Chemokine CCL18 predicts intraventricular hemorrhage in very preterm infants

Background. Intraventricular hemorrhage (IVH) in very preterm infants is a common disease associated with long-term consequences. Risk factors of IVH remain to be further defined. Aims. To determine whether specific immunoproteins at birth predict the risk of IVH and whether their receptors are localized at the bleeding site. Methods. A prospective cohort consisted of 163 infants born before 32 weeks of gestation. Altogether 107 cord blood immunoproteins and 12 cytokines from peripheral blood obtained 1 and 7 days after birth were analyzed. Serial brain ultrasounds were assessed. Immunohistochemistry of a chemokine receptor from 14 autopsies was studied. Results. Low levels of cord chemokine CCL18 (chemokine (C-C motif) ligand 18) robustly predicted the risk of IVH grade II-IV when ante-and neonatal risk factors were considered. Cord CCL18 increased from 32 weeks to term. During the first week after very preterm birth CCL18 increased as the risk of new IVH cases decreased. CCL18 receptor, CCR3, was detectable in choroid plexus, periventricular capillary endothelium, ependymal cells, and in germinal matrix. Conclusion. Low cord blood CCL18 is an independent risk factor of IVH. CCL18 may inhibit signal transduction of its receptor in periventricular cells. Defining the function and regulation of CCL18 may help to decrease the risk of IVH.