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Boskabadi, H., Moradi, A., & Zakerihamidi, M. (2019). Interleukins in diagnosis of perinatal asphyxia: A systematic review. International Journal of Reproductive BioMedicine (IJRM), 17(5), 303–314. https://doi.org/10.18502/ijrm.v17i5.4598
https://doi.org/10.18502/ijrm.v17i5.4598
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- Cited by 4 articles
authors
-
Hassan Boskabadi
Hassan Boskabadi
Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
-
Ali Moradi
Ali Moradi
Orthopedic Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
-
Maryam Zakerihamidi
Maryam Zakerihamidi
Department of Midwifery, Faculty of Medical Sciences, Islamic Azad University, Tonekabon Branch, Tonekabon, Iran.
Published Date
- Jun 18, 2019
Interleukins in diagnosis of perinatal asphyxia: A systematic review
Abstract
Background: Biochemical markers including interleukins (ILs) has been proposed for early diagnosis of asphyxia. Objective: This study has aimed to systematically review the significance of IL measurements in the diagnosis of perinatal asphyxia.
Materials and Methods: PubMed, Cochrane Library, Web of Science, Embase, and Scopus databases before 2017 were searched for the following keywords: asphyxia, neonatal, interleukin, and diagnosis. A total of 13 out of 300 searched papers were finally selected for evaluation. Interleukins under study were IL6 and interleukin 1β (IL-1β). Interleukins had been measured in 10 studies by serum samples, 2 studies by samples of Cerebro Spinal Fluid (CSF), and 1 study by sample of umbilical cord blood. The inclusion criteria were: studies on neonates, with adequate information from the test results and studies using markers other than ILs to detect asphyxia; however, studies with only abstracts available were excluded.
Results: Research on the issue suggests that IL6 > 41 Pg/dl has the sensitivity of 84.88% and the specificity of 85.43%, whereas IL-1β > 4.7 Pg/dl has the sensitivity of 78% and specificity of 83% in the diagnosis of neonatal asphyxia. Among diagnostic ILs for neonatal asphyxia, combination of IL6 and IL-1β had the highest sensitivity, that is, 92.9%.
Conclusion: IL6 and IL-1β of serum samples were used in the early diagnosis of perinatal asphyxia and are useful predictors for the outcomes of perinatal asphyxia and its intensity. In addition, simultaneous evaluation of IL-1β and IL6 can improve the sensitivity of the early diagnosis of perinatal asphyxia.
References
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between serum interleukin-6 levels and severity of perinatal asphyxia. Asian Biomedicine 2010; 4: 79–85.
[2] Boskabadi H, Zakerihamidi M, Sadeghian MH, Avan A, Ghayour-Mobarhan M, Ferns GA. Nucleated red blood
cells count as a prognostic biomarker in predicting the complications of asphyxia in neonates. J Matern Fetal
Neonatal Med 2017; 30: 2551–2556.
[3] Boskabadi H, Ashrafzadeh F, Doosti H, Zakerihamidi M. Assessment of risk factors and prognosis in asphyxiated infants. Iran J Pediatr 2015; 25: e2006.
[4] Costello AM, Manandhar DS. Perinatal asphyxia in less developed countries. Arch Dis Child Fetal Neonatal Ed
1994; 71: F1–F3.
[5] Dixon G, Badawi N, Kurinczuk JJ, Keogh JM, Silburn SR, Zubrick SR, et al. Early developmental outcomes after
newborn encephalopathy. Pediatrics 2002; 109: 26–33.
[6] Utomo MT. Risk factors for birth asphyxia. Folia Medica indonesiana 2011; 47: 211–214.
[7] Naithani M, Simalti AK. Biochemical markers in perinatal asphyxia. J Nepal Paediatr Soc 2011; 31: 151–156.
[8] Boskabadi H, Maamouri G, Rezagholizade Omran F, Mafinejad S, Tara F, Rayman MP, et al. Effect of prenatal selenium supplementation on cord blood selenium and lipid profile. Pediatr Neonatol 2012; 53: 334–339.
[9] Boskabadi H, Maamouri G, Sadeghian MH, GhayourMobarhan M, Heidarzade M, Shakeri MT, et al. Early diagnosis of perinatal asphyxia by nucleated red blood cell count: a case-control study. Arch Iran Med 2010; 13: 275–281.
[10] Sävman K, Blennow M, Gustafson K, Tarkowski E, Hagberg H. Cytokine response in CSF after birth asphyxia. PediatrRes 1998; 43: 746–751.
[11] Boskabadi H, Omidian M, Tavallai S, Mohammadi S, Parizadeh M, Ghayour Mobarhan MG, et al. Serum Hsp70 antigen: early diagnosis marker in perinatal asphyxia. Iran J Pediatr 2015; 25: e381.
[12] Dammann O, Leviton A. Infection remote from the brain, neonatal white matter damage, and cerebral palsy in the preterm infant. Semin Pediatr Neurol 1998; 5: 190–201.
[13] Okazaki K, Kuboi T, Kusaka T, Kondo M, Kimura H. Pathophysiological roles of cytokines in the brain during perinatal asphyxia. Ann Pediatr Child Health 2015; 3: 1030–1039.
[14] Oppenheim JJ. Cytokines: past, present, and future. Int J Hematol 2001; 74: 3–8.
[15] Dammann O, Leviton A. Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn. Pediatr Res 1997; 42: 1–8.
[16] Dihné M, Block F. Focal ischemia induces transient expression of IL-6 in the substantia nigra pars reticulata. Brain Res2001; 889: 165–173.
[17] Chiesa C, Pellegrini G, Panero A, De Luca T, Assumma M, Signore F, et al. Umbilical cord interleukin-6 levels are elevated in term neonates with perinatal asphyxia. Eur J Clin Invest 2003; 33: 352–358.
[18] Paliwal P, Varma M, Mulye S, Paliwal M, Shaikh M. Study of neurological marker in perinatal asphyxia and its correlation with different stages of hypoxic ischemic encephalopathy. Int J Sci Study 2014; 2: 40–43.
[19] Silveira Rde C, Procianoy RS. Levels of interleukin-6 and tumor necrosisfactor-alpha in the CSF of full-term newborns with hypoxic-ischemic encephalopathy. J Pediatr (Rio J) 2003; 79: 297–302.
[20] Martin-Ancel A, Garcia-Alix A, Pascual-Salcedo D, Cabanas F, Valcarce M, Quero J. Interleukin-6 inthe CSF after perinatal asphyxia is related to early and late neurological manifestations. Pediatrics 1997; 100:
789–794.
[21] Shang Y, Mu L, Guo X, Li Y, Wang L, Yang W, et al. Clinical significance of interleukin-6, tumor necrosis factor- α and high-sensitivity C-reactive protein in neonates with hypoxic-ischemic encephalopathy. Exp Ther Med 2014; 8:1259–1262.
[22] Yi-hong Z, Lan-fen T,Dang A, Zan-cai S, Yu-li J. Relationship of interleukin-6 and insulin-like growth factor1 serumlevels with brain damage in neonatal asphyxia. Journal of Guangdong Medical College 2004; 1: 007.
[23] Boskabadi H, Maamouri G, TavakolAfshari J, Shakeri perinatal asphyxia. Iranian Journal of Neonatology 2010; 1: 24–29.
[24] Oygür N, Sönmez Ö, Saka O, Yegin O. Predictive value of plasma and CSF tumour necrosis factor-αand interleukin1β concentrations on outcome of full term infants with hypoxic–ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 1998; 79: F190–F193.
[25] Boskabadi H, Maamouri G, Tavakkol Afshari J, Zakerihamidi M, Kalateh Molaee M, Bagheri F, et al. Combination of Serum interleukin-1β and 6 concentrations levels in thediagnosis perinatal asphyxia. Arch Iran Med 2015; 19: 312–316.
[26] Fotopoulos S, Pavlou K, Skouteli H, Papassotiriou I, Lipsou N, Xanthou M. Early markers of brain damage in premature low-birth-weight neonates who suffered from perinatal asphyxia and/or infection. Biol Neonate 2001; 79: 213–218.
[27] Alsulaimani AA, Abuelsaad ASA, Mohamed NM. Inflammatory cytokines in neonatal hypoxic ischemic encephalopathy and their correlation with brain marker S100 protein: A case control study in Saudi Arabia. J Clin Cell Immunol 2015; 6: 2–9.
[28] Hagberg H, Gilland E, Bona E, Hanson LA, Hahn-Zoric M, Blennow M, et al. Enhanced expression of interleukin (IL)-1 and IL-6 messenger RNA and bioactive protein after hypoxia-ischemia in neonatal rats. Pediat Res 1996; 40: 603–609.
[29] Selmaj KW, Farooq M, Norton WT, Raine CS, Brosnan CF. Proliferation of astrocytes in vitroin response to cytokines. A primary role for tumor necrosis factor. J Immunol 1990;144: 129–135.
[30] Kharazmi A, Nielsen H, Rechnitzer C, Bendtzen K. Interleukin 6 primes human neutrophil and monocyte oxidative burst response. Immunol Lett 1989; 21: 177–184.
[31] Aly H, Khashaba MT, El-Ayouty M, El-Sayed O, Hasanein BM. IL-1β, IL-6 and TNF-α and outcomes of neonatal
hypoxic ischemic encephalopathy. Brain Dev 2006; 28: 178–182.
[32] Shalak LF, Laptook AR, Jafri HS, Ramilo O, Perlman JM. Clinical chorioamnionitis, elevated cytokines, and brain injury in term infants. Pediatrics 2002; 110: 673–680.
[33] Suzuki S, Tanaka K, Suzuki N. Ambivalent aspects of interleukin-6 in cerebral ischemia: inflammatory versus neurotrophicaspects. J Cereb Blood Flow Metab 2009; 29: 464–479.
[34] Jenkins DD, Rollins LG, Perkel JK, Wagner CL, Katikaneni LP, Bass WT, et al. Serum cytokines in a clinical trial of hypothermia for neonatal hypoxic-ischemic encephalopathy. J Cereb Blood Flow Metab 2012; 32: 1888–1896.
[35] Xing Z, Gauldie J, Cox G, Baumann H, Jordana M, Lei XF, et al. IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest 1998; 101: 311–320.
[36] Vila N, Castillo J, Dávalos A, Chamorro Á. Proinflammatory cytokines and early neurological worsening in ischemic stroke. Stroke 2000; 31: 2325–2329.
[37] Nelson KB, Grether JK. Causes of cerebral palsy. Curr Opin Pediatr 1999; 11: 487–491.
[38] Matsuda S, Wen TC, Morita F, Otsuka H, Igase K, Yoshimura H, et al. Interleukin-6 prevents ischemia-induced learning disability and neuronal and synaptic loss in gerbils. Neurosci Lett 1996; 204: 109–112.
[39] Okazaki K, Nishida A, Kato M, Kozawa K, Uga N, Kimura H. Elevation of cytokine concentrations in asphyxiated neonates. Biol Neonate 2005; 89: 183–189.
[40] Yoon BH, Romero R, Park JS, Kim CJ, Kim SH, Choi JH, et al. Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years. Am J Obstet Gynecol 2000; 182: 675–681.
[41] Tekgul H, Yalaz M, Kutukculer N, Ozbek S, Kose T, Akisu M, et al. Value of biochemical markers for outcome in term infants with asphyxia. Pediatr Neurol 2004; 31: 326–332.
[42] Liu J, Feng ZC. Increased umbilical cord plasma interleukin-1β levels was correlated with adverse outcomes of neonatal hypoxic-ischemic encephalopathy. J Trop Pediatr 2010; 56: 178–182.
[43] Oygur N, Sonmez O, Saka O, Yegin O. Predictive values of plasma and CSF TNF and interleukin 1 concentrations on outcome of full term infants with hypoxic ischemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 1998; 79: F190–F193.
[44] Martin D, Chinookoswong N, Miller G. The interleukin1 receptor antagonist (rhIL-1ra) protects against cerebral infarction in a rat model of hypoxia-ischemia. Exp Neurol 1994; 130: 362–367.
between serum interleukin-6 levels and severity of perinatal asphyxia. Asian Biomedicine 2010; 4: 79–85.
[2] Boskabadi H, Zakerihamidi M, Sadeghian MH, Avan A, Ghayour-Mobarhan M, Ferns GA. Nucleated red blood
cells count as a prognostic biomarker in predicting the complications of asphyxia in neonates. J Matern Fetal
Neonatal Med 2017; 30: 2551–2556.
[3] Boskabadi H, Ashrafzadeh F, Doosti H, Zakerihamidi M. Assessment of risk factors and prognosis in asphyxiated infants. Iran J Pediatr 2015; 25: e2006.
[4] Costello AM, Manandhar DS. Perinatal asphyxia in less developed countries. Arch Dis Child Fetal Neonatal Ed
1994; 71: F1–F3.
[5] Dixon G, Badawi N, Kurinczuk JJ, Keogh JM, Silburn SR, Zubrick SR, et al. Early developmental outcomes after
newborn encephalopathy. Pediatrics 2002; 109: 26–33.
[6] Utomo MT. Risk factors for birth asphyxia. Folia Medica indonesiana 2011; 47: 211–214.
[7] Naithani M, Simalti AK. Biochemical markers in perinatal asphyxia. J Nepal Paediatr Soc 2011; 31: 151–156.
[8] Boskabadi H, Maamouri G, Rezagholizade Omran F, Mafinejad S, Tara F, Rayman MP, et al. Effect of prenatal selenium supplementation on cord blood selenium and lipid profile. Pediatr Neonatol 2012; 53: 334–339.
[9] Boskabadi H, Maamouri G, Sadeghian MH, GhayourMobarhan M, Heidarzade M, Shakeri MT, et al. Early diagnosis of perinatal asphyxia by nucleated red blood cell count: a case-control study. Arch Iran Med 2010; 13: 275–281.
[10] Sävman K, Blennow M, Gustafson K, Tarkowski E, Hagberg H. Cytokine response in CSF after birth asphyxia. PediatrRes 1998; 43: 746–751.
[11] Boskabadi H, Omidian M, Tavallai S, Mohammadi S, Parizadeh M, Ghayour Mobarhan MG, et al. Serum Hsp70 antigen: early diagnosis marker in perinatal asphyxia. Iran J Pediatr 2015; 25: e381.
[12] Dammann O, Leviton A. Infection remote from the brain, neonatal white matter damage, and cerebral palsy in the preterm infant. Semin Pediatr Neurol 1998; 5: 190–201.
[13] Okazaki K, Kuboi T, Kusaka T, Kondo M, Kimura H. Pathophysiological roles of cytokines in the brain during perinatal asphyxia. Ann Pediatr Child Health 2015; 3: 1030–1039.
[14] Oppenheim JJ. Cytokines: past, present, and future. Int J Hematol 2001; 74: 3–8.
[15] Dammann O, Leviton A. Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn. Pediatr Res 1997; 42: 1–8.
[16] Dihné M, Block F. Focal ischemia induces transient expression of IL-6 in the substantia nigra pars reticulata. Brain Res2001; 889: 165–173.
[17] Chiesa C, Pellegrini G, Panero A, De Luca T, Assumma M, Signore F, et al. Umbilical cord interleukin-6 levels are elevated in term neonates with perinatal asphyxia. Eur J Clin Invest 2003; 33: 352–358.
[18] Paliwal P, Varma M, Mulye S, Paliwal M, Shaikh M. Study of neurological marker in perinatal asphyxia and its correlation with different stages of hypoxic ischemic encephalopathy. Int J Sci Study 2014; 2: 40–43.
[19] Silveira Rde C, Procianoy RS. Levels of interleukin-6 and tumor necrosisfactor-alpha in the CSF of full-term newborns with hypoxic-ischemic encephalopathy. J Pediatr (Rio J) 2003; 79: 297–302.
[20] Martin-Ancel A, Garcia-Alix A, Pascual-Salcedo D, Cabanas F, Valcarce M, Quero J. Interleukin-6 inthe CSF after perinatal asphyxia is related to early and late neurological manifestations. Pediatrics 1997; 100:
789–794.
[21] Shang Y, Mu L, Guo X, Li Y, Wang L, Yang W, et al. Clinical significance of interleukin-6, tumor necrosis factor- α and high-sensitivity C-reactive protein in neonates with hypoxic-ischemic encephalopathy. Exp Ther Med 2014; 8:1259–1262.
[22] Yi-hong Z, Lan-fen T,Dang A, Zan-cai S, Yu-li J. Relationship of interleukin-6 and insulin-like growth factor1 serumlevels with brain damage in neonatal asphyxia. Journal of Guangdong Medical College 2004; 1: 007.
[23] Boskabadi H, Maamouri G, TavakolAfshari J, Shakeri perinatal asphyxia. Iranian Journal of Neonatology 2010; 1: 24–29.
[24] Oygür N, Sönmez Ö, Saka O, Yegin O. Predictive value of plasma and CSF tumour necrosis factor-αand interleukin1β concentrations on outcome of full term infants with hypoxic–ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 1998; 79: F190–F193.
[25] Boskabadi H, Maamouri G, Tavakkol Afshari J, Zakerihamidi M, Kalateh Molaee M, Bagheri F, et al. Combination of Serum interleukin-1β and 6 concentrations levels in thediagnosis perinatal asphyxia. Arch Iran Med 2015; 19: 312–316.
[26] Fotopoulos S, Pavlou K, Skouteli H, Papassotiriou I, Lipsou N, Xanthou M. Early markers of brain damage in premature low-birth-weight neonates who suffered from perinatal asphyxia and/or infection. Biol Neonate 2001; 79: 213–218.
[27] Alsulaimani AA, Abuelsaad ASA, Mohamed NM. Inflammatory cytokines in neonatal hypoxic ischemic encephalopathy and their correlation with brain marker S100 protein: A case control study in Saudi Arabia. J Clin Cell Immunol 2015; 6: 2–9.
[28] Hagberg H, Gilland E, Bona E, Hanson LA, Hahn-Zoric M, Blennow M, et al. Enhanced expression of interleukin (IL)-1 and IL-6 messenger RNA and bioactive protein after hypoxia-ischemia in neonatal rats. Pediat Res 1996; 40: 603–609.
[29] Selmaj KW, Farooq M, Norton WT, Raine CS, Brosnan CF. Proliferation of astrocytes in vitroin response to cytokines. A primary role for tumor necrosis factor. J Immunol 1990;144: 129–135.
[30] Kharazmi A, Nielsen H, Rechnitzer C, Bendtzen K. Interleukin 6 primes human neutrophil and monocyte oxidative burst response. Immunol Lett 1989; 21: 177–184.
[31] Aly H, Khashaba MT, El-Ayouty M, El-Sayed O, Hasanein BM. IL-1β, IL-6 and TNF-α and outcomes of neonatal
hypoxic ischemic encephalopathy. Brain Dev 2006; 28: 178–182.
[32] Shalak LF, Laptook AR, Jafri HS, Ramilo O, Perlman JM. Clinical chorioamnionitis, elevated cytokines, and brain injury in term infants. Pediatrics 2002; 110: 673–680.
[33] Suzuki S, Tanaka K, Suzuki N. Ambivalent aspects of interleukin-6 in cerebral ischemia: inflammatory versus neurotrophicaspects. J Cereb Blood Flow Metab 2009; 29: 464–479.
[34] Jenkins DD, Rollins LG, Perkel JK, Wagner CL, Katikaneni LP, Bass WT, et al. Serum cytokines in a clinical trial of hypothermia for neonatal hypoxic-ischemic encephalopathy. J Cereb Blood Flow Metab 2012; 32: 1888–1896.
[35] Xing Z, Gauldie J, Cox G, Baumann H, Jordana M, Lei XF, et al. IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest 1998; 101: 311–320.
[36] Vila N, Castillo J, Dávalos A, Chamorro Á. Proinflammatory cytokines and early neurological worsening in ischemic stroke. Stroke 2000; 31: 2325–2329.
[37] Nelson KB, Grether JK. Causes of cerebral palsy. Curr Opin Pediatr 1999; 11: 487–491.
[38] Matsuda S, Wen TC, Morita F, Otsuka H, Igase K, Yoshimura H, et al. Interleukin-6 prevents ischemia-induced learning disability and neuronal and synaptic loss in gerbils. Neurosci Lett 1996; 204: 109–112.
[39] Okazaki K, Nishida A, Kato M, Kozawa K, Uga N, Kimura H. Elevation of cytokine concentrations in asphyxiated neonates. Biol Neonate 2005; 89: 183–189.
[40] Yoon BH, Romero R, Park JS, Kim CJ, Kim SH, Choi JH, et al. Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years. Am J Obstet Gynecol 2000; 182: 675–681.
[41] Tekgul H, Yalaz M, Kutukculer N, Ozbek S, Kose T, Akisu M, et al. Value of biochemical markers for outcome in term infants with asphyxia. Pediatr Neurol 2004; 31: 326–332.
[42] Liu J, Feng ZC. Increased umbilical cord plasma interleukin-1β levels was correlated with adverse outcomes of neonatal hypoxic-ischemic encephalopathy. J Trop Pediatr 2010; 56: 178–182.
[43] Oygur N, Sonmez O, Saka O, Yegin O. Predictive values of plasma and CSF TNF and interleukin 1 concentrations on outcome of full term infants with hypoxic ischemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 1998; 79: F190–F193.
[44] Martin D, Chinookoswong N, Miller G. The interleukin1 receptor antagonist (rhIL-1ra) protects against cerebral infarction in a rat model of hypoxia-ischemia. Exp Neurol 1994; 130: 362–367.