Dear Editor Danrolf de Jesus and Dr Jesus M Garcia Calleja
Re: MS#9952457645244487
We are most grateful for the helpful comments of the referees. The following are our
response to each of their comments. We have revised our manuscript accordingly.
We are attaching two copies of the revised manuscript for your consideration, in one
we highlight the changes we have made.
Yours truly,
Yingjie Zheng
Response to reviewers’ comments on MS#9952457645244487
1. English language writing
We have our manuscript reviewed by Professor Monhun Ng from University of
Hongkong.
2. The title is weak. I would resentence it, and would not use past tense in a title.
The language has been corrected and the title has been changed to “Should chronic
hepatitis B mothers breastfeed? A meta analysis”.
3. Most included studies (94%) are Chinese studies, almost all from Chinese
journals, which is difficult for researchers or readers outside of China to get a
hold of these articles. Looking from another perspective, this study provides us
with information that would be difficult to reach and there would be a
language barrier.
Our meta analysis included 32 studies, and 30 of them are from China:
(1) 2 are indexed in PUBMED: 1 study is from Hongkong [study 2: Lancet 1988,
2(8618):1032], and the other study from Shanghai [study 8: Int J Clin Pract 2003,
57(2):100-102].
(2) Carefully evaluating the quality of studies based on Newcastle-Ottawa Quality
Assessment Scale (NOS), we can confirm another Chinese study with high quality
[study 15]. Similar rating has been done for the rest Chinese studies. And all the
studies meet our criterion of inclusion and exclusion.
(3) It’s not surprising that Chinese scientists are much interested in breastfed
transmitted hepatitis B infection since the disease is highly epidemic in this
country.
Thus, we believe that this meta analysis should lost much information if the
Chinese studies have been excluded.
Actually for any meta analysis, the completeness of the included studies should be
ensured. Language barrier should be a common problem. To be a scientist, I think it’s
my responsibility to introduce high-quality Chinese studies into the world and an
international cooperation should effectively overcome this problem.
4. The authors present their results clearly, with figures and tables, but are
lacking with making clearer sentences for the reader to understand the
methodology.
We correct it accordingly.
5. Abstract: Don’t use the past tense.
We have corrected the abstract, and re-written the results and conclusion.
6.
Introduction: Second paragraph, first sentence. Here you are making a
statement I would advice to state a reference.
We have re-written the paragraph and added one reference.
7. Introduction: Fourth paragraph: The last sentence in this paragraph, what do
you mean with uncomfortable?
We have re-written the whole paragraph.
8. I would already start defining high infectivity in this section. High HBV DNA
levels? HBeAg-positiveness?
We have re-written the whole paragraph.
9. Is my understanding correct in this? That your aim was to understand whether
immunization helps to prevent CHB infection in infants born to CHB infected
women, especially those with high infectivity.
Yes.
10. Methods: First paragraph, data sources… Add the starting date of the search
from year…to December 31, 2010.
We have added this information.
11. Methods: Paragraph 4, The last sentence, general characteristics of the
participants… are the participants the mothers? Or the infants? Its not clear in
the methods.
We change “participants” to “babies”.
12. Methods: 5th paragraph, Please explain fourth and 2nd outcome of NOS, its
not clear to the reader.
In NOS, the 4th item under selection is “Demonstration that outcome of interest
was not present at start of study” and the 2nd item under outcome is “Was
follow-up long enough for outcomes to occur”.
We add this information in our manuscript.
13. Methods: Statistical analysis section, Because of the language some things are
left unclear. What is Begger’s test? I tried to find reference 21, but havent’t
come across, I did find Biometrics 2000, Jun 56 (2) 455-63.
We add a reference to Begger’s test. Reference 21 is for the method of
nonparametric trim and fill.
14. Results: What is meant by backward check? Do you mean manual reference
checking?
Backward search means that the reference lists of potentially relevant
manuscripts were scanned backward to obtain extra suitable studies. We add this
information in the Methods section.
15. In the 3rd paragraph you mention that 1 study did not mention if the feeding
methods were decided by the mother. Is this important for your results?
Analysis? If yes, explain the reason. If not, leave it out.
Only one study randomized the feeding methods. I think it’s important and add
this information.
16. 6th paragraph, I believe you mean Subgroup analysis showed.
Yes.
17. Discussion
We have re-written it.
18. This is how I understand the research question, but it is formulated differently
in the abstract, introduction and conclusion.
We have re-written it.
19. My main methodological question is why 'risk difference' was used instead of
'risk ratio'? The a priori chance of infection is low to start with, so one can
never show a large difference between the groups. Using risk ratio would
better highlight the differences between the two groups compared.
We use RD instead of RR due to: (1) we are much concerned about breastfed
transmitted HBV and want to quantify the risk in the breast-fed infants that is
attributable to breastfeeding if it really exists. (2) The calculation of RDs is easy to
implement in common software for the studies with zero outcome in both groups.
During the analysis, those studies are often automatically excluded by the
software if RR or OR is used as measurement of effect. (3) We also calculate RR,
and the results are similar. We give one result below (see Figure 1). The RRs and
its 95% confidential limits in those studies (De Martino M 1985; Gu XQ 2003;
Zhang JH 2005; Chen H 2008; SUN LY 2010) with zero outcomes in both groups
were firstly calculated with Monte-Carlo simulation and then integrated into the
other 27 studies for further analysis. (4) The linear relationship between RDs and
RRs was showed in Figure 2.
RR
Figure 1 Effect of breastfeeding on occurrence of chronic hepatitis B infection among the
infants born of CHB mothers analyzed by random-effect model (RR: risk difference; CI:
confidence interval)
3.0
RRs
2.5
2.0
1.5
1.0
0.5
0.0
-0.08
-0.06
-0.04
-0.02
0.00
RDs
0.02
0.04
0.06
0.08
Figure 2 the relationship between RRs and RDs of the 32 studies.
20. The funnel plots are nice to see, but do not add much information. This
information can be given in words.
We agree to the reviewer’s comments. But the funnel plots would help the
readers to visually judge how the publication bias happens.
21. Other major modifications

We re-write the sections of Result, Discussion and Conclusion;

We reformat and replace Table 1 with a new one;

We replace Figure 3 with a new one. Only “RD” in the vertical axis has been
changed to “RDs”.

Other revisions can be found in our manuscript with the tracked changes.