Impact of First-trimester Preeclampsia Screening on Perinatal and Maternal Morbidity (RANSPRE) (RANSPRE)

March 24, 2026 updated by: Assistance Publique - Hôpitaux de Paris

Impact of First-trimester Preeclampsia Screening on Perinatal and Maternal Morbidity : a Multicenter Randomized Trial

The purpose of this study is to determine whether first-trimester screening for preeclampsia based on the FMF algorithm (a combination of maternal clinical, sonographic and biochemical parameters), improves maternal or perinatal health.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Preeclampsia (PE) complicates 2% of pregnancies and is a leading cause of severe maternal and perinatal complications. There is no curative treatment, and the only recognized beneficial primary prevention is low-dose aspirin. Meta-analyses of randomized trials show that the administration of aspirin, started before 16 weeks of gestation (WG) and at the dosage of 100-160 mg/d in pregnant women at high risk of PE, is associated with a 50% to 60% reduction in the rates of PE, prematurity and perinatal mortality. The group of patients benefiting most from aspirin is pregnant women with a history of PE. That is why all guidelines recommend early preventive administration of aspirin in pregnant women with PE in a previous pregnancy. However, patients with a history of PE represent a small fraction of pregnant women, and PE mostly occurs in women who do not have a history of PE, especially nulliparas. Recently, several national societies decided to broaden the indications for aspirin prevention on the basis of the number of known maternal risk factors. These recommendations lead to a wide use of low-dose aspirin in up to 30% of pregnant women. In order to better target patients at risk of PE among all pregnant women, screening tests have been developed integrating clinical characteristics, uterine Doppler (UD) parameters and biomarkers in a single score. The study by Poon et al. paved the way for early detection of PE. An algorithm based on maternal characteristics, UD parameters and serum levels of PlGF and PAPP-A between 11 and 14 WG yielded detection rates of 93% and 36% for the prediction of early- and late-onset PE, respectively, at 5% false-positive rate (FPR), which were superior to the detection rates of the traditional checklist-based approach, which relies on maternal factors only. This algorithm developed by the Fetal Medicine Foundation (FMF) has since evolved and is now integrated in the combined test for PE screening known as the FMF triple test (a combination of maternal characteristics with mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and serum PlGF). In a subsequent study using a risk cutoff of 1 in 100 for the predicted probability of preterm PE, a screen-positive rate of 10% has been reported, with detection rates for early-onset, preterm, and term PE of 88%, 69%, and 40%, respectively.

Very recently, the ASPRE study evaluated the impact of aspirin in patients identified at high risk of PE on the basis of this FMF test. Screening was offered to 26,941 women and identified 2,641 high-risk patients of whom 1,776 were randomized to aspirin or placebo. This trial showed a reduction in the incidence of PE <37 WG, occurring in 13/798 in the aspirin group versus 35/822 in the placebo group (p=0.004), but with no significant effect on the overall rate of PE and most importantly on perinatal morbidity. Screening had to be applied to almost 27,000 women for a benefit of 23 avoided cases of preterm PE, with no demonstrated effect on the health of the women and children. The ASPRE study is important but does not demonstrate the benefit of routinely implementing PE screening in the general population. Indeed, there is currently no randomized study comparing a group of women to which the screening procedure would be applied to a group of women without screening, the only design able to provide strong evidence of a benefit. In addition, implementing a national screening program in pregnant women may induce adverse events, especially iatrogenicity (more hospitalizations, more ultrasound examinations, more consultations) and anxiety. Such a screening program is also associated with an increase of direct and indirect health costs.

To consider implementing screening for PE in the general population, it is then essential to demonstrate its benefits on robust health outcomes and not only on the PE diagnosis, as well as to assess its potential adverse consequences and costs. This evaluation is all the more crucial since while this screening is not recommended by any national guideline, it is currently offered ton an increasing number of women.

The RANSPRE study will therefore be the first trial to test the impact on perinatal and maternal health outcomes of a screening procedure for preeclampsia in the first trimester of pregnancy associated with aspirin treatment of pregnant women screened at risk. A medical - economic evaluation allowing a cost-effectiveness analysis will also be carried out. The results of this study will constitute essential information relevant to the French health care system that will guide policymaking for the prevention of PE in the general population of pregnant women. If the results shows a benefit, they will provide further strong evidence for the dissemination in routine care of this screening with a demonstrated benefit for health. If they show no benefit or high adverse iatrogenic impact and costs, this will constitute important knowledge that will avoid the spread of a potentially deleterious practice. This project is part of the priority axis "health prevention in the general population" (Primary care).

The primary objective of the study is to evaluate the impact of first-trimester PE screening (FMF triple test) on the incidence of severe perinatal morbidity. The primary outcome is a composite criterion characterizing severe perinatal morbidity including one of the following criteria :

  • perinatal mortality : stillbirth ≥ after 20 WG or with birth weight > 500g, or death of a newborn within the first 7 days of life.
  • prematurity <34 WG: birth before 34 WG
  • birth weight <3° percentile. Secondary objectives are: (i) to evaluate the impact of first-trimester PE screening on: the incidence of preeclampsia, the incidence of components of moderate and severe maternal morbidity, the incidence of components of moderate and severe perinatal morbidity; (ii) to evaluate the impact of first-trimester PE screening on potential adverse events: iatrogenicity, over-medicalization, women's satisfaction and anxiety status; (iii) to evaluate the impact of first-trimester PE screening and costs effectiveness.

Patients will be recruited in 22 maternity centers at university hospitals in France. The inclusion period during pregnancy is between 11 WG and 14. This period is the timeframe when pregnant women are systematically seen in routine care for the first trimester ultrasound and for Down Syndrome screnning. The intervention will be associated to first trimester routine management. Eligible women will be identified early in pregnancy at their first prenatal visit to the maternity hospital. Inclusion in the study will be performed at the time of the first-trimester ultrasound because the measurements of uterine Dopller indices are required for the screening. The FMF algorithm used in the study for PE screening is based on a combination of maternal clinical parameters (medical history, maternal characteristics, pregnancy characteristics, mean arterial pressure), sonographic parameters (uterine Doppler with measurement of mean pulsatility index) and biochemical parameters (PlGF concentration). Women agreeing to participate in the RANSPRE trial will be randomized either to the experimental group with first-trimester screening for PE or to the control group with usual care without screening for PE.

All patients will be asked to complete self-administered questionnaires at 20 (+/2) WG and during the postpartum period (within 30 days after delivery) assessing women's satisfaction and women's anxiety. These questionnaires will be collected for women included until 31/01/2025. A notebook will be given to patients of group A1 to monitor aspirin observance and to record potential side-effects related to aspirin.

An intention-to-treat analysis will be performed as the principal analysis.

Study Type

Interventional

Enrollment (Estimated)

14500

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria :

  • Pregnancy between 11 and 14 WG
  • Age ≥18 years
  • Affiliated to or beneficiary of a health insurance system (including AME)
  • Signed informed consent

Exclusion Criteria :

  • Gestational age <11 WG or >14 WG
  • Known ectopic pregnancy
  • Known non-ongoing pregnancy
  • Known multiple pregnancy
  • History of PE in a previous pregnancy
  • Pregnancies complicated by major fetal abnormality identified at the first-trimester ultrasound if performed before randomization
  • Absence of health insurance
  • Contra-indication to aspirin (bleeding disorders such as von Willebrand's disease, active peptic ulceration, hypersensitivity to aspirin, active peptic ulceration, NSAID-exacerbated respiratory disease, severe liver or heart dysfunction)
  • Women taking low-dose aspirin regularly and started before pregnancy (except ART indication)
  • Age <18 years
  • Poor understanding of the French language

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: With first trimester preeclampsia screening
Risk assessment of developing preeclampsia between 11 and 14 WG based on maternal parameters, blood pressure measurement, Doppler measurements of the uterine arteries and maternal PlGF concentration. Patients at high risk of preeclampsia are treated with aspirin.
Procedure: First-trimester preeclampsia screening (FMF triple test)

An algorithm assessing the risk of developing preeclampsia combining maternal parameters, blood pressure measurement, Doppler measurements of the uterine arteries and maternal PlGF concentrations.

For women in the screening group, a Doppler study of the uterine arteries and a blood test to quantify PlGF concentrations will be performed within 2 days of randomization, allowing the risk to be calculated according to the screening test. For women with a positive screening test (i.e. predicted risk> 1/100), a treatment with aspirin will be prescribed at 160 mg/day, started as soon as possible and before 15 WG, and taken up to 36 WG, in the absence of contraindications. For women with negative screening, usual pregnancy monitoring without aspirin will be offered.
No Intervention: Without first trimester preeclampsia screening
Usual prenatal care

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Severe perinatal morbidity
Time Frame: From birth up to 7 days of life

The primary outcome will be severe perinatal morbidity defined by a composite criterion including at least one of the following:

  • perinatal mortality (stillbirth ≥ 20 WG or with birth weight > 500 g or neonatal death within 7 days of life) or prematurity < 34 WG or birth weight < 3° percentile.
  • prematurity < 34 WG: birth before ≥ 34 WG
  • birth weight < 3° percentile
From birth up to 7 days of life

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Impact of first-trimester PE screening on potential adverse events
Time Frame: From inclusion up to discharge from hospital (max 30 days)
- Overmedicalization and iatrogenesis: total number of ultrasound exams during pregnancy, total number of prenatal visits (planned, emergency), total number of hospitalizations during pregnancy and number of days, antihypertensive treatment, heparin treatment
From inclusion up to discharge from hospital (max 30 days)
Aspirin side effects
Time Frame: From inclusion up to discharge from hospital (max 30 days)
Aspirin side effects: epigastric pain during pregnancy, vaginal bleeding during pregnancy, other notable bleeding complication requiring hospitalization during pregnancy, nasal bleeding requiring packing during pregnancy, neonatal hemorrhage.
From inclusion up to discharge from hospital (max 30 days)
Women's perception of information received and screening
Time Frame: At 20 WG (+/- 2 weeks)
Assessed using self-administered questions developed for the trial at 20 weeks of gestation.
At 20 WG (+/- 2 weeks)
To evaluate the impact of first-trimester PE screening on costs and cost effectiveness 1
Time Frame: From inclusion up to discharge from hospital (max 30 days)
- Direct costs of prenatal, delivery, postnatal maternal care and neonatal care
From inclusion up to discharge from hospital (max 30 days)
To evaluate the impact of first-trimester PE screening on costs and cost effectiveness 2
Time Frame: From inclusion up to discharge from hospital (max 30 days)
- Total costs
From inclusion up to discharge from hospital (max 30 days)
To evaluate the impact of first-trimester PE screening on costs and cost effectiveness 3
Time Frame: From inclusion up to discharge from hospital (max 30 days)
- Incremental cost-effectiveness ratio: difference in costs/reduction in the incidence of severe perinatal morbidity
From inclusion up to discharge from hospital (max 30 days)
Women's anxiety 2
Time Frame: At 20 WG (+/- 2 weeks)
Anxiety will be assessed using the self-administered Pregnancy-Related Anxiety Questionnaire (PRAQ-R2), validated in French, at 20 weeks of gestation (+/- 2 weeks). These questionnaires will be collected for women included until 31/01/2025.
At 20 WG (+/- 2 weeks)
Women's anxiety 1
Time Frame: At 20 WG (+/- 2 weeks) and day 2 postpartum (+/- 2 days)
Anxiety will be assessed using the State-Trait Anxiety inventory State (STAI-S) self-administered questionnaire, validated in French, at 20 weeks of gestion (+/- 2 weeks) and at day 2 postpartum. All patients will be asked to complete self-administered questionnaires at 20 (+/2) WG and during the postpartum period (within 30 days after delivery) assessing women's satisfaction and women's anxiety. These questionnaires will be collected for women included until 31/01/2025."
At 20 WG (+/- 2 weeks) and day 2 postpartum (+/- 2 days)
Incidence of preeclampsia
Time Frame: From inclusion up to discharge from hospital after delivery (max 30 days)
PE defined as gestational hypertension (GH: systolic BP ≥140 and/or diastolic BP ≥90 mm Hg) and proteinuria ≥ 0.30g/day (or PCr ratio ≥30 mg/mmol, or two at least ++ on dipstick analysis if no 24-hour collection is available), at or after 20 WG and up to discharge from hospital after delivery. PE also defined according to the 2018 ISSHP in the absence of proteinuria in case of GH with maternal organ dysfunction: • creatinine ≥90 µmol/L • transaminases >40 IU/L • eclampsia, altered mental status, blindness, stroke, severe headache unresponsive to medication, and persistent visual scotomata) • platelet count <150000/μL, DIVC, hemolysis • Fetal weight <3° centile, abnormal umbilical artery Doppler (PI>90° centile), or stillbirth - Early-onset PE <34 WG, late-onset PE ≥34 WG-Superimposed pre-eclampsia when a woman with chronic hypertension develops proteinuria (in the absence of preexisting proteinuria) or any of the maternal organ dysfunction consistent with preeclampsia, after 20 W.
From inclusion up to discharge from hospital after delivery (max 30 days)
Incidence of components of moderate and severe maternal morbidity
Time Frame: From inclusion up to discharge from hospital after delivery (max 30 days)

Assessed during pregnancy and up to discharge from hospital after delivery (max 30 days)

  • Severe maternal morbidity (EPIMOMS composite criterion)
  • Postpartum hemorrhage (>500 mL), severe postpartum hemorrhage (>1000 mL), in the 24 hours of delivery as assessed by clinicians in charge of delivery
  • Gestational hypertension
  • Cesarean delivery
  • Abruptio placenta
  • Maternal ICU admission
  • Maternal death
  • HELLP Syndrome
From inclusion up to discharge from hospital after delivery (max 30 days)
Incidence of components of moderate and severe perinatal morbidity
Time Frame: During pregnancy and up to discharge from hospital (max 30 days) - Intraventricular hemorrage grade II or above-Anemia requiring blood transfusion-Respiratory distress
  • Perinatal death (stillbirth or neonatal death within 7 days of life)
  • Transfer to NICU
  • Miscarriage defined by fetal loss before 20 weeks of gestation
  • Stillbirth defined by intra uterine or perpartum fetal death at or after 20 WG
  • Perinatal death (stillbirth defined by intra uterine or perpartum fetal death at or after 20 WG or neonatal death within 7 days of life)
  • Gestational age at delivery
  • Prematurity < 37 WG, <32 WG, < 28WG
  • At delivery, Apgar score <7 at 5 min, umbilical cord pH <7.00 and Base excess >-12
  • Birth weight, birth weight percentile for gestational age < 32 WG, birth weight < 3° percentile for gestational age, birth weight < 10° percentile for gestational according to the EPOPE charts
  • Transfer to NICU from delivery and up to discharge from hospital (max 30 days)
  • Small vulnerable newborn (SVN): among live newborns, all neonates with preterm birth < 37 WG or birth weight < 2500g or birth weight < 10e sex adjusted WHO standards (SGA).
During pregnancy and up to discharge from hospital (max 30 days) - Intraventricular hemorrage grade II or above-Anemia requiring blood transfusion-Respiratory distress

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

URC-CIC Paris Descartes Necker Cochin
INSERM, Epopé team

Investigators

  • Study Director: Catherine DENEUX, MD, PhD, Institut National de la Santé Et de la Recherche Médicale, France

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 6, 2023

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

February 1, 2027

Study Registration Dates

First Submitted

July 7, 2022

First Submitted That Met QC Criteria

August 29, 2022

First Posted (Actual)

August 30, 2022

Study Record Updates

Last Update Posted (Actual)

March 27, 2026

Last Update Submitted That Met QC Criteria

March 24, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP211047
  • 2022-A00374-39 (Other Identifier: ID-RCB Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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