How to monitor pregnancies complicated by fetal growth restriction and delivery before 32 weeks: post-hoc analysis of TRUFFLE study.
OBJECTIVE
In the recent TRUFFLE study, it appeared that, in pregnancies complicated by fetal growth restriction (FGR) between 26 and 32 weeks' gestation, monitoring of the fetal ductus venosus (DV) waveform combined with computed cardiotocography (CTG) to determine timing of delivery increased the chance of infant survival without neurological impairment. However, concerns with the interpretation were raised, as DV monitoring appeared to be associated with a non-significant increase in fetal death, and some infants were delivered after 32 weeks, at which time the study protocol no longer applied. This secondary sensitivity analysis of the TRUFFLE study focuses on women who delivered before 32 completed weeks' gestation and analyzes in detail the cases of fetal death.


METHODS
Monitoring data of 317 pregnancies with FGR that delivered before 32 weeks were analyzed, excluding those with absent outcome data or inevitable perinatal death. Women were allocated randomly to one of three groups of indication for delivery according to the following monitoring strategies: (1) reduced fetal heart rate short-term variation (STV) on CTG; (2) early changes in fetal DV waveform; and (3) late changes in fetal DV waveform. Primary outcome was 2-year survival without neurological impairment. The association of the last monitoring data before delivery and infant outcome was assessed by multivariable analysis.


RESULTS
Two-year survival without neurological impairment occurred more often in the two DV groups (both 83%) than in the CTG-STV group (77%), however, the difference was not statistically significant (P = 0.21). Among the surviving infants in the DV groups, 93% were free of neurological impairment vs 85% of surviving infants in the CTG-STV group (P = 0.049). All fetal deaths (n = 7) occurred in the groups with DV monitoring. Of the monitoring parameters obtained shortly before fetal death in these seven cases, an abnormal CTG was observed in only one case. Multivariable regression analysis of factors at study entry demonstrated that a later gestational age, higher estimated fetal weight-to-50thpercentile ratio and lower umbilical artery pulsatility index (PI)/fetal middle cerebral artery-PI ratio were significantly associated with normal outcome. Allocation to DV monitoring had a smaller effect on outcome, but remained in the model (P < 0.1). Abnormal fetal arterial Doppler before delivery was significantly associated with adverse outcome in the CTG-STV group. In contrast, abnormal DV flow was the only monitoring parameter associated with adverse outcome in the DV groups, while fetal arterial Doppler, STV below the cut-off used in the CTG-STV group and recurrent decelerations in fetal heart rate were not.


CONCLUSIONS
In accordance with the findings of the TRUFFLE study on monitoring and intervention management of very preterm FGR, we found that the proportion of infants surviving without neuroimpairment was not significantly different when the decision for delivery was based on changes in DV waveform vs reduced STV on CTG. The uneven distribution of fetal deaths towards the DV groups was probably a chance effect, and neurological outcome was better among surviving children in these groups. Before 32 weeks, delaying delivery until abnormalities in DV-PI or STV and/or recurrent decelerations in fetal heat rate occur, as defined by the study protocol, is likely to be safe and possibly benefits long-term outcome. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, The Netherlands.
W
http://orcid.org/0000-0002-7243-2115
W
Ganzevoort
Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, The Netherlands.
N
N
Mensing Van Charante
Fetal Medicine Unit, St George's, University of London & St George's University Hospitals NHS Foundation Trust, Molecular and Clinical Sciences Research Institute, London, UK.
B
B
Thilaganathan
Maternal Fetal Medicine Unit, University of Brescia, Brescia, Italy.
F
F
Prefumo
Center for Mother and Child of the Phillips University, Marburg, Germany.
B
B
Arabin
Fetal Medicine Unit, Department of Obstetrics and Gynaecology, University Medical Centre Groningen, Groningen, The Netherlands.
C M
CM
Bilardo
Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria.
C
C
Brezinka
Perinatal Center, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
J B
JB
Derks
Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
A
A
Diemert
Division of Obstetrics and Prenatal Medicine, Department of Obstetrics and Gynaecology, Erasmus MC, Rotterdam, The Netherlands.
J J
JJ
Duvekot
Children's Hospital, Buzzi, University of Milan, Milan, Italy.
E
E
Ferrazzi
Department of Obstetrics and Gynecology, Maggiore Hospital, University of Parma, Parma, Italy.
T
T
Frusca
Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
K
K
Hecher
University College London Institute for Women's Health Ringgold Standard Institution - Neonatology, London, UK.
N
N
Marlow
Department of Gynecology and Obstetrics, University Federico II of Naples, Naples, Italy.
P
P
Martinelli
Section of Perinatal Medicine, Department of Obstetrics and Gynecology, Technical University, Munich, Germany.
E
E
Ostermayer
Fetal Medicine Unit, St George's, University of London & St George's University Hospitals NHS Foundation Trust, Molecular and Clinical Sciences Research Institute, London, UK.
A T
AT
Papageorghiou
Department of Obstetrics, Vivantes Clinic Neukölln, Berlin, Germany.
D
D
Schlembach
Section of Perinatal Medicine, Department of Obstetrics and Gynecology, Technical University, Munich, Germany.
K T M
KTM
Schneider
Department of Obstetrics and Gynecology, University of Turin, Turin, Italy.
T
T
Todros
Department of Obstetrics and Gynecology, Maggiore Hospital, University of Parma, Parma, Italy.
A
A
Valcamonico
Perinatal Center, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
G H A
GHA
Visser
Department of Neonatology, Emma Children's Hospital Academic Medical Centre, Amsterdam, The Netherlands.
A
A
Van Wassenaer-Leemhuis
Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, Imperial College London, London, UK.|Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
C C
http://orcid.org/0000-0002-2104-5561
CC
Lees
Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, The Netherlands.
H
H
Wolf
D000328:Adult; D015148:Cardiotocography; D002493:Central Nervous System Diseases / Q000151:congenital / Q000517:prevention & control*; D002675:Child, Preschool; D005260:Female; D005317:Fetal Growth Retardation / Q000000981:diagnostic imaging*; D005322:Premature Rupture of Fetal Membranes / Q000000981:diagnostic imaging*; D005865:Gestational Age; D006340:Heart Rate, Fetal; D006801:Humans; D007223:Infant; D062071:Infant, Extremely Premature; D008297:Male; D020768:Middle Cerebral Artery / Q000502:physiology; D011247:Pregnancy; D011673:Pulsatile Flow; D016019:Survival Analysis; D016896:Treatment Outcome; D016216:Ultrasonography, Prenatal; D055988:Uterine Artery / Q000502:physiology
cardiotocography; ductus venosus; fetal growth restriction; intrauterine growth restriction