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

Bronacha Mylrea-Foley, Jim G. Thornton, Edward Mullins, Neil Marlow, Kurt Hecher, Christina Ammari, Birgit Arabin, Astrid Berger, Eva Bergman, Amarnath Bhide, Caterina Bilardo, Julia Binder, Andrew Breeze, Jana Brodszki, Pavel Calda, Rebecca Cannings-John, Andrej Černý, Elena Cesari, Irene Cetin, Andrea Dall'astaAnke Diemert, Cathrine Ebbing, Torbjørn Eggebø, Ilaria Fantasia, Enrico Ferrazzi, Tiziana Frusca, Tullio Ghi, Jenny Goodier, Patrick Greimel, Wilfried Gyselaers, Wassim Hassan, Constantin von Kaisenberg, Alexey Kholin, Philipp Klaritsch, Ladislav Krofta, Peter Lindgren, Silvia Lobmaier, Karel Marsal, Giuseppe M. Maruotti, Federico Mecacci, Kirsti Myklestad, Raffaele Napolitano, Eva Ostermayer, Aris Papageorghiou, Claire Potter, Federico Prefumo, Luigi Raio, Jute Richter, Ragnar Kvie Sande, Dietmar Schlembach, Ekkehard Schleußner, Tamara Stampalija, Basky Thilaganathan, Julia Townson, Herbert Valensise, Gerard H. A. Visser, Ling Wee, Hans Wolf, Christoph C. Lees*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Article numbere055543
JournalBMJ Open
Issue number4
Publication statusPublished - 15 Apr 2022

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