body mass index greater than 30, family history of preeclampsia, sociodemographic characteristics, and personal history factors). In the absence of high risk factors for preeclampsia, current evidence does not support the use of prophylactic low-dose aspirin for the prevention of early pregnancy loss, fetal growth restriction, stillbirth, or preterm birth.\n

Aspirin reduces the incidence of preterm preeclampsia by 62% in pregnant individuals at high risk of preeclampsia. However, aspirin might be associated with an increased risk of peripartum bleeding, which could be mitigated by discontinuing aspirin before term (37 weeks of gestation) and by an accurate selection of individuals at higher risk of preeclampsia in the first trimester of pregnancy.To determine whether aspirin discontinuation in pregnant individuals with normal soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1:PlGF) ratio between 24 and 28 weeks of gestation was noninferior to aspirin continuation to prevent preterm preeclampsia.Multicenter, open-label, randomized, phase 3, noninferiority trial conducted in 9 maternity hospitals across Spain. Pregnant individuals (n = 968) at high risk of preeclampsia during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at 24 to 28 weeks of gestation were recruited between August 20, 2019, and September 15, 2021; of those, 936 were analyzed (intervention: n = 473; control: n = 463). Follow-up was until delivery for all participants.Enrolled patients were randomly assigned in a 1:1 ratio to aspirin discontinuation (intervention group) or aspirin continuation until 36 weeks of gestation (control group).Noninferiority was met if the higher 95% CI for the difference in preterm preeclampsia incidences between groups was less than 1.9%.Among the 936 participants, the mean (SD) age was 32.4 (5.8) years; 3.4% were Black and 93% were White. The incidence of preterm preeclampsia was 1.48% (7/473) in the intervention group and 1.73% (8/463) in the control group (absolute difference, -0.25% [95% CI, -1.86% to 1.36%]), indicating noninferiority.Aspirin discontinuation at 24 to 28 weeks of gestation was noninferior to aspirin continuation for preventing preterm preeclampsia in pregnant individuals at high risk of preeclampsia and a normal sFlt-1:PlGF ratio.ClinicalTrials.gov Identifier: NCT03741179 and ClinicalTrialsRegister.eu Identifier: 2018-000811-26.

To systematically evaluate the efficacy of low molecular weight heparin (LMWH) to prevent preeclampsia in high risk pregnant women without thrombophilia.

Effective screening for term preeclampsia is provided by a combination of maternal factors with measurements of mean arterial pressure, serum placental growth factor and serum soluble fms-like tyrosine kinase-1 at 35 to 37 weeks of gestation, with detection rate of about 75%, at screen positive rate of 10%. However, there is no known intervention to reduce the incidence of the disease. In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1,120 women with singleton pregnancies at high-risk of term preeclampsia to receive pravastatin, at a dose of 20 mg per day, or placebo from 35 to 37 weeks of gestation until delivery or 41 weeks. The primary outcome was delivery with preeclampsia at any time after randomization. The analysis was performed according to intention-to-treat. A total of 29 women withdrew consent during the trial. Preeclampsia occurred in 14.6% (80/548) participants in the pravastatin group and in 13.6% (74/543) in the placebo group. Allowing for the effect of risk at the time of screening and participating centre, the mixed effects Cox regression showed no evidence of an effect of pravastatin; hazard ratio (statin/placebo) 1.08 (95% confidence interval: 0.78, 1.49; p=0.65). There was no evidence of interaction between the effect of pravastatin, estimated risk of preeclampsia, previous pregnancy history, adherence and aspirin treatment. There was no significant between-group difference in the incidence of any secondary outcomes, including gestational hypertension, stillbirth, abruption, delivery of small for gestational age neonates, neonatal death or neonatal morbidity. There was no significant between-group difference in the treatment effects on serum placental growth factor and soluble fms-like tyrosine kinase-1 concentrations 1 and 3 weeks after randomization Adherence was good, with reported intake of 80% or more of the required number of tablets in 89% of participants. There were no significant between-group differences in neonatal adverse outcomes or other adverse events. Pravastatin in women at high risk of term preeclampsia did not reduce the incidence of delivery with preeclampsia. URL: https://www.isrctn.com Unique Identifier ISRCTN16123934.