Relationship between serum erythropoietin levels and brain injury in preterm infants

CHEN Guang-Fu; LI Hui-Tao; HUANG Jin-Jie; WANG Zhang-Xing; LI Yun; YANG Chuan-Zhong; WU Ben-Qing; LIU Wen-Lan; LIU Li-Hui; KONG Qi; LIU Rong-Tian

doi:10.7499/j.issn.1008-8830.2016.10.006

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Chinese Journal of Contemporary Pediatrics ›› 2016, Vol. 18 ›› Issue (10) : 947-952. DOI: 10.7499/j.issn.1008-8830.2016.10.006

CLINICAL RESEARCH

Relationship between serum erythropoietin levels and brain injury in preterm infants

CHEN Guang-Fu¹, LI Hui-Tao², HUANG Jin-Jie³, WANG Zhang-Xing⁴, LI Yun¹, YANG Chuan-Zhong², WU Ben-Qing³, LIU Wen-Lan¹, LIU Li-Hui¹, KONG Qi¹, LIU Rong-Tian¹

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Abstract

Objective To study the relationship between the levels of erythropoietin (EPO) in serum and brain injury in preterm infants. Methods Three hundred and four preterm infants (gestational age: 28-34 weeks) born between October 2014 and September 2015 were enrolled in this study. Brain injury was diagnosed using cerebral ultrasound and MRI. The levels of EPO, S100 protein, neuron-specific enolase (NSE) and myelin basic protein (MBP) in serum were detected using ELISA. To compare the incidence of brain injury in different serum EPO levels in preterm infants, and the relationship between brain injury and serum EPO levels was analyzed. Results The incidence rate of brain injury in preterm infants was 41.1% (125/304). The incidence rate of brain injury in the low EPO level group was significantly higher than that in the middle-high EPO level groups (P < 0.01). The serum levels of S100 protein, NSE, and MBP in the brain injury groups were significantly higher than in the control group (P < 0.01). The serum EPO levels were negatively correlated with serum S100 protein concentration and NSE levels (P < 0.05). According to the multiple logistic regression analysis, low gestational age, low birth weight, asphyxia, prolonged mechanical ventilation, anemia and low serum EPO levels were the risk factor for brain injury in preterm infants. Conclusions There is a higher incidence rate of brain injury in preterm infants with lower serum EPO levels. The serum EPO levels may be correlated with brain injury in preterm infants.

Key words

Erythmpoietin / Brain injury / Risk factor / Preterm infant

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CHEN Guang-Fu, LI Hui-Tao, HUANG Jin-Jie, WANG Zhang-Xing, LI Yun, YANG Chuan-Zhong, WU Ben-Qing, LIU Wen-Lan, LIU Li-Hui, KONG Qi, LIU Rong-Tian. Relationship between serum erythropoietin levels and brain injury in preterm infants[J]. Chinese Journal of Contemporary Pediatrics. 2016, 18(10): 947-952 https://doi.org/10.7499/j.issn.1008-8830.2016.10.006

References

[1] 中国医师协会新生儿专业委员会. 早产儿脑损伤诊断与防治专家共识[J]. 中国当代儿科杂志, 2012, 14(12): 883-884.
[2] Juul SE, Ferriero DM. Pharmacologic neuroprotective strategies in neonatal brain injury[J]. Clin Perinatol, 2014, 41(1): 119-131.
[3] Mazur M, Miller RH, Robinson S. Postnatal erythropoietin treatment mitigates neural cell loss after systemic prenatal hypoxic-ischemic injury[J]. J Neurosurg Pediatr, 2010, 6(3): 206-221.
[4] Sirén AL, Fasshauer T, Bartels C, et al. Therapeutic potential of erythropoietin and its structural or functional variants in the nervous system[J]. Neurotherapeutics, 2009, 6(1): 108-127.
[5] 龙莎莎, 程国强. 早产儿脑白质损伤治疗的循证医学进展[J]. 临床儿科杂志, 2015, 33(3): 287-290.
[6] 王晓琴, 王莹, 李红. 早产儿脑损伤的危险因素[J]. 中国新生儿科杂志, 2015, 30(4): 286-288.
[7] Hassell KJ, Ezzati M, Alonso-Alconada D, et al. New horizons for newborn brain protection: enhancing endogenous neuroprotection[J]. Arch Dis Child Fetal Neonatal Ed, 2015, 100(6): F541-F552.
[8] 中华医学会儿科学分会新生儿学组, 《中华儿科杂志》编辑委员会. 早产儿脑室周围-脑室内出血与脑室周围白质软化的诊断建议[J]. 中华儿科杂志, 2007, 45(1): 34-36.
[9] 马力, 温晓红, 杨海波, 等. 影响早产儿脑损伤的相关因素分析[J]. 中国当代儿科杂志, 2016, 18(6): 471-475.
[10] 周丛乐. 早产儿脑白质损伤[M]//周丛乐. 新生儿神经病学. 第1 版. 人民卫生出版社, 2012: 376-383.
[11] Panigrahy A, Wisnowski JL, Furtado A, et al. Neuroimaging biomarkers of preterm brain injury: toward developing the preterm connectome[J]. Pediatr Radiol, 2012, 42(Suppl 1): S33-S61.
[12] Jantzie LL, Miller RH, Robinson S. Erythropoietin signaling promotes oligodendrocyte development following prenatal systemic hypoxic-ischemic brain injury[J]. Pediatr Res, 2013, 74(6): 658-667.
[13] 张冬梅, 王来栓. 早产儿脑病研究进展[J]. 国际儿科学杂志, 2012, 39(2): 173-176.
[14] Marret S, Marchand-Martin L, Picaud JC, et al. Brain injury in very preterm children and neurosensory and cognitive disabilities during childhood: the EPIPAGE cohort study[J]. PLoS One, 2013, 8(5): e62683.
[15] Wu YW, Gonzalez FF. Erythropoietin: a novel therapy for hypoxic-ischaemic encephalopathy?[J]. Dev Med Child Neurol, 2015, 57(Suppl 3): 34-39.
[16] Traudt CM, Juul SE. Erythropoietin as a neuroprotectant for neonatal brain injury: animal models[J]. Methods Mol Biol, 2013, 982: 113-126.
[17] Leuchter RH, 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[J]. JAMA, 2014, 312(8): 817-824.
[18] Ma W, Kantarjian H, Zhang K, et al. Significant association between polymorphism of the erythropoietin gene promoter and myelodysplastic syndrome[J]. BMC Med Genet, 2010, 11: 163.
[19] Douglas-Escobar M, Weiss MD. Biomarkers of brain injury in the premature infant[J]. Front Neurol, 2013, 3: 185.
[20] Hergenroeder GW, Redell JB, Moore AN, et al. Biomarkers in the clinical diagnosis and management of traumatic brain injury[J]. Mol Diagn Ther, 2008, 12(6): 345-358.
[21] Rees S, Hale N, De Matteo R, et al. Erythropoietin is neuroprotective in a preterm ovine model of endotoxin-induced brain injury[J]. J Neuropathol Exp Neurol, 2010, 69(3): 306-319.
[22] Lemus-Varela ML, Flores-Soto ME, Cervantes-Munguía R, et al. Expression of HIF-1 alpha, VEGF and EPO in peripheral blood from patients with two cardiac abnormalities associated with hypoxia[J]. Clin Biochem, 2010, 43: 234-239.
[23] Alexander ML, Hill CA, Rosenkrantz TS, et al. Evaluation of the therapeutic benefit of delayed administration of erythropoietin following early hypoxic-ischemic injury in rodents[J]. Dev Neurosci, 2012, 34(6): 515-524.
[24] Yu Z, Tang L, Chen L, et al. Erythropoietin reduces brain injury after intracerebral hemorrhagic stroke in rats[J]. Mol Med Rep, 2013, 8(5): 1315-1322.
[25] Barton SK, Tolcos M, Miller SL, et al. Ventilation-Induced Brain Injury in Preterm Neonates: A Review of Potential Therapies[J]. Neonatology, 2016, 110(2): 155-162.