Dear Dr Stock,

Thank you for submitting your manuscript entitled "Racial Differences in the Association of Low Apgar Scores and Mortality in the United States: a cohort study of 6,809,653 infants" for consideration by PLOS Medicine.

Your manuscript has now been evaluated by the PLOS Medicine editorial staff and I am writing to let you know that we would like to send your submission out for external peer review.

However, before we can send your manuscript to reviewers, we need you to complete your submission by providing the metadata that is required for full assessment. To this end, please login to Editorial Manager where you will find the paper in the 'Submissions Needing Revisions' folder on your homepage. Please click 'Revise Submission' from the Action Links and complete all additional questions in the submission questionnaire.

Please re-submit your manuscript within two working days, i.e. by Dec 14 2021 11:59PM.

Login to Editorial Manager here: https://www.editorialmanager.com/pmedicine

Once your full submission is complete, your paper will undergo a series of checks in preparation for peer review. Once your manuscript has passed all checks it will be sent out for review.

Feel free to email us at plosmedicine@plos.org if you have any queries relating to your submission.

Kind regards,

Beryne Odeny

PLOS Medicine

Dear Dr. Stock,

Thank you very much for submitting your manuscript "Racial Differences in the Association of Low Apgar Scores and Mortality in the United States: a cohort study of 6,809,653 infants" (PMEDICINE-D-21-05026R1) for consideration at PLOS Medicine.

Your paper was evaluated by a senior editor and discussed among all the editors here. It was also sent to independent reviewers, including a statistical reviewer. The reviews are appended at the bottom of this email and any accompanying reviewer attachments can be seen via the link below:

Considering these reviews, we would be grateful if you could please revise your manuscript to respond to comments raised by reviewers. We would strongly recommend that you pay special attention to the reviewer #2's comments regarding the premise of your research question and your approach. Please note that further consideration is dependent on the submission of a manuscript that addresses all reviewer concerns.

[LINK]

In light of these reviews, I am afraid that we will not be able to accept the manuscript for publication in the journal in its current form, but we would like to consider a revised version that addresses the reviewers' and editors' comments. Obviously we cannot make any decision about publication until we have seen the revised manuscript and your response, and we plan to seek re-review by one or more of the reviewers.

In revising the manuscript for further consideration, your revisions should address the specific points made by each reviewer and the editors. Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments, the changes you have made in the manuscript, and include either an excerpt of the revised text or the location (eg: page and line number) where each change can be found. Please submit a clean version of the paper as the main article file; a version with changes marked should be uploaded as a marked up manuscript.

In addition, we request that you upload any figures associated with your paper as individual TIF or EPS files with 300dpi resolution at resubmission; please read our figure guidelines for more information on our requirements: http://journals.plos.org/plosmedicine/s/figures. While revising your submission, please upload your figure files to the PACE digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at PLOSMedicine@plos.org.

We expect to receive your revised manuscript by Mar 31 2022 11:59PM. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

We ask every co-author listed on the manuscript to fill in a contributing author statement, making sure to declare all competing interests. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. If new competing interests are declared later in the revision process, this may also hold up the submission. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT. You can see our competing interests policy here: http://journals.plos.org/plosmedicine/s/competing-interests.

Please use the following link to submit the revised manuscript:

https://www.editorialmanager.com/pmedicine/

Your article can be found in the "Submissions Needing Revision" folder.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

We look forward to receiving your revised manuscript.

Sincerely,

Beryne Odeny,

PLOS Medicine

plosmedicine.org

-----------------------------------------------------------

Requests from the editors:

1) Please revise your title according to PLOS Medicine's style. Your title must be nondeclarative and not a question. It should begin with main concept if possible. Please place the study design in the subtitle (i.e., after a colon), e.g., a retrospective cohort study.

2) Please include line numbers in your next draft.

3) Is there a chance you can obtain more recent data from this setting?

4) Please conclude the “Introduction” with a clear description of the study question or hypothesis. The description of the database can be moved to the methods section.

5) Abstract:

a) Please ensure that all numbers presented in the abstract are present and identical to numbers presented in the main manuscript text.

b) Please quantify the main results (please present both 95% CIs and p values).

c) In the last sentence of the Abstract Methods and Findings section, please describe the main limitation(s) of the study's methodology.

6) At this stage, we ask that you include a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract. Please see our author guidelines for more information: https://journals.plos.org/plosmedicine/s/revising-your-manuscript#loc-author-summary

7) Did your study have a prospective protocol or analysis plan? Please state this (either way) early in the Methods section.

a) If a prospective analysis plan (from your funding proposal, IRB or other ethics committee submission, study protocol, or other planning document written before analyzing the data) was used in designing the study, please include the relevant prospectively written document with your revised manuscript as a Supporting Information file to be published alongside your study, and cite it in the Methods section. A legend for this file should be included at the end of your manuscript.

b) If no such document exists, please make sure that the Methods section transparently describes when analyses were planned, and when/why any data-driven changes to analyses took place.

c) In either case, changes in the analysis-- including those made in response to peer review comments-- should be identified as such in the Methods section of the paper, with rationale.

8) Thank you for providing the STROBE checklist as Supporting Information.

a) Please add the following statement, or similar, to the Methods: "This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline (S1 Checklist)."

b) When completing the checklist, please use section and paragraph numbers, rather than page numbers.

9) In your statistical analyses, please account for clustering of observations at hospital and county levels. Generalized Estimating Equations (GEE) or hierarchical/ multilevel models, among others, may be useful in this case.

10) Did you adjust for maternal comorbidity or medication use? If not, please consider this or acknowledge the lack of adjustment as a limitation

11) Please provide p values in addition to 95% CIs in the main text and tables

12) Please define the abbreviations in Tables and Figures e.g, GED, BMI, SD

13) Please remove the “Role of the funding source”, “Data sharing”, and “conflict of interest” statement in the methods section. This information is captured in the metadata obtained in the submission form

14) Please remove the “Competing Interests”, “Data availability,” and “Funding” statements at the end of the main text. This information is captured in the metadata obtained in the submission form.

15) References:

a) Please select the PLOS Medicine reference style in your citation manager. In-text reference call outs should be presented as follows noting the absence of spaces within the square brackets, e.g., "... services [1,2]."

b) References should have no more and no less than six names before et al. For references with more than six names, please ensure that et al., is inserted after six names

c) Please ensure that journal name abbreviations consistently match those found in the National Center for Biotechnology Information (NCBI) databases. https://journals.plos.org/plosmedicine/s/submission-guidelines#loc-references.

Comments from the reviewers:

Reviewer #1: Thank you for the opportunity to review this manuscript. This is overall a well written paper.

1. My comments are mainly related to the test of interactions. By using stratified analysis, the author claims that the association between Apgar scores and mortality varies across racial groups. However, whether the difference in the association between Apgar scores and mortality across racial groups is statistically significant or not has not been tested or presented. In order to acheive this, the author may need to used the adjusted model with interaction beteeen Apgar Score category and racial group. With one racial group as a reference group, ratio of AOR needs to be tested and presented.

2. The resoluiton of Figure 2 needs to be increased.

Reviewer #2: This study examines assess whether the association between low Apgar score and mortality in infants varies across racial groups.

This is a well written paper, and the analysis appears to be appropriate (having said this I would recommend that the paper is reviewed by a statistical reviewer).

The sample size is of course impressive - but I am afraid that this cannot remedy the other concerns I have with the paper.

A large part of the introduction is making the argument that while Apgar scores have been widely used and are highly predictive of infant mortality, the scores have largely been developed and validated in White populations. I suspect the authors are speaking about predictive validity - mortality. If so, this is of course an important issue. The authors also talk about validating the scores to assess infant status at birth. This is of course an entirely different matter and would involve a study comparing the gold standard judgement (presumably conducted by a physician) with the scores recorded on a birth chart/card. The authors even describe how Black infants have been shown to be assigned lower Apgar scores than White infants. This was reinforced by the later description of how there was a lack of research on the 'racial differences in the applicability of the scores..".

Reading this, I was inclined to conclude that validating Apgar scores (not just predictive validity) or trying to understand these differentials might be the focus of the study. But this is not the case. The paper, in my reading simply shows that in a country where Black infants are twice as likely to die as White infants (cited by the authors) that Apgar scores predict this and that Non-Hispanic Black and Non-Hispanic Other groups have higher odds of being assigned a low score. Without wishing to sound dismissive - how is this interesting? Is that not exactly what would be expected.

Had the paper been set up to show how systematic racism was implicated in the assigning of Apgar scores - i.e. higher or lower scores compared to gold standard and compared to other race groups - now that would be really interesting. If the study was able to show how Apgar scores differed by race from gold standard (irrespective of infant birth status) - that would be interesting.

As a result I do not think the paper passes muster in terms of novelty for a public health journal of the stature of PLOS Medicine. It should definitely be published but perhaps in a specialist journal such as an Obstetric journal.

Reviewer #3: Thank you for the opportunity to review this manuscript. In this paper, the authors examine the association of low Apgar scores and infant mortality across different racial groups using vital statistics data of infants born in the US. The paper finds that the five-minute Apgar score is strongly associated with infant mortality but identified differences in the strength of association between across different racial groups. Specifically, the strength of association between low Apgar score and mortality was reduced in Black and non-Hispanic non- Asian groups suggestive of reduced predictive ability of mortality in these groups.

The authors have examined an important topic that could make a significant contribution to the literature. The study has some significant implications for the interpretation and applicability of Apgar scores and their prediction of mortality across different racial groups.

Overall, this is a good paper but could be improved by being more in-depth in its descriptions and analysis of the findings and the meaning of the results as currently some sections are quite superficial. The methods section could be more detailed and the results section is currently very brief. The authors need to more specifically outline what the findings mean for the application and use of Apgar scores across different racial groups apart from stating that caution should be taken when interpreting the scores. I was expecting to see a section on why was the study done, what do these findings mean etc. to really highlight the key takeaway points - this would be helpful in drawing out the key findings of this paper as well.

More attention should be paid to detail as there were repeating text in the manuscript and parts that have not been updated after previous revisions (e.g STROBE statement page numbers)

I have made some further specific comments below for the authors consideration to revise the manuscript.

Specific comments

ABSTRACT

p2, Methods and findings: The detailed description in the results of how many infants of each race were included and excluded cases is not essential for the abstract. Perhaps you can keep the % and drop the n. I would suggest to review this and focus on presenting the most important results.

INTRODUCTION

p3, para 1-2: I would recommend the text in paragraph 2 of the introduction be moved up into paragraph 1 (after the first sentence) and the detail about the Apgar score from the second sentence be moved down into a separate paragraph. This is so the problem your study is investigating is upfront. The detail of the components of Apgar score is not so important that it needs to be in the first paragraph.

p4, para 2: missing word - "and" before "discrimination"

p5, para 1: The last sentence of the introduction ("The database consists of…") is not essential here and would be more appropriate in the methods section where a description of the data source is provided.

METHODS

The ethics sub-section can be placed towards the end of the methods section. The ethics statement is also repeated in the Study Population section at the beginning of page 4. This can be removed.

The methods section does not follow the STROBE checklist and the page numbers in the checklist do not match the current manuscript (e.g there is no Study Design section in the methods but the checklist in the Appendix indicates it is on pages 8-11 in the manuscript). This should be the first section or combined with study population. I would suggest the authors structure the methods section using similar headings to the strobe statement. The "Database" sub-heading should be "Data sources" for example.

Also, the current STROBE statement checklist is missing the first column that indicates which section of the manuscript the information can be found.

p7, para 2: Outcomes, exposures, covariates - this section needs to be better organised. I would suggest describing the outcome variable first followed by the explanatory variables.

p8, top paragraph: There is a bit of a mix up or description of analysis and variables in this section as well - the part on what was adjusted for should be in the analysis section but the definition of the variables should remain in this section. Handling of missing values also belongs in the analysis section.

Figure 1: please improve the quality of the flow diagram (font is currently blurred) and consider reducing amount of text and perhaps include the use of boxes.

RESULTS

p10, para 1: All of the numbers and % in the table do not need to be repeated in the text. Suggest to mention the % for race without the numbers in the text.

On the other hand, on p13 there is no description of the magnitude of the odds described at all. Instead of stating that there is only a lower or higher odds, the authors can be more specific - for example, "…non-Hispanic black infants had almost two times higher odds of being assigned a low Apgar score…" Otherwise the information in the text is not very informative.

p15-16. Please indicate which table the statement made in the third sentence in paragraph 1 is located.

There is no need to describe the chi-square test here - this belongs in the methods/analysis section.

The main results/tables of your study are in the Appendix - I would suggest to move (some) of these to the main manuscript. The unadjusted analyses I would think were less important and could be in the appendix.

Overall, the description of your results is very brief given the amount of results and tables included.

Tables S6-S8 in the Appendix need to be fit to the page as the last columns are cut off. Suggest to include the word documents with the original tables rather than an image.

DISCUSSION

p16, first para: The first paragraph of a discussion should highlight the most important findngs of the paper. However the authors describe the unadjusted results.

Please also avoid repeating results but rather explaining or interpreting the data in the discussion

Reviewer #4: Thanks for allowing me to review your very interesting manuscript. I have several comments, and some questions which may lead to some revisions.

1. I am curious as to why you excluded births to mothers under the age of 15? Whilst the numbers are likely to be small they are a high-risk group, more likely to have births of compromised babies due to fetal growth restriction and other problems of placental dysfunction. I note that you did include women who did not complete 8th grade at school and if this group is included then perhaps the very young should also be there. Could you elaborate on your reasons for their exclusion?

2. Similarly, the inclusion of births up to 44 + 6 weeks of gestation is unusual as this might imply a problem of data accuracy. Even without intervention, which is almost universal now before 42 + 6 weeks, very few pregnancies would progress beyond 43 weeks and certainly not beyond 44. Why such a high figure?

3. What is the origin of the list of congenital abnormalities that have been excluded? It contains many obvious severe conditions (e.g., anencephaly) but also some others which are quite common and not really associated with infant mortality (e.g., hypospadias).

4. I noted that the explanation about the exemption from full ethics review is repeated in the sections on Ethics and Study Population which is a duplication.

5.The overall smoking rates are much lower than I would have expected (6.8%). In my own country (Australia) we are still seeing rates of 10-15% overall, and these vary a lot between different ethnic groups. Can you comment on this, and if you can validate this figure against any other data source? As it is a risk factor for both neonatal and infant mortality it is important to get this right in any analysis, especially when calculation the adjusted OR.

6. Finally, I am curious as to the predictive value of the Apgar scores for both neonatal mortality (the original use) and later infant mortality. Whilst some causes of infant mortality are linked to conditions which have their origins in the perinatal period many others are not necessarily linked (e.g. trauma, drowning etc). Have you looked separately at the infant deaths which occur beyond 28 days (about 50% of the total cohort of deaths), rather than including all deaths in the infant mortality numbers, which includes the early and late neonatal ones

Reviewer #5: Thank you for the opportunity to review this manuscript. Overall the analyses are well conducted and the manuscript well written. I have a few minor edits to suggest:

1. The following text should be combined combined with the Inclusion and Exclusion Criteria to make a single continuous paragraph on study population, which also means that the gestational age criteria do not need to be stated twice:

"Study Population

This population cohort study evaluated singleton infants born between 37+0 and 44+6 weeks between January 1, 2016 and December 31, 2017 in the United States."

2. The 2nd sentence of the Study Population paragraph should be added to the Database paragraph: "All data were nonidentifiable and publicly available through the NCHS Division of Vital Statistics and complied with the NCHS, Centers for Disease Control and Prevention (CDC) Data User 6

Agreement Terms and Conditions.23,24"

3. The rest of the Study Population paragraph is an exact repeat from the Ethics paragraph and should be deleted, except the last sentence on Strobe reporting guidelines which can be moved to the end of the methods section.

4. I did not quite follow the logic for the following: "the findings suggest that the odds of mortality based on a low Apgar score are underestimated in these groups" and suggest this statement be deleted. The remainder of the discussion and conclusion are much clearer in their interpretations.

Any attachments provided with reviews can be seen via the following link:

[LINK]

Dear Dr. Stock,

Thank you very much for re-submitting your manuscript "Associations between low Apgar scores and mortality by race in the United States: a cohort study of 6,809,653 infants" (PMEDICINE-D-21-05026R2) for review by PLOS Medicine.

I have discussed the paper with my colleagues and it was also seen again by three reviewers. I am pleased to say that provided the remaining editorial and production issues are dealt with we are planning to accept the paper for publication in the journal.

The remaining issues that need to be addressed are listed at the end of this email. Any accompanying reviewer attachments can be seen via the link below. Please take these into account before resubmitting your manuscript:

[LINK]

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

In revising the manuscript for further consideration here, please ensure you address the specific points made by each reviewer and the editors. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments and the changes you have made in the manuscript. Please submit a clean version of the paper as the main article file. A version with changes marked must also be uploaded as a marked up manuscript file.

Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. If you haven't already, we ask that you provide a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract.

We expect to receive your revised manuscript within 1 week. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

We ask every co-author listed on the manuscript to fill in a contributing author statement. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT.

Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript.

Please note, when your manuscript is accepted, an uncorrected proof of your manuscript will be published online ahead of the final version, unless you've already opted out via the online submission form. If, for any reason, you do not want an earlier version of your manuscript published online or are unsure if you have already indicated as such, please let the journal staff know immediately at plosmedicine@plos.org.

If you have any questions in the meantime, please contact me or the journal staff on plosmedicine@plos.org.  

We look forward to receiving the revised manuscript by May 17 2022 11:59PM.   

Sincerely,

Beryne Odeny,

PLOS Medicine

plosmedicine.org

------------------------------------------------------------

Requests from Editors:

1) Abstract:

a) Please structure your abstract using the PLOS Medicine headings (Background, Methods and Findings, Conclusions).

b) Please combine the Methods and Findings sections into one section, “Methods and findings”

c) In the last sentence of the Abstract Methods and Findings section, please describe the main limitation(s) of the study's methodology

Comments from Reviewers:

Reviewer #1: Thank you for addressing reviewers' comments and improving the manuscript. My questions in the previous round has been suffuciently answered.

1. In Table 2 and Table 3, why there's only one p-value for multiple tests for interaction? For instance, in Table 2, there should be seperate p-values for Non-Hispanic white vs Hispanic, and Non-Hispanic white vs Non-hispanic black. In table 3, there should be p-value for normal vs intermedaite comparison, and p-value for normal vs low comparison.

2. According to the Office of Management and Budget Standars for the Classification of Federal Data on Race and Ethnicity, Hispanic ethnicity is recorded as distinct from race. In this paper, the author used different category and treated Hispanic as a mutually exclusive racial group from other racial groups. Explanation is needed for the selction of the categories for the analysis.

Reviewer #2: The authors have responded to reviewer comments

Reviewer #3: Thank you to the authors for their efforts to address the comments and revise the manuscript. The revisions made have improved the manuscript somewhat but I'm afraid there remain some substantial issues which need to be addressed particularly in relation to the methods section and discussion. I have outlined these below:

Minor revisions

ABSTRACT

Line 45 - Stating the limitations is not needed in the abstract

Line 49 (findings) - In the sentence, "A total of 6, 728,829 infants…" the percentages should be included after the numbers for easier interpretation. It's not clear why they were removed from the previous version.

Line 52 - abbreviations (AOR) are usually not used in an abstract - please check with journal requirements. As it is not used multiple times in the abstract it may not be necessary.

AUTHORS' SUMMARY

This is a very nice overall summary. Just one small suggestion:

Line 90 - please remove the "n" as it doesn't add anything here and it is stated clearly in the title of the paper.

Major revisions

METHODS

The methods section needs reorganisation - grouping study design, setting and participants is not following the STROBE guidelines and these are all very different topics, especially participants (study setting may not be needed). This section now also discusses the exclusion and inclusion criteria.

There are now two sections with the heading of "variables" one called "quantitative variables" - all Generally, there should be description of the variables - dependent and independent. The statistical analysis should be separate. Please closely review the STROBE guidelines and other similar papers for order and content of the methods section.

I do not have statistical expertise but is this multivariable regression not multivariate?

Line 213 (Statistical methods and Quantitative Variables) - Please separate out this section into paragraphs as it is too long as one piece of text.

Line 251 - this statement on STROBE should be at the beginning of the methods not in the Ethics statement.

RESULTS

All of the figures are still very low quality and not clear.

Table 1 - this table is very hard to read and has no lines - please format and add some spacing between the variables.

DISCUSSION

There seems to be a disconnect between the first paragraph of the discussion and the author's summary around the implications of the findings. The discussion is very positive and supportive of the Apgar score while the Authors' summary is more critical indicating that Apgar scores are less useful among non-White populations. The overall conclusions should be based on the results only and need to be consistently communicated throughout the paper.

In my previous review I indicated that the authors should avoid only restating the results in the discussion but instead elaborate on what their results mean. Instead of doing this the text was just removed. The discussion cannot consist only of a summary and implications. The results need to be discussed more adequately and critically.

Any attachments provided with reviews can be seen via the following link:

[LINK]

Dear Dr. Stock,

Thank you very much for re-submitting your manuscript "Associations between low Apgar scores and mortality by race in the United States: a cohort study of 6,809,653 infants" (PMEDICINE-D-21-05026R3) for review by PLOS Medicine.

I have looked at the paper and it was also seen again by one reviewer. I am pleased to say that provided the remaining minor editorial and production issues are dealt with we are planning to accept the paper for publication in the journal.

The remaining issues that need to be addressed are listed at the end of this email. Any accompanying reviewer attachments can be seen via the link below. Please take these into account before resubmitting your manuscript:

[LINK]

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

In revising the manuscript for further consideration here, please ensure you address the specific points made by each reviewer and the editors. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments and the changes you have made in the manuscript. Please submit a clean version of the paper as the main article file. A version with changes marked must also be uploaded as a marked up manuscript file.

Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. If you haven't already, we ask that you provide a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract.

We expect to receive your revised manuscript within 1 week. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

We ask every co-author listed on the manuscript to fill in a contributing author statement. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT.

Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript.

Please note, when your manuscript is accepted, an uncorrected proof of your manuscript will be published online ahead of the final version, unless you've already opted out via the online submission form. If, for any reason, you do not want an earlier version of your manuscript published online or are unsure if you have already indicated as such, please let the journal staff know immediately at plosmedicine@plos.org.

If you have any questions in the meantime, please contact me or the journal staff on plosmedicine@plos.org.  

We look forward to receiving the revised manuscript by Jun 07 2022 11:59PM.   

Sincerely,

Beryne Odeny,

Senior Editor 

PLOS Medicine

plosmedicine.org

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Requests from Editors:

1. Abstract: please revise the subheading "Interpretation" to "Conclusion" in line with PLOS Medicine's style

2. Discussion section: please delete the subheadings including "Findings in context", "Implications" and "Strengths and Limitations"

Comments from Reviewers:

Reviewer #3: Thank you to the authors for the revisions to the manuscript. The paper is now much clearer and flows well. I have no further comments on this version.

I look forward to seeing this published.

Any attachments provided with reviews can be seen via the following link:

[LINK]

Dear Dr Stock, 

On behalf of my colleagues and the Academic Editor, Dr. Mark Tomlinson, I am pleased to inform you that we have agreed to publish your manuscript "Associations between low Apgar scores and mortality by race in the United States: a cohort study of 6,809,653 infants" (PMEDICINE-D-21-05026R4) in PLOS Medicine.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. Please be aware that it may take several days for you to receive this email; during this time no action is required by you. Once you have received these formatting requests, please note that your manuscript will not be scheduled for publication until you have made the required changes.

In the meantime, please log into Editorial Manager at http://www.editorialmanager.com/pmedicine/, click the "Update My Information" link at the top of the page, and update your user information to ensure an efficient production process. 

PRESS

We frequently collaborate with press offices. If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximise its impact. If the press office is planning to promote your findings, we would be grateful if they could coordinate with medicinepress@plos.org. If you have not yet opted out of the early version process, we ask that you notify us immediately of any press plans so that we may do so on your behalf.

We also ask that you take this opportunity to read our Embargo Policy regarding the discussion, promotion and media coverage of work that is yet to be published by PLOS. As your manuscript is not yet published, it is bound by the conditions of our Embargo Policy. Please be aware that this policy is in place both to ensure that any press coverage of your article is fully substantiated and to provide a direct link between such coverage and the published work. For full details of our Embargo Policy, please visit http://www.plos.org/about/media-inquiries/embargo-policy/.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Thank you again for submitting to PLOS Medicine. We look forward to publishing your paper. 

Sincerely, 

Beryne Odeny 

PLOS Medicine