A History of Neonatal Uterine Bleeding and Its Significance

Round 1

Reviewer 1 Report

The manuscript by Benagiano is a fine piece of work about the history of neonatal bleeding. However, some issues have to be answered/corrected.

1. Introduction - the abbreviation of NUB needs to be explained one sentence earlier.
2. You mentioned that the interest about NUB was renewed because of a brief article (ref 2), which, however, is from 2021. This is somehow misleading.
3. Page 2 - please replace statement by statements.
4. Table 1 - No. 13, ref 33. On page 7 the case is described as follows: birth 21 March, mucus/bleeding on March 25/26 which stopped on March 28. This results in bleeding onset at day 4/5 after birth which lasted for 2/3 days. In your description the onset was on day 5 for 5 days. No. 32, ref 34 on page 7, the onset of bleeding was on the third day in the text and on day 4 in the Table.
5. Table 1 - Why is the case described by Engström [51] not included?
6. Table 1 - If we summarize the historical data, the majority of cases (n=21) showed bleeding from day 1 to day 5 which lasted for 4-5 days (n=10). These data agree very well with modern data and can be included if you like.
7. Page 3/4 - Several times it was not clear whether you referred to Cullingworth from ref 7 or ref 48. Please specify.
8. Page 3 - The acknowledgment should be shifted to the end of the manuscript in the paragraph - Acknowledgment
9. Page 3 and 4 - The first case described by an Israeli was by Maimonides in the XII century, which is equal to medieval times, but not to ancient times. I also checked the book by Leviticus but I do not agree with the authors that neonatal bleeding was mentioned. But because I am not an expert, maybe I am wrong, please clarify this issue.
10. Page 4 - You mentioned Johann and Joannis Georg Schenk and the XVII century. Johannes/Joannis (1531-1598) was the father of Johann (1560-1620) who published several issues from his father. From the reference it looks like as if you refer to the father (who lived in the XVI century). Please clarify.
11. Page 6 - Two times you gave the name of Schurig as Schuring, please correct.
12. Page 6 -Please replace van derWiel by van der Wiel
13. Page 7 - in the third paragraph a different font was used, please replace. Also please replace "This, however, probably..." by " This, however, is probably..."
14. Page 9 the sentence "...less often can was..." seems to by a typo, please correct.
15. Page 9, refs 71-76 - A short calculation showed 208/4578 cases (4.5%) with visible neonatal bleeding, maybe you can include this information if you like.
16. Page 11 - Last sentence. If we think about the low number of visible NUB of ~5% the conclusion seems to be justified. However, as shown by you in other manuscripts about NUB the numbers of occult cases are considerably higher (~25-61%), thus, the conclusion seems not to be justified. In my opinion it indicates a different strength of reaction to the progesterone withdrawal which, however, seems to occur in many newborns.
17. Ref 6 - Menstruation in small letters please
18. Ref 14- Please indicate the pages you are referring to.
19. Ref 15 - Please replace Shenaton by Shnaton
20. Ref 16 - Please replace Weisheip by Weisheipl
21. Refs 37-40 The correct writing is "Medicinisches Correspondez-Blatt des Württembergischen Ärztlichen Vereines"
22. Ref 37 Please replace Geschlectistheilen by Geschlechtstheilen
23. Ref 40 Please replace Geschlechts heilen by Geschlechtstheilen
24. Ref 42 correct is Journal für Kinderkrankheiten
25. Ref 52 Please add SC to Burney and correct is "Vulva und"
26. Ref 58 I found it as "Über Genitalblutungen neugeborener Mädchen"
27. Ref 63 Please add FJ to Drake. I found the title as "Vaginal hemorrhage in the newborn"
28. Ref 80 correct is "Naturforscher und Ärzte"

Author Response

The manuscript by Benagiano is a fine piece of work about the history of neonatal bleeding. Many thanks to the reviewer.

However, some issues have to be answered/corrected.

1. Introduction - the abbreviation of NUB needs to be explained one sentence earlier. Done as requested.
2. You mentioned that the interest about NUB was renewed because of a brief article (ref 2), which, however, is from 2021. This is somehow misleading. We have corrected the order of the references. This refers to the article from 2013.
3. Page 2 - please replace statement by statements. This is now corrected.
4. Table 1 - No. 13, ref 33. On page 7 the case is described as follows: birth 21 March, mucus/bleeding on March 25/26 which stopped on March 28. This results in bleeding onset at day 4/5 after birth which lasted for 2/3 days. In your description the onset was on day 5 for 5 days. We have corrected this in the table as pointed out.

No. 32, ref 34 on page 7, the onset of bleeding was on the third day in the text and on day 4 in the Table. We have revised based on the original text which indicates onset of bleeding on day 5.

1. Table 1 - Why is the case described by Engström [51] not included? As indicated in the table legend, table 1 includes those cases identified by Cullingworth who does not mention Engström.
2. Table 1 - If we summarize the historical data, the majority of cases (n=21) showed bleeding from day 1 to day 5 which lasted for 4-5 days (n=10). These data agree very well with modern data and can be included if you like. We have made reference to this observation in the text.
3. Page 3/4 - Several times it was not clear whether you referred to Cullingworth from ref 7 or ref 48. Please specify. Thank you for this observation which we have addressed.
4. Page 3 - The acknowledgment should be shifted to the end of the manuscript in the paragraph – Acknowledgment. We have followed this recommendation.
5. Page 3 and 4 - The first case described by an Israeli was by Maimonides in the XII century, which is equal to medieval times, but not to ancient times. We have correct the reference to Medieval times.  I also checked the book by Leviticus but I do not agree with the authors that neonatal bleeding was mentioned. But because I am not an expert, maybe I am wrong, please clarify this issue. We have reviewed the point raised and agree with the referee that this is no explicit mention of NUB. Our view is that an inference could be made based on the distinction drawn in references 14 and 15. We have altered the wording from mention to inference to indicate this.
6. Page 4 - You mentioned Johann and Joannis Georg Schenk and the XVII century. Johannes/Joannis (1531-1598) was the father of Johann (1560-1620) who published several issues from his father. From the reference it looks like as if you refer to the father (who lived in the XVI century). Please clarify. We can confirm that the text available to us is dated MDCLXV and refers to Joannis Schenckii a Grafenberg
7. Page 6 - Two times you gave the name of Schurig as Schuring, please correct. We have corrected the spelling to Schurig.
8. Page 6 -Please replace van derWiel by van der Wiel. We have corrected the typo.
9. Page 7 - in the third paragraph a different font was used,(we have corrected this). please replace. Also please replace "This, however, probably..." by " This, however, is probably..."(we have corrected this)
10. Page 9 the sentence "...less often can was..." seems to by a typo, please correct. We have addressed the typo.
11. Page 9, refs 71-76 - A short calculation showed 208/4578 cases (4.5%) with visible neonatal bleeding, maybe you can include this information if you like. We have included this in the text.
12. Page 11 - Last sentence. If we think about the low number of visible NUB of ~5% the conclusion seems to be justified. However, as shown by you in other manuscripts about NUB the numbers of occult cases are considerably higher (~25-61%), thus, the conclusion seems not to be justified. In my opinion it indicates a different strength of reaction to the progesterone withdrawal which, however, seems to occur in many newborns. Many thanks, We have added a caveat to reflect the important point raised.
13. Ref 6 - Menstruation in small letters please done
14. Ref 14- Please indicate the pages you are referring to. Done
15. Ref 15 - Please replace Shenaton by Shnaton . Done
16. Ref 16 - Please replace Weisheip by Weisheipl. Done
17. Refs 37-40 The correct writing is "Medicinisches Correspondez-Blatt des Württembergischen Ärztlichen Vereines" Corrected as advised
18. Ref 37 Please replace Geschlectistheilen by Geschlechtstheilen
19. Ref 40 Please replace Geschlechts heilen by Geschlechtstheilen
20. Ref 42 correct is Journal für Kinderkrankheiten
21. Ref 52 Please add SC to Burney  Our searches indicate the name as Busey (no initials) and we have pointed out that we have not been able to verify this further. and correct is "Vulva und" Corrected
22. Ref 58 I found it as "Über Genitalblutungen neugeborener Mädchen" done
23. Ref 63 Please add FJ to Drake. I found the title as "Vaginal hemorrhage in the newborn" Corrected to FI Drake, title corrected
24. Ref 80 correct is "Naturforscher und Ärzte" Done

Many thanks for this detailed critique for which we are most grateful.

Reviewer 2 Report

This is a well written and interesting historical reflection of neonatal uterine bleeding. The manuscript describes historical comments regarding neonatal uterine bleeding from a variety of texts, highlighting that neonatal uterine bleeding was mentioned well before understanding of the physiology of this condition.  I have no comments related to this manuscript.

Author Response

Reviewer 2

This is a well written and interesting historical reflection of neonatal uterine bleeding. The manuscript describes historical comments regarding neonatal uterine bleeding from a variety of texts, highlighting that neonatal uterine bleeding was mentioned well before understanding of the physiology of this condition.  I have no comments related to this manuscript.

 Many thanks. Much appreciated.

Round 2

Reviewer 1 Report

The authors have corrected carefully all issues mentioned. However, I still found some minor typos:

Refs 39/40 Please replace Vereine by Vereines

Ref 42 Please replace eingeiretene by eingetretene

Ref 74 Please replace Gebursth by Geburtsh

Congratulations to this fine piece of work. I enjoyed the reading a lot.

Author Response

Refs 39/40 Please replace Vereine by Vereines Done with thanks

Ref 42 Please replace eingeiretene by eingetretene Done with thanks

Ref 74 Please replace Gebursth by Geburtsh Done with thanks