EXPERIMENTALLY-INDUCED INTRAUTERINE INFECTION CAUSES FETAL BRAIN WHITE-MATTER LESIONS IN RABBITS

OBJECTIVE: Periventricular leukomalacia, a common brain white matter l esion in preterm neonates, is a major risk factor for cerebral palsy. Epidemiologic studies have demonstrated an association between infecti on and periventricular leukomalacia. The purpose of this study was to determine whether ascending intrauterine infection could cause brain w hite matter lesions in the fetal rabbit.STUDY DESIGN: Rabbits with tim ed pregnancies underwent hysteroscopy at 20 to 21 days of gestation (7 0%). Animals were allocated in a ratio of 2:1 for inoculation with eit her Escherichia coli (0.2 mi containing 10(3) to 10(4) colony-forming units) or sterile saline solution. Both groups were treated with ampic illin-sulbactam (Unasyn, 100 mg/kg per day; Pfizer, Seoul) every 8 hou rs until they were killed 5 to 6 days after hysteroscopy. Histologic e xamination of the placentas and fetal brains was conducted. RESULTS: F orty-five animals underwent hysteroscopy; 31 were inoculated with E. c oli and 14 with sterile saline solution. At the time the animals were killed, the rate of intrauterine infection was higher and there were f ewer live fetuses in the E. coli-inoculated animals than in the saline solution group. Histologic evidence of brain white matter damage was identified in 12 fetuses born to 10 E. coli-inoculated rabbits but non e in the saline solution group lo < 0.05). All rabbits with brain whit e matter lesions had evidence of intrauterine infection. Evidence of w hite matter damage included increased karyorrhexis, rarefaction, and d isorganization of white matter. Apoptosis was demonstrated in areas of white matter damage by immunohistochemical studies. CONCLUSION: Exper imental ascending intrauterine infection can cause fetal brain white m atter lesions.