Effect of aspirin on biomarker profile in women at high-risk for preeclampsia

Background: There is limited evidence in the literature regarding the temporal changes of preeclampsia-related biomarkers during pregnancy in high-risk women who develop preeclampsia despite the administration of aspirin prophylaxis.

Objectives: To compare the temporal changes in mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) across gestation in women screened high-risk for preterm preeclampsia receiving aspirin prophylaxis and low-risk women without aspirin treatment.

Study design: This was a prospective longitudinal nested case-control study of 2007 women with singleton pregnancies who participated in the first-trimester screen-and-prevent program for preeclampsia at the Prince of Wales Hospital, Hong Kong SAR, China, between January 2020 and May 2023. The risk of developing preterm preeclampsia was determined using the Fetal Medicine Foundation triple test (maternal factors, MAP, UtA-PI and PlGF). High-risk women (adjusted risk ≥1:100) were administered a daily dose of aspirin at either 100 or 160 mg according to maternal weight, starting before 16 weeks until 36 weeks or until delivery or the onset of preeclampsia before 36 weeks. Low-risk women were matched based on maternal age, weight, and the date of the scan. The participants were followed up at 12-15⁺⁶, 20-24⁺⁶ and 30-37⁺⁶ weeks to measure MAP, UtA-PI, PlGF and sFlt-1 at each visit. The level of biomarker was expressed as multiple of median (MoM). Log₁₀ transformation was applied to make the data Gaussian distribution prior to statistical analysis. A linear mixed-effects analysis was performed to compare the longitudinal changes of these biomarkers across gestation between the study groups.

Results: Our study involved 403 low-risk women without preeclampsia, 1471 high-risk women without preeclampsia, and 133 high-risk women who developed preeclampsia. The low-risk group had significantly lower estimated marginal mean log₁₀ MAP MoM, log₁₀ UtA-PI MoM, log₁₀ sFlt-1 MoM and higher estimated marginal mean log₁₀ PlGF MoM across gestation than the high-risk groups (p values <0.001). Among high-risk women, those who developed preeclampsia experienced a significantly higher estimated marginal mean log₁₀ MAP MoM (0.06378 vs 0.02985; p<0.001), log₁₀ UtA-PI MoM (0.08651 vs 0.02226; p<0.001), log₁₀ sFlt-1 MoM (0.13204 vs 0.01234; p<0.001) and lower estimated marginal mean log₁₀ PlGF MoM (-0.33504 vs -0.16388; p<0.001) across gestation in comparison to those without preeclampsia. In the individual gestational timepoint analysis, compared to high-risk women without preeclampsia, those who developed preeclampsia experienced higher log₁₀ MAP MoM in all three trimesters, higher log₁₀ UtA-PI MoM and lower log₁₀ PlGF MoM in the second- and third-trimesters, and higher log₁₀ sFlt-1 MoM in the third-trimester.

Conclusion: The study has demonstrated that high-risk women who develop preeclampsia experience consistently high MAP level from the first-trimester and remain unchanged during pregnancy, high UtA-PI level and low PlGF level starting from the second-trimester, and high sFlt-1 level in the third-trimester compared to those who do not develop preeclampsia despite the administration of low-dose aspirin. These findings underscore the role of these biomarkers in further risk stratification for the development of preeclampsia among high-risk women following aspirin administration.