Intrauterine growth restriction caused by underlying congenital cytomegalovirus infection

Background. Human cytomegalovirus (HCMV) is the major viral etiology of congenital infection and birth defects. Fetal transmission is high (30%-40%) in primary maternal infection, and symptomatic babies have permanent neurological, hearing, and vision defects. Recurrent infection is infrequently transmitted (2%) and largely asymptomatic. Congenital infection is also associated with intrauterine growth restriction (IUGR). Methods. To investigate possible underlyingHCMVinfection in cases of idiopathic IUGR,we studiedmaternal and cord sera and placentas from 19 pregnancies. Anti-HCMVantibodies, hypoxia-related factors, and cmvIL-10 weremeasuredinsera. Placental biopsyspecimenswere examined for viralDNA, expressionof infectedcell proteins, and pathology. Results. Among 7 IUGR cases, we identified 2 primary and 3 recurrent HCMV infections. Virus replicated in glandular epitheliumand lymphatic endotheliumin the decidua, cytotrophoblasts, and smoothmuscle cells in blood vessels of floating villi and the chorion. Large fibrinoids with avascular villi, edema, and inflammation were significantly increased. Detectionofviralproteinsintheamnioticepitheliumindicatedtransmissionin2cases ofIUGRwithprimaryinfectionand 3 asymptomatic recurrent infections. Conclusions. CongenitalHCMVinfectionimpairs placentaldevelopmentand functions and shouldbe consideredas an underlying cause of IUGR, regardless of virus transmission to the fetus.