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HCV (Hepatitis C) infections in children and pregnancy are less understood than in adults.

Epidemiology

Worldwide the prevalence of Hepatitis C virus (HCV) infection in pregnant women and children has been estimated to 1-8% and 0.05-5% respectively. The vertical transmission rate has been estimated to be 3-5% and there is a high rate of spontaneous clearance (25-50%) in the children. Higher rates have been reported for both vertical transmission (18%, 6-36% and 41%). and prevalence in children (15%).

It has been estimated that 240,000 children in the United States have antibodies to the hepatitis C virus and that 68,000 to 100,000 are chronically infected. In Australia it has been estimated that 125-250 children are infected vertically with HCV each year. Worldwide it has been estimated that 10-60,000 children are infected each year with Hepatitis C.

Transmission

In developed countries transmission around the time of birth is now the leading cause of HCV infection in children. All genotypes appear to have the same risk of transmission. In the absence of virus in the mother's blood transmission seems to be rare.

Factors associated with an increased rate of infection include membrane rupture of longer than 6 hours before delivery and procedures exposing the infant to maternal blood. Caesarean sections are not recommended. Transmission is 2- to 4-fold higher in women coinfected with HIV.

Subsequent pregnancies

Infection around the time of birth in one child does not increase the risk in a subsequent pregnancy.

Clinical course in pregnancy

Acute hepatitis C is a rare event in pregnancy.

In chronic cases a significant reduction in mean alanine aminotransferase levels may occur albeit with a rebound during the postpartum period. The viral RNA levels may rise toward the end of pregnancy.

Platlet counts may be lower than normal in ~10% of cases.

There is an increased risk of cholestasis during pregnancy.

There is no increased risk of miscarriage in chronic carriers but there is an increased risk of preterm birth, low birth weight and congenital anomalies.

Recommendations for management in pregnancy

Amniocentesis

The Society of Obstetricians and Gynecologists of Canada recommendations state that amniocentesis does not appear to significantly increase the risk of vertical transmission but that women in whom this proceedure is being carried out upon should be warned of this possibility. Other non invasive methods should be used in preference where possible. If amniocentesis is required every effort should be made to avoid penetration of the placenta.

Drugs

It is recommended that pregnant women with Hepatitis C should avoid alcohol and paracetamol.

Vaccination

Vaccination for Hepatitis A and/or B should be carried out in accordance with the usual local guidelines.

Breast feeding

Breast feeding is considered safe if the nipples are not damaged.

Antenatal screening

This has been considered in the UK but expert opinion is currently against it.

Caesarian section

This is not routinely recommended but should be carried out as indicated by the local guidelines.

Clinical course in children

HCV infection is frequently found in children who have previously been presumed to have non-A, non-B hepatitis and cryptogenic liver disease. The presentation in childhood may be asymptomatic or with elevated liver function tests. While infection is commonly asymptomatic both cirrhosis with liver failure and hepatocellular carcinoma may occur in childhood.

Children tend to have a lower viral load, lower alanine transferase values and milder histological derangement compared to adults with chronic hepatitis C.

The prognosis for those infected by blood transfusion or perinatally appears to be worse than for those without known risk factors.

Diagnosis in neonates and infants

Guidelines for the investigation of babies born to hepatitis C positive mothers have been published.

In children born to hepatitis C virus antibody positive but hepatitis C virus RNA negative mothers, the alanine aminotransferase and hepatitis C virus antibodies should be investigated at 18-24 months of life. If both the alanine aminotransferase value is normal and hepatitis C virus antibody is not found, follow up should be interrupted.

In children born to hepatitis C virus RNA positive mothers, alanine aminotransferase and hepatitis C virus RNA should be investigated at 3 months of age. Of these

(1) hepatitis C virus RNA positive children should be considered infected if viremia is confirmed by a second assay performed by the 12th month of age

(2) hepatitis C virus RNA negative children with abnormal alanine aminotransferase should be tested again for viremia at 6-12 months and for antibodies to the hepatitis C virus at 18 months

(3) hepatitis C virus RNA negative children with normal alanine aminotransferase should be tested for antibodies to the hepatitis C virus and have their alanine aminotransferase reestimated at 18-24 months. They should be considered non infected if both the alanine aminotransferase is normal and the antibody levels to the hepatitis C virus are undetectable.

The presence of anti hepatitis C virus antibody beyond the 18th month of age in a never viremic child with normal alanine aminotransferase is likely consistent with past hepatitis C virus infection.

Treatment

Pregnancy

Currently treatment for hepatitis C during pregnancy is not recommended as the interferon and ribavirin combination is contraindicated during pregnancy.

Although interferon alone appears to be relatively safe in pregnancy before using it a clear and compelling case should be made for its use. Given that pregnancy is of limited duration and that is does not seem to affect the natural history of Hepatitis C infection it seems unlikely that interferon should be used during pregnancy and that treatment should be deferred until after delivery.

Ribavirin is absolutely contraindicated during pregnancy as it is highly teratogenic.

Children

Treatment of children has been with interferon and ribavirin. In general children tolerate the treatment well. The response to treatment is similar to that in adults and shows similar dependence on the genotype. Recurrence after transplant is universal and the outcomes after transplant is usually poor.

Treatment with interferon alone produces a response rate of ~40%.

In children treatment should be initiated within 12 weeks of the detection of the viral RNA if viral clearance has not not occurred within this time. Given the difficulties with establishing a diagnosis of hepatitis C infection in infancy, this recommendation does not apply to infants.

Both pegylated interferon and ribavirin are unsuitable for use in pregnancy and infancy: newer methods of treatment are urgently required.

References

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• Hepatitis C
• Healthcare-associated infections