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Three Part Question

In [infants of HCV infected mothers] does [avoidance of breast feeding] decrease [ maternal-infant transmission of HCV]

Clinical Scenario

You are the neonatal registrar reviewing a newborn infant whose mother is infected with HCV (but not infected with human immunodeficiency virus (HIV)). She wishes to breast feed but is concerned about whether this would affect the risk of her infant acquiring HCV infection. You would like your decision to be based on sound evidence.

Search Strategy

Medline 1966-2006 and EMBASE 1980- 2006 (using OVID interface).
Cochrane Library (2006, issue 3).
Hepatitis C"(MeSH term) AND "breastfeeding"/"breastmilk"(MeSH term) AND "transmission, vertical"(keyword).

Search Outcome

We found 44 articles in Medline and EMBASE and none in the Cochrane Library. 33 articles were irrelevant. All of the relevant articles were observational studies (cohort studies or case-series). We did not find any systematic reviews or randomised controlled trials.
Eight of the observational studies were small with data reported for less than about 100 mother-infant pairs (Zanetti 1995,Polywka 1999, Kumar 1998, Tajari 2001, Polywka 1997, Zimmerman 1995, Lin 1995, Spencer 1997). Three were large cohort studies undertaken by clinical networks (EPHCVN 2001, Gibb 2000, Resti 1998). These are described in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Resti et al 1998 Italy.	442 mother-child pairs. Follow up of infants of 275 mothers who were HCV RNA positive (and HIV negative).Breastfeeding status known for all infants: 87 were breast-fed.	Observational - cohort (level 2b)	HCV infection in children diagnosed by PCR and antibody testing on follow up until 24 months.	Proportion of infected children among those who breastfed (7%) was not statistically significantly different to that among the non-breastfed infants (4%).	Drop out- 39 pairs
European Paediatric HCV network, 2001 Europe, 7 countries	971 mother–child pairs. Mothers seropositive for HCV but not for HIV. Breastfeeding status known in 887 pairs. 319 infants were breast fed.	Observational Cohort (level 2b)	HCV infection in children diagnosed by PCR and antibody testing on follow-up until 18 months.	Proportion of infected children among those who breast fed (6.6%) was not statistically significantly different to that among the non-breast fed infants (6.3%).	Maternal viremic load (quantitative PCR) and clinical status (symptomatic liver disease or not) not known.
Gibb et al, 2000 UK and Eire	441 mother–child pairs (but 22 mothers known to be coinfected with HIV and HIV status not known in 91 mothers). Breast feeding status known in 414 pairs. 59 infants were breast fed.	Observational cohort (level 2b)	HCV infection in children diagnosed by PCR and antibody testing on follow-up until 24 months.	Proportion of infected children among those who breast fed (7.7%) was not statistically significantly different to that among the non-breast fed infants (6.7%).	Maternal viremic load (quantitative PCR) not known in most cases. Unknown HIV status in 20% of mothers

Comment(s)

HCV infection is a major worldwide cause of chronic liver disease, including hepatic fibrosis, cirrhosis, and hepatocellular carcinoma (AAP 1998; Poynard 2003). Mother to infant transmission is now the principal route of infection in childhood. The rate of mother to infant transmission of HCV is about 6% (Schwimmer 2000; Thomas 1998). HCV is a blood borne virus but has been detected in colostrum and breast milk in low levels (Kumar 1998). We wished to determine whether evidence exists that avoiding breast feeding reduces the risk of mother to infant HCV infection. We did not find any randomised controlled trials of this intervention. We did find several observational studies. Most were small single-centre studies (less than about 100 mother infant pairs) and therefore underpowered to assess whether the transmission was affected. We found three larger multi-centre cohort studies in which a total of 1854 mother infant pairs participated.( EPHCVN 2001, Gibb 2000, Resti 1998). We did not find evidence that avoidance of breast feeding is an effective intervention for preventing mother to infant transmission of HCV. This is consistent with evidence from other cohort studies that indicate that most infants who acquire HCV infection do so in utero or in the peripartum period (Mok 2005; Resti 1998). The studies were all undertaken in European countries within the past 10 years. They were generally of good methodolgical quality with valid definitions of inclusion criteria and outcomes and near-complete cohort follow up. Only one of the studies specifically examined the effect of breast feeding avoidance in mothers with HCV viraemia. Since transmission from a mother with no RNA detectable at delivery is extremely rare (Dore 1997), this may have been a confounding variable in the other studies where the HCV viral status was not assessed. We specifically aimed to evaluate the evidence in women who were not co-infected with HIV. This was possible for two studies but not for the third where a 5% of participants were HIV positive. A subgroup anlysis was not possible. HIV co-infection is a contra-indication ot breast-feeding in high-income countries.

Editor Comment

HCV, hepatitis C virus; PCR, polymerase chain reaction.

Clinical Bottom Line

Approximately 6% of babies born to hepatitis C (HCV) infected mothers will develop HCV infection (grade A). Avoidance of breast feeding is not an effective intervention for preventing mother-to-infant transmission of HCV (grade B).

References

1. Resti M, Azzari C, Mannelli F,Tuscany Study Group on Hepatitis C Virus infection in Children Mother to child transmission of hepatitis C virus:prospective study of risk factors and timing of infection in children born to women seronegative for HIV-1 . BMJ 1998;317:437-441.
2. Zanetti AR,Tanzi E, Paccagnini S, Principi N, Pizzocolo G, Lombardy Study Group on Vertical HCV Transmission. Mother-to-infant transmission of hepatitis C virus. Lancet 1995; 345:289-291.
3. Polywka S, Schroter M, Feucht H, Zollner B, Laufs R Low risk of vertical transmission of Hepatitis C virus by breast milk. Clin Inf Dis 1999;29:1327-1329.
4. Kumar R, Shahul S. Role of breast-feeding in transmission of Hepatitis C virus to infants of HCV-infected mothers. J Hepatol 1998;29:191-197.
5. Tajari H, Miyoshi Y, Funada S, Etani Y, Abe J, et al. Prospective study of mother-to-infant transmission of hepatitis C virus. Pediatr Inf Dis J 2001;20:10-14.
6. Polywka S, Feucht H, Zollner B, Laufs R. Hepatitis C virus infection in pregnancy and their risk of mother-to-child transmission . Eur J Clin Microbiol Infec Dis 1997;16:121-124.
7. Zimmermann R, Perucchini, Fauchere JC, Jemelka HJ, Geyer M. Hepatitis C in breast milk. Lancet 1995;345:928.
8. Lin HH, Kao JH, Hsu HY. Absence of infection in breast-fed infants born to hepatitis C virus-infected mothers. J Pediatrics 1995;126:589-591.
9. Spencer JD, Latt N, Beeby PJ, Collins E, Saunders JB. Transmission of hepatitis C virus to infants of human immunodeficiency virus-negative intravenous drug-using mothers:rate of infection and assessment of risk factors for transmission. J Viral Hepatitis. 1997;4:395-409.
10. Poynard T, Yuen MF, Ratziv V, Lai CL. Viral Hepatitis C. Lancet 2003;362:2095-2100.
11. Schwimmer JB, Balistreri WF. Transmission, natural history, and treatment of hepatitis C virus infection in the pediatric population. Sem Liver Dis 2000;20:37-46.
12. Thomas SL, Newell ML, Peckham CS, Ades AE, Hall AJ. A review of hepatitis C virus (HCV) vertical transmission: risks of transmission to infants born to mothers with and without HCV viraemia or human immunodeficiency virus infection. Int J Epidemiol 1998;27:108-17.
13. Dal Molin G, D'Agaro P, Ansaldi F, Ciana G, Fertz C, Alberico S, et al. Mother-to-infant transmission of hepatitis C virus: rate of infection and assessment of viral load and IgM anti-HCV as risk factors. J Med Virol 2002;67:137-42.
14. Dore GJ, Kaldor JM, McCaughan GW. Systematic review of role of polymerase chain reaction in defining infectiousness among people infected with hepatitis C virus. BMJ 1997;315:333-7.
15. Mok J, Pembrey L, Tovo PA, Newell ML, European Paediatric Hepatitis C Virus Network. When does mother to child transmission of hepatitis C virus occur? Arch Dis Child 2005;90:F156-60.
16. European Paediatric Hepatitis C Virus Network. Effects of mode of delivery and infant feeding on the risk of mother-to-child transmission of hepatitis C virus. BJOG 2001;108:371–7.
17. Gibb DM, Goodall RL, Dunn DT, et al. Mother-to-child transmission of hepatitis C virus: evidence for preventable peripartum transmission. Lancet 2000;356:904–7.