Higher risk of hepatitis C virus perinatal transmission from drug user mothers is mediated by peripheral blood mononuclear cell infection.

Maternal injection drug use and peripheral blood mononuclear cell infection by hepatitis C virus are important risk factors for perinatal transmission of the virus. The aim of present study was to evaluate the independent association of these two factors on perinatal transmission. Forty-eight consecutive mothers who transmitted infection to their offspring and 122 consecutive mothers who did not, together with their children, were examined. Both maternal injection drug use and peripheral blood mononuclear cell infection were significantly more frequent in infected than in uninfected children (respectively P = 0.04; odds ratio 2.33, 95% confidence intervals 1.02-5.42 and P < 10(-6); odds ratio and 95% confidence intervals not calculable due to zero values). Multivariate analysis confirmed the link between maternal peripheral blood mononuclear cell infection and perinatal transmission (P < 10(-6); odds ratio and 95% confidence intervals not calculable due to zero values) but no association was found with maternal injection drug use. The high risk of perinatal transmission found in injection drug use mothers is dependent on maternal peripheral blood mononuclear cell infection by hepatitis C virus. Peripheral blood mononuclear cell infection represents one of the most important risk factors for hepatitis C virus perinatal transmission.

Hepatitis C virus infection.

The prevalence of chronic hepatitis C infection in the general paediatric population varies between 0.1 and 15% around the world, with the highest numbers noted in endemic areas of Africa. The risk of viral transmission from an infected mother to her child is approximately 5% and there are currently no effective preventative measures to lower it. All children born to infected mothers should be tested for hepatitis C. The progression to liver damage in infected children is slow. However, in the perspective of 15-20 years of infection or in the presence of other risk factors, such as concomitant chronic disease, a progression to more severe liver damage can be seen. Thus, the use of antiviral treatment may be of importance. Treatment combinations of interferon and ribavirin seem to be at least as effective in children as in adults. However, the negative effect on growth of interferon requires specific attention by paediatricians.

Virus de la hepatitis B. Presentación / Presentation

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[Hepatitis C and pregnancy]. / Hépatite C et grossesse.

PURPOSE: Today, the natural course of hepatitis C virus (HCV) infection during pregnancy and the prevalence of mother-to-child transmission are better known. CURRENT KNOWLEDGE AND KEY POINTS: Antenatal screening for HCV infection needs to be proposed to women with risk factors. Viral replication needs to be confirmed by PCR in pregnant women with antibodies against HCV. To date, the clinical course of pregnancy and the mode of delivery have not been changed by HCV infection. Rates of vertical transmission of HCV are about 6% in women with HCV alone and 15% in women co-infected with HIV. A screening for HCV markers is required 18 months after delivery for infants born to HCV mothers. Because of the relatively low rate of HCV vertical transmission, pregnancy can be allowed in infected women. However, taking into account the efficacy of new antiviral strategies, treatment of HCV infection could be proposed before pregnancy. FUTURE PROSPECTS AND PROJECTS: In case of HCV infection, a careful follow-up of both mother and newborns is required. Long-term follow-up of infected infants is needed to assess the consequences of perinatal HCV infection.

[Update on maternal-fetal infections by hepatitis C, HIV and cytomegalovirus]. / Mise au point sur les infections materno-foetales par l'hépatite C, le V.I.H. et le cytomégalovirus.

Maternal infections with hepatitis C virus, human cutomegalovirus and HIV and their management problems continue to raise concern in obstetrics. What should we recommend to decrease the incidence of hepatitis C virus congenital infection? We know that congenital human cytomegalovirus infection can lead to major neurological disease with sensorineuronal loss. The current lack of trusted prognostic elements to predict impact on the infected fetus makes any prenatal diagnosis questionable. Should we thus track the initial maternal antibody status and the newborn infection? For the last 10 years, HIV mother-to-infant transmission has decreased from 25% to less than 3%. The new problem is how to answer the more and more frequent request for pregnancy from an infected woman. The treatment must be adapted to the pregnancy in order to reduce the risks for the mother and the infant. All these questions emphasize the problems of viral infection which will require answers in the years to come.

Vertical transmission of hepatitis C virus infection: usefulness of viremia detection in HIV-seronegative hepatitis C virus-seropositive mothers.

Seventy mother-newborn pairs were studied for hepatitis C viremia to evaluate the risk of vertical transmission of hepatitis C virus from human immunodeficiency virus-negative mothers. Forty-five mothers were hepatitis C virus-RNA positive: 4 to 45 children were positive at birth and during follow-up. The level of viremia plays an important role in vertical transmission.

Natural history of perinatal hepatitis C virus infection.

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.

Neonatal hepatobiliary disorders.

Neonatal hepatobiliary disorders are now better understood due primarily to new discoveries in molecular genetics, virology, and immunology. Because they are almost always pathologic and require early intervention, the neonatologist must recognize infants with these hepatocellular and ductal cholestatic problems occurring in the first few weeks of life. This article focuses mainly on new developments regarding neonatal metabolic disorders and their potential for gene therapy; perinatal infections, especially those caused by hepatitis B virus, hepatitis C virus, and human immunodeficiency virus; and recent concepts of neonatal hepatitis and biliary atresia, including a review of predictors that influence outcome for infants undergoing Kasai portoenterostomy and liver transplantation.

Vertical transmission of hepatitis C virus in low-risk pregnant women.

To assess the prevalence of hepatitis C virus (HCV) infection in pregnant women and the rate of vertical transmission in infected mothers belonging to a low-risk group, 1,388 women were tested for HCV antibody at delivery. Twenty-five anti-HCV-positive women with no apparent source of HCV exposure were recruited. A reverse transcriptase-polymerase chain reaction (RT-PCR) and a new quantitative branched DNA-based signal amplification assay (bDNA) were used to detect HCV RNA. The rate of anti-HCV positivity in pregnant women was 2.5% (36 of 1,388). Of the 25 cohort mothers, 18 (72%) were positive for HCV RNA by RT-PCR, 13 of whom were also positive by the bDNA assay (sensitivity 72.2%). Of the 25 infants of low-risk mothers tested at birth, 22 were anti-HCV positive, two were weakly reactive, one was negative, and none was viremic. Neither active humoral immunoresponse nor HCV RNA was detected in any of the infants over a period of 12 months. These data suggest a relatively high prevalence of anti-HCV in unselected pregnant women and a poor efficiency of vertical transmission of HCV in a low-risk population, irrespective of the viral burden of the mother-to-be.

Vertical transmission of hepatitis C virus infection.

Vertical transmission of hepatitis C virus (HCV) was studied in 58 infants of 55 mothers (3 sets of twins). HCV RNA analyses by the polymerase chain reaction (PCR) and alanine aminotransferase (ALT) were performed on consecutive blood samples from birth to 18 months of age (0, 3, 9 and 18 months). Data on factors possibly influencing mother-to-infant transmission of HCV, such as concomitant human immunodeficiency virus (HIV) and hepatitis B virus infection during pregnancy, maternal HCV RNA status at delivery, mode of delivery, prematurity and breastfeeding habits were collected. In addition, 6 older siblings (age 4-10 years) of the infants were tested once for anti-HCV. Of the 55 mothers 52 (95%) had a history of intravenous drug use (IVDU). Two mothers were HIV positive. 40/54 (75%) tested mothers were HCV RNA positive. 16 (27%) infants were delivered by Caesarean section, and 50 (86%) infants were breastfed. All infants were HCV RNA negative on all occasions and anti-HCV negative at the age of 18 months. Maternally acquired anti-HCV antibodies disappeared and were not detected by 9 months in 78%. One of the 6 older siblings was anti-HCV and HCV RNA positive. We conclude that the risk of vertical HCV transmission is low in infants of HCV-positive/HIV-negative mothers, and that breastfeeding seems to be safe in this group.

A unique, predominant hepatitis C virus variant found in an infant born to a mother with multiple variants.

To demonstrate vertical transmission of hepatitis C virus (HCV) from an HCV-infected, non-human immunodeficiency virus type 1-infected mother to her infant and to assess the distribution of viral species in the mother and infant, the hypervariable region of the gene encoding the putative envelope glycoprotein E2 (E2HV) was sequenced in three mothers and one mother-infant pair. The data indicate that (i) quasi-species distributions of HCV E2HV variants were found in all four mothers, (ii) a single predominant HCV E2HV variant was found in the infant of a mother shown to have nine predominant E2HV variants, and (iii) the infant's E2HV variant was highly related to, but not identical with, the nine variants identified in the mother at the time of birth. These findings indicate that HCV is transmitted from mother to infant and raise the possibility that the transmission occurs in utero.

[Hepatitis C and pregnancy: is it necessary to screen for the risk of vertical transmission?]. / Hépatite C et grossesse: faut-il dépister le risque de transmission verticale?

The diagnosis of the risk for vertical infection with the virus of hepatitis C rests on the finding of specific antibodies in the mother. It is rare to see clinical signs of infection in the newborn. More frequently asymptomatic transmission of the viral genome occurs. As it is important to watch newborn infants at risk it is recommended that pregnant women who have a risk factor should have serum screening.