Association between the stage of labour during caesarean delivery with adverse maternal and neonatal outcomes among referred mothers to tertiary centres in resource-limited settings

Objective Although the caesarean delivery (CD) rate has substantially increased, little is known about its impacts when performed in the first and second stages of labour on fetomaternal outcomes, especially among referred mothers. Thus, this study aimed to investigate the association between CDs performed during the first and second stages of labour and poor maternal and neonatal outcomes among mothers referred to tertiary centres. Setting This retrospective cohort study analysed medical records of mother–infant pairs from September 2020 to May 2023 in Southern Ethiopia. Participants We retrospectively collected data from 848 participants who underwent emergency CD on a referral basis during the study period. Primary outcome measure The primary outcomes of interest were adverse maternal and neonatal outcomes. Data were analysed using descriptive and inferential statistics. Results Of the 848 CDs, 722 (85.2%) and 126 (14.8%) were performed at the first and second stages of labour, respectively. Caesarean sections performed at the second stage were higher with nulliparity, increased maternal age, and birth weight. Compared with the first-stage CD, the second-stage CD was associated with a significantly increased risk of adverse maternal (OR 3.7, 95% CI 2.4 to 5.7) and neonatal outcomes (OR 2.0; 95% CI 1.3 to 2.9), including neonatal death. Conclusion Second-stage CDs have an increased risk of adverse maternal and neonatal outcomes. Strengthening and improving obstetric emergency surgical services and intensive neonatal care for those populations would help decrease the maternal and fetal negative consequences.

Introduction Line 56.SPPH not defined Thank you for your constructive comments.We clearly define the term severe postpartum hemorrhage in abstract and method section.Line 136 Line 57.Could births replace deliveries?Thank you for your constructive comments.We replaced the term deliveries by births.Line 57 Line 59 severe PPH written despite SPPH being used previously.Also used in lines 78, 79, 82 and throughout the whole text.If you are going to keep severe PPH then drop the SPPH and be consistent throughout.Thank you for your constructive comments.We have made corrections throughout the documents, including lines 78, 79, 82 and throughout the documents.Line 70 CD used but no previous referral to this as caesarean delivery.Thank you for your constructive comments.We have made corrections as suggested.Line 70-71 Line 74-76 'However, it is unclear whether the available risk assessment tools can predict PPH in women who underwent CD, regardless of their mode of delivery'.Not sure what this means There is assessment tools used to predict the risk of PPH; however, it's not specifically designed to predict severe PPH amongst women who underwent cesarean deliveries.Thereby, there is paucity of evidence whether those prediction tools could be useful in these scenarios.
We made it clear by expressing the main point using other words.Line 74-76 Line 83 states "severe PPH may also occur in women with no known risk factors (4)".Thank you for your constructive comments.We corrected as PPH instead of severe PPH.Line 83 But this is the same for PPH, and there is no reference here to the fact that a SPPH could be a poorly managed PPH, or a well-managed PPH could prevent SPPH.Thank you for your constructive comments.Concerning the reference to the fact that a severe PPH could be a poorly managed PPH or a well-managed PPH could prevent severe PPH; we apparently described it in a well manner.Line 59 Line 84.This paragraph needs rewording, as currently is not clear.Thank you for your constructive comments.We made rewording as suggested.Line 84 Line 85 after (29) requires a colon rather than a full stop, as this changes the sense of these important messages.Thank you for your constructive comments.We made correction as suggested.Line 85 Line 91.Refers to existing variation needing consideration in light of potential differences according to mode of birth.But this has not been considered previously.Neither has the fact that some countries use different definitions of PPH for CS or VB and the impact of this on PPH rates and progression to SPPH.Also seems to be referring to PPH at the start of this para, not SPPH.Thank you for your constructive comments.We made correction as PPH instead of severe PPH as suggested.
Line 91 Line 92 should tart with In spite, rather than spite.Thank you for your constructive comments.We made correction of typo error.Line 92 Line 95. "modifiable risk factors can be intervened" is ambitious, given that many of the woman have no risk factors, presumably apart from emergency CS in labour.Thank you for your constructive comments.According to study, not many women but some have no risk factors; thus it allows the clinicians to intervene on the known modifiable risk factor, that's what we mean.Line 95-96 Line 102 aims to "reduce the prevalence of PPH after caesarean delivery" but this is not the same as SPPH.Thank you for your constructive comments.We made it to reduce the prevalence of severe PPH instead of PPH as suggested.Line 102 Methods Line 107.Does this refer to any missing documentation?Thank you for constructive comments.Of course it also refers to any missing documentation.Line 107 Line 120.H/O abortion ever?Abnormal uterine bleeding, and single/multiple pregnancy presumably in current pregnancy?Thank you for your constructive comments.We made it clear as follows; Previous history of abortion and abnormal uterine bleeding, current singleton or twin pregnancy.Line 120 Line 121.What is prepartum anaemia?Is this a history of anaemia outside pregnancy, or is it booking HB/ferritin levels?Presumably severe pre-eclampsia (? How defined) HELLP, APH (would this not be covered by abnormal uterine bleeding) in current pregnancy.Thank you for your constructive comments.We tried to look at their definitions under operational definitions.APH is not covered by abnormal uterine bleeding, and prepartum anemia also not includes history of anemia outside pregnancy.Line 141….. Line 121 should it not be HELLP syndrome, not HEELP as written?Thank you for your constructive comments.We made corrections as suggested.Line 121 Line 118-125.I would suggest you group these as pre-pregnancy, pregnancy acquired, intrapartum factors.This would make this section easier to follow.Thank you for your suggestions.We made revisions in a suggested way of grouping.
Line 118-123 Line 129. Would be clearer if you break down prophylaxis and treatment especially if you use misoprostal prophylactically, as many places don't, so this would be of interest to readers in other jurisdictions.Thank you for your constructive comments.We made corrections by breaking down the prevention and treatment of PPH as suggested.
Lines 128, 131 & 133-139 Line 131.I'm not sure whether in actual fact only oxytocin is used for prophylaxis, in which case the sentence above needs tweaking.Thank you for your constructive comments.We made revisions concerning prophylaxis and treatment approach of PPH in our setting.
Line 134-136 Line 134.When was baseline?Early in labour/prior to CS or earlier in pregnancy?Thank you for your constructive comments.We define baseline hemoglobin: the last measurement of hemoglobin level prior to cesarean section, and included under operational definitions.Line 145 How would the clinician evaluate-as you relying on visualisation or measurement, or maternal symptoms of anaemia?Thank you for your constructive comments.As the retrospective nature of study design we relied on measurement than clinical observations.The narration of diagnosis methods has been used to describe the trends in our institution.For the record, we clearly describe how we diagnose severe PPH.
Line 141-144 Results Would be interesting to see how many women were excluded due to incomplete data.Therefore what proportion of total CS births were the 728 included women?Thank you for your constructive comments.We included the participants excluded due to incomplete data as suggested.
Line 110-114 & 174-175 Line 155.Presumably the 2 groups were those with, and those without SPPH?Please explain in text.Please define poor antenatal follow up-how many visits, reasons for non-compliance etc etc. Thank you for your constructive comments.We made corrections as suggested.However, as this study is not aimed to investigate the reasons for non-compliance rate, it is difficult to discuss here.
Line 176-178 Line 161.Remove s from obstetrics Thank you for your constructive comments.We made corrections as suggested.Lines 183-84 Line 164. who are "their counterparts"?Thank you for your constructive comments.In this context, it is obviously clear that their counterparts are those women who presented with 2 or more CS history, APH and severe preeclampsia.
Line 187 Table 2: presumably preterm was 28+1-37+0 but this needs to be defined.Thank you for your constructive comments.We included it under operational definitions.
Line 160 Failed instrumental delivery, could this be relabelled failed instrumental vaginal birth Thank you for your constructive comments.We made corrections as suggested.
Line 176 & 188 Malpresentation-please define.Does this include Breech?If yes, might be work separating as a noncephalic presentation.Thank you for your constructive comments.We made corrections as suggested.
Line 188 Discussion Line 197.Again, it would be useful to see how this 728 is representative of the overall population.Could these 728 introduce bias?Thank you for your constructive comments.We included the number of participants who were excluded because of incomplete documentation.To avoid repetitions, we included it in method and result sections. .Is it appropriate to compare the Ethiopia with the US? Due to the complexity of the health system in the US, comparison is often difficult.What was the rationale for inclusion of these countries?Are the health systems comparable?Thank you for your constructive comments.The main reason comparing our results with the US is because of the paucity of studies investigating severe PPH among intrapartum cesarean deliveries.We also clearly point out the justifications for the observed differences including the health system.Line 234-236 Line 206.It has been argued that number of units transfused is more reflective of health service policies, resource availability and clinician management than severity of bleed.This could be particularly the case here as the authors have alluded to lack of availability of some blood products.Thank you for your constructive comments.As I mentioned earlier we determine the severity of bleeding based on the derangement of hemoglobin measurement than clinical observation because of retrospective nature of the study design.We also clearly state management protocols of the institution.
Line 143-146 Line 208.It has also been argued that estimating blood loss at CS id more accurate than other modes of birth, due to the weighing of all swabs and dressings routinely undertaken in theatre.Thank you for your constructive comments.Unsurprisingly, estimating blood loss during CS is relatively more accurate; but the challenging issues have been aroused because of underestimation by obstetricians as confirmed by many studies.
That's why we relied on hemoglobin measurement, amount of blood transfusion and hemostatic interventions than underestimated blood loss for this study.

Lines 144-146
Line 225 states that women with severe pre-eclampsia and eclampsia, but previously eclampsia was not mentioned, rather HELLP syndrome.Were there no women in the study with HELLP?Subsequently in Line 227 the authors appear to suggest that severe pre-eclampsia and eclampsia resulting in HELLP syndrome cause coagulopathies leading to PPH.But PE has long been identified as a risk factor for PPH in the absence of HELLP.Thank you for your constructive comments.We made corrections as suggested.The number of HELLP syndrome and eclampsia were insignificant, that why we left to include.Line 250-252 Line 230.Were the mothers with 2 or more previous CS births at increased risk due to abnormal placentation (praevia, accreta, increta, percreta) associated with previous uterine scarring?This is not covered in the potential explanation of uterine atony or adhesions.Thank you for your constructive insights.We included the increased risk of abnormal placentation has an impact in PPH.
Line 258 Line 245.Would be interesting to discuss the impact of GA versus local anaesthesia in light of practice in your service.Commonly these days even the sickest mothers tend to have CS under regional anaesthesia, and yet the PPH rate continues to rise.Thank you for your constructive comments.We believe that to comment the impact of GA vs regional anesthesia in PPH need further investigation; otherwise without controlling the confounding factors it could be difficult for discussion.
Line 264-265 Line 255.Again, what proportion of women in your service would have a classical incision?In the UK and Australia a classical incision is commonly only used with an extremely preterm infant, which would be excluded from your study (<28 weeks).You also mention CS in labour and worth the growing concerns around full cervical dilatation CS and subsequent mid-trimester pregnancy loss or PTB, utilisation of a higher incision at this time could be topical and improve subsequent pregnancy outcomes and could be a great discussion point.This also might be more significant than proposing further trials re use of classical incisions.Thank you for your constructive comments.We made corrections as suggested.
As we described it in result section, only 20/728 women were underwent classic incision.Likewise, by removing the statement says "future studies are needed to determine this matter", we included the importance of adapting guidelines that tailored to reduce classical incision.Line 284-286 Line 268.Rather than simply the inclusion of anaesthesiologists should you not be advocated for a multidisciplinary highly skilled team?Thank you for your constructive comments.We made corrections as suggested.Line 292-293 Line 273.Describes the value of using pre and post Hb level comparisons and requirement for blood, but these only work in retrospect.So whilst reliable, they are of limited use in managing the situation as you need to wait for the blood test results to be available.Thank you for your good insights.We included this critical point in the limitation.Using the value of hemoglobin difference before and after CS and requirement for blood transfusion might delay the diagnosis of severe PPH as the clinicians need to wait the blood test results.Line 279.States the limitation of the study was that known risk factors such as pregnancy interval and previous H/O PPH were not included in the analysis and yet in the results it states that previous PPH was a contributory factor.Or were these women all excluded form the analyses, and therefore there were an additional 437 women who underwent CS but were excluded form this analyses.Or were all 728 women included but there was missing data for 437, in which case the analyses were on 291 cases?Thank you for your constructive comments.We made corrections as suggested.We are saying that women (>60%) were referred from other institutions where their previous medical records are unknown.We didn't say previous history of PPH was a contributory factor in the result section.Line 290 Conclusion Line 284 You state that the incidence of SPPH after CS was relatively high, and yet you have shown that it is not dissimilar to other published literature.You identify no new findings regarding risk factors to those already published in the literature.There is no new information around how to identify predictors or for policymakers to identify screening tools.Thank you for your constructive comments.We revised as it's relatively similar with other studies.And also we state recommendation based on our finding.
As far as our knowledge, this paper is among few studies focused on severe PPH following cesarean deliveries and contains plenty of new information.We have revised the conclusion and recommendation for stakeholders.
Line 311-315 General Caesarean delivery should be changed to caesarean section or caesarean birth.There are several typos throughout the text.Thank you for your constructive comments.We made corrections throughout the documents.I think the discussion could be presented more effectively.The authors talk about strategies to prevent and manage PPH, they also state that TXA and certain blood products are unavailable I their service, I would have liked to see more information about whether these data could be used to support introduction of TXA particularly, given it is cheap and requires no special storage.There are trials of introducing different blood products and tranexamic acid into our setting, but the existing bureaucracy challenges its translation into clinical practice.We will receive this suggestion even to evaluate the changes in the overall rate of severe PPH after introducing different blood products and tranexamic acid into our setting.
Line-N/a References Formatting of references not consistent throughout document.Some have only primary author, et al, others have full lost of authors.Some have date after authors, other have it after name of journal Thank you for your constructive comments.We made corrections as suggested.

References
Khan's review of causes of maternal death is now 17 years old with data predating that.Is there nothing more contemporary available?Thank you for your constructive comments.We replaced it with other reference as suggested Some of the other references are similarly quite old-is there any more contemporaneous evidence in the literature, given that the demography of women (age, BMI), service configuration (changes in doctors hours, scope of midwifery practice) and prevention and management of PPH (TXA, ) have all been modified in recent years?Thank you for your constructive comments.We replaced it with other reference as suggested.My recommendation would be MAJOR REVISION.The reasons for this are: Throughout the text it states severe PPH and PPH interchangeably.I am not always sure which you are referring too.Thank you for your time, consideration and constructive comments; it helped us to improve our manuscript in many ways.We made corrections and proof readings throughout the documents.

Line-throughout the documents
The methods require more detail, for example regarding wen the first blood test is taken for comparison and therefore diagnosis of SPPH, it states baseline, but when is that?Thank you for your constructive comments.We clearly described it under operation definition section.
Line 154-156 The stats are confusing, and could be more simply presented.Thank you for your constructive comments.We made critical revisions as suggested.
Line 164-170 The data collection points are not logically presented.Thank you for your constructive comments.We critically revised the data collection points as suggested  The discussion is weak and could be strengthened, given the available data..The strengths and limitations are not well describes, indeed the strength could be considered a weakness, as reliance of blood results can cause delay in treatment, and therefore this measurement of blood loss is only useful retrospectively.the work does not support the conclusions.Thank you for your constructive comments.
We tried our best to strengthen the discussion including the strength and limitations in a logical ways.[233][234][235] Reviewer 2 A careful read of strengths and weaknesses/limitations in lines 52-59 and lines 257-269 means that these two sections need to be compared and the article summary section should be a summary of what is in lines 257-269.