Reviewer’s report
Title: 
Review of Recent Evidence on the Management of Heartburn in Pregnant
and Breastfeeding Women
Version: 
0 
Date: 
16 Jan 2022
Reviewer's report:
I read the article entitled "Review of Recent Evidence on the Management of
Heartburn in Pregnant and Breastfeeding Women". 
There is a strong need for such publications because pregnancy, especially
breastfeeding and GERD are underestimated issues.
However starting from the "personality" of the manuscript, I have raised many
issues. This is a review article eventhough written as a format of metaanalysis
somehow. 
* Methodology is full with literature discussion which is not the correct place. 
* Many non-pregnancy mechanisms of GERD pathogenesis have been given in
the introduction. This is out of the focus of the paper. 
* There is not a regular order within the text according to drugs or sections; such
as methodology afterwards drugs without a major title.
* All of a sudden, endoscopy and obesity have appeared. I am not sure about the
place even there is a need for such sections in the manuscript. If obesity takes a
place, other life style changes should be discussed as well.
* "GERD, pregnancy, breastfeeding, lactation, treatment, mucosal protectant,
potassium, competitive acid blocker, P-CAB, promotility, prokinetic" were
included for the search as keywords; why PPIs, H2RA, alginate, AA were not
included but other relatively less common medications were included such as P-
CAP etc?
* I do not agree with the treatment algorithms given by the authors. They are
very simplistic. According to those treatment algorithms, all GERDs should be
treated with the same approach irrespective from the severity of symptoms. A
pregnant 
woman with a mild symptom once a week should be treated differently
than a pregnant "patient" with much more severe symptoms. 
* "Potential adverse effects which have been associated with long-term PPI use
includes kidney disease, dementia, bone fracture, myocardial infarction,
infections, micronutrient deficiencies, and gastrointestinal malignancies [31].
Many studies refused those side effects esp cancers, kidney disease, dementia,
myocardial infarction. It is not possible to mention a clear relation under the
knowledge of current literature. This data is also not related with the focus of the
manuscript.
* This study is about only prolactin secretion (Anderson PO. Treating
gastroesophageal reflux and heartburn while breastfeeding. Breastfeed Med.
2018;13(7):463). There is clearly no data regard to justify this conclusion
"Different H2RAs are excreted in breast milk at lower amounts than the doses
administered to infants" or following paragraph if there is any other study
supporting the hypothesis. 
* I had a hard time to find the original version of this study which finally found;
"In a study involving 12 mothers taking pantoprazole, pantoprazole was
undetectable for 80% of the day. The highest concentration of pantoprazole in
breast milk after 7 days of therapy was only 150 
μ
g/L on average [38]".The
refererence mentioned by the authors is wrong and a review article. This is the
correct one. Bor S, Karacaoglu S, Ergun P, et al. The levels of pantoprazole in
human breast milk and plasma: Two compartment model. Neurogastroenterol
Motil 2017;29:79-80. Abstract. doi:10.1111/nmo.13180. 
* This sentence is not clear; "Promotility drugs enhances gastric emptying,
which reduces the time that gastric acids sits in the stomach". Does it mean acid
pocket?
* Metoclopramide is also related with QT prolongation especially drugs with
similar side effects. This should be mentioned. 
* References at table 1 belong to review articles not to the specific references. 
* "acid taste in mouth" is not within the typical symptoms of GERD although it
is commonly referred in Far East studies. 
* There are much better figures regarding the acid pocket in the literature.
Publons Reviewer Recognition
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registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
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Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
No
Reviewer’s report
Title: 
Review of Recent Evidence on the Management of Heartburn in Pregnant
and Breastfeeding Women
Version: 
0 
Date: 
16 Jan 2022
Reviewer's report:
I read the article entitled "Review of Recent Evidence on the Management of
Heartburn in Pregnant and Breastfeeding Women". 
There is a strong need for such publications because pregnancy, especially
breastfeeding and GERD are underestimated issues.
However starting from the "personality" of the manuscript, I have raised many
issues. This is a review article eventhough written as a format of metaanalysis
somehow. 
* Methodology is full with literature discussion which is not the correct place. 
* Many non-pregnancy mechanisms of GERD pathogenesis have been given in
the introduction. This is out of the focus of the paper. 
* There is not a regular order within the text according to drugs or sections; such
as methodology afterwards drugs without a major title.
* All of a sudden, endoscopy and obesity have appeared. I am not sure about the
place even there is a need for such sections in the manuscript. If obesity takes a
place, other life style changes should be discussed as well.
* "GERD, pregnancy, breastfeeding, lactation, treatment, mucosal protectant,
potassium, competitive acid blocker, P-CAB, promotility, prokinetic" were
included for the search as keywords; why PPIs, H2RA, alginate, AA were not
included but other relatively less common medications were included such as P-
CAP etc?
* I do not agree with the treatment algorithms given by the authors. They are
very simplistic. According to those treatment algorithms, all GERDs should be
treated with the same approach irrespective from the severity of symptoms. A
pregnant 
woman with a mild symptom once a week should be treated differently
than a pregnant "patient" with much more severe symptoms. 
* "Potential adverse effects which have been associated with long-term PPI use
includes kidney disease, dementia, bone fracture, myocardial infarction,
infections, micronutrient deficiencies, and gastrointestinal malignancies [31].
Many studies refused those side effects esp cancers, kidney disease, dementia,
myocardial infarction. It is not possible to mention a clear relation under the
knowledge of current literature. This data is also not related with the focus of the
manuscript.
* This study is about only prolactin secretion (Anderson PO. Treating
gastroesophageal reflux and heartburn while breastfeeding. Breastfeed Med.
2018;13(7):463). There is clearly no data regard to justify this conclusion
"Different H2RAs are excreted in breast milk at lower amounts than the doses
administered to infants" or following paragraph if there is any other study
supporting the hypothesis. 
* I had a hard time to find the original version of this study which finally found;
"In a study involving 12 mothers taking pantoprazole, pantoprazole was
undetectable for 80% of the day. The highest concentration of pantoprazole in
breast milk after 7 days of therapy was only 150 
μ
g/L on average [38]".The
refererence mentioned by the authors is wrong and a review article. This is the
correct one. Bor S, Karacaoglu S, Ergun P, et al. The levels of pantoprazole in
human breast milk and plasma: Two compartment model. Neurogastroenterol
Motil 2017;29:79-80. Abstract. doi:10.1111/nmo.13180. 
* This sentence is not clear; "Promotility drugs enhances gastric emptying,
which reduces the time that gastric acids sits in the stomach". Does it mean acid
pocket?
* Metoclopramide is also related with QT prolongation especially drugs with
similar side effects. This should be mentioned. 
* References at table 1 belong to review articles not to the specific references. 
* "acid taste in mouth" is not within the typical symptoms of GERD although it
is commonly referred in Far East studies. 
* There are much better figures regarding the acid pocket in the literature.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
No
Please review this paper.
user
Reviewer’s report
Title: 
Review of Recent Evidence on the Management of Heartburn in Pregnant
and Breastfeeding Women
Version: 
0 
Date: 
16 Jan 2022
Reviewer's report:
I read the article entitled "Review of Recent Evidence on the Management of
Heartburn in Pregnant and Breastfeeding Women". 
There is a strong need for such publications because pregnancy, especially
breastfeeding and GERD are underestimated issues.
However starting from the "personality" of the manuscript, I have raised many
issues. This is a review article eventhough written as a format of metaanalysis
somehow. 
* Methodology is full with literature discussion which is not the correct place. 
* Many non-pregnancy mechanisms of GERD pathogenesis have been given in
the introduction. This is out of the focus of the paper. 
* There is not a regular order within the text according to drugs or sections; such
as methodology afterwards drugs without a major title.
* All of a sudden, endoscopy and obesity have appeared. I am not sure about the
place even there is a need for such sections in the manuscript. If obesity takes a
place, other life style changes should be discussed as well.
* "GERD, pregnancy, breastfeeding, lactation, treatment, mucosal protectant,
potassium, competitive acid blocker, P-CAB, promotility, prokinetic" were
included for the search as keywords; why PPIs, H2RA, alginate, AA were not
included but other relatively less common medications were included such as P-
CAP etc?
* I do not agree with the treatment algorithms given by the authors. They are
very simplistic. According to those treatment algorithms, all GERDs should be
treated with the same approach irrespective from the severity of symptoms. A
pregnant 
woman with a mild symptom once a week should be treated differently
than a pregnant "patient" with much more severe symptoms. 
* "Potential adverse effects which have been associated with long-term PPI use
includes kidney disease, dementia, bone fracture, myocardial infarction,
infections, micronutrient deficiencies, and gastrointestinal malignancies [31].
Many studies refused those side effects esp cancers, kidney disease, dementia,
myocardial infarction. It is not possible to mention a clear relation under the
knowledge of current literature. This data is also not related with the focus of the
manuscript.
* This study is about only prolactin secretion (Anderson PO. Treating
gastroesophageal reflux and heartburn while breastfeeding. Breastfeed Med.
2018;13(7):463). There is clearly no data regard to justify this conclusion
"Different H2RAs are excreted in breast milk at lower amounts than the doses
administered to infants" or following paragraph if there is any other study
supporting the hypothesis. 
* I had a hard time to find the original version of this study which finally found;
"In a study involving 12 mothers taking pantoprazole, pantoprazole was
undetectable for 80% of the day. The highest concentration of pantoprazole in
breast milk after 7 days of therapy was only 150 
μ
g/L on average [38]".The
refererence mentioned by the authors is wrong and a review article. This is the
correct one. Bor S, Karacaoglu S, Ergun P, et al. The levels of pantoprazole in
human breast milk and plasma: Two compartment model. Neurogastroenterol
Motil 2017;29:79-80. Abstract. doi:10.1111/nmo.13180. 
* This sentence is not clear; "Promotility drugs enhances gastric emptying,
which reduces the time that gastric acids sits in the stomach". Does it mean acid
pocket?
* Metoclopramide is also related with QT prolongation especially drugs with
similar side effects. This should be mentioned. 
* References at table 1 belong to review articles not to the specific references. 
* "acid taste in mouth" is not within the typical symptoms of GERD although it
is commonly referred in Far East studies. 
* There are much better figures regarding the acid pocket in the literature.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
No
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