Fetal Hemoglobin as a Predictive Biomarker for Retinopathy of Prematurity: A Prospective Multicenter Cohort Study in Portugal

Fevereiro-Martins, M; Aguiar, L; Inácio, Â; Cardoso, C; Santos, AC; Marques-Neves, C; Guimarães, H; Pinto, R; Bicho, M

http://hdl.handle.net/10400.26/54277

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Background/Objectives: Retinopathy of prematurity (ROP) is a leading cause of vision impairment in preterm infants, with its pathogenesis linked to oxygen exposure. Red blood cell (RBC) transfusions, commonly performed in neonatal intensive care units (NICUs), reduce fetal hemoglobin (HbF) fraction, altering oxygen dynamics and potentially contributing to ROP. We aimed to investigate the relationship between RBC transfusions, HbF percentage, and ROP, evaluating HbF as a potential predictive biomarker. Methods: A multicenter, prospective study was conducted across eight Portuguese NICUs, involving infants born at <32 weeks gestational age (GA) or <1500 g. ROP staging followed the International Classification of ROP (ICROP2). Clinical data were collected during hospitalization, and HbF fractions were measured from blood samples in the first four weeks of life using standardized methods. Infants were stratified by ROP presence and treatment requirement. Statistical analysis was performed using SPSS 28.0, with p < 0.05. Results: Eighty-two infants (mean GA: 28.1 ± 2.1 weeks, birth weight: 1055.8 ± 258.3 g) were included. Among them, 29 (35.4%) presented ROP and 4 (4.9%) required treatment. Infants with ROP had more RBC transfusions and lower HbF percentages than those without ROP (p < 0.05). Lower HbF was associated with more RBC transfusions (p < 0.001). Kaplan-Meier survival curves showed a higher ROP risk in infants with reduced HbF (p < 0.05). Conclusions: Low HbF percentage in the first four weeks of life may increase ROP risk in preterm infants. HbF could serve as a biomarker for ROP prediction. Interventions preserving HbF may reduce ROP risk. Further studies are needed to validate HbF as a biomarker and refine prevention strategies.