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1. Phase-rectified signal averaging method to predict perinatal outcome in infants with very preterm fetal growth restriction- a secondary analysis of TRUFFLE-trial.

Author

Lobmaier SM, Mensing van Charante N, Ferrazzi E, Giussani DA, Shaw CJ, Müller A, Ortiz JU, Ostermayer E, Haller B, Prefumo F, Frusca T, Hecher K, Arabin B, Thilaganathan B, Papageorghiou AT, Bhide A, Martinelli P, Duvekot JJ, van Eyck J, Visser GH, Schmidt G, Ganzevoort W, Lees CC, and Schneider KT

Subjects
Adult, Apgar Score, Developmental Disabilities diagnosis, Developmental Disabilities etiology, Female, Fetal Growth Retardation physiopathology, Humans, Infant, Newborn, Longitudinal Studies, Male, Predictive Value of Tests, Pregnancy, Prognosis, ROC Curve, Cardiotocography methods, Fetal Growth Retardation diagnosis, Heart Rate, Fetal physiology, Signal Processing, Computer-Assisted
Abstract

Background: Phase-rectified signal averaging, an innovative signal processing technique, can be used to investigate quasi-periodic oscillations in noisy, nonstationary signals that are obtained from fetal heart rate. Phase-rectified signal averaging is currently the best method to predict survival after myocardial infarction in adult cardiology. Application of this method to fetal medicine has established significantly better identification than with short-term variation by computerized cardiotocography of growth-restricted fetuses., Objective: The aim of this study was to determine the longitudinal progression of phase-rectified signal averaging indices in severely growth-restricted human fetuses and the prognostic accuracy of the technique in relation to perinatal and neurologic outcome., Study Design: Raw data from cardiotocography monitoring of 279 human fetuses were obtained from 8 centers that took part in the multicenter European "TRUFFLE" trial on optimal timing of delivery in fetal growth restriction. Average acceleration and deceleration capacities were calculated by phase-rectified signal averaging to establish progression from 5 days to 1 day before delivery and were compared with short-term variation progression. The receiver operating characteristic curves of average acceleration and deceleration capacities and short-term variation were calculated and compared between techniques for short- and intermediate-term outcome., Results: Average acceleration and deceleration capacities and short-term variation showed a progressive decrease in their diagnostic indices of fetal health from the first examination 5 days before delivery to 1 day before delivery. However, this decrease was significant 3 days before delivery for average acceleration and deceleration capacities, but 2 days before delivery for short-term variation. Compared with analysis of changes in short-term variation, analysis of (delta) average acceleration and deceleration capacities better predicted values of Apgar scores <7 and antenatal death (area under the curve for prediction of antenatal death: delta average acceleration capacity, 0.62 [confidence interval, 0.19-1.0]; delta short-term variation, 0.54 [confidence interval, 0.13-0.97]; P=.006; area under the curve for prediction Apgar <7: average deceleration capacity <24 hours before delivery, 0.64 [confidence interval, 0.52-0.76]; short-term variation <24 hours before delivery, 0.53 [confidence interval, 0.40-0.65]; P=.015). Neither phase-rectified signal averaging indices nor short-term variation showed predictive power for developmental disability at 2 years of age (Bayley developmental quotient, <95 or <85)., Conclusion: The phase-rectified signal averaging method seems to be at least as good as short-term variation to monitor progressive deterioration of severely growth-restricted fetuses. Our findings suggest that for short-term outcomes such as Apgar score, phase-rectified signal averaging indices could be an even better test than short-term variation. Overall, our findings confirm the possible value of prospective trials based on phase-rectified signal averaging indices of autonomic nervous system of severely growth-restricted fetuses., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Published
2016
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2. Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol

Author

Mylrea-Foley, Bronacha, Thornton, Jim G, Mullins, Edward, Marlow, Neil, Hecher, Kurt, Ammari, Christina, Arabin, Birgit, Berger, Astrid, Bergman, Eva, Bhide, Amarnath, Bilardo, Caterina, Binder, Julia, Breeze, Andrew, Brodszki, Jana, Calda, Pavel, Cannings-John, Rebecca, Černý, Andrej, Cesari, Elena, Cetin, Irene, Dall'Asta, Andrea, Diemert, Anke, Ebbing, Cathrine, Eggebø, Torbjørn, Fantasia, Ilaria, Ferrazzi, Enrico, Frusca, Tiziana, Ghi, Tullio, Goodier, Jenny, Greimel, Patrick, Gyselaers, Wilfried, Hassan, Wassim, Von Kaisenberg, Constantin, Kholin, Alexey, Klaritsch, Philipp, Krofta, Ladislav, Lindgren, Peter, Lobmaier, Silvia, Marsal, Karel, Maruotti, Giuseppe M, Mecacci, Federico, Myklestad, Kirsti, Napolitano, Raffaele, Ostermayer, Eva, Papageorghiou, Aris, Potter, Claire, Prefumo, Federico, Raio, Luigi, Richter, Jute, Sande, Ragnar Kvie, Schlembach, Dietmar, Schleußner, Ekkehard, Stampalija, Tamara, Thilaganathan, Basky, Townson, Julia, Valensise, Herbert, Visser, Gerard Ha, Wee, Ling, Wolf, Hans, Lees, TRUFFLE 2 Collaborators List: Andrea Smith, Christoph C., Andrew, Sharp, Andy, Simm, Angela, Ramoni, Barry, Lloyd, Bianca, Masturzo, Christine, Morfeld, Christopher, Lloyd, Claudia, Seidig, Danielle, Thornton, Elena, Mantovani, Emanuela, Taricco, Bertucci, Emma, Erich, Cosmi, Eva, Ostermayer, Ferenc, Macsali, Ferrari, Francesca, Francesco, D'Antonio, Francesco, Picciotto, Gareth, Waring, Georgios, Rembouskos, Giuseppe, Cali, Giuseppe, Rizzo, Grazia Maria Tiralongo, Ilaria, Fantasia, Ilaria Giuditta Ramezzana, Ilenia, Mappa, Ioannis, Kyvernitakis, Iris, Derwig, Iris, Dressler-Steinbach, Jiří, Vojěch, Jørgen, Linde, Julia, Binder, Karen, Melchiorre, Kate, Walker, Kinga, Chalubinski, Kristiina, Rull, Kristina, Kernell, Lars, Brodowski, Laura, Sarno, Ligita, Jokibkiene, Liina, Rajasalu, Lina-Ana, Fryszer, Louisa, Jones, Magdalena, Bednarek-Jędrzejek, Makrina, Savvidou, Maria, Stefopoulou, Marianna, Rambaldi, Mark, Kilby, Nia, Jones, Nicola, Fratelli, Nishigandh, Deole, Patrick, Greimel, Petra, Pateisky, Pilar, Palmrich, Ralf, Schild, Roland, Devlieger, Sabina, Ondrová, Sarah, Gumpert, Sasha, Taylor, Saskia, Schmidt, Sebastian, Kwiatkowski, Serena, Caterina, Serena, Ottanelli, Serena, Simeone, Sergio, Ferrazzani, Silvia, Salvi, Silvia, Visentin, Sofia, Amylidi-Mohr, Spyros, Bakalis, Stefan, Verlohren, Susanne, Dargel, Sven, Kehl, Tanja, Groten, Tatjana, Radaelli, Tinne, Mesens, Tiziana, Fanelli, Torbjørn, Eggebø, Tullio, Ghi, Tuuli, Haabpiht, Wassim, Hassan, Yvonne, Heiman, Zulfiya, Khodzhaeva, Baskaran, Thilaganathan, Christoph, Brezinka, Sanne, Gordijn, Wessel, Ganzevoort, Abin Thomas Andrea Smith, Abin, Thomas, Mylrea-Foley, Bronacha, Thornton, Jim G, Mullins, Edward, Marlow, Neil, Hecher, Kurt, Ammari, Christina, Arabin, Birgit, Berger, Astrid, Bergman, Eva, Bhide, Amarnath, Bilardo, Caterina, Binder, Julia, Breeze, Andrew, Brodszki, Jana, Calda, Pavel, Cannings-John, Rebecca, Černý, Andrej, Cesari, Elena, Cetin, Irene, Dall'Asta, Andrea, Diemert, Anke, Ebbing, Cathrine, Eggebø, Torbjørn, Fantasia, Ilaria, Ferrazzi, Enrico, Frusca, Tiziana, Ghi, Tullio, Goodier, Jenny, Greimel, Patrick, Gyselaers, Wilfried, Hassan, Wassim, Von Kaisenberg, Constantin, Kholin, Alexey, Klaritsch, Philipp, Krofta, Ladislav, Lindgren, Peter, Lobmaier, Silvia, Marsal, Karel, Maruotti, Giuseppe M, Mecacci, Federico, Myklestad, Kirsti, Napolitano, Raffaele, Ostermayer, Eva, Papageorghiou, Ari, Potter, Claire, Prefumo, Federico, Raio, Luigi, Richter, Jute, Sande, Ragnar Kvie, Schlembach, Dietmar, Schleußner, Ekkehard, Stampalija, Tamara, Thilaganathan, Basky, Townson, Julia, Valensise, Herbert, Visser, Gerard Ha, Wee, Ling, Wolf, Han, Lees, Christoph C, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), and National Institute for Health Research

Subjects
fetal medicine, Cardiotocography, PREDICTION, 610 Medicine & health, Reproduktionsmedicin och gynekologi, TRUFFLE 2 Collaborators List, Ultrasonography, Prenatal, 1117 Public Health and Health Services, Fetal, Medicine, General & Internal, AGE, Heart Rate, Pregnancy, Obstetrics, Gynecology and Reproductive Medicine, General & Internal Medicine, GROWTH RESTRICTION, Humans, Prenatal, Child, Randomized Controlled Trials as Topic, maternal medicine, Obstetrics and gynaecology, ultrasonography, Science & Technology, Fetal Growth Retardation, Infant, Newborn, Infant, 1103 Clinical Sciences, General Medicine, Heart Rate, Fetal, Newborn, ddc, DOPPLER, Fetal Weight, Settore MED/40, Female, Premature Birth, Life Sciences & Biomedicine, 1199 Other Medical and Health Sciences, Human
Abstract

IntroductionFollowing the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years.Methods and analysisWomen with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is Ethics and disseminationThe Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy.Trial registration numberMain sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

Published
2022

3. Comparative analysis of 2-year outcomes in GRIT and TRUFFLE trials

Author

Ganzevoort, W., Thornton, J. G., Marlow, N., Thilaganathan, B., Arabin, B., Prefumo, F., Lees, C., Wolf, H., Van Bulck, B, Kalakoutis, G M, Sak, P, Schneider, K T M, Karpathios, S E, Major, T, Todros, T, Arduini, D, Flumini, C, Tenore, A C, Roncaglia, N, Frusca, T, Ferretti, G, Weinans, M J N, Roosmalen, J, Slikke, J W, Geijn, H, Pernet, P J M, Wolf, H, Stigter, R H, Wilczynski, J, Vasco, E, Abdullah, M, Novak‐Antolic, Z, Danielian, P, Jenkinson, S D, Welch, C R, Griffin, C, Gee, H, Tuffnell, D, Cresswell, J, Tariq, T, Sengupta, B, Tydeman, G, Churchill, D, Bewley, S, Fusi, L, Lindow, S W, Johal, W, Fairlie, F M, Neales, K, Mason, G, Scudamore, I, Konje, J, Walkinshaw, S A, Griffiths, M, Dawson, A, Mires, G, Johanson, R, Fraser, R B, Ibbs, P Hendy, Steel, S A, Ramsay, M, Robins, J B, Heard, M J, Tonge, H M, Manyonda, I T, Walker, J, Maresh, M, Yoong, A, Soothill, P, Cameron, H, Byrne, D, Beattie, B, Bober, S, Van Damme, M, Kyriakides, S, Pokorna, P, Zimmerman, A, Tsitsikas, H, Mani, E, Bosisio, P, Mastritta, E, Nicocia, M, Fabris, C, Eken, P, De Vries, L, Kubicka, Z, Ramalho, R, Rashid, M, Cerar‐Kornhauser, L, Thomas, S, Elliman, A, Sim, T, Swaminathan, S, Walker, L, McCormick, D, Sibanda, Z, Hughes, J, Kilding, J, O'Hara, A, Harpin, V, Porter, N, Pandey, S, Murtagh, K, Burton, K, MacGregor, R, Stewart, B, Klenke, H, Hallam, P, Kai, N, Graham, M, Harrison, A, Saharia, E, McGhee, T, Rowsell, P, Howie, P, Parmar, Max, Field, D, Grant, A, Steer, P, Breart, G, Levene, M, Torgeson, D, Kitzinger, S, Marlowe, N, Wolke, Dieter, Johnson, A, Arabin, Birgit, Bilardo, Caterina M, Brezinka, Christoph, Cornette, Jerome M J, Derks, Jan B, Diemert, Anke, Duvekot, Johannes J, Ferrazzi, Enrico, Fratelli, Nicola, Frusca, Tiziana, Ganzevoort, Wessel, Hecher, Kurt, Leemhuis, Aleid, Lees, Christoph C, Lobmaier, Silvia, Marlow, Neil, Martinelli, Pasquale, Maso, Gianpaolo, Missfelder‐Lobos, Hannah, Napolitano, Raffaele, Ostermayer, Eva, Papageorghiou, Aris T, Prefumo, Federico, Schlembach, Dietmar, Thilaganathan, Baskaran, Todros, Tullia, Valcamonico, Adriana, Visser, Gerard H A, Wolf, Hans, Kingdom, John, Marsal, Karel, Thornton, Jim, Valensise, Herbert, Athena Institute, APH - Global Health, APH - Quality of Care, Obstetrics and gynaecology, Papageorghiou, AT, Obstetrics and Gynaecology, AR&D - Amsterdam Reproduction & Development, and APH - Digital Health

Subjects
short‐term variation, Technology, FLOW, INFANTS, cardiotocography, ductus venosus, fetal growth restriction, monitoring, short-term variation, Umbilical Arteries, Cohort Studies, 0302 clinical medicine, Obstetrics and gynaecology, Pregnancy, GROWTH RESTRICTION, Cardiotocography, 030212 general & internal medicine, Randomized Controlled Trials as Topic, Fetal Growth Retardation, 030219 obstetrics & reproductive medicine, Radiological and Ultrasound Technology, medicine.diagnostic_test, Obstetrics, Radiology, Nuclear Medicine & Medical Imaging, short term variation, Pregnancy Outcome, Obstetrics & Gynecology, Obstetrics and Gynecology, Gestational age, General Medicine, Original Papers, TRUFFLE Study Group, Settore MED/40, Pulsatile Flow, Gestation, Female, Life Sciences & Biomedicine, INTERVENTION, Blood Flow Velocity, Ductus venosus, Cohort study, medicine.medical_specialty, Birth weight, FETAL HEART-RATE, Ultrasonography, Prenatal, 03 medical and health sciences, SDG 3 - Good Health and Well-being, FETUSES, medicine, Humans, Radiology, Nuclear Medicine and imaging, Obstetrics & Reproductive Medicine, Fetal Death, GRIT Study Group, Original Paper, Fetus, Science & Technology, business.industry, Infant, Newborn, Acoustics, Reproductive Medicine, 1114 Paediatrics and Reproductive Medicine, business
Abstract

Objective To explore the effect on perinatal outcome of different fetal monitoring strategies for early‐onset fetal growth restriction (FGR). Methods This was a cohort analysis of individual participant data from two European multicenter trials of fetal monitoring methods for FGR: the Growth Restriction Intervention Study (GRIT) and the Trial of Umbilical and Fetal Flow in Europe (TRUFFLE). All women from GRIT (n = 238) and TRUFFLE (n = 503) who were randomized between 26 and 32 weeks' gestation were included. The women were grouped according to intervention and monitoring method: immediate delivery (GRIT) or delayed delivery with monitoring by conventional cardiotocography (CTG) (GRIT), computerized CTG (cCTG) only (GRIT and TRUFFLE) or cCTG and ductus venosus (DV) Doppler (TRUFFLE). The primary outcome was survival without neurodevelopmental impairment at 2 years of age. Results Gestational age at delivery and birth weight were similar in both studies. Fetal death rate was similar between the GRIT and TRUFFLE groups, but neonatal and late death were more frequent in GRIT (18% vs 6%; P, This article's abstract has been translated into Spanish and Chinese. Follow the links from the http://onlinelibrary.wiley.com/doi/10.1002/uog.20354/abstract to view the translations. This article has been selected for Journal Club. Click https://www.isuog.org/resource/uog-journal-club-January-2020.html to view slides and discussion points.

Published
2020

4. 2 Year Neurodevelopmental and Intermediate Perinatal Outcomes in Infants With Very Preterm Fetal Growth Restriction (TRUFFLE): A Randomised Trial

Author

Lees, Christoph C., Marlow, Neil, Van Wassenaer-Leemhuis, Aleid, Arabin, Birgit, Bilardo, Caterina M., Brezinka, Christoph, Calvert, Sandra, Derks, Jan B., Diemert, Anke, Duvekot, Johannes J., Ferrazzi, Enrico, Frusca, Tiziana, Ganzevoort, Wessel, Hecher, Kurt, Martinelli, Pasquale, Ostermayer, Eva, Papageorghiou, Aris T., Schlembach, Dietmar, Schneider, K. T M, Thilaganathan, Baskaran, Todros, Tullia, Valcamonico, Adriana, Visser, Gerard H A, Wolf, Hans, Aktas, Ayse, Borgione, Silvia, Chaoui, Rabih, Cornette, Jerome M J, Diehl, Thilo, Van Eyck, Jim, Fratelli, Nicola, Van Haastert, Inge Lot, Lobmaier, Silvia, Lopriore, Enrico, Missfelder-Lobos, Hannah, Mansi, Giuseppina, Martelli, Paola, Maso, Gianpaolo, Maurer-Fellbaum, Ute, Van Charante, Nico Mensing, De Tollenaer, Susanne Mulder, Napolitano, Raffaele, Oberto, Manuela, Oepkes, Dick, Ogge, Giovanna, Van Der Post, Joris, Prefumo, Federico, Preston, Lucy, Raimondi, Francesco, Reiss, Irwin K M, Scheepers, H. C J, Schuit, Ewoud, Skabar, Aldo, Spaanderman, Marc, Weisglas-Kuperus, Nynke, Zimmermann, Andrea, Moore, Tamanna, Johnson, Samantha, Rigano, Serena, Other Research, Neonatology, Other departments, Amsterdam Public Health, Obstetrics and Gynaecology, Obstetrics and gynaecology, Reproductive Origins of Adult Health and Disease (ROAHD), RS: GROW - Developmental Biology, RS: GROW - R4 - Reproductive and Perinatal Medicine, Obstetrie & Gynaecologie, MUMC+: MA Medische Staf Obstetrie Gynaecologie (9), APH - Amsterdam Public Health, ARD - Amsterdam Reproduction and Development, Christoph C., Lee, Neil, Marlow, Aleid van Wassenaer, Leemhui, Birgit, Arabin, Caterina M., Bilardo, Christoph, Brezinka, Sandra, Calvert, Jan B., Derk, Anke, Diemert, Johannes J., Duvekot, Enrico, Ferrazzi, Tiziana, Frusca, Wessel, Ganzevoort, Kurt, Hecher, Martinelli, Pasquale, Eva, Ostermayer, Aris T., Papageorghiou, Dietmar, Schlembach, K. T. M., Schneider, Baskaran, Thilaganathan, Tullia, Todro, Adriana, Valcamonico, Gerard H. A., Visser, Hans, Wolf, for the TRUFFLE study, group, Borgione, Silvia, Fratelli, Nicola, Lobmaier, Silvia, Lopriore, Enrico, Mansi, Giuseppina, Martelli, Paola, Maso, Gianpaolo, Napolitano, Raffaele, Oberto, Manuela, Prefumo, Federico, Raimondi, Francesco, Rigano, Serena, and Obstetrics & Gynecology

Subjects
Male, Percentile, Pediatrics, Cardiotocography, CHILDREN, Umbilical Arteries, law.invention, Primary outcome, Randomized controlled trial, Heart Rate, law, Central Nervous System Diseases, Pregnancy, Fetal growth, Clinical endpoint, Prenatal, GESTATION, Child, PREDICTORS, Non-U.S. Gov't, Ultrasonography, Medicine(all), Fetal Growth Retardation, medicine.diagnostic_test, Medicine (all), Research Support, Non-U.S. Gov't, Pregnancy Outcome, Obstetrics and Gynecology, Gestational age, Pulsed, General Medicine, Heart Rate, Fetal, Very preterm, Neonatal morbidity, DOPPLER, Europe, Multicenter Study, PREECLAMPSIA, Ultrasonography, Doppler, Pulsed, Child, Preschool, Infant, Extremely Premature, Randomized Controlled Trial, Gestation, Female, Gestational Age, Humans, Infant, Newborn, Ultrasonography, Prenatal, INTERVENTION, Ductus venosus, Human, Reversed flow, medicine.medical_specialty, Extremely Premature, Research Support, PARAMETERS, Fetal, AGE, HEART-RATE VARIATION, SDG 3 - Good Health and Well-being, medicine, Journal Article, Preschool, Fetus, Intention-to-treat analysis, business.industry, RETARDED FETUSES, Infant, Newborn, medicine.disease, Umbilical Arterie, Central Nervous System Disease, business
Abstract

No consensus exists for the best way to monitor and when to trigger delivery in mothers of babies with fetal growth restriction. We aimed to assess whether changes in the fetal ductus venosus Doppler waveform (DV) could be used as indications for delivery instead of cardiotocography short-term variation (STV). In this prospective, European multicentre, unblinded, randomised study, we included women with singleton fetuses at 26-32 weeks of gestation who had very preterm fetal growth restriction (ie, low abdominal circumference [ 95th percentile]). We randomly allocated women 1:1:1, with randomly sized blocks and stratified by participating centre and gestational age ( 95th percentile; DV p95), or late DV changes (A wave [the deflection within the venous waveform signifying atrial contraction] at or below baseline; DV no A). The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley III developmental score of less than 85, at 2 years of age. We assessed outcomes in surviving infants with known outcomes at 2 years. We did an intention to treat study for all participants for whom we had data. Safety outcomes were deaths in utero and neonatal deaths and were assessed in all randomly allocated women. This study is registered with ISRCTN, number 56204499. Between Jan 1, 2005 and Oct 1, 2010, 503 of 542 eligible women were randomly allocated to monitoring groups (166 to CTG STV, 167 to DV p95, and 170 to DV no A). The median gestational age at delivery was 30·7 weeks (IQR 29·1-32·1) and mean birthweight was 1019 g (SD 322). The proportion of infants surviving without neuroimpairment did not differ between the CTG STV (111 [77%] of 144 infants with known outcome), DV p95 (119 [84%] of 142), and DV no A (133 [85%] of 157) groups (ptrend=0·09). 12 fetuses (2%) died in utero and 27 (6%) neonatal deaths occurred. Of survivors, more infants where women were randomly assigned to delivery according to late ductus changes (133 [95%] of 140, 95%, 95% CI 90-98) were free of neuroimpairment when compared with those randomly assigned to CTG (111 [85%] of 131, 95% CI 78-90; p=0.005), but this was accompanied by a non-significant increase in perinatal and infant mortality. Although the difference in the proportion of infants surviving without neuroimpairment was non-significant at the primary endpoint, timing of delivery based on the study protocol using late changes in the DV waveform might produce an improvement in developmental outcomes at 2 years of age. ZonMw, The Netherlands and Dr Hans Ludwig Geisenhofer Foundation, Germany

Published
2015

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