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Elevated endogenous erythropoietin concentrations are associated with increased risk of brain damage in extremely preterm neonates.

Korzeniewski SJ, Allred E, Logan JW, Fichorova RN, Engelke S, Kuban KC, O'Shea TM, Paneth N, Holm M, Dammann O, Leviton A, ELGAN study investigato - PLoS ONE (2015)

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, and Detroit, MI, United States of America; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States of America; Department of Epidemiology & Biostatistics, Michigan State University, East Lansing, MI, United States of America.

ABSTRACT

Background: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

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Odds ratios (and 95% confidence intervals) for ventriculomegaly (A.) and hypoechoic lesion (B.) calculated with logistic regression models.The three risk groups: ISSI only: (an inflammation-related protein concentration in the highest quartile on two days); hyperEPO only (an EPO concentration in the highest quartile on day 14); and ISSI+hyperEPO are each compared to the referent group that consists of newborns who had neither ISSI nor hyperEPO. All models are adjusted for gestational age.
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pone.0115083.g001: Odds ratios (and 95% confidence intervals) for ventriculomegaly (A.) and hypoechoic lesion (B.) calculated with logistic regression models.The three risk groups: ISSI only: (an inflammation-related protein concentration in the highest quartile on two days); hyperEPO only (an EPO concentration in the highest quartile on day 14); and ISSI+hyperEPO are each compared to the referent group that consists of newborns who had neither ISSI nor hyperEPO. All models are adjusted for gestational age.

Mentions: ^ cerebral palsy subtype and MDI and PDI category odds ratios were modeled using multinomial logistic regression


Elevated endogenous erythropoietin concentrations are associated with increased risk of brain damage in extremely preterm neonates.

Korzeniewski SJ, Allred E, Logan JW, Fichorova RN, Engelke S, Kuban KC, O'Shea TM, Paneth N, Holm M, Dammann O, Leviton A, ELGAN study investigato - PLoS ONE (2015)

Odds ratios (and 95% confidence intervals) for ventriculomegaly (A.) and hypoechoic lesion (B.) calculated with logistic regression models.The three risk groups: ISSI only: (an inflammation-related protein concentration in the highest quartile on two days); hyperEPO only (an EPO concentration in the highest quartile on day 14); and ISSI+hyperEPO are each compared to the referent group that consists of newborns who had neither ISSI nor hyperEPO. All models are adjusted for gestational age.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4368546&req=5

pone.0115083.g001: Odds ratios (and 95% confidence intervals) for ventriculomegaly (A.) and hypoechoic lesion (B.) calculated with logistic regression models.The three risk groups: ISSI only: (an inflammation-related protein concentration in the highest quartile on two days); hyperEPO only (an EPO concentration in the highest quartile on day 14); and ISSI+hyperEPO are each compared to the referent group that consists of newborns who had neither ISSI nor hyperEPO. All models are adjusted for gestational age.
Mentions: ^ cerebral palsy subtype and MDI and PDI category odds ratios were modeled using multinomial logistic regression

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, and Detroit, MI, United States of America; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States of America; Department of Epidemiology & Biostatistics, Michigan State University, East Lansing, MI, United States of America.

ABSTRACT

Background: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus