Perinatal morbidity and mortality in early‐onset fetal growth restriction: cohort outcomes of the trial of randomized umbilical and fetal flow in Europe (TRUFFLE)
Open accessAbstract
Objectives: Few data exist for counseling and perinatal management of women after an antenatal diagnosis of early‐onset fetal growth restriction. Yet, the consequences of preterm delivery and its attendant morbidity for both mother and baby are far reaching. The objective of this study was to describe perinatal morbidity and mortality following early‐onset fetal growth restriction based on time of antenatal diagnosis and delivery. Methods: We report cohort outcomes for a prospective multicenter randomized management study of fetal growth restriction (Trial of Randomized Umbilical and Fetal Flow in Europe (TRUFFLE)) performed in 20 European perinatal centers between 2005 and 2010. Women with a singleton fetus at 26–32 weeks of gestation, with abdominal circumference < 10 th percentile and umbilical artery Doppler pulsatility index > 95 th percentile, were recruited. The main outcome measure was a composite of fetal or neonatal death or severe morbidity: survival to discharge with severe brain injury, bronchopulmonary dysplasia, proven neonatal sepsis or necrotizing enterocolitis. Results: Five‐hundred and three of 542 eligible women formed the study group. Mean ± SD gestational age at diagnosis was 29 ± 1.6 weeks and mean ± SD estimated fetal weight was 881 ± 217 g; 12 (2.4%) babies died in utero. Gestational age at delivery was 30.7 ± 2.3 weeks, and birth weight was 1013 ± 321 g. Overall, 81% of deliveries were indicated by fetal condition and 97% were by Cesarean section. Of 491 liveborn babies, outcomes were available for 490 amongst whom there were 27 (5.5%) deaths and 118 (24%) babies suffered severe morbidity. These babies were smaller at birth (867 ± 251 g) and born earlier (29.6 ± 2.0 weeks). Death and severe morbidity were significantly related to gestational age, both at study entry and delivery and also with the presence of maternal hypertensive morbidity. The median time to delivery was 13 days for women without hypertension, 8 days for those with gestational hypertension, 4 days for pre‐eclampsia and 3 days for HELLP syndrome. Conclusions: Fetal outcome in this study was better than expected from contemporary reports: perinatal death was uncommon (8%) and 70% survived without severe neonatal morbidity. The intervals to delivery, death and severe morbidity were related to the presence and severity of maternal hypertensive conditions. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.
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In TRUFFLE, maternal hypertension was present in 50% of pregnancies during the study and 70% of pregnancies at the time of delivery.
“In TRUFFLE, maternal hypertension was present in 50% of pregnancies during the study and 70% of pregnancies at the time of delivery.”
From Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction (2020) · cites this paper as [80]
The Results (page unavailable in our copy) report that 368 women (73%) had a hypertensive condition at delivery, supporting the claim's approximate 70%. They do not report 50% during the study; instead, they say the proportion with a gestational hypertensive condition increased by 13% between study entry and delivery. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe single most important prognostic factor in preterm fetuses with growth restriction is the gestational age at delivery.
“The single most important prognostic factor in preterm fetuses with growth restriction is the gestational age at delivery.80,83”
From Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction (2020) · cites this paper as [80]
The Results (page not available) say gestational age at delivery was strongly related to infant outcome, and babies with poor outcomes were delivered earlier. They do not identify it as the single most important prognostic factor; the Discussion instead calls maternal hypertension the major determinant of adverse outcome. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe pulsatility index, resistance index, or systolic-to-diastolic ratio can be used for quantification of the Doppler waveform in the umbilical artery, although recent studies have generally used either the pulsatility index or resistance index.
“The pulsatility index (PI), resistance index (RI), or systolicto-diastolic (S/D) ratio can be used for quantification of the Doppler waveform in the umbilical artery, although recent studies have generally used either the PI or RI.5,16,28,30,80,83”
From Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction (2020) · cites this paper as [80]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThe risks of stillbirth for AEDV and REDV are higher than the risk of infant mortality or severe morbidity at 33e34 weeks for AEDV and at 30e32 weeks for REDV as reported in TRUFFLE.
“These risks of stillbirth are higher than the risk of infant mortality or severe morbidity at 33e34 weeks for AEDV and at 30e32 weeks for REDV as reported in TRUFFLE.80”
From Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction (2020) · cites this paper as [80]
Table 4 (section labeled Discussion; page unavailable) reports neonatal death and severe morbidity by gestational age at delivery, providing TRUFFLE outcomes relevant to the comparison. But it does not separate AEDV from REDV or compare those groups’ stillbirth risks with infant outcomes at the stated weeks; that comparison is not established by this source. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe presence of a standardized protocol for diagnosis and management appears to be associated with more favorable outcomes, as evidenced in the TRUFFLE trial.
“Furthermore, the presence of a standardized protocol for diagnosis and management appears to be associated with more favorable outcomes, as evidenced in the better-than-expected perinatal morbidity and mortality in the Trial of Randomized Umbilical and Fetal Flow in Europe (TRUFFLE).80”
From Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction (2020) · cites this paper as [80]
Pregnant women with hypertension had a significantly shorter median interval from study enrollment to delivery, and newborns of mothers with hypertension were delivered at an earlier gestational age and had lower birthweights.
“Pregnant women with hypertension had a significantly shorter median interval from study enrollment to delivery, and newborns of mothers with hypertension were delivered at an earlier gestational age and had lower birthweights.80”
From Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction (2020) · cites this paper as [80]
The presence of maternal hypertension was one of the most important independent determinants of poor outcomes.
“The presence of maternal hypertension was one of the most important independent determinants of poor outcomes.16,80”
From Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction (2020) · cites this paper as [80]
Maternal hypertensive disease is common in early-onset fetal growth restriction and plays an important role in pregnancy outcomes.
“Maternal hypertensive disease is common in early-onset FGR and plays an important role in pregnancy outcomes.”
From Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction (2020) · cites this paper as [80]
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- Authors
- Lees, C., Marlow, N., Arabin, B., Bilardo, C. M., Brezinka, C., Derks, J. B., Duvekot, J., Frusca, T., Diemert, A., Ferrazzi, E., Ganzevoort, W., Hecher, K., Martinelli, P., Ostermayer, E., Papageorghiou, A. T., Schlembach, D., Schneider, K. T. M., Thilaganathan, B., Todros, T., van Wassenaer‐Leemhuis, A., Valcamonico, A., Visser, G. H. A., Wolf, H., & the TRUFFLE Group
- Affiliations
- Rosie Hospital (GB)
- University College London (GB)
- Isala (NL)
- University Medical Center Groningen (NL)
- Innsbruck Medical University (AT)
- Wilhelmina Children's Hospital (NL)
- Erasmus MC (NL)
- University of Brescia (IT)
- University Medical Center Hamburg-Eppendorf (DE)
- University of Milan (IT)
- Amsterdam UMC Location University of Amsterdam (NL)
- Federico II University Hospital (IT)
- Technical University of Munich (DE)
- St George's Hospital (GB)
- Medical University of Graz (AT)
- University of Turin (IT)
- Department of Neonatology Emma Children's Hospital Academic Medical Centre Amsterdam The Netherlands
- University Medical Center Utrecht (NL)
- Corresponding author
- Lees, C.
- ORCID
- Venue
- Ultrasound in Obstetrics & Gynecology
- Publisher
- Wiley
- Published
- 2013-09-23
- Volume
- 42
- Issue
- 4
- Pages
- 400-408
- ISSN
- 0960-7692 (ISSN-L)
- 1469-0705
- OpenAlex
- W1757974377
- Semantic Scholar
- 903b89ac05d154a0d0b6d59241f938d0831bb3ab
- Cited by
- 540
- References
- 22
- Citations by year
- 2026: 41 · 2025: 26 · 2024: 42 · 2023: 56 · 2022: 42 · 2021: 62 · 2020: 51 · 2019: 50 · 2018: 50 · 2017: 43 · 2016: 24 · 2015: 27 · 2014: 19 · 2013: 6 · 2012: 1
- FWCI
- 28.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Ultrasound in Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- National Institute for Health and Care Research (NF-SI-0512-10034)
- Imperial College London
- Imperial College Healthcare NHS Trust
- Universiteit Leiden
- ZonMw (94506556, 2509 AE)
- Radboud Universiteit
- Universiteit Maastricht
- Leids Universitair Medisch Centrum
- Università degli Studi di Torino
- Università degli Studi di Brescia
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Infant Development and Preterm Care
- Keywords
- early-onset fetal growth restriction, perinatal morbidity, perinatal mortality, preterm birth, prenatal diagnosis, gestational age at delivery, gestational hypertension, HELLP syndrome, neonatal brain injury, bronchopulmonary dysplasia, neonatal sepsis, necrotizing enterocolitis, truffles
- MeSH terms
- Adult, Europe, Female, Fetal Growth Retardation, Fetus, Gestational Age, Humans, Pregnancy, Pregnancy Outcome, Prospective Studies, Umbilical Arteries, Perinatal Care, Kaplan-Meier Estimate, Perinatal Mortality
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