Exposure to Ambient Particulate Matter during Pregnancy: Implications for Infant Telomere Length

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This paper investigates the correlation between prenatal exposure to ambient particulate matter (PM2.5) and infant telomere length, a potential mediating factor in the association between fetal exposure to air pollution and disease development. The analysis explores links between PM2.5 exposure during different pregnancy trimesters and infant telomere length at one month old. Results indicate that PM2.5 exposure in the 2nd and 3rd trimesters correlates with longer infant telomere length. The study also examines associations with factors like maternal depression, age, and infant sex. There are some problems, which must be solved before it is considered for publication.

1) The study has a small sample size (n=74), which may limit the generalizability of the findings.

2) The paper lacks a comprehensive discussion of the potential mechanisms underlying the observed associations between PM2.5 exposure and telomere length.

3)It is worth noting a substantial divergence in PM2.5 concentration between indoor and outdoor environments. The study overlooks personalized exposure estimates, a factor that could introduce variability in exposure levels and should be considered.

4）It is advisable to clearly expound on the significance of the research in either the introduction or conclusion, emphasizing its contribution to the field and the implications of the findings for future research or public health policies.

5）Add some graphs to visualize the obtained data. Enhancing the paper with graphical representations of the obtained data would not only improve its visual appeal but also facilitate a more accessible and nuanced interpretation of the results for readers.

Comments on the Quality of English Language

The English quality of this paper is good,only some minor sentences need to be modified.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This is an excellent manuscript evaluating the relationship between prenatal PM2.5 exposure and infant telomere length.  It provides a valuable contribution to the literature on reproductive and developmental effects of air pollution by: focusing on an endpoint beyond the traditional metrics of birth weight and preterm birth, namely telomere length; disaggregating effects by trimester to help elucidate windows of susceptibility; incorporating maternal characteristics, especially multiple stress indicators; and framing the work in context of the overall mixed results in this area.  The analysis and presentation of the results are well-designed to highlight the main findings, and the discussion section is strong, pointing out potential explanations for and implications of the results, as well as considering alternatives.

The use of stepwise regression is a good way to identify strong predictors from among many candidate variables.  However, the authors should expand the discussion of the model building process, including more details on variable inclusion and exclusion criteria, the order of variable selection and deselection, and whether sensitivity analyses were performed.  This is important for building confidence in the findings.

I have several specific comments for the authors to consider:

1. L116: The information in Section 2.3 is very valuable for understanding the qPCR protocols used and potentially conducting follow-on experiments.  If space is needed in the manuscript, some of the details could be moved to supplemental information.
2. L204-206: What is meant by covariate probability?  This is a good place to describe model construction and variable selection in more detail.
3. L226: This should be p=0.000 rather than p<0.000.
4. L228-229: Although the variables in the model only explain 34% of the variance, the authors point out elsewhere that many factors affect telomere length, including some not explicitly considered in this study, such as inflammation and telomerase activity, so even this modest association is informative.  Suggest including an explanation of this in the Discussion section.
5. L254-258: The indications of lower vulnerability during the first trimester and the lack of evidence for a concentration-dependent response are interesting findings that bear investigation in future studies.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf