The impact of chronic intrauterine inflammation on the physiologic and neurodevelopmental consequences of intermittent umbilical cord occlusion in fetal sheep.

OBJECTIVE: To determine the effect of intrauterine inflammation on fetal responses to umbilical cord occlusion (UCO). STUDY DESIGN: In pregnant sheep, lipopolysaccharide (LPS) or saline (SAL) was infused intra-amniotically for 4 weeks from 80 days of gestation (d). At 110 d, fetuses were instrumented for UCOs (5 × 2-minutes, 30-minute intervals: LPS + UCO, n = 6; SAL + UCO, n = 8) or no UCO (sham, n = 6) on 117 and 118 d. Tissues were collected at 126 d. RESULTS: Fetal physiological responses to UCO were similar between LPS + UCO and SAL + UCO. Histologic chorioamnionitis and increased amniotic fluid interleukin 8 (IL-8) were observed in LPS + UCO pregnancies (versus SAL + UCO, P < .05). CNPase-positive oligodendrocyte number in the cerebral white matter was lower in LPS + UCO and SAL + UCO than sham (P < .05); there was no effect on astrocytes or activated microglia/macrophages. Two of the SAL + UCO fetuses had white matter lesions; none were observed in LPS + UCO or sham. CONCLUSION: Chronic pre-existing intrauterine inflammation did not exacerbate fetal brain injury induced by intermittent UCO.