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Current Pediatric Reviews

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ISSN (Print): 1573-3963
ISSN (Online): 1875-6336

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Research Article

Longitudinal Assessment of Preterm Infants Treated with Erythropoiesis Stimulating Agents

Author(s): Robin K. Ohls*, Jean Lowe, Ronald A. Yeo, Shrena Patel, Sarah Winter, Richard A. Campbell, Shawna Baker and John Phillips

Volume 19, Issue 4, 2023

Published on: 21 December, 2022

Page: [417 - 424] Pages: 8

DOI: 10.2174/1573396319666221219114704

Price: $65

Abstract

Objective: We previously reported improved neurodevelopment at 2 and 4 years among preterm infants treated with erythropoietin or darbepoetin, known as erythropoiesis-stimulating agents (ESAs). We now characterize longitudinal outcomes through 6 years.

Methods: Children randomized to ESAs or placebo were evaluated at 6 years. Healthy-term children served as controls. Tests of cognition and executive function (EF) were performed.

Results: Cognitive/EF scores remained similar between 4 and 6 years within each group (ESA: 43 children; placebo: 17 children; term: 21 children). ESA recipients scored higher than placebo on Full-Scale IQ (94.2 ± 18.6 vs. 81.6 ± 16.7, p = 0.022), and Performance IQ (97.3 ± 16.2 vs. 81.7 ± 15.2, = 0.005). Aggregate EF trended better for the ESA group. Term controls scored better than placebo on all measures. ESA and term controls scored similarly on cognitive and EF tests.

Conclusion: ESA recipients had better outcomes than placebo recipients, and were similar to term children. ESAs may improve long-term cognition and executive function in preterm infants.

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Graphical Abstract

[1]
McGowan EC, Vohr BR. Neurodevelopmental follow-up of preterm infants. What is new? Pediatr Clin North Am 2019; 66(2): 509-23.
[http://dx.doi.org/10.1016/j.pcl.2018.12.015] [PMID: 30819351]
[2]
Houdt CA, Oosterlaan J, Wassenaer-Leemhuis AG, Kaam AH, Aarnoudse-Moens CSH. Executive function deficits in children born pre-term or at low birthweight: A meta‐analysis. Dev Med Child Neurol 2019; 61(9): 1015-24.
[http://dx.doi.org/10.1111/dmcn.14213] [PMID: 30945271]
[3]
Aarnoudse-Moens CSH, Oosterlaan J, Duivenvoorden HJ, van Goudoever JB, Weisglas-Kuperus N. Development of preschool and aca-demic skills in children born very preterm. J Pediatr 2011; 158(1): 51-6.
[http://dx.doi.org/10.1016/j.jpeds.2010.06.052] [PMID: 20708749]
[4]
Iwai M, Stetler RA, Xing J, et al. Enhanced oligodendrogenesis and recovery of neurological function by erythropoietin after neonatal hypoxic/ischemic brain injury. Stroke 2010; 41(5): 1032-7.
[http://dx.doi.org/10.1161/STROKEAHA.109.570325] [PMID: 20360553]
[5]
Juul SE, Beyer RP, Bammler TK, McPherson RJ, Wilkerson J, Farin FM. Microarray analysis of high-dose recombinant erythropoietin treatment of unilateral brain injury in neonatal mouse hippocampus. Pediatr Res 2009; 65(5): 485-92.
[http://dx.doi.org/10.1203/PDR.0b013e31819d90c8] [PMID: 19190543]
[6]
Vairano M, Russo CD, Pozzoli G, et al. Erythropoietin exerts anti-apoptotic effects on rat microglial cells in vitro. Eur J Neurosci 2002; 16(4): 584-92.
[http://dx.doi.org/10.1046/j.1460-9568.2002.02125.x] [PMID: 12270034]
[7]
Sugawa M, Sakurai Y, Ishikawa-Ieda Y, Suzuki H, Asou H. Effects of erythropoietin on glial cell development; oligodendrocyte matura-tion and astrocyte proliferation. Neurosci Res 2002; 44(4): 391-403.
[http://dx.doi.org/10.1016/S0168-0102(02)00161-X] [PMID: 12445627]
[8]
Jantzie LL, Getsy PM, Firl DJ, Wilson CG, Miller RH, Robinson S. Erythropoietin attenuates loss of potassium chloride co-transporters following prenatal brain injury. Mol Cell Neurosci 2014; 61: 152-62.
[http://dx.doi.org/10.1016/j.mcn.2014.06.009] [PMID: 24983520]
[9]
Jantzie LL, Corbett CJ, Firl DJ, Robinson S. Postnatal erythropoietin mitigates impaired cerebral cortical development following subplate loss from prenatal hypoxia–ischemia. Cereb Cortex 2015; 25(9): 2683-95.
[http://dx.doi.org/10.1093/cercor/bhu066] [PMID: 24722771]
[10]
Ohls RK, Christensen RD, Kamath-Rayne BD, et al. A randomized, masked, placebo-controlled study of darbepoetin administered to preterm infants. Pediatrics 2013; 132(1): e119-27.
[http://dx.doi.org/10.1542/peds.2013-0143]
[11]
Bayley N. Bayley scales of infant and toddler development. (3rd ed.), San Antonio, TX: Harcourt Assessment 2006.
[12]
Ohls RK, Kamath-Rayne BD, Christensen RD, et al. Cognitive outcomes of preterm infants randomized to darbepoetin, erythropoietin, or placebo. Pediatrics 2014; 133(6): 1023-30.
[http://dx.doi.org/10.1542/peds.2013-4307] [PMID: 24819566]
[13]
Ohls RK, Cannon DC, Phillips J, et al. Preschool assessment of preterm infants treated with Darbepoetin and erythropoietin. Pediatrics 2016; 137(3)e20153859
[http://dx.doi.org/10.1542/peds.2015-3859] [PMID: 26908704]
[14]
Wechsler D. The Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). (3rd ed.), San Antonio, TX: The Psychological Corpora-tion 2002.
[15]
Phillips JP, Yeo RA, Caprihan A, Cannon DC, Patel S. Neuroimaging in former preterm children who received erythropoiesis stimulating agents. Pediatr Res 2017; 82(4): 685-90.
[PMID: 28553989]
[16]
Neubauer AP, Voss W, Wachtendorf M, Jungmann T. Erythropoietin improves neurodevelopmental outcome of extremely preterm in-fants. Ann Neurol 2010; 67(5): 21977.
[http://dx.doi.org/10.1002/ana.21977] [PMID: 20437563]
[17]
Natalucci G, Latal B, Koller B, et al. Effect of early prophylactic high-dose recombinant human erythropoietin in very preterm infants on neurodevelopmental outcome at 2 years: A randomized clinical trail. JAMA 2016; 315(19): 2079-85.
[http://dx.doi.org/10.1001/jama.2016.5504] [PMID: 27187300]
[18]
Song J, Sun H, Xu F, et al. Recombinant human erythropoietin improves neurological outcomes in very preterm infants. Ann Neurol 2016; 80(1): 24-34.
[http://dx.doi.org/10.1002/ana.24677] [PMID: 27130143]
[19]
Gasparovic C, Caprihan A, Yeo RA, et al. The long-term effect of erythropoiesis stimulating agents given to preterm infants: A 1H-MRS study on neurometabolites in early childhood. Pediatr Radiol 2018; 48(3): 374-82.
[http://dx.doi.org/10.1007/s00247-017-4052-1] [PMID: 29335880]
[20]
Leuchter RHV, Gui L, Poncet A, et al. Association between early administration of high-dose erythropoietin in preterm infants and brain MRI abnormality at term-equivalent age. JAMA 2014; 312(8): 817-24.
[http://dx.doi.org/10.1001/jama.2014.9645] [PMID: 25157725]
[21]
O’Gorman RL, Bucher HU, Held U, Koller BM, Hüppi PS, Hagmann CF. Tract-based spatial statistics to assess the neuroprotective effect of early erythropoietin on white matter development in preterm infants. Brain 2015; 138(2): 388-97.
[http://dx.doi.org/10.1093/brain/awu363] [PMID: 25534356]
[22]
Juul SE, Comstock BA, Wadhawan R, et al. A randomized trial of erythropoietin for neuroprotection in preterm infants. N Engl J Med 2020; 382(3): 233-43.
[http://dx.doi.org/10.1056/NEJMoa1907423] [PMID: 31940698]
[23]
Bierer R, Peceny MC, Hartenberger CH, Ohls RK. Erythropoietin concentrations and neurodevelopmental outcome in preterm infants. Pediatrics 2006; 118(3): e635-40.
[http://dx.doi.org/10.1542/peds.2005-3186] [PMID: 16908620]
[24]
Brown MS, Eichorst D, LaLa-Black B, Gonzalez R. Higher cumulative doses of erythropoietin and developmental outcomes in preterm infants. Pediatrics 2009; 124(4): e681-7.
[http://dx.doi.org/10.1542/peds.2008-2701] [PMID: 19786428]
[25]
Maxwell JR, Ohls RK. Update on erythropoiesis-stimulating agents administered to neonates for neuroprotection. Neoreviews 2019; 20(11): e622-35.
[http://dx.doi.org/10.1542/neo.20-11-e622] [PMID: 31676737]
[26]
Anderson PJ, Doyle LW. Cognitive and educational deficits in children born extremely preterm. Semin Perinatol 2008; 32(1): 51-8.
[http://dx.doi.org/10.1053/j.semperi.2007.12.009] [PMID: 18249240]
[27]
Burnett AC, Youssef G, Anderson PJ, Duff J, Doyle LW, Cheong JLY. Exploring the “Preterm Behavioral Phenotype” in children born extremely preterm. J Dev Behav Pediatr 2019; 40(3): 200-7.
[http://dx.doi.org/10.1097/DBP.0000000000000646] [PMID: 30801416]
[28]
Mulder H, Hoofs H, Verhagen J, van der Veen I, Leseman PP. Psychometric properties and convergent and predictive validity of an ex-ecutive function test battry for two-year-olds. Front Ped 2014; 5: 1-17.
[29]
Lowe JR, Duncan AF, Bann CM, et al. Early working memory as a racially and ethnically neutral measure of outcome in extremely pre-term children at 18-22months. Early Hum Dev 2013; 89(12): 1055-61.
[http://dx.doi.org/10.1016/j.earlhumdev.2013.08.009] [PMID: 23993309]

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