PONE-D-22-29184Evaluation of first trimester maternal serum inhibin-A for preeclampsia screeningPLOS ONE

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This work was supported by a grant from the Health and Medical Research Fund, Hong Kong SAR, China (HMRF-18190821). The study sponsor had no role in the study design, collection, analysis, and interpretation of the data; or in the writing of the article. The base-cohort study “Prospective validation of prediction algorithms for preeclampsia in the first-, second- and third-trimesters of pregnancy” was supported by a grant from Department of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong Kong (CUHK), Hong Kong SAR.

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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: 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?

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Reviewer #1: Yes

Reviewer #2: Yes

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

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Reviewer #1: Yes

Reviewer #2: Yes

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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: Not withstanding its acknowledged low dose aspirin issue limitation and retrospective design, this is a clearly described, statistically sound and biomedically important contribution to the current literature dealing with early pregnancy biomarkers that may help predict preeclampsia later in a pregnancy.

Although the conclusion of the study is in one sense "negative" in so far as the study results do not support the use of inhibin as a biomarker in place of or in addition to currently used options (such as PlGF in particular), it is important to report such an outcome, if for no other reason than to minimise others wasting time and effort in pursing the same possibility.

I see no value in nitpicking minor and/or trivial issues and recommend the manuscript's publication as submitted.

Reviewer #2: This is an interesting paper that aimed at investigating whether maternal serum inhibin-A at 11-13 weeks could be as an alternative to PlGF or as an additional biomarker within the FMF screening test for preterm PE. In a nested case-control study, the authors found that replacing PlGF by inhibin-A or adding inhibin-A as an additional biomarker in and to the FMF triple screening test for preterm PE does not improve screening performance and will fail to identify pregnancies that are currently identified by the FMF triple test. It is a nicely conducted study and well written manuscript. I suggest modifying the following issues before the publication of the paper:

1) What can be the reason for lower inhibin-A levels in parous women with no previous history of PE? This could be shortly discussed.

2) Table 1: by looking at the differences between groups in many comparisons, several in the term PE vs control comparisons (e.g. IVF, nulliparous, etc) could be significant. Please double check the numbers.

3) It is stated that tests were considered statistically significant if the p-value was <0.05. What was the threshold after Bonferroni correction?

4) It is stated that “inhibin-A in the currently used FMF triple test does not significantly improve the screening performance could be explained by the concept of diminishing marginal returns and the fact that inhibin-A levels correlate with PlGF levels in PE groups.” However, there was no testing of any correlation. Please perform the test or remove the statement.

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Reviewer #1: No

Reviewer #2: No

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Evaluation of first trimester maternal serum inhibin-A for preeclampsia screening

PONE-D-22-29184R1

Dear Dr. Poon,

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,

Ahmed Mohamed Maged, MD

Academic Editor

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Additional Editor Comments (optional):

All reviewers comments were clarified

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: 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

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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: The authors have adequately addressed the minor corrections/amendments suggested by the review process.

Reviewer #2: The authors have revised their manuscript according to the comments of the reviewers, therefore, now it is acceptable for publication.

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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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