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 Ն100 copies per 10 5 of polymorphonuclear leukocytes (PMNLs) in 39 of 44 samples; in the other 5 cases, the number of copies per 10 5 PMNLs was Ͻ100. 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 Ͻ1000 copies per 10 5 PMNLs, 19 did not develop sequelae (negative predictive value: 95%), whereas 2 of 3 with a viral blood load of Ͼ10 000 copies did develop sequelae.CONCLUSIONS. Different viremia value ranges are correlated to a different risk of sequelae: ϳ70% sequelae were found in newborns with a qPCR higher than 10 000 copies per 10 5 PMNLs. Low neonatal viral blood load detected by pp65 antigenemia test and qPCR was highly predictive of absence of sequelae: DNAemia Ͻ1000 copies per 10 5 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.H UMAN CYTOMEGALOVIRUS (CMV) is a ubiquitous human-specific DNA virus that belongs to t...

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ABSTRACT. Thrombotic disease is rare in neonates. The main risk factors at this age are perinatal asphyxia, maternal diabetes, sepsis, polycythemia, dehydration, a low cardiac output, and in primis the catheterization of central lines. Another important risk factor is inherited thrombophilia. Arterial thrombosis is even more rare than venous thrombosis and less related to most of the risk factors listed above; it occurs more frequently in the iliac, femoral, and cerebral arteries but very rarely in the aorta. Most of the described cases of aortic thrombosis are associated with the catheterization of an umbilical artery and involve the descending tract and the renal arteries; very few relate to the ascending tract and the aortic arch. The possible role of virus-induced primary vascular endothelium damage in the etiopathogenesis of neonatal arterial thrombosis has been previously hypothesized. Herpesviruses, particularly human cytomegalovirus (HCMV), can infect endothelial cells and directly damage intact vascular endothelium, altering its thromboresistant surface as a result of procoagulant activity mediated by specific viral surface phospholipids, necessary for the coagulation enzyme complex assembly that leads to thrombin generation. We describe a case of congenital aortic arch thrombosis. The clinical, laboratory, and virologic pictures; the anatomopathologic findings (fully compatible with viral infection); the detection of HCMV in various tissues (including the aorta); and the absence of other causes of aortic thrombosis make it possible to attribute the case to a severe congenital HCMV infection with multiple organ involvement, after the primary infection of the mother. We describe a case of congenital aortic arch thrombosis in which, on the basis of clinical and virologic findings (and having excluded other thrombosis-favoring conditions), the most likely cause was a severe congenital HCMV infection with multiple organ involvement. The hemostatic system disorders and hemodynamic disturbances related to viral cardiac damage explain the clinical features of the case and indicate that congenital HCMV infection should be included among the causes of neonatal aortic thrombosis. CASE REPORTA female infant was delivered by cesarean section after 37 weeks of gestation because ultrasonography revealed fetal cardiomegaly, cardiac hypertrophy, and pericardial effusion, and it was difficult to image the aorta and aortic flow. Moreover, the pregnancy was complicated by intrauterine growth retardation (IUGR) and oligohydramnios. Genetic amniocentesis performed during the 18th week of gestation revealed a fetal 46XX karyotype. Maternal serologic tests for transmissible infections were performed only during the first trimester of pregnancy; the mother was immune to toxoplasmosis and rubella and negative for HCMV, hepatitis C, hepatitis B, and human immunodeficiency virus; the presence of herpes simplex viruses was not investigated. The pregnancy was uncomplicated until the 30th week, when fetal echography first revealed I...

Risk factors affecting vertical hepatitis C virus (HCV) transmission are not completely known, if we exclude maternal HIV coinfection. We hypothesized that immunogenetic factors related to maternal or neonatal HLA profiles may affect HCV vertical transmission. HLA typing (microcytotoxicity assay on blood samples) was performed in 18 infants affected by vertically transmitted HCV infection and in 17 serum-reverted infants. (Serum-reversion is defined as antibody negative by 1 year of age and persistently HCV-RNA negative.) Moreover, HLA typing was performed in 20 mothers. Logistic regression analysis showed a significant negative association between children's HLA-DR13 antigens and risk of HCV vertical transmission (p Ͻ 0.01). This association persisted in a model including the maternal HIV status: HLA DR13 and maternal HIV coinfection showed a separate, opposite effect on vertical HCV infection (p Ͻ 0.01 and p Ͻ 0.001, respectively). The relative risk estimate for the ratio of not-infected to infected children in the presence of DR13 was 8.4 (95% confidence bounds, 1.1-60.8). Breastfeeding did not affect the risk of vertical HCV transmission. Maternal HLA profile did not relate to vertical infection. The present study reveals a significant association between HLA-DR13 and the likelihood of seroreversion in infants born to HCV-infected mothers. The findings of the present study could help in better understanding the pathogenesis of vertical HCV infection and in better identifying the cases at higher risk, which would be useful for the development of prevention strategies. It is possible that DR13 modulates the immune response to viruses, enhancing their clearance and, thus, in the case of HCV, exerting a protective role against the development of vertical infection. Infants born to HCV-infected mothers are at risk of vertical infection. The transmission rate ranges from almost 3.5% to 15%, the higher risk being associated with maternal HIV coinfection (1). No association has been found between breastfeeding and HCV transmission; also type of delivery has no effect on the risk of infection although definitive conclusions can be provided only by larger data sets (2). Other factors have been studied, such as maternal viral load, but definitive results are not available at the moment. The role of the immune response related to the HLA profile has been extensively studied in HCV-infected adults, especially concerning the severity of liver disease. In this respect it has been shown that specific HLA class II antigens (DR4, DR11, DR12, DR13, DR16) are able to present some specific HCV epitopes stimulating an acute T-cell response with consequent viral elimination (3). Also some HLA class I antigens have been shown to be able to enhance the immune response to HCV (4). No studies are available on the possible correlation between HLA genotype and risk of vertical HCV infection.The present study was conducted to investigate the possible role of maternal and children's HLA genotype on the risk of vertical HCV infection. METH...