Higher aspirin dose may attenuate severe pre-eclampsia risk among high-risk women with obesity

Doubling the routine aspirin dose used for pre-eclampsia prevention appears to help lower the risk of developing pre-eclampsia with severe features among high-risk pregnant women with obesity, according to the results of the open-label ASPREO trial.

The incidence of pre-eclampsia with severe features among participants who received aspirin at 162 mg daily was lower than among those who received a daily dose of 81 mg (35 percent vs 40 percent; relative risk [RR], 0.88, 95 percent credible interval [CrI], 0.64­–1.22). [SMFM 2024, abstract 43]

The posterior probability for treatment benefit with the 162-mg daily aspirin dose was 78 percent, noted primary investigator Dr Farah Amro of McGovern Medical School at The University of Texas Health Science Center at Houston, Texas, US.

While low-dose aspirin is routinely recommended to prevent pre-eclampsia in high-risk pregnancies, the optimal dosage remains unclear. The finding suggests that a daily aspirin dose of 162 mg may be more effective than 81 mg, particularly in pregnant women with obesity, Amro said.

For ASPREO, Amro and colleagues enlisted 343 women who were 12–20 weeks into their pregnancy. These women had a body mass index (BMI) of 30 kg/m² and at least one factor rendering them at high risk of severe pre-eclampsia (ie, a history of pre-eclampsia, pregestational diabetes, gestational diabetes diagnosed <20 weeks, or at least stage I hypertension [130/80 mm Hg]).

Of the women, 220 agreed to participate in the trial and were randomly assigned to receive aspirin at a daily dose of 162 mg (median age 30.0 years, 47 percent Black, median BMI 37 kg/m², median gestational age 15 weeks) or 81 mg (median age 29.0 years, 55 percent Black, median BMI 38 kg/m², median gestational age 15 weeks).

Adherence to medications was evaluated at 4 weeks and at 32–36 weeks after enrolment. The primary outcome of pre-eclampsia with severe features was determined based on physician diagnosis in participants who delivered at 20 weeks. Bayesian methodology was applied in the analyses.

The prevalence of the following high-risk factors was similar between the 162-mg and 81-mg dose groups: history of pre-eclampsia (34 percent vs 29 percent), diabetes mellitus (42 percent vs 46 percent), and stage I hypertension (29 percent vs 32 percent).

Primary outcome data were unavailable for 11 participants, including four who delivered before 20 weeks of gestation. As such, a total of 107 participants in the 162-mg dose group and 102 in the 81-mg dose group were included in the analyses.

Aside from the incidence of severe pre-eclampsia, the only other outcome that significantly differed between the two groups was the median gestational age at delivery, which was lower in 162-mg dose group (36.0 vs 37.2 weeks; p=0.04).

There were no significant differences seen in the other secondary outcomes such as rates of preterm delivery (54 percent vs 44 percent; RR, 1.23, 95 percent CrI, 0.93–1.62 p=0.14), delivery due to pre-eclampsia <37 weeks (21 percent vs 21 percent; RR, 1.00, 95 percent CrI, 0.59–1.70 p>0.99), small for gestational age (6.5 percent vs 3.9 percent; RR, 1.23, 95 percent CrI, 0.93–1.62 p=0.14), abruption (2.8 percent vs 3.0 percent; RR, 0.93, 95 percent CrI, 0.19–4.52 p=0.90), postpartum haemorrhage (10.0 percent vs 8.8 percent; RR, 1.17, 95 percent CrI, 0.50–2.69 p=0.70), and severe maternal morbidity (8.4 percent vs 11.0 percent; RR, 0.78, 95 percent CrI, 0.34–1.80 p=0.60).

Overall, the ASPREO data warrant further investigation through a larger, multicentre phase III trial, Amro said.