Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol
Authors: Mylrea-Foley Bronacha , Thornton Jim G , Mullins Edward , Marlow Neil , Hecher Kurt , Ammari Christina , Arabin Birgit , Berger Astrid , Bergman Eva , Bhide Amarnath , Bilardo Caterina , Binder Julia , Breeze Andrew , Brodszki Jana , Calda Pavel , Cannings-John Rebecca , Černý Andrej , Cesari Elena , Cetin Irene , Dall'Asta Andrea , Diemert Anke , Ebbing Cathrine , Eggebø Torbjørn , Fantasia Ilaria , Ferrazzi Enrico , Frusca Tiziana , Ghi Tullio , Goodier Jenny , Greimel Patrick , Gyselaers Wilfried , Hassan Wassim , Von Kaisenberg Constantin , Kholin Alexey , Klaritsch Philipp , Krofta Ladislav , Lindgren Peter , Lobmaier Silvia , Marsal Karel , Maruotti Giuseppe M , Mecacci Federico , Myklestad Kirsti , Napolitano Raffaele , Ostermayer Eva , Papageorghiou Aris , Potter Claire , Prefumo Federico , Raio Luigi , Richter Jute , Sande Ragnar Kvie , Schlembach Dietmar , Schleußner Ekkehard , Stampalija Tamara , Thilaganathan Basky , Townson Julia , Valensise Herbert , Visser Gerard HA , Wee Ling , Wolf Hans , Lees Christoph C 
Published: April 2022

Introduction

Following 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 analysis

Women 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 dissemination

The 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 number

Main 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.