Management of Early-onset Fetal Growth Restriction: Angiogenic Factors Versus Feto-placental Doppler (Early GRAFD)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 340
- 试验地点
- 27
- 主要终点
- Fetal and Neonatal complications
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Major fetal malformations or genetic disorders
- •Fetal death
- •Refusal to give informed consent
- •Stage IV FGR
研究组 & 干预措施
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.
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.
干预措施: soluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF) (Diagnostic Test)
结局指标
主要结局
Fetal and Neonatal complications
时间窗: During 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 outcome
时间窗: During 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.
次要结局
- Number of ultrasounds per participant(During pregnancy (before and after 37 weeks))
- Maternal perceived stress(At inclusion and 4 weeks later)
- Other perinatal outcomes(During pregnancy and up to 28 days after delivery)