Elevated Endogenous Erythropoietin Concentrations Are Associated with Increased Risk of Brain Damage in Extremely Preterm Neonates
Open Access
- 20 March 2015
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 10 (3), e0115083
- https://doi.org/10.1371/journal.pone.0115083
Abstract
We sought to determine, in very preterm infants, whether elevated perinatal erythropoietin (EPO) concentrations are associated with increased risks of indicators of brain damage, and whether this risk differs by the co-occurrence or absence of intermittent or sustained systemic inflammation (ISSI). Protein concentrations were measured in blood collected from 786 infants born before the 28th week of gestation. EPO was measured on postnatal day 14, and 25 inflammation-related proteins were measured weekly during the first 2 postnatal weeks. We defined ISSI as a concentration in the top quartile of each of 25 inflammation-related proteins on two separate days a week apart. Hypererythropoietinemia (hyperEPO) was defined as the highest quartile for gestational age on postnatal day 14. Using logistic regression and multinomial logistic regression models, we compared risks of brain damage among neonates with hyperEPO only, ISSI only, and hyperEPO+ISSI, to those who had neither hyperEPO nor ISSI, adjusting for gestational age. Newborns with hyperEPO, regardless of ISSI, were more than twice as likely as those without to have very low (< 55) Mental (OR 2.3; 95% CI 1.5-3.5) and/or Psychomotor (OR 2.4; 95% CI 1.6-3.7) Development Indices (MDI, PDI), and microcephaly at age two years (OR 2.4; 95%CI 1.5-3.8). Newborns with both hyperEPO and ISSI had significantly increased risks of ventriculomegaly, hemiparetic cerebral palsy, microcephaly, and MDI and PDI < 55 (ORs ranged from 2.2-6.3), but not hypoechoic lesions or other forms of cerebral palsy, relative to newborns with neither hyperEPO nor ISSI. hyperEPO, regardless of ISSI, is associated with elevated risks of very low MDI and PDI, and microcephaly, but not with any form of cerebral palsy. Children with both hyperEPO and ISSI are at higher risk than others of very low MDI and PDI, ventriculomegaly, hemiparetic cerebral palsy, and microcephaly.Keywords
This publication has 48 references indexed in Scilit:
- Elevated Concentrations of Inflammation-Related Proteins in Postnatal Blood Predict Severe Developmental Delay at 2 Years of Age in Extremely Preterm InfantsThe Journal of Pediatrics, 2012
- Neuroprotective potential of erythropoietin and its derivative carbamylated erythropoietin in periventricular leukomalaciaExperimental Neurology, 2011
- Maternal Microbe-Specific Modulation of Inflammatory Response in Extremely Low-Gestational-Age NewbornsmBio, 2011
- Inflammation-related proteins in the blood of extremely low gestational age newborns. The contribution of inflammation to the appearance of developmental regulationCytokine, 2011
- The ELGAN study of the brain and related disorders in extremely low gestational age newbornsEarly Human Development, 2009
- IL-6 and Stat3 Are Required for Survival of Intestinal Epithelial Cells and Development of Colitis-Associated CancerCancer Cell, 2009
- Attenuation of monocyte proinflammatory cytokine responses toNeisseria meningitidisin children by erythropoietinClinical and Experimental Immunology, 2008
- Biological and Technical Variables Affecting Immunoassay Recovery of Cytokines from Human Serum and Simulated Vaginal Fluid: A Multicenter StudyAnalytical Chemistry, 2008
- Observer variability assessing US scans of the preterm brain: the ELGAN studyPediatric Radiology, 2007
- Trichomonas vaginalisLipophosphoglycan Triggers a Selective Upregulation of Cytokines by Human Female Reproductive Tract Epithelial CellsInfection and Immunity, 2006