Dear Dr. van Weelden,

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.

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ACADEMIC EDITOR: Please respond to all reviewers comments

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We look forward to receiving your revised manuscript.

Kind regards,

Ahmed Mohamed Maged, MD

Academic Editor

PLOS ONE

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When submitting your revision, we need you to address these additional requirements.

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2. Thank you for stating the following financial disclosure:

“No peer reviewed  external funding was received for this study. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article. This work was supported by University Fund Eindhoven, by Máxima Fund and by the PPP Allowance TKI HTSM, made available by Top Sector Holland High Tech to the University Fund Eindhoven to stimulate public–private partnerships, grant number PPS23-2-03529539. Manufacturer Nemo Healthcare B.V. has loaned two NemoRemote devices for use in this study at no costs.”

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses??>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable??>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

Reviewer #1: As the statistical reviewer I will focus on methods and reporting. the power calculations are appropriate.

Major

1) For the primary outcome an one sample t-test is proposed. against what hypothesised mean? I would advise against heavily relying on p-value based tests and statistical significance considering the sample.

2) how will missing data be handled, or none are expected?

3) how will the EQ-5D and other questionnaires be analysed, as the authors say?

Minor

1) Will changes over time be assessed and how?

Reviewer #2: This study protocol describes a prospective, single-center feasibility study evaluating self-administered remote electrophysiological cardiotocography (eCTG) in high-risk pregnancies between 32 and 37 weeks’ gestation. The concept is highly topical and clinically relevant, given the growing interest in telemonitoring and patient-autonomous obstetric care.

1. The operationalization of “interpretability” is subjective. To increase reproducibility, specify objective quantitative thresholds (e.g., continuous FHR signal >80 % of recording time; uterine activity identifiable in >90 % epochs) and give detail training/standardization of assessors.

2. The calculation (n = 60) is based on feasibility proportions from a 1990s home-CTG study, not on modern eCTG signal behavior. The authors should provide power considerations for the primary outcome (≥90 % successful recordings, 95 % CI ≥ 82.5 %), with an explicit formula or simulation demonstrating how 60 subjects suffice to assess signal reliability.

3. Describe how eCTG results will be validated against conventional CTG during monitoring. Are clinicians blinded to the mode of acquisition when interpreting the trace? Outline a feedback mechanism if discrepancies arise (e.g., when eCTG signal is reassuring but Doppler CTG shows decelerations).

4. The manuscript lists comprehensive inclusion/exclusion criteria but should elaborate on criteria for early termination in case of persistent signal failure or maternal stress.

5. Consider adding an adverse-event monitoring flow diagram showing reporting hierarchy (participant → site investigator → METC).

Reviewer #3: Dear Authors - It was a privilege to review your manuscript – “Remote electrophysiological cardiotocography (eCTG), evaluation of feasibility in complicated pregnancies from 32 until 37 weeks gestational age in a home@hospital setting (HASTA): A prospective cohort study protocol.”

This is a well-conceived, clinically relevant feasibility protocol addressing a pressing implementation gap: whether self-administered electrophysiological CTG (eCTG) can deliver interpretable fetal monitoring in late preterm, high-risk pregnancies. The rationale is strong (motion/BMI robustness; autonomy; potential cost relief), the target population is appropriate (32–37 weeks; pre-eclampsia/FGR/PPROM), and the design prudently simulates home use within a monitored hospital environment. With some clarifications, especially around the definition of outcomes, this well-thought-out protocol will provide decision-ready evidence to inform remote fetal monitoring pathways. Integrating the study with an electronic health record system for extraction of maternal health data and transmission of results for reading and interpretation will underpin case identification, monitoring workflows, and outcomes ascertainment in the study.

General comment: HASTA - Thank you for providing the clarification on the acronym HASTA. For a global audience, it will be helpful to provide clarification of what it stands for in this context of this study.

Short Title: Feasibility remote eCTG monitoing home@hospital (Feasibility [of] remote… [missing word])

(.. eCTG monitoing [correct the typo – “monitoring”])

Abstract: Home monitoring may reduce the psychological and family burden, improve patient satisfaction and lower health care costs. (Revision – add a comma “,” between separated items)

Abstract: signal quality is hardly affected by obesity and motion than conventional CTG, (This sentence is unclear due to its grammatical structure. The use of “hardly” and “than” in a comparative expression is generally incorrect. Consider replacing “hardly” with “less” or other appropriate phrasing for a global audience.)

Abstract - Methods: “Remote self-administered eCTG will be performed daily during hospital admission, or at least twice a week at the outpatient clinic.” (The description of the study design is not clear – the cohort design is explained to be a hospital-based study, while in the methods, there is a mention of outpatient clinics [which is not generally considered a hospital setting except for hospital-based outpatient clinics]. Clearly define what will be considered a “hospital setting” in the context of this study. For ease of referencing, you should define, for the study, what is considered a hospital setting.)

Abstract/Methods: Definition of the primary outcomes (Consider reviewing and clarifying the parameters of the primary outcome. The sentence in this section seems contradictory – “successful eCTG recordings, defined as … due to signal loss”.

Furthermore, in Line 191, you define a different set of parameters for the primary outcomes. )

Keywords: Second Trimester (This should be corrected to “third” trimester – the cohort group is GA 32 – 37 weeks)

Line 170 – (Correct “in-“ to the complete word “inclusion” for standardization for Table 2 header)

Table 2 (In your description of HELLP Syndrome key punctuations, commas (“,”), to distinguish each component of the HELLP syndrome as separate items.)

General review comments - (The overall use of future tenses in some places and past or present tenses was noticed in some places. There are confusing “verb tense” reconciliations. Consider making the scenario and objectives clear in the abstract and introduction and maintain the consistency of the verb-tense agreements throughout the manuscript. Careful attention must be paid to appropriately reflecting ongoing activities versus proposed activities. For example, Line 122-123: “The study will be conducted…” vs Line 123-124 – “The study is conducted…”"

Line 191-194 (Include the SOP as an appendix and insert the appropriate reference to indicate it)

Line 277 (The initial introduction of an acronym must be completely outlined before independently using the acronym subsequently - consider lettering out “Physical Examination” upon this initial introduction.)

Line 336-338 (Correct the sentence for clarity. “…will [be] systematically recorded and evaluated as part of the feasibility assessment.)

Line 268 (Consider replacing “electronic patient file” with a more standardized nomenclature – “electronic medical record”.)

Reviewer #4: Congratulations on your scientific work. This is an engaging and relevant topic that will significantly contribute to enhancing the evaluation and follow-up of pregnant women requiring fetal well-being monitoring. We look forward to the forthcoming results, which will undoubtedly have a meaningful impact on the treatment costs of these patients within the healthcare system.

Reviewer #5: Overall Summary

This manuscript presents a very interesting study with a neat design for a prospective cohort. The construction and conceptual framework are robust, and the study's aim has the potential to lead to a significant breakthrough in fetal wellbeing monitoring. While the foundation is strong, several minor issues require addressing before publication can be recommended.

Major Comments

Sample Size Justification: The proposed sample size of 60 subjects is ambitious given the epidemiology of the conditions under study. The prevalence of severe preeclampsia is approximately 2%, and fetal growth restriction is only slightly higher. To recruit a sufficient number of cases, the study likely requires a facility with an annual delivery rate of approximately 3,600. The authors should explicitly state this as a key parameter in their sample size calculation to clarify the feasibility and generalizability of their recruitment strategy.

Definition of Fetal Growth Restriction (FGR): The diagnostic criteria for FGR provided in Table 2 are vague and do not reflect current clinical standards. The definition used aligns more closely with Small for Gestational Age (SGA), which is a distinct entity with different management and prognostic implications (Chen & Li, 2023, Ultrasound in Obstetrics & Gynecology). Contemporary guidelines, such as those reviewed by Giouleka et al. (2023, Obstetrical & Gynecological Survey), define FGR as an estimated fetal weight below the 3rd percentile, or below the 10th percentile combined with Doppler abnormalities (e.g., Umbilical Artery PI >95th percentile or Cerebroplacental Ratio <5th percentile). Adopting this updated, precise definition is critical for accurate patient stratification and interpretation of results.

Minor Comments

Methodological Transparency: The timeline for the study and the process for sequential inclusion, exclusion, and dropout are clearly described. The proposed statistical analysis plan is sound and appropriate for the study design.

Declaration of Commercial Instrument: The study utilizes a specific, proprietary device (the NEMO healthcare system). As this may introduce a systematic instrumental bias and only one brand currently offers this technology, this relationship should be explicitly disclosed in a conflict of interest statement to ensure full transparency and address any potential ethical considerations.

Recommendation

Minor Revisions.

This is a promising paper with a strong foundational design. The concerns regarding sample size justification and the definition of FGR are critical to address, but with these revisions, the manuscript will be significantly strengthened and suitable for publication.

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Reviewer #1: No

Reviewer #2: Yes: Burak Bayraktar

Reviewer #3: Yes: Babajide Adewumi

Reviewer #4: Yes: JOAO FELIX DIAS

Reviewer #5: Yes: Juan Carlos Bello-Muñoz

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Remote electrophysiological cardiotocography (eCTG), evaluation of feasibility in complicated pregnancies from 32 until 37 weeks gestational age in a home@hospital setting (HASTA): A prospective cohort study protocol.

PONE-D-25-50846R1

Dear Dr. van Weelden,

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,

Ahmed Mohamed Maged, MD

Academic Editor

PLOS One

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

Reviewer #1: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses??>

Reviewer #1: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable??>

Reviewer #1: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete??>

The PLOS Data policy

Reviewer #1: Yes

**********

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

Reviewer #1: Yes

**********

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

Reviewer #1: I am satisfied with the authors' responses and the resulting changes to the paper. I have no further comments to make.

**********

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

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