Management of Fetal Growth Restriction at Term: Angiogenic Factors Versus Feto-placental Doppler (GRAFD)

Vall d'Hebron University Hospital (HUVH)

Status: Completed

Conditions: Fetal Growth Retardation

Treatments: Procedure: Management based on sFlt-1/PlGF values

Study type: Interventional

Funder types: Other

Identifiers

NCT04502823

PR(AMI)527/2019

Details and patient eligibility

About

Open randomized non-inferiority controlled trial to examine the use of angiogenic factors (instead of feto-placental Doppler) for fetal growth restriction at term to reduce the rate of labor inductions, without worsening perinatal outcomes.

Full description

Pregnant women with estimated fetal weight (EFW) < 10th centile between 36+0 and 37+6 weeks of gestation (WG) will receive complete ultrasonographic assessment consisting of feto-placental Doppler, amniotic fluid measurement and biophysical profile assessment. The cases not meeting any exclusion criteria will be offered to participate in this trial. After giving their informed consent a blood sample will be drawn in all of them and they will undergo randomization into two arms.

1. Intervention arm: In women allocated to the intervention group, the soluble fms-like tyrosine kinase/placental growth factor (sFlt-1/PlGF) result will be revealed to the investigators that will act according to the results of sFlt/PlGF:

   • Fetuses with sFlt-1/PlGF ≥38, elective delivery will be recommended at ≥37 weeks.
   • Fetuses with sFlt-1/PlGF <38, weekly follow up will be recommended until delivery (at ≥40 weeks).

2. Control arm: In women allocated to the control group, the sFlt-1/PlGF result will be blinded to caregivers. Routine Doppler-based clinical care will be used to counsel women. Following the Doppler classification:

   • Fetuses with EFW below the 3rd centile or below the 10th centile accompanied by any impaired fetoplacental Doppler, elective delivery will be recommended at at ≥37 weeks.
   • Fetuses with EFW above the 3rd centile without any fetoplacental Doppler abnormality, elective delivery will be recommended at at ≥40 weeks.

In both arms, fetuses will receive weekly follow-up from randomization to delivery consisting on feto-placental Doppler sFlt-1/PlGF and CTG. If any of the following is present at any time, earlier delivery will be recommended:

• sFlt-1/PlGF ≥38 (only in the intervention group),
• absent or reverse end-diastolic flow at the umbilical artery Doppler or DV PI>95th centile
• non-reassuring CTG
• preeclampsia
• diminished fetal movements
• biophysical profile ≤ 6 or oligohydramnios (deepest pocket <2 cm).

Enrollment: 1,088 patients

Sex: Female

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Pregnant women ≥ 16 years of age.
2. Singleton pregnancy.
3. Ultrasonographic estimated fetal weight <10th centile.
4. Gestational age between 36+0 and 37+6 weeks.

Exclusion criteria

1. Major fetal malformations or genetic disorders.
2. Fetal death.
3. Absent or reverse end-diastolic flow in umbilical artery Doppler or DV PI>95th centile.
4. Non-reassuring cardiotocography (CTG).
5. Preeclampsia.
6. Diminished fetal movements.
7. Biophysical profile ≤ 6.
8. Oligohydramnios
9. Refusal to give informed consent.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,088 participants in 2 patient groups

Control Group

No Intervention group

Description:

Clinical practice: Management by Doppler and CTG findings. In women allocated to the control group, the sFlt-1/PlGF result will be blinded to caregivers. Routine Doppler-based clinical care will be used to counsel women. Following the Doppler classification: * Fetuses with an EFW below the 3rd centile or below the 10th centile accompanied by any impaired fetoplacental Doppler, elective delivery will be recommended immediately (within 24h) at ≥37 weeks. * Fetuses with an EFW above the 3rd centile without any fetoplacental Doppler abnormality, elective delivery will be recommended at at ≥40 weeks.

Intervention Group

Experimental group

Description:

Management based on sFlt-1/PlGF values

Treatment:

Procedure: Management based on sFlt-1/PlGF values