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Systematic Review
Peer-Review Record

Pregnancy Outcomes in Women with Biventricular Circulation and a Systemic Right Ventricle: A Systematic Review

J. Clin. Med. 2024, 13(23), 7281; https://doi.org/10.3390/jcm13237281
by Triantafyllia Grantza 1,*, Alexandra Arvanitaki 1,2,*, Amalia Baroutidou 1, Ioannis Tsakiridis 3, Apostolos Mamopoulos 3, Andreas Giannopoulos 4, Antonios Ziakas 1 and George Giannakoulas 1
Reviewer 1: Anonymous
Reviewer 2: Anonymous
J. Clin. Med. 2024, 13(23), 7281; https://doi.org/10.3390/jcm13237281
Submission received: 28 October 2024 / Revised: 20 November 2024 / Accepted: 22 November 2024 / Published: 29 November 2024

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is a very interesting article about the maternal and fetal outcomes among pregnant women with biventricular circulation and systemic right ventricle.

The methodology of this systematic review and meta-analysis  is well conducted, however, there are some weakness point:

-firstly, authors didn’t declare the MESH terms used in the literature search

-a flow chart diagram demonstrating inclusion and esclusion criteria in the final selection of articles is missing

-Table 3 and 6 are not well depicted; they could be more impressive

-there is only the forest plot about subgroup analysis for NYHA class between d-TGA and ccTGA group; while authors declared to not observe no statistical difference regarding worsening sRV function, need for hospitalization, prematurity but none of these was reported in the Figure 3, as previously mentioned

Comments on the Quality of English Language

Overall, English level is good.

Author Response

 

Dear Sir/Madame,

 

Thank you very much for taking the time to review this manuscript. We believe that our manuscript has been substantially improved following a thorough revision based on reviewer’s thoughtful comments and we hope to be fit for publication in Journal of Clinical Medicine. Please find the detailed responses below.

 

Reviewer 1: The methodology of this systematic review and meta-analysis is well conducted, however, there are some weakness points:

 

1.     Firstly, authors didn’t declare the MESH terms used in the literature search.

Authors’ Response: We thank the reviewer for pointing this out. We have included the literature search, including the MESH terms in the supplementary appendix; appendix S1, page 3-4, PubMed search. We have also made a comment in main manuscript to highlight it as follows:

“The search strategy used in PubMed (MESH terms included) and the Cochrane database are presented in Supplemental Material, appendix 1. “

 

 

2.     A flow chart diagram demonstrating inclusion and exclusion criteria in the final selection of articles is missing.

 

Authors’ Response: We thank the reviewer for their comment. A Prisma 2020 flow diagram for new systematic reviews which included searches of databases and registers was included in the supplementary appendix; Figure S1, page 8.

 

3.     Table 3 and 6 are not well depicted; they could be more impressive.

 

Authors’ Response: We thank the reviewer for their suggestion. All information provided for each case was included. Unfortunately, no further details could be extracted from original studies.

 

4.     There is only the forest plot about subgroup analysis for NYHA class between d-TGA and ccTGA group; while authors declared to not observe no statistical difference regarding worsening sRV function, need for hospitalization, prematurity but none of these was reported in the Figure 3, as previously mentioned.

 

Authors’ Response: We thank the reviewer for their remark. Forest plots of subgroup analysis of outcomes without a statistically significant difference between the two groups were added on supplementary appendix; Table S4, page 14.

 

 

 

Your sincerely,

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript provides a systematic review of pregnancy outcomes in women with biventricular circulation and a systemic right ventricle, focusing on maternal and neonatal complications. It is a valuable topic due to the high-risk nature of pregnancy in this population, where evidence is limited. Although the review is based on observational retrospective studies, which could introduce bias in the results, and reduce the strength of the evidence, the methodology is solid, and the message is clear: “pregnancy in asymptomatic or mildly symptomatic women with a biventricular circulation and sRV can be well tolerated”.

I would like to commend the authors for conducting this thorough and well-structured analysis, following the PRISMA guidelines comprehensively.

 

Please find below some individual comments:

1)        The authors state that “high statistical heterogeneity was observed among the included studies”. Beyond the subgroup analyses, sensitivity analyses (e.g. leave-one-out analyses) could also be conducted to explore the impact of each individual study on the overall results (Maybe a particular study is driving the heterogeneity). This would increase robustness of the results.

2)        In the same vein, the authors might consider using the GRADE approach to evaluate the certainty of evidence for each outcome. This would provide a systematic assessment of the quality of the evidence, especially in the context of observed heterogeneity

3)        “A worsening of NYHA class during pregnancy occurred more often in the d-TGA

group than ccTGA (18% vs 6%, p value= 0.03)”.

The authors could elaborate more on the clinical implications of the higher incidence of worsening NYHA class during pregnancy in the d-TGA group, in the discussion section.

Author Response

Dear Sir/Madame,

 

Thank you very much for taking the time to review this manuscript. We believe that our manuscript has been substantially improved following a thorough revision based on reviewer’s thoughtful comments and we hope to be fit for publication in Journal of Clinical Medicine. Please find the detailed responses below.

 

Reviewer 2:

1)     The authors state that “high statistical heterogeneity was observed among the included studies”. Beyond the subgroup analyses, sensitivity analyses (e.g. leave-one-out analyses) could also be conducted to explore the impact of each individual study on the overall results (Maybe a particular study is driving the heterogeneity). This would increase robustness of the results.

 

Authors’ Response: We thank the reviewer for their comment. Sensitivity analysis, using the leave-one-out method, was conducted in order to increase robustness of our results. We have modified manuscript accordingly as follows:

“Apart from the subgroup analysis, we tried to elucidate the source of heterogeneity further with sensitivity analysis; by performing leave-one-out analysis. Statistical heterogeneity among individual studies was obtained using the Cochrane’s Q test and the I2 statistic; value >50% indicated substantial heterogeneity, so sensitivity analysis was conducted. After removing the outlier studies, the I2 didn’t decrease under 50%, suggesting that these studies did not alter the overall conclusions and weren’t the only ones that contributed to heterogeneity. “

 

 

2) In the same vein, the authors might consider using the GRADE approach to evaluate the certainty of evidence for each outcome. This would provide a systematic assessment of the quality of the evidence, especially in the context of observed heterogeneity.

 

Authors’ Response: We thank the reviewer for their remark. Indeed, GRADE approach was performed to evaluate the overall certainty of evidence. Risk of bias assessment of the included studies was also rated by Newcastle- Ottawa Scale, and publication bias by funnel plot and Egger’s regression test. GRADE approach was updated on pages 4, 14 of the manuscript. Risk of bias and publication bias assessments were included in supplementary appendix; Table S3 & S4, respectively, page 12-13.

“The overall rating of the quality of evidence was assessed by GRADE approach. Since the included studies were observational, the initial evaluation started at low certainty. The quality was downgraded for three elements, including potential risk of bias, inconsistency due to substantial heterogeneity and potential publication bias. However, certainty was upgraded for illustrating a dose-response relationship, as the results were proportional to the degree of outcomes. Certainty of evidence was rated as low, driven by study limitations, substantial heterogeneity and potential publication bias. “

 

 

3) “A worsening of NYHA class during pregnancy occurred more often in the d-TGA group than ccTGA (18% vs 6%, p value= 0.03)”. The authors could elaborate more on the clinical implications of the higher incidence of worsening NYHA class during pregnancy in the d-TGA group, in the discussion section.

 

Authors’ Response: We thank the reviewer for their comment. We have added a comment regarding clinical implications of NYHA worsening on discussion section, page 16 of manuscript.

“A worsening of NYHA class during pregnancy occurred more often in the d-TGA group than ccTGA (18% vs 6%, p value= 0.03). Although NYHA classification may be a subjective measure of symptoms, worsening of NYHA class reflects a reduction in exercise capacity in pregnant women with a d-TGA and an atrial switch operation, which could be associated with chronotropic incompetence, limited tolerance to haemodynamic changes during pregnancy and susceptibility to heart failure and arrhythmia [32]. On the other hand, women with a ccTGA seem to tolerate pregnancy better compared to those with a d-TGA. However, the difference in symptom worsening could not be translated into a difference in maternal or fetal outcomes between the two groups. “

 

 

 

 

Your sincerely,

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