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Chemokine CCL18 predicts intraventricular hemorrhage in very preterm infants
Hanna Kallankari1, Tuula Kaukola, Marja Ojaniemi
1Institute of Clinical Medicine, Department of Pediatrics, University of Oulu, FIN-90014, Oulu, Finland.
Insights
Low cord blood chemokine (C-C motif) ligand 18 (CCL18) is a significant risk factor for intraventricular hemorrhage (IVH) in preterm infants. Higher CCL18 levels correlate with decreased IVH risk, suggesting a protective role.
Area of Science:
- Neonatal Medicine
- Immunology
- Perinatal Research
Background:
- Intraventricular hemorrhage (IVH) is a prevalent condition in very preterm infants, often leading to long-term complications.
- Identifying reliable risk factors for IVH is crucial for effective prevention and management strategies.
Purpose of the Study:
- To investigate whether specific immunoproteins present at birth can predict the risk of IVH in very preterm infants.
- To determine the localization of immunoprotein receptors at potential IVH bleeding sites.
Main Methods:
- A prospective cohort study involving 163 infants born before 32 weeks gestation.
- Analysis of 107 cord blood immunoproteins and peripheral blood cytokines (1 and 7 days post-birth).
- Serial brain ultrasounds and immunohistochemistry of chemokine receptor CCR3 in 14 autopsies.
Main Results:
- Low cord blood levels of chemokine (C-C motif) ligand 18 (CCL18) independently predicted IVH (grade II-IV), even after accounting for other risk factors.
- CCL18 levels increased from 32 weeks gestation to term and also increased during the first week post-birth as IVH risk decreased.
- The CCL18 receptor, CCR3, was found in key brain areas including the choroid plexus, periventricular capillaries, ependymal cells, and germinal matrix.
Conclusions:
- Low cord blood CCL18 is an independent predictor of IVH in very preterm infants.
- CCL18 may exert a protective effect by potentially inhibiting signal transduction via its receptor in periventricular cells.
- Further research into CCL18's function and regulation could lead to novel strategies for reducing IVH risk.
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.
