levated levels of S100B protein are a well-established marker of central nervous system (CNS) damage. Fetal anemia resulting from hemolytic disease of the fetus and newborn (HDFN) often necessitates intrauterine transfusions (IUTs) and represents a significant risk factor for CNS injury. However, it remains uncertain whether S100B protein levels can reliably predict which fetuses are at higher risk for CNS complications in this context. Furthermore, the potential role of measuring S100B concentrations before IUT in prenatal assessments, and its relationship to the severity of anemia and fetal cerebral blood flow, remains poorly understood. This study aims to investigate the concentration of S100B protein in cord blood from newborns with HDFN-related fetal anemia requiring IUT. The study group comprises pregnancies complicated by HDFN with abnormal middle cerebral artery (MCA) blood flow, indicating the need for IUT. In this group, S100B protein levels will be measured before each IUT, with additional measurements if further transfusions are required. The control group consists of pregnancies with HDFN that do not require IUT. Cord blood samples will be collected at birth to evaluate S100B protein levels in both groups. Additionally, fetal MCA blood flow will be monitored, and in the study group, fetal hemoglobin and hematocrit levels will be assessed before each IUT. The primary endpoints of the study include the measurement of cord blood S100B protein levels before IUT in the study group and at birth in both groups. Secondary endpoints will explore the potential correlations between S100B protein levels and umbilical cord blood gas parameters (e.g., pH, BE, lactate), fetal cerebral blood flow parameters (e.g., MCA-PSV values), and blood count parameters (e.g., hemoglobin and hematocrit levels), both before IUT in the study group and after birth in both groups.