Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity and mortality. In an uncontrolled study published in 2005, administration of CMV-specific hyperimmune globulin to pregnant women with primary CMV infection significantly reduced the rate of intrauterine transmission, from 40% to 16%.

OBJECTIVE. Human cytomegalovirus (CMV) is a ubiquitous human-specific DNA virus and is the main cause of congenital virus infection in developed countries leading to psychomotor impairment and deafness. Diagnostic techniques for CMV detection have greatly improved during recent years with the advent of sophisticated serological and virological methods. The aim of the present study was to assess the diagnostic and prognostic value of detection and quantification of virus in neonatal blood samples of symptomatic and asymptomatic newborns with CMV congenital infection.METHODS. Between January 1997 and December 2003, we studied 99 newborns who were born to women with primary, recurrent, and undefined CMV infection during pregnancy. CMV congenital infection was identified by isolation of the virus in urine within the second week of life. Fifty-eight of 99 infants were infected and were assessed clinically for disease in the newborn period and classified as having symptomatic or asymptomatic infection on the basis of physical, instrumental, and laboratory findings. The infants were followed up from birth according to a protocol of the tertiary NICU at the University of Bologna in a prospective study of long-term sequelae of congenital infection. Forty-seven blood samples were obtained from 47 infants in the neonatal period: 34 were examined for pp65 antigenemia test and 44 for qualitative and quantitative polymerase chain reaction (PCR and qPCR). Sequelae at 12 months were evaluated in a group of 50 infants.RESULTS. Antigenemia was positive in only 10 of 34 samples of infected newborns (29.4% sensitivity). PCR was performed in 44 samples of infected newborns and was positive in all (100% sensitivity). qPCR showed a finding of ≥100 copies per 105 of polymorphonuclear leukocytes (PMNLs) in 39 of 44 samples; in the other 5 cases, the number of copies per 105 PMNLs was <100. Between symptomatic and asymptomatic newborns, the mean values of viral blood load determined by qPCR turned out to be significantly higher in symptomatic newborns. Mean values of neonatal blood viral load were statistically higher in newborns who developed sequelae than in those who did not. Of 20 children with a neonatal viral blood load of 10000 copies did develop sequelae.CONCLUSIONS. Different viremia value ranges are correlated to a different risk of sequelae: ∼70% sequelae were found in newborns with a qPCR higher than 10000 copies per 105 PMNLs. Low neonatal viral blood load detected by pp65 antigenemia test and qPCR was highly predictive of absence of sequelae: DNAemia <1000 copies per 105 PMNLs has a negative predictive value of 95%. As an independent predictive factor of outcome, neonatal viremia is another useful element for neonatal counseling and therapeutic choices in symptomatic and asymptomatic newborns.

Congenital cytomegalovirus (CMV) infection is the leading cause of congenital viral infection and brain disease in children in developed countries, occurring in approximately 1% of all live births (from about 0.3% to 2.4%). Mother–child transmission is mainly the result of primary maternal CMV infection, which carries a risk of transmission varying from 14.2% to 52.4% (combined prevalence of 32.4%) [ 1 x 1 Kenneson, A and Cannon, MJ. Review and meta‐analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol. 2007; 17: 253–276 Crossref | PubMed | Scopus (645) | Google Scholar See all References 1 ]. Ten per cent of congenitally infected newborns are symptomatic at birth, and permanent neurological injury occurs in up to 60% of these infants [ 2 x 2 Gaytant, MA, Steegers, EA, Semmekrot, BA, Merkus, HM, and Galama, JM. Congenital cytomegalovirus infection: review of the epidemiology and outcome. Obstet Gynecol Surv. 2002; 57: 245–256 Crossref | PubMed | Scopus (208) | Google Scholar See all References , 3 x 3 Ross, DS, Dollard, SC, Victor, M, Sumartojo, E, and Cannon, MJ. The epidemiology and prevention of congenital cytomegalovirus infection and disease: activities of the Centers for Disease Control and Prevention Workgroup. J Womens Health (Larchmt). 2006; 15: 224–229 Crossref | PubMed | Scopus (59) | Google Scholar See all References ]. Even with antiviral therapy, these injuries are often irreversible. Neurological outcomes may include cerebral palsy, mental retardation, sensorineural hearing loss, seizures, and visual impairments. Microcephaly, periventricular calcifications, hydrocephalus, cerebellar atrophy and polymicrogyria have been shown to be strong predictors of an adverse neurological outcome [ 4 x 4 van Gelder‐Hasker, MR, van Wezel‐Meijler, G, de Groot, L, van Geijn, HP, and de Vries, JI. Peri‐ and intraventricular cerebral sonography in second‐ and third‐trimester high‐risk fetuses: a comparison with neonatal ultrasound and relation to neurological development. Ultrasound Obstet Gynecol. 2003; 22: 110–120 Crossref | PubMed | Scopus (21) | Google Scholar See all References 4 ].