Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol

Abstract

IntroductionFollowing the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years.Methods and analysisWomen with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18–32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children’s Abilities-Revised questionnaire.Ethics and disseminationThe Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy.Trial registration numberMain sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

Antenatal corticosteroids and perinatal outcome in late fetal growth restriction: analysis of prospective cohort

“…However, meaningful conclusions from this analysis can be evaluated to generate the research hypothesis. Another limitation of the study is that evaluation of the effect of steroids on perinatal outcome was not the aim of the TRUFFLE‐2 feasibility study, the latter being designed to explore the best predictors of outcome in order to investigate in a randomized trial the optimal timing of delivery in late FGR 20 . Additionally, receiving corticosteroids < 14 days before delivery may be associated with a higher obstetric risk and bias results.…”

Current practice in the diagnosis and management of fetal growth restriction: An international survey

“…The TRUFFLE-2 randomized controlled trial, currently ongoing, aims to explore this question. 28 Delivery is, instead, delayed until 39 weeks in the case of a small fetus but with normal Doppler studies (i.e. SGA), but it is expedited if there is also a drop in the fetal growth.…”

“…The highest heterogeneity was encountered for late FGR with signs of cerebral blood flow redistribution, reflecting the current debate on the topic. The TRUFFLE‐2 randomized controlled trial, currently ongoing, aims to explore this question 28 …”

Looking back on preterm birth – The successes and failures

“…have shown no difference in the preterm birth rates of small‐for‐gestational‐age fetuses over the last decade 2 . A multicenter randomized control trial addressing optimal timing of delivery in late preterm small‐for‐gestational‐age fetuses is currently underway and we remain optimistic that the results will help to address preterm birth rates within this specific population group 7 . In the setting of HDP, emerging evidence now supports the use of prediction models for preeclampsia with prescription of low‐dose aspirin in those at high risk reducing the rates of preterm disease by 62% 8 .…”