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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: https://doi.org/10.1136/bmj.38719.435833.7C (Published 09 February 2006) Cite this as: BMJ 2006;332:328

Authors’ reply

EDITOR – We thank for the response by Kanagasabapathy et al., ‘Effect
of Hepatitis B Vaccine and Immunoglobulin’ published on 24 February 2006
on our Cochrane Hepato-Biliary Group systematic review (1).

We agree with Kanagasabapathy et al. that the risk of perinatal
transmission of hepatitis B is lower, if mothers are positive for
hepatitis B surface antigen but negative for hepatitis B e antigen
compared to mothers positive for both. However, we think, this observation
is not an argument for excluding those trials assessing interventions in
mother with unknown hepatitis B e antigen status from our meta-analysis.
We included trials according to our protocol, i.e., mothers being positive
for hepatitis B surface antigen irrespective of hepatitis B e antigen
status (2). This protocol, specifying the inclusion criteria of the
trials, is peer-reviewed and published in The Cochrane Library (2).
Furthermore, we did several subgroup analyses according to mother’s
hepatitis B e antigen status (positive compared to negative compared to
unknown) to support the statement ‘evidence on immunisation for infants of
mothers positive for hepatitis B surface antigen but negative for
hepatitis B e antigen is weak.’ Because of space limits, we were not able
to present these analyses in the BMJ but it will be available in The
Cochrane Library 2006, Issue 2 (3). For example, for mothers being
positive for hepatitis surface antigen and e antigen, hepatitis B events
are significantly lower in infants receiving hepatitis B immunoglobulin
than in infants getting placebo or no intervention (relative risk 0.51,
95% confidence interval 0.42 to 0.61, 9 trials). While for mothers with
unknown and negative hepatitis B e antigen, the prevention effect of
hepatitis B immunoglobulin was not different compared with placebo or no
intervention (relative risk 0.73, 95% confidence interval 0.38 to 1.42, 2
trials; relative risk 0.24, 95% confidence interval 0.01 to 4.06, 1
trial).

We emphasise that our review identified a lack of randomised clinical
trials on mothers negative for hepatitis B e antigen (1). This is not as
same as saying that we should not immunise infants born to those mothers.
Whether to immunise those infants is an individual or national decision,
based on our review and other studies.

We agree that the effects of hepatitis B vaccine and immunoglobulin
on low birth weight infants should be further evaluated in randomised
trials. We specifically wrote this in our review (1). In addition, the
effects of vaccine and immunoglobulin on clinical outcomes during longer
follow-up should also be further evaluated.

We are interested to see new evidence supporting the use of hepatitis
B vaccine and immunoglobulin in acute hepatitis B during pregnancy. If new
evidence fulfils our inclusion criteria, we will be happy to include it
when updating our review in the future.

References:

(1). Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Effect of hepatitis B
immunisation in newborn infants of mothers positive for hepatitis B
surface antigen: systematic review and meta-analysis. BMJ 2006;332:328-
336, doi:10.1136/bmj.38719.435833.7C

(2). Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Hepatitis B prophylaxis
for newborns of hepatitis B surface antigen-positive mothers [protocol for
a Cochrane review]. The Cochrane Database of Systematic Reviews 2004,
Issue 2: CD004790.

(3). Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Hepatitis B immunisation
for newborn infants of hepatitis B surface antigen-positive mothers. The
Cochrane Database of Systematic Reviews 2006, Issue 2. Art.
No.:CD004790.pub2. DOI: 10.1002/14651858.CD004790.pub2

Competing interests:
None declared

Competing interests: No competing interests

23 March 2006
Yan Gong
research assistant
Jesper Brok, Elizabeth H. Boxall, Chuanfang Lee, and Christian Gluud
Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, H:S Rigshospitalet, 2100, Denmark