Blood collected on dry blood spots is fit for newborn screening of sickle cell disease (SCD) by different analytical systems.

Sickle cell disease (SCD) is a severe hereditary hemoglobinopathy with the highest burden in sub-Saharan Africa. Timely diagnosis via newborn screening is critical to enabling low-cost, life-saving interventions, yet its implementation remains inconsistent worldwide. This study assessed the performance and analytical stability of dried blood spot (DBS) samples collected on Guthrie cards for quantifying hemoglobin S (Hb S), using three high-performance liquid chromatography (HPLC) platforms and one capillary electrophoresis system. Simulated neonatal samples at three Hb S concentrations (non-carrier, carrier, and affected) were analyzed at three timepoints (immediate, 1 week, and 2 weeks post-collection). Across all methods, Hb S quantification was highly reproducible, with inter-timepoint variation remaining within the predefined critical threshold for the vast majority of the measurements. While minor discrepancies were observed for fetal hemoglobin (Hb F), all methods correctly classified samples for SCD screening purposes. These findings confirm that Guthrie card-based DBS is a robust and practical matrix for Hb S detection, suitable for transport and delayed analysis-even across different analytical platforms. Limitations include the use of spiked rather than native SCD neonatal samples and ambient-temperature shipping. Nonetheless, the results support broader adoption of DBS in SCD screening programs, particularly in low-resource or decentralized settings, and highlight the need for further standardization of Hb F quantification.