Posthemorrhagic hydrocephalus (PHH) is a rare but serious outcome among premature babies in the NICU, with consequences including mortality and severe neurodevelopmental disabilities. The causes of PHH are still not entirely understood, and its prevention and treatment are controversial. Various cerebrospinal fluid biomarkers have been studied in infants with PHH in order to recognize the causes, diagnose brain injury, and predict neurodevelopmental outcomes. This systematic review summarizes studies on biomarkers of extracellular matrix activity, fibrinolysis/coagulation, hypoxia/cell death, and inflammation in the cerebrospinal fluid of infants with PHH.
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- Posthemorrhagic hydrocephalus
- Posthemorrhagic ventricular dilation
- Volpe JJ: Neurology of the Newborn, ed 5. Amsterdam, Elsevier Health Sciences, 2008.
- Batton DG, Holtrop P, DeWitte D, Pryce C, Roberts C: Current gestational age-related incidence of major intraventricular hemorrhage. J Pediatr 1994;125:623–625.
- Heuchan AM, Evans N, Henderson Smart DJ, Simpson JM: Perinatal risk factors for major intraventricular haemorrhage in the Australian and New Zealand Neonatal Network, 1995–97. Arch Dis Child Fetal Neonatal Ed 2002;86:F86–F90.
- Sheth RD: Trends in incidence and severity of intraventricular hemorrhage. J Child Neurol 1998;13:261–264.
- Murphy BP, Inder TE, Rooks V, Taylor GA, Anderson NJ, Mogridge N, et al: Posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome. Arch Dis Child Fetal Neonatal Ed 2002;87:F37–F41.
- Allan WC, Dransfield DA, Tito AM: Ventricular dilation following periventricular-intraventricular hemorrhage: outcome at age 1 year. Pediatrics 1984;73:158–162.
- Davis SL, Tooley WH, Hunt JV: Developmental outcome following posthemorrhagic hydrocephalus in preterm infants. Comparison of twins discordant for hydrocephalus. Am J Dis Child 1987;141:1170–1174.
- Sasidharan P, Marquez E, Dizon E, Sridhar CV: Developmental outcome of infants with severe intracranial-intraventricular hemorrhage and hydrocephalus with and without ventriculoperitoneal shunt. Childs Nerv Syst 1986;2:149–152.
- du Plessis AJ: Posthemorrhagic hydrocephalus and brain injury in the preterm infant: dilemmas in diagnosis and management. Semin Pediatr Neurol 1998;5:161–179.
- Whitelaw A: Intraventricular haemorrhage and posthaemorrhagic hydrocephalus: pathogenesis, prevention and future interventions. Semin Neonatol 2001;6:135–146.
- Galbreath E, Kim SJ, Park K, Brenner M, Messing A: Overexpression of TGF-beta 1 in the central nervous system of transgenic mice results in hydrocephalus. J Neuropathol Exp Neurol 1995;54:339–349.
- Whitelaw A, Christie S, Pople I: Transforming growth factor-beta1: a possible signal molecule for posthemorrhagic hydrocephalus? Pediatr Res 1999;46:576–580.
- Heep A, Stoffel-Wagner B, Bartmann P, Benseler S, Schaller C, Groneck P, et al: Vascular endothelial growth factor and transforming growth factor-beta1 are highly expressed in the cerebrospinal fluid of premature infants with posthemorrhagic hydrocephalus. Pediatr Res 2004;56:768–774.
- Heep A, Bartmann P, Stoffel-Wagner B, Bos A, Hoving E, Brouwer O, et al: Cerebrospinal fluid obstruction and malabsorption in human neonatal hydrocephaly. Childs Nerv Syst 2006;22:1249–1255.
- Chow LC, Soliman A, Zandian M, Danielpour M, Krueger RC Jr: Accumulation of transforming growth factor-beta2 and nitrated chondroitin sulfate proteoglycans in cerebrospinal fluid correlates with poor neurologic outcome in preterm hydrocephalus. Biol Neonate 2005;88:1–11.
- Lipina R, Reguli S, Novackova L, Podesvova H, Brichtova E: Relation between TGF-beta 1 levels in cerebrospinal fluid and ETV outcome in premature newborns with posthemorrhagic hydrocephalus. Childs Nerv Syst 2010;26:333–341.
- Heep A, Stoffel-Wagner B, Soditt V, Aring C, Groneck P, Bartmann P: Procollagen I C-propeptide in the cerebrospinal fluid of neonates with posthaemorrhagic hydrocephalus. Arch Dis Child Fetal Neonatal Ed 2002;87:F34–F36.
- Okamoto T, Takahashi S, Nakamura E, Nagaya K, Hayashi T, Shirai M, et al: Matrix metalloproteinases in infants with posthemorrhagic hydrocephalus. Early Hum Dev 2008;84:137–139.
- Koehne P, Hochhaus F, Felderhoff-Mueser U, Ring-Mrozik E, Obladen M, Buhrer C: Vascular endothelial growth factor and erythropoietin concentrations in cerebrospinal fluid of children with hydrocephalus. Childs Nerv Syst 2002;18:137–141.
- Whitelaw A, Odd DE: Intraventricular streptokinase after intraventricular hemorrhage in newborn infants. Cochrane Database Syst Rev 2007; CD000498.
- Whitelaw A, Evans D, Carter M, Thoresen M, Wroblewska J, Mandera M, et al: Randomized clinical trial of prevention of hydrocephalus after intraventricular hemorrhage in preterm infants: brain-washing versus tapping fluid. Pediatrics 2007;119:e1071–e1078.
- Hansen AR, Lapp C, Brugnara C: Plasminogen activator inhibitor-1: defining characteristics in the cerebrospinal fluid of newborns. J Pediatr 2000;137:132–134.
- Hansen A, Whitelaw A, Lapp C, Brugnara C: Cerebrospinal fluid plasminogen activator inhibitor-1: a prognostic factor in posthaemorrhagic hydrocephalus. Acta Paediatr 1997;86:995–998.
- Whitelaw A, Mowinckel MC, Fellman V, Abildgaard U: Endogenous tissue plasminogen activator in neonatal cerebrospinal fluid. Eur J Pediatr 1996;155:117–119.
- Whitelaw A: Endogenous fibrinolysis in neonatal cerebrospinal fluid. Eur J Pediatr 1993;152:928–930.
- Whitelaw A, Creighton L, Gaffney P: Fibrinolysis in cerebrospinal fluid after intraventricular haemorrhage. Arch Dis Child 1991;66:808–809.
- Reinhold A, Zhang J, Gessner R, Felderhoff-Mueser U, Obladen M, Dame C: High thrombopoietin concentrations in the cerebrospinal fluid of neonates with sepsis and intraventricular hemorrhage may contribute to brain damage. J Interferon Cytokine Res 2007;27:137–145.
- Bejar R, Saugstad OD, James H, Gluck L: Increased hypoxanthine concentrations in cerebrospinal fluid of infants with hydrocephalus. J Pediatr 1983;103:44–48.
- Savman K, Nilsson UA, Blennow M, Kjellmer I, Whitelaw A: Non-protein-bound iron is elevated in cerebrospinal fluid from preterm infants with posthemorrhagic ventricular dilatation. Pediatr Res 2001;49:208–212.
- Felderhoff-Mueser U, Buhrer C, Groneck P, Obladen M, Bartmann P, Heep A: Soluble Fas (CD95/Apo-1), soluble Fas ligand, and activated caspase 3 in the cerebrospinal fluid of infants with posthemorrhagic and nonhemorrhagic hydrocephalus. Pediatr Res 2003;54:659–664.
- Whitelaw A, Rosengren L, Blennow M: Brain specific proteins in posthaemorrhagic ventricular dilatation. Arch Dis Child Fetal Neonatal Ed 2001;84:F90–F91.
- Savman K, Blennow M, Hagberg H, Tarkowski E, Thoresen M, Whitelaw A: Cytokine response in cerebrospinal fluid from preterm infants with posthaemorrhagic ventricular dilatation. Acta Paediatr 2002;91:1357–1363.
- Schmitz T, Heep A, Groenendaal F, Huseman D, Kie S, Bartmann P, et al: Interleukin-1beta, interleukin-18, and interferon-gamma expression in the cerebrospinal fluid of premature infants with posthemorrhagic hydrocephalus – markers of white matter damage? Pediatr Res 2007;61:722–726.
- White RP, Leffler CW, Bada HS: Eicosanoid levels in CSF of premature infants with posthemorrhagic hydrocephalus. Am J Med Sci 1990;299:230–235.
- Whitelaw A, Jary S, Kmita G, Wroblewska J, Musialik-Swietlinska E, Mandera M, et al: Randomized trial of drainage, irrigation and fibrinolytic therapy for premature infants with posthemorrhagic ventricular dilatation: developmental outcome at 2 years. Pediatrics 2010;125:e852–e858.
Stephanie Merhar, MD
Division of Neonatology, Cincinnati Children’s Hospital
3333 Burnet Ave ML 7009
Cincinnati, OH 45229 (USA)
Tel. +1 513 257 7749, E-Mail email@example.com
Received: October 7, 2010
Accepted after revision: December 9, 2010
Published online: July 27, 2011
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 0, Number of References : 35
Neonatology (Fetal and Neonatal Research)
Vol. 101, No. 1, Year 2012 (Cover Date: December 2011)
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