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Effect of hepatitis B immunisation in newborn infants of mothers positive for hepatitis B surface antigen: systematic review and meta-analysis

BMJ 2006; 332 doi: (Published 09 February 2006) Cite this as: BMJ 2006;332:328

Effect of Hepatitis B Vaccine and Immunoglobulin

EDITOR- We read with interest the systematic review and meta-analysis
on the effect of Hepatitis B immunisation in newborn infants of mothers
positive for hepatitis B surface antigen(1). We recognise the difficulty
in conducting the first meta-analysis on this subject using some small
sample size trials and many with low methodological quality. As one might
expect from the Cochrane Collaboration Group, the authors have undertaken
an extensive search for published and unpublished trials on this subject.

The risk of perinatal transmission if the mother is positive for
HbsAg and HbeAg is higher compared to when the mother is positive for
HbsAg only(2). Therefore, even if there is no intervention at birth
(vaccine/HBIG), one would expect a significantly lower number of infected
infants from mothers who are positive for HbsAg only. Although it might
have led to exclusion of some of the good quality trials, we felt that
trials that did not report HbeAg status of mothers should have been
excluded from the meta-analysis.

We also know that low birth weight babies are less likely to mount an
adequate immune response to Hepatitis B vaccine(3), and yet 10 of the
trials studied had excluded low birth weight babies. Excluding low birth
weight babies from studies may well inflate the beneficial effect of
immunisation. Furthermore, the follow up period of some of the trials that
were included in the meta-analysis was very short at only 6 months which
makes it difficult to conclude infection is absent, given the long
incubation period.

The trials were very disparate. Trials differed in vaccination
schedules, age of child at vaccination, dose of HBIG and vaccine types
which affected the outcome, for example, one trial(4) used Hepatitis B
vaccine (plasma derived) and HBIG at birth and at 6 weeks, when 2nd dose
of HBIG is not usual and not recommended in the UK.

The statement “evidence on immunisation for infants of mothers
positive for hepatitis B surface antigen but negative for hepatitis B e
antigen is weak” (“What this study adds” section(1)) is not supported by
the meta-analysis. Although the authors admit that the applicability of
their findings to mothers negative for HbeAg is limited, in our view, the
inclusion of the above statement with the meta-analysis results may lead
to less use of this very effective and safe vaccine. This may also have
more impact in countries where universal hepatitis B immunization (1991
WHO recommendation) is not adopted.

It is reassuring to see that the new revised UK policy to prevent
hepatitis B in newborn babies is comprehensive, i.e., Hepatitis B vaccine
and HBIG are recommended when the mother of the newborn is HbsAg +ve and
HbeAg +ve, or when HbsAg +ve, HbeAg –ve and anti-Hbe –ve, or when HbeAg
status is unknown, and in acute hepatitis B during pregnancy; if the
mother is HbsAg +ve and anti-Hbe +ve then only Hepatitis B vaccine is

It is evident from this meta-analysis that some newborns were not
protected even when they had HBIG and vaccine, and we agree with the
authors suggestion that more good quality trials are needed to investigate
the possible factors such as timing of infection i.e., intrauterine or
perinatal, optimal schedule of intervention, circumstances at delivery,
method of delivery etc.

Sundhar Rajhan Shunmugam Kanagasabapathy F2 in Public Health

Katy Elders Specialist Registrar in Public Health

Samuel Ghebrehewet Consultant in Communicable Disease Control

Cheshire & Merseyside Health Protection Team,
Health Protection Agency,
Chester Microbiology Laboratory,
Countess of Chester Health Park,
Liverpool Road,
Chester CH2 1UL


1. Chuanfang Lee, Yan Gong, Jesper Brok, Elizabeth H Boxall,
Christian Gludd. Effect of hepatitis B immunisation in newborn infants of
mothers positive for hepatits B surface antigen: systematic review and
meta-analysis. BMJ 2006;328-332.

2. Beasley RP, Trepo C, Stevens CE, Szmuness W. The e antigen and
vertical transmission of hepatitis B surface antigen. Am J Epidemiol
1977;105:94 -8

3. Losonsky GA, Wassermann SS, Stephens I et al. Hepatitis B
vaccination of premature infants: a reassessment of current
recommendations for delayed immunization. Paediatrics 1999:103 (2):E14

4. Farmer K, Gunn T, Woodfield DG. A combination of Hepatitis B
vaccine and immunoglobulin does not protect all infants born to hepatitis
B e antigen positive mothers. NZ med J 1987;100:412-4.

5. Immunisation against Infectious Disease (revised) Nov 2005
Department of Health,Welsh Office, Scottish Office Department of Health,
DHSS (Northern Ireland).

Competing interests:
None declared

Competing interests: No competing interests

24 February 2006
Sundhar Rajhan Shunmugam Kanagasabapathy
Foundation Year 2
Katy Elders, Samuel Ghebrehewet
Health Protection Agency,Countess of Chester Health Park,Chester CH2 1UL