2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE)
A randomised trial
The Lancet , Volume 385 - Issue 9983 p. 2162- 2172
Background: No consensus exists for the best way to monitor and when to trigger delivery in mothers of babies with fetal growth restriction. We aimed to assess whether changes in the fetal ductus venosus Doppler waveform (DV) could be used as indications for delivery instead of cardiotocography short-term variation (STV).
Methods: In this prospective, European multicentre, unblinded, randomised study, we included women with singleton fetuses at 26.32 weeks of gestation who had very preterm fetal growth restriction (ie, low abdominal circumference [<10th percentile] and a high umbilical artery Doppler pulsatility index [>95th percentile]). We randomly allocated women 1:1:1, with randomly sized blocks and stratifi ed by participating centre and gestational age, to three timing of delivery plans, which diff ered according to antenatal monitoring strategies: reduced cardiotocograph fetal heart rate STV (CTG STV), early DV changes, or late DV changes. The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley III developmental score of less than 85, at 2 years of age. We assessed outcomes in surviving infants with known outcomes at 2 years. We did an intention to treat study for all participants for whom we had data. Safety outcomes were deaths in utero and neonatal deaths and were assessed in all randomly allocated women. This study is registered with ISRCTN, number 56204499.
Findings: Between Jan 1, 2005 and Oct 1, 2010, 503 of 542 eligible women were randomly allocated to monitoring groups. The median gestational age at delivery was 30.7 weeks, and DV no A groups. 12 fetuses died in utero and 27 neonatal deaths occurred. Of survivors, more infants where women were randomly assigned to delivery according to late ductus changes were free of neuroimpairment when compared with those randomly assigned to CTG, but this was accompanied by a non-signifi cant increase in perinatal and infant mortality.
Interpretation: Although the diff erence in the proportion of infants surviving without neuroimpairment was non-signifi cant at the primary endpoint, timing of delivery based on the study protocol using late changes in the DV waveform might produce an improvement in developmental outcomes at 2 years of age. Funding: ZonMw, The Netherlands and Dr Hans Ludwig Geisenhofer Foundation, Germany.
|for the TRUFFLE study group|
|Organisation||Department of Gynaecology & Obstetrics|
Lees, C, Marlow, N, van Wassenaer-Leemhuis, A.G, Arabin, B, Bilardo, C.M, Brezinka, C.A, … Wolf, H. (2015). 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE). The Lancet, 385(9983), 2162–2172. doi:10.1016/S0140-6736(14)62049-3