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PEDIATRICS Vol. 110 No. 4 October 2002, pp. 673-680

Clinical Chorioamnionitis, Elevated Cytokines, and Brain Injury in Term Infants

Lina F. Shalak, MD, Abbot R. Laptook, MD, Hasan S. Jafri, MD, Octavio Ramilo, MD and Jeffrey M. Perlman, MB

From the Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

--> Objectives. To determine the initial inflammatory cytokine response in term infants born to mothers with clinical chorioamnionitis and to assess whether the cytokine response is associated with birth depression, abnormal neurologic examination, and hypoxic-ischemic encephalopathy (HIE).

Methods. Infants who were exposed to chorioamnionitis and admitted to the neonatal intensive care unit (n = 61) were studied prospectively. Cytokine concentrations were measured from umbilical cord blood and at 6 and 30 hours after birth. Control values (n = 50) were determined from cord blood of healthy term infants. Enzyme-linked immunosorbent assays were performed for interleukin (IL)-1ß; IL-6; IL-8; regulated on activation, normal T-cell expressed and secreted (RANTES); macrophage inflammatory protein-1; and tumor necrosis factor-. Serial blinded neurologic examinations using a modified Dubowitz score were performed simultaneously at 6 and 30 hours.

Results. Cord IL-6 (1071 ± 1517 vs 65 ± 46 pg/mL), IL-8 (2580 ± 9834 vs 66 ± 57 pg/mL), and RANTES (95 917 ± 16 518 vs 54 000 ± 14 306 pg/mL) concentrations only were higher in infants with chorioamnionitis versus control infants. IL-6 increased at 6 hours to 1451 ± 214 pg/mL, followed by a 5-fold decline at 30 hours in contrast to progressive decreases over time in IL-8 and RANTES. There was no relationship between cytokines and birth depression. Modified Dubowitz score correlated with IL-6 at 6 hours (r = 0.5). Infants with HIE/seizures (n = 5) had significantly higher cytokine concentrations at 6 hours versus infants without either (n = 56): IL-6 (3130 vs 1219 pg/mL), IL-8 (5433 vs 780 pg/mL), and RANTES (97 396 vs 46 914 pg/mL).

Conclusions. There was a significant association between abnormalities in the neurologic examination and cytokine concentrations, with the highest cytokines concentrations observed in infants who developed HIE/seizures.

Key Words: hypoxic-ischemic encephalopathy • chorioamnionitis • cytokines • chemokines

Abbreviations: HIE, hypoxic-ischemic encephalopathy • NICU, neonatal intensive care unit • MDS, modified Dubowitz score • SD, standard deviation • IL, interleukin • TNF, tumor necrosis factor • RANTES, regulated on activation, normal T-cell expressed and secreted • MIP, macrophage inflammatory protein • MRI, magnetic resonance imaging • CSF, cerebrospinal fluid

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Received for publication Oct 17, 2001; Accepted Mar 26, 2002.

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Chorioamnionitis and Neonatal Brain Damage: The Unrecognized Iatrogenic Cause

Cory A Mermer

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