title: Phase-rectified signal averaging method to predict perinatal outcome in infants with very preterm fetal growth restriction- a secondary analysis of TRUFFLE-trial.
abstract: BACKGROUND
  Phase-rectified signal averaging, an innovative signal processing technique, can be used to investigate quasi-periodic oscillations in noisy, nonstationary signals that are obtained from fetal heart rate. Phase-rectified signal averaging is currently the best method to predict survival after myocardial infarction in adult cardiology. Application of this method to fetal medicine has established significantly better identification than with short-term variation by computerized cardiotocography of growth-restricted fetuses.
  
  
  OBJECTIVE
  The aim of this study was to determine the longitudinal progression of phase-rectified signal averaging indices in severely growth-restricted human fetuses and the prognostic accuracy of the technique in relation to perinatal and neurologic outcome.
  
  
  METHODS
  Raw data from cardiotocography monitoring of 279 human fetuses were obtained from 8 centers that took part in the multicenter European "TRUFFLE" trial on optimal timing of delivery in fetal growth restriction. Average acceleration and deceleration capacities were calculated by phase-rectified signal averaging to establish progression from 5 days to 1 day before delivery and were compared with short-term variation progression. The receiver operating characteristic curves of average acceleration and deceleration capacities and short-term variation were calculated and compared between techniques for short- and intermediate-term outcome.
  
  
  RESULTS
  Average acceleration and deceleration capacities and short-term variation showed a progressive decrease in their diagnostic indices of fetal health from the first examination 5 days before delivery to 1 day before delivery. However, this decrease was significant 3 days before delivery for average acceleration and deceleration capacities, but 2 days before delivery for short-term variation. Compared with analysis of changes in short-term variation, analysis of (delta) average acceleration and deceleration capacities better predicted values of Apgar scores <7 and antenatal death (area under the curve for prediction of antenatal death: delta average acceleration capacity, 0.62 [confidence interval, 0.19-1.0]; delta short-term variation, 0.54 [confidence interval, 0.13-0.97]; P=.006; area under the curve for prediction Apgar <7: average deceleration capacity <24 hours before delivery, 0.64 [confidence interval, 0.52-0.76]; short-term variation <24 hours before delivery, 0.53 [confidence interval, 0.40-0.65]; P=.015). Neither phase-rectified signal averaging indices nor short-term variation showed predictive power for developmental disability at 2 years of age (Bayley developmental quotient, <95 or <85).
  
  
  CONCLUSIONS
  The phase-rectified signal averaging method seems to be at least as good as short-term variation to monitor progressive deterioration of severely growth-restricted fetuses. Our findings suggest that for short-term outcomes such as Apgar score, phase-rectified signal averaging indices could be an even better test than short-term variation. Overall, our findings confirm the possible value of prospective trials based on phase-rectified signal averaging indices of autonomic nervous system of severely growth-restricted fetuses.
authors.affiliation: Frauenklinik und Poliklinik, Technische Universität München, Munich, Germany. Electronic address: silvia.lobmaier@tum.de.
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Lobmaier
authors.affiliation: Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: Mensing van Charante
authors.affiliation: Children's Hospital Buzzi, University of Milan, Milan, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Ferrazzi
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Dino A
authors.initials: DA
authors.lastname: Giussani
authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Shaw
authors.affiliation: Medizinische Klinik und Deutsches Herzzentrum München der Technischen Universität München, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Müller
authors.affiliation: Frauenklinik und Poliklinik, Technische Universität München, Munich, Germany.
authors.forename: Javier U
authors.initials: JU
authors.lastname: Ortiz
authors.affiliation: Frauenklinik und Poliklinik, Technische Universität München, Munich, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Ostermayer
authors.affiliation: Institute for Medical Statistics and Epidemiology (IMSE), Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Haller
authors.affiliation: Maternal-Fetal Medicine Unit, University of Brescia, Brescia, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Prefumo
authors.affiliation: Maternal-Fetal Medicine Unit, University of Brescia, Brescia, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Frusca
authors.affiliation: Department of Obstetrics and Fetal Medicine, University Medical Center, Hamburg-Eppendorf, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Hecher
authors.affiliation: Department of Perinatology, Isala Clinics, Zwolle, Overijssel, the Netherlands.
authors.forename: Birgit
authors.initials: B
authors.lastname: Arabin
authors.affiliation: Fetal Medicine Unit, St. George's Hospital, St George's University of London, London, UK.
authors.forename: Baskaran
authors.initials: B
authors.lastname: Thilaganathan
authors.affiliation: Fetal Medicine Unit, St. George's Hospital, St George's University of London, London, UK.
authors.forename: Aris T
authors.initials: AT
authors.lastname: Papageorghiou
authors.affiliation: Fetal Medicine Unit, St. George's Hospital, St George's University of London, London, UK.
authors.forename: Amarnath
authors.initials: A
authors.lastname: Bhide
authors.affiliation: Department of Neuroscience, Reproductive Science and Dentistry, University of Naples Federico II, Napoli, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Martinelli
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Duvekot
authors.affiliation: Department of Perinatology, Isala Clinics, Zwolle, Overijssel, the Netherlands.
authors.forename: Jim
authors.initials: J
authors.lastname: van Eyck
authors.affiliation: Department of Perinatal Medicine, University Medical Center, Utrecht, the Netherlands.
authors.forename: Gerard H A
authors.initials: GH
authors.lastname: Visser
authors.affiliation: Medizinische Klinik und Deutsches Herzzentrum München der Technischen Universität München, Munich, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Schmidt
authors.affiliation: Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Wessel
authors.initials: W
authors.lastname: Ganzevoort
authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, UK; Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Lees
authors.affiliation: Frauenklinik und Poliklinik, Technische Universität München, Munich, Germany.
authors.forename: Karl T M
authors.initials: KT
authors.lastname: Schneider
mesh_terms: D000328:Adult; D001034:Apgar Score; D015148:Cardiotocography / Q000379:methods*; D002658:Developmental Disabilities / Q000175:diagnosis / Q000209:etiology; D005260:Female; D005317:Fetal Growth Retardation / Q000175:diagnosis* / Q000503:physiopathology; D006340:Heart Rate, Fetal / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D011237:Predictive Value of Tests; D011247:Pregnancy; D011379:Prognosis; D012372:ROC Curve; D012815:Signal Processing, Computer-Assisted
keywords: CTG; PRSA; STV; fetal growth restriction; phase-rectified signal averaging; short-term variation