Prevention Of Preterm Preeclampsia Research Articles

Prediction and prevention of preterm preeclampsia in a Canadian referral hospital

Recent guidelines recommend a validated multiple marker algorithm to assess for risk of preterm preeclampsia (PE) to improve appropriate use of low dose aspirin (LDA). Our objective was to evaluate feasibility and impact of screening implementation for preterm PE during the 11-to-14-week ultrasound appointment.

First-trimester preeclampsia screening and prevention: impact on patient satisfaction and anxiety

Preeclampsia affects between 2% and 5% of pregnant people in North America. First-trimester preeclampsia screening based on the Fetal Medicine Foundation risk calculation algorithm combined with treatment of high-risk patients with aspirin effectively reduces the incidence of preterm preeclampsia more than the currently used risk factor-based screening. However, the impact of such screening on patient satisfaction and maternal anxiety is unknown. This study aimed to assess the impact of first-trimester prediction and prevention of preterm preeclampsia on patient satisfaction and anxiety. Consenting pregnant patients participating in a local first-trimester (11-13+6 weeks) preterm preeclampsia screening and prevention implementation study1 were contacted 6 weeks postpartum to complete an online patient satisfaction survey, designed to assess their satisfaction with the screening program and their levels of trait anxiety (using an abbreviated version of the State-Trait Anxiety Inventory [STAIT-5]). In addition to assessing overall patient satisfaction, the level of patient satisfaction was stratified and compared according to levels of patient risk for preterm preeclampsia. Between June 2021 and December 2021, surveys were emailed to 765 participants. The response rate was 47.80% (358/765). Overall, 93% of participants reported high levels of satisfaction with preterm preeclampsia screening (70%-100%), and 98% stated that they would recommend the screening to all pregnant patients. With respect to levels of satisfaction with the program's support in reducing feelings of worry and anxiety, 87.9% of the total sample reported high satisfaction (70%-100%). The level of clinically significant symptoms of anxiety did not differ significantly between low- and high-risk groups (8% vs 10.8%, respectively). Overall, first-trimester preeclampsia screening was associated with high patient satisfaction and did not lead to differences in patient anxiety between those with high- and low-risk screen results.

Pre-eclampsia.

Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. Women who survive pre-eclampsia have reduced life expectancy, with increased risks of stroke, cardiovascular disease and diabetes, while babies from a pre-eclamptic pregnancy have increased risks of preterm birth, perinatal death and neurodevelopmental disabilityand cardiovascular and metabolic disease later in life. Pre-eclampsia is a complex multisystem disease, diagnosed by sudden-onset hypertension (>20 weeks of gestation) and at least one other associated complication, including proteinuria, maternal organ dysfunction or uteroplacental dysfunction. Pre-eclampsia is found only when a placenta is or was recently present and is classified as preterm (delivery <37 weeks of gestation), term (delivery ≥37 weeks of gestation) and postpartum pre-eclampsia. The maternal syndrome of pre-eclampsia is driven by a dysfunctional placenta, which releases factors into maternal blood causing systemic inflammation and widespread maternal endothelial dysfunction. Available treatments target maternal hypertension and seizures, but the only 'cure' for pre-eclampsia is delivery of the dysfunctional placenta and baby, often prematurely. Despite decades of research, the aetiology of pre-eclampsia, particularly of term and postpartum pre-eclampsia, remains poorly defined. Significant advances have been made in the prediction and prevention of preterm pre-eclampsia, which is predicted in early pregnancy through combined screening and is prevented with daily low-dose aspirin, starting before 16 weeks of gestation. By contrast, the prediction of term and postpartum pre-eclampsia is limited and there are no preventive treatments. Future research must investigate the pathogenesis of pre-eclampsia, in particular of term and postpartum pre-eclampsia, and evaluate new prognostic tests and treatments in adequately powered clinical trials.

The Implementation of Preeclampsia Screening and Prevention (IMPRESS) Study

Preeclampsia affects between 2% and 5% of pregnancies and is one of the leading causes of perinatal morbidity and mortality worldwide. Despite strong evidence that the combination of systematic preeclampsia screening based on the Fetal Medicine Foundation preeclampsia risk calculation algorithm with treatment of high-risk patients with low-dose aspirin reduces the incidence of preterm preeclampsia more than currently used risk-factor-based screening, real-world implementation studies have not yet been done in Canada. This study aimed to assess the operational feasibility of implementing first-trimester screening and prevention of preterm preeclampsia (<37 weeks) alongside a publicly funded first-trimester combined screening program for aneuploidies. This was a prospective implementation study. Consecutive pregnant patients referred for first-trimester combined screening (11-13+6 weeks) were offered screening for preeclampsia based on the Fetal Medicine Foundation algorithm concomitantly with their aneuploidy screen. Consenting participants were screened using maternal risk factors, mean arterial pressure, uterine artery Doppler pulsatility index, pregnancy-associated plasma protein-A, and placental growth factor. Risk for preterm preeclampsia (<37 weeks) was calculated using the Fetal Medicine Foundation algorithm, and individuals with a risk score ≥1 per 100 were recommended to use aspirin (162 mg once daily at bedtime, <16-36 weeks). Implementation metrics assessed included: acceptability, operational impact, proportion of aspirin initiation, quality and safety measures, and screen performance. Between December 1, 2020 and April 23, 2021, 1124 patients consented to preeclampsia screening (98.3% uptake), and 92 (8.2%) screened positive. Appointments for patients receiving first-trimester combined screening aneuploidy and preeclampsia screening averaged 6 minutes longer than first-trimester combined screening alone, and adding uterine artery Doppler pulsatility index averaged 2 minutes. Of the 92 patients who screened as high-risk for preeclampsia, 72 (78.3%) were successfully contacted before 16 weeks' gestation. Of these, 62 (86.1%) initiated aspirin, and 10 (13.9%) did not. Performance audit identified a consistent negative bias with mean arterial pressure measurements (median multiple of the median <1 in 10%); other variables were satisfactory. There were 7 cases of preterm preeclampsia (0.69%): 5 and 2 in the high- and low-risk groups, respectively. Screening detected 5 of 7 (71.4 %) preterm preeclampsia cases, with improved performance after adjustment for aspirin treatment effect. This study confirms the operational feasibility of implementing an evidence-based preeclampsia screening and prevention program in a publicly funded Canadian setting. This will facilitate implementation into clinical service and the scaling up of this program at a regional and provincial level.

When to give aspirin to prevent preeclampsia: application of Bayesian decision theory

There is good evidence that first-trimester assessment of the risk for preterm preeclampsia and treatment of the high-risk group with aspirin reduces the incidence of preterm preeclampsia. Furthermore, there is evidence that aspirin is associated with an increased risk of maternal and neonatal hemorrhagic complications. Against this background, there are ongoing debates whether aspirin should be recommended for all women or to a subpopulation of women predicted to be at increased risk of developing preeclampsia. Moreover, if a strategy of the prediction and prevention of preterm preeclampsia is to be used, what method should be used for the prediction, and what risk cutoff should be used to decide on who to treat? This study aimed to compare the policies of universal treatment, stratified treatment, and no treatment with aspirin. Decisions about aspirin prophylaxis were considered from the perspective of the Bayesian decision theory. Using this approach, the treatment policies were evaluated for risks of preterm preeclampsia, effects of aspirin, and trade-offs between the harms and benefits of the treatment. Evidence on the risk of preterm preeclampsia was taken from the Screening programme for pre-eclampsia study, which was a first-trimester screening study for the prediction of preeclampsia. Evidence of the effect of aspirin was taken from the Aspirin for Evidence-Based Preeclampsia Prevention trial, which was a trial of aspirin vs placebo in the prevention of preterm preeclampsia. The trade-off between the benefits and harms of aspirin was specified by addressing the question, "What is the maximum number of women that should be treated to prevent 1 case of preterm preeclampsia?" The number can be considered as an exchange rate between the harms and benefits of using aspirin to prevent preterm PE. Given the uncertainty about the harms associated with aspirin, the treatment policies were compared across a wide range of exchange rates. For exchange rates between 10 and 1000 women treated with aspirin to prevent 1 case of preterm preeclampsia, the net benefit achieved from the risk assessment and targeted treatment of women at high risk of preterm preeclampsia was higher than that from women with no treatment or women with universal treatment with aspirin. Universal treatment with aspirin should be avoided. Risk-based screening should be used, and the cutoff for taking aspirin should be determined from the consideration of the trade-off between the benefits and harms and detection, false-positive, and screen-positive rates.

From first-trimester screening to risk stratification of evolving pre-eclampsia in second and third trimesters of pregnancy: comprehensive approach.

Preeclampsia and associated hypertensive disorders of pregnancy represent a leading cause of global maternal and neonatal morbidity and mortality. Identification of women at high risk for developing preterm-preeclampsia and prophylaxis with low-dose aspirin has the potential to significantly reduce the rate of preterm-preeclampsia. In addition, risk assessment and monitoring of women in the second and third trimester of pregnancy, to aid in early detection of evolving disease, timely referral to specialist care, and active monitoring of women with confirmed or suspected preeclampsia is essential for improving maternal and neonatal outcomes. The angiogenesis-related biomarkers sFlt-1 and PlGF have been shown to have clinical value to aid in the prediction, diagnosis, and risk stratification of preeclampsia when used either alone or in combination with other risk factors. However, currently there is no consensus on the optimum strategy to link first trimester screening for preterm-preeclampsia with appropriate second and third trimester risk assessment strategies. This opinion paper will outline the current evidence for first trimester preeclampsia screening and prevention, as well as the evidence for various risk stratification approaches for detection of evolving preeclampsia through the second and third trimesters of pregnancy, and proposes a potential model integrating these tools. This article is protected by copyright. All rights reserved.

The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: A pragmatic guide for first-trimester screening and prevention.

The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: A pragmatic guide for first-trimester screening and prevention.

Aspirin for Evidence-Based Preeclampsia Prevention trial: influence of compliance on beneficial effect of aspirin in prevention of preterm preeclampsia

The Aspirin for Evidence-Based Preeclampsia Prevention trial was a multicenter study in women with singleton pregnancies. Screening was carried out at 11-13 weeks' gestation with an algorithm that combines maternal factors and biomarkers (mean arterial pressure, uterine artery pulsatility index, and maternal serum pregnancy-associated plasma protein A and placental growth factor). Those with an estimated risk for preterm preeclampsia of >1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg/d) vs placebo from 11-14 until 36 weeks' gestation. Preterm preeclampsia with delivery at <37 weeks' gestation, which was the primary outcome, occurred in 1.6% (13/798) participants in the aspirin group, as compared with 4.3% (35/822) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74). We sought to examine the influence of compliance on the beneficial effect of aspirin in prevention of preterm preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial. This was a secondary analysis of data from the trial. The proportion of prescribed tablets taken was used as an overall measure of compliance. Logistic regression analysis was used to estimate the effect of aspirin on the incidence of preterm preeclampsia according to compliance of <90% and ≥90%, after adjustment for the estimated risk of preterm preeclampsia at screening and the participating center. The choice of cut-off of 90% was based on an exploratory analysis of the treatment effect. Logistic regression analysis was used to investigate predictors of compliance ≥90% among maternal characteristics and medical history. Preterm preeclampsia occurred in 5/555 (0.9%) participants in the aspirin group with compliance ≥90%, in 8/243 (3.3%) of participants in the aspirin group with compliance <90%, in 22/588 (3.7%) of participants in the placebo group with compliance ≥90%, and in 13/234 (5.6%) of participants in the placebo group with compliance <90%. The odds ratio in the aspirin group for preterm preeclampsia was 0.24 (95% confidence interval, 0.09-0.65) for compliance ≥90% and 0.59 (95% confidence interval, 0.23-1.53) for compliance <90%. Compliance was positively associated with family history of preeclampsia and negatively associated with smoking, maternal age <25 years, Afro-Caribbean and South Asian racial origin, and history of preeclampsia in a previous pregnancy. The beneficial effect of aspirin in the prevention of preterm preeclampsia appears to depend on compliance.

Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history

The Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention trial demonstrated that in women who were at high risk for preterm preeclampsia with delivery at <37 weeks' gestation identified by screening by means of an algorithm that combines maternal factors and biomarkers at 11-13 weeks' gestation, aspirin administration from 11 to 14 until 36 weeks' gestation was associated with a significant reduction in the incidence of preterm preeclampsia (odds ratio 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). We sought to examine whether there are differences in the effect of aspirin on the incidence of preterm preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial in subgroups defined according to maternal characteristics and medical and obstetrical history. This was a secondary analysis of data from the Aspirin for Evidence-Based Preeclampsia Prevention trial. Subgroup analysis was performed to assess evidence of differences in the effect of aspirin on incidence of preterm preeclampsia in subgroups defined by maternal age (<30 and ≥30 years), body mass index (<25 and ≥25 kg/m2), racial origin (Afro-Caribbean, Caucasian and other), method of conception (natural and assisted), cigarette smoking (smoker and non-smoker), family history of preterm preeclampsia (present and absent), obstetrical history (nulliparous, multiparous with previous preterm preeclampsia and multiparous without previous preterm preeclampsia), history of chronic hypertension (present and absent). Interaction tests were performed on the full data set of patients in the intention to treat population and on the data set of patients who took ≥ 90% of the prescribed medication. Results are presented as forest plot with P values for the interaction effects, group sizes, event counts and estimated odds ratios. We examined whether the test of interaction was significant at the 5% level with a Bonferroni adjustment for multiple comparisons. There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history. In participants with chronic hypertension preterm preeclampsia occurred in 10.2% (5/49) in the aspirin group and 8.2% (5/61) in the placebo group (adjusted odds ratio, 1.29; 95% confidence interval, 0.33-5.12). The respective values in those without chronic hypertension were 1.1% (8/749) in the aspirin group and 3.9% (30/761) in the placebo group (adjusted odds ratio, 0.27; 95% confidence interval, 0.12-0.60). In all participants with adherence of ≥90% the adjusted odds ratio in the aspirin group was 0.24 (95% confidence interval, 0.09-0.65); in the subgroup with chronic hypertension it was 2.06 (95% confidence interval, 0.40-10.71); and in those without chronic hypertension it was 0.05 (95% confidence interval, 0.01-0.41). For the complete data set the test of interaction was not significant at the 5% level (P= .055), but in those with adherence ≥90%, after adjustment for multiple comparisons, the interaction was significant at the 5% level (P= .0019). The beneficial effect of aspirin in the prevention of preterm preeclampsia may not apply in pregnancies with chronic hypertension. There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history.