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Fetal Hemoglobin as a Predictive Biomarker for Retinopathy of Prematurity: A Prospective Multicenter Cohort Study in
Mariza Fevereiro-Martins1,2,3, Laura Aguiar1,2, Ângela Inácio1,2
1Ecogenetics and Human Health Unit, Environmental Health Institute (ISAMB), Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisbon, Portugal.
Insights
Low fetal hemoglobin (HbF) levels in preterm infants may increase the risk of retinopathy of prematurity (ROP). Monitoring HbF could help predict ROP and guide interventions to preserve it, potentially reducing vision impairment.
Area of Science:
- Neonatal Medicine
- Ophthalmology
- Hematology
Background:
- Retinopathy of prematurity (ROP) is a significant cause of vision loss in premature infants, with oxygen exposure implicated in its development.
- Red blood cell (RBC) transfusions in neonatal intensive care units (NICUs) can lower fetal hemoglobin (HbF) levels, potentially influencing ROP pathogenesis.
- Understanding the interplay between RBC transfusions, HbF, and ROP is crucial for developing effective preventative strategies.
Purpose of the Study:
- To investigate the association between RBC transfusions, HbF percentage, and the incidence of ROP in preterm infants.
- To evaluate the potential of HbF as a predictive biomarker for ROP development.
- To explore interventions aimed at preserving HbF to mitigate ROP risk.
Main Methods:
- A prospective, multicenter study involving preterm infants (<32 weeks GA or <1500 g) across eight Portuguese NICUs.
- ROP staging was performed using the International Classification of ROP (ICROP2) criteria.
- HbF fractions were measured in the first four weeks of life, with statistical analysis comparing infants with and without ROP.
Main Results:
- Of 82 infants, 35.4% developed ROP, and 4.9% required treatment.
- Infants with ROP exhibited a higher number of RBC transfusions and lower HbF percentages compared to those without ROP (p < 0.05).
- Lower HbF levels were significantly correlated with increased RBC transfusions (p < 0.001) and a higher risk of ROP (p < 0.05).
Conclusions:
- Reduced HbF percentage in early life is associated with an increased risk of ROP in preterm infants.
- HbF may serve as a valuable predictive biomarker for ROP.
- Strategies to preserve HbF levels could potentially reduce ROP incidence, warranting further investigation and validation.
Abstract:
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.
