Studies clarify risk factors of vertical HCV transmission

January 2006

Breast-feeding does not increase the risk of mother-to-child transmission (MTCT) of the hepatitis C virus (HCV), according to two recently published, complimentary studies — one conducted in Europe and the other conducted by the CDC — of vertical transmission.

Although breast-feeding is a known risk for HIV transmission, both multicenter studies found that it was not associated with transmission of HCV, and neither was cesarean-section delivery.

Risk factors significantly associated with transmission were the time in labor, found in both studies, and the use of internal fetal monitoring devices, which the CDC study identified. Increased viral loads, earlier rupture of membranes and HIV coinfection were factors found in both studies that were also associated with increased risk of transmission.

The overall rate of vertical HCV transmission was 6.2% in the European study and 3.7% in the CDC study. Furthermore, the European study found that infant girls are twice as likely to have the virus than infant boys.

Taken together, the findings from both studies expand upon preliminary data from smaller studies of maternal-fetal transmission of HCV.

“Our results provide information that can be used for counseling regarding the risk of transmission through breast-feeding, the timing of follow-up to distinguish infected from uninfected infants and the course of infection during the first five years of life,” the CDC researchers concluded in their study. “The study also provides insight into risk factors that might facilitate and interventions that might prevent perinatal HCV transmission.”

Perinatal transmission

Eric E. Mast, MD, MPH, of the division of viral hepatitis at the CDC, and colleagues followed 242 mothers with HCV and their 244 infants in Houston from 1993 through 1996 and in Honolulu from 1994 through 1998. They assessed risk factors for perinatal HCV transmission and the natural history of infection among infants who acquired the virus.

Of these women, 61.6% reported past incarceration, 52.3% reported a history of injection drug use and 19.8% reported a blood transfusion before donor screening.

The researchers followed the infants from birth until 12 months of age. They collected maternal serum at enrollment and delivery and collected infant serum from the umbilical cord and from a peripheral venous site at birth and at eight well-child visits, according to the study protocol. At these visits, Mast and colleagues also collected breast milk samples and information on illnesses and physical examination results.

They tested for HCV antibodies, detection of HCV RNA and genotyping. They followed children with HCV each year until they reached 5 years of age.

Overall, 3.7% of the infants acquired HCV. None of the infants born to mothers without detectable HCV RNA at delivery developed the infection compared with 4.6% of infants born to mothers with HCV-RNA. The rate of transmission from mothers coinfected with HIV was 25% compared with 3.8% of those without HIV infection. In multivariate analysis restricted to HCV RNA-positive mothers, membrane rupture 6 h and internal fetal monitoring were associated with transmission of HCV to infants.

“If duration of membrane rupture and internal fetal monitoring are confirmed to be associated with transmission, interventions may be possible to decrease the risk of transmission,” Mast and colleagues wrote. “Our findings support existing recommendations to avoid internal fetal monitoring and prolonged labor after rupture of membranes in HCV-infected women.”

Gender difference

The larger of the two studies, conducted by the European Paediatric Hepatitis C Virus Network, involved 1,479 mother-and-child pairs whom researchers enrolled at 33 centers in Italy, Spain, Germany, Ireland, the United Kingdom, Norway and Sweden.

Researchers recorded maternal, delivery and infant information on specific registration and follow-up forms. Data collection included the mothers’ likely mode of HCV acquisition, maternal HIV coinfection, receipt of antiretrovirals during pregnancy, viremia, mode of delivery, birth weigh (in grams), gestational age and breast or formula feeding, according to the study.

The researchers examined the infants and collected blood for polymerase chain reaction for HCV RNA and anti-HCV antibody tests at birth; 6 weeks old; 3, 6, 9, 12 and 24 months old; and every six months if they had HCV or every year if they did not.

This multicenter, prospective study found a 6.2% rate in vertical transmission. The risk of transmission increased for those who had HIV (8.7%); however, elective caesarean-section delivery, infant prematurity, mode of feeding and maternal history of injection drug use were not associated with HCV transmission.

“Our results strongly suggest that women should not be offered an elective caesarean section or be discouraged from breast-feeding on the basis of hepatitis C infection alone,” said Pier-Angelo Tovo, MD, lead researcher of the study, in a release.

The researchers determined that there is a gender difference in HCV: girls were twice as likely to acquire HCV as boys (8.2% vs. 4.2%, respectively). The researchers hypothesized that this result may reflect hormonal or genetic differences between men and women in susceptibility or response to infection.

In an accompanying editorial, R. Palmer Beasley, MD, of The University of Texas Health Science Center at Houston, emphasized the European study’s novel finding of a gender difference in transmission rates and suggested that higher HCV rates in female newborns may be due to excess mortality in infected boys in utero.

“Overall, the observation of higher hepatitis C virus infection rates in female infants is in accord with recent observations of similar excesses in HIV infection of female infants,” Beasley said. The studies were both published in The Journal of Infectious Diseases.

For more information:

• Mast EE, Huang L-Y, Seto DSY, et al. Risk factors for perinatal transmission of hepatitis C virus (HCV) and the natural history of HCV infection acquired in infancy. J Infect Dis. 2005;192:1880-1889.
• European Paediatric Hepatitis C Virus Network. A significant sex — but no elective cesarean section — effect on mother-to-child transmission of hepatitis C virus infection. J Infect Dis. 2005;192:1872-1879.
• Beasley RP. Nature usually favors females. J Infect Dis. 2005;192:1865-1866.
• Galli L, Puliti D, Chiappini E, et al. Italian Register for HIV infection in children. Lower mother-to-child HIV-1 transmission in boys is independent of type of delivery and antiretroviral prophylaxis. J Acquir Immune Defic Syndr. 2005;40:479-485.