Content of review 1, reviewed on December 14, 2022

The present manuscript details the scope of our understanding of the neuroendocrine regulation of the autonomic accommodations required by pregnancy. Overall, I found this manuscript well-conceived and well-executed. It presents a compelling case for the need for further research.

While there are gaps in the literature connecting the hormones of pregnancy and the autonomic functions under consideration, there is enough circumstantial evidence to support the manuscript’s main arguments and these gaps make clear suggestions for future research. Indeed, the size of the gaps in such basic elements of physiology cries out for more study. The end product is a clear vision for the research strategy of an early career investigator.

The well-constructed figures are a strength of this manuscript.

There were several times throughout the manuscript where evidence for a given hormone’s function during pregnancy was drawn from analogous studies in non-pregnant animals. I will concede that this is likely the best we can do at present, but is it safe to assume that these systems function the similarly during pregnancy as during non-pregnancy? That is to say, is pregnancy a difference in degree or a difference in kind when compared to a normally cycling female?

Lines 22-26: Does the association between estrogen and sleep apnea survive controlling for obesity? It seems like increased adiposity would drive both high estrogen levels and increase risk for sleep apnea.

Line 29: seems like it needs to be reworded; is a “how” missing after “oestrogen”?

Page 8, Lines 1-10: This section is a good example of where inclusion of effect sizes would be helpful and illustrative. This is a common issue across our field, where we focus on statistical significance and ignore effect size. For example, the reader is told that heart rate increases, but not by how much. I remember being struck by the magnitude of cardiovascular changes during pregnancy. To learn that blood volume can increase ~50% is still a striking thought. I would love to see more language specifying the magnitude of autonomic changes during pregnancy. I suspect that highlighting these dramatic changes will further bolster the importance of this work.

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    © 2022 the Reviewer.

Content of review 2, reviewed on May 01, 2023

I appreciate the author taking my suggestions into consideration and I would like to think that the manuscript has been improved as a result.

My only remaining note of substance is that I still don't quite understand why oxytocin and vasopressin were left out of this work. Is there a relevant review that could be included that addresses the role of those hormones in the autonomic adaptations during pregnancy?

As a minor note, on line 19 of what was page 34 for me (a paragraph that starts with "During pregnancy, blood volume..." the final sentence of the paragraph mentions a decrease in blood volume during pregnancy that I think should have read increase.

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    © 2023 the Reviewer.

Content of review 3, reviewed on September 14, 2023

I appreciate the author addressing my earlier comments.

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    © 2023 the Reviewer.

References

    T., G. 2023. The role of maternal hormones in regulating autonomic functions during pregnancy. Journal of Neuroendocrinology.