PONE-D-19-21810

How much synthetic oxytocin is infused during labour? A review and analysis of regimens used in 12 countries

PLOS ONE

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1. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, please give more details on how the survey was distributed, hoe many participants per each country were invited (and the inclusion and exclusion criteria used), how participating countries were chosen.

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Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: Yes

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5. Review Comments to the Author

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Reviewer #1: Interesting and well-designed study. Needs minor editing for compound sentences and minor grammatical errors, such as changing "exceeded" to "exceeds" from lines 188-193.

Tables are very detailed, but I think Table 3 is actually too much detail; consider changing this to brief paragraph summaries of different countries' criteria. Similarly- The second part of Table 5, demonstrating all of the possible dosing per each algorithm, detracts from the impact of the work rather than adding to it. I realize this table is the bulk of the outcome of your carefully crafted study, but it is unlikely that a reader would carefully analyze the math. Perhaps including one or two country's data, with an appendix or link out to the full data set? The example at line 404 is terrific and could be bolstered by adding a contrasting example. The big picture differences in initial dose, escalation protocols, and total dose are the staggering outcomes, and you have laid these out well without needing such detail.

The multitude of recent studies and meta-analysis regarding induction at 39 weeks and improved maternal and neonatal outcomes would argue against your tenet of over-medicalizing labor, but looking at the association of bad outcomes with possible injudicious use of exogenous oxytocin remains very important- did you look at any institutional data on cesarean rate, uterine rupture rate, or any other discrete poor outcomes of the differing protocols? Clearly could be a robust additional study but would entice the reader to think about the implications of these differences.

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Reviewer #1: Yes: Margaret Larkey Dow

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How much synthetic oxytocin is infused during labour? A review and analysis of regimens used in 12 countries

PONE-D-19-21810R1

Dear Authors,

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

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Salvatore Andrea Mastrolia, M.D.

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PLOS ONE

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

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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: (No Response)

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

Reviewer #1: (No Response)

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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: (No Response)

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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: (No Response)

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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: This study highlights and makes efforts to quantify the considerable variance in synthetic oxytocin administration in several countries, extrapolating timing to max doses and multiple other clinically relevant issues with shocking variability, particularly given its nearly ubiquitous use on labor units. It was an ambitious undertaking, but in its original form it was difficult to appreciate the major findings. The authors took great care to incorporate previous feedback and have added very high impact graphics (notable Figures 1 and 2). Multiple tables were carefully redone, highlighting important data and making them digestible. The manuscript also contains some significant reworking that emphasizes important findings, no longer getting bogged down in a sea of data. This is an important study that is significantly more readable and more powerful in its rewritten form. It is likely to generate much needed renewed interest in exacting appropriate use of this drug.

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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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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: Yes: Margaret Dow