Therapeutics · Anti-Infective and Anti-Inflammatory Agents
Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies)
Rai R,Cohen H,Dave M,Regan L
Published January 25, 1997BMJ (Clinical Research Ed.), 314(7076), 253-257
Rai, R., Cohen, H., Dave, M., & Regan, L. (1997). Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ (Clinical Research Ed.), 314(7076), 253-257. https://doi.org/10.1136/bmj.314.7076.253
Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ. 1997;314(7076):253-257. doi:10.1136/bmj.314.7076.253
Rai, R., et al. "Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies)." BMJ (Clinical Research Ed.), vol. 314, no. 7076, 1997, pp. 253-257.
Adding heparin to aspirin raised live births in antiphospholipid loss
A 1997 randomized trial of 90 women with recurrent miscarriage and persistent antiphospholipid antibodies compared two treatments. Aspirin plus heparin led to live birth in about 7 out of 10 pregnancies, against about 4 out of 10 with low dose aspirin alone. After 13 weeks, the groups did not differ in outcome.
Key Findings
Live birth followed 32 of 45 pregnancies (71%) on aspirin plus heparin and 19 of 45 (42%) on aspirin alone; odds ratio 3.37 (95% confidence interval 1.40 to 8.10).
Miscarriage occurred in 26 pregnancies on aspirin alone and in 13 on aspirin with heparin.
After 13 weeks of gestation, outcomes in the two treatment groups did not differ.
Twelve of the 51 pregnancies that succeeded (24%) were delivered before 37 weeks.
Median lumbar spine bone density fell by 5.4% in women given heparin, measured from 12 weeks of gestation to after delivery. No woman had a vertebral fracture.
Interpretation
A computer generated list assigned the women to treatment. The analysis counted every pregnancy in its assigned group. The women came from one London clinic for recurrent miscarriage. Assignment came once ultrasound showed a fetal heartbeat, so the results cover pregnancies that had reached that point. The trial was not blinded, since the authors judged twice daily placebo injections unethical. Each woman had weekly scans and support in the first trimester. Women with systemic lupus, a previous blood clot, a uterine abnormality or a multiple pregnancy were excluded. The authors write that future studies should look at heparin before conception and at stopping it after 13 weeks.
RRM Context
Restorative reproductive medicine starts with evaluation before treatment. The women here qualified through antibody testing: positive results on at least two occasions more than eight weeks apart, before they became pregnant. The authors report that 15% of women with three or more losses in a row have persistent antibodies. A repeated loss with no identified cause is an undiagnosed loss.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
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).
Design
Randomised controlled trial.
Setting
Specialist clinic for recurrent miscarriages.
Subjects
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.
Intervention
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.
Main Outcome Measures
Rate of live births with the two treatments.
Results
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%).
Conclusion
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.
