There are several means of transmitting the hepatitis C virus (HCV) from person-to-person, and vertical transmission is estimated to occur in about 5% of all cases.¹ This involves transmitting the virus from mother to child during pregnancy or delivery. In women co-infected with HCV and HIV—the virus that causes AIDS—the rate of vertical transmission is believed to be higher.

Now, doctors have zeroed in on some of the circumstances surrounding vertical HCV transmission in a new study from Europe.² Their findings are published in the March issue of the journal Archives of Disease in Childhood: Fetal and Neonatal Edition.

"The exact time during pregnancy or delivery when HCV transmission occurs is unclear," wrote the researchers led by Mary Louise Newell, PhD, a professor of Pediatric Epidemiology at the Institute of Child Health at University College London, and her colleagues. "Development of successful strategies to prevent mother to child transmission of HCV depends on understanding the timing of transmission and associated factors."

How Does Vertical Transmission Happen?
Hepatitis C can be transmitted from mother to fetus during pregnancy through the exchange of blood in the placenta, but also during delivery due to close contact between the blood of the mother and baby, as well as other secretions, explained Lucy Pembrey, BSc, MSc, a research fellow at the Institute of Child Health, and one of the study's investigators. "There is no reliable evidence to quantify any risk of transmission through breastfeeding, and this is generally assumed to be very low, if it occurs at all," Pembrey told Priority Healthcare.

The research involved 54 newborns who were tested within three days of birth. Their mothers were tested for the study, as well. Seventeen children tested positive for HCV infection and 37 were negative. While more children born to women co-infected with hepatitis C and HIV tested positive by age three days, this finding was not considered significant.

Acquiring Infection During Pregnancy
Nearly a third of the children "were positive in the first three days of life and could be assumed to have acquired infection in utero," wrote Newell and her associates.

In addition, since 40 percent of infants born to women who had tested positive for HCV (using polymerase chain reaction (PCR) tests) were themselves positive for the infection, it suggested that women who are viremic during pregnancy may be more likely to transmit the virus before delivery, Newell and her team wrote.

Acquiring Infection During Delivery
Of the 37 children who tested negative for hepatitis C within three days following their births, 27 tested positive three months later, Newell's group learned, suggesting that they had acquired the viral infection either late in pregnancy or during delivery.

Since some children born to infected mothers don't always immediately test positive, it's important to monitor them, the researchers pointed out. "All children born to HCV-infected women should be followed up until at least 12 months of age," Pembrey said. That's because "infected children can test negative for HCV RNA [a sensitive test that looks for genetic material associated with the virus] by PCR early in life or at older ages," she said. In some cases, the virus can be hidden, thus avoiding detection, so a negative PCR test result should be confirmed by an antibody test, as well, added Pembrey.

Nine children who tested positive three months after birth could not be linked with the timing of infection. However, it appears they did not contract the infection through breastfeeding, Newell and her team wrote.

The method of delivery (29 percent of the children were born using elective Caesarean sections) and the child's sex had no relationship with the timing of viral transmission. However, those who were infected during pregnancy were more likely to have a lower birth weight and were infected with the genotype 1 strain of the virus—the most common strain that is the hardest to treat.³ "The reason for this is unclear and further investigation is necessary," Newell's team wrote.

Managing Infected Mothers and Children
The researchers also noted that maternal therapy using interferon alfa and the anti-viral drug, ribavirin, to lower viral load, and in turn, lower the risk of vertical transmission, is not possible. That's because the medications are not indicated for pregnant women. Still, physicians can best manage expectant mothers infected with hepatitis C by "an elective Caesarean section delivery and avoidance of invasive obstetric procedures" that "could reduce contact between mother and infant," Pembrey explained. "However, there is no evidence to suggest that elective Caesarean section reduces the risk of HCV transmission, and there are thus currently no interventions to offer HCV-infected pregnant women," she said.

Children who test positive are rarely treated during their first 5 years since they typically have no symptoms during that time, Pembrey explained, but are monitored by pediatricians at least once per year. But due to the promising results of combination therapy in adults, "treatment of children may increase in the future," she added.

Study: Treatment Should be Started Early
After analyzing all the data, the investigators concluded that much of vertical transmission of HCV occurs during pregnancy. "These results suggest that at least one third and up to a half of infected children acquired infection in utero," they wrote. "Although postpartum transmission cannot be excluded, these data suggest that it is rare."

"Our results suggest that, if effective treatment were to become available, it would need to be initiated early in pregnancy, as at least one third of transmission occurs in [pregnancy]," the researchers added.

Pediatric Hepatitis: Unanswered Questions
According to experts, most infants infected with hepatitis C at birth have no symptoms and can do well during childhood. However, there haven't been enough medical studies published examining the prognosis of children with HCV as they grow older. Currently, there are no licensed treatments or guidelines to treat infants or children infected with HCV. However, children with elevated levels of a liver enzyme that indicates liver damage known as alanine aminotransferase (ALT) should be referred to a specialist familiar with managing pediatric hepatitis.⁴

According to the Centers for Disease Control and Prevention (CDC), children should wait to be tested for HCV until they are at least 18 months of age, as antibodies from the mother remain in the infant's circulation until that time. Maternal antibodies may or may not be indicative of HCV infection. If testing is desired before 18 months of age, tests to detect genetic material associated with hepatitis C known as HCV RNA should be performed, the CDC recommends.⁴ HCV RNA testing should then be repeated at a follow-up visit with the child's physician, the agency states.

What's Next?
Pembrey says her group plans to publish related studies in the future. One, expected this summer, examines the natural history of vertically acquired HCV infection, and another is evaluating the potential risk factors associated with this type of transmission.

"It is important to identify risk factors for vertical transmission of HCV to enable development of interventions to reduce the risk," Pembrey told Priority Healthcare. "Further work is [also] needed on the natural history of vertically acquired HCV infection to identify factors associated with disease progression, especially in the longer term, and to assess the possible association between HCV infection and non-liver serious manifestations, such as autoimmune disease."

1. Zanetti AR, Tanzi E, Newell ML. Mother-to-infant transmission of hepatitis C virus. J Hepatol 1999;Suppl 1:96-100.
2. Mok J, Pembrey L, Tovo PA, Newell ML; The European Paediatric Hepatitis C Virus Network. When does mother to child transmission of hepatitis C virus occur? Arch Dis Child Fetal Neonatal Ed 2005 Mar;90(2):F156-60.
3. NIH Consensus Statement on Management of Hepatitis C. NIH Consens State Sci Statements 2002 Jun 10-12;19(3):1-46.
4. National Center for Infectious Diseases. Centers for Disease Control and Prevention (CDC). Frequently Asked Questions About Hepatitis C. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/c/faq.htm#2c. Accessed March 30, 2005.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.