Endogenous erythropoietin concentrations and association with retinopathy of prematurity and brain injury in preterm infants.

Nancy M Fahim,Michael K Georgieff,Raghavendra B Rao,Scott Naisbitt,Lei Zhang,Terrie E Inder,Emma Duerden

doi:10.1371/journal.pone.0252655

Abstract

BackgroundEndogenous erythropoietin (EPO) concentrations vary widely in preterm infants and may be associated with perinatal risk factors and neurological outcomes. Erythropoietin is elevated in fetal hypoxia but is also a potential neuroprotectant.MethodsIn a prospective study of 27 infants ≤ 30 weeks gestation, serum erythropoietin concentrations were measured during the first month of life, on day 1 and weeks 1, 2, and 4, and related to perinatal risk factors and outcomes including retinopathy of prematurity and cerebral injury evaluated near term-equivalent post menstrual age using magnetic resonance imaging with quantitative scoring.ResultsLower birth weight was associated with higher EPO concentrations throughout the first 2 weeks of life (r = -0.6, p < 0.01). Higher day 1 and week 1 EPO concentrations were associated with lower Apgar score at 1 minute (r = - 0.5) and 5 minutes (r = -0.7), respectively (p < 0.01). Higher day 1 EPO concentrations and 2-week area under the curve were associated with increased risk (p = 0.01) and severity (r = 0.5, p < 0.02) of retinopathy of prematurity. Higher EPO concentrations at 2 weeks were associated with increased total brain injury score (r = 0.5, p < 0.05).ConclusionElevated endogenous erythropoietin concentrations in the first two weeks of life are associated with lower birth weight and increased risk of adverse outcomes.

Highlights

IntroductionSurvival has improved over the past two decades, children born preterm are at increased risk for cerebral palsy and cognitive and neurobehavioral deficits including lowered IQ, autism spectrum disorders, attention deficit hyperactivity disorder, anxiety disorders, and learning disabilities [1, 2]
Preterm birth is a major public-health challenge
In a prospective study of 27 infants 30 weeks gestation, serum erythropoietin concentrations were measured during the first month of life, on day 1 and weeks 1, 2, and 4, and related to perinatal risk factors and outcomes including retinopathy of prematurity and cerebral injury evaluated near term-equivalent post menstrual age using magnetic resonance imaging with quantitative scoring

Summary

Introduction

Survival has improved over the past two decades, children born preterm are at increased risk for cerebral palsy and cognitive and neurobehavioral deficits including lowered IQ, autism spectrum disorders, attention deficit hyperactivity disorder, anxiety disorders, and learning disabilities [1, 2]. Erythropoietin (EPO), a hematopoietic growth factor, has gained significant interest as a potential neuroprotective agent in this population. Endogenously produced EPO contributes to the reduction of ischemic cerebral injury in models of ischemic or hypoxic preconditioning [6, 7]. Endogenous erythropoietin (EPO) concentrations vary widely in preterm infants and may be associated with perinatal risk factors and neurological outcomes. Erythropoietin is elevated in fetal hypoxia but is a potential neuroprotectant

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Conclusion