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Management of Early-onset Fetal Growth Restriction: Angiogenic Factors Versus Feto-placental Doppler

Not Applicable
Not yet recruiting
Conditions
Fetal Growth Retardation
Preeclampsia
Placenta Diseases
Interventions
Diagnostic Test: soluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF)
Registration Number
NCT05284474
Lead Sponsor
Hospital Universitari Vall d'Hebron Research Institute
Brief Summary

This is a multicentre, open-label, randomized controlled trial. A total of 340 singleton pregnancies with an EFW ≤10th percentile between 26+0 and 31+6 weeks will be recruited and randomly allocated to either the control or the intervention group. In the control group, standard Doppler-based management will be used. In the intervention group, different soluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF) cutoffs will be incorporated to the current protocol to adjust the frequency of ultrasounds and to plan elective delivery.

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
Female
Target Recruitment
340
Inclusion Criteria
  • Pregnant women of at least 18 years old
  • Singleton pregnancy
  • Ultrasonographic EFW ≤10th percentile between 26+0 and 31+6 weeks of gestation
  • Gestational age confirmed by fetal crown-rump length measurement during the first trimester scan (from 11+0 to 13+6 weeks of gestation) or by in vitro fertilization dates.
Exclusion Criteria
  • Major fetal malformations or genetic disorders
  • Fetal death
  • Refusal to give informed consent
  • Stage IV FGR

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Studysoluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF)Doppler protocol (as in controls) + sFlt-1/PlGF ratio cutoffs will be incorporated as follows: * \<38: Ultrasound biweekly in stage I FGR and every four weeks in SGA. In both cases delivery at ≥39-40 weeks. * 38-110: In stage I FGR and SGA ultrasound weekly. Delivery at ≥37 weeks. * \>110: In stage I FGR and SGA ultrasound weekly. Delivery at ≥36 weeks. * \>110 and concurrent preeclampsia: In stage I FGR and SGA ultrasound every 48h-72h. Delivery at ≥34 weeks. * \>201: Ultrasound every 48-72h, delivery at ≥34+0 weeks. If concurrent preeclampsia, delivery at ≥32+0 weeks. * \>655: Ultrasound every 48-72h, delivery at ≥32+0 weeks. If concurrent preeclampsia, delivery at ≥30+0 weeks. * \>1000: In cases with concurrent PE, delivery at ≥29+0 weeks.
Primary Outcome Measures
NameTimeMethod
Fetal and Neonatal complicationsDuring pregnancy and up to 28 days after delivery

stillbirth, neonatal death, artery cord pH ≤7.0, respiratory distress syndrome, required invasive ventilatory support, grade III or IV intraventricular hemorrhage, neonatal sepsis, necrotizing enterocolitis, neonatal seizures, pneumonia, meningitis, broncopulmonary dysplasia, hypoxic ischemic encephalopathy, Apgar score \<7 at 5 minutes, or elective delivery at \<28 weeks of gestation.

Composite adverse maternal outcomeDuring pregnancy and up to 28 days after delivery

Progression to PE with severity features; progression to hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome (LDH \>600 IU/L, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevated more than twice the upper limit of normal, and the platelet count less than 100 X 109/L); eclampsia, stroke, hepatic hematoma or rupture; oliguria (urine output of \<400 mL during 24 hours, or need for treatment with furosemide to maintain urine output at \>400 mL for 24 hours); cardiovascular dysfunction (need for inotropic support, left ventricle failure, or myocardial infarction); placental abruption; maternal death; maternal admission to intensive care unit \>48 hours, and/or requirement for blood transfusion.

Secondary Outcome Measures
NameTimeMethod
Maternal perceived stressAt inclusion and 4 weeks later

Mean and sd or median and IQR of the score obtained in the perceived stress scale in each group

Other perinatal outcomesDuring pregnancy and up to 28 days after delivery

transient tachypnea, non-invasive ventilatory support, hypoglycemia, neonatal jaundice (treated with phototherapy), rate of elective deliveries \< 30 weeks, \<34 weeks and \< 37 weeks for FGR and/or PE, birthweight \<3 rd and \<10th percentiles, mode of delivery (vaginal, instrumental vaginal delivery and Cesarean), rate of Cesarean delivery for abnormal CTG, median maternal stay in ICU, median neonatal stay in N-ICU, maternal corticosteroids (single dose, complete course), prenatal magnesium sulfate (at least 4h) for preterm delivery.

Number of ultrasounds per participantDuring pregnancy (before and after 37 weeks)

Mean and sd or median and IQR in each group

Trial Locations

Locations (27)

Hospital Universitari Germans Trias i Pujol

🇪🇸

Badalona, Spain

Complejo Hospitalario Universitario de A Coruña

🇪🇸

A Coruña, Spain

Hospital Universitario General de Alicante

🇪🇸

Alicante, Spain

Vall d'hebron Barcelona Hospital Campus

🇪🇸

Barcelona, Spain

Hospital Universitari Dexeus

🇪🇸

Barcelona, Spain

Hospital de la Santa Creu i Sant Pau

🇪🇸

Barcelona, Spain

Hospital Universitario Puerta del Mar

🇪🇸

Cadiz, Spain

Hospital General Universitario de Elche

🇪🇸

Elche, Spain

Hospital Universitario de Getafe

🇪🇸

Getafe, Spain

Hospital Universitario de Cabueñes

🇪🇸

Gijón, Spain

Hospital Universitari de Girona Doctor Josep Trueta

🇪🇸

Girona, Spain

Hospital Universitario San Cecilio

🇪🇸

Granada, Spain

Hospital Universitario de Jerez de la Frontera

🇪🇸

Jerez De La Frontera, Spain

Hospital Materno Infantil de Gran Canaria

🇪🇸

Las Palmas De Gran Canaria, Spain

Hospital Universitari Arnau de Vilanova

🇪🇸

Lleida, Spain

Hospital Clínico San Carlos

🇪🇸

Madrid, Spain

Hospital Universitari Son Espases

🇪🇸

Palma De Mallorca, Spain

Corporació Sanitària Parc Taulí

🇪🇸

Sabadell, Spain

Hospital Universitari Son Llàtzer

🇪🇸

Palma De Mallorca, Spain

Hospital Universitario de Canarias

🇪🇸

Santa Cruz De Tenerife, Spain

Hospital Universitario Virgen de Valme

🇪🇸

Sevilla, Spain

Virgen Macarena

🇪🇸

Sevilla, Spain

Consorci Sanitari de Terrassa

🇪🇸

Terrassa, Spain

Hospital Universitario Joan XXIII de Tarragona

🇪🇸

Tarragona, Spain

Hospital Universitari Mútua Terrassa

🇪🇸

Terrassa, Spain

Hospital Universitario de Torrejón

🇪🇸

Torrejón De Ardoz, Spain

Hospital Clínico Universitario Lozano Blesa

🇪🇸

Zaragoza, Spain

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