Early Identification of the Maternal, Placental and Fetal Dialog in Gestational Diabetes and Its Prevention
Round 1
Reviewer 1 Report
The authors summarize the findings of the medical literature about Gestational Diabetes, its detection and its prevention.
- The literature is not up-to-date. There are current reviews and studies about additional biomarkers that have not been included in this review.
- English language needs thorough editing.
- The authors have not conformed their manuscript in a comprensive way (e.g. The rationale is not well defined. The search strategy is not included, and aims are formulated generally but not concretely.)
- There is a lack of figures that could be useful in this review. The tables are overwhelming and unnecessary.
Author Response
The authors summarize the findings of the medical literature about Gestational Diabetes, its detection and its prevention.
- The literature is not up-to-date. There are current reviews and studies about additional biomarkers that have not been included in this review.
Response: We thank the reviewer for this comment. As described in our review, there are over 500 different biomarkers that were investigated as GDM predictors. In the context of an invited mini-review, we chose to focus on eight biomarkers (plus two glycemic markers) that in our literature review were found to be significantly investigated and with predictive potential. A recent scoping review (Bogdanet et al. Emerging Protein Biomarkers for the Diagnosis or Prediction of Gestational Diabetes-A Scoping Review. J Clin Med April 2021) reviewed the literature for markers with at least 5 citations between 2017–2020 and summarized 15 biomarkers including 7 of the 8 markers we described. However, if there is a specific marker that the reviewer feels should be added to the review – we are happy to include it. Also, the references list was updated, with the addition of recent studies and reviews.
- English language needs thorough editing.
Response: The manuscript has undergone full English editing and was revised accordingly.
- The authors have not conformed their manuscript in a comprensive way (e.g. The rationale is not well defined. The search strategy is not included, and aims are formulated generally but not concretely.)
Response: We thank the reviewer for this comment. This was an invited mini-review, specifically not a systematic review, and therefore was designated and written as such. Description of search methods and inclusion criteria was therefore out of the scope of this manuscript. Nevertheless, in order to better describe the aims of our review, we have revised the introduction section (page 2, lines 43-45).
- There is a lack of figures that could be useful in this review. The tables are overwhelming and unnecessary.
Response: We thank the reviewer for this comment. A figure which illustrates different mechanisms leading to GDM with related biomarkers has been added to the manuscript. Regarding tables – other reviewers found them useful and important, and therefore we will leave this to the editor's decision.
Reviewer 2 Report
The manuscript is well written and nicely explains the topic. However, to further improve its scientific quality, a major revision is recommended.
-Among the well-recognized clinical risk factors for GDM, advanced maternal age (i.e., 35 years instead of 40) and overweight/obesity (BMI of 25 and above in Caucasians) should be included. Also, it would be nice to quantify the contribution of each clinical predictor to an increased risk of GDM (i.e., a range of odds ratios from different models, if available).
-Pregnancy-related proteins (i.e., PAPP-A, b-hCG) are routinely measured in obstetric practice as biochemical parts of the first-trimester combined test (FTCT). It might be of interest for the reader to assess the role of FTCT as an early predictor of GDM development.
-Compared to typical universal screening at 24-28 weeks of gestation, targeted-selective screening procedures (as the ones recommended by the Italian and UK National Health Services), retain the potential to GDM early on and with significant benefits on the risk of fetal/abdominal overgrowth, and possibly future childhood obesity. Disadvantages include difficulties in the accurate identification of all women at risk for GDM and its complications, depending on which combination of risk factors is being used. I would suggest stressing the concept that the search and validation of novel circulating biomarkers and predictive models for use in early pregnancy (or in the periconceptional period) are vital to improve the diagnosis and outcomes of GDM, for mothers, newborns and the society as a whole.
-I would suggest updating and shortening the reference list, by preferring articles published within the last 5 years. Some recent references to be considered: doi: 10.3390/ijerph16193654 ; doi: 10.1016/j.coph.2021.06.003 .
Author Response
- Among the well-recognized clinical risk factors for GDM, advanced maternal age (i.e., 35 years instead of 40) and overweight/obesity (BMI of 25 and above in Caucasians) should be included. Also, it would be nice to quantify the contribution of each clinical predictor to an increased risk of GDM (i.e., a range of odds ratios from different models, if available).
Response: We thank the reviewer for this important comment. Table 1 has been updated accordingly. We have added an odds ratio for gestational diabetes deriving from large studies and systematic reviews (Table 1).
- Pregnancy-related proteins (i.e., PAPP-A, b-hCG) are routinely measured in obstetric practice as biochemical parts of the first-trimester combined test (FTCT). It might be of interest for the reader to assess the role of FTCT as an early predictor of GDM development.
Response: We thank the reviewer for this comment. Indeed, some studies have evaluated the use of FTCT as a GDM predictor with conflicting results, and probably affected mainly by the contribution of low PAPP-A. We have added a paragraph discussing the FTCT value (Page 6, lines 210-219).
- Compared to typical universal screening at 24-28 weeks of gestation, targeted-selective screening procedures (as the ones recommended by the Italian and UK National Health Services), retain the potential to GDM early on and with significant benefits on the risk of fetal/abdominal overgrowth, and possibly future childhood obesity. Disadvantages include difficulties in the accurate identification of all women at risk for GDM and its complications, depending on which combination of risk factors is being used. I would suggest stressing the concept that the search and validation of novel circulating biomarkers and predictive models for use in early pregnancy (or in the periconceptional period) are vital to improve the diagnosis and outcomes of GDM, for mothers, newborns and the society as a whole.
Response: We thank the reviewer for this important comment. We have emphasized the importance of GDM diagnosis in section 3 – "importance of GDM prediction". In order to further stress the importance of this issue, we have added this to the "conclusions" section (page 9, lines 351-353).
- I would suggest updating and shortening the reference list, by preferring articles published within the last 5 years. Some recent references to be considered: doi: 10.3390/ijerph16193654 ; doi: 10.1016/j.coph.2021.06.003 .
Response: We thank the reviewer for this comment. the reference list has been shortened and both references were added.
Round 2
Reviewer 2 Report
Dear Authors,
The manuscript has been satisfactorily revised according to this reviewer's comments. I have only a minor concern.
In lines 226-228, I would suggest explaining that, based on current evidence, it is still uncertain whether one or the other of the two factors (namely, FTCT value and PAPP-A levels - this latter as either absolute or MOMs terms) is better to predict GDM.
Author Response
We thank the reviewer for this comment. The manuscript was revised accordingly (page 7, lines 229-231).
