Outcome in early-onset fetal growth restriction is best combining computerized fetal heart rate analysis with ductus venosus Doppler: insights from the Trial of Umbilical and Fetal Flow in Europe

TRUFFLE investigators

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

Background: Early-onset fetal growth restriction represents a particular dilemma in clinical management balancing the risk of iatrogenic prematurity with waiting for the fetus to gain more maturity, while being exposed to the risk of intrauterine death or the sequelae of acidosis. Objective: The Trial of Umbilical and Fetal Flow in Europe was a European, multicenter, randomized trial aimed to determine according to which criteria delivery should be triggered in early fetal growth restriction. We present the key findings of the primary and secondary analyses. Study Design: Women with fetal abdominal circumference <10th percentile and umbilical pulsatility index >95th percentile between 26-32 weeks were randomized to 1 of 3 monitoring and delivery protocols. These were: fetal heart rate variability based on computerized cardiotocography; and early or late ductus venosus Doppler changes. A safety net based on fetal heart rate abnormalities or umbilical Doppler changes mandated delivery irrespective of randomized group. The primary outcome was normal neurodevelopmental outcome at 2 years. Results: Among 511 women randomized, 362/503 (72%) had associated hypertensive conditions. In all, 463/503 (92%) of fetuses survived and cerebral palsy occurred in 6/443 (1%) with known outcome. Among all women there was no difference in outcome based on randomized group; however, of survivors, significantly more fetuses randomized to the late ductus venosus group had a normal outcome (133/144; 95%) than those randomized to computerized cardiotocography alone (111/131; 85%). In 118/310 (38%) of babies delivered <32 weeks, the indication was safety-net criteria: 55/106 (52%) in late ductus venosus, 37/99 (37%) in early ductus venosus, and 26/105 (25%) in computerized cardiotocography groups. Higher middle cerebral artery impedance adjusted for gestation was associated with neonatal survival without severe morbidity (odds ratio, 1.24; 95% confidence interval, 1.02–1.52) and infant survival without neurodevelopmental impairment at 2 years (odds ratio, 1.33; 95% confidence interval, 1.03–1.72) although birthweight and gestational age were more important determinants. Conclusion: Perinatal and 2-year outcome was better than expected in all randomized groups. Among survivors, 2-year neurodevelopmental outcome was best in those randomized to delivery based on late ductus venosus changes. Given a high rate of delivery based on the safety-net criteria, deciding delivery based on late ductus venosus changes and abnormal computerized fetal heart rate variability seems prudent. There is no rationale for delivery based on cerebral Doppler changes alone. Of note, most women with early-onset fetal growth restriction develop hypertension.

Original languageEnglish
Pages (from-to)S783-S789
JournalAmerican Journal of Obstetrics and Gynecology
Volume218
Issue number2
DOIs
Publication statusPublished - 1 Feb 2018

Cite this

@article{c8771b8552f94480bfea736ff50f19b5,
title = "Outcome in early-onset fetal growth restriction is best combining computerized fetal heart rate analysis with ductus venosus Doppler: insights from the Trial of Umbilical and Fetal Flow in Europe",
abstract = "Background: Early-onset fetal growth restriction represents a particular dilemma in clinical management balancing the risk of iatrogenic prematurity with waiting for the fetus to gain more maturity, while being exposed to the risk of intrauterine death or the sequelae of acidosis. Objective: The Trial of Umbilical and Fetal Flow in Europe was a European, multicenter, randomized trial aimed to determine according to which criteria delivery should be triggered in early fetal growth restriction. We present the key findings of the primary and secondary analyses. Study Design: Women with fetal abdominal circumference <10th percentile and umbilical pulsatility index >95th percentile between 26-32 weeks were randomized to 1 of 3 monitoring and delivery protocols. These were: fetal heart rate variability based on computerized cardiotocography; and early or late ductus venosus Doppler changes. A safety net based on fetal heart rate abnormalities or umbilical Doppler changes mandated delivery irrespective of randomized group. The primary outcome was normal neurodevelopmental outcome at 2 years. Results: Among 511 women randomized, 362/503 (72{\%}) had associated hypertensive conditions. In all, 463/503 (92{\%}) of fetuses survived and cerebral palsy occurred in 6/443 (1{\%}) with known outcome. Among all women there was no difference in outcome based on randomized group; however, of survivors, significantly more fetuses randomized to the late ductus venosus group had a normal outcome (133/144; 95{\%}) than those randomized to computerized cardiotocography alone (111/131; 85{\%}). In 118/310 (38{\%}) of babies delivered <32 weeks, the indication was safety-net criteria: 55/106 (52{\%}) in late ductus venosus, 37/99 (37{\%}) in early ductus venosus, and 26/105 (25{\%}) in computerized cardiotocography groups. Higher middle cerebral artery impedance adjusted for gestation was associated with neonatal survival without severe morbidity (odds ratio, 1.24; 95{\%} confidence interval, 1.02–1.52) and infant survival without neurodevelopmental impairment at 2 years (odds ratio, 1.33; 95{\%} confidence interval, 1.03–1.72) although birthweight and gestational age were more important determinants. Conclusion: Perinatal and 2-year outcome was better than expected in all randomized groups. Among survivors, 2-year neurodevelopmental outcome was best in those randomized to delivery based on late ductus venosus changes. Given a high rate of delivery based on the safety-net criteria, deciding delivery based on late ductus venosus changes and abnormal computerized fetal heart rate variability seems prudent. There is no rationale for delivery based on cerebral Doppler changes alone. Of note, most women with early-onset fetal growth restriction develop hypertension.",
keywords = "antepartum surveillance, cardiotocography, intrauterine growth restriction, neurodevelopmental handicap, perinatal outcome, Trial of Umbilical and Fetal Flow in Europe, umbilical artery Doppler",
author = "{TRUFFLE investigators} and Tiziana Frusca and Tullia Todros and Christoph Lees and Bilardo, {Caterina M.} and Kurt Hecher and Visser, {Gerard H.A.} and Papageorghiou, {Aris T.} and Neil Marlow and Baskaran Thilaganathan and {van Wassenaer-Leemhuis}, Aleid and Karel Marsal and Birgit Arabin and Christoph Brezinka and Derks, {Jan B.} and Anke Diemert and Duvekot, {Johannes J.} and Enrico Ferrazzi and Ganzevoort, {J. W.} and Pasquale Martinelli and Eva Ostermayer and Dietmar Schlembach and Herbert Valensise and Jim Thornton and Hans Wolf",
year = "2018",
month = "2",
day = "1",
doi = "10.1016/j.ajog.2017.12.226",
language = "English",
volume = "218",
pages = "S783--S789",
journal = "American Journal of Obstetrics and Gynecology",
issn = "0002-9378",
publisher = "Mosby Inc.",
number = "2",

}

Outcome in early-onset fetal growth restriction is best combining computerized fetal heart rate analysis with ductus venosus Doppler : insights from the Trial of Umbilical and Fetal Flow in Europe. / TRUFFLE investigators.

In: American Journal of Obstetrics and Gynecology, Vol. 218, No. 2, 01.02.2018, p. S783-S789.

Research output: Contribution to journalReview articleAcademicpeer-review

TY - JOUR

T1 - Outcome in early-onset fetal growth restriction is best combining computerized fetal heart rate analysis with ductus venosus Doppler

T2 - insights from the Trial of Umbilical and Fetal Flow in Europe

AU - TRUFFLE investigators

AU - Frusca, Tiziana

AU - Todros, Tullia

AU - Lees, Christoph

AU - Bilardo, Caterina M.

AU - Hecher, Kurt

AU - Visser, Gerard H.A.

AU - Papageorghiou, Aris T.

AU - Marlow, Neil

AU - Thilaganathan, Baskaran

AU - van Wassenaer-Leemhuis, Aleid

AU - Marsal, Karel

AU - Arabin, Birgit

AU - Brezinka, Christoph

AU - Derks, Jan B.

AU - Diemert, Anke

AU - Duvekot, Johannes J.

AU - Ferrazzi, Enrico

AU - Ganzevoort, J. W.

AU - Martinelli, Pasquale

AU - Ostermayer, Eva

AU - Schlembach, Dietmar

AU - Valensise, Herbert

AU - Thornton, Jim

AU - Wolf, Hans

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Background: Early-onset fetal growth restriction represents a particular dilemma in clinical management balancing the risk of iatrogenic prematurity with waiting for the fetus to gain more maturity, while being exposed to the risk of intrauterine death or the sequelae of acidosis. Objective: The Trial of Umbilical and Fetal Flow in Europe was a European, multicenter, randomized trial aimed to determine according to which criteria delivery should be triggered in early fetal growth restriction. We present the key findings of the primary and secondary analyses. Study Design: Women with fetal abdominal circumference <10th percentile and umbilical pulsatility index >95th percentile between 26-32 weeks were randomized to 1 of 3 monitoring and delivery protocols. These were: fetal heart rate variability based on computerized cardiotocography; and early or late ductus venosus Doppler changes. A safety net based on fetal heart rate abnormalities or umbilical Doppler changes mandated delivery irrespective of randomized group. The primary outcome was normal neurodevelopmental outcome at 2 years. Results: Among 511 women randomized, 362/503 (72%) had associated hypertensive conditions. In all, 463/503 (92%) of fetuses survived and cerebral palsy occurred in 6/443 (1%) with known outcome. Among all women there was no difference in outcome based on randomized group; however, of survivors, significantly more fetuses randomized to the late ductus venosus group had a normal outcome (133/144; 95%) than those randomized to computerized cardiotocography alone (111/131; 85%). In 118/310 (38%) of babies delivered <32 weeks, the indication was safety-net criteria: 55/106 (52%) in late ductus venosus, 37/99 (37%) in early ductus venosus, and 26/105 (25%) in computerized cardiotocography groups. Higher middle cerebral artery impedance adjusted for gestation was associated with neonatal survival without severe morbidity (odds ratio, 1.24; 95% confidence interval, 1.02–1.52) and infant survival without neurodevelopmental impairment at 2 years (odds ratio, 1.33; 95% confidence interval, 1.03–1.72) although birthweight and gestational age were more important determinants. Conclusion: Perinatal and 2-year outcome was better than expected in all randomized groups. Among survivors, 2-year neurodevelopmental outcome was best in those randomized to delivery based on late ductus venosus changes. Given a high rate of delivery based on the safety-net criteria, deciding delivery based on late ductus venosus changes and abnormal computerized fetal heart rate variability seems prudent. There is no rationale for delivery based on cerebral Doppler changes alone. Of note, most women with early-onset fetal growth restriction develop hypertension.

AB - Background: Early-onset fetal growth restriction represents a particular dilemma in clinical management balancing the risk of iatrogenic prematurity with waiting for the fetus to gain more maturity, while being exposed to the risk of intrauterine death or the sequelae of acidosis. Objective: The Trial of Umbilical and Fetal Flow in Europe was a European, multicenter, randomized trial aimed to determine according to which criteria delivery should be triggered in early fetal growth restriction. We present the key findings of the primary and secondary analyses. Study Design: Women with fetal abdominal circumference <10th percentile and umbilical pulsatility index >95th percentile between 26-32 weeks were randomized to 1 of 3 monitoring and delivery protocols. These were: fetal heart rate variability based on computerized cardiotocography; and early or late ductus venosus Doppler changes. A safety net based on fetal heart rate abnormalities or umbilical Doppler changes mandated delivery irrespective of randomized group. The primary outcome was normal neurodevelopmental outcome at 2 years. Results: Among 511 women randomized, 362/503 (72%) had associated hypertensive conditions. In all, 463/503 (92%) of fetuses survived and cerebral palsy occurred in 6/443 (1%) with known outcome. Among all women there was no difference in outcome based on randomized group; however, of survivors, significantly more fetuses randomized to the late ductus venosus group had a normal outcome (133/144; 95%) than those randomized to computerized cardiotocography alone (111/131; 85%). In 118/310 (38%) of babies delivered <32 weeks, the indication was safety-net criteria: 55/106 (52%) in late ductus venosus, 37/99 (37%) in early ductus venosus, and 26/105 (25%) in computerized cardiotocography groups. Higher middle cerebral artery impedance adjusted for gestation was associated with neonatal survival without severe morbidity (odds ratio, 1.24; 95% confidence interval, 1.02–1.52) and infant survival without neurodevelopmental impairment at 2 years (odds ratio, 1.33; 95% confidence interval, 1.03–1.72) although birthweight and gestational age were more important determinants. Conclusion: Perinatal and 2-year outcome was better than expected in all randomized groups. Among survivors, 2-year neurodevelopmental outcome was best in those randomized to delivery based on late ductus venosus changes. Given a high rate of delivery based on the safety-net criteria, deciding delivery based on late ductus venosus changes and abnormal computerized fetal heart rate variability seems prudent. There is no rationale for delivery based on cerebral Doppler changes alone. Of note, most women with early-onset fetal growth restriction develop hypertension.

KW - antepartum surveillance

KW - cardiotocography

KW - intrauterine growth restriction

KW - neurodevelopmental handicap

KW - perinatal outcome

KW - Trial of Umbilical and Fetal Flow in Europe

KW - umbilical artery Doppler

UR - http://www.scopus.com/inward/record.url?scp=85044587648&partnerID=8YFLogxK

U2 - 10.1016/j.ajog.2017.12.226

DO - 10.1016/j.ajog.2017.12.226

M3 - Review article

VL - 218

SP - S783-S789

JO - American Journal of Obstetrics and Gynecology

JF - American Journal of Obstetrics and Gynecology

SN - 0002-9378

IS - 2

ER -