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Umbilical vein interleukin-6 levels in very low birth weight infants developing intraventricular hemorrhage

  • Rajeev Kassal
    Affiliations
    Division of Neonatology, Department of Pediatrics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, One Robert Wood Johnson Place, MEB 312C, New Brunswick, NJ 08903-0019, USA
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  • Mujahid Anwar
    Affiliations
    Division of Neonatology, Department of Pediatrics, St Peter's University Hospital, New Brunswick, NJ, USA
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  • Fawaz Kashlan
    Affiliations
    Division of Neonatology, Department of Pediatrics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, One Robert Wood Johnson Place, MEB 312C, New Brunswick, NJ 08903-0019, USA
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  • John Smulian
    Affiliations
    Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Medicine and Dentistry-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
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  • Mark Hiatt
    Affiliations
    Division of Neonatology, Department of Pediatrics, St Peter's University Hospital, New Brunswick, NJ, USA
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  • Thomas Hegyi
    Correspondence
    Corresponding author. Tel.: +1 732 235 7354; fax: +1 732 235 6609.
    Affiliations
    Division of Neonatology, Department of Pediatrics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, One Robert Wood Johnson Place, MEB 312C, New Brunswick, NJ 08903-0019, USA
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      Abstract

      To assess the relationship between perinatal infection/inflammation as reflected by umbilical vein interleukin-6 (IL-6) levels and the development of periventricular–intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants, we tested the hypothesis that VLBW infants who develop IVH have higher concentrations of IL-6 in an umbilical vein sample compared to infants without IVH. An inception cohort of 69 VLBW infants was followed from birth until discharge or death to determine the development of IVH by serial neuroultrasounds. Umbilical vein IL-6 levels were measured using commercially available ELISA kit (Endogen Laboratories, Woburn, MA) and compared in IVH and control cohorts. Twenty-two (32%) infants developed IVH, including 18 (82%) with grade I or II and 4 (18%) with grade III or IV. One of these infants also developed periventricular leukomalacia. The umbilical vein IL-6 levels were significantly elevated in infants with IVH with median value of 87 pg/ml (25th percentile value 30 pg/ml and 75th percentile value 310 pg/ml) compared with infants without IVH, with a median value of 0 pg/ml (25th percentile value 0 pm/ml and 75th percentile value 4 pg/ml) (P=0.007). Umbilical vein IL-6 levels are elevated in neonates who subsequently develop IVH.

      Keywords

      Abbreviations:

      IL-6 (interleukin-6), IVH (periventricular–intraventricular hemorrhage), nl (natural logarithm), pg (picograms), GBS (Group B Streptococcus), RDS (respiratory distress syndrome), PIH (pregnancy induced hypertension/preeclampsia), PDA (patent ductus arteriosus), IUGR (intrauterine growth retardation), NUS (neuroultrasound), IMV (intermittent mandatory ventilation), PPV (positive pressure ventilation), BBB (blood–brain barrier), CSF (cerebrospinal fluid), VLBW (very low birth weight infants (<1501g birth weight))
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      References

        • Dykes F.D.
        • Lazzara A.
        • Ahmann P.
        • Blumenstein B.
        • Schwartz J.
        • Brann A.W.
        Intraventricular hemorrhage: a prospective evaluation of etiopathogenesis.
        Pediatrics. 1980; 66: 42-49
        • Garcia-Prats J.A.
        • Procianoy R.S.
        • Adams J.M.
        • Rudolph A.J.
        The hyaline membrane disease-intraventricular hemorrhage relationship in the very low birth weight infant: perinatal aspects.
        Acta Paediatr Scand. 1982; 71: 79-84
        • Gomez R.
        • Romero R.
        • Ghezzi F.
        • Yoon B.H.
        • Mazor M.
        • Berry S.M.
        The fetal inflammatory response syndrome.
        Am J Obstet Gynecol. 1998; 179: 194-202
        • Hashim I.A.
        • Walsh A.
        • Hart C.A.
        • Shenkin A.
        Cerebrospinal fluid interleukin-6 and its diagnostic value in the investigation of meningitis.
        Ann Clin Biochem. 1995; 32: 289-296
        • Kashlan F.
        • Smulian J.
        • Shen-Schwarz S.
        • Anwar M.
        • Hiatt M.
        • Hegyi T.
        Umbilical vein interleukin-6 and tumor necrosis factor alpha plasma concentrations in the very preterm infant.
        Pediatr Infect Dis. 2000; 19: 238-243
        • Kauma S.W.
        • Herman K.
        • Wang Y.
        • Walsh S.W.
        Differential mRNA expression and production of interleukin-6 in placental trophoblast and villous core compartments.
        Am J Reprod Immunol. 1993; 30: 131-135
        • Kossmann T.
        • Hans V.
        • Imhof H.G.
        • Trentz O.
        • Morganti-Kossmann M.C.
        Interleukin-6 released in human cerebrospinal fluid following traumatic brain injury may trigger nerve growth factor production in astrocytes.
        Brain Res. 1996; 713: 143-152
        • Martin-Ancel A.
        • Garcia-Alix A.
        • Pascual-Salcedo D.
        • Cabanas F.
        • Valcarce M.
        • Quero J.
        Interleukin-6 in the cerebrospinal fluid after perinatal asphyxia is related to early and late neurological manifestations.
        Pediatrics. 1997; 100: 789-794
        • Oleksowicz L.
        • Mrowiec Z.
        • Zuckerman D.
        • Isaacs R.
        • Dutcher J.
        • Puszkin E.
        Platelet activation induced by interleukin-6: evidence for a mechanism involving arachidonic acid metabolism.
        Thromb Haemost. 1994; 72: 302-308
        • Paneth N.
        • Pinto-Martin J.
        • Gardiner J.
        • Wallenstein S.
        • Katsikiotis V.
        • Hegyi T.
        • et al.
        Incidence and timing of germinal matrix/intraventricular hemorrhage in low birth weight infants.
        Am J Epidemiol. 1993; 137: 1167-1176
        • Papile L.A.
        • Burstein J.
        • Burstein R.
        • Koffler H.
        Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weight less than 1500 g.
        J Pediatr. 1978; : 529-534
        • Partridge J.C.
        • Babcock D.S.
        • Steichen J.J.
        • Han B.K.
        Optimal timing for diagnostic cranial ultrasound in low-birth-weight infants: detection of intracranial hemorrhage and ventricular dilation.
        J Pediatr. 1983; 102: 281-287
        • Perlman J.M.
        • Volpe J.J.
        Intraventricular hemorrhage in extremely small premature infants.
        Am J Dis Child. 1986; 140: 1122-1124
        • Shankaran S.
        • Bauer C.R.
        • Bain R.
        • Wright L.L.
        • Zachary J.
        Relationship between antenatal steroid administration and grades III and IV intracranial hemorrhage in low birth weight infants. The NICHD neonatal research network.
        Am J Obstet Gynecol. 1995; 173: 305-312
        • Slungaard A.
        • Vercellotti G.M.
        • Walker G.
        • Nelson R.D.
        • Jacob H.S.
        Tumor necrosis factor-alpha/cachectin stimulates eosinophil oxidant production and toxicity towards human endothelium.
        J Exp Med. 1990; 171: 2025-2041
        • Szymonowicz W.
        • Yu V.Y.
        • Wilson F.E.
        Antecedents of periventricular haemorrhage in infants weighing 1250 g or less at birth.
        Arch Dis Child. 1984; 59: 13-17
        • Tarkowski E.
        • Rosengren L.
        • Blomstrand C.
        • Wikkelso C.
        • Jensen C.
        • Ekholm S.
        • et al.
        Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke.
        Stroke. 1995; 26: 1393-1398
        • Volpe J.J.
        • Herscovitch P.
        • Perlman J.M.
        • Raichle M.E.
        Positron emission tomography in the newborn: extensive impairment of regional cerebral blood flow with intraventricular hemorrhage and hemorrhagic intracerebral involvement.
        Pediatrics. 1983; 72: 589-601
        • Wada H.
        • Tanigawa M.
        • Wakita Y.
        • Nakase T.
        • Minamikawa K.
        • Kaneko T.
        • et al.
        Increased plasma level of Interleukin-6 in disseminated intravascular coagulation.
        Blood Coagul Fibrinolysis. 1993; 4: 583-590
        • Weeks J.W.
        • Reynolds L.
        • Taylor D.
        • Lewis J.
        • Wan T.
        • Gall S.A.
        Umbilical cord blood interleukin-6 levels and neonatal morbidity.
        Obstet Gynecol. 1997; 90: 815-818
        • Westlin W.F.
        • Gimbrone Jr., M.A.
        Neutrophil-mediated damage to human vascular endothelium. Role of cytokine activation.
        Am J Pathol. 1993; 142: 117-128
        • Yoon B.H.
        • Romero R.
        • Kim C.J.
        • Jun J.K.
        • Gomez R.
        • Choi J.H.
        • et al.
        Amniotic fluid Interleukin-6: a sensitive test for antenatal diagnosis of acute inflammatory lesions of preterm placenta and prediction of perinatal morbidity.
        Am J Obstet Gynecol. 1995; 172: 960-970
        • Yoon B.H.
        • Romero R.
        • Kim C.J.
        • Koo J.N.
        • Choe G.
        • Syn H.C.
        • et al.
        High expression of tumor necrosis factor-alpha and interleukin-6 in periventricular leukomalacia.
        Am J Obstet Gynecol. 1997; 177: 406-411
        • Yoon B.H.
        • Romero R.
        • Yang S.H.
        • Jun J.K.
        • Kim I.O.
        • Choi J.H.
        • et al.
        Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with white matter lesions associated with periventricular leukomalacia.
        Am J Obstet Gynecol. 1996; 174: 1433-1440