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

Abstract

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.

Objective: This study aimed to compare the temporal changes in mean arterial pressure, uterine artery pulsatility index, placental growth factor, and soluble fms-like tyrosine kinase-1 across gestation in women identified as having 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 Special Administrative Region, China, between January 2020 and May 2023. The risk of developing preterm preeclampsia was determined using the Fetal Medicine Foundation triple test (maternal factors, mean arterial pressure, uterine artery pulsatility index, and placental growth factor). 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 according to maternal age, weight, and the date of the scan. The participants were followed up at 12 to 15⁺⁶, 20 to 24⁺⁶, and 30 to 37⁺⁶ weeks to measure mean arterial pressure, uterine artery pulsatility index, placental growth factor, and soluble fms-like tyrosine kinase-1 at each visit. The level of biomarker was expressed as multiple of the median. Log₁₀ transformation was applied to fit the data to a Gaussian distribution before 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 mean arterial pressure multiple of the median, log₁₀ uterine artery pulsatility index multiple of the median, and log₁₀ soluble fms-like tyrosine kinase-1 multiple of the median, and higher estimated marginal mean log₁₀ placental growth factor multiple of the median across gestation compared with the high-risk groups (P<.001). Among high-risk women, those who developed preeclampsia exhibited a significantly higher estimated marginal mean log₁₀ mean arterial pressure multiple of the median (0.06378 vs 0.02985; P<.001), log₁₀ uterine artery pulsatility index multiple of the median (0.08651 vs 0.02226; P<.001), and log₁₀ soluble fms-like tyrosine kinase-1 multiple of the median (0.13204 vs 0.01234; P<.001), and lower estimated marginal mean log₁₀ placental growth factor multiple of the median (-0.33504 vs -0.16388; P<.001) across gestation compared with those without preeclampsia. In the individual gestational time point analysis, compared with high-risk women without preeclampsia, those who developed preeclampsia exhibited higher log₁₀ mean arterial pressure multiple of the median in all 3 trimesters, higher log₁₀ uterine artery pulsatility index multiple of the median and lower log₁₀ placental growth factor multiple of the median in the second and third trimesters, and higher log₁₀ soluble fms-like tyrosine kinase-1 multiple of the median in the third trimester.

Conclusion: This study demonstrated that high-risk women who developed preeclampsia consistently exhibited high mean arterial pressure levels from the first trimester that remained unchanged during pregnancy, high uterine artery pulsatility index levels and low placental growth factor levels starting from the second trimester, and high soluble fms-like tyrosine kinase-1 levels in the third trimester compared with those who did 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.

Keywords: Fetal Medicine Foundation; PlGF; aspirin; biomarkers; high-risk; longitudinal analysis; low-risk; mean arterial pressure; placental growth factor; preeclampsia; prevention; sFlt-1; screening; soluble fms-like tyrosine kinase-1; temporal changes; triple test; uterine artery pulsatility index.