Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Study of Cord Blood Erythropoietin, Leptin and Adiponectin Levels in Neonates with Hypoxic Ischemic Encephalopathy

Author(s): Adel A. Hagag*, Mohamed S. El Frargy and Amal E. Abd El-Latif

Volume 20, Issue 2, 2020

Page: [213 - 220] Pages: 8

DOI: 10.2174/1871530319666190725110619

Price: $65

Abstract

Background: Hypoxic ischemic encephalopathy (HIE) is a serious condition which results in neonatal morbidity and mortality. Early prediction of HIE especially in the first six hours of birth leads to early treatment with better prognosis.

Aim: The aim of this study was to compare the concentrations of leptin, adiponectin, and erythropoietin between normal neonates and those with HIE for the possible use of these markers for assessment of the degree of HIE and as markers for early prediction of HIE.

Patients and Methods: This study was carried out on 50 appropriate for gestational age (AGA) neonates with HIE born in Tanta University Hospital during the period from June 2016 to March 2018 (Group I). This study also included 50 appropriate for gestational age (AGA) normal neonates not suffering from any complications and matched with group I in age and sex as a control group (Group II). For all neonates in both groups, the following were done: Complete prenatal, natal, and postnatal history, assessment of APGAR score at 5 and 10 minutes, complete clinical examination with special account on clinical evidence of encephalopathy including hypotonia, abnormal oculomotor or pupillary movements, weak or absent suckling, apnea, hyperpnea, or seizures, measurement of cord blood gases and measurement of serum erythropoietin, leptin and adiponectin levels by ELISA immediately after birth.

Results: There were no significant differences between Group I and Group II regarding gestational age, male to female ratio, mode of delivery, and weight while there were significant differences regarding Apgar score at 1 and 5 minutes with significantly lower Apgar score at 1 and 5 minutes in group I compared with Group II. There were significantly lower cord blood PH and adiponectin level and significantly higher cord blood Leptin and erythropoietin in group I compared with group II. There were significant differences between cord blood adiponectin, leptin, erythropoietin, and PH in different degrees of HIE with significantly lower cord blood adiponectin and PH and significantly higher cord blood leptin and erythropoietin in severe degree of hypoxia compared with moderate degree and in moderate degree compared with mild degree of hypoxia. There was a significant positive correlation between cord blood erythropoietin and leptin and a significant negative correlation between cord blood erythropoietin and both adiponectin and PH in studied neonates with hypoxia. ROC curve showed that EPO had the best sensitivity and specificity followed by leptin then adiponectin while the PH had the least sensitivity and specificity as early predictors of hypoxic neonates.

Conclusion and Recommendations: Neonates with HIE had lower cord blood PH and adiponectin levels and higher leptin and erythropoietin levels than normal healthy neonates at birth and during the early postnatal period. The significant differences between cord blood erythropoietin, leptin, and adiponectin between neonates with hypoxia compared with normal neonates may arouse our attention about the use of these markers in the cord blood as early predictors of neonatal HIE which can lead early treatment and subsequently better prognosis.

Keywords: Hypoxic ischemic encephalopathy, cord blood erythropoietin, cord blood adiponectin, leptin, neonates, neonatal hypoxia.

« Previous Next »
Graphical Abstract

[1]
Graham, E.M.; Ruis, K.A.; Hartman, A.L.; Northington, F.J.; Fox, H.E. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am. J. Obstet. Gynecol., 2008, 199(6), 587-595.
[http://dx.doi.org/10.1016/j.ajog.2008.06.094] [PMID: 19084096]
[2]
van Handel, M.; Swaab, H.; de Vries, L.S.; Jongmans, M.J. Long-term cognitive and behavioral consequences of neonatal encephalopathy following perinatal asphyxia: a review. Eur. J. Pediatr., 2007, 166(7), 645-654.
[http://dx.doi.org/10.1007/s00431-007-0437-8] [PMID: 17426984]
[3]
Nonomura, M.; Harada, S.; Asada, Y.; Matsumura, H.; Iwami, H.; Tanaka, Y.; Ichiba, H. Combination therapy with erythropoietin, magnesium sulfate and hypothermia for hypoxic-ischemic encephalopathy: an open-label pilot study to assess the safety and feasibility. BMC Pediatr., 2019, 19(1), 13.
[http://dx.doi.org/10.1186/s12887-018-1389-z] [PMID: 30621649]
[4]
Lawn, J.; Shibuya, K.; Stein, C. No cry at birth: global estimates of intrapartum stillbirths and intrapartum-related neonatal deaths. Bull. World Health Organ., 2005, 83(6), 409-417.
[PMID: 15976891]
[5]
Bozzola, E.; Meazza, C.; Arvigo, M.; Travaglino, P.; Pagani, S.; Stronati, M.; Gasparoni, A.; Bianco, C.; Bozzola, M. Role of adiponectin and leptin on body development in infants during the first year of life. Ital. J. Pediatr., 2010, 36, 26.
[http://dx.doi.org/10.1186/1824-7288-36-26] [PMID: 20298581]
[6]
Valūniene, M.; Verkauskienė, R.; Boguszewski, M.; Dahlgren, J.; Lašienė, D.; Lašas, L.; Wikland, K.A. Leptin levels at birth and in early postnatal life in small- and appropriate-for-gestational-age infants. Medicina (Kaunas), 2007, 43(10), 784-791.
[http://dx.doi.org/10.3390/medicina43100100] [PMID: 17998795]
[7]
Tzschoppe, A.; Struwe, E.; Rascher, W.; Dörr, H.G.; Schild, R.L.; Goecke, T.W.; Beckmann, M.W.; Hofner, B.; Kratzsch, J.; Dötsch, J. Intrauterine growth restriction (IUGR) is associated with increased leptin synthesis and binding capability in neonates. Clin. Endocrinol. (Oxf.), 2011, 74(4), 459-466.
[http://dx.doi.org/10.1111/j.1365-2265.2010.03943.x] [PMID: 21138460]
[8]
Mantzoros, C.S.; Sweeney, L.; Williams, C.J.; Oken, E.; Kelesidis, T.; Rifas-Shiman, S.L.; Gillman, M.W. Maternal diet and cord blood leptin and adiponectin concentrations at birth. Clin. Nutr., 2010, 29(5), 622-626.
[http://dx.doi.org/10.1016/j.clnu.2010.03.004] [PMID: 20363059]
[9]
Valerio, A.; Dossena, M.; Bertolotti, P.; Boroni, F.; Sarnico, I.; Faraco, G.; Chiarugi, A.; Frontini, A.; Giordano, A.; Liou, H.C.; De Simoni, M.G.; Spano, P.; Carruba, M.O.; Pizzi, M.; Nisoli, E. Leptin is induced in the ischemic cerebral cortex and exerts neuroprotection through NF-kappaB/c-Rel-dependent transcription. Stroke, 2009, 40(2), 610-617.
[10]
Lesseur, C.; Armstrong, D.A.; Murphy, M.A.; Appleton, A.A.; Koestler, D.C.; Paquette, A.G.; Lester, B.M.; Marsit, C.J. Sex specific associations between placental leptin promoter DNA methylation and infant neurobehavior. Psychoneuroendocrinology, 2014, 40, 1-9.
[11]
Kumral, A.; Yesilirmak, D.C.; Sozmen, S.; Ergur, B.U.; Tugyan, K.; Ozbal, S.; Guclu, S.; Duman, N.; Ozkan, H. Effect of leptin treatment on neonatal hypoxic-ischemic brain injury. J. Matern. Fetal Neonatal Med., 2012, 25(2), 141-146.
[http://dx.doi.org/10.3109/14767058.2011.565834] [PMID: 21627548]
[12]
Wang, C.H.; Wang, W.T.; Cheng, S.Y.; Hung, W.T.; Wu, T.L.; Hsueh, C.M. Leptin and interleukin-1beta modulate neuronal glutamate release and protect against glucose-oxygen-serum deprivation. Curr. Neurovasc. Res., 2010, 7(3), 223-237.
[http://dx.doi.org/10.2174/156720210792231859] [PMID: 20560877]
[13]
Pittas, A.G.; Joseph, N.A.; Greenberg, A.S. Adipocytokines and insulin resistance. J. Clin. Endocrinol. Metab., 2004, 89(2), 447-452.
[http://dx.doi.org/10.1210/jc.2003-031005] [PMID: 14764746]
[14]
Sivan, E.; Mazaki-Tovi, S.; Pariente, C.; Efraty, Y.; Schiff, E.; Hemi, R.; Kanety, H. Adiponectin in human cord blood: relation to fetal birth weight and gender. J. Clin. Endocrinol. Metab., 2003, 88(12), 5656-5660.
[http://dx.doi.org/10.1210/jc.2003-031174] [PMID: 14671149]
[15]
Vinberg, M.; Højman, P.; Pedersen, B.K.; Kessing, L.V.; Miskowiak, K.W. Effects of erythropoietin on body composition and fat-glucose metabolism in patients with affective disorders. Acta Neuropsychiatr., 2018, 30(6), 342-349.
[http://dx.doi.org/10.1017/neu.2018.16] [PMID: 29880069]
[16]
Chang, Y.L.; Chao, A.S.; Peng, H.H.; Chang, S.D.; Su, S.Y.; Chen, K.J.; Cheng, P.J.; Wang, T.H. Increased Fetal Plasma Erythropoietin in Monochorionic Twin Pregnancies With Selective Intrauterine Growth Restriction and Abnormal Umbilical Artery Doppler. Twin Res. Hum. Genet., 2016, 19(4), 383-388.
[http://dx.doi.org/10.1017/thg.2016.38] [PMID: 27161360]
[17]
Summanen, M.; Seikku, L.; Rahkonen, P.; Stefanovic, V.; Teramo, K.; Andersson, S.; Kaila, K.; Rahkonen, L. Comparison of Umbilical Serum Copeptin Relative to Erythropoietin and S100B as Asphyxia Biomarkers at Birth. Neonatology, 2017, 112(1), 60-66.
[http://dx.doi.org/10.1159/000456063] [PMID: 28351056]
[18]
Executive summary: Neonatal encephalopathy and neurologic outcome, 2nd edition. Report of the American College of Obstetricians and Gynecologists' Task Force on Neonatal Encephalopathy. Obstet Gynecol, 2014. Apr. 123(4), 896-901
[19]
Sarnat, H.B.; Sarnat, M.S. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch. Neurol., 1976, 33(10), 696-705.
[http://dx.doi.org/10.1001/archneur.1976.00500100030012] [PMID: 987769]
[20]
Evagelidou, E.N.; Giapros, V.I.; Challa, A.S.; Kiortsis, D.N.; Tsatsoulis, A.A.; Andronikou, S.K. Serum adiponectin levels, insulin resistance, and lipid profile in children born small for gestational age are affected by the severity of growth retardation at birth. Eur. J. Endocrinol., 2007, 156(2), 271-277.
[http://dx.doi.org/10.1530/eje.1.02337] [PMID: 17287418]
[21]
Hoggard, N.; Haggarty, P.; Thomas, L.; Lea, R.G. Leptin expression in placental and fetal tissues: does leptin have a functional role? Biochem. Soc. Trans., 2001, 29(Pt 2), 57-63.
[http://dx.doi.org/10.1042/bst0290057] [PMID: 11356127]
[22]
Koester-Weber, T.; Valtueña, J.; Breidenassel, C.; Beghin, L.; Plada, M.; Moreno, S.; Huybrechts, I.; Palacios, G.; Gómez-Martínez, S.; Albers, U.; De Henauw, S.; Maiani, G.; Kafatos, A.; Molnar, D.; Sjöstrom, M.; Widhalm, K.; Manios, Y.; Moreno, L.A.; Marcos, A.; Castillo, M.J.; Stehle, P.; Gonzalez-Gross, M. Reference values for leptin, cortisol, insulin and glucose, among European adolescents and their association with adiposity: the HELENA study. Nutr. Hosp., 2014, 30(5), 1181-1190.
[PMID: 25365025]
[23]
Sawyer, S.T.; Krantz, S.B.; Sawada, K. Receptors for erythropoietin in mouse and human erythroid cells and placenta. Blood, 1989, 74(1), 103-109.
[PMID: 2546618]
[24]
Imai, N.; Kawamura, A.; Higuchi, M.; Oh-eda, M.; Orita, T.
Kawaguchi, T.; Ochi, N. Physicochemical and biological comparison of recombinant human erythropoietin with human urinary erythropoietin. J. Biochem., 1990, 107(3), 352-359.
[http://dx.doi.org/10.1093/oxfordjournals.jbchem.a123050] [PMID: 2341370]
[25]
Shah, P.; Riphagen, S.; Beyene, J.; Perlman, M. Multiorgan dysfunction in infants with post-asphyxial hypoxic-ischaemic encephalopathy. Arch. Dis. Child. Fetal Neonatal Ed., 2004, 89(2), F152-F155.
[http://dx.doi.org/10.1136/adc.2002.023093] [PMID: 14977901]
[26]
Martín-Ancel, A.; García-Alix, A.; Gayá, F.; Cabañas, F.; Burgueros, M.; Quero, J. Multiple organ involvement in perinatal asphyxia. J. Pediatr., 1995, 127(5), 786-793.
[http://dx.doi.org/10.1016/S0022-3476(95)70174-5] [PMID: 7472837]
[27]
Abdel-Azeem, M. El-Mazary.; Khalid, A. Nasif.; Gehan, L. Abdel-Hakeem.; Tahra, Sherif.; Ebtesam, Farouk.; Ebtesam, M. El-Gezawy. Adiponectin, leptin and insulin levels at birth and in early postnatal life in neonates with hypoxic ischemic encephalopathy. J. Diabetes Metab. Disord., 2015, 14, 87.
[http://dx.doi.org/10.1186/s40200-015-0219-1]
[28]
Sweetman, D.U.; Onwuneme, C.; Watson, W.R.; Murphy, J.F.; Molloy, E.J. Perinatal Asphyxia and Erythropoietin and VEGF: Serial Serum and Cerebrospinal Fluid Responses. Neonatology, 2017, 111(3), 253-259.
[http://dx.doi.org/10.1159/000448702] [PMID: 27902983]
[29]
Chaiban, J.T.; Bitar, F.F.; Azar, S.T. Effect of chronic hypoxia on leptin, insulin, adiponectin, and ghrelin. Metabolism, 2008, 57(8), 1019-1022.
[http://dx.doi.org/10.1016/j.metabol.2007.02.011] [PMID: 18640376]
[30]
Summanen, M.; Seikku, L.; Rahkonen, P.; Stefanovic, V.; Teramo, K.; Andersson, S.; Kaila, K.; Rahkonen, L. Comparison of Umbilical Serum Copeptin Relative to Erythropoietin and S100B as Asphyxia Biomarkers at Birth. Neonatology, 2017, 112(1), 60-66.
[http://dx.doi.org/10.1159/000456063] [PMID: 28351056]
[31]
Ibrahim, M.H.; Moustafa, A.N.; Saedii, A.A.F.; Hassan, E.E. Cord blood erythropoietin and cord blood nucleated red blood cells for prediction of adverse neonatal outcome associated with maternal obesity in term pregnancy: prospective cohort study. J. Matern. Fetal Neonatal Med., 2017, 30(18), 2237-2242.
[http://dx.doi.org/10.1080/14767058.2016.1243101] [PMID: 27690727]

Rights & Permissions Print Cite
Article Metrics
13
1
© 2024 Bentham Science Publishers | Privacy Policy