The Placenta in Fetal Death: Molecular Evidence of Dysregulation of Inflammatory, Proliferative, and Fetal Protective Pathways

( Am J Obstet Gynecol . 2025;232:328.e1-9. DOI: 10.1016/j.ajog.2024.06.011) Fetal death, affecting over 2 million cases globally each year, remains poorly understood despite its prevalence. About 60% of fetal deaths after 28 weeks of gestation are unexplained and without known risk factors. Evidence increasingly suggests that the placenta plays a vital role in this condition, specifically placental vascular malperfusion, placental senescence, and hypoxic-ischemic stress. The placenta is responsible for producing hormones, cytokines, and growth factors that regulate the relationship between the mother and fetus. Disruptions in the release of these substances have been linked to fetal death. Expression and function of these substances may be altered by clinical scenarios such as inflammation and infection.