Management of Early-onset Fetal Growth Restriction: Angiogenic Factors Versus Feto-placental Doppler (earlyGRAFD)
Fetal Growth Retardation, Preeclampsia, Placenta Diseases
About this trial
This is an interventional diagnostic trial for Fetal Growth Retardation focused on measuring fetal growth restriction, small for gestational age, PlGF, sFlt-1, Doppler
Eligibility Criteria
Inclusion Criteria:
- Pregnant women of at least 18 years old
- Singleton pregnancy
- Ultrasonographic EFW ≤10th percentile between 24+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
Sites / Locations
- Complejo Hospitalario Universitario de A Coruña
- Hospital Universitario General de Alicante
- Hospital Universitari Germans Trias i Pujol
- Vall d'hebron Barcelona Hospital Campus
- Hospital de la Santa Creu i Sant Pau
- Hospital Universitari Dexeus
- Hospital Universitario Puerta del Mar
- Hospital General Universitario de Elche
- Hospital Universitario de Getafe
- Hospital Universitario de Cabueñes
- Hospital Universitari de Girona Doctor Josep Trueta
- Hospital Universitario San Cecilio
- Hospital Universitario de Jerez de la Frontera
- Hospital Universitari Arnau de Vilanova
- Hospital Universitari Son Espases
- Hospital Universitari Son Llàtzer
- Corporació Sanitària Parc Taulí
- Hospital Universitario de Canarias
- Hospital Universitario Virgen de Valme
- Hospital Universitario Joan XXIII de Tarragona
- Consorci Sanitari de Terrassa
- Hospital Universitari Mútua Terrassa
- Hospital Universitario de Torrejón
- Hospital Clínico Universitario Lozano Blesa
Arms of the Study
Arm 1
Arm 2
No Intervention
Experimental
Control
Study
Small fetuses will be classified into 5 severity stages and managed as follows: SGA: Estimated fetal weight (EFW) between p3 and p10 with normal Dopplers. Ultrasound/2 weeks, elective vaginal delivery at ≥39-40 weeks. Stage I: EFW ≤p3 p or EFW p3-10 + UA PI >p95 and/or UtA PI >p95, and, at ≥32 weeks, CPR and/or MCA PI <p5, in 2 occasions >12 hours apart. Ultrasound weekly, elective vaginal delivery at ≥37 weeks. Stage II: AEDF UA in 2 occasions >12 hours apart. Ultrasound every 48-72h, elective Cesarean delivery at ≥34 weeks. Fetal lung maturation at ≥ 33 weeks. Stage III: DV PI > p95 (or absent DV "a" wave) or reversed end-diastolic UA >50% of cycles, in both cases in two occasions > 6 hours apart. Ultrasound every 24-48h, elective Cesarean delivery at ≥30 weeks. Fetal lung maturation at ≥ 28 weeks. Stage IV: reversed DV "a" wave in two occasions > 6 hours apart. Elective Cesarean delivery at ≥26 weeks. Fetal lung maturation at ≥ 25+5 weeks.
Doppler protocol (as in controls) + sFlt-1/PlGF ratio cutoffs will be incorporated as follows: <38: Ultrasound biweekly in stage I FGR and every three weeks in SGA. In both cases delivery at ≥39-40 weeks. 38-85: In stage I FGR and SGA ultrasound weekly. Delivery at ≥37 weeks. >85: In stage I FGR and SGA ultrasound every 72h-96h. Delivery at ≥37 weeks. >110: In stage I FGR and SGA ultrasound every 48h-72h. Delivery at ≥36 weeks. If concurrent preeclampsia, delivery at ≥34+0 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 ≥28+0 weeks.