A FETAL SYSTEMIC INFLAMMATORY RESPONSE IS FOLLOWED BY THE SPONTANEOUSONSET OF PRETERM PARTURITION

OBJECTIVE: There is no evidence for the participation of the human fet us in the mechanisms responsible for the onset of preterm labor. We pr opose that preterm labor in the setting of infection results from the actions of proinflammatory cytokines secreted as part of the fetal and /or maternal host response to microbial invasion. The objective of thi s study was to determine whether a systemic fetal inflammatory respons e, defined as an elevation of fetal plasma interleukin-6 concentration s, has a temporal relationship with the commencement of labor. STUDY D ESIGN: After informed consent was obtained, amniocentesis and cordocen tesis were performed in 41 patients with preterm premature rupture of membranes who were not in labor on admission. Amniotic fluid was cultu red for both aerobic and anaerobic bacteria, as well as for mycoplasma s. Fetal plasma interleukin-8 was assayed by a sensitive and specific immunoassay. Statistical analyses included contingency tables and surv ival analysis with time-dependent Cox regression hazard modeling. RESU LTS: Microbial invasion of the amniotic cavity was present in 58.5% (2 4/41) of patients. Fetuses with fetal plasma interleukin-8 concentrati ons >11 pg/mL had a higher rate of spontaneous preterm delivery within 48 and 72 hours of the procedure than those with fetal plasma interle ukin-8 levels less than or equal to 11 pg/mL (88% vs 29% and 88% vs 35 %, respectively; P < .05 for all comparisons). Moreover, patients with initiation of labor and delivery within 48 hours of the procedure had a higher proportion of fetuses with plasma interleukin-8 values >11 p g/mL than patients delivered >48 hours (58% [7/12] vs 8% [1/13], respe ctively; P < .05). Survival analysis indicated that fetuses with eleva ted fetal plasma interleukin-8 levels had a shorter cordocentesis-to-d elivery interval than those without elevated fetal plasma interleukin- 6 concentrations (median 0.8 days [range 0.1 to 5] vs median 6 days [r ange 0.2 to 33.6], respectively; P < .05). Time-dependent Cox regressi on hazard modeling indicated that fetal plasma interleukin-6 level was the only covariate significantly associated with the duration of preg nancy after we adjusted for gestational age, amniotic fluid interleuki n-6 level, and the microbiologic state of the amniotic cavity (P < .01 ). CONCLUSION: A systemic fetal proinflammatory cytokine response is f ollowed by the onset of spontaneous preterm parturition in patients wi th preterm premature rupture of membranes.