Roger Gadsby

Diana Ivanova

Emma Trevelyan

Jane Luise Hutton

Sarah Johnson

https://doi.org/10.1186/s12884-020-03478-7

Figure 1

Figure 2

Figure 3

The onset of nausea and vomiting of pregnancy: a prospective cohort study

<p>This preprint is available for <a href='/article/rs-36764/latest.pdf' target='_blank'>download as a PDF</a>.</p>

BMC Pregnancy and Childbirth

CC BY 4.0

Background
Nausea and vomiting are experienced by most women during pregnancy. The onset is usually related to Last Menstrual Period (LMP) the date of which is often unreliable. This study describes the time to onset of nausea and vomiting symptoms from date of ovulation and compares this to date of last menstrual period
Methods
Prospective cohort of women seeking to become pregnant, recruited from 12 May 2014 to 25 November 2016, in the United Kingdom. Daily diaries of nausea and vomiting were kept by 256 women who were trying to conceive. The main outcome measure is the number of days from last men­strual period (LMP) or luteinising hormone surge until onset of nausea or vomiting.


Results
Almost all women (88%) had Human Chorionic Gonadotrophin rise within 8 to 10 days of ovulation; the equivalent interval from LMP was 20 to 30 days. Many (67%) women experience symp­toms within 11 to 20 days of ovulation.


Conclusions
Onset of nausea and vomiting occurs earlier than previously reported and there is a narrow window for onset of symptoms. This indicates that its etiology is associated with a specific developmental stage at the foetal-maternal interface.

Trial registration NCT01577147

Recommendation: Accept without revision
Form responses:
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Comments to Author:
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Thank you for replying to my remarks, I am satisfied with how they were addressed.

My only hesitation is the sparsity of details of the statistical methods in the Methods section; however, if the editors are satisfied with the level of detail, I do not have further requests.

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* Declaration of competing interests: **I declare that I have no competing interests**
* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**
* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**
* Are the methods sufficiently described to allow the study to be repeated?: **Yes**
* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**
* Is the presentation of the work clear?: **Yes**
* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**


Recommendation: Accept without revision
Form responses:
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Comments to Author:
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Thank you for the prompt revision.* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**
* Declaration of competing interests: **I declare that I have no competing interests**
* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**
* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**
* Are the methods sufficiently described to allow the study to be repeated?: **Yes**
* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**
* Is the presentation of the work clear?: **Yes**
* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**


Recommendation: Reject
Form responses:
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Comments to Author:
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The question being asked is of minimal interest and makes little contribution to the understanding of nausea and vomiting in pregnancy.
The relationship between ovulation date and LMP for dating pregnancy is well recognised.
The population is highly skewed, the statistical assessment (by a third party) is excessive with breakdown of subgroups being completely arbitrary and presumably post hoc . There is no adjustment for multiple comparisons and the statistical comparisons are of little biological importance eg Symptoms start slightly later with increasing age (Figure ??), by almost one day for an increase of 3 years (regression coeffecient 0.295, standard error 0.094).
The statement that : "The close connection between onset of NVP symptoms and date of ovulation reinforces the theory that the aetiology of the condition is biological, rather than psychiatric, and is based on the emerging physiology at the foetal-maternal interface." is simplistic. No recent research suggests this disease is anything other than biological and the confirmation that timing of onset varies by a few days when comparing  ovulation and LMP is inconsequential.* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**
* Declaration of competing interests: **'I declare that I have no competing interests**
* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**
* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**
* Are the methods sufficiently described to allow the study to be repeated?: **Yes**
* Is the use of statistics and treatment of uncertainties appropriate?: **No**
* Is the presentation of the work clear?: **Yes**
* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**


Recommendation: Accept after minor essential revisions
Form responses:
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Comments to Author:
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This is an interesting study on the onset of nausea and vomiting of pregnancy. In general, it is a common problem of early pregnancy; however, the exact timing needs to be examined.

Background
1. Please move the second paragraph to the discussion section. Instead of this please write what the national guidelines state regarding the diagnosis and management of nausea and vomiting of pregnancy. In particular, please cite PMID: 31634919 and comment.
Methods
1.     How did you estimate study sample?
2.     Please use the Strobe statement for your sections.
Results
1.     Please revise Figure ???
Discussion
1.     Please mention first the interpretation and then the strengths and limitations.
* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**
* Declaration of competing interests: **I declare that I have no competing interests**
* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**
* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**
* Are the methods sufficiently described to allow the study to be repeated?: **Yes**
* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**
* Is the presentation of the work clear?: **Yes**
* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**


Recommendation: Accept after minor essential revisions
Form responses:
---

Comments to Author:
---
Thank you for conducting and reporting this prospective cohort study about the timing of NVP onset. The meticulous approach of the study enables valuable day-to-day observation of NVP symptoms.


Background

The background presents clear justification for the study.

P. 2, line 46: "Nausea and vomiting (NVP)" -> "Nausea and vomiting of pregnancy (NVP)"

P. 2, lines 27-28: "In this paper we study the onset of NVP in relation to the date of ovulation and NVP" should perhaps read "In this paper we study the onset of NVP in relation to the date of ovulation and LMP"?


Methods

The data collection methods described are appropriate for the the study. The statistical methods section lacks details of the analysis methods employed.

A flowchart or other depiction of the study flow including numbers of possible missing entries or samples. 100% coverage of daily diaries and daily urine samples for hundreds of women for several weeks would be remarkable; one assumes that some may have been missed, but how many? If the coverage was 100%, it is worth noting.

P. 3. line 14: The follow-up questionnaire contents could be described to clarify its role in the study.


Results

The results are detailed and interesting. As many other studies have no ovulation timing data, the extensive comparison of timings of LMP, ovulation and NVP is very useful.

P. 3, lines 38-41: "For the table - - were continuous" section discusses methods rather than results and could be moved to the methods section?

Please go through the final figure numbering to omit the "??"s in the text.


Discussion

The main findings, strengths, limitations and interpretation are clearly presented and relevant.

The possible effects of different starting timing of the pregnancy diaries and the proportion of missing follow-up questionnaires (depending on the role of the follow-up questionnaires in the study) could be discussed, too.


Conclusion

The conclusion is pertinent.


Other

P. 6, line 46, Abbreviations: Please include NVP
P. 7, line 57, Figure 1 caption: "hCP" should read "hCG"
* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**
* Declaration of competing interests: **I declare that I have no competing interests.**
* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**
* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**
* Are the methods sufficiently described to allow the study to be repeated?: **Yes**
* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**
* Is the presentation of the work clear?: **Yes**
* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**


The onset of nausea and vomiting of pregnancy: a prospective cohort study

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