Translational perinatal medicine in non-immune fetal hydrops: from prenatal to modern cellular therapies

Abstract

Introduction. Non-immune fetal hydrops (NIHF) represents one of the most severe conditions in fetal medicine, characterized by the pathological accumulation of fluid in at least two fetal compartments and associated with high perinatal mortality. Its heterogeneous etiology includes genetic anomalies, cardiovascular pathologies, congenital infections, and idiopathic causes. Recent advances in prenatal diagnostics have improved early etiological identification; however, therapeutic options remain limited. Translational perinatal medicine aims to integrate insights from cellular biology and regenerative medicine into fetal management, including the use of cellular therapies and intrauterine transplantation strategies. The objective of this study is to evaluate the potential role of modern cellular therapies in the management of NIHF. Materials and Methods. A narrative review of recent scientific literature published between 2022 and 2025 in PubMed, Scopus, and Web of Science was conducted, including review articles and experimental studies. Data were synthesized descriptively, and results from experimental studies were analyzed comparatively. Results. Current literature confirms that the prognosis of NIHF largely depends on the prenatal etiological diagnosis and the timeliness of therapeutic intervention. The development of stem cell– based therapies, including transamniotic administration of mesenchymal and hematopoietic stem cells, has shown promising effects on fetal hematopoiesis, placental inflammation, and fetal survival in experimental models. Innovative strategies, such as transamniotic stem cell therapy, enable systemic fetal cell distribution through minimally invasive approaches. Furthermore, extracellular vesicles derived from amniotic fluid–derived stem cells have demonstrated regenerative potential in compromised fetal lung development, a mechanism relevant to the progression of fetal hydrops. These approaches support a transition from purely supportive care toward targeted biological interventions. Conclusions The integration of advanced prenatal diagnostics with cellular therapies represents a promising approach in managing non-immune fetal hydrops. Translational perinatal medicine enables the shift from understanding pathogenic mechanisms to fetal regenerative interventions. Future studies are needed to validate the safety and efficacy of intrauterine cellular transplantation and improve neonatal outcomes.