title: Thromboprophylaxis for recurrent miscarriage in women with or without thrombophilia. HABENOX: a randomised multicentre trial.
abstract: Recurrent miscarriage affects 1-2% of women. In more than half of all recurrent miscarriage the cause still remains uncertain. Thrombophilia has been identified in about 50% of women with recurrent miscarriage and thromboprophylaxis has been suggested as an option of treatment. A randomised double-blind (for aspirin) multicentre trial was performed among 207 women with three or more consecutive first trimester (<13 weeks) miscarriages, two or more second trimester (13-24 weeks) miscarriages or one third trimester fetal loss combined with one first trimester miscarriage. Women were analysed for thrombophilia. After complete work-up, women were randomly allocated before seven weeks' gestation to either enoxaparin 40 mg and placebo (n=68), enoxaparin 40 mg and aspirin 100 mg (n=63) or aspirin 100 mg (n=76). The primary outcome was live-birth rate. Secondary outcomes were pregnancy complications, neonatal outcome and adverse effects. The trial was ended prematurely because of slow recruitment. A live birth rate of 71% [relative risk (RR) 1.17, 95% confidence interval (CI) 0.92-1.48] was found for enoxaparin and placebo and 65% [RR 1.08, 95% CI 0.83-1.39] for enoxaparin and aspirin when compared to aspirin alone (61%, reference group). In the whole study group the live birth rate was 65% (95% CI 58.66-71.74) for women with three or more miscarriages (n=204). No difference in pregnancy complications, neonatal outcome or adverse effects was observed. No significant difference in live birth rate was found with enoxaparin treatment versus aspirin or a combination of both versus aspirin in women with recurrent miscarriage.
authors.affiliation: Department of Obstetrics, Gynaecology and Reproductive Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Jantien
authors.initials: J
authors.lastname: Visser
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Ulander
authors.forename: Frans M
authors.initials: FM
authors.lastname: Helmerhorst
authors.forename: Katja
authors.initials: K
authors.lastname: Lampinen
authors.forename: Laure
authors.initials: L
authors.lastname: Morin-Papunen
authors.forename: Kitty W M
authors.initials: KW
authors.lastname: Bloemenkamp
authors.forename: Risto J
authors.initials: RJ
authors.lastname: Kaaja
mesh_terms: D000026:Abortion, Habitual / Q000209:etiology / Q000517:prevention & control*; D000293:Adolescent; D000328:Adult; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D057239:Early Termination of Clinical Trials; D017984:Enoxaparin / Q000009:adverse effects / Q000627:therapeutic use*; D005060:Europe; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005865:Gestational Age; D006801:Humans; D050498:Live Birth; D018579:Patient Selection; D011247:Pregnancy; D019851:Thrombophilia / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D017984:Enoxaparin; D005343:Fibrinolytic Agents; D001241:Aspirin