title: Does low-molecular-weight heparin influence fetal growth or uterine and umbilical arterial Doppler in women with a history of early-onset uteroplacental insufficiency and an inheritable thrombophilia? Secondary randomised controlled trial results.
abstract: OBJECTIVE
  Does low-molecular-weight heparin (LMWH) added to low-dose aspirin influence fetal growth and flow velocity in uterine and umbilical arteries in women with an inheritable thrombophilia and previous early-onset uteroplacental insufficiency?
  
  
  METHODS
  Secondary outcomes of the FRUIT-RCT.
  
  
  METHODS
  Multicentre, international.
  
  
  METHODS
  The FRUIT-RCT included 139 women with inheritable thrombophilia before 12 weeks of gestation. Inclusion criteria were previous delivery before 34 weeks of gestation with a hypertensive disorder of pregnancy and/or small-for-gestational-age infant and an inheritable thrombophilia.
  
  
  METHODS
  After randomisation to either daily LMWH with aspirin, or aspirin only, ultrasound measurements were performed at 22-24, 28-30 and 34-36 weeks of gestation. Development during gestation of growth, birthweight and flow velocity of the umbilical artery was examined using the linear mixed model. Uterine artery flow velocity at a single time-point (22-24 weeks) was examined using a chi-square test.
  
  
  METHODS
  Fetal growth over time including birthweight, using Scandinavian, Dutch and customised growth curves; and flow velocity within the uterine and umbilical arteries.
  
  
  RESULTS
  No difference of fetal growth over time could be demonstrated between the study arms, regardless of which reference criteria were used. The flow velocity within the uterine artery and umbilical artery did not differ between study arms.
  
  
  CONCLUSIONS
  The addition of LMWH to aspirin did not influence fetal growth or umbilical artery flow velocity over time; nor did it influence uterine artery flow velocity.
  
  
  CONCLUSIONS
  LMWH does not influence fetal growth or uterine or umbilical flow velocities.
authors.affiliation: Department of Obstetrics and Gynaecology, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: Cnh
authors.initials: C
authors.lastname: Abheiden
authors.affiliation: Department of Obstetrics and Gynaecology, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: M E
authors.initials: ME
authors.lastname: Van Hoorn
authors.affiliation: Robinson Research Institute, University of Adelaide, Women's and Children's Hospital, North Adelaide, SA, Australia.
authors.forename: W M
authors.initials: WM
authors.lastname: Hague
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Kostense
authors.affiliation: Department of Obstetrics and Gynaecology, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands.
authors.forename: M G
authors.initials: MG
authors.lastname: van Pampus
authors.affiliation: Department of Obstetrics and Gynaecology, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: Jip
authors.initials: J
authors.lastname: de Vries
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D001724:Birth Weight / Q000187:drug effects; D001783:Blood Flow Velocity / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005317:Fetal Growth Retardation / Q000139:chemically induced* / Q000175:diagnosis; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D016014:Linear Models; D008297:Male; D010927:Placental Insufficiency / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000188:drug therapy* / Q000503:physiopathology; D011446:Prospective Studies; D019851:Thrombophilia / Q000188:drug therapy* / Q000503:physiopathology; D018608:Ultrasonography, Doppler; D016216:Ultrasonography, Prenatal; D014469:Umbilical Arteries / Q000000981:diagnostic imaging / Q000503:physiopathology; D055988:Uterine Artery / Q000000981:diagnostic imaging / Q000503:physiopathology
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D001241:Aspirin
keywords: Aspirin; fetal growth restriction; hypertensive disorders; inheritable thrombophilia; low-molecular-weight heparin; umbilical and uterine artery Doppler