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

<b>Background/Objectives:</b> 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 hemoglo...

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Main Authors: Mariza Fevereiro-Martins, Laura Aguiar, Ângela Inácio, Carlos Cardoso, Ana Carolina Santos, Carlos Marques-Neves, Hercília Guimarães, Rui Pinto, Manuel Bicho
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/1/110
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author Mariza Fevereiro-Martins
Laura Aguiar
Ângela Inácio
Carlos Cardoso
Ana Carolina Santos
Carlos Marques-Neves
Hercília Guimarães
Rui Pinto
Manuel Bicho
author_facet Mariza Fevereiro-Martins
Laura Aguiar
Ângela Inácio
Carlos Cardoso
Ana Carolina Santos
Carlos Marques-Neves
Hercília Guimarães
Rui Pinto
Manuel Bicho
author_sort Mariza Fevereiro-Martins
collection DOAJ
description <b>Background/Objectives:</b> 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. <b>Methods:</b> 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 <i>p</i> < 0.05. <b>Results:</b> 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 (<i>p</i> < 0.05). Lower HbF was associated with more RBC transfusions (<i>p</i> < 0.001). Kaplan–Meier survival curves showed a higher ROP risk in infants with reduced HbF (<i>p</i> < 0.05). <b>Conclusions:</b> 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.
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spelling doaj-art-abcb3b4e77bc491999ce7f86e04518422025-01-24T13:24:03ZengMDPI AGBiomedicines2227-90592025-01-0113111010.3390/biomedicines13010110Fetal Hemoglobin as a Predictive Biomarker for Retinopathy of Prematurity: A Prospective Multicenter Cohort Study in PortugalMariza Fevereiro-Martins0Laura Aguiar1Ângela Inácio2Carlos Cardoso3Ana Carolina Santos4Carlos Marques-Neves5Hercília Guimarães6Rui Pinto7Manuel Bicho8Ecogenetics and Human Health Unit, Environmental Health Institute (ISAMB), Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisbon, PortugalEcogenetics and Human Health Unit, Environmental Health Institute (ISAMB), Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisbon, PortugalEcogenetics and Human Health Unit, Environmental Health Institute (ISAMB), Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisbon, PortugalClinical Analysis Laboratory Dr. Joaquim Chaves, Rua Aníbal Bettencourt, nº3, Edificio CORE, 2790-225 Carnaxide, PortugalEcogenetics and Human Health Unit, Environmental Health Institute (ISAMB), Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisbon, PortugalEcogenetics and Human Health Unit, Environmental Health Institute (ISAMB), Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisbon, PortugalDepartment of Gynecology, Obstetrics and Pediatrics, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, PortugalClinical Analysis Laboratory Dr. Joaquim Chaves, Rua Aníbal Bettencourt, nº3, Edificio CORE, 2790-225 Carnaxide, PortugalEcogenetics 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<b>Background/Objectives:</b> 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. <b>Methods:</b> 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 <i>p</i> < 0.05. <b>Results:</b> 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 (<i>p</i> < 0.05). Lower HbF was associated with more RBC transfusions (<i>p</i> < 0.001). Kaplan–Meier survival curves showed a higher ROP risk in infants with reduced HbF (<i>p</i> < 0.05). <b>Conclusions:</b> 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.https://www.mdpi.com/2227-9059/13/1/110retinopathy of prematurityneonatal diseasesfetal hemoglobinpathophysiologyinnovative therapeutic approachesneonatal anemia
spellingShingle Mariza Fevereiro-Martins
Laura Aguiar
Ângela Inácio
Carlos Cardoso
Ana Carolina Santos
Carlos Marques-Neves
Hercília Guimarães
Rui Pinto
Manuel Bicho
Fetal Hemoglobin as a Predictive Biomarker for Retinopathy of Prematurity: A Prospective Multicenter Cohort Study in Portugal
Biomedicines
retinopathy of prematurity
neonatal diseases
fetal hemoglobin
pathophysiology
innovative therapeutic approaches
neonatal anemia
title Fetal Hemoglobin as a Predictive Biomarker for Retinopathy of Prematurity: A Prospective Multicenter Cohort Study in Portugal
title_full Fetal Hemoglobin as a Predictive Biomarker for Retinopathy of Prematurity: A Prospective Multicenter Cohort Study in Portugal
title_fullStr Fetal Hemoglobin as a Predictive Biomarker for Retinopathy of Prematurity: A Prospective Multicenter Cohort Study in Portugal
title_full_unstemmed Fetal Hemoglobin as a Predictive Biomarker for Retinopathy of Prematurity: A Prospective Multicenter Cohort Study in Portugal
title_short Fetal Hemoglobin as a Predictive Biomarker for Retinopathy of Prematurity: A Prospective Multicenter Cohort Study in Portugal
title_sort fetal hemoglobin as a predictive biomarker for retinopathy of prematurity a prospective multicenter cohort study in portugal
topic retinopathy of prematurity
neonatal diseases
fetal hemoglobin
pathophysiology
innovative therapeutic approaches
neonatal anemia
url https://www.mdpi.com/2227-9059/13/1/110
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