Non-protein-bound iron is elevated in cerebrospinal fluid from preterm infants with posthemorrhagic ventricular dilatation

Posthemorrhagic ventricular dilatation (PHVD) is closely associated with wh ite matter injury and neurologic disability in the preterm infant. An impor tant factor in periventricular white matter damage may be the specific vuln erability of iron-rich immature oligodendroglia to reactive oxygen species toxicity. Non-protein-bound iron (NPBI) is a potent catalyst in the generat ion of hydroxyl radicals (Fenton reaction). Our objective was to determine whether NPBI is increased in cerebrospinal fluid (CSF) from preterm infants with PHVD compared with preterm control infants. Samples of CSF were obtai ned from 20 infants with PHVD and 10 control subjects. The level of NPBI wa s determined by a new spectrophotometric method using batho-phenanthroline as a chelator. To evaluate the effect of hemolysis, CSF and blood were mixe d in different proportions, spun, frozen and thawed, and then analyzed for NPBI. NPBI was found in 75% (15 of 20) of infants with PHVD and in 0% (0 of 10) of control infants (p = 0.0002). Hemolysis induced in vitro did not re sult in any significant levels of NPBI. Within the group with PHVD, NPBI co ncentrations in CSF did not correlate with disability, parenchymal brain le sions, or the need for shunt surgery. NPBI was increased in CSF from preter m infants with PHVD, and the increase could not be explained by hemolysis a lone. Free iron may help to explain the association between intraventricula r hemorrhage and white matter damage.