Neutralizing antibodies to hepatitis C virus in perinatally infected children followed up prospectively.

Little is known about the presence and role of neutralizing antibodies (NtAbs) in perinatal hepatitis C virus (HCV) infection. Using HCV pseudoparticles, NtAbs were studied longitudinally in 12 HCV-infected children with or without evidence of acute hepatitis during the first year of life. Broadly reactive NtAbs of maternal origin did not prevent vertical HCV transmission or progression to chronicity. NtAbs against homologous genotype or subtype appeared during the chronic phase and were more abundant and sustained in children with acute hepatitis. Cross-reactive NtAbs were present in both groups of children, but their appearance did not correlate with better control of viremia or HCV clearance.

Evolution of hepatitis C viral quasispecies and hepatic injury in perinatally infected children followed prospectively.

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. The sequences reported in this paper have been deposited in the GenBank database (accession nos. DQ 504441-DQ 507112).

Spatial working memory deficits in children at ages 3-4 who were low birth weight, preterm infants.

The aim of this study was to investigate attention and perceptual and spatial working memory abilities in preterm, low birth weight preschool children without evident brain disorders as determined by normal cerebral ultrasound findings and normal motor development. The authors evaluated 19 preterm and 19 typically developing children who were matched for IQ and chronological age. Results indicated that children born prematurely without major neurological deficits and with a normal cognitive level may have specific difficulty in sustained attention, visuospatial processing, and spatial working memory when evaluated at ages 3-4. This finding is relevant for understanding the qualitative aspects of cognitive development in preterm children and the neurobiological substrate underlying this development.