ACOG Conference Coverage

Aspirin Reduces Inflammation, Cell Death at the Fetal-Maternal Interface While Indomethacin Shows Cytotoxicity

Anthony Calabro, MA

Key Highlights

  • Aspirin reduced cell death by up to 84% in key placental cell types in a diseased model.
  • Indomethacin increased cytotoxicity across all fetal-maternal interface cell lines.
  • Aspirin also decreased the proinflammatory cytokine IL-8 at the cellular level.

In a cellular-level investigation of common nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin demonstrated a protective effect by reducing inflammation and cell death in placental tissues, while indomethacin, an NSAID used to treat acute pain or inflammation, was associated with increased cytotoxicity across all tested cell types. These findings were presented at the American College of Obstetricians and Gynecologists 2025 Annual Clinical & Scientific Meeting in Minneapolis, MN.

NSAIDs are commonly used in obstetric care, yet their effect at the cellular level of the placental-maternal interface are not fully understood. Understanding whether NSAIDs are cytotoxic or protective in this environment could potentially help clinicians manage inflammatory conditions during pregnancy.

This study aimed to explore the cytotoxic and anti-inflammatory properties of two widely used NSAIDs—aspirin and indomethacin—using an advanced in vitro model that mimics the fetal-maternal interface.

For their study, the researchers employed a microfluidic fetal membrane–placental organ-on-chip model composed of seven distinct cell types representative of the fetal-maternal interface. Therapeutic concentrations of aspirin (2 µg/mL, equivalent to 81 mg) and indomethacin (15 µg/mL) were applied to this system under both nondiseased and lipopolysaccharide (LPS)-simulated diseased states. Supernatants were analyzed for lactate dehydrogenase as a marker of cytotoxicity and for inflammatory cytokines, including IL-8.

Baseline cytotoxicity in the control group was approximately 20% in cell types such as amniotic epithelial cells (AEC), amniotic mesenchymal cells, cytotrophoblasts, and syncytiotrophoblasts (STB). Exposure to LPS increased cell death across five cell types. Aspirin significantly reduced cell death—by 84% in AEC and 48.7% in STB—under inflammatory conditions. Additionally, aspirin reduced levels of the proinflammatory cytokine IL-8, while indomethacin treatment resulted in increased cytotoxicity in all cell lines tested. Statistical analysis using three-way ANOVA confirmed these findings with high significance (P < .0001).

“Indomethacin demonstrates cell cytotoxicity at all layers of the feto-maternal interface,” the authors concluded. “On the other hand, aspirin demonstrated an improvement in cell death in a diseased state which can support the continued use of aspirin for the promotion of placental angiogenesis.”

Reference
Collins A. Commonly used nonsteroidal anti-inflammatory drug (NSAIDs) in obstetrics and associated placental cytotoxicity. Obstet Gynecol. 2025;145(Supp 6):1-102.