Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies) A randomized study of thromboprophylaxis in women with unexplained consecutive recurrent miscarriages.
To determine whether treatment with low dose aspirin and heparin leads to a higher rate of live births than that achieved with low dose aspirin alone in women with a history of recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin antibodies (or anticardiolipin antibodies).
                Randomised controlled trial.
                Specialist clinic for recurrent miscarriages.
                90 women (median age 33 (range 22-43)) with a history of recurrent miscarriage (median number 4 (range 3-15)) and persistently positive results for phospholipid antibodies.
                Either low dose aspirin (75 mg daily) or low dose aspirin and 5000 U of unfractionated heparin subcutaneously 12 hourly. All women started treatment with low dose aspirin when they had a positive urine pregnancy test. Women were randomly allocated an intervention when fetal heart activity was seen on ultrasonography. Treatment was stopped at the time of miscarriage or at 34 weeks' gestation.
                Rate of live births with the two treatments.
                There was no significant difference in the two groups in age or the number and gestation of previous miscarriages. The rate of live births with low dose aspirin and heparin was 71% (32/45 pregnancies) and 42% (19/45 pregnancies) with low dose aspirin alone (odds ratio 3.37 (95% confidence interval 1.40 to 8.10)). More than 90% of miscarriages occurred in the first trimester. There was no difference in outcome between the two treatments in pregnancies that advanced beyond 13 weeks' gestation. Twelve of the 51 successful pregnancies (24%) were delivered before 37 weeks' gestation. Women randomly allocated aspirin and heparin had a median decrease in lumbar spine bone density of 5.4% (range -8.6% to 1.7%).
                Treatment with aspirin and heparin leads to a significantly higher rate of live births in women with a history of recurrent miscarriage associated with phospholipid antibodies than that achieved with aspirin alone. To compare the effect of aspirin and enoxaparin on live births in women with unexplained recurrent miscarriages, as well as secondary outcomes including birth weight, uterine and umbilical blood flows, and congenital malformations.
                Multicenter randomized comparative cohort study.
                Four centers including two university hospitals, a peripheral general hospital, and a community health clinic.
                One hundred seven patients were randomized, 104 were available for analysis; 54 were randomized to enoxaparin and 50 to aspirin.
                Treatment with enoxaparin or aspirin in subsequent pregnancy.
                Subsequent live births or miscarriage, and the incidence of obstetric complications.
                Both groups had a similar live birth rate (relative risk = 0.92, 95% confidence interval: 0.58-1.46). In primary aborters, live births occurred in 17 of 18 (94%) enoxaparin-treated pregnancies compared to 18 of 22 (81%) aspirin-treated pregnancies. In the aspirin group, two pregnancies were terminated: for tricuspid insufficiency and for hemolysis, elevated liver enzymes, low platelet (HELLP) syndrome. One enoxaparin-treated infant was growth restricted (2,020 g) at 36 weeks. Preeclampsia was found in three aspirin-treated patients. Preterm delivery, placental Doppler blood flow, apgar scores, and mean birth weights were similar in both groups. In the aspirin group, one infant underwent orchidectomy after testicular torsion in utero, and one infant had hypoglycemia and convulsions.
                Both regimens were associated with a high live birth rate and few late pregnancy complications.
There is a paucity in studies on the efficacy and safety of aspirin and heparin in women with a history of at least two miscarriages without apparent causes other than inherited thrombophilia. The two reviewed trials studied different treatments and only one study was placebo-controlled. Neither of the studies showed a benefit of one treatment over the other. Therefore, the use of anticoagulants in this setting is not recommended. However, large randomised placebo-controlled trials are still urgently needed.