Association of Umbilical Placental Vascular Disease With Fetal Acute Inflammatory Cytokine Responses

Abstract

We examined the hypothesis that fetal proinflammatory cytokine release is a feature of placental vascular disease causing fetal compromise. We measured the concentrations of fetal proinflammatory cytokines interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and interleukin-8 (IL-8) in the presence of vascular disease in the umbilical placental villous circulation. Vascular disease was identified by high-resistance umbilical artery Doppler flow velocity waveform studies. We measured levels of the inflammatory cytokines IL-6 and TNF-alpha and the chemokine IL-8 in fetal blood. Blood was collected from the umbilical vein at delivery, and serum was stored at -70C until assayed using chemiluminescent and enzyme-linked immunosorbent assay methods. We studied 36 normal pregnancies delivered by elective cesarean at term and 50 pregnancies with a high-resistance umbilical artery Doppler flow velocity waveform pattern indicative of fetal placental vascular disease delivered by elective cesarean because of potential fetal compromise. In the presence of umbilical placental vascular disease there were significantly higher levels of IL-6 (median 5.3 pg/mL, P <.05) and IL-8 (median 26.5 pg/mL, P <.01) compared with normal pregnancies (median value of IL-6 and IL-8 were below assay threshold). There was no difference for TNF-alpha, with the median results undetectable in both groups. We found higher concentrations of IL-6 and IL-8 in the fetal circulation in the presence of umbilical placental vascular disease.