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.