Stopping aspirin at 24-28 weeks of gestation has no disadvantage, compared with continuing aspirin full term, for preventing preterm preeclampsia in women at high risk of preeclampsia who have a normal fms-like tyrosine kinase 1 to placental growth factor (sFlt-1:PlGF) ratio, a randomized controlled trial has found.
The findings were published online in JAMA.
Editorialists advise careful consideration
However, in an accompanying editorial, Ukachi N. Emeruwa, MD, MPH, with the division of maternal fetal medicine, department of obstetrics, gynecology, and reproductive sciences at the University of California, San Diego, and colleagues noted that the questions surrounding continuing or discontinuing aspirin in this high-risk population need further consideration.
They added that the results from this study – conducted in nine maternity hospitals across Spain – are hard to translate for the U.S. population.
In this study, Manel Mendoza, PhD, with the maternal fetal medicine unit, department of obstetrics, at the Universitat Autònoma de Barcelona, and colleagues compared the two approaches because of the potential to mitigate peripartum bleeding by discontinuing aspirin before full term (37 weeks’ gestation) and by an accurate selection of women in the first trimester at higher risk of preeclampsia.
Aspirin cuts preterm preeclampsia by 62% in women at high risk
While aspirin might be associated with an increased risk of peripartum bleeding, aspirin has been proven to reduce the incidence of preterm preeclampsia by 62% in pregnant women at high risk of preeclampsia.
In the multicenter, open-label, randomized, phase 3, noninferiority trial, pregnant women who had a high risk of preeclampsia during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at 24-28 weeks’ gestation were recruited between Aug. 20, 2019, and Sept. 15, 2021. Of those, 936 were analyzed (473 in the intervention group [stopping aspirin] and 473 in the control group [continuing]).
Screening for risk of preterm preeclampsia included analyzing maternal factors, uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein A, and placental growth factor. Follow-up was until delivery for all participants.
Incidence of preterm preeclampsia was 1.48% in the intervention group (discontinuing aspirin) and 1.73% in the control group (continuing aspirin until 36 weeks of gestation; absolute difference, –0.25%; 95% confidence interval, –1.86% to 1.36%), which indicates noninferiority for stopping aspirin. The bar for noninferiority was less than a 1.9% difference in preterm preeclampsia incidences between groups.
Researchers did find a higher incidence of minor antepartum bleeding in the group that continued aspirin (7.61% in the low-dose aspirin discontinuation group vs. 12.31% in the low-dose aspirin continuation group; absolute difference, –4.70; 95% CI, –8.53 to –0.87).
Differences in U.S. guidelines
Dr. Emeruwa and colleagues noted the study challenges a growing body of evidence favoring increasingly widespread use of low-dose aspirin in pregnancy.
They called the study “well designed and provocative,” but wrote that the findings are hard to interpret for a U.S. population. Some key differences in the U.S. preeclampsia prevention guidelines, compared with the practices of the study’s authors, included the reliance on clinical maternal factors in the United States for screening for low-dose aspirin prophylaxis as opposed to molecular biomarkers; a different aspirin dose prescribed in the United States (81 mg daily), compared with international societies (150 mg daily); and a lack of a recommendation in the United States to stop prophylactic low-dose aspirin at 36 weeks.
Dr. Emeruwa and colleagues also questioned the scope of the outcome measure used.
They wrote that limiting outcomes to preterm preeclampsia dims the effects of all types of preeclampsia on perinatal and maternal outcomes and that early-onset preeclampsia at less than 34 weeks “occurs in just 0.38% of pregnancies, while 3%-5% are affected by late-onset preeclampsia.”