Link Between Umbilical Cord Blood Adipokines and Early Childhood Health

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Review report

In general, the manuscript is very well written, with a clear and coherent structure. However, I have a significant critique regarding Table 1.

Table 1 lists studies that examine the association between umbilical cord blood and the neurological development of children. From my perspective, this table requires substantial revision.

1.     In the first column, the study population is presented. I recommend including maternal anthropometric data as well as child anthropometric data, as the cohort partially consists of women with overweight or obesity, and their children (normal weight, macrosomic, etc.) are being assessed for neurological abnormalities. This distinction is critical for the interpretation of the results.

2.     In the second column, the outcome is presented. I recommend, that the methodology should be specified. Was it measured objectively and if yes how, or collected through questionnaires, etc. And (for example) what kind of “neurodevelopment scores/measures“ were done. This is important to evaluate and interpret the findings.

Additionally, regarding the table:

3.     the first row contains an incorrect source citation (Rastogi & Lang, 2020). The cited reference points to an article by Castro-Rodriguez et al. (Castro-Rodriguez, J. A., Forno, E., Casanello, P., Padilla, O., Krause, B. J., & Uauy, R. (2020). Leptin in Cord Blood Associates with Asthma Risk at Age 3 in the Offspring of Women with Gestational Obesity. Annals of the American Thoracic Society, 17(12), 1583–1589. https://doi.org/10.1513/AnnalsATS.202001-080OC.), whose authors conducted the study. Please always ensure the use of the primary source and clearly specify the study population accordingly. In this case, the number "N=140" is incorrect. The correct figure is "N=339 children" (140 offspring were born from normal-weight mothers, 80 from overweight mothers, and 119 from obese mothers). Only the offspring of obese mothers with high cord blood leptin levels exhibit a 30% higher asthma risk at age 3.

Minor revision:

There are some little typos in the manuscript.

Line 208: A dot is missing after the source.

Line 209: There are two spaces behind the source.

Line 215 vs. 236: I am not a native speaker but I wonder why there are different types of spelling (pro-inflammatory vs. proinflammatory). Pleas check for consistent spelling, if there is no reason for writing it differently.

Finally, I have a general comment that may, but need not, be taken into account in a revision. The review describes the individual aspects well, but physical activity is never listed under “environmental influences”. In addition to diet, smoking behavior, drug use and body composition, exercise and an inactive lifestyle also play an important role in childhood development. It is becoming increasingly accepted that exercise can also influence the adipokine profile (leptin) and therefore also might have an influence on neurological development.

Author Response

Please see attached document

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review the manuscript entitled "Link Between Umbilical Cord Blood Adipokines and Early Childhood Health"

This was a nice review that contributes to the field of significance of adipokines in feto-maternal circulation. The authors not only demonstrate the significance of adipokines in mather-fetus/infant dyad but also describe the potential role of adiponectin and leptin for postnatal development of offsprings. 

Major comments:

1. The authors in section 1.3 and 1.4 describe the role of leptin and adiponectin in pregnancy however no information about the concentration of these adipokines in maternal circulation. Moreover, the possible factors affecting concentration of leptin and adiponectin in these sections should be discussed. These issues should be clearly described. The possible changes in relation to maternal BMI values and some disease such as GDM is essential to understand by readers that the possible changes in leptin and adiponectin during pregnancy might have an impact on prenatal development of the fetus.

2. Similarly, the section regarding adipokines in cord blood plasma was described, however no information about concentration of leptin and adiponectin. DEspite that the authors had pointed out the sex-specific differences in adipokines level, in my opinion other issues such as gestational age, and birth weight of newborns, should be also discussed.

3. The association between levels of leptin and adipokines in umbilical cord blood on early child neurological and immune health otcomes should be detailed discussed.

4. The limiting factors on assotiations leptin and adiponectin in umbical cord plasma and chilren health shuld be describe.

Minor comments:

1.  Table 1. Please add a row with information about methods used for determination of leptin and adiponectin concentrations.

2.  I suggest replace the word ‘correlation’ by ‘association’ in the Head of Table 1

Author Response

Please see attached document

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Many thanks for the revision. In my opinion, the manuscript has now been successfully revised and can be published. 

Author Response

Comment 1: Many thanks for the revision. In my opinion, the manuscript has now been successfully revised and can be published. 

We thank the reviewer for their comment

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for responding to my comments and for the clarifications provided. I appreciate your efforts to improve the manuscript; however, I believe that some key sections need further revision to reach an adequate level of quality. Here are my main observations:

1)      In the text of the manuscript should be information about concentration of adiponectin and leptin. These two adipokines play an important role in the regulation of insulin secretion, glucose and lipid metabolism, and belong to a group of molecules called appetite-regulating adipokines, however their levels are different. My recommendation: please add to the subchapter 1.3 and 1.4 suitable paragraph regarding leptin and adiponectin concentration

2)      Limiting and disturbing factors should be discussed

In present form the conclusion is in a laconic form. In my opinion this part has not been discussed enough. The authors should note the main limitations of the current state of knowledge in the area of leptin and adiponectin levels in  Early Childhood Health.  The authors should focused on indicate the main issues regarding leptin and adiponectin in  early  childhood health, namely:

•   Whether the results presented by different work’s group are consistent
•   Whether the size of the groups was sufficient
•   Whether the factors that confound the results of the studies were sufficiently discussed by authors

Finally, the  guidelines for future research should be outlined.

 3)      I recommend the changes in subchapter numbering, as follows: 1. Introduction, 2. Developmental Origins of Health and Disease, 3. Adipokines in Pregnancy, 4. Role of Leptin and Adiponectin in Pregnancy, 5. Role of leptin and adiponectin in Early  Childhood Health  (5.1  Child Inflammatory Disease, 5.2. Early Childhood Neurological Disease), 6. Conclusion and Future perspectives

4) In table 1 in the column Sex-effect only one study confirm the impact of sex on adipokines concentration, while in the subchapter  "Sex-specific Differences in Adipokines" was noted that "Sex-specific differences in umbilical cord blood adipokines have been reported in various studies...." I recommend add the one more table to the manuscript with the information of the impact of sex on adiponectin and leptin level

If you address these points, the manuscript will have an even stronger foundation and be better positioned to meet editorial requirements.

Author Response

Please see the attached document

Author Response File: Author Response.docx

Round 3

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have addressed all my concerns