Some women who have experienced a pregnancy loss can increase their odds of a live birth in the next pregnancy simply by taking aspirin, investigators reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.
A team led by Enrique F. Schisterman, Ph.D., conducted a randomized trial of 1,228 healthy young women who had had up to two prior pregnancy losses, but did not have infertility and were attempting to conceive again.
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Low-dose aspirin was associated with somewhat higher rates of minor vaginal bleeding and minor gastrointestinal upset.
The women were assigned evenly to take low-dose aspirin (81 mg) or placebo daily, along with folic acid, for up to six menstrual cycles or, if they conceived, up to the 36th week of pregnancy.
Results showed that low-dose aspirin was associated with an absolute 9.2% increase in the rate of live birth among the subset of women who met restricted criteria for pregnancy loss, namely a single pregnancy loss before 20 weeks’ gestation in the past year, reported Dr. Schisterman, who is a senior investigator and chief of the epidemiology branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Rockville, Md.
The benefit was mainly due to early effects. "There was an effect on becoming pregnant and early pregnancy [maintenance], but there were no differences after that," he elaborated. "The implications of that are not only that aspirin will help women become pregnant, but if you start too late, then the effects of aspirin are not there any more."
Analyses in the group with restricted criteria suggested that only about 11 women would need to be treated with low-dose aspirin to achieve one additional live birth.
In contrast, there was no significant benefit of low-dose aspirin among the subset of women who met general criteria for pregnancy loss that required one or two pregnancy losses at any time in the past, but excluded those meeting restricted criteria.
Low-dose aspirin was associated with somewhat higher rates of minor vaginal bleeding and minor gastrointestinal upset, but the drug was not associated with pregnancy loss or with an increased risk of major fetal, neonatal, or maternal complications.
An attendee wondered about the difference between the two subsets of women having differing histories of pregnancy loss, saying, "You would expect more or less the same effect."
Dr. Schisterman maintained that the two groups were not all that similar. "I am not sure I would expect the same result, although when we did some analyses in which we compared those who had a single loss in the restricted stratum to those who had a single loss in the general stratum, we found attenuated but in a similar direction results in the general stratum," he commented. "So it seems that the number of losses is the driving force. But we are still analyzing that data."
Another attendee raised the issue of the timing of the previous pregnancy loss in the subset meeting restricted criteria. "Were you able to identify any influence of the gestational age of the previous loss on the effectiveness of aspirin in the next pregnancy, the randomized pregnancy?" he asked.
"Not yet," Dr. Schisterman replied, noting that all of the losses were fairly early. However, here too, analyses are still ongoing.
Giving some background to the trial, he noted, "We know that inflammation and abnormal blood flow, especially in the uterus, endometrium, ovaries, and placenta, ... are unifying features of outcomes like infertility, pregnancy loss, preeclampsia, preterm delivery, and small for gestational age. So clearly, an ideal therapy that would reduce inflammation and improve blood flow will be the one that we are looking for. Low-dose aspirin could be such a therapy."
The drug has seldom been studied when given in the preconceptional period, but there is a strong rationale for such use, he maintained.
"It impacts endometrial vascularization and placentation. It has very well documented anti-inflammatory effects. It has very few maternal and fetal side effects. It’s safe, widely available, and more importantly, it’s cheap – it costs $2 for the whole pregnancy to treat a woman," he elaborated.
Women enrolled in the trial, known as EAGeR (The Effects of Aspirin in Gestation and Reproduction), were aged 18-39 years. They were roughly evenly split between meeting the restricted criteria and the general criteria for previous pregnancy loss.
On average, the women were 29 years old and had a body mass index of about 27 kg/m2. Most were married and white.
Overall, there was only a trend toward a higher rate of live births in the low-dose aspirin group compared with the placebo group (57.8% vs. 52.7%, P = .09), reported Dr. Schisterman.