A REVIEW OF HEMOLYTIC DISEASE OF THE FETUS AND NEWBORN: CLINICAL CHARACTERISTICS, IMMUNO-HEMATOLOGICAL INSIGHTS, AND EVOLVING THERAPEUTIC STRATEGIES

Abstract

Hemolytic disease of the fetus and newborn (HDFN) remains a clinically significant alloimmune condition despite advances in prevention, diagnosis, and management. This review aims to examine the clinical characteristics, immunohematological mechanisms, diagnostic approaches, and evolving therapeutic strategies associated with HDFN. A systematic literature review was conducted using PubMed, MEDLINE, EMBASE, and Google Scholar, covering studies published between 2020 and 2026. Relevant peer-reviewed articles addressing epidemiology, pathophysiology, diagnosis, and treatment outcomes were included and synthesized. Findings indicate that immunohematological factors, particularly antibody type (e.g., RhD, Kell), IgG subclasses (IgG1, IgG3), and elevated monocyte monolayer assay (MMA) indices (>20%), are strong predictors of disease severity. While the incidence of RhD-mediated HDFN has declined, severe cases persist, especially those associated with non-RhD antibodies. Advances in noninvasive diagnostics, such as fetal RHD genotyping, have improved early detection and targeted prophylaxis. Middle cerebral artery peak systolic velocity (MCA-PSV) Doppler remains the gold standard for detecting fetal anemia, although its reliability decreases following intrauterine transfusion (IUT). Therapeutically, IUT continues to be the cornerstone intervention, achieving survival rates of up to 97%, though risks increase in early gestation. Adjunctive therapies such as intravenous immunoglobulin (IVIG) demonstrate variable effectiveness. Emerging treatments, particularly FcRn inhibitors (e.g., nipocalimab), show promising potential in reducing maternal antibody transfer, decreasing the need for invasive procedures, and improving survival outcomes. Complications, including cholestasis and neutropenia, are more frequent in severe cases but are generally manageable. In conclusion, although significant progress has been made, HDFN remains a persistent clinical burden, highlighting the need for improved antenatal screening, standardized management protocols, and wider access to advanced diagnostics and emerging therapies