OBJECTIVES: To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction. METHODS: This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10th percentile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 percentile points from the 20-week scan. Composite adverse outcome comprised both immediate adverse birth outcome and major neonatal morbidity. Using a range of cut-off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored. RESULTS: The study population comprised 856 women. There were two (0.2%) intrauterine deaths. Median gestational age at delivery was 38 (interquartile range (IQR), 37-39) weeks and birth weight was 2478 (IQR, 2140-2790) g. Compared with infants with normal outcome, those with composite adverse outcome (n = 93; 11%) were delivered at an earlier gestational age (36 vs 38 weeks) and had a lower birth weight (1900 vs 2540 g). The first Doppler observation of MCA pulsatility index < 5th percentile and UCR Z-score above gestational-age-specific thresholds (1.5 at 32-33 weeks and 1.0 at 34-36 weeks) had the highest relative risks (RR) for composite adverse outcome (RR 2.2 (95% CI, 1.5-3.2) and RR 2.0 (95% CI, 1.4-3.0), respectively). After adjustment for confounders, the association between UCR Z-score and composite adverse outcome remained significant, although gestational age at delivery and birth-weight Z-score had a stronger association. CONCLUSION: In this prospective multicenter study, signs of cerebral blood flow redistribution were found to be associated with adverse outcome in late preterm singleton pregnancies at risk of fetal growth restriction. Whether cerebral redistribution is a marker describing the severity of fetal growth restriction or an independent risk factor for adverse outcome remains unclear, and whether it is useful for clinical management can be answered only in a randomized trial. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Center for Fetal Medicine Karolinska University Hospital Stockholm Sweden

Centre for Trials Research College of Biomedical and Life Sciences Cardiff University Cardiff UK

Department of Gynecology and Obstetrics UZ Leuven and Department of Regeneration and Development KU Leuven Leuven Belgium

Department of Health Sciences University of Florence Obstetrics and Gynecology Careggi University Hospital Florence Italy

Department of Medicine Surgery and Health Sciences University of Trieste Trieste Italy

Department of Neurosciences Reproductive and Dentistry Sciences University of Naples 'Federico II' Naples Italy

Department of Obstetrics and Fetal Medicine University Medical Centre Hamburg Eppendorf Hamburg Germany

Department of Obstetrics and Gynaecology General University Hospital and 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Obstetrics and Gynaecology University Medical Center Groningen University of Groningen Groningen The Netherlands

Department of Obstetrics and Gynaecology Ziekenhuis Oost Limburg Genk and Department Physiology Hasselt University Diepenbeek Belgium

Department of Obstetrics and Gynecology Amsterdam University Medical Centers University of Amsterdam Amsterdam Reproduction and Development Research Institute Amsterdam The Netherlands

Department of Obstetrics and Gynecology ASST Spedali Civili di Brescia and University of Brescia Brescia Italy

Department of Obstetrics and Gynecology Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Department of Clinical Sciences and Community Health Università degli Studi di Milano Milan Italy

Department of Obstetrics and Gynecology Haukeland University Hospital Bergen Norway

Department of Obstetrics and Gynecology Klinikum Rechts Der Isar Technical University of Munich Munich Germany

Department of Obstetrics and Gynecology Medical University of Graz Graz Austria

Department of Obstetrics and Gynecology Medical University of Innsbruck Innsbruck Austria

Department of Obstetrics and Gynecology Stavanger University Hospital Stavanger and Department of Clinical Science University of Bergen Bergen Norway

Department of Obstetrics and Gynecology University Hospital of Bern Bern Switzerland

Department of Obstetrics and Gynecology University of Parma Parma Italy

Department of Obstetrics and Gynecology Vittore Buzzi Children's Hospital University of Milan Milan Italy

Department of Obstetrics Charite Humboldt University Berlin and Clara Angela Foundation Berlin Germany

Department of Obstetrics Division of Woman and Baby University Medical Center Utrecht Utrecht The Netherlands

Department of Pediatric Surgery and Neonatology Lund University Skane University Hospital Lund Sweden

Department of Perinatal Medicine University of Utrecht Utrecht The Netherlands

Department of Surgery Division of Obstetrics and Gynecology Tor Vergata University Policlinico Casilino Hospital Rome Italy

Department of Women's and Children's Health Uppsala University Uppsala Sweden

Faculty of Medicine and Life Sciences Hasselt University Agoralaan Diepenbeek Belgium

Fetal Medicine Unit Leeds General Infirmary Leeds Teaching Hospitals NHS Trust Leeds UK

Fetal Medicine Unit St George's University Hospitals NHS Foundation Trust and Molecular and Clinical Sciences Research Institute St George's University of London London UK

Fetal Medicine Unit University College London Hospitals NHS Foundation Trust London UK

Imperial College School of Medicine Imperial College London and Department of Fetal Medicine Queen Charlotte's and Chelsea Hospital Imperial College NHS trust London UK

Institute for the Care of Mother and Child Prague Czech Republic and 3rd Medical Faculty Charles University Prague Czech Republic

School of Clinical Sciences University of Nottingham Division of Obstetrics and Gynaecology Maternity Department City Hospital Nottingham UK

St Olav's Hospital Trondheim Norway

The Princess Alexandra Hospital NHS Trust Harlow UK

UCL Elizabeth Garrett Anderson Institute for Women's Health University College London London UK

Unit of Fetal Medicine and Prenatal Diagnosis Institute for Maternal and Child Health IRCCS Burlo Garofolo Trieste Italy

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