How to monitor pregnancies complicated by fetal growth restriction and delivery below 32 weeks: a post-hoc sensitivity analysis of the TRUFFLE-study.
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
OBJECTIVES: In the recent TRUFFLE study it appeared that, in pregnancies complicated by fetal growth restriction (FGR) between 26 and 32 weeks, monitoring of the ductus venosus (DV) combined with computerised cardiotocography (cCTG) as a trigger for delivery, increased the chance of infant survival without neurological impairment. However, concerns in interpretation were raised as DV monitoring appeared associated with a non-significant increase in fetal death, and part of the infants were delivered after 32 weeks, after which the study protocol was no longer applied. This secondary sensitivity analysis focuses on women who delivered before 32 completed weeks, and analyses fetal death cases in detail. METHODS: We analysed the monitoring data of 317 women who delivered before 32 weeks, excluding women with absent infant outcome data or inevitable perinatal death. The association of the last monitoring data before delivery and infant outcome was assessed by multivariable analysis. RESULTS: The primary outcome (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). Nevertheless, in surviving infants 93% was free of neurological impairment in the DV groups versus 85% in the CTG-STV group (p = 0.049). All fetal deaths (n = 7) occurred in women allocated to DV monitoring, which explains this difference. Assessment of the monitoring parameters that were obtained shortly before fetal death in these 7 cases showed an abnormal CTG in only one. Multivariable regression analysis of factors at study entry demonstrated that higher gestational age, larger estimated fetal weight 50th percentile ratio and lower U/C ratio were significantly associated with the (normal) primary outcome. Allocation to the DV groups had a smaller effect, but remained in the model (p < 0.1). Assessment of the last monitoring data before delivery showed that in the CTG-STV group abnormal fetal arterial Doppler was significantly associated with adverse outcome. In contrast, in the DV groups an abnormal DV was the only fetal monitoring parameter that was associated with adverse infant outcome, while fetal arterial Doppler, STV below CTG-group cut-off or recurrent fetal heart rate decelerations were not. CONCLUSIONS: In accordance with the results of the overall TRUFFLE study of the monitoring-intervention management of very early severe FGR we found that the difference in the proportion of infants surviving without neuroimpairment (the primary endpoint) was non-significant when comparing timing of delivery with or without changes in the DV waveform. However, the uneven distribution of fetal deaths towards the DV groups was likely by chance, and among surviving children neurological outcomes were better. Before 32 weeks, delaying delivery until abnormalities in DVPI or STV and/or recurrent decelerations occur, as defined by the study protocol, is therefore probably safe and possibly benefits long-term outcome.
Date Issued
2017-02-09
Date Acceptance
2017-01-23
Citation
Ultrasound in Obstetrics and Gynecology, 2017, 49, pp.769-777
ISSN
0960-7692
Publisher
Wiley
Start Page
769
End Page
777
Journal / Book Title
Ultrasound in Obstetrics and Gynecology
Volume
49
Copyright Statement
© 2017 International Society of Ultrasound in Obstetrics & Gynecology. This is the accepted version of the following article: Ganzevoort, W., Mensing van Charante, N., Thilaganathan, B., Prefumo, F., Arabin, B., Bilardo, C., Brezinka, C., Derks, J., Diemert, A., Duvekot, J., Ferrazzi, E., Frusca, T., Hecher, K., Marlow, N., Martinelli, P., Ostermayer, E., Papageorghiou, A., Schlembach, D., Schneider, K., Todros, T., Valcamonico, A., Visser, G., van Wassenaer-Leemhuis, A., Lees, C., Wolf, H. and on behalf of the TRUFFLE Group (2016), How to monitor pregnancies complicated by fetal growth restriction and delivery below 32 weeks: a post-hoc sensitivity analysis of the TRUFFLE-study. Ultrasound Obstet Gynecol. Accepted Author Manuscript. doi:10.1002/uog.17433, which has been published in final form at https://dx.doi.org/10.1002/uog.17433
Subjects
Science & Technology
Technology
Life Sciences & Biomedicine
Acoustics
Obstetrics & Gynecology
Radiology, Nuclear Medicine & Medical Imaging
cardiotocography
ductus venosus
fetal growth restriction
intrauterine growth restriction
PLACENTAL INSUFFICIENCY
DOPPLER
OUTCOMES
TRIAL
FLOW
TRUFFLE Group
1114 Paediatrics And Reproductive Medicine
Obstetrics & Reproductive Medicine
Publication Status
Published