title: Longitudinal study of computerized cardiotocography in early fetal growth restriction.
abstract: OBJECTIVE
  To explore whether, in early fetal growth restriction (FGR), the longitudinal pattern of fetal heart rate (FHR) short-term variation (STV) can be used to identify imminent fetal distress and whether abnormalities of FHR recordings are associated with 2-year infant outcome.
  
  
  METHODS
  The original TRUFFLE study assessed whether, in early FGR, delivery based on ductus venosus (DV) Doppler pulsatility index (PI), in combination with safety-net criteria of very low STV on cardiotocography (CTG) and/or recurrent FHR decelerations, could improve 2-year infant survival without neurological impairment in comparison with delivery based on CTG monitoring only. This was a secondary analysis of women who delivered before 32 weeks and had consecutive STV data recorded > 3 days before delivery and known infant outcome at 2 years of age. Women who received corticosteroids within 3 days of delivery were excluded. Individual regression line algorithms of all STV values, except the last one before delivery, were calculated. Life tables and Cox regression analysis were used to calculate the daily risk for low STV or very low STV and/or FHR decelerations (below DV group safety-net criteria) and to assess which parameters were associated with this risk. Furthermore, it was assessed whether STV pattern, last STV value or recurrent FHR decelerations were associated with 2-year infant outcome.
  
  
  RESULTS
  One hundred and forty-nine women from the original TRUFFLE study met the inclusion criteria. Using the individual STV regression lines, prediction of a last STV below the cut-off used by the CTG monitoring group had sensitivity of 42% and specificity of 91%. For each day after study inclusion, the median risk for low STV (CTG group cut-off) was 4% (interquartile range (IQR), 2-7%) and for very low STV and/or recurrent FHR decelerations (below DV group safety-net criteria) was 5% (IQR, 4-7%). Measures of STV pattern, fetal Doppler (arterial or venous), birth-weight multiples of the median and gestational age did not usefully improve daily risk prediction. There was no association of STV regression coefficients, a low last STV and/or recurrent FHR decelerations with short- or long-term infant outcomes.
  
  
  CONCLUSIONS
  The TRUFFLE study showed that a strategy of DV monitoring with safety-net criteria of very low STV and/or recurrent FHR decelerations for delivery indication could increase 2-year infant survival without neurological impairment. This post-hoc analysis demonstrates that, in early FGR, the daily risk of abnormal CTG, as defined by the DV group safety-net criteria, is 5%, and that prediction is not possible. This supports the rationale for CTG monitoring more often than daily in these high-risk fetuses. Low STV and/or recurrent FHR decelerations were not associated with adverse infant outcome and it appears safe to delay intervention until such abnormalities occur, as long as DV-PI is within normal range. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
authors.affiliation: Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: H
authors.identifier: http://orcid.org/0000-0003-3924-2149
authors.initials: H
authors.lastname: Wolf
authors.affiliation: Center for Mother and Child of the Phillips University, Marburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Arabin
authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, UK.|Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
authors.forename: C C
authors.identifier: http://orcid.org/0000-0002-2104-5561
authors.initials: CC
authors.lastname: Lees
authors.affiliation: Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Oepkes
authors.affiliation: Maternal-Fetal Medicine Unit, University of Brescia, Brescia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Prefumo
authors.affiliation: Fetal Medicine Unit, St George's, University of London and St George's University Hospitals NHS Foundation Trust, Molecular and Clinical Sciences Research Institute, London, UK.
authors.forename: B
authors.initials: B
authors.lastname: Thilaganathan
authors.affiliation: Department of Obstetrics and Gynaecology, University of Turin, Turin, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Todros
authors.affiliation: Department of Perinatal Medicine, University Medical Center, Utrecht, The Netherlands.
authors.forename: G H A
authors.initials: GHA
authors.lastname: Visser
authors.affiliation: Department of Obstetrics and Gynaecology, University Medical Center, University of Groningen, Groningen, The Netherlands.
authors.forename: C M
authors.identifier: http://orcid.org/0000-0003-1894-0626
authors.initials: CM
authors.lastname: Bilardo
authors.affiliation: Department of Perinatal Medicine, University Medical Center, Utrecht, The Netherlands.
authors.forename: J B
authors.initials: JB
authors.lastname: Derks
authors.affiliation: Department of Obstetrics and Fetal Medicine, University Medical Center, Hamburg, Eppendorf, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Diemert
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Duvekot
authors.affiliation: Department of Woman, Mother and Neonate, Buzzi Children's Hospital, University of Milan, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ferrazzi
authors.affiliation: Department of Obstetrics and Gynecology, Maggiore Hospital, University of Parma, Parma, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Frusca
authors.affiliation: Department of Obstetrics and Fetal Medicine, University Medical Center, Hamburg, Eppendorf, Germany.
authors.forename: K
authors.identifier: http://orcid.org/0000-0002-3172-1164
authors.initials: K
authors.lastname: Hecher
authors.affiliation: Department of Neonatology, Institute for Women's Health, University College Hospitals London, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Marlow
authors.affiliation: Department of Neuroscience, Dentistry and Reproductive Sciences, University of Naples Federico II, Naples, Italy.
authors.forename: P
authors.identifier: http://orcid.org/0000-0003-1911-7762
authors.initials: P
authors.lastname: Martinelli
authors.affiliation: Division of Perinatal Medicine, Department of Obstetrics and Gynecology, Technical University, Munich, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Ostermayer
authors.affiliation: Fetal Medicine Unit, St George's, University of London and St George's University Hospitals NHS Foundation Trust, Molecular and Clinical Sciences Research Institute, London, UK.
authors.forename: A T
authors.initials: AT
authors.lastname: Papageorghiou
authors.affiliation: Department of Obstetrics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: H C J
authors.initials: HCJ
authors.lastname: Scheepers
authors.affiliation: Department of Obstetrics, Vivantes Clinic Neukölln, Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Schlembach
authors.affiliation: Division of Perinatal Medicine, Department of Obstetrics and Gynecology, Technical University, Munich, Germany.
authors.forename: K T M
authors.initials: KTM
authors.lastname: Schneider
authors.affiliation: Maternal-Fetal Medicine Unit, University of Brescia, Brescia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Valcamonico
authors.affiliation: Department of Neonatology, Emma Children's Hospital Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: van Wassenaer-Leemhuis
authors.affiliation: Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: W
authors.identifier: http://orcid.org/0000-0002-7243-2115
authors.initials: W
authors.lastname: Ganzevoort
mesh_terms: D000328:Adult; D015148:Cardiotocography; D002675:Child, Preschool; D005260:Female; D005317:Fetal Growth Retardation / Q000000981:diagnostic imaging* / Q000401:mortality / Q000503:physiopathology; D005318:Fetal Heart / Q000502:physiology*; D006340:Heart Rate, Fetal / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging* / Q000502:physiology; D011247:Pregnancy; D011256:Pregnancy Outcome; D011673:Pulsatile Flow; D016019:Survival Analysis; D016216:Ultrasonography, Prenatal
keywords: cardiotocography; ductus venosus; fetal growth restriction; fetal monitoring; preterm; short-term variation