title: Low-molecular-weight heparin plus aspirin versus aspirin alone in pregnant women with hereditary thrombophilia to improve live birth rate: meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  To determine in women with hereditary thrombophilia whether the use of the combination of low-molecular-weight heparin (LMWH) and aspirin (ASA) is better than ASA alone.
  
  
  METHODS
  Meta-analysis of randomized controlled trials evaluating LMWH + ASA compared to ASA in pregnant women with hereditary thrombophilia in order to improve live birth rate. A systematic literature search was conducted in 5 databases (PubMed, Cochrane Controlled Trials Register, EMBASE, Scopus and ISI Web of Knowledge). Trial selection, data extraction, and quality assessment were performed independently by two authors. The main outcome measure was live birth rate. Secondary outcomes included rates of first-trimester miscarriage, prematurity, pre-eclampsia, and low birth weight for gestational age babies.
  
  
  RESULTS
  Four trials were included in the quantitative synthesis in a total of 222 randomized women. Effect of LMWH + ASA versus ASA with regard to live births was evaluable in all four randomized controlled trials with a similar overall treatment effect for the therapies OR 1.7 (95 % CI 0.72-4.0) and without heterogeneity (I (2) = 0 %). No significant differences or heterogeneity were observed between groups for secondary outcomes, namely first-trimester miscarriages OR 0.69 (0.22-2.16), prematurity OR 0.99 (0.4-2.08), pre-eclampsia OR 1.49 (0.63-3.5), and small for gestational age babies OR 2.08 (0.96-4.47).
  
  
  CONCLUSIONS
  There were no significant differences in live birth weight and other pregnancy outcomes between LMWH + ASA versus ASA. However, these findings were based on few trials presenting methodological limitations. Therefore, there is no evidence to support any incremental benefit of adding LMWH to ASA alone in women with inherited thrombophilia.
authors.affiliation: Obstetric Unit, Coimbra University Hospital Centre, Rua Miguel Torga, 3030-165, Coimbra, Portugal. analuisareia@gmail.com.|Faculty of Medicine, Coimbra University, Coimbra, Portugal. analuisareia@gmail.com.
authors.forename: Ana Luísa
authors.identifier: http://orcid.org/0000-0003-2371-8907
authors.initials: AL
authors.lastname: Areia
authors.affiliation: Obstetric Unit, Coimbra University Hospital Centre, Rua Miguel Torga, 3030-165, Coimbra, Portugal.
authors.forename: Etelvina
authors.initials: E
authors.lastname: Fonseca
authors.affiliation: CINTESIS, Center for Research in Health Technologies and Information Systems Faculty of Medicine, Porto University, Porto, Portugal.
authors.forename: Miguel
authors.initials: M
authors.lastname: Areia
authors.affiliation: Obstetric Unit, Coimbra University Hospital Centre, Rua Miguel Torga, 3030-165, Coimbra, Portugal.|Faculty of Medicine, Coimbra University, Coimbra, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Moura
mesh_terms: D000026:Abortion, Habitual / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D000925:Anticoagulants / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D001724:Birth Weight; D005260:Female; D005865:Gestational Age; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D050498:Live Birth; D011225:Pre-Eclampsia / Q000188:drug therapy; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D019851:Thrombophilia / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D001241:Aspirin
keywords: Aspirin; Heparin, low-molecular-weight; Pregnancy; Pregnancy, high-risk; Thrombophilia, hereditary