Red Blood Cell Disorders in Newborns: Bridging Traditional and Modern Diagnostics

Neonatal red blood cell (RBC) disorders encompass a diverse range of inherited and acquired conditions with significant clinical implications. Due to the unique morphological and biochemical characteristics of neonatal erythrocytes, accurate diagnosis is often challenging but critical for effective management.

This review aims to synthesize current knowledge on the diagnosis of neonatal RBC disorders, highlighting the integration of traditional morphological analysis with advanced biochemical and molecular techniques.

A comprehensive literature review was conducted to examine diagnostic approaches to neonatal enzymopathies, membrane disorders, and hemoglobinopathies. The roles of peripheral blood smear (PBS) analysis, enzyme activity assays, and genetic testing-including next-generation sequencing (NGS)-were evaluated in the context of current clinical practice.

Peripheral blood smear examination remains a foundational tool for identifying characteristic RBC morphologies. Enzymatic deficiencies such as G6PD and pyruvate kinase deficiency, membrane disorders including hereditary spherocytosis and elliptocytosis, and hemoglobinopathies such as thalassemias and sickle cell disease require integrated diagnostic strategies. Advances in molecular diagnostics have enhanced diagnostic precision and expanded the ability to perform early, genotype-driven interventions.

A multidisciplinary diagnostic approach that combines morphology, biochemistry, and genetics is essential for the accurate identification and management of neonatal RBC disorders. Bridging traditional microscopy with modern genomic tools offers the potential for earlier diagnosis, personalized treatment, and improved clinical outcomes in neonatal hematology.