To estimate the risk of mother-to-child transmission of hepatitis C virus (HCV) and identify correlates of transmission, 245 perinatally exposed singleton children followed prospectively beyond 18 months of age were studied. Overall, 28 (11.4%) of the 245 children acquired HCV infection. Transmission occurred in 3 of 80 children (3.7%) whose mothers had HCV infection alone and in 25 of 165 (15.1%; P õ .01) whose mothers had concurrent infection with human immunodeficiency virus type 1 (HIV-1). The percentage of HIV-1-infected children was similar (22 of 165, 13.3%), but each virus was transmitted independently; only six infants (3.6%) were coinfected with HCV and HIV-1. The risk of HCV transmission was not associated with maternal HIV-1-related symptoms, intravenous drug use, prematurity, low birth weight, or breast-feeding, whereas it was lower with cesarean section than with vaginal delivery (5.6% vs. 13.9%, P Å .06). This suggests that transmission occurs mainly around the time of delivery.birth weight, mode of delivery, and type of feeding were also Mother-to-child transmission of hepatitis C virus (HCV) is investigated. widely documented. However, in different investigations the estimated risk of infection ranged from zero to 100% [1 -15]. This variability derives from differences in methods used toPatients and Methods define the child's infection status, duration of follow-up, and size and features of the populations studied.Patients. A cohort of 245 children born to HCV-infected Transmission of HCV may occur in utero via the transplacenwomen were enrolled at 12 participating centers. In three cental route at any time during pregnancy, at the time of delivery, ters all parturients were screened for HCV-seropositivity; in and postnatally through breast-feeding. Several factors might the remaining centers, HCV testing was mostly performed only favor or hamper infection of the offspring. Identification of for women who had a history of IVDU or were known to be these factors would allow the adoption of rational preventive HIV-1-infected. Only singleton at-risk infants identified within strategies and the offer of specific counseling, but little is the first 2 weeks of life and followed up for at least 18 months known about the timing and correlates of transmission. High were included in this study. levels of viremia [5 -7], certain HCV genotypes [8], and materData collection. Specific information was collected by nal coinfection with HIV-1 [1, 2, 4, 7, 9, 15] have been associquestionnaire on maternal risk factors for HCV infection ated with increased HCV transmission rates, although the re-(IVDU, transfusions, sexual contact with an infected partner, sults are controversial [10 -13]; breast milk does not seem to other, unknown), mother's HIV-1 infection status at delivery have a significant role [13 -15].(presence or absence of specific antibody), length of pregnancy The aim of this study was to quantitate the risk of HCV (weeks), mode of delivery (vaginal, elective/emergency cesarinfection in children born to...

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Perinatal infection with hepatitis C virus (HCV) is characterized by a wide range of alanine aminotransferase (ALT) levels. The mechanisms responsible for this variability are unknown. We examined whether the evolution of the HCV quasispecies was associated with different ALT profiles in perinatally infected children. Sequences within HCV envelope 1 and 2 genes, inclusive of the hypervariable region 1, the viral load, and the nascent humoral immunity were analyzed in serial serum samples from 12 perinatally infected children prospectively followed for a median of 53 months. These patients were selected to represent two different ALT patterns during the first year of life: 6 had high levels (maximum values ranging from 4.2 to 30 times the normal upper limit), and 6 had normal or slightly elevated levels (<2 times the normal upper limit). Two patterns of viral evolution were identified according to the ALT profiles. Biochemical evidence of hepatic injury was invariably associated with a mono-or oligoclonal viral population, whereas mild or no liver damage correlated with the early emergence of a heterogeneous viral quasispecies. Consistent with selective immune pressure, amino acid changes occurred almost exclusively within the hypervariable region 1 and were temporally associated with antibody seroconversion; at this time, the difference in genetic diversity between the two groups was highly significant (P ‫؍‬ 0.002). The two patterns of viral evolution persisted over time and did not correlate with viral load or genotype. Our study demonstrates that, in perinatally infected children, the evolution of HCV quasispecies correlates with hepatic injury.perinatal hepatitis C virus infection ͉ genetic variability ͉ alanine aminotransferase levels M aternal-infant transmission is the dominant route for acquisition of hepatitis C virus (HCV) infection in children in developed countries, with an estimated transmission rate of Ϸ5% (1-3). Age and mode of infection are assumed to influence the progression of HCV disease in adults, but limited data are available on the natural history of perinatally acquired HCV infection (4, 5). Recent studies suggest that 80% of these children develop chronic infection (6-8), a rate similar to that documented in adults (9) but higher than that reported in children with posttransfusion HCV infection (10). Persistent HCV infection in infants and children is associated with minimal or mild liver damage and very rarely with advanced liver disease (5,(11)(12)(13)(14). However, perinatal HCV infection is associated with a wide range of aminotransferase levels during the first year of life (5, 7). Whereas some infants reach serum concentrations of alanine aminotransferase (ALT) compatible with acute hepatitis, others show normal or slightly elevated levels (5, 7). The mechanisms responsible for the different ALT profiles seen in perinatal HCV infection are unknown but are likely the result of a complex interplay between viral factors and host immunity. One of the most effective strategies enacted ...

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In order to outline the natural course of perinatal hepatitis C virus (HCV) infection, we prospectively followed seven HCV-positive children for a mean period of 65.1 months (range, 26-90 months). Physical examination findings, growth, and bilirubin and immunoglobulin levels were constantly normal. All children were still viremic at last analysis. HCV-RNA was almost constantly detected throughout follow-up, with the exception of the first days of life. All children had initial increases (of variable duration) in alanine aminotransferase values: four children subsequently had normal or borderline values for years, with exacerbation of inflammatory activity in two cases. IgM antibodies to HCV were found in three of the seven patients. Autoantibodies developed in two children. Liver biopsy, performed on five patients, documented different degrees of chronic persistent hepatitis. Thus, recovery from perinatal HCV infection seems unlikely, and chronic hepatitis develops in most infected children, including those with prolonged intervals of remission of inflammatory activity.

We investigated the polymorphisms of the promoter region of the MBL2 gene, which codifies for the Mannose-binding protein (MBP). The study population included 90 children with vertically acquired HIV-infection, further divided on the basis of the disease rate, 27 HIV exposed-uninfected children, and 74 healthy control subjects matched for ethnic origin to evaluate the MBP involvement in the risk of HIV-1 infection and to assess the role of the MBP promoter in AIDS progression. A region of 380 bp in the promoter of the MBL2 gene was analysed by PCR and direct sequencing of both DNA strands. We found that the polymorphism at position −550 influences the risk of HIV-infection and AIDS progression. Also a 6 bp deletion at position −328 was correlated with HIV-1 infection. This study indicates that the promoter of the MBL2 gene influences vertical transmission of HIV and the course of perinatal infection. Genes and Immunity (2000) 1, 346-348.

To determine the rate of vertical transmission of hepatitis C virus (HCV), we prospectively studied 45 babies born to anti-HCV-positive women with or without concomitant infection with the human immunodeficiency virus (HIV). We performed a second-generation recombinant immunoblotting assay, alanine transaminase (ALT) evaluation, and HCV-RNA testing on sera from 27 infants of HCV+, HIV- mothers and 18 babies of HCV+, HIV+ women, at birth and thereafter. After birth, HCV antibodies progressively disappeared within 12 months in all children but one, whose mother was HCV+, HIV+; this child was the only one who showed detectable levels of HCV-RNA and abnormal ALT values throughout the follow-up (range, 12 to 27 months). Viremia was persistently negative, and ALT levels were continuously normal in the remaining infants, showing that "seronegative" infection with HCV was absent in both groups. Clearance of passively acquired anti-HCV antibodies was found to be slower among babies born to HIV+ mothers (22.3% vs. 3.8% at 12 months, P = .03) and children whose mothers showed three or four anti-HCV reactivities by immunoblotting maintained anti-HCV for longer periods compared with babies born to mothers with one or two anti-HCV reactivities (P = .0001). Seventeen of 27 babies born to HCV+, HIV- mothers were breast-fed, and none of them was infected, confirming the apparent safety for HCV of breast milk. In summary, according to our study, vertical transmission of HCV is an infrequent event, and the presence of HIV in the mother is not an important co-factor for transmission of HCV infection.

We evaluated the growth pattern, bone age, insulin-like growth factor I (IGF I) secretion and thyroid function in 24 perinatally infected children: 9 asymptomatic or paucisymptomatic (group 1) and 15 with a more advanced disease state and treated with zidovudine (group 2). Statural and ponderal growth were compared with those of 37 at-risk children who seroreverted. During the two-year follow-up, 22% of children in group 1 had impaired growth, 33% bone age delay, 45% reduced IGF I levels but none had thyroid dysfunction. In group 2, 53% had growth failure, 53% bone age delay, 86% reduced IGF I levels and 40% thyroid dysfunction. Among seroreverters, none showed growth impairment; statistically significant differences were found for height, weight and height velocity between perinatally infected children and seroreverters. Since auxological and hormonal evaluations run parallel to the clinical course of infection, these indices may be useful in monitoring disease progression.