PONE-D-21-20144

Risk of infection in neonates born in accidental out-of-hospital deliveries.

PLOS ONE

Dear Dr. Lung Chang

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PLOS ONE

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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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

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: No

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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: Thank you for this excellent piece of work. Please could you clarify these issues:

1. Regarding the title, it would be valuable to state where the study took place, and whether it was in an urban, peri urban or rural setting. This helps those of us who have never been to your unit understand the context better.

2. Again, the place of study should be included in the abstract for clarity.

3. The outborn cohort is very small, but this certainly speaks to the excellent care provision in your setting. In your setting, are many babies born electively at home, under the care of a doula or midwife?

4. Please clarify this sentence (on line 57 - 58): " Duration and antimicrobial therapy were recorded."

5. Please define what the local antibiotic policy is, in reference to the statement on line 141 - 142: In accordance with the common practices of the facility, 152 (96.2%) OHD neonates were administered antibiotics".

6. This sentence on line 163 ". Khupakonke et al. also demonstrated LBW to be a predicting factor of OHD [11]." feels out of place, and should probably be kept in the introduction.

7. The rest of the paper does not mention the prognosis of the patients, so the sentence on line 167 "The prognostic outcomes of OHD neonates require further research. " does not need to be included.

Reviewer #2: Abstract:

Page 2 line 14, the sentence “the OHD group was comprised of more teenage mothers than adult mothers” technically is not right. The OHD group comprised of more teenage mothers compared to the in-hospital deliveries category.

Study variables:

Does Neonatal age here refer to Gestational age?

“Cerebrospinal fluid (CSF) and gastric juice (GJ) cultures were collected when patients exhibited signs or symptoms of sepsis, including fever, respiratory distress with desaturation, seizure, apnea, tachycardia or bradycardia” but there is no mention of CSF in the results.

Outcome measures:

Page 6 line 72: “…indicating that pathogens are related to OHD.” Granted, infections associated with OHDs are more likely to be Early Onset infections but sentence should be rephrased since it is ambiguous and gives an impression of causality.

Results:

Characteristics of OHD neonates - Hospital stay would be better expressed as a median

Table 2 – Some of the percentages are not correct both under the infection & non infection columns.

What denominators were used for the Prematurity calculations?

The sub-optimal cord practices percentages for both the infection and non-infection columns are incorrect, should be 25% & 18% respectively.

Hospital stay would be better expressed as a median

Etiology of OHD in neonates with infection:

The text on the various pathogens isolated from the cultures should be rewritten as it contains a fair amount of redundancy. Since there was only one blood isolate with the remainder as GJs, it can be made to reflect that as opposed to the numerous GJ mentions.

Page 12 line 145 – percentage value of neonates with sub-optimal cord separation is supposed to be 18.4% based on a denominator of 158, as opposed to the 22.7% that is reported

General comments:

Percentage values for Prematurity seems to be inconsistent throughout the study, sometimes it is 23.2% (Page 2 line 8, page 8 table 1 etc.) and at other times 18.4% (Page 15 Table 4). It would seem different denominators are used interchangeably? When is the 158 used and when is the 125 used?

Accidental, Unexpected and Unplanned seems to be used interchangeably to qualify OHDs. Can the authors stick to one? Perhaps “accidental” would be most appropriate since that is what is used in the title of the study.

Typographical / Grammatical errors

Page 2 line 6 /7 “This study also investigated risk factors…” should read “This study also investigated both maternal and neonatal risk factors…”

Page 2 line 13 should read “Forty-nine (31%) OHD mothers lacked antenatal care…”

Page 2 line 14 / 15 should read “Neonatal infection was more prevalent among…”

Page 16 line 187 should read “The neonatal gastrointestinal tract is considered sterile, but diverse microbiota flora is present soon after birth”

Page 16 line 188, “colonization” typo error

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Reviewer #1: Yes: Lyndal Gibbs

Reviewer #2: No

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Risk of infection in neonates born in accidental out-of-hospital deliveries.

PONE-D-21-20144R1

Dear Dr. Chang,

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,

Kazumichi Fujioka

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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 #2: (No Response)

Reviewer #3: 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 #2: Yes

Reviewer #3: Yes

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

Reviewer #2: Yes

Reviewer #3: Yes

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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 #2: Yes

Reviewer #3: 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 #2: Yes

Reviewer #3: Yes

**********

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 #2: Abstract

Line 5: Could it be specified where the urban setting is? For example, urban setting in Taiwan?

Statistical analyses

Line 81: Since length of hospital stay has now been expressed as a median, the statistical analyses should be modified to reflect that.

Typographical errors

Line 16: Neonatal infection was more prevalent among OHDs than for in hospital deliveries

Line 25: OHD should be made plural

Line 93: The GA ranged from 27 to 41 weeks with a mean of …. (The word “age” should be deleted)

Line 105: … and 10 (6.3%) claimed to be unaware of their pregnancy. The word “claimed” here seems inappropriate, gives the impression, the authors do not believe the mothers. Merriam-Webster defines the word claim as “to assert in the face of possible contradiction”. Is that the case here?

Line 130: should read “inside toilet bowls” instead of ‘in toilet bowls’

Line 132: should read “other places” instead of ‘in other places’

Line 138: Twelve OHD neonates had a spinal tap done and all CSF cultures were sterile.

Line 164: …conceal the adverse “effects” of the place where labour occurred, instead of conceal the adverse “factors” of the place where labour occurred

Reviewer #3: Review comments on Manuscript Number: ONE-D-21-20144R1. Entitled "Risk of infection in neonates born in accidental out-of-hospital deliveries."

Overall, the idea of research is very interesting, organized and well written reasonable. The authors have done great effort to accomplish this work. They fulfilled all reviewers' comments and made necessary changes throughput the manuscript.

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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 #2: Yes: Dr Naana Ayiwa Wireko Brobby

Reviewer #3: No