Dear Dr. Zhu,

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.

Please submit your revised manuscript by Feb 09 2026 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.. 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,

Kazumichi Fujioka

Academic Editor

PLOS One

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“National Key Research and Development

Program of China, Grant/Award Number:

2022YFC2703500; 4+X Clinical Research

Project of Women's Hospital, School of

Medicine, Zhejiang University,

Grant/Award Number: ZDFY2021‐4X205”

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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?

Reviewer #1: Partly

Reviewer #2: Yes

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

Reviewer #1: Yes

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??>

Reviewer #1: No

Reviewer #2: Yes

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Reviewer #1: Thank you for the opportunity to review the manuscript entitled “Postnatal cytomegalovirus infection and bronchopulmonary dysplasia in very low birth weight infants: influence of diagnostic criteria and viral load in a propensity score-matched cohort study”. This study addresses an important and clinically relevant issue in neonatal intensive care-the association between pCMV infection and BPD in VLBWIs. However, several major methogological and interpretive concerns should be addressed before its being considered for publication.

1.The manuscript needs careful writing editing. Many sentences contain grammatical mistakes and wrong sentence structure, which make the article difficult to understand.

2.Introduction: Necessary references need to be added to the concept of cCMV and pCMV.

3.Study population: I’m confused with the inclusion and exclusion criteria. What’s the protocol for CMV screening in the unit? Are there any changes in CMV screening during the 11-year period? When was CMV testing done for these pCMV infants?

4.Results: There is no need to repeat the data in the results in text, which have been shown in the tables very clearly. Are there any infants received Ganciclovir therapy?

5. Discussion: There is logistic problem in the first sentence of the last paragraph on Page 7. “but the 2001 NICHD standard shows significant differences in stratified diagnosis”, why “but” here?

6.The discussion on the high viral load and BPD is rather general and far fetched. More evidence should be provided to demonstrate the relationship between high CMV load and severity of BPD.

7.What are the possible infection routes for these pCMV infants?

8.In the limitations the author mentioned “the control group comprised both untested infants and those with negative test results”. I think there is a high probability of bias here, affecting the credibility of the results.

9.There are also a lot of formatting issue in the tables.

Reviewer #2: Thank you for the opportunity to review "postnatal cytomegalovirus infection and bronchopulmonary dysplasia in very low birth weight infants: influence of diagnostic criteria and viral load in a propensity score matched cohort study." The authors ask a novel study question of if postnatal CMV infection is associated with 3 clinically distinct definitions of BPD using propensity score matching and hypothesize that an association will be identified. The authors found that the association of pCMV infection with BPD was influenced by diagnostic criteria of BPD and that higher viral load was associated with more severe respiratory morbidity. These findings have biological plausibility and represent a potentially modifiable risk factor for BPD. Thank you for addressing my concerns.

Major concerns:

1) Matching was performed using GA, BW, SGA, sex, and birth year; however, even after matching, infants with pCMV had higher rates of late-onset sepsis, transfusion, steroid use, diuretic exposure, and longer respiratory support. These differences likely reflect underlying illness severity, which may simultaneously increase the probability of CMV testing and the risk of BPD. This limitation should be acknowledged more explicitly, and conclusions should avoid overstating causality. These imbalances also suggest notable residual confounding and potentially incomplete control of early illness severity. Did the authors consider using a more robust 1:2, 1:3, or 1:4 match? This more robust approach may improve the match and would strengthen the results. Alternatively, the authors could exact match on GA week, BW category/SGA status, sex, birth year, and use propensity score matching on a number of other variables to improve the causal inference of the study. In any case, the authors should provide balance diagnostics (i.e., standardized mean differences before and after matching) for the cohort to help the orient the reader to the strength of the results.

2) I think using a limited set of variables to perform the match with is justified in the sense that GA, BW, sex likely contribute the most to an infant's severity of illness and risk of BPD. However, did the authors consider whether additional early clinical factors available prior to CMV testing (i.e., early IMV, surfactant use, Apgar scores, early sepsis evaluations) should have been included?

3) Several adjusted covariates including transfusions, diuretics, glucocorticoids, and late-onset sepsis may occur after pCMV infection and therefore function as effect modifiers or mediators and not confounders. Globally, we do this all of the time in neonatology studies given the nature of the research and difficulty of parsing out time-varying covariates in our infants with outcomes at one point in time based on clinical diagnostic criteria as opposed to a pathologic diagnosis irrespective of time. However, including these variables may bias effect estimates. Did the authors consider a sensitivity analysis to only include variables that would occur before pCMV diagnosis?

Minor concerns:

1) The manuscript currently emphasizes that newer definitions “better capture” the severity attributable to pCMV. Although plausible, alternative explanations should be acknowledged such as the 2001 NICHD definition misclassifying infants on noninvasive respiratory support but low FiO2 as mild BPD. Alternatively, modern criteria classify infants based on respiratory support modality, which may track with prolonged illness trajectories regardless of pCMV etiology. Differences may reflect criteria sensitivity, not necessarily pathophysiologic differences. The discussion could be expounded upon with this nuance.

2) For the tables, please use a consistent case. For example Table 2, capitalize the first letter of the first word throughout. There are also numerous instances of variability in the authors referring to BPD severity as mild, moderate, or severe or Grade I-III (or 1-3 depending on the definition). Being consistent throughout would help the uninitiated reader.

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Reviewer #1: No

Reviewer #2: No

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NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

Dear Dr. Zhu,

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.

Please submit your revised manuscript by Apr 30 2026 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.. 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.

• A 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 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 . 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,

Kazumichi Fujioka

Academic Editor

PLOS One

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

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. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: All comments have been addressed

**********

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

Reviewer #2: Partly

**********

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

Reviewer #2: Yes

**********

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 #2: Yes

**********

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

Reviewer #2: Yes

**********

Reviewer #2: The revised manuscript is improved compared with the prior version. The authors have clarified several aspects of the analytic approach, particularly the matching strategy, and the inclusion of standardized mean differences (SMDs) before and after matching meaningfully improves the transparency of the analysis. The additional modeling framework incorporating pre-diagnosis clinical variables is also helpful and provides useful context for the primary findings. Overall, I believe the authors have made thoughtful revisions in response to the initial review.

However, I continue to have some concern regarding the specification of the matching strategy and the residual imbalance that remains in one of the matching variables. The current analysis matches on gestational age, birth weight, SGA status, sex, and birth year. Because SGA is intrinsically derived from the relationship between gestational age and birth weight, including all three variables simultaneously in the matching algorithm may introduce redundancy and may make it more difficult to achieve optimal covariate balance, particularly given the relatively small exposed cohort. Consistent with this concern, the post-matching balance diagnostics indicate that SGA remains the most imbalanced variable after matching, with a standardized mean difference exceeding 0.20, whereas gestational age and birth weight appear reasonably well balanced. Given that SGA was itself included as a matching variable, this residual imbalance is notable and raises the possibility that the current matching specification may be somewhat over-constrained.

The authors may wish to consider whether a different matching approach would provide improved balance and interpretability. For example, matching on gestational age, birth weight, sex, and birth year alone would capture the primary baseline determinants of prematurity-related risk while avoiding potential redundancy introduced by including SGA simultaneously with gestational age and birth weight. SGA could then be incorporated as a covariate in adjusted models rather than as a matching variable. Alternatively, if the authors prefer to retain the current matching specification, the residual imbalance in SGA should be explicitly acknowledged in the manuscript. Specifically, the manuscript should note that SGA remained imbalanced after matching (SMD >0.20), discuss the potential implications for interpretation of the findings, and clarify that this may reflect the close relationship between gestational age, birth weight, and SGA status. Addressing this issue, either by reconsidering the matching specification or by more explicitly acknowledging the remaining imbalance and its implications, would strengthen the methodological clarity of the manuscript.

**********

what does this mean? ). If published, this will include your full peer review and any attached files.). 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 For information about this choice, including consent withdrawal, please see our Privacy Policy .-->

Reviewer #2: No

**********

[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.]

To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures

You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation.

NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

Postnatal cytomegalovirus infection and bronchopulmonary dysplasia in very low birth weight infants: Influence of diagnostic criteria and viral load in a propensity score–matched cohort study

PONE-D-25-54667R2

Dear Dr. Zhu,

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.

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Kind regards,

Kazumichi Fujioka

Academic Editor

PLOS One

Additional Editor Comments (optional):

Well Revised

Reviewers' comments: