NATAP
Reports

Highlights from
Digestive Disease Week

May 20-23, 2001
Atlanta, Georgia

HCV & Pregnancy, risk factors for transmission: breastfeeding, c-section, use of forceps in delivery
    
C-section may reduce HCV transmission; use of forceps in vaginal delivery may increase risk of transmission

The findings in the studies outlined below suggest that caesarean section delivery was associated with reduced risk of transmitting HCV from mother to child. The study also found that vaginal delivery using forceps was associated with a greater risk of HCV transmission from mother to child. Similar to HIV exposing the infant to higher amounts of maternal secretions or fluids may increase the risk of transmission to the child.

Studies suggest that high HCV viral loads in the mother can increase risk of HCV transmission. Although the mechanism whereby HIV infection facilitates vertical transmission of hepatitis C is uncertain, it has been suggested that the risk is conferred primarily by the high hepatitis C viral loads in HIV-coinfected women (N Engl J Med 1994;330:744-750[Abstract/Full Text], J Infect Dis 1994;169:638-641). It can be gleaned from the handful of studies in which quantitative PCR was performed that the average level of viremia is greater in mothers who transmit the infection than in those who do not. Indeed, the risk of vertical transmission is almost entirely confined to those mothers with viral titers > 10(6) copies/mL (Int J Epidemiol 1998;27:108-117[Abstract], Lancet 1995;345:289-291). Conversely, transmission of hepatitis C to infants of seropositive mothers with no detectable viral RNA during pregnancy seems to be exceedingly rare (BMJ 1997;315:333-337[Abstract/Full Text], 1998;317:437-441). But 2/30 mothers with <10(6) copies/ml transmitted HCV, and 8 transmissions have been detected in studies reviewed from mothers without detectable virus.

A second study finds that C-section reduced HCV transmission from mother to child by 60% in HCV/HIV coinfected mothers, but C-section in HCV-alone infected women did not reduce transmission of HCV. Women with HIV who breastfed were 4 times more likely to transmit HCV, but women with HCV alone were not more likely to transmit HCV due to breastfeeding. Study results appear mixed as some studies show c-section may reduce transmission of HCV and breastfeeding may increase HCV transmission. Although breast-feeding clearly confers many benefits to mother and infant alike, based on available data it seems prudent to advise women with detectable hepatitis C RNA of the potential risk of transmitting the virus through breast-feeding Coinfected women were twice as likely in this study to transmit HCV than HCV monoinfected.

C-Section May Reduce HCV Transmission
     
(Gastroenterology April 18 2001)

The mechanisms whereby hepatitis C is transmitted from mother to child are poorly delineated. Gibb et al. evaluated data from 3 hospitals in Ireland and from a British pediatric surveillance study to provide estimates of the rate of mother-to-infant transmission of hepatitis C, and to identify risk factors for transmission of the virus. A total of 441 mother-infant pairs in which the mother was known to be infected with hepatitis C during pregnancy (92%), or the child was found to be positive for the hepatitis C virus within 90 days of birth (8%), were analyzed longitudinally. The overall rate of vertical transmission of hepatitis C in this study was 6.7%, increasing to 18.6% in mothers coinfected with HIV. The slow clearance of maternal antibodies in infants born to hepatitis C-infected mothers is highlighted by the finding that half of uninfected children remained seropositive at 8 months of age and 5% continued to be seropositive at 13 months.

Conversely, hepatitis C RNA was identified by polymerase chain reaction (PCR) in only 22% of infected neonates younger than 1 month, but was detected in 97% of infected infants after that time period. Newborns delivered by cesarean section had a lower, albeit nonsignificant, incidence of acquiring the hepatitis C virus than those undergoing vaginal delivery. However, a significantly diminished rate of vertical transmission was noted when infants delivered by elective cesarean section were compared with the combined group of children delivered vaginally or by emergency cesarean section. In fact, none of the 31 children delivered by elective cesarean section became chronically infected. Rates of hepatitis C in breast-fed infants were no different than in infants who were exclusively bottle-fed.

Effects of mode of delivery and infant feeding on the risk of mother-to-child transmission of hepatitis C virus. European Paediatric Hepatitis C Virus Network.
       European Paediatric Hepatitis C Virus Network.

OBJECTIVE: To investigate the effects of mode of delivery and infant feeding on the risk of mother-to-child transmission of hepatitis C virus. DESIGN: Pooled retrospective analysis of prospectively collected data. SAMPLE: Data on hepatitis C virus seropositive mothers and their children identified around delivery were sent from 24 centres of the European Paediatric Hepatitis C Virus Network.

MAIN OUTCOME MEASURES: Hepatitis C virus infection status of children born to hepatitis C virus infected women.

RESULTS: A total of 1,474 hepatitis C virus infected women were identified, of whom 503 (35%) were co-infected with HIV. Co-infected women were more than twice as likely to transmit hepatitis C virus to their children than women with hepatitis C virus infection alone. Overall 9.2% (136/1,474) of children were hepatitis C virus infected. Among the women with hepatitis C virus infection-only, multivariate analyses did not show a significant effect of mode of delivery and breastfeeding: caesarean section vs vaginal delivery OR = 1.17, P = 0.66; breastfed versus non-breastfed OR = 1.07, P = 0.83. However, HIV co-infected women delivered by caesarean section were 60% less likely to have an infected child than those delivered vaginally (OR = 0.36, P = 0.01) and those who breastfed were about four times more likely to infect their children than those who did not (OR = 6.41, P = 0.03). HIV infected children were three to four times more likely also to be hepatitis C virus infected than children without HIV infection (crude OR = 3.76, 95% CI 1.89-7.41).

CONCLUSIONS: These results do not support a recommendation of elective caesarean section or avoidance of breastfeeding for women with hepatitis C virus infection only, but the case for HIV infected women undergoing caesarean section delivery and avoiding breastfeeding is strengthened if they are also hepatitis C virus infected.

Mother To Child Transmission of HCV: a case control study of risk factors; use of forceps during vaginal delivery found to increase risk of transmission, as in HIV

The aim of this study presented at DDW May 2001 (author: Sophie Poiraud, Hosp Tenon, Paris, France) was to evaluate risk factors for vertical transmission (mother-to-child) of HCV, using a case-control method of study which has flaws. Mother to child transmission of HCV has been found to be about 5-7% but 3 times higher in HIV –infected women. The authors of this study say transmission factors remain unclear as transmission may occur in utero, during delivery, or postnatally. The authors propose that invasive procedures such as amnio centesis or use of forceps could increase risk of transmission. So, this study evaluates amniocentesis, mode of delivery, and breast feeding as risk factors for HCV transmission from mother-to-child.

There were 52 cases of HCV-RNA positive children after 1 month of age of HCV antibody positive after 18 months of age, without a history of blood transfusion or surgery. These children were compared to 113 controls: children who were HCV-RNA negative and/or antibody negative after 1 month. 42-47% of the women had a history of IVDU.

The study authors found vaginal delivery with the use of forceps is the main risk factor for HCV transmission in this study (odds ratio 3.15; 3 times more likely to occur; p=0.038). The authors reported these results are similar to data published in HIV vertical transmission after delivery with obstetric interventions.

Elective Cesarean Section: The authors said that in a recent study, delivery by elective c-section before membrane rupture was associated with a lower transmission risk than vaginal or emerging c-section delivery. None of the 31 children delivered by c-section showed evidence of HCV infection. However, the authors found two cases of HCV transmission despite c-section in this study. C-section delivery is associated with high rates of maternal morbidity. Therefore, the authors feel that in view of the serious short-term and long-term implications of c-section for the mother, they believe that a policy of routine elective c-section cannot be justified. There has been conflicting data on this, as some studies suggest the type of delivery affected transmission while others suggest maybe not.

Breast Feeding and Episiotomy: the authors reported that in keeping with previous studies and the IASL Intl Conference, they observed no increase in transmission among women who breastfed. During spontaneous vaginal delivery, episotomy does not increase the risk of HCV transmission. I do not think these findings from this small study can rule out the possibility that amniocentesis may increase the risk of HCV transmission from mother-to-child. There have been conflicting data on whether breastfeeding can increase risk of transmission.

DDW Abstract--

Mother To Child Transmission of Hepatitis C Virus: A Case-Control Study of Risk Factors
    Sophie Poiraud, Hosp Tenon, Paris France; Joseph Cohen, Hosp Bicetre, Kremlin-Bicetre France; Xavier Amiot, Nadia Berkane, Antoine Flahault, Hosp Tenon, Paris France; Elisabeth Dussaix, Hosp Paul-Brousse, Villejuif France; Pauline Jouet, Hosp Tenon, Paris France; Olivier Bernard, Hosp Bicetre, Kremlin-Bicetre France; Jean-Didier Grange, Hosp Tenon, Paris France

Background : Mother-to-child transmission rate of hepatitis C virus (HCV) is low, less than 10 % in women not co-infected with HIV. Because most of published studies have included a small number of HCV-RNA positive children (N < 10), the transmission risk factors remain unclear. Invasive procedures, such as amniocentesis or use of forceps, could increase the risk of transmission. The aim of the study was to evaluate the risk factors for vertical transmission of HCV, using a case-control design.

Patients and methods: all children born to HCV-RNA positive, anti-HIV negative mothers were included in the study (patient group). Incident cases were HCV-RNA positive children after one month of age. Controls were HCV-RNA negative after 1 month of age and/or anti-HCV negative children. The following risk factorswere analyzed : amniocentesis, vaginal or caesarean-section delivery, use of forceps, episiotomy, maternal breast-feeding or bottle-feeding.

Results: from January, 1992, to August, 2000, 161 mother-child pairs (51 cases and 110 controls) were included. The mean mother age was 31.2±5.9 years in the patient group compared with 32.6±5.2 years in the control group (NS). Caesarean-section delivery rate was 13 % in the patient group and 22.9 % in the control group (p = 0.27). Vaginal delivery rate with forceps was 39.5 % in the patient group and 25 % in the control group (p = 0.13). Episiotomy rate was 61 % in the patient group and 57.9 % in the control group (p = 0.83). Amniocentesis rate was 16.6 % in the patient group and 25.3 % in the control group (p=0.27). Breastfeeding rate was 56.2 % in the patient group and 43.4 % in the control group (p = 0.16). Logistic regression analysis showed that vaginal delivery with forceps was the only significant and independent factor associated with vertical transmission (OR = 3.24, 95% CI [1.03;10.10], p=0.04). We performed a secondary analysis for all variables limited to the 123 children of different mothers. The estimation of the OR related to the way of delivery was very close in this secondary analysis.

Conclusions: our study demonstrates an increased HCV vertical transmission risk during vaginal delivery with use of forceps compared with caesarean-section delivery. Episiotomy does not appear as a risk factor during vaginal delivery. Maternal breast-feeding was not found to be a risk factor (nevertheless, we cannot exclude a risk with a ratio lower than 3). Furthermore, amniocentesis does not increase the risk of mother-to-child transmission of HCV.

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