PONE-D-25-02483Process evaluation of a randomised controlled trial aimed at improving health behaviours and vitamin D status during pregnancy: Implementation of the SPRING trialPLOS ONE

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“This work was supported by the UK Medical Research Council [MC_PC_21003; MC_PC_21001] and National Institute for Health and Care Research National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust. The work leading to these results was supported by the European Union’s Seventh Framework Programme (FP7/2007–2013), projects EarlyNutrition, ODIN and LifeCycle under grant agreements numbers 289346, 613977 and 733206, and by the BBSRC (HDHL-Biomarkers, BB/P028179/1 and BB/P028187/1), as part of the ALPHABET project, supported by an award made through the ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL), Horizon 2020 grant agreement number 696295. We are extremely grateful to Merck GmbH for the kind provision of the Vigantoletten supplement. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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3. Thank you for stating the following in the Competing Interests section:

“Janis Baird, Mary Barker and Wendy Lawrence have received grant research support from Danone Nutricia Early Nutrition. Cyrus Cooper has received consultancy, lecture fees and honoraria from AMGEN, GSK, Alliance for Better Bone Health, MSD, Eli Lilly, Pfizer, Novartis, Servier, Merck, Medtronic and Roche. Members of Hazel Inskip’s team have received grant research support from Nestec and Danone Nutricia Early Life Nutrition. Nicholas Harvey has received consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Servier, Shire, UCB, Consilient Healthcare, Theramex, Kyowa Kirin and Internis Pharma.”

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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: Partly

Reviewer #2: Yes

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

Reviewer #1: No

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: Yes

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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: Differences between groups were assessed using normal univariate statistics for continuous data and non parametric for non normal data. For the subgroup analyses, multiple linear regression models were used to compare the intervention and control groups. The R square values on the multiple regression might be helpful. To account for differences between the groups at baseline, analyses were adjusted for potential confounders. The analysis as discussed in the statistical section was routine as one would expect in this type of application. The analysis was done appropriately but could have been improved. Also, the analysis was presented somewhat fragmented. There were many pieces to try to digest separately. Groups were compared but at various times. What about a group or time effect overall? Was there any group by interaction effect? Figure S3 raises issues as to what is possibly the best intervention compared to control?

Fidelity, dose, and reach were evaluated descriptively. It is not really clear how much this added to the entire objectives of the study which mainly was to compare the vitamin D to the Healthy Conversation groupings. The design of the study was of the factorial nature. Sample size calculations were implemented.

One tries to get an idea of the flow of the study in a graphic and Figure S3 was not very helpful. A good schematic of the mechanics of the study showing what happens and when would have been more helpful.

The conclusion appears to dwell on intervention delivery and the mechanics of such. Where exactly is there a statement that states the women’s nutritional status was improved or not overall?

Reviewer #2: The manuscript is clearly written and of high quality. The results are very valuable for contextualizing the study's efficacy findings and to understand the implementation, dose and reach of the intervention.

Introduction/Methods: Please provide brief background information on the Healthy Conversation Skills intervention, especially whether this intervention has been implemented and evaluated among pregnant women in other settings, and if so, what the general results were regarding its efficacy.

Intervention Line 131: Please clarify the context of Vitamin D supplementation among pregnant women in the study area. Are women in the study area advised by their health care providers to take their own Vitamin D supplementation or were they relying on it being given by the hospital? If the former, could some participants in both control and intervention groups have taken Vitamin D and could that have confounded the final trial's efficacy results?

Line 136: Participants were recruited at less than 17 weeks’ gestation. Participants recruited between 15-17 weeks would have missed their baseline appointment at 14 weeks. When did they receive their capsules?

Line 154: same question as above for the Healthy Conversations with women at 14 weeks and the baseline interview at 14 weeks.

Line 171: “Pill counts were conducted at the 19- and 34-week appointments..”: We assume pill counts were self-reported, please specify.

Results Line 320-322: Pregnant women were recruited from the main maternity hospital in Southhampton. The Reach results can be contextualised with respect to how representative the maternity hospital setting is of all pregnant women in Southhampton. Please clarify if some Southhampton women seek antenatal care at other types of health facilities other than this maternity hospital. This could contextualise why the SPRING sample included higher proportions of older women and lower proportions of younger women. Could it be that younger women access antenatal care from the maternity hospital at late stages in their pregnancy (beyond 17 weeks) or younger women and those from ethnic minorities access care from other types of facilities?

The focus of the Healthy Conversation was determined by what each woman wanted to discuss as the primary health behaviour (e.g. physical activity/diet/other). Women with low educational attainment and obese women were more likely to never discus physical activity as the primary health behaviour. This could be due to lack of awareness/knowledge/health literacy on the importance of physical activity or perceived behavioural control, or lack of motivation, among other reasons. While not the focus of the study, could the authors recommend or comment on ways in which this intervention, or future interventions, could promote women (particularly those with low educational attainment or who are obese) to start talking about ways to improve their physical activity during pregnancy and to recognise the importance of physical activity.

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Reviewer #1: No

Reviewer #2: Yes: Ronel Sewpaul

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Process evaluation of a randomised controlled trial aimed at improving health behaviours and vitamin D status during pregnancy: Implementation of the SPRING trial

PONE-D-25-02483R1

Dear Dr. Baird,

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.

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Kind regards,

Francis Xavier Kasujja

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 #1: 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 #1: (No Response)

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

Reviewer #1: (No Response)

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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 #1: (No Response)

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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 #1: (No Response)

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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 #1: (No Response)

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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 #1: No

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