1. Identification of Potential Risk Factors for Mother-to- Infant HCV Transmission Slideset on: Mast EE, Hwang LY, Seto DS, 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.

2. clinicaloptions.com/hep Perinatal HCV Transmission: Membrane Rupture and Internal Fetal Monitoring Background  Approximately 40,000 infants born to HCV-infected mothers in the United States each year  Risk factors for perinatal HCV transmission include presence of maternal HCV RNA during delivery and maternal HIV/HCV coinfection –Other risk factors and natural history of HCV infection in infected infants not well defined  Current study followed HCV-infected women and their infants to determine risk factors for mother-to-infant HCV transmission –Natural history of infection among those infants who contracted HCV also evaluated Mast EE, et al. J Infect Dis. 2005;192:1880-1889.

3. clinicaloptions.com/hep Perinatal HCV Transmission: Membrane Rupture and Internal Fetal Monitoring Study Design  Prospective study, 242 women enrolled in 1993  Infants born to HCV- infected mothers followed from birth until  12 months  Maternal serum collected at enrollment and delivery  Mothers at enrollment –79.5% HCV RNA positive –4.6% HIV positive –2.9% HIV/HCV RNA positive  Breast milk and infant serum collected at birth and at 8 well-child visits –Anti-HCV/anti-HIV antibodies –HCV RNA (serum and BM) –HCV genotype –Serum ALT levels  Infants defined as HCV+ if HCV RNA detected in serum at  2 follow-up visits or if infants anti-HCV+ at  24 months of age Mast EE, et al. J Infect Dis. 2005;192:1880-1889.

4. clinicaloptions.com/hep Perinatal HCV Transmission: Membrane Rupture and Internal Fetal Monitoring Main Findings  9 of 244 infants infected with HCV (3.7%; 95% CI: 1.8%- 7.1%) –All mothers had detectable HCV RNA at delivery (P =.12) –Infection rate among those infants: 4.6% (9/190) –HCV transmission more likely from HIV/HCV-coinfected mothers vs HCV-monoinfected mothers –25.0% vs 3.8%; RR: 6.5 (95% CI: 1.6-26.4) –1 of 2 HCV-infected infants born to HIV/HCV-coinfected mothers also HIV infected –HCV RNA levels significantly higher in HIV/HCV-coinfected women vs HIV-negative women (1.48 x 10 7 vs 2.38 x 10 6 copies/mL [P <.001]) Mast EE, et al. J Infect Dis. 2005;192:1880-1889.

5. clinicaloptions.com/hep Perinatal HCV Transmission: Membrane Rupture and Internal Fetal Monitoring Maternal Risk Factors for Mother-to- Infant HCV Transmission Identified Mast EE, et al. J Infect Dis. 2005;192:1880-1889. Maternal Characteristic Infected Infants, n (%) Univariate AnalysisMultivariate Analysis RR (95% CI)P ValueAdjusted OR (95% CI) HCV RNA level, copies/mL.03*  ≤ 10 6 1 (1.6)--  10 6 -10 7 2 (2.3)--  ≥ 10 7 4 (11.8)-- Fetal monitoring  Internal3 (18.8)7.7 (1.9-31.6).026.7 (1.1-35.9)  External4 (2.4)-- Duration of membrane rupture, hrs.02*  < 10 (0)--  1-51 (1.7)--  ≥ 66 (8.6)--9.3 (1.5-179.7) CI, confidence interval; OR, odds ratio; RR, relative risk. *Cochran-Armitage test for trend.

6. clinicaloptions.com/hep Perinatal HCV Transmission: Membrane Rupture and Internal Fetal Monitoring Other Outcomes  63 mothers breast-fed for median of 1 month  HCV RNA detected in ≥ 1 colostrum or breast milk sample from 19 out of 37 HCV RNA–positive mothers –None of these mothers transmitted HCV to infants –HCV RNA detection in colostrum or breast milk not related to serum HCV RNA load  HCV RNA detectable in all 9 infected infants at 2 months –Anti-HCV profiles varied considerably between infants –None showed clinical signs or symptoms of hepatitis during 5 years of follow-up –Abnormal ALT levels detected ≥ 1 time for all infants –3 infants resolved infection, became HCV RNA negative, and achieved normal ALT levels at 12-18 months of age Mast EE, et al. J Infect Dis. 2005;192:1880-1889.

7. clinicaloptions.com/hep Perinatal HCV Transmission: Membrane Rupture and Internal Fetal Monitoring Key Conclusions  Duration of membrane rupture and internal fetal monitoring identified as risk factors for mother-to-infant HCV transmission  No association between breast-feeding and HCV transmission identified  Rate of HCV transmission from HIV/HCV-infected mothers to infants found to be higher than that for HCV- monoinfected mothers  Further prospective studies needed to evaluate potential changes in birthing procedures or fetal monitoring Mast EE, et al. J Infect Dis. 2005;192:1880-1889.