Women in the two aspirin arms took calcium carbasalate (Ascal) equivalent to acetylsalicylic acid 80 mg daily from the day of randomization until 36 weeks of gestational age. Nadroparin 2,850 IU was injected after a pregnancy was confirmed by ultrasound from 6 weeks of gestational age until the end of pregnancy.
The average age was about 33 years, and the median number of unexplained miscarriages was three. Among the women who were randomized, 103 completed treatment in each of the aspirin-plus-nadroparin and placebo arms; 104 took all treatments in the aspirin-only group.
The author could find no significant differences in subgroup analyses of women with inherited thrombophilia, preceding live birth, age less than 36 years, or three or more previous miscarriages. The investigators did see a trend toward improved live birth rate in 47 women with inherited thrombophilia, however (relative risk ratio 1.56, P = .18).
The study was underpowered to draw a conclusion on whether women with inherited thrombophilia might benefit from anticoagulant prophylaxis, Dr. Kaandorp said, promising to explore this question. “At this moment I think we should not treat those women, but should do another trial in that population,” he said.
'We couldn't find the beneficial effects in our study of three treatment arms—[there was] no difference at all.'
Source DR. KAANDORP
My Take
Study Confirms Common Sense
In women in whom no specific cause is found for miscarriage, no specific treatment should be used. Thus a treatment that is specific for pregnant women with inherited thrombophilia or antiphospholipid syndrome should not be given to pregnant women without such diagnoses. If you use aspirin in midpregnancy, you increase the risk of pregnancy loss and placental abruption. So if there is no proven benefit to this treatment, this seems like a bad deal. On the other hand, if a woman comes into an ob.gyn.'s office having had two miscarriages and says, “Do something,” some physicians may say, “Give them what they want.”
But this study has shown that aspirin does not prevent recurrent idiopathic miscarriages and does cause bruising. Low-molecular-weight heparin is probably even worse in terms of potential risks and complications.
If you do not find the problem you are looking for—that is, inherited thrombophilia or antiphospholipid syndrome—treatment is dangerous and not helpful.
Are these data new? Prior studies of aspirin use in pregnancy have demonstrated an increased risk of placental abruption in aspirin-treated women. The current study confirmed what logic told you was the right thing to do: Don't use them.
In practice I occasionally see physicians prescribe a treatment for a pregnant patient, saying, “What harm can it do?” It was that kind of thinking that led to the DES debacle some 40 years ago. When dealing with pregnancy, you can't say, “What harm can it do?” because the results can be disastrous. It is good that these researchers performed this study because it confirmed what most rational physicians know: We should use only treatments definitely shown to work, especially during pregnancy.
GERSON WEISS, M.D., is the chairman of the department of obstetrics and gynecology at New Jersey Medical School, Newark. He said he had no relevant disclosures.
