Evaluation of the Effect of Low-Dose Aspirin on Biochemical and Biophysical Biomarkers for Placental Disease in Low-Risk Pregnancy: Secondary Analysis of a Multicenter RCT

Abstract

Objective To assess the effect of aspirin use in low-risk pregnancy on: (1) pregnancy-associated plasma protein-A (PAPP-A) and placental-like growth factor (PLGF); (2) urinary albumin-to-creatinine ratio (ACR) and blood pressure; (3) fetal growth parameters; and (4) placental histopathology. Study Design This secondary analysis from the T rial of low-dose aspirin with an E arly S creening T est for preeclampsia and growth restriction randomized controlled trial was based on low-risk nulliparous women randomized at 11 weeks to (1) aspirin 75 mg; (2) no aspirin; and (3) aspirin based on the preeclampsia Fetal Medicine Foundation screening test. At baseline, women underwent assessment of blood pressure, PAPP-A, PLGF, and ACR, repeated 9 to 10 weeks postaspirin, in addition to fetal growth assessment. Gross and histopathological placental analyses were performed in line with Amsterdam criteria. Results A total of 445 subjects were included (aspirin n = 163 [36.6%]; no aspirin n = 282 [63.4%]). Although the fetal-to-placental weight ratio was significantly greater in the aspirin group (7.5 [±1.3] vs. 7.3 [±1.4], p = 0.045), as was change in ultrasound assessed estimated fetal weight from second to third trimesters (1,624.5 g [±235.1] vs. 1,606.2 [±189.4], p = 0.042), this was invalidated by the lack of a difference in birth weight. Aspirin did not significantly impact on change in serum or urine preeclampsia biomarkers, maternal blood pressure, or placental histopathology. Conclusion Aspirin use in low-risk pregnancy does not appear to impact on preeclampsia biomarkers, fetal growth, or placental pathology.

An Examination of the Effect of Aspirin and Salicylic Acid on Soluble Fms-like Tyrosine Kinase-1 Release from Human Placental Trophoblasts

“…Mayer-Pickel et al showed that 75-150 mg/day aspirin overall did not affect the plasma sFlt1/PlGF ratio throughout gestation in women regardless of obstetric outcomes, although there appeared to be a transient reduction of the sFlt1/PlGF ratio at 11-14 weeks gestation, but not later, in a subset women with a pathologic first-trimester screening for preeclampsia risk [26]. Mone et al recently evaluated the effect of aspirin (75 mg/day) on low-risk pregnant women and found no effect on serum biomarkers, including PlGF and pregnancy-associated plasma protein-A (PAPP-A); no sFlt1 data were reported in their study [27]. Thus, the available clinical evidence for a role of LDA in sFlt1 modulation is sparse and inconclusive, and further clinical biomarker investigation is needed to provide a definitive answer.…”

“…To date, available randomized clinical trials have not documented a reduction of plasma sFlt1 by LDA in pregnant women [25][26][27]; therefore, although plausible, this putative mechanism of action merits careful examination, considering that sFlt1 plays a critical role in connecting placental pathologies to maternal symptoms. If confirmed, aspirin's effect on sFlt1 might be exploitable for the development of next-generation therapies with better potency and/or efficacy.…”

Effect of Low-Dose Aspirin on Soluble FMS-Like Tyrosine Kinase 1/Placental Growth Factor (sFlt-1/PlGF Ratio) in Pregnancies at High Risk for the Development of Preeclampsia

“…The effect of aspirin on angiogenic factors, such as sFlt-1 and PlGF is the subject of ongoing interest and has been examined in several in vitro studies [27,28,29,30,31].…”

“…Mone et al aimed to determine the impact of low-dose aspirin in low-risk pregnancies on several biomarkers such as PAPP-A and PlGF as well as on maternal blood pressure, fetal growth parameters, and histological findings of the placenta [31]. The authors could not find any significant impact of low-dose aspirin on these parameters.…”