Inadequate Status and Low Awareness of Folate in Switzerland—A Call to Strengthen Public Health Measures to Ensure Sufficient Intakes
, Nina Wehrli 1, Kurt Bärlocher 2, Maria Andersson 3 and Janice Sych 4Round 1
Reviewer 1 Report
I would like to thank the authors for this well written manuscript. The study was clear and easy to follow. My comments below.
Methods section
Why are the author using bootstrapped CI (l.151)? To my knowledge, this is appropriate for large numbers. Clarification would be appreciated in the context of this work.
Discussion section
l.289 In addition to citation 31, the comments of Kancheria et al (Nutrients 2020, 12, 1352; doi:10.3390/nu12051352) could enrich the references on the fortification debate.
l.330 Limitations of self reported supplementation behavior reporting, could be discussed because there is a risk of overestimation of appropriate behaviour. However the difference in supplementation has been described in national claims database recently, thus conforting the results of the survey (Nutrients 2020, 12(10), 3170; doi:10.3390/nu12103170)
Minor edits
Additionnaly, there are a several minor revisions that I would recommend to perform, they are listed below.
Consistency and proper formatting of numbers :
l.52 50'000: use format 50,000
l.56 215'000: use format -> 215,000
l.46 Reference 10 should be at the end of the sentence
l.68 Unclear what 2002/03 means : is it year range ? (2002-2003)
l.125 Supplementary table could be referred as "Table A1, Appendix A" (as it is the usual choice in Nutrients)
Table 1 : RBC folate is referring to median concentration ? please do tell. Confidence intervals are usually
Author Response
We would like to thank the reviewer for the valueable comments. We have replied to the comments one by one below.
Methods section
Why are the author using bootstrapped CI (l.151)? To my knowledge, this is appropriate for large numbers. Clarification would be appreciated in the context of this work.
Our reply: Thank you for pointing this out. We have adapted the results and are now presenting interquartile range instead of a bootstrapped CI (see table 1).
Discussion section
l.289 In addition to citation 31, the comments of Kancheria et al (Nutrients 2020, 12, 1352; doi:10.3390/nu12051352) could enrich the references on the fortification debate.
Our reply: Than you for this comments. We have added the suggested reference (Line 290).
l.330 Limitations of self reported supplementation behavior reporting, could be discussed because there is a risk of overestimation of appropriate behaviour. However the difference in supplementation has been described in national claims database recently, thus conforting the results of the survey (Nutrients 2020, 12(10), 3170; doi:10.3390/nu12103170)
Our reply: Thank you for this suggestion. We have added a short section pointing this out to the discussion (lines 342-347).
Minor edits
Additionnaly, there are a several minor revisions that I would recommend to perform, they are listed below.
Consistency and proper formatting of numbers :
l.52 50'000: use format 50,000
l.56 215'000: use format -> 215,000
l.46 Reference 10 should be at the end of the sentence
l.68 Unclear what 2002/03 means : is it year range ? (2002-2003)
l.125 Supplementary table could be referred as "Table A1, Appendix A" (as it is the usual choice in Nutrients)
Our reply: Thank you for those comments. We have adapted the text accordingly.
Table 1 : RBC folate is referring to median concentration ? please do tell. Confidence intervals are usually
Our reply: Yes, that is correct, and we have added this information in the corresponding footnote of Table 1 – (Line135).
Methods section
Why are the author using bootstrapped CI (l.151)? To my knowledge, this is appropriate for large numbers. Clarification would be appreciated in the context of this work.
Our reply: Thank you for pointing this out. We have adapted the results and are now presenting interquartile range instead of a bootstrapped CI (see table 1).
Discussion section
l.289 In addition to citation 31, the comments of Kancheria et al (Nutrients 2020, 12, 1352; doi:10.3390/nu12051352) could enrich the references on the fortification debate.
Our reply: Than you for this comments. We have added the suggested reference (Line 290).
l.330 Limitations of self reported supplementation behavior reporting, could be discussed because there is a risk of overestimation of appropriate behaviour. However the difference in supplementation has been described in national claims database recently, thus conforting the results of the survey (Nutrients 2020, 12(10), 3170; doi:10.3390/nu12103170)
Our reply: Thank you for this suggestion. We have added a short section pointing this out to the discussion (lines 342-347).
Minor edits
Additionnaly, there are a several minor revisions that I would recommend to perform, they are listed below.
Consistency and proper formatting of numbers :
l.52 50'000: use format 50,000
l.56 215'000: use format -> 215,000
l.46 Reference 10 should be at the end of the sentence
l.68 Unclear what 2002/03 means : is it year range ? (2002-2003)
l.125 Supplementary table could be referred as "Table A1, Appendix A" (as it is the usual choice in Nutrients)
Our reply: Thank you for those comments. We have adapted the text accordingly.
Table 1 : RBC folate is referring to median concentration ? please do tell. Confidence intervals are usually
Our reply: Yes, that is correct, and we have added this information in the corresponding footnote of Table 1 – (Line135).
Reviewer 2 Report
The authors have presented an interesting account on folate awareness to strengthen the public health measures to ensure sufficient intake of folate in Switzerland. I really appreciate the authors long run effort to complete this project with the awakening call for nutritional requirements in terms of sufficient folate intake. Authors here in this study have targeted the folate requirements during periconceptional period and its risk in neural tube defects. To address their question, authors have designed the study thoroughly and selected enough subjects to conclude. I have some minor concerns and suggestions to make this article easily understandable to readers and to convey the message that authors are trying to.
Table 1; clearly depict the overall status of folate in WRA and PW in Switzerland. The results suggest that there is a major difference the folate concentrations between the groups. I have following questions,
- Is there any differences with in the group? Ex: PW with and without supplement and same in WRA with and without supplement.
- If so, can authors discuss that data? because it will give a clear evidence of lack of folate awareness.
- Though the authors did appropriate statistical test, I would like to suggest performing post-hoc Tukey’s test to compare the differences between the groups.
Authors in their study also considering male subjects, it would be good if they discuss some aspects of folate deficiency associated with anemia (all age groups and irrespective of sex). So that it will convey a general message regarding folate deficiency including neural tube defect.
Including a graphical flow chart of methodology will give a quick glance to readers.
Is there any information about poverty and folate awareness in PW??
Author Response
We would like to thank the reviewer for the valueable comments. We have replied to the comments one by one below.
The authors have presented an interesting account on folate awareness to strengthen the public health measures to ensure sufficient intake of folate in Switzerland. I really appreciate the authors long run effort to complete this project with the awakening call for nutritional requirements in terms of sufficient folate intake. Authors here in this study have targeted the folate requirements during periconceptional period and its risk in neural tube defects. To address their question, authors have designed the study thoroughly and selected enough subjects to conclude. I have some minor concerns and suggestions to make this article easily understandable to readers and to convey the message that authors are trying to.
Table 1; clearly depict the overall status of folate in WRA and PW in Switzerland. The results suggest that there is a major difference the folate concentrations between the groups. I have following questions,
- Is there any differences with in the group? Ex: PW with and without supplement and same in WRA with and without supplement.
- If so, can authors discuss that data? because it will give a clear evidence of lack of folate awareness.
Our reply: Thank you for this comment. We have added information on the difference in folate status between women who did take supplements and those who did not (Lines 170 and table 1). We have also added a sentence to the discussion pointing out the importance of this finding (Lines 269).
- Though the authors did appropriate statistical test, I would like to suggest performing post-hoc Tukey’s test to compare the differences between the groups.
Our reply: As suggested above, we have added some further statistical comparisons, specifically on the effect of supplements in both WRA and PW. This was done using Mann-Whitney U test as our data are not normally distributed. Furthermore, we have re-done the comparison of RBC folate between trimesters using Kruskal-Wallis test. (By mistake this was first done using ANOVA, which is not correct since the data are not normally distributed. The text in the statistical part as well as the results have been updated accordingly.
Authors in their study also considering male subjects, it would be good if they discuss some aspects of folate deficiency associated with anemia (all age groups and irrespective of sex). So that it will convey a general message regarding folate deficiency including neural tube defect.
Our reply: Thank you for this suggestion. We did consider including other aspects of folate deficiency, however, we have finally decided not to do this, to avoid overloading the discussion with too much. Even though we did include men in the survey, the questions asked were mainly focused around the effects of folate in the periconceptional period, and thus we decided to keep the discussion focused on this topic.
Including a graphical flow chart of methodology will give a quick glance to readers.
Our reply: Thank you for this suggestion. We have thought about a graphical flow chart. However, as there is not really any flow of participants with only one time point in each of the studies, we feel this will not add much clarity and would prefer to not include a chart. If we include a flow chart, this could include two boxes for the survey on awareness, namely one with all participants who accessed the survey and a second one with those completing. For the folate status, all women who gave venous blood samples were included in the study, so there would be just one box, unless we would include all women who took part in the original iodine study in a first box with a second one including only those with venous blood samples. However, as we do not describe the sample of women who took only part in the iodine study here, we feel this might be more confusing rather than making it clearer. Nevertheless, if requested, we are of course happy to provide a graphical overview.
Is there any information about poverty and folate awareness in PW??
Our reply: In the folate-knowledge survey we did investigate the effect of income as well as education on the answers and did show an effect for some answers. The general tendency was that participants with lower education and income were less aware of the importance of folate (discusses in line 320 and following). This influence was also shown in previous studies as discussed around lines 317.
Our lowest income category was below 6000, with no additional questions on poverty in the study group. Table 2 shows that the highest percentage of study participants were in the highest income category. This was also the case in the recent National Nutrition Survey menuCH (Pestoni et al. Nutrients 2019, 11, 126). Generally in surveys the subgroup in with the lowest income is challenging to reach. Similar to low education, we also expect that folate awareness issues might be even lower in low income and poverty subgroups. Indeed it would be valuable information to collect in follow-up studies.
Lines 178 and Lines 375 were modified to emphasize this point.
