Preterm Bebeklerde Umbilikal Kord Kanı İnterferon γ ile Uyarılabilen Protein-10 (IP-10) Düzeyleri ile Klinik ve Laboratuvar Parametreleri Arasındaki İlişki
Year 2024,
Volume: 11 Issue: 3, 145 - 151, 18.12.2024
Ulviye Kırlı
,
Ener Cagri Dınleyıcı
,
Neslihan Tekın
,
Arif Aksıt
Abstract
İnterferon γ ile uyarılabilen protein-10 (IP-10) güçlü inflamatuar mediatörlerden biridir. Çalışmamızda antenatal erken membran rüptürü (PPROM), fetal inflamatuar yanıt sendromu (FIRS) ve prematüreliğe bağlı morbiditeleri olan veya olmayan prematüre bebeklerde kordon kanı IP-10 düzeylerinin karşılaştırılması amaçlanmıştır. 37. gebelik haftasının altında doğan 85 prematüre bebek çalışmaya dahil edildi. Doğum anında umbilikal korddan alınan kan örneklerinde ELİSA yöntemi ile interlökin (IL)-6 ve IP-10 düzeyleri ölçüldü. Tüm olgularda prematüreliğe bağlı gelişebilecek komplikasyonlar (respiratuar distres sendromu, erken ve geç başlangıçlı sepsis, nekrotizan enterokolit, intraventriküler kanama, prematüre retinopatisi, bronkopulmoner displazi) ve mortalite kaydedildi. Kordon kanında 11 pg/ml üzerinde olan IL-6 düzeyleri FIRS olarak kabul edildi. PPROM’lu grupta (n=27, %31.8) kordon kanında medyan IP-10 seviyesi diğer gruplara göre anlamlı derecede yüksek bulundu (IP-10=345.6 pg/ml vs. 28.3 pg/ml, p<0.001). FIRS saptanan olgularda (n=36, %42.4) kordon kanında medyan IP-10 düzeyi FIRS saptanmayanlara göre anlamlı derecede yüksek saptandı (p<0.001). Erken başlangıçlı sepsis gelişen olgularda da kordon kanında medyan IP-10 seviyesi anlamlı derecede yüksek idi (p=0.019). Prematüreliğe bağlı diğer morbiditeler ile kordon kanı IP-10 düzeyi arasında anlamlı bir ilişki bulunamadı. Çalışmamızda fetal inflamasyonu olan ve erken başlangıçlı sepsis gelişen prematüre bebeklerde kordon kanında IP-10 seviyelerinin yüksek olduğu saptanmıştır. Kordon kanında yüksek IP-10 seviyesi, neonatal sepsis gelişen/gelişecek prematüre bebeklerde intrauterin inflamasyonu göstermek için erken bir belirteç olarak kullanılabilir.
References
- Goldenberg RL, Culhane JF, Iams JD, et al. Epidemiology and causes of preterm birth. Lancet. 2008;371(9606):75-84.
- Griggs KM, Hrelic DA, Williams N, et al. Preterm labor and birth: A clinical review. MCN Am J Matern Child Nurs. 2020;45(6):328-37.
- Viscardi RM, Muhumuza CK, Rodriguez A, et al. Inflammatory markers in intrauterine and fetal blood and cerebrospinal fluid compartments are associated with adverse pulmonary and neurologic outcomes in preterm infants. Pediatr Res. 2004;55(6):1009-17.
- Garlanda C, Botazzi B, Bastone A, et al. Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition and female fertility. Annu Rev Immunol. 2005;23:337-66.
- Stoll BJ, Kliegman RM. The high-risk infant. In: Behrman RE, Kliegman RM, Jenson HB, editors. Nelson textbook of pediatrics. 16th ed. Philadelphia: WB Saunders, 2000;pp 474-85.
- Manes TD, Pober JS, Kluger MS. Endothelial cell-T lymphocyte interactions: IP-10 stimulates rapid transendothelial migration of human effector but not central memory CD4+ T-cells. Requirements for shear stress and adhesion molecules. Transplantation. 2006;82(1):9-14.
- Liu M, Guo S, Hibbert JM, et al. CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. Cytokine Growth Factor Rev. 2011;22(3):121-30.
- Kuo PT, Zeng Z, Salim N, et al. The role of CXCR3 and its chemokine ligands in skin disease and cancer. Front Med (Lausanne). 2018;5:271.
- Kim J, Choi JY, Park SH, et al. Therapeutic effect of anti-C-X-C motif chemokine 10 (CXCL10) antibody on C protein-induced myositis mouse. Arthritis Res Ther. 2014;16(3):R126.
- Fotopoulos S, Mouchtouri A, Xanthou G, et al. Inflammatory chemokine expression in the peripheral blood of neonates with perinatal asphyxia and perinatal or nosocomial infections. Acta Paediatr. 2005;94(6):800-6.
- Chen HL, Hung CH, Tseng HI, et al. Plasma IP-10 as a predictor of serious bacterial infection in infants less than 4 months of age. J Tropical Pediatr. 2009;55(2):103-8.
- Kallapur SG, Jobe AH, Ikegami M, et al. Increased IP-10 and MIG expression after intra-amniotic endotoxin in preterm lamb lung. Am J Respir Crit Care Med. 2003;167(5):779-86.
- Gomez R, Romero R, Ghezzi F, et al. The fetal inflammatory response syndrome. Am J Obstet Gynecol. 1998;179(1):194-202.
- Engle WA; American Academy of Pediatrics Committee on Fetus and Newborn. Age terminology during the perinatal period. Pediatrics. 2004;114(5):1362-4.
- Whitsett JA, Rice WR, Warner BB, et al. Acute respiratory disorders. In: Mac Donald MG, Mullet MD, Seshia MMK, editors. Avery’s Neonatology. 6th ed. Philadelphia: Lippincott Williams and Wilkins, 2005;pp 569-76.
- Haque KN. Definitions of bloodstream infection in the newborn. Pediatr Crit Care Med. 2005;6(3):45-9.
- Neu J. Necrotizing enterocolitis: the search for unifying pathogenic theory leading to prevention. Pediatr Clin North Am. 1996;43(2):409-32.
- Owens R. Intraventriculer hemorrhage in the premature neonate. Neonatal Netw. 2005;24(3):55-71.
- Katz TA, Koam AH, Schuit E, et al. Comparison of new bronchopulmonary dysplasia definitions on long-term outcomes in preterm infants. J Pediatr. 2023;253:86-93.
- International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005;123(7):991-9.
- Stoll BJ, Hansen NI, Bell EF, et al. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012. JAMA. 2015;314(10):1039-51.
- Gravett MG, Novy MS, Rosenfeld RG, et al. Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers. JAMA. 2004;292(4):462-9.
- Garg A, Jaiswal A. Evaluation and Management of Premature Rupture of Membranes: A Review Article. Cureus. 2023;15(3):e36615.
- Jantien L van der Hetden. Preterm prelabor rupture of membranes: different gestational ages, different problems. Thesis. 2014.
- Andrews WW, Hauth SC, Goldenberg RL, et al. Amniotic fluid interleukin-6; correlation with upper genital tract microbial colonization and gestational age in women delivered after spontaneous labor versus indicated delivery. Am J Obstet Gynecol. 1995;173(2):606-12.
- Chang Y, Li W, Shen Y, et al. Association between interleukin-6 and preterm birth: a meta-analysis. Ann Med. 2023:55(2):2284384.
- Cornette L. Fetal and neonatal inflammatory response and adverse outcome. Semin Fetal Neonatal Med. 2004;9(6): 459-70.
- Flannery DD, Puopolo KM. Neonatal early-onset sepsis. Neoreviews. 2022;23(11):756-70.
- Dol J, Hughes H, Bonet M, et al. Timing of neonatal mortality and severe morbidity during the postnatal period: a systematic review. JBI Evid Synth. 2023;21(1):98-199.
- Chıossi G, Tommosa MD, Monari F, et al. Neonatal outcomes and risk of neonatal sepsis in an expectantly managed cohort of late preterm prelabor rupture of membranes. Eur J Obstet Gynecol Reprod Biol. 2021;261:1-6.
- Gezer A, Parafit-Yalciner E, Guralp O, et al. Neonatal morbidity mortality outcomes in preterm premature rupture of membranes. J Obstet Gynaecol. 2013;33(1):38-42.
- Ng PC, Li K, Leung TF, et al. Early prediction of sepsis-induced disseminated intravascular coagulation with interleukin-10, interleukin-6, and RANTES in preterm infants. Clin Chem. 2006;52(6):1181-9.
- Ng PC, Li K, Chui KM, et al. IP-10 is an early diagnostic marker for identification of late-onset bacterial infection in preterm infants. Pediatr Res. 2007;61(1):93-8.
- Rallis D, Balomenou F, Kappatou K, et al. C-reactive protein in infants with no evidence of early-onset sepsis. J Matern Fetal Neonatal Med. 2022;35(25):5659-64.
- Tang Q, Zhang L, Li H, et al. The fetal inflammation response syndrome and adverse neonatal outcomes: a meta-analysis. J Matern Fetal Neonatal Med. 2021;34(23):3902-14.
- Sorakin Y, Romero R, Mele L, et al. Umbilical cord serum interleukin-6, C-reactive protein, and myeloperoxidase concentrations at birth and association with neonatal morbidities and long-term neurodevelopmental outcomes. Am J Perinatol. 2014;31(8):717-26.
The Relationship Between Umbilical Cord Blood Interferon γ-Inducible Protein-10 (IP-10) Levels and Clinical and Laboratory Parameters in Preterm Infants
Year 2024,
Volume: 11 Issue: 3, 145 - 151, 18.12.2024
Ulviye Kırlı
,
Ener Cagri Dınleyıcı
,
Neslihan Tekın
,
Arif Aksıt
Abstract
Interferon γ-inducible protein-10 (IP-10) is one of the potent inflammatory mediators. This research aims to compare cord blood IP-10 levels in preterm infants with or without antenatal preterm prelabor rupture of the membranes (PPROM), fetal inflammatory response syndrome (FIRS) and prematurity related morbidities. We enrolled 85 newborns with gestational age below 37 weeks. Umbilical cord blood samples were obtained at delivery and stored. Cord blood IP-10 and interleukin (IL)-6 levels measured with ELISA test. All enrolled preterm infants have been followed-up for prematurity related conditions including respiratory distress syndrome, early and late onset sepsis, necrotising enterocolitis, intraventricular haemorrhage, premature retinopathy, bronchopulmonary dysplasia and mortality. FIRS defined as IL-6 levels of umbilical cord above 11 pg/ml. Cord blood median IP-10 levels were significantly higher in PPROM group (n=27, 31.8%) than in the group without PPROM (IP-10=345.6 pg/ml vs. 28.3 pg/ml, p<0.001). Cord blood median IP-10 levels were significantly higher in preterm infants with FIRS (n=36, 42.4%) compared to infants without FIRS (p<0.001). Cord blood median IP-10 levels were also higher in preterm infants with early onset sepsis than those without early onset sepsis (p=0.019). We did not observe relationship between cord blood IP-10 levels and other prematurity-related complications. Increased cord blood IP-10 levels have been observed in preterm infants with fetal inflammation and who developed early onset sepsis. Cord blood IP-10 could be considered an early marker for intrauterine inflammation and its effect on fetal outcomes, such as the development of neonatal sepsis in preterm infants.
References
- Goldenberg RL, Culhane JF, Iams JD, et al. Epidemiology and causes of preterm birth. Lancet. 2008;371(9606):75-84.
- Griggs KM, Hrelic DA, Williams N, et al. Preterm labor and birth: A clinical review. MCN Am J Matern Child Nurs. 2020;45(6):328-37.
- Viscardi RM, Muhumuza CK, Rodriguez A, et al. Inflammatory markers in intrauterine and fetal blood and cerebrospinal fluid compartments are associated with adverse pulmonary and neurologic outcomes in preterm infants. Pediatr Res. 2004;55(6):1009-17.
- Garlanda C, Botazzi B, Bastone A, et al. Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition and female fertility. Annu Rev Immunol. 2005;23:337-66.
- Stoll BJ, Kliegman RM. The high-risk infant. In: Behrman RE, Kliegman RM, Jenson HB, editors. Nelson textbook of pediatrics. 16th ed. Philadelphia: WB Saunders, 2000;pp 474-85.
- Manes TD, Pober JS, Kluger MS. Endothelial cell-T lymphocyte interactions: IP-10 stimulates rapid transendothelial migration of human effector but not central memory CD4+ T-cells. Requirements for shear stress and adhesion molecules. Transplantation. 2006;82(1):9-14.
- Liu M, Guo S, Hibbert JM, et al. CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. Cytokine Growth Factor Rev. 2011;22(3):121-30.
- Kuo PT, Zeng Z, Salim N, et al. The role of CXCR3 and its chemokine ligands in skin disease and cancer. Front Med (Lausanne). 2018;5:271.
- Kim J, Choi JY, Park SH, et al. Therapeutic effect of anti-C-X-C motif chemokine 10 (CXCL10) antibody on C protein-induced myositis mouse. Arthritis Res Ther. 2014;16(3):R126.
- Fotopoulos S, Mouchtouri A, Xanthou G, et al. Inflammatory chemokine expression in the peripheral blood of neonates with perinatal asphyxia and perinatal or nosocomial infections. Acta Paediatr. 2005;94(6):800-6.
- Chen HL, Hung CH, Tseng HI, et al. Plasma IP-10 as a predictor of serious bacterial infection in infants less than 4 months of age. J Tropical Pediatr. 2009;55(2):103-8.
- Kallapur SG, Jobe AH, Ikegami M, et al. Increased IP-10 and MIG expression after intra-amniotic endotoxin in preterm lamb lung. Am J Respir Crit Care Med. 2003;167(5):779-86.
- Gomez R, Romero R, Ghezzi F, et al. The fetal inflammatory response syndrome. Am J Obstet Gynecol. 1998;179(1):194-202.
- Engle WA; American Academy of Pediatrics Committee on Fetus and Newborn. Age terminology during the perinatal period. Pediatrics. 2004;114(5):1362-4.
- Whitsett JA, Rice WR, Warner BB, et al. Acute respiratory disorders. In: Mac Donald MG, Mullet MD, Seshia MMK, editors. Avery’s Neonatology. 6th ed. Philadelphia: Lippincott Williams and Wilkins, 2005;pp 569-76.
- Haque KN. Definitions of bloodstream infection in the newborn. Pediatr Crit Care Med. 2005;6(3):45-9.
- Neu J. Necrotizing enterocolitis: the search for unifying pathogenic theory leading to prevention. Pediatr Clin North Am. 1996;43(2):409-32.
- Owens R. Intraventriculer hemorrhage in the premature neonate. Neonatal Netw. 2005;24(3):55-71.
- Katz TA, Koam AH, Schuit E, et al. Comparison of new bronchopulmonary dysplasia definitions on long-term outcomes in preterm infants. J Pediatr. 2023;253:86-93.
- International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005;123(7):991-9.
- Stoll BJ, Hansen NI, Bell EF, et al. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012. JAMA. 2015;314(10):1039-51.
- Gravett MG, Novy MS, Rosenfeld RG, et al. Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers. JAMA. 2004;292(4):462-9.
- Garg A, Jaiswal A. Evaluation and Management of Premature Rupture of Membranes: A Review Article. Cureus. 2023;15(3):e36615.
- Jantien L van der Hetden. Preterm prelabor rupture of membranes: different gestational ages, different problems. Thesis. 2014.
- Andrews WW, Hauth SC, Goldenberg RL, et al. Amniotic fluid interleukin-6; correlation with upper genital tract microbial colonization and gestational age in women delivered after spontaneous labor versus indicated delivery. Am J Obstet Gynecol. 1995;173(2):606-12.
- Chang Y, Li W, Shen Y, et al. Association between interleukin-6 and preterm birth: a meta-analysis. Ann Med. 2023:55(2):2284384.
- Cornette L. Fetal and neonatal inflammatory response and adverse outcome. Semin Fetal Neonatal Med. 2004;9(6): 459-70.
- Flannery DD, Puopolo KM. Neonatal early-onset sepsis. Neoreviews. 2022;23(11):756-70.
- Dol J, Hughes H, Bonet M, et al. Timing of neonatal mortality and severe morbidity during the postnatal period: a systematic review. JBI Evid Synth. 2023;21(1):98-199.
- Chıossi G, Tommosa MD, Monari F, et al. Neonatal outcomes and risk of neonatal sepsis in an expectantly managed cohort of late preterm prelabor rupture of membranes. Eur J Obstet Gynecol Reprod Biol. 2021;261:1-6.
- Gezer A, Parafit-Yalciner E, Guralp O, et al. Neonatal morbidity mortality outcomes in preterm premature rupture of membranes. J Obstet Gynaecol. 2013;33(1):38-42.
- Ng PC, Li K, Leung TF, et al. Early prediction of sepsis-induced disseminated intravascular coagulation with interleukin-10, interleukin-6, and RANTES in preterm infants. Clin Chem. 2006;52(6):1181-9.
- Ng PC, Li K, Chui KM, et al. IP-10 is an early diagnostic marker for identification of late-onset bacterial infection in preterm infants. Pediatr Res. 2007;61(1):93-8.
- Rallis D, Balomenou F, Kappatou K, et al. C-reactive protein in infants with no evidence of early-onset sepsis. J Matern Fetal Neonatal Med. 2022;35(25):5659-64.
- Tang Q, Zhang L, Li H, et al. The fetal inflammation response syndrome and adverse neonatal outcomes: a meta-analysis. J Matern Fetal Neonatal Med. 2021;34(23):3902-14.
- Sorakin Y, Romero R, Mele L, et al. Umbilical cord serum interleukin-6, C-reactive protein, and myeloperoxidase concentrations at birth and association with neonatal morbidities and long-term neurodevelopmental outcomes. Am J Perinatol. 2014;31(8):717-26.