Inflammatory markers in intrauterine and fetal blood and cerebrospinal fluid compartments are associated with adverse pulmonary and neurologic outcomes in preterm infants

Recent evidence strongly implicates the inflammatory response to intrauterine infection in the pathogenesis of neonatal brain and king injury. We hypothesized that lung and brain injury in preterm infants occurs during a common developmental window of vulnerability as the result of an inflammatory response in different compartments. To determine whether inflammatory markers in these compartments are associated with bronchopulmonary dysplasia (BPD) or cranial ultrasound (CUS) abnormalities in infants <33 wk gestation age (GA) and < 1501 g birth weight, we analyzed placental pathology and serum and cerebrospinal fluid (CSF) IL-6, IL-1beta, and tumor necrosis factor-alpha (TNF-alpha) concentrations in 276 infants. Logistic regressions were performed stratified by GA. Histologic chorioamnionitis was significantly associated with BPD in infants less than or equal to 28 wk GA (OR 3.6. p = 0.027). Maternal stage of chorioamnionitis significantly correlated with severity of BPD. Presence of a fetal inflammatory response indicated by fetal vasculitis or elevated cytokines was not associated with the development of BPD. Serum IL-6 greater than or equal to 17 pg/mL was associated with an abnormal CUS in infants >28 wk GA (OR 3.36 p = 0.023) but not less than or equal to28 wk GA. CSF concentrations of IL-6 greater than or equal to6.5 pg/mL and TNF-alpha greater than or equal to3 pg/mL were associated with abnormal CUS in infants less than or equal to28 wk GA (IL-6 OR 3.0: TNF-alpha OR 3.5; p < 0.05 each case) but not ≥28 wk GA. These data suggest that in infants ≤28 wks GA, BPD may be initiated by inflammatory mediators in amniotic fluid, but brain injury may involve variations in the systemic inflammatory response.