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Both reviewers have found that the revisions adequately address their previous concerns and recommend acceptance of the manuscript in its current form.
no comment
Thank you for incorporating the comments and the edits look good.
no comment
no comment
I have no additional comments, Authors have appropriately addressed my concerns.
I have no additional comments, Authors have appropriately addressed my concerns.
I have no additional comments, Authors have appropriately addressed my concerns.
As you can see, both Reviewers 2 and 3 have provided important suggestions for how your articles should be improved. It is important to respond to their comments
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The manuscript overall is interesting and well-written.
Some minor comments regarding the methods:
1. Since the manuscript is focused on outcomes after the 20th week of pregnancy, it is unclear why wouldn't time to event analysis be considered but used logistic regression model instead.
2. It is unclear which variables were included in the multivariable logistic regressions.
3. The result of multivariate logistic regression would be shown clearer in a table.
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See below
See below
See below
The paper is well written and uses standard definitions of preeclampsia. however, the clinical characteristics of women with preeclampsia is not shown. The number of twin pregnancies is reasonable, but the parameters described are not specific to twin pregnancy, and were not compared to another group. The utility of "predictors" at 24-28 weeks is complex and prediction analysis would usually use ROC curves and predictive value. That said, The prediction of consequences given the gestations chosen is likely to be of greater value that the diagnosis per se.
There is wide spread use of novel biomarkers which would increase the utility of this paper to other groups. The biomarkers chosen contain considerable overlap between diagnostic groups and it is hard to see how that would provide utility in every day practice. The combining of multiple factors may better help prediction of morbidity outcomes.
Language is clear and professional. The paper is well organized with a consistent and correct structure.
However, provided background needs more detail. Indeed, several studies have explored predictive markers of PE in twin pregnancies (e.g. PMID: 31936659, PMID: 37533238, PMID: 36149818 etc...).
The paper is original and its research question is within the scope of the journal. Research question appears well defined, relevant, and meaningful. Ethical standards are respected.
Authors stated that "Blood samples were analyzed using automated hematology and biochemical systems". However, it should be specified the technique/system used to measure each analyte under study to allow for replication. Also, for the definition of PE did Authors use also fetal parameters ? E.g. SGA fetuses, altered uterine doppler ultrasound? Also, why Authors did not perform a separate analysis for early onset vs. late onset PE? Or between HDP-non-PE and PE?
The following sentence is a repetition: "Levels of serological markers were compared between women who developed PE and those who did not using independent sample t/t tests or Mann-Whitney U tests".
Regarding uric acid, it would be useful to report uric acid to creatinine ratio since it has been recently shown how the ratio could help differentiate uric acid hyperproducers from uric acid underexcretors, the latter being less associated with the development of cardiovascular diseases. A recent study has shown how serum uric acid to serum creatinine ratio is associated with adverse pregnancy outcomes and PE development. To this reviewer's best knowledge no reports have explored the ratio in a cohort of twin pregnancies.
Results of the present study are of clear interest and merit. However, I do believe one of the main learning points here has not been addressed. Hemoglobin, hematocrit and creatinine also reflect hemodilution state which is a crucial point in regulating maternal hemodynamics. The latter plays a central role in the pathogenesis of PE and is of crucial importance for the management of high risk patients (see PMID: 38350640). Higher hemoconcentration leads to a reduced circulating volume with a consequent decrease in cardiac output and supply to the growing fetus.
In Table 1 please do not report both dichotomic values (i.e. if in the table you choose to report nulliparity prevalence, reporting also multiparous output is not needed since is total minus nulliparity; same for all other variables like autoimmune disease yes and no etc....).
In Figure 2 and Figure 3, how were values on x axis chosen ? This should be specified both in methods section and Figure legend. Also, it would be useful to specify p values inside each panel.
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