title: Placental growth factor as a marker of fetal growth restriction caused by placental dysfunction.
abstract: Discriminating between placentally-mediated fetal growth restriction and constitutionally-small fetuses is a challenge in obstetric practice. Placental growth factor (PlGF), measurable in the maternal circulation, may have this discriminatory capacity.
  
  
  
  Plasma PlGF was measured in women presenting with suspected fetal growth restriction (FGR; ultrasound fetal abdominal circumference <10th percentile for gestational age) at sites in Canada, New Zealand and the United Kingdom. When available, placenta tissue underwent histopathological examination for lesions indicating placental dysfunction, blinded to PlGF and clinical outcome. Lesions were evaluated according to pre-specified severity criteria and an overall severity grade was assigned (0-3, absent to severe). Low PlGF (concentration <5th percentile for gestational age) to identify placental FGR (severity grade≥2) was assessed and compared with routine parameters for fetal assessment. For all cases, the relationship between PlGF and the sampling-to-delivery interval was determined.
  
  
  
  Low PlGF identified placental FGR with an area under the receiver-operator characteristic curve of 0.96 [95% CI 0.93-0.98], 98.2% [95% CI 90.5-99.9] sensitivity and 75.1% [95% CI 67.6-81.7] specificity. Negative and positive predictive values were 99.2% [95% CI 95.4-99.9] and 58.5% [95% CI 47.9-68.6], respectively. Low PlGF outperformed gestational age, abdominal circumference and umbilical artery resistance index in predicting placental FGR. Very low PlGF (<12 pg/mL) was associated with shorter sampling-to-delivery intervals than normal PlGF (13 vs. 29.5 days, P < 0.0001).
  
  
  
  Low PlGF identifies small fetuses with significant underlying placental pathology and is a promising tool for antenatal discrimination of FGR from fetuses who are constitutionally-small.
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, University of British Columbia, 4500 Oak Street, Vancouver, British Columbia, V6H 3N1, Canada. Electronic address: sbenton@uottawa.ca.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Benton
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand. Electronic address: l.mccowan@auckland.ac.nz.
authors.forename: Lesley M
authors.initials: LM
authors.lastname: McCowan
authors.affiliation: Maternal and Fetal Health Research Centre, University of Manchester, 5th Floor, St. Mary's Hospital, Oxford Road, Manchester, M13 9WL, United Kingdom. Electronic address: Alexander.Heazell@manchester.ac.uk.
authors.forename: Alexander E P
authors.initials: AE
authors.lastname: Heazell
authors.affiliation: Department of Pathology, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, Ontario, K1H 8L1, Canada. Electronic address: dgrynspan@cheo.on.ca.
authors.forename: David
authors.initials: D
authors.lastname: Grynspan
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, University of British Columbia, 4500 Oak Street, Vancouver, British Columbia, V6H 3N1, Canada. Electronic address: jhutcheon@cfri.ca.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Hutcheon
authors.affiliation: Department of Pathology, Children's and Women's Health Centre of British Columbia, 4500 Oak Street, Vancouver, British Columbia, V6H 2N9, Canada. Electronic address: csenger@cw.bc.ca.
authors.forename: Christof
authors.initials: C
authors.lastname: Senger
authors.affiliation: Nuffield Department of Population Health, Institute of Health Sciences, University of Oxford, Old Road, Oxford, OX3 7LF, United Kingdom. Electronic address: orlaith.burke@ndph.ox.ac.uk.
authors.forename: Orlaith
authors.initials: O
authors.lastname: Burke
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand. Electronic address: Yuen.Chan@monashhealth.org.
authors.forename: Yuen
authors.initials: Y
authors.lastname: Chan
authors.affiliation: Liggins Institute, University of Auckland, Private Bag 92019, Victoria Street West, Auckland, 1142, New Zealand. Electronic address: j.harding@auckland.ac.nz.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Harding
authors.affiliation: Sprott Centre for Stem Cell Research, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada. Electronic address: jyockell@ohri.ca.
authors.forename: Julien
authors.initials: J
authors.lastname: Yockell-Lelièvre
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, University of British Columbia, 4500 Oak Street, Vancouver, British Columbia, V6H 3N1, Canada. Electronic address: yhu@cw.bc.ca.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Women's Health Academic Centre, King's College London, 10th Floor North Wing, St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, United Kingdom. Electronic address: lucy.chappell@kcl.ac.uk.
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Chappell
authors.affiliation: Women's Health Academic Centre, King's College London, 10th Floor North Wing, St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, United Kingdom. Electronic address: melanie.griffin@kcl.ac.uk.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Griffin
authors.affiliation: Women's Health Academic Centre, King's College London, 10th Floor North Wing, St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, United Kingdom. Electronic address: andrew.shennan@kcl.ac.uk.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Shennan
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, University of British Columbia, 4500 Oak Street, Vancouver, British Columbia, V6H 3N1, Canada. Electronic address: LMagee@sgul.ac.uk.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Magee
authors.affiliation: Department of Obstetrics and Gynaecology, University of Ottawa, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada.
authors.forename: Andrée
authors.initials: A
authors.lastname: Gruslin
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, University of British Columbia, 4500 Oak Street, Vancouver, British Columbia, V6H 3N1, Canada. Electronic address: pvondade@sgul.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: von Dadelszen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D036861:Delivery, Obstetric; D005260:Female; D005317:Fetal Growth Retardation / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D006801:Humans; D010920:Placenta / Q000473:pathology*; D000072483:Placenta Growth Factor / Q000097:blood*; D010927:Placental Insufficiency / Q000175:diagnosis* / Q000473:pathology; D011247:Pregnancy; D016216:Ultrasonography, Prenatal; D055815:Young Adult
chemical_list: D015415:Biomarkers; D000072483:Placenta Growth Factor
keywords: Diagnosis; Fetal growth restriction; Placental dysfunction; Placental growth factor; Placental lesions