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

Browse trials for

• Pre-Eclampsia 879
• Fetal Growth Retardation 263
• Placenta Diseases 24

Keywords

• fetal growth restriction
• small for gestational age
• PlGF
• sFlt-1
• Doppler

Study arms

• No intervention
  Control

  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. * 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. * Stage IV: reversed DV "a" wave in two occasions \> 6 hours apart. Elective Cesarean delivery at ≥26 weeks.

• Experimental
  Study

  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.

  Diagnostic Test: soluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF)

Interventions

• Diagnostic testsoluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF)

  soluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF) will be incorporated to the management of early-onset small fetuses (estimated fetal weight ≤10th percentile)

Primary outcomes

1. Fetal and Neonatal complications

   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.

   Time frame: During pregnancy and up to 28 days after delivery

2. Composite adverse maternal outcome

   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.

   Time frame: During pregnancy and up to 28 days after delivery

Secondary outcomes

1. Maternal perceived stress

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

   Time frame: At inclusion and 4 weeks later

2. Other perinatal outcomes

   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.

   Time frame: During pregnancy and up to 28 days after delivery

3. Number of ultrasounds per participant

   Mean and sd or median and IQR in each group

   Time frame: During pregnancy (before and after 37 weeks)

Individual participant data

Plan to share: Undecided