PONE-D-24-05779EFFECT OF TOPICAL EMOLLIENT OIL APPLICATION ON WEIGHT GAIN OF PRETERM NEWBORNS: A SYSTEMATIC REVIEW AND META-ANALYSISPLOS ONE

Dear Dr. Getaneh,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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The manuscript under review is a critical and relevant systematic review, however the reviewers have highlighted some major concerns and I concur. I would suggest that the authors carefully respond to all the concerns raised by the reviewers (especially around missing studies) and revise the manuscript as suggested. I would also encourage the authors to give special consideration to the langauge and editing when resubmitting.

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Please submit your revised manuscript by Apr 25 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Rehana Abdus Salam

Academic Editor

PLOS ONE

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Additional Editor Comments:

The manuscript under review is a critical and relevant systematic review, however the reviewers have highlighted some major concerns and I concur. I would suggest that the authors carefully respond to all the concerns raised by the reviewers (especially around missing studies) and revise the manuscript as suggested. I would also encourage the authors to give special consideration to the langauge and editing when resubmitting.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: In this systematic review and meta-analysis, the authors reviewed the existing literature on the efficacy of topical applications of emollient application on weight gain in pre-term newborns. The application of topical emollients has been showing several benefits on preterm newborns and severely malnourished children in terms of weight gain, protection from infections, increased fatty acid levels, and reduced mortality. This systematic review and meta-analysis would generate substantial evidence on the efficacy of emollients on pre-term newborns' weight gain from global studies. This study followed a standard methodological technique to do a systematic review and meta-analysis. It is also well written, and the results are well presented. However, the authors need to consider the following suggestions to revise this manuscript to make it compatible for publication.

Comments:

1. There was a published systematic review by Rehana AS et al., 2013 ( DOI: 10.1186/1471-2458-13-S3-S31) that mentioned the efficacy of emollient therapy on newborns’ weight gain. The authors of this study should justify how this review would generate additional evidence and value over the previous article by Rehana AS et al.

2. The authors mentioned that the rationale of this study is to synthesise current evidence on interventions to improve survival outcomes in preterm infants, and emollient therapy would be one of the important management strategies. However, based on existing evidence of the beneficial effects of emollient therapy, the WHO has already recommended the application of ‘natural’ oils (e.g. sunflower and coconut oil) to the body of preterm or LBW infants to increase weight gain ( DOI: 10.1016/j.eclinm.2023.102155). Priority for further research has been set to “Which emollients (which oils, which composition) are most effective and safe? And their optimal regime (dose, frequency, duration) and mode of application” (DOI: 10.1016/j.eclinm.2023.102126). Thus, the authors should describe strong arguments on how the findings of this review study add further value to the scientific community.

3. The authors concluded with that “Therefore, Policymakers and health planners should

give great emphasis on implementation of the use of emollient oils in the routine care of preterm infants to assist with weight gain..” As per my previous comment, the policy makers ( e.g. WHO) has already considered and recommended emollient therapy in to a standard management therapy. The author should mention what further benefit can be achieved from this study.

4. The study included 17 articles published between 2000 to July 2023. But I wonder if they missed more important RCTs on this topic that were published in this time frame. For example, Kumar V et al, 2022 (doi: 10.1093/ajcn/nqab430.); Sankaranarayanan K, et al., 2005, PMID: 16208048; Kumar J et al, 2012 (DOI: 10.1007/s12098-012-0869-7). Authors should revise their search and include all missed articles.

5. The authors did the pooled analysis on the mean weight gain after emollient therapy, and it showed significant results. However, their studies were highly heterogeneous. They differ in terms of emollient type, duration and dose. Thus, it may reduce the strength of the study results. Although the authors did subgroup analysis on the pooled analysis, the sample size is too low to strengthen the results. For example, the coconut oil group had two studies, 5ml/kg/day oil group had two studies.

6. The authors did a quality evaluation of the studies by using the Cochrane Risk of Bias Tool for Randomized Controlled Trials (Higgins et al., 2011), which is an old tool. The ‘RoB 2’ has been revised in August 2019. So, the author should use the updated tool for a better acceptability of their methodology.

7. As the authors mentioned, the weight gain is multifactorial. Yes, it depends on the combination of the type of emollient oil, its dose and duration. Pooled analysis on homogenous methodological studies can further refute the findings of this study. Thus, research priority has been set to assess the efficacy of the best emollient oil across all available oils for a specific dose and duration. The authors should describe this point, describe the weakness of the heterogeneous study analysis, and come up with some recommendations for future RCTs.

Reviewer #2: The authors of ‘Effect Of Topical Emollient Oil Application On Weight Gain Of Preterm Newborns: A Systematic Review And Meta-Analysis’ have worked on a relevant topic and the review is well performed but my major concern is that this would need thorough language correction and editing.

Other comments

The background does not cite all the previous systematic reviews that have been done for this intervention looking at weight and also other outcomes.

Rationale for this systematic review needs to be strengthened

Methods should start with objectives

The authors should mention that how many authors were contacted for full texts and missing data and how many responded

Was ROB 1 used or ROB 2 used for quality assessment.

Methods should define the planned sub-groups

What was the time or age at which weight was measured.

For conclusion, the authors need to make the clinical relevance of about 50g gain in weight and also mention that over what time this change occurred.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-24-05779R1EFFECT OF TOPICAL EMOLLIENT OIL APPLICATION ON WEIGHT GAIN OF PRETERM NEWBORNS: A SYSTEMATIC REVIEW AND META-ANALYSISPLOS ONE

Dear Dr. Getaneh,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

I would like to thank the authors for revising the draft based on reviewers feedback. The draft reads significantly better, however, I think that there are still three major points for authors consideration before the manuscript can be considered for publication. I would suggest that the authors address the three major concerns under the heading of 'Overall comments' and also consider some minor revisions below:

OVERALL: 

1. I would like the authors to address one of the comments from the reviewers on the clinical significance of the difference in mean weight of 52 gms from a policy perspective. The reviewer commented that "I would like the authors to still make the clinical relevance of about 50g gain in weight and also mention that over what time this change occurred. This is important before advocating for its recommendation." Authors can disucss this finding in the 'Discussion' section and frame the conclusion accordingly.

2. In the abstract and the methodology section, the authors have referred to the outcome of interest as 'weight gain' rather than 'weight'. I suggest that the authors refer to the outcome of interest as 'weight' since the outcome of interest is 'weight' and not 'weight gain'. 'weight gain' was a finding of the review.

3. The PRISMA checklist requires the authors to report assessments of certainty (or confidence) in the body of evidence for each outcome assessed. However, the authors have not reported GRADE certainity of the outcomes. I would suggest that the authors assess and report the certainity of evidence for the outcomes of interest.

==============================

Please submit your revised manuscript by May 26 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Rehana Abdus Salam

Academic Editor

PLOS ONE

Additional Editor Comments:

I would like to thank the authors for revising the draft based on reviewers feedback. The draft reads significantly better, however, I think that there are still three major points for authors consideration before the manuscript can be considered for publication. I would suggest that the authors address the three major concerns under the heading of 'Overall comments' and also consider some minor revisions below:

OVERALL:

1. I would like the authors to address one of the comments from the reviewers on the clinical significance of the difference in mean weight of 52 gms from a policy perspective. The reviewer commented that "I would like the authors to still make the clinical relevance of about 50g gain in weight and also mention that over what time this change occurred. This is important before advocating for its recommendation." Authors can disucss this finding in the 'Discussion' section and frame the conclusion accordingly.

2. In the abstract and the methodology section, the authors have referred to the outcome of interest as 'weight gain' rather than 'weight'. I suggest that the authors refer to the outcome of interest as 'weight' since the outcome of interest is 'weight' and not 'weight gain'. 'weight gain' was a finding of the review.

3. The PRISMA checklist requires the authors to report assessments of certainty (or confidence) in the body of evidence for each outcome assessed. However, the authors have not reported GRADE certainity of the outcomes. I would suggest that the authors assess and report the certainity of evidence for the outcomes of interest.

ABSTRACT:

1. The last sentence of the background and first sentence of the methods section are redundantly stating the objective of the review. I would suggest that the authors state the objective only once (either in background or methods) in the abstract.

2. I would suggest rephrasing 'pooled mean weight gain difference' to 'pooled difference in mean weight gain'.

INTRODUCTION:

1. I would suggest authors use standard format of referencing when referring to the previous review, hence either use the last name of the first author (Salam R.A etal) or remove the review authors' name from the sentence to state that "A systematic review conducted in 2013 found that emollient therapy......".

2. I would suggest that the authors move the refereence to the previous systematic review by Salam et al. at the end of the third paragraph to bring all the evidence together for the reader to get an overall background.

METHODS:

1. Correct: 'Publication status: published articles or grey literature'

2. Correct:'the outcome of interest: all research articles that investigated the effect of emollient oil on preterm neonates' weights were included.'

3. Correct: 'Outcome - weight'

4. Correct: 'Additionally, cross-reference search was carried out to include other related studies from ......'.

5. Please add a reference for the Rayan online software.

6. I would suggest that the authors add references to the six articles excluded from the final analysis because the unavailability of the full texts.

7. Primary outcome: 'Estimate the effect of emollient application on weight in preterm newborns (mean difference in grams).'

RESULTS:

1. Correct: 'The primary focus of these studies was to examine the effect of emollient oil therapy on weight in preterm neonates'

2. Characteristics of included studies: I would suggest that the authors specify the range of the mean gestational age as well as the baseline mean weight of the preterm babies from the included studies. These could potentially add context to the heterogeinity in the results.

3. I would suggest that the authors incorporate evidence certainity in the results section.

DISCUSSION:

1. I would suggest authors add some discussion around certainity of evidence for the outcomes reproted.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: The authors have significantly addressed the comments and improved the manuscript.

I would like the authors to still make the clinical relevance of about 50g gain in weight and also mention that over what time this change occurred. This is important before advocating for its recommendation.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (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. Registration is free. 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 PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

EFFECT OF TOPICAL EMOLLIENT OIL APPLICATION ON WEIGHT OF PRETERM NEWBORNS: A SYSTEMATIC REVIEW AND META-ANALYSIS

PONE-D-24-05779R2

Dear Dr. Getaneh,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Rehana Abdus Salam

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: