title: Low-molecular-weight heparin added to aspirin in the  prevention of recurrent early-onset pre-eclampsia in women  with inheritable thrombophilia: the FRUIT-RCT.
abstract: BACKGROUND
  Early-onset hypertensive disorders (HD) of pregnancy and small-for-gestational age infants (SGA) are associated with placental vascular thrombosis, these often recur and are also associated with inheritable thrombophilia. Aspirin reduces the recurrence risk.
  
  
  OBJECTIVE
  Adding low-molecular-weight heparin (LMWH) to aspirin at < 12 weeks gestation reduces the recurrence of HD in women with previous early-onset HD (pre-eclampsia, hemolysis, elevated liver enzymes and low platelets [HELLP] syndrome and eclampsia) and/or SGA, in the context of inheritable thrombophilia without antiphospholipid antibodies.
  
  
  METHODS
  In a multicenter randomized control trial (RCT), 139 women included were< 12 weeks gestation.
  
  
  METHODS
  previous delivery< 34 weeks gestation with HD and/or SGA; inheritable thrombophilia (protein C deficiency, protein S deficiency, activated protein C resistance, factor V Leiden heterozygosity and prothrombin gene G20210A mutation heterozygosity); and no antiphospholipid antibodies detected.
  
  
  METHODS
  either daily LMWH (dalteparin, 5000 IU weight-adjusted dosage) with aspirin 80 mg or aspirin 80 mg alone.
  
  
  METHODS
  
  
  
  METHODS
  recurrent HD onset (i) < 34 weeks gestation and (ii) irrespective of gestational age.
  
  
  RESULTS
  recurrent SGA, preterm birth, maternal/neonatal hospitalization, spontaneous abortion and individual HD. Analysis by intention-to-treat.
  
  
  RESULTS
  Low-molecular-weight heparin with aspirin reduced recurrent HD onset < 34 weeks gestation (risk difference [RD] 8.7%: confidence interval [CI] of RD 1.9–15.5%; P = 0.012; number needed to treat [NNT] 12). Recurrent HD irrespective of gestational age was not different between the arms. No women withdrew as a result of adverse effects.
  
  
  BACKGROUND
  http://www.isrctn.org) (isrctn87325378).
  
  
  CONCLUSIONS
  Adding LMWH to aspirin at < 12 weeks gestation reduces recurrent HD onset < 34 weeks gestation in women with inheritable thrombophilia and prior delivery for HD/SGA <34 weeks. However, close monitoring of the mother and fetus remains important throughout pregnancy.
authors: Department of Obstetrics and Gynaecology, VU University Medical Center, Amsterdam, the Netherlands. jip.devries@vumc.nl
authors: Johanna I P
authors: JI
authors: de Vries
authors: M G
authors: MG
authors: van Pampus
authors: W M
authors: WM
authors: Hague
authors: P D
authors: PD
authors: Bezemer
authors: J H
authors: JH
authors: Joosten
mesh_terms: D001241:Aspirin / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D005865:Gestational Age; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006801:Humans; D011225:Pre-Eclampsia / Q000188:drug therapy / Q000517:prevention & control*; D011247:Pregnancy; D055502:Secondary Prevention; D019851:Thrombophilia / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D006495:Heparin, Low-Molecular-Weight; D001241:Aspirin