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Department of Pediatrics, Faculty of Medicine of Ribeiro Preto, University of So Paulo, Av. Bandeirantes 3900, 14049-900, Ribeiro Preto, SP, Brazil
Molecular Virology Laboratory, Oswaldo Cruz Institute, Av. Brasil 4365, Manguinhos, Rio de Janeiro, Brazil
c
Human Milk Bank, University Hospital, Faculty of Medicine of Ribeiro Preto, University of So Paulo, Av. Santa Luzia, 387 Jardim Sumar, CEP 14025-090,
Ribeiro Preto, So Paulo, Brazil
d
Department of Internal Medicine, Faculty of Medicine of Ribeiro Preto, University of So Paulo, Av. Bandeirantes 3900, 14049-900, Ribeiro Preto, SP, Brazil
b
a r t i c l e
i n f o
Article history:
Received 29 December 2008
Received in revised form 14 April 2009
Accepted 19 April 2009
Keywords:
Hepatitis B virus
Human milk donor
Human milk bank
Lactating women
a b s t r a c t
Background: Blood screening for hepatitis B virus (HBV) is not universally performed for donor selection
in human milk banks.
Objectives: To evaluate the frequency of detection of HBV surface antigen (HBsAg) and HBV-DNA in
colostrum of HBV-infected nursing mothers before and after Holder pasteurization.
Study design: Forty-two concentrated breast milk samples were obtained within two postnatal weeks from
24 HBsAg-positive women (4 HBeAg-positive and 20 HBeAg-negative, anti-HBe-positive) were tested for
the presence of HBsAg and HBV-DNA before and after Holder pasteurization (30 min at 62.5 C).
Results: Before pasteurization, HBsAg and HBV-DNA were found in 14/24 (58%), and 20/24 (75%) rst
milk samples, respectively, obtained by 4 days after delivery. At least one marker was detected in 20/24
(83%) milk samples. Both markers were identied in milk of HBeAg-positive mothers, and most mothers
with anti-HBe in blood had at least one HBV marker. Once detected, viral markers were frequently found
in milk samples subsequently obtained from the same woman. Holder pasteurization did not affect the
probability of detecting HBsAg (8/18, 44%), HBV-DNA (12/18, 67%), or at least one of them (15/18, 83%).
Conclusions: Although the biological implications of these ndings remain to be determined, considering
that HBV is highly contagious and most recipients of banked human milk are preterm infants, these
ndings should be taken into account when donors are enlisted for human milk banks without serological
screening.
2009 Elsevier B.V. All rights reserved.
1. Background
After the rst demonstration more than 30 years ago of hepatitis B virus (HBV) surface antigen (HBsAg) in the milk of a HBV
female carrier,1 this antigen was detected in none2 to 71.4%3,4 of
milk samples tested. HBV virions (Dane particles) were identied in
4 of 10 milk samples by electron microscopy.3 HBe antigen (HBeAg)
was also found in human milk.5 More recently, after the advent of
molecular biology techniques, an overall HBV-DNA-positive rate of
about 43%69 was detected in milk of HBV-infected women from
countries with a high carrier rate.
Donor selection and techniques of milk processing and storage in human milk banks are measures taken in Europe and
North America10,11 to prevent infection in recipient infants in contrast to countries with fewer resources which do not require that
milk donors be screened for HBV. Instead, lactating women are
usually only verbally screened and milk safety relies on Holder
pasteurization12 (heating to 62.5 C for 30 min followed by cooling
282
4. Results
Before pasteurization
After pasteurization
Colostrum
HBsAg
HBV-DNA
At least one marker
0.37
0.55
0.67
0.32
0.39
0.92
a
b
283
Table 2
HBsAg and HBV-DNA in serial samples of breast milk, tested before and after pasteurization.
Mother number
1
2
3
4
5
6
7
8
9
10
a
2nd (4 days)
3rd (9 days)
HBsAga
HBV-DNAa
HBsAg
HBV-DNA
HBsAg
HBV-DNA
HBsAg
HBV-DNA
/
/
+/+
/+
+/+
/
/
+/
+/+
+/+
+/+
+/
+/
/
+/+
+/+
+/+
+/+
/
+/
/
/
+/
/
+/+
+/
/
+/
+/
+/+
+/
+/+
+/
/
/+
+/
+/+
+/+
+/
+/+
/
/
+/+
/+
/+
/
+/+
+/+
+/
+/+
+/
+/+
284
2. Beasley RP, Stevens CE, Shiao Is, Hsien chieh M. Letter: Breast-feeding and hepatitis B. Lancet 1975;2:1089.
3. Boxall EH. Letter: Breast-feeding and hepatitis B. Lancet 1975;2:979.
4. Lee AK, Ip HM, Wong VC. Mechanisms of maternalfetal transmission of hepatitis B virus. J Infect Dis 1978;138:66871.
5. Lin JY, Lu JC, Kuan TY, Liu WT. Characterization of hepatitis B e antigen from
human breast milk. Zhonghua Minguo wei sheng wu ji mian yi xue za zhi
1986;19:819.
6. Yang X, Cui MX, Liu BG. Breast-feeding by mothers with positive serum hepatitis
B virus test. Zhonghua fu chan ke za zhi 1994;29(5868):635.
7. Lin HH, Hsu HY, Chang MH, Chen PJ, Chen DS. Hepatitis B virus in the colostra of
HBeAg-positive carrier mothers. J Pediatr Gastroenterol Nutr 1993;17:20710.
8. Yang D, Li Y, Song J. Signicance of detection of HBV-DNA and CMV-DNA by
polymerase chain reaction in screening mothers milk. Hunan yi ke da xue xue
bao 1999;24:446.
9. Mitsuda T, Yokota S, Mori T, Ibe M, Ookawa N, Shimizu H, et al. Demonstration
of mother-to-infant transmission of hepatitis B virus by means of polymerase
chain reaction. Lancet 1989;2:8868.
10. Jones F. History of North American donor milk banking: one hundred years of
progress. J Hum Lact 2003;19:3138.
11. Balmer SE, Williams AF. Guidelines for the establishment and operation of
human milk banks in the UK. J Hosp Infect 1995;31:1556.
12. Tully MR. Excelencia em bancos de leite humano: uma visao do futurothe First
International Congress on Human Milk Banking. J Hum Lact 2001;17:513.
13. Tully DB, Jones F, Tully MR. Donor milk: whats in it and whats not. J Hum Lact
2001;17:1525.
14. Hamprecht K, Vochem M, Baumeister A, Boniek M, Speer CP, Jahn G. Detection
of cytomegaloviral DNA in human milk cells and cell free milk whey by nested
PCR. J Virol Methods 1998;70:16776.
15. Niel C, Moraes MT, Gaspar AM, Yoshida CF, Gomes SA. Genetic diversity of hepatitis B virus strains isolated in Rio de Janeiro, Brazil. J Med Virol 1994;44:1806.
16. Gomes SA, Yoshida CF, Niel C. Detection of hepatitis B virus DNA in hepatitis
B surface antigen-negative serum by polymerase chain reaction: evaluation of
different primer pairs and conditions. Acta Virol 1996;40:1338.
17. Huang YH, Wu JC, Chang TT, Sheen IJ, Huo TI, Lee PC, et al. Association of core promoter/precore mutations and viral load in e antigen-negative chronic hepatitis
B patients. J Viral Hepat 2006;13:33642.
18. Prince AM, Brotman B. Perspectives on hepatitis B studies with chimpanzees.
ILAR J 2001;42:858.
19. Schultz U, Grgacic E, Nassal M. Duck hepatitis B virus: an invaluable model
system for HBV infection. Adv Virus Res 2004;63:170.
20. Beasley RP, Stevens CE, Shiao IS, Meng HC. Evidence against breast-feeding as a
mechanism for vertical transmission of hepatitis B. Lancet 1975;2:7401.
21. Pan CQ, Zhang JX. Natural history and clinical consequences of hepatitis B virus
infection. Int J Med Sci 2005;2:3640.
22. Nowak T, Niedrig M, Bernhardt D, Hilfenhaus J. Inactivation of HIV, HBV, HCV
related viruses and other viruses in human plasma derivatives by pasteurisation. Dev Biol Stand 1993;81:16976.
23. Hilfenhaus J, Groner A, Nowak T, Weimer T. Analysis of human plasma products:
polymerase chain reaction does not discriminate between live and inactivated
viruses. Transfusion 1997;37:93540.
24. Seidel BM, Schulze B, Schubert S, Borte M. Oral mucosal immunocompetence
in preterm infants in the rst 9 months of life. Eur J Pediatr 2000;159:789.
25. Rognum TO, Thrane S, Stoltenberg L, Vege A, Brandtzaeg P. Development of
intestinal mucosal immunity in fetal life and the rst postnatal months. Pediatr
Res 1992;32:1459.
26. Poovorawan Y, Sanpavat S, Pongpunglert W, Chumdermpadetsuk S, Sentrakul P,
Vandepapeliere P, et al. Long term efcacy of hepatitis B vaccine in infants born
to hepatitis B e antigen-positive mothers. Pediatr Infect Dis J 1992;11:81621.
27. Freitas da Motta MS, Mussi-Pinhata MM, Jorge SM, Tachibana Yoshida CF, Sandoval de Souza CB. Immunogenicity of hepatitis B vaccine in preterm and full
term infants vaccinated within the rst week of life. Vaccine 2002;20:155762.