•Abnormal uterine artery Doppler entails placenta-insufficiency related risks.•Combined uterine artery Doppler and sFlt-1/PlGF provide criteria for tight follow-up.•sFlt-1/PlGF performs better in ...high-risk pregnancies for detecting adverse events when applying a cutoff of 38 or greater.
To determine the optimal cutoff value for the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio to predict maternal and fetal adverse events in pregnancies with uterine artery Doppler scans results above the 95th percentile in the late second trimester.
Retrospective, observational cohort study on 116 asyntomatic patients with abnormal uterine artery Doppler scans at gestational week 25. The sFlt-1/PlGF ratio was determined within the weeks 25 to 29 of gestation and ROC curve analysis performed. The diagnostic validity of different cutoff values to predict severe maternal and fetal complications, i.e. preeclampsia, fetal growth restriction, placental abruption, and fetal death, was analyzed.
An ideal cutoff for sFlt-1/PlGF ratios in pregnancies with abnormal uterine artery Doppler in the second trimester.
Applying a cutoff point of 38, the area under the ROC curve was 0.89, generally considered low risk in fetal and maternal complication prediction. The sensitivity was 32.1%, the specificity 98.4%, the positive predictive value (PPV) 94.4%, and the negative predictive value (NPV) 63.3%. A cutoff value of 10, leading to the highest Youden index, performed best at detecting overall complications, increasing sensitivity to 69.8% and the NPV to 76.8%. at the cost of a reduced specificity and PPV.
In pregnancies with abnormal uterine artery Doppler in the second trimester, an sFlt-1/PlGF cutoff value greater than equal to 38 improves its predictive power for adverse events.
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.
Background There is little knowledge about the significance of extremely high values (>655) for the ratio of sFlt-1 (soluble fms-like tyrosine kinase 1) to PlGF (placental growth factor). We aim to ...describe the time-to-delivery interval and maternal and perinatal outcomes when such values are demonstrated while assessing suspected or confirmed placental dysfunction based on clinical or sonographic criteria. Methods and Results A multicenter retrospective cohort study was performed on 237 singleton gestations between 20+0 and 37+0 weeks included at the time of first demonstrating a sFlt-1/PlGF ratio >655. Clinicians were aware of this result, but standard protocols were followed for delivery indication. Main outcomes were compared for women with and without preeclampsia at inclusion. In those with preeclampsia (n=185, of whom 77.3% had fetal growth restriction), severe preeclampsia features and fetal growth restriction in stages III or IV were present in 49.2% and 13.5% cases, respectively, at inclusion and in 77.3% and 28.6% cases, respectively, at delivery. In the group without preeclampsia (n=52, 82.7% had fetal growth restriction), these figures were 0% and 30.8%, respectively, at inclusion and 21.2% and 50%, respectively, at delivery. Interestingly, 28% of women without initial preeclampsia developed it later. The median time to delivery was 4 days (interquartile range: 1-6 days) and 7 days (interquartile range: 3-12 days), respectively (
<0.01). Overall, perinatal mortality was 62.1% before 24 weeks; severe morbidity surpassed 50% before 29 weeks but became absent from 34 weeks. Maternal serious morbidity was high at any gestational age. Conclusions An sFlt-1/PlGF ratio >655 is almost invariably associated with preeclampsia or fetal growth restriction that progresses rapidly. In our tertiary care settings, we observed that maternal adverse outcomes were high throughout gestation, whereas perinatal adverse outcomes diminished as pregnancy advanced.
This study aims to evaluate the safety of discontinuing aspirin treatment at 24-28 weeks in women at high risk after first-trimester combined screening for preeclampsia (PE) and normal placental ...growth factor (PlGF) levels at 24-28 weeks of gestation.INTRODUCTIONThis study aims to evaluate the safety of discontinuing aspirin treatment at 24-28 weeks in women at high risk after first-trimester combined screening for preeclampsia (PE) and normal placental growth factor (PlGF) levels at 24-28 weeks of gestation.This is a post hoc analysis of the StopPRE trial, conducted at nine Spanish maternity hospitals from September 2019 to September 2021. In the StopPRE trial, all high-risk single pregnancies identified during first-trimester screening for PE were treated with 150 mg of daily aspirin. Out of 1604 eligible women with a soluble fms-like tyrosine kinase-1 to PlGF ratio (sFlt-1/PlGF) ≤38 at 24-28 weeks, 968 were randomly assigned in a 1:1 ratio to either continue aspirin until 36 weeks (control group) or discontinue it (intervention group). In this secondary analysis, only women with PlGF ≥100 pg/mL at 24-28 weeks were included. As in the StopPRE trial, the non-inferiority margin was set at a 1.9% difference in preterm PE incidence between the groups.MATERIAL AND METHODSThis is a post hoc analysis of the StopPRE trial, conducted at nine Spanish maternity hospitals from September 2019 to September 2021. In the StopPRE trial, all high-risk single pregnancies identified during first-trimester screening for PE were treated with 150 mg of daily aspirin. Out of 1604 eligible women with a soluble fms-like tyrosine kinase-1 to PlGF ratio (sFlt-1/PlGF) ≤38 at 24-28 weeks, 968 were randomly assigned in a 1:1 ratio to either continue aspirin until 36 weeks (control group) or discontinue it (intervention group). In this secondary analysis, only women with PlGF ≥100 pg/mL at 24-28 weeks were included. As in the StopPRE trial, the non-inferiority margin was set at a 1.9% difference in preterm PE incidence between the groups.Among the 13 983 screened pregnant women, 1984 (14.2%) were deemed high-risk for preterm PE, of which 397 (20.0%) were ineligible, 636 declined participation, and 32 were excluded. Ultimately, 919 women with PlGF >100 pg/mL were randomized and included in this analysis. Preterm PE occurred in 0.9% of the intervention group (4 out of 465) and 1.5% of the control group (7 out of 454), indicating non-inferiority of aspirin discontinuation. There were no significant differences between the groups in adverse pregnancy outcomes before 37 weeks, at <34 weeks, or ≥37 weeks. Minor antepartum hemorrhage incidence was significantly lower in the intervention group (absolute difference, -5.96; 95% CI, -10.10 to -1.82).RESULTSAmong the 13 983 screened pregnant women, 1984 (14.2%) were deemed high-risk for preterm PE, of which 397 (20.0%) were ineligible, 636 declined participation, and 32 were excluded. Ultimately, 919 women with PlGF >100 pg/mL were randomized and included in this analysis. Preterm PE occurred in 0.9% of the intervention group (4 out of 465) and 1.5% of the control group (7 out of 454), indicating non-inferiority of aspirin discontinuation. There were no significant differences between the groups in adverse pregnancy outcomes before 37 weeks, at <34 weeks, or ≥37 weeks. Minor antepartum hemorrhage incidence was significantly lower in the intervention group (absolute difference, -5.96; 95% CI, -10.10 to -1.82).Discontinuation of aspirin treatment at 24-28 weeks in women with PlGF levels ≥100 pg/mL was non-inferior to continuing until 36 weeks for preventing preterm PE. However, these findings should be interpreted with caution, as they originate from a subanalysis of the StopPRE trial.CONCLUSIONSDiscontinuation of aspirin treatment at 24-28 weeks in women with PlGF levels ≥100 pg/mL was non-inferior to continuing until 36 weeks for preventing preterm PE. However, these findings should be interpreted with caution, as they originate from a subanalysis of the StopPRE trial.
Abstract
Introduction
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.
Objective
To assess whether aspirin treatment can be discontinued in pregnancies with normal uterine artery pulsatility index (≤90th percentile) at 24–28 weeks.
Design
Post‐hoc analysis of a clinical ...trial.
Setting
Nine maternity hospitals in Spain.
Population or Sample
Pregnant individuals at high risk of pre‐eclampsia at 11–13 weeks and normal uterine artery Doppler at 24–28 weeks.
Methods
All participants received treatment with daily aspirin at a dose of 150 mg. Participants were randomly assigned, in a 1:1 ratio, either to continue aspirin treatment until 36 weeks (control group) or to discontinue aspirin treatment (intervention group), between September 2019 and September 2021. In this secondary analysis, women with a UtAPI >90th percentile at 24–28 weeks were excluded. The non‐inferiority margin was set at a difference of 1.9% for the incidence of preterm pre‐eclampsia.
Main outcome measures
Incidence of preterm pre‐eclampsia.
Results
Of the 1611 eligible women, 139 were excluded for UtAPI >90th percentile or if UtAPI was not available. Finally, 804 were included in this post‐hoc analysis. Preterm pre‐eclampsia occurred in three of 409 (0.7%) women in the aspirin discontinuation group and five of 395 (1.3%) women in the continuation group (−0.53; 95% CI −1.91 to 0.85), indicating non‐inferiority of aspirin discontinuation.
Conclusions
Discontinuing aspirin treatment at 24–28 weeks in women with a UtAPI ≤90th percentile was non‐inferior to continuing aspirin treatment until 36 weeks for preventing preterm pre‐eclampsia.
ABSTRACT Preeclampsia affects up to 4% of pregnancies and is marked by the development of hypertension and proteinuria after 20 weeks of gestation. Complications associated with the disorder include ...preterm birth, fetal growth restriction, placental abruption, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, seizures, and other end organ damage. Aspirin has been shown to reduce the incidence of preterm preeclampsia by 62%. However, it can also lead to peripartum bleeding. Screening for preeclampsia in the first trimester (11 to 13 weeks' gestation) can help identify up to 60% of pregnant individuals who will develop preterm preeclampsia. If preeclampsia screening is conducted during this first trimester, aspirin can be initiated earlier and discontinued earlier to mitigate the risk of peripartum bleeding. In addition, increased soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1:PlGF) ratio is associated with preeclampsia weeks before its clinical onset. An sFlt-1:PlGF of ≤38 has been shown to accurately exclude preeclampsia in pregnant individuals with suspected disease. The aim of this study was to compare the effect of discontinuing aspirin in pregnant individuals at 24 and 28 weeks' gestation with a normal sFlt-1:PlGF ratio of ≤38 against those who continued aspirin treatment until 36 weeks of gestation. This was an open-label, randomized, noninferiority trial conducted at 9 maternity hospitals in Spain. Included were adult individuals with singleton pregnancies who had live births, were found to be at high risk of preeclampsia at the first-trimester screening, and a normal sFlt-1:PlGF between 24 and 28 weeks of gestation. Participants were randomly assigned 1:1 to discontinue aspirin (intervention group) or continue aspirin treatment (control group). The primary outcome was delivery due to preterm preeclampsia (before 37 weeks' gestation). Noninferiority was met if the higher 95% confidence interval (CI) for the difference in the incidences of preterm preeclampsia between the 2 groups was <1.9%. A total of 964 pregnant individuals, who were identified as high-risk for preterm preeclampsia and prescribed 150 mg of aspirin daily at bedtime, were eligible for the analysis. The rates of preterm preeclampsia in the intervention and control groups were 1.48% and 1.73%, respectively (absolute difference, −0.25% 95% CI, −1.86% to 1.36%). In conclusion, the threshold for noninferiority was not met. In pregnant individuals at high risk of preeclampsia and a normal sFlt-1:PlGF ratio of ≤38, discontinuing aspirin at 24 to 28 weeks' gestation was noninferior to continuing aspirin until 36 weeks to prevent preterm preeclampsia.
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