THE FETAL INFLAMMATORY RESPONSE SYNDROME

OBJECTIVE: The objective of this study was to determine the frequency and clinical significance of a systemic inflammatory response as defin ed by an elevated plasma interleukin-g concentration in fetuses with p reterm labor or preterm premature rupture of membranes. STUDY DESIGN: Amniocenteses and cordocenteses were performed in 157 patients with pr eterm labor and preterm premature rupture of membranes. Written inform ed consent and multi-institutional review board approvals were obtaine d. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as mycoplasmas. Amniotic fluid and fetal plasma interleukin-6 con centrations were measured with a sensitive and specific immunoassay. S tatistical analyses included contingency tables, receiver operating ch aracteristic curve analysis, and multiple logistic regression. RESULTS : One hundred five patients with preterm labor and 52 patients with pr eterm premature rupture of membranes were included in this study. The overall prevalence of severe neonatal morbidity (defined as the presen ce of respiratory distress syndrome, suspected or proved neonatal seps is, pneumonia, bronchopulmonary dysplasia, intraventricular hemorrhage , periventricular leukomalacia, or necrotizing enterocolitis) among su rvivors was 34.8% (54/155). Neonates in whom severe neonatal morbidity developed had higher concentrations of fetal plasma interleukin-6 tha n fetuses without development of severe neonatal morbidity (median 14. 0 pg/mL, range 0.5 to 900 vs median 5.2 pg/mL, range 0.3 to 900, respe ctively; P < .005). Multivariate analysis was performed to explore the relationship between the presence of a systemic fetal inflammatory re sponse and subsequent neonatal outcome. To preserve a meaningful tempo ral relationship between the results of fetal plasma interleukin-6 con centrations and the occurrence of severe neonatal morbidity, the analy sis was restricted to 73 fetuses delivered within 7 days of cordocente sis who survived. The prevalence of severe neonatal morbidity in this subset of patients was 53.4% (39n3). A fetal plasma interleukin-6 cuto ff value of 11 pg/mL was used to define the presence of a systemic inf lammatory response. The prevalence of a fetal plasma interleukin-6 lev el >11 pg/mL was 49.3% (36/73). Fetuses with fetal plasma interleukin- 8 concentrations >11 pg/mL had a higher rate of severe neonatal morbid ity than did those with fetal plasma interleukin-8 levels less than or equal to 11 pg/mL (77.8% [28/36] vs 29.7% [11/37], respectively; P < .001). Stepwise logistic regression analysis demonstrated that the fet al plasma interleukin-g concentration was an independent predictor of the occurrence of severe neonatal morbidity (odds ratio 4.3, 95% confi dence interval 1 to 18.5) when adjusted for gestational age at deliver y, the cause of preterm delivery (preterm labor or preterm premature r upture of membranes), clinical chorioamnionitis, the cordocentesis-to- delivery interval, amniotic fluid culture, and anmiotic fluid interleu kin-6 results. CONCLUSION: A systemic fetal inflammatory response, as determined by an elevated fetal plasma interleukin-B value, is an inde pendent risk factor for the occurrence of severe neonatal morbidity.