Aspirin discontinuation in pregnancies at high risk for preterm preeclampsia

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For pregnant women at high risk of preeclampsia and a normal soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1:PlGF) ratio, aspirin discontinuation at 24 to 28 weeks’ gestation was comparable to aspirin continuation for preventing preterm preeclampsia, according to a clinical trial published in JAMA.

The authors noted that aspirin decreases the incidence of preterm preeclampsia by 62% in pregnant women at high risk of preeclampsia.

But aspirin may be linked to an increased risk of peripartum bleeding, which could be mitigated by discontinuing aspirin before term (37 weeks of gestation) and by accurately selecting women at higher risk of preeclampsia in the first trimester of pregnancy.

The open-label, randomized noninferiority study, which was conducted at 9 maternity hospitals across Spain, recruited 968 pregnant women at high risk of preeclampsia during the first-trimester screening and with an sFlt-1:PlGF ratio of 38 or less at 24 to 28 weeks’ gestation, between August 2019 and September 2021.

Of the 936 women analyzed, the mean age was 32.4 years; 93% were White and 3.4% were Black.

Overall, 473 women were in the intervention group that discontinued aspirin and 463 women were in the control group that continued taking aspirin until 36 weeks’ gestation.

Noninferiority was defined as the higher 95% confidence interval (CI) being less than 1.9% for the difference in preterm preeclampsia incidences between the two groups. The incidence of preterm preeclampsia was 1.48% in the intervention group and 1.73% in the control group, for an absolute difference of -0.25%; 95% CI: -1.86% to 1.36%. Median gestational age at delivery for women with or without preterm preeclampsia was 35.1 weeks (P = 0.42).

There were also no significant differences between the two groups for adverse outcomes with delivery before 37 weeks of gestation or delivery before 34 weeks of gestation.

Because a daily dose of aspirin of 100 mg or more begun after 16 weeks’ gestation may be connected to an increased relative risk of placental abruption and other bleeding complications, “most guidelines recommend to discontinue aspirin at term and before onset of labor, which is the time where the risk of bleeding is greatest in pregnant individuals,” the authors wrote.

To reduce the incidence of women exposed to aspirin during pregnancy, guidelines also recommend setting the threshold for classifying women at high risk of preeclampsia in the first trimester to a maximum screen positive rate of 10% to 15%.

Despite the safety concerns of taking aspirin throughout pregnancy, recommendations are not consistent when to stop aspirin, according to the authors.

The study used a daily aspirin dose of 150 mg, which is one of the highest doses recommended for preventing preeclampsia. Hence, discontinuing aspirin may have led to a significant reduction in severe bleeding complications.

“However, an association between earlier discontinuation of aspirin treatment and a reduction in rarer bleeding complications, such as placental abruption, maternal intracranial hemorrhage, postpartum hemorrhage, and/or neonatal intraventricular hemorrhage, was not observed,” the authors wrote.

The investigators advocate larger studies to assess these rare outcomes.

Aspirin was also discontinued before labor in both groups, thereby reducing the likelihood of finding differences in the rates of postpartum and neonatal hemorrhages.

Reference

Mendoza M, Bonacina E, Garcia-Manau P. Aspirin discontinuation at 24 to 28 weeks' gestation in pregnancies at high risk of preterm preeclampsia: a randomized clinical trial. JAMA. Published online February 21, 2023. doi:10.1001/jama.2023.0691