Yoon, EH; Kimx, CJ; Juti, JK; Park, KH; Chix, JG; Gotnez, R; Romero, R
abstract
OBJECTIVE: Periventricular lenkomalacia, a common brain white matter lesion in preterm neonates, is a major risk factor for cerebral palsy. Epidemiologie studies have demonstrated an association between infection and periventricular leukomalacia. The purpose of this study was to determine if ascending intrauterine infection could cause brain white matter lesions in the fetal rabbit. STUDY DESIGN: Timed-pregnant rabbits were subjected to hysteroscopy at 20-21 days of gestation (70%). Animals were randomly allocated in a ratio of 3:1 for inoculation with either E. coli (0.2 ml containing 10! or 104 dm) or sterile saline. Both groups were treated with ampicillin-sulbactam (100 mg/kg/day; Unasyn; Pfizer, Seoul, Korea) every 8 hours until euthanasia was performed 5 to 6 days after hysteroscopy. Histologie examination of the placentae and fetal brains was conducted. RESULTS: Forty animals were subjected to hysteroscopy; 31 were inoculated with E. coli and 9 with sterile saline. E. ro-inoculated animals had a higher rate of intrauterine infection and fewer live fetuses at euthanasia than those in the saline group. Histologie evidence of brain white matter damage was found more frequently in fetuses with intrauterine infection than in those without infection [8% (12/159) vs. 0% (0/103); p < 0.005]. Evidence of white matter damage included increased karyorrhexis, rarefaction and disorganization of white matter. Apoptosis was also demonstrated in areas of white matter damage by immunohistochemistry. CONCLUSION: Experimental ascending intrauterine infection can cause fetal brain white matter lesions.