Discontinuing aspirin at 24-28 weeks gestation does not appear to affect preeclampsia risk

Discontinuing aspirin at 24 to 28 weeks of gestation was noninferior to continuing aspirin until 36 weeks of gestation to prevent preterm preeclampsia among high-risk individuals, according to a randomized clinical trial published in JAMA.

Manel Mendoza, PhD, an associate clinical professor at the Universitat Autònoma de Barcelona and investigator of the research group of Maternal-Fetal Medicine at the Vall d'Hebron Research Institute in Spain, and colleagues wrote that, for pregnant women at high risk for preeclampsia, aspirin has been shown to reduce the incidence of preterm preeclampsia by 62%.

However, Mendoza and colleagues wrote, aspirin may also be linked to an increased risk for peripartum bleeding. That risk, though, may be mitigated by discontinuing aspirin before the pregnancy goes to term and by “an accurate selection” of those at higher risk for preeclampsia in the first trimester of their pregnancy.

The researchers conducted a randomized clinical trial to better understand if discontinuing aspirin between 24 and 28 weeks during pregnancy was noninferior to aspirin continuation for preventing preterm preeclampsia.

Mendoza and colleagues conducted the trial in nine maternity hospitals across Spain. They enrolled 936 participants — 93% of whom were white and 3.4% of whom were Black — who had a high risk for preeclampsia during the first-trimester screening. All participants had a normal soluble fms-like tyrosine kinase–1 to placental growth factor ratio.

The researchers then randomly assigned the participants in a 1:1 ratio to an intervention group of aspirin discontinuation — 473 participants — or a control group of aspirin continuation until term — 463 participants.

They found that the incidence of preterm preeclampsia was 1.73% in the control group and 1.48% in the intervention group — an absolute difference of 0.25% (95% CI, 1.86 to 1.36), indicating noninferiority.

Mendoza and colleagues also found a greater incidence of pregnancy complications at 37 weeks of gestation or more in the control group in what they said was “the most unexpected result of this study.”

“Aspirin is believed to delay the onset of preeclampsia, thereby converting what would be, without treatment, preterm preeclampsia into term preeclampsia,” they wrote. “For this reason, it would have been reasonable to expect that the incidence of term preeclampsia was greater in the intervention group and not the opposite.”

In a related editorial, Ukachi N. Emeruwa, MD, MPH, a clinical fellow at New York-Presbyterian Hospital, and colleagues wrote that the study “challenges a growing body of evidence trending toward increasingly widespread use of low-dose aspirin in pregnancy,” referencing a recent analysis that showed at least 50.4% of pregnancies in the United States were eligible for low-dose aspirin based on guidance from the U.S. Preventive Services Task Force.

“Perhaps unsurprisingly, owing to potential barriers to selective implementation and the perceived safety of low-dose aspirin, support is growing in the U.S. for its use in all pregnancies,” they wrote.

Emeruwa and colleagues also wrote that, “though well-designed and provocative in its findings, this study is difficult to interpret in a U.S. population.”

They highlighted key differences in U.S. preeclampsia prevention guidelines compared with those specified by Mendoza and colleagues, such as:

1. “the exclusive use of clinical maternal factors in the U.S. as opposed to molecular biomarkers for screening for low-dose aspirin prophylaxis;”
2. a difference in the dosage of aspirin recommended in the U.S. compared with international societies — 81 mg vs. 150 mg, respectively; and
3. the lack of a U.S. recommendation to discontinue prophylactic low-dose aspirin at 36 weeks of gestation.

“Given the conflicting evidence in the literature to date, it remains unclear whether low-dose aspirin is associated with a clinically significant increase in antepartum bleeding,” Emeruwa and colleagues wrote. “Without an increase in bleeding complications, there is no rationale to recommend discontinuation of low-dose aspirin for preeclampsia prevention prior to delivery.”

References:

• Emeruwa UN, et al. JAMA. 2023;doi:10.1001/jama.2022.24906.
• Mendoza M, et al. JAMA. 2023;doi:10.1001/jama.2023.0691.