PONE-D-25-01288Differential linear brain growth patterns in preterm neonates based on birth gestational age and steroid exposure: A retrospective chart reviewPLOS ONE

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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: Yes

Reviewer #2: Partly

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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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: No

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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: This is an extremely instructive research on the differences in brain growth between extremely preterm infants and very preterm infants. I will only point out the issues that might be problematic, in my honest opinion.

- Line 47 – please, add ”at term equivalence”, either at the end of the conclusion or at the beginning

- Line 99 and lines 297-298 – moderately preterm infants have a GA of 32-33 weeks and late preterm infants have GAs of 34-36 weeks. This is also the way the cited resource uses the classification

- Line 100 – please add ”in these infants” to the next sentence (”Moreover, in these infants there is an association […]”)

- Line 173 – I believe the authors mean ”≥” instead of ”>”, otherwise I wonder where are the infants needing only one dose of surfactant – not including those seem wrong on many levels

- For Table 1 and the Figures – I recommend the authors stop using Group 1 and Group 2 and keep using EP(I) and VP(I), it becomes confusing which is which

- Table 1 and lines 201-207 – I strongly recommend the authors use SGA instead of IUGR, as the definition they use is that of SGA. Later on, in the Discussions section (lines 327-338), they may admit to using the term SGA as a proxy for fetal/intrauterine growth restriction

- Just out of personal curiosity: is the reason listed in lines 361-364 also valid for the small number of VP infants? I was intrigued when first reading the manuscript by the number of VPI, which is smaller that the number of EPI, it is usually the other way round... or is it another reason for the disproportionate groups? I think the authors should at least attempt to explain this

- In Figures 1 and 3 – please, correct ”Corpus callosum”

Reviewer #2: I appreciate the opportunity to review this interesting manuscript on brain growth between EP and VP using a large study population. However, it seems to have several significant problems as below.

Major points

1. Abstract: The conclusions didn’t include the effect of antenatal steroids, but the title included that. It is better to be unified.

2. Introduction: The rationale for the aims of this study should be clarified by citing adequate papers. The effect of antenatal steroids on brain growth in preterm infants has already been reported in a few studies; doi: 10.1016/j.ejogrb.2024.08.034., doi: 10.1542/peds.2004-0326.etc. Then, please describe any new findings that the authors have tried to add.

2. Study design: The authors should show the flowchart of the study population. Were the placental abruption included in this study?

3. Table 1: Information including histological amnionitis and funisitis also have some effect on neonatal brain growth. This information is necessary to understand the results of this study. Please show them.

4. Table 1: If two doses of antenatal steroids mean a complete course of antenatal steroids, the population seems too low (10.1% vs. 8.4 %). If it is correct, is the low prevalence of antenatal steroids common in Canada? Please describe and discuss it.

5. Results. (L225): What does ‘two or more antenatal corticosteroids’ mean? Two doses are a single complete course. If multiple courses are included, those populations should be divided into groups from a complete course of antenatal steroids.

6. Results. The authors also should show the Maternal and neonatal characteristics regarding the comparison shown in Table 2.

7. Results. (L244-251): It is confusing. Did the authors compare the data between single

255 versus no exposure, which is shown in Table 2. The sentences described the comparison between none or one dose of steroids versus a complete course of antenatal steroids.

8. Results. The population of a complete course of antenatal steroids (n=31) is too small to adjust for seven factors, including antenatal steroids, sex, gestational age, bronchopulmonary dysplasia, intraventricular hemorrhage(Grade 1-2), hemodynamically significant patent ductus arteriosus, sepsis. Please consult a statistician. Then the authors should discuss the limitations of this study.

9. Discussion. It is too long. Please focus on the results of this study and explain straightforwardly.

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Reviewer #1: Yes:  Andreea AVASILOAIEI

Reviewer #2: No

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Differential linear brain growth patterns in preterm neonates based on birth gestational age and steroid exposure: A retrospective chart review

PONE-D-25-01288R1

Dear Dr. Goyal,

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.

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Kind regards,

Kazumichi Fujioka

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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: Yes

Reviewer #2: I Don't Know

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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

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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: All of my comments have been addressed. I believe the manuscript is suited to be published in the present form.

Reviewer #2: I appreciate your great effort to answer my questions. All concernes have been adequately addressed.

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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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