W Ganzevoort1, N Mensing Van Charante1, B Thilaganathan2, F Prefumo3, B Arabin4, C M Bilardo5, C Brezinka6, J B Derks7, A Diemert8, J J Duvekot9, E Ferrazzi10, T Frusca11, K Hecher8, N Marlow12, P Martinelli13, E Ostermayer14, A T Papageorghiou2, D Schlembach15, K T M Schneider14, T Todros16, A Valcamonico11, G H A Visser7, A Van Wassenaer-Leemhuis17, C C Lees18,19, H Wolf1. 1. Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, The Netherlands. 2. 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. 3. Maternal Fetal Medicine Unit, University of Brescia, Brescia, Italy. 4. Center for Mother and Child of the Phillips University, Marburg, Germany. 5. Fetal Medicine Unit, Department of Obstetrics and Gynaecology, University Medical Centre Groningen, Groningen, The Netherlands. 6. Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria. 7. Perinatal Center, Wilhelmina Children's Hospital, Utrecht, The Netherlands. 8. Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 9. Division of Obstetrics and Prenatal Medicine, Department of Obstetrics and Gynaecology, Erasmus MC, Rotterdam, The Netherlands. 10. Children's Hospital, Buzzi, University of Milan, Milan, Italy. 11. Department of Obstetrics and Gynecology, Maggiore Hospital, University of Parma, Parma, Italy. 12. University College London Institute for Women's Health Ringgold Standard Institution - Neonatology, London, UK. 13. Department of Gynecology and Obstetrics, University Federico II of Naples, Naples, Italy. 14. Section of Perinatal Medicine, Department of Obstetrics and Gynecology, Technical University, Munich, Germany. 15. Department of Obstetrics, Vivantes Clinic Neukölln, Berlin, Germany. 16. Department of Obstetrics and Gynecology, University of Turin, Turin, Italy. 17. Department of Neonatology, Emma Children's Hospital Academic Medical Centre, Amsterdam, The Netherlands. 18. Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, Imperial College London, London, UK. 19. Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
Abstract
OBJECTIVES: 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-50th percentile 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.
OBJECTIVES: 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-50th percentile 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.
Authors: Liona C Poon; Laura A Magee; Stefan Verlohren; Andrew Shennan; Peter von Dadelszen; Eyal Sheiner; Eran Hadar; Gerard Visser; Fabricio Da Silva Costa; Anil Kapur; Fionnuala McAuliffe; Amala Nazareth; Muna Tahlak; Anne B Kihara; Hema Divakar; H David McIntyre; Vincenzo Berghella; Huixia Yang; Roberto Romero; Kypros H Nicolaides; Nir Melamed; Moshe Hod Journal: Int J Gynaecol Obstet Date: 2021-07 Impact factor: 4.447
Authors: Catherine E Aiken; Jane L Tarry-Adkins; Ana-Mishel Spiroski; Anna M Nuzzo; Thomas J Ashmore; Alessandro Rolfo; Megan J Sutherland; Emily J Camm; Dino A Giussani; Susan E Ozanne Journal: FASEB J Date: 2019-03-19 Impact factor: 5.834