PONE-D-20-12352

Pro-atrial natriuretic peptide and pro-adrenomedullin before cardiac surgery in children. Can we predict the future?

PLOS ONE

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Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: No

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: I read with interest the article entitled “ Pro-atrial natriuretic peptide and pro-adrenomedullin before cardiac surgery in children. Can we predict the future?” The subject is interesting and quite innovative, sample size good. Results are interesting and consisting. The article however has a few limitations that should be addressed.

Major comments

-English and format need to be revised.

-Abstract and introduction are a bit wordy.

Methods:

- A prospective study conducted almost ten years ago (2012-2013)?

- Sample time is only pre-operative? When? The lack of post-surgical values is a clear limitation of the present work

-Complicated outcome and major complications after pediatric cardiac surgery definitions should be consistent with literature. We advise to see and cite similar articles on other biomarkers

Cantinotti M, Giordano R, Scalese M, Molinaro S, Della Pina F, Storti S, Arcieri L, Murzi B, Marotta M, Pak V, Poli V, Iervasi G, Kutty S, Clerico A.Prognostic role of BNP in children undergoing surgery for congenital heart disease: analysis of prediction models incorporating standard risk factors. Clin Chem Lab Med. 2015 Oct;53(11):1839-46.

Cantinotti M, Storti S, Lorenzoni V, Arcieri L, Moschetti R, Murzi B, Spadoni I, Passino C, Clerico A.

The combined use of neutrophil gelatinase-associated lipocalin and brain natriuretic peptide improves risk stratification in pediatric cardiac surgery.

Clin Chem Lab Med. 2012 Nov;50(11):2009-17

Cantinotti M, Lorenzoni V, Storti S, Moschetti R, Murzi B, Marotta M, Crocetti M, Molinaro S, Clerico A, Portman M, Iervasi G Thyroid and brain natriuretic Peptide response in children undergoing cardiac surgery for congenital heart disease- age-related variations and prognostic value. Circ J. 2013;77(1):188-97.

Methods and results:

-Did you evaluate differences among neonates, infants, and children? If not, it may be of worth since for BNP the trend was quite different. You state something in the limitation section, but this point should be elucidated and detailed better, also in the tables.

-In the tables please specify the type of CHDs

-Inclusion/exclusion criteria re not well defined. Did you include only cardiopulmonary bypass surgery?

Discussion: comparison with other biomarkers are required

Limitation section need to implement.

Minor comments

CVC= I would rather use pediatric cardiac surgery without abbreviation

Reviewer #2: To the Authors

General Considerations

The aim of this study was to evaluate the utility of proANP and proADM determined before cardiovascular surgery for predicting need for high respiratory or inotropic support in the post-operative period. Authors enrolled 113 patients (51% males, median age 2.1 years, interquartile range 0.6-6.6 years) admitted to the neonatal intensive care unit after cardiovascular surgery. Authors considered as primary endpoints were a high respiratory support, considered as the need for more than 72 hours of mechanical ventilation after cardiovascular surgery, and a high inotropic support, in the first 24 hours after surgery. Furthermore, Secondary endpoints were the presence of complications after surgery, including Prolonged length of stay in ICU and mortality. The most important result of this study is that a high proANP determined before cardiovascular surgery may identify those patients who will need higher respiratory and inotropic support in the post-operative period.

The manuscript is concise and the results are clearly reported. I have only one observation to address to the Authors. It is well known that B-type natriuretic peptides (especially BNP and NT-proBNP) are the first line biomarkers for screening of heart failure and are also reliable prognostic markers in children undergoing cardiac surgery (Authors should cite the important review: Cantinotti M et al. Heart Fail Rev 2014;19:727-42). Therefore, the original data related to this article are that also some A-type natriuretic peptides, such as proANP, can have a prognostic role in paediatric patients admitted to the neonatal intensive care. Authors should explain because clinicians should prefer the assay of proANP in respect to that of BNP or NT-proBNP in children undergoing cardiac surgery. Accordingly, an important limitation of this study is that Authors should due to compare the prognostic accuracy of proANP to that of BNP or NT-proBNP. Authors should discuss this important point in revised manuscript.

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Reviewer #1: Yes: Massimiliano Cantinotti

Reviewer #2: No

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Pro-atrial natriuretic peptide and pro-adrenomedullin before cardiac surgery in children. Can we predict the future?

PONE-D-20-12352R1

Dear Dr. Jordan,

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,

Claudio Passino, MD

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

**********

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

Reviewer #1: Yes

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 #1: Yes

Reviewer #2: Yes

**********

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: Authors correctly addressed all points raised by the reviewers.

I have just a request. If data have been partly already published, this should be clearly stated. Again, quite strange a prospective study date bake 2013

Reviewer #2: Authors revised the manuscript in accordance with the suggestions made by the Reviewers. The manuscript is now significantly improved.

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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.

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Reviewer #1: Yes: Massimiliano Cantinotti

Reviewer #2: No