Article Text

  1. H Mikkonen1,
  2. T Kaukola1,
  3. J Tuimala2,
  4. R Herva3,
  5. M Perhomaa4,
  6. S Kingsmore5,
  7. M Hallman1
  1. 1Department of Pediatrics, University of Oulu, Oulu, Finland,
  2. 2The Finnish IT Center for Science, Espoo, Finland,
  3. 3Department of Pathology, University of Oulu, Oulu, Finland,
  4. 4Department of Radiology, University of Oulu, Oulu, Finland,
  5. 5National Center for Genome Resources, Santa Fe, New Mexico, USA


Objective: Intrauterine inflammation and fetal inflammatory response are reportedly risk factors for brain injury in very preterm infants. We investigated the role of cytokines and histological chorioamnionitis (HCA) in predicting intraventricular haemorrhage (IVH).

Methods: We studied a prospective cohort of 163 surviving infants born before 32 weeks of gestation in Oulu University Hospital between 1998 and 2002. Altogether, 107 immunoproteins were analysed from cord blood. The placentas were evaluated for HCA. The infants underwent serial brain ultrasound assessments. Together with antenatal risk factors the biomarkers were evaluated using classification and regression trees analysis. This new data mining method identifies the continuous factor that best associates with the trait.

Results: The incidence of IVH grades 2–4 was 14%. Infants with IVH grades 2–4 had a lower level of cord serum PARC/CCL18 compared with infants with no IVH or IVH grade 1 (p = 0.002). In the logistic regression model PARC/CCL18 independently predicted IVH grades 2–4 (odds ratio (OR) 5.75, 95% CI 1.94 to 17.08, p = 0.04). None of the common pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8, TNF-α) were associated with IVH grades 2–4. In the whole preterm cohort HCA did not associate with IVH. However, among the infants born <28 weeks of gestation HCA correlated with IVH grades 2–4 (p = 0.005) and in the logistic regression model HCA independently predicted IVH grades 2–4 (OR 8.89, 95% CI 1.58 to 50.05, p = 0.013).

Conclusion: Chorioamnionitis and a low level of cord blood PARC/CCL18 predicted IVH in very preterm infants. This is the first report associating the novel chemokine with the risk of haemorrhage.

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