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Growing evidence that aspirin can prevent preterm birth (PTB) was presented at the 3rd European Spontaneous Preterm Birth Congress in Edinburgh, Scotland. Adding to data later this summer will be results from an open-label randomized, controlled trial (RCT) of low-dose aspirin with early screening for preeclampsia and growth restriction.
A review of the current evidence and perspective on its clinical implications were presented by Fionnuala McAuliffe, MB BCh BAO (Honours) DCH MD FRCPI, FRCOG FRPI. Dr. McAuliffe is principal investigator of the RCT and chair and professor of obstetrics and gynecology at University College Dublin in Ireland. The trial is an acceptability and feasibility study of low-risk women taking aspirin and their compliance and scheduled to be published in BMJ Open.
Addressing the Congress attendees, she said that “a number of studies point to the effectiveness of aspirin taken by pregnant women. At the moment, the data shows that aspirin reduces preeclampsia and preterm birth in women who are at risk for preeclampsia.”
In the United Kingdom, aspirin is often prescribed to prevent preeclampsia, but not as often in the United States. “Aspirin reduces both preeclampsia and preterm deliveries in women at risk for preeclampsia,” Dr. McAuliffe said. “If preeclampsia is reduced, then preterm birth is also reduced...You could argue that it might simply be cheaper to give everyone aspirin rather than trying to figure out if a certain individual is at risk of pre-eclampsia or not by conducting expensive blood and ultrasound tests in early pregnancy,” she said.
Aspirin is an antiplatelet agent that improves blood flow and vascular formation in the placenta by reducing the thromboxane and increasing the vasodilator prostacyclin. “Preeclampsia, of course, is a disease of the placenta that results from a placenta not developing properly from very early in pregnancy,” Dr. McAuliffe explained. “The association between preterm birth and preeclampsia is strong. If a woman develops preeclampsia prior to 37 weeks, she will need to deliver because of the risk to her health.”
As for safety, many studies conclude that aspirin has no adverse fetal sequelae in doses less than 150 mg per day and that aspirin does not increase the risk of congenital malformations. However, one study found that vaginal bleeding is more common: 3.9% for low-dose aspirin versus 1.3 for placebo.
The data to support aspirin date back more than 10 years, showing that the drug reduces risk of PTB by 7% to 14%. “This is robust data compiled from more than 40,000 women at risk of preeclampsia,” Dr. McAuliffe said. “The question then becomes can we extrapolate the data to all pregnant women?”
Dr. McAuliffe cited examples of women who are given aspirin only during a follow-up pregnancy after experiencing preeclampsia during their previous pregnancy. “These women are concerned that they were not offered aspirin to begin with,” she said. “Thus, there is interest in offering aspirin to all pregnant women.”
However, currently there is no concrete evidence that aspirin reduces the rate of preeclampsia in low-risk women.
Numerous studies of women who are at risk for preeclampsia show a risk reduction with daily aspirin, with a decrease in preeclampsia ranging from 17% to 24%, a decrease in PTB of between 8% and 14% and a reduction in small for gestational age (SGA) spanning from 10% to 20%.
Specifically, a multicenter, randomized placebo-controlled trial of low-dose aspirin (80 mg) to prevent recurrent preterm labor in 406 women found that incidence of PTB < 37 weeks’ gestation was reduced by 35%, as reported in BMC Pregnancy and Childbirth in 2017.
Similarly, for the same gestation period, incidence of PTB fell by 20%, according to a study of 11,920 nulliparous mothers in seven low- and middle-income countries who were given aspirin supplementation during pregnancy, again as reported in BMC Pregnancy and Childbirth in 2017.
Dr. McAuliffe was co-author of a viewpoint in the American Journal of Obstetrics and Gynecology in 2016 that posed the question: Should we recommend universal aspirin for all pregnant women? In support of the proposal, the authors listed efficacy in at-risk women, safety, cost and international impact. “Aspirin is incredibly inexpensive,” Dr. McAuliffe said. “It can be easily stored at room temperature, so potentially there is a huge international impact.”
Two reasons against the recommendation are lack of evidence of efficacy in low-risk women and potential side effects.
The trial of aspirin to prevent preeclampsia (TEST), for which Dr. McAuliffe is the principal investigator, was carried out at two hospitals in Ireland to determine if low-risk, first-time mothers would be interested in taking aspirin during pregnancy and actually adhere to the protocol of once-daily aspirin (75 mg).
Of the 1,054 eligible women approached to participate in the study, 52.8% agreed. And of the 179 women who were randomized to take aspirin, 96% complied with the protocol. “In the United States, the dose is quite similar at 80 mg,” Dr. McAuliffe noted. When study patients were asked if they would be willing to take aspirin during a subsequent pregnancy, 92.5% of those who took aspirin and 91.5% of those who did not said yes.
A separate study conducted by Dr. McAuliffe and colleagues, which has been submitted for publication, is a cost-effectiveness analysis of aspirin in 21,641 low-risk nulliparous women in Ireland. The economic analysis compared universal aspirin to a Fetal Medicine Foundation screening test and then offering aspirin to those who screened positive.
“We found that it was less expensive to give everyone aspirin rather than detecting within the population those who are at risk of preeclampsia, and then prescribing low-dose aspirin,” Dr. McAuliffe said.
The universal aspirin net savings was estimated as roughly $1.8 million, whereas universal screening and treatment tallied about $1.7 million annually for Ireland. “These data, if extrapolated to the United States, would amount to very considerable savings,” Dr. McAuliffe said.
However, before recommending universal aspirin, “we need to research and further consider the consequences,” Dr. McAuliffe said. “But it is important to start that conversation. I am cautiously optimistic that both clinicians and patients may embrace aspirin for all pregnant women.”
Dr. McAuliffe reports no relevant financial disclosures.