PONE-D-21-02707

Birth weight rather than birth length is associated with childhood behavioural problems in a Czech ELSPAC cohort

PLOS ONE

Dear Dr. Bienertová-Vašků,

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.

This manuscript is quite well written and the results are of interest (novelty not being a publication criteria for this journal). However both reviewers have major concerns about the manuscript, especially in relation to the weighting used in the statistical analysis. If the authors decide that they will revise the manuscript modifying this (or at least rebutting the concerns robustly) is key. Reviewer 1 also has other concerns about the statistical analysis which also require robust responses, and reviewer 2 needs clarification of a number of different points, which I agree with.

Currently I feel that the data availability is not compatible with publication in this journal. At a very minimum more information is needed as to how other investigators may gain access to the data.

Please submit your revised manuscript by May 09 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Clive J Petry, PhD

Academic Editor

PLOS ONE

Journal Requirements:

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

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

3. Thank you for including your ethics statement that the research was approved by ELSPAC Law and Ethics Committee and local research ethics committees.

a. Please amend your current ethics statement to include the full name of all of the ethics committee/institutional review board(s) that approved the ELSPAC study.

b. Once you have amended this/these statement(s) in the Methods section of the manuscript, please add the same text to the “Ethics Statement” field of the submission form (via “Edit Submission”).

For additional information about PLOS ONE ethical requirements for human subjects research, please refer to http://journals.plos.org/plosone/s/submission-guidelines#loc-human-subjects-research.

4. Thank you for stating the following after the Acknowledgments Section of your manuscript:

'This study has recieved support from RECETOX research infrastructure (Ministry of Education, Youth and Sports of the Czech Republic: LM2018121), Horizon 2020 Teaming 2 project (857560) and the Ministry of Education, Youth and Sports of the Czech Republic (CZ.02.1.01/0.0/0.0/17_043/ 0009632 and CZ.02.1.01/0.0/0.0/15_003/ 0000469).'

We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

a. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

'NO - The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.'

b. Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

[Note: HTML markup is below. Please do not edit.]

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: Partly

Reviewer #2: Partly

**********

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

Reviewer #1: No

Reviewer #2: No

**********

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: No

Reviewer #2: No

**********

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: Yes

**********

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: This study examines the relationship between birth weight, birth length and childhood behaviour. I think the paper has some merits but I also have some key concerns, which I detail below. I wish the authors all the best taking his work forward.

A first major issue that emerges from my own reading of the paper concerns the methods used. Why is a binary response constructed for each behavior problem? Why is the original variable not used? I do not understand why it is necessary to dichotomize the variable with the corresponding loss of information that it implies. I think that you can estimate an OLS model. Perhaps a fixed effects model will be better in order to control the effect of unmeasured characteristics of the family (biased estimates). I would like to see the results of a such model.

Moreover, the decision to weight the data is not well justified. It is said that the method was selected to account for the somewhat different proportion of socio-economic characteristics in the Included and Excluded dataset. I understand that there is some pattern that leads to non-response, such as that families with lower socio-economic status tend to respond less or, perhaps it is a problem of the sample….. It is necessary to better specify the use of weighting, since it is true that it reduces bias but weighted often increases variances of the estimates and its use must be well justified.

Four weighted logistic regression models were fitted, one for each behavior problem and separated by birth weight and birth length. I understand that Tables 4 and 5 show the OR for the relationship of birth weight and birth length respectively, but it does not show the significance of the rest of the variables included in each model or any measure of the statistical quality of the model to compare, for example the AIC, BIC, ...

In the other hand, subjects with full information were in the Included dataset, and all other subjects, who had at least one missing data point, were in the Excluded dataset. I understand that these two databases do not have subjects in common but the Included dataset have 1796 subjects and the Excluded 3834, and that differs from the 3311 total subjects (Table 1). Also, line 198 talks about mothers in both datasets, so, I need a better explanation.

Regarding the Strengths and Difficulties Questionnaire, the explanation provided is not very clear. First it is said that it contains 25 items scored 0 to 2, what does each value correspond to? Them, these are separated into five subscales measured from 0 to 10. How is it related to the previous score? I understand that each subscale contains different items to value, isn’t it? It is necessary to improve.

Finally, last major issue concerns the contribution of your study with the extant knowledge. While I agree that the topic is interesting, I think that these findings do not provide anything new. Maybe it would be interesting to analyze differences between sex or between some socioeconomic characteristics of the family.

Lastly, some lower priority comments:

- Explain why behaviour problems are analysed at age 7 and not at age 8 or 6 for example.

- The first time the acronym WHO is used is on line 46, but its definition is on line 72.

- When we talk about association between variables, we can say significant or non-significant association with a certain risk. The term “weak association” is not adequate.

- There is an error on line 238: 0,97 would have to be 0,79

Reviewer #2: In the current study, the authors investigate whether anthropometric measures at birth are associated with later behavioural outcomes in childhood. While the study has some merit, I believe that some changes need to be made to the current manuscript before it is suitable for publication. These changes broadly include giving more context and background around the time period at which the data were collected and clearly articulating the stress that this may have caused to the pregnant mother and developing foetus.

I also have some concerns around the use of inverse-probability weights to account for missing data rather than measurement invariance and the interpretation of some negligible effects as significant. Detailed feedback is given below.

Abstract

1. Give the sample size here

2. Page 2, Line 25 should say “the Strengths and Difficulties Questionnaire” rather than “a Strengths and Difficulties Questionnaire”.

Introduction

1. Page 2, line 43 – what is meant by “evolutionary” forces regarding nutrition and stress? An explanation of this is needed here.

2. On page 3, lines 66 – 68 – the authors state that some studies focus on exploring behavioural problems in children belonging to the full birth weight spectrum, but then say that the studies differ in methodology, sample size and analytical approach. What is the extent of the differences and why might it pose a problem? It’s quite common for studies to vary in methodology, sample size and even analyses, but a robust effect should be apparent across sound methods. For example, one study may have 200 participants, and another may have 20,000. I would still consider the sample size of 200 acceptable if other methods were sound, and not necessarily a limitation. Essentially, this section is quite vague and needs more information.

3. On page 4, the authors note that the ELSPAC study centres all employ a common methodology. What exactly is meant by this – was the recruitment procedure the same? The questions asked the same?

4. On page 4, the authors also mention that the aim of the study was to provide data free of recall bias. How exactly was this bias reduced? For example, the SDQ still requires some level of recollection. Was the study only asking about events in the 2 weeks prior, month prior, etc.? Were women recruited during pregnancy rather than postnatally?

5. The authors mention that the Czech Republic, which the cohort was from, was a post-communist country undergoing a period of economic transition at the time. I think some more context around the importance of this period is needed and why it might be relevant to child development. Was it a period of stress for the mothers? This needs to be clearly articulated, and the context will be informative for non-European readers.

6. The last sentence on page 4 (“we then compare the results with outcomes obtained using the concurrent ELSPAC cohort from United Kingdom, referred to as ALSPAC (33) as well as other studies employing Strength and Difficulties Questionnaires (SDQs) to measure behavioural problems”) sounds like data from ALSPAC and other studies are being analysed and compared to ELSPAC data within the results. I don’t think this sentence is necessary, as it is to be expected that these comparisons would be made within the discussion. Rather, I would suggest stating hypotheses instead (perhaps based on what some of these studies have found).

Methods

1. The authors note at the start of page 6 that detailed information about the study is available elsewhere. While detailed information certainly isn’t expected, I still think that a brief description of the study is needed. E.g. was the cohort recruited before birth? Is it representative of other births in the Czech Republic? The authors also mention “ethical issues” – is this referring to ethics approval for the study, or were there specific ethical concerns around the study’s methodology/data collection/handling of participants?

2. Page 7, line 150 – give a reference for the International Standard Classification of Education.

3. In the statistical analysis section, I would recommend that the authors give the Ns for the included and excludes subjects.

4. What was the rationale for the use of inverse probability weighting (IPW) rather than multiple imputation (MI) to account for the impact of missing data? While IPW does adjust for differences between those included and those excluded in the sample, MI has the benefit of accounting for missing data while not reducing sample size. A combined approach could also be used here.

Results

1. Page 11 – were the differences between boys and girls tested statistically? If so, indicate that these were statistically significant p-values. If not, then I’m not sure we can really say that males and females scored differently without statistical testing.

2. I would recommend indicating significant effects in the tables, particularly Tables 4 and 5. Perhaps bolding the OR and C.I. numbers for significant effects.

3. For the birthweight models, I don’t see the value in interpreting effects where the confidence interval contains 1, even if considered weak. My concern is that it can be misleading – indicating a more meaningful effect than what is actually present.

Discussion

1. As stated with regard to the results, the effects were very weak for models with conduct problems and prosociality as the outcome, with the C.I.s containing 1. Interpreting these models as significant is a bit misleading, suggesting that there may be a more meaningful effect.

2. Page 15, line 269 – what is meant by “genetic environment”?

3. Page 15, lines 274-275 – the statement “though this was no longer apparent in our birth weight model adjusted for birth length” isn’t needed, as it is redundant given the sentence that follows.

4. For the first two sentences on page 16, it’s not clear how exactly this relates to why there may be differences between ELSPAC and ALSPAC. I think elaboration on this point is needed and clearly stating why this might impact results.

5. The authors mention that previous studies have observed some sex differences. Given the results of these previous studies, why were no interaction effects with sex tested?

6. The paragraph spanning pages 17-18 (lines 317-339) needs to be more cohesive in the message that it is trying to convey. I think it needs to remind the readers that birth weight/length can be an index of prenatal stress impacting the prenatal environment and consequently prenatal development. The authors could then discuss that this may impact brain development, due to the foetus adapting to the stressful environment, and this consequently plays a role in how the child responds and behaves in the postnatal environment. Essentially, I think the paragraph could more clearly lay out the possible pathway between prenatal stress to birthweight to child behaviour.

7. Page 19, line 363 – change “did not” to “have not”.

**********

6. 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 #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Birth weight rather than birth length is associated with childhood behavioural problems in a Czech ELSPAC cohort

PONE-D-21-02707R1

Dear Dr. Bienertová-Vašků,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Clive J Petry, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

I believe that the various revisions made have improved this manuscript and that it is now acceptable for publication.

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: All comments have been addressed

**********

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

**********

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

Reviewer #2: Yes

**********

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

**********

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

**********

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: The authors have addressed all comments. My main recommendation would be to proofread the manuscript, as there are some grammatical errors, particularly in some of the revised content. My other suggestion would be to rephrase the term "data free of recall bias" on page 4 line 88 to "data with reduced recall bias".

**********

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: No