Induction of antenatal periventricular leukomalacia by hemorrhagic hypotension in the chronically instrumented fetal sheep.

Our purpose was to determine whether systemic hypotension induced by rapid withdrawal of fetal blood would induce periventricular leukomalacia in the brain of premature fetal sheep. At 113 days' gestation, systemic hypotension (mean blood pressure <30 mm Hg) was induced by withdrawing approximately 35% of the fetoplacental blood volume in the hemorrhage group (n = 6), whereas in the control group (n = 4) isovolemic exchange transfusion was carried out. Six days after the insult, fetal brains were removed and processed for histologic analysis. Five of the 6 fetuses in the hemorrhage group exhibited periventricular white-matter lesions, consisting of nodular coagulation necrosis or diffuse axonal swellings or both. No abnormal findings other than these lesions were detected in the fetal brains in either experimental group. Hemorrhagic hypotension antenatally induced brain lesions similar to those of periventricular leukomalacia, suggesting that it is an essential element in the pathogenesis of periventricular leukomalacia in premature fetuses.