Algorithm-Based Timing of Delivery Using the sFlt-1/PlGF Ratio in Early-Onset Severe Preeclampsia. (MAP 2 Study : Management Based on Angiogenic Markers in Preeclampsia 2 Study )

Summary

Preeclampsia is a serious pregnancy complication caused by abnormal placental development and function. It can lead to high blood pressure and damage to organs such as the liver, kidneys, brain, or cardiovascular system. In these cases, the only definitive treatment is delivery. However, deciding when to deliver is challenging: delaying delivery increases risks for both mother and baby, while delivering too early increases complications related to prematurity.

This study aims to evaluate whether a blood test measuring the sFlt-1/PlGF ratio an angiogenic marker that reflects placental function and predicts complications more accurately than traditional clinical criteria can help determine the optimal timing of delivery in women with severe preeclampsia between 30 weeks and 33 weeks plus 6 days of gestation. It is a multicenter, randomized controlled clinical trial conducted in 11 referral hospitals in Spain and will include 386 singleton pregnancies.

Participants will be randomly assigned to one of two groups. In the control group, standard expectant management will be followed, aiming to continue the pregnancy until 34 weeks if maternal and fetal conditions remain stable, and the sFlt-1/PlGF results will be masked. In the study group, delivery timing will be guided by the sFlt-1/PlGF ratio: if the ratio is greater than 655, delivery will be planned from 30 weeks onward; if greater than 110, delivery will be planned from 34 weeks; and if 110 or lower, pregnancy may continue until 37 weeks.

The study has two primary outcomes. The first is a composite of severe maternal complications, including neurological, hepatic, renal, respiratory, or cardiovascular dysfunction, severe hypertension, placental abruption, or fetal death. The second is a composite of neonatal complications, including admission to the neonatal intensive care unit or neonatal death.

The goal is to demonstrate that using angiogenic markers reduces maternal complications without significantly increasing neonatal complications. If successful, this approach could support more individualized management of early-onset severe preeclampsia, improving maternal safety while carefully balancing the risks of prematurity for the newborn.

Conditions

• Severe Preeclampsia

Interventions

OTHER

sFlt-1/PlGF ratio-guided management algorithm

Management will be optimized based on angiogenic factor results. The sFlt-1/PlGF ratio will be determined at 30.0 weeks or at diagnosis between 30.0 and 33.6 weeks of gestation, and weekly measurements will be repeated. Based on predefined thresholds, delivery will be planned as follows: if sFlt-1/PlGF \>655, planned delivery will occur after fetal lung maturation if gestational age is \<35 weeks; if sFlt-1/PlGF \<655 and ≥110, planned delivery will occur after 34 weeks (with prior lung maturation if gestational age is \<35 weeks); and if sFlt-1/PlGF \<110, planned delivery will occur at 37 weeks. If immediate delivery criteria are met, delivery will be recommended regardless of the ratio.

OTHER

Usual Care

The control arm will receive usual care for severe preeclampsia according to each center's clinical protocols. The sFlt-1/PIGF ratio will be determined at 30 weeks or diagnosis between 30 and 33.6 weeks of gestation, and weekly measurements will be repeated, but the ratio will not be available to the clinician or researchers

Sponsors & Collaborators

• Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.

  collaborator UNKNOWN

• Instituto de investigación Hospital 12 de Octubre

  collaborator UNKNOWN

• Hospital de Sant Pau

  collaborator OTHER

• Fundació Sant Joan de Déu

  collaborator OTHER

• Hospital Universitario La Paz

  collaborator OTHER

• Hospital Materno-Infantil de Canarias. Las Palmas de Gran Canaria. Spain

  collaborator UNKNOWN

• Hospital Son Llatzer

  collaborator OTHER

• Hospital Clinico Universitario San Cecilio

  collaborator OTHER

• Hospital Universitario Virgen de la Arrixaca

  collaborator OTHER

• Fundacion Para La Investigacion Hospital La Fe

  collaborator OTHER

• Hospital Vall d'Hebron

  collaborator OTHER

• Hospital Clinic of Barcelona

  lead OTHER

Principal Investigators

• Francesc Figueras Retuerta, PhD · Hospital Clinic of Barcelona

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-07-01

Primary Completion

2029-09-30

Completion

2029-12-31

Countries

• Spain

Study Locations