PONE-D-21-15843Continued versus discontinued oxytocin after the active phase of labor: an updated systematic review and meta-analysis.PLOS ONE

Dear Dr. Nie,

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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: Partly

Reviewer #2: Yes

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

Reviewer #1: N/A

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?

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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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: The regimens of oxytocin during labour vary widely between different guidelines or even individual medical centers, that is why this study about oxytocin administration beyond the active phase is interesting.

Please, provide an explanation for the following comments:

1- If oxytocin discontinuing could decrease the risk of cesarean delivery, how this effect decreased in women who had cesarean operation? Is that affected by other factors like previous cesarean section or other factors that require cesarean intervention?

2- Oxytocin is a drug, regarding dosing protocol: would not different doses result in different responses?

3- The included studies reported different inclusion criteria for the patients, which in turn can affect the analysis?

4- Chorioamnionitis is analyzed, but some patients were enrolled with PROM. How could these affect the result?

5- In table 5, provide a row / column with the total number of events of each arm of the study?

6- Many studies have multiple high risk of bias points, How such studies can be trusted to get an accurate and reliable analysis?

Reviewer #2: Overall, this is an interesting relevant research question and represent a valuable addition to the Labor management approaches. The authors have collected sufficient dataset from the eligible trials and analyzed relevant variables that directly linked to the handled question. The analysis and results interpretation were clear, direct, and illustrated in a well-organized structure. The discussion structure and sequence were enriching and highlighted the important issues related to the study results.

The objective is clearly stated through informative title reflect the true nature of the review; page (1) and the well- structured introduction context; page (2, 3). The methodology was detailed and suitable for the research idea. Performing manual search of references (page (3) method section, Literature search paragraph, last sentence) and Publication bias assessment using the GRADE approach (page (4) method section, Data abstraction, second paragraph, third sentence), are thought to reinforce the design and the quality assessment, respectively. The results were clearly illustrated and neutrally discussed, with useful summary in the pooled outcomes; table (6) page (14) and the analysis was sufficient as well. The authors discussed the oxytocin effect using not just maternal outcomes but also neonatal and delivery interval as well which provide more accuracy to the conclusion; page (16) paragraph 3.3 and 3.4. The thorough discussion was well-structured and handled the relevant literature with results implication along with the existed conflict between using Continued vs discontinued oxytocin based on the available evidence (page 17, paragraph 3). Figures and tables were clearly presented and correctly labelled.

Minor issues:

1) In Method section in Data abstraction part, page (4) first paragraph; the author mentioned an extracted variable (setting, mentioned as a part of General information) that was not obtained in the characteristics table; page (7).

2) In Result section, there are two mistakes in the reported data compared with the labelled analysis figures.

- page (13), Maternal outcomes paragraph, Fifth sentence: ''Moreover, we found a possible increased risk of chorioamnionitis in the OD group without significant heterogeneity [RR (95% CI): 2.77 (1.02–5.08), P=0.05] (Fig 5e)''. RR is supposed to be 2.27 as shown in fig 5e. Also, the number of trials from which these results were analyzed and the number of patients are recommended to mentioned in this sentence.

- Page (16), Induction delivery interval paragraph, second sentence: ''The pooled result indicated that discontinuation may prolong the active stage of labor compared to continued oxytocin [MD (95% CI): 2.28 (2.86–41.71), P=0.02]''. RR is supposed to be 22.28 as shown in fig 5g.

3) In Discussion Section in Comparison and Implication parts (Page 17 and 18, respectively), there was a lack of reported statistical data of the results and conclusions discussed from the literature. The statistical data are important and reinforce the flow of the discussion.

In brief, the paper is generally well thought out and written, accessible data statistically analyzed in sufficient detailed manner, the conclusions well supported by the data presented in the results and figures, and with no conflict of interests. Thus, we recommend its acceptance, with some minor corrections regarding the issues previously mentioned.

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Reviewer #1: No

Reviewer #2: Yes: Gena M Elassall

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Continued versus discontinued oxytocin after the active phase of labor: an updated systematic review and meta-analysis.

PONE-D-21-15843R1

Dear Dr. Nie,

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,

Giovanni Delli Carpini

Academic Editor

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: Yes

**********

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

Reviewer #1: 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

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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

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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: (No Response)

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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