The adjusted relative risk (aRR) of obesity was 1.50 times higher for those born LGA by weight and 1.51 times for LGA by both weight and height. Length at birth was not associated with obesity risk. Similarly, women born LGA by ponderal index had BMI 1.0 kg/m2 greater and an aRR of obesity 1.39 times higher than those born AGA. Swedish women born LGA by weight or ponderal index had an increased risk of obesity in adulthood, irrespective of their birth length. Thus, increased risk of adult obesity seems to be identifiable from birth weight and ignoring proportionality.While there is evidence that being born large-for-gestational-age (LGA) is associated with an increased risk of obesity later in life, the data are conflicting. Thus, we aimed to examine the associations between proportionality at birth and later obesity risk in adulthood. This was a retrospective study using data recorded in the Swedish Birth Register. Anthropometry in adulthood was assessed in 195,936 pregnant women at 10–12 weeks of gestation. All women were born at term (37–41 weeks of gestation). LGA was defined as birth weight and/or length ≥2.0 SDS. Women were separated into four groups: appropriate-for-gestational-age according to both weight and length , LGA by weight only , LGA by length only , and LGA by both weight and length . Women born LGA based on length, weight, or both had BMI 0.12, 1.16, and 1.08 kg/m Furthermore, the prevalence of obesity doubled from 1980 to 2015 in over 70 countries1. This is particularly concerning considering the associations between obesity and many chronic diseases, such as diabetes, cardiovascular disease2, and some cancers3, as well as an increased risk of mortality4. In addition, a high BMI in adolescence is associated with a high prevalence of cardiovascular death in adulthood6. Thus, it is imperative that we improve our understanding of the factors that promote obesity from an early age, so that we may identify those at greatest risk and develop strategies to prevent the development of obesity.Obesity is a rapidly growing problem, and it was estimated that in 2015 there were 107.7 million children and 603.7 million adults with obesity worldwide10. In many countries, the prevalence of infants born LGA has increased over the last few decades15. The proportion of newborns weighing >4000 g ranges from less than 1% to 14.9% in developing countries13, and is as high as 20% in Nordic countries12. However, the long-term impact of being born LGA is not completely understood, with one study finding that LGA children were at greater risk of developing metabolic syndrome at aged 6–11 only if their mothers had gestational diabetes mellitus13. In addition, if their mothers did not have gestational diabetes then there was little difference in the rates of obesity at ages 6–11 for those born LGA compared with those born apropriate-for-gestational-age (AGA)13. Similarly, another study found no difference in the risk of being overweight/obesity at ages 15–20 years if born LGA compared with those born AGA14.Several studies have previously shown that being born large-for-gestational-age (LGA) is a predictor of obesity in adulthood15. However, a lower ponderal index (weight in relation to length) at birth has been linked to lower total body fat in childhood16. It has been also suggested that proportionally heavier infants may be at greater risk of poor cardiovascular and metabolic outcomes later in life17. Only two studies have examined whether proportionality at birth was related to obesity risk beyond childhood, and only one included female participants. The first study examined the association between birth weight and length and obesity risk in young male conscripts18. They reported that a high birth weight was associated with an increased risk of obesity at age 18 years, and this association remained even when the increased weight was proportional to length. The second study reported that both higher weight and ponderal index at birth were associated with an increased risk of obesity for men, but not for women19. However, their conclusion that birth weight was unrelated to risk of obesity in women contradicts at least one previous study9. Additionally, two studies report that being born long for gestational age alone does not increase the risk of obesity in adults21. Overall, there are few studies on the associations between birth proportionality and long-term health outcomes. This is particularly true for studies reporting on outcomes in women, despite sex-specific differences being frequently identified in the long-term effects of early life events22.Less is known regarding the association between being born long for gestational age or being born proportionately large (long and heavy) and the risks of developing obesity, as most studies have focused on offspring weight aloneAs such, the role that birth weight and proportionality play in determining the risk of obesity in later life for females is unclear. Thus, in the present study we aimed to assess the risk of adult obesity among a large cohort of Swedish women who were born too large by weight and/or length in comparison to those born AGA.et al.23, informed consent is generally not required for large registry-based studies in Sweden and other Nordic countries, where it is assumed that participants do not object to registry-based research, as long as the study has been approved by the relevant ethics committee. The authors add that this is “part of the informal contract between the individual and the state (…), given that health care is traditionally virtually free of charge (…), and registry-based data are maintained for the purpose of health care quality improvement and national statistics”23.Ethics approval for this study was granted by the Regional Ethical Review Board in Uppsala, Sweden (Dnr2011/141). This investigation was carried out in accordance with approved national and international guidelines for medical research. Informed consent was not required as this is a register-based study on anonymized data where participants were neither identified nor contacted. As explained by Ludvigsson 24. Information is prospectively collected during pregnancy from the first antenatal visit and subsequently forwarded to the Birth Register.This was a retrospective study using data recorded in the Swedish Birth Register. This Register records data on more than 99% of births in the country, and for the study period it had a low error rate for the main parameters of relevance, such as birth weight, date of last menstrual period, birth order, and classification as singleton or multiple25], presence of congenital malformations (ICD-9 740–759 and ICD-10 Q0–Q99), preterm birth (<37 weeks of gestation)27, and post-term birth (≥42 weeks of gestation)30.We examined data recorded on 303,301 pregnant women (born in 1973–1988 in Sweden) during their first antenatal visit (mostly 10–12 weeks of gestation), who gave birth in 1991–2009 and were aged ≥18 years. For women with two or more pregnancies in the study period, data were only included for the first recorded pregnancy. Exclusion criteria were non-Nordic ethnicity, extremely short stature (≤130 cm), being born small-for-gestational-age ” model also adjusted for current height.Age and demographic data at birth were compared between groups using univariate general linear regression models. The comparison group for all analyses were women who were born AGA for both weight and length. Anthropometric differences in adulthood were examined with generalized linear regression models. All adjusted models included the smoking habit of the woman’s mother during pregnancy34.Logistic regression models were run to evaluate binary outcomes (i.e. likelihood of overweight and/or obesity in adulthood), with adjusted models accounting for the smoking habit of the woman’s mother during pregnancy, birth order, year of birth, current regular smoking (pre-pregnancy and/or during pregnancy), and age. Analyses were performed in SAS v9.4  and SPSS v24 . All tests were two-tailed, with significance level adjusted for multiple comparisons using the Tukey-Kramer methodFrom the initial population of 303,301, we studied 195,936 women who met inclusion criteria Fig. . The stu2 and 1.08 kg/m2 greater than those born AGA, respectively; however, the difference was only 0.12 kg/m2 for women LGA by length only  and 1.51  among women born LGA by weight or both, respectively, compared with those in the AGA group Fig. . The ris2 greater than those born AGA  were born LGA by ponderal index, who were 1.22 SDS heavier and 0.48 SDS shorter at birth than those born AGA  Fig. . In contThis study found that, on average, Swedish women born LGA by weight were 50% more likely to have obesity in adulthood, even if they were proportionally longer at birth. Women who were classified as LGA by ponderal index (i.e. were heavier and shorter than those born AGA) were also more likely to have obesity in adulthood. Women born LGA by length alone were not at increased risk of obesity. Of note there was a change in the distribution of LGA phenotype over the study period, with more girls born LGA by weight and fewer LGA by length only. Our data indicate that the most accurate way to identify those at greater risk of obesity in adulthood are those who are born LGA based on weight, and this association was not mitigated if the babies were also born proportionally longer. This is particularly important given the proportional increase observed in the rate of girls born LGA by weight and the corresponding decrease in the annual rates of those born LGA by length only.18. In that study, infants who were above the 95th percentile for birth weight had a higher risk of being overweight or having obesity at age 18 years. Similarly to our study, the increased risk was observed among heavy infants who had a normal birth length as well as those who were above the 95th percentile at birth for both weight and length18. They found that infants who were born above the 95th percentile for length alone did not have an increased risk of overweight or obesity later in life18.Our findings on Swedish women corroborate a previous study on 18-year-old male conscripts in Sweden35. Conversely, our results differ to those reported by Eriksson et al. who found no relationship between high birth weight or ponderal index and increased risk of obesity in adulthood for Finnish women19. However, their study differs on three key aspects: a) the use of self-reported heights and weights that often lead to underestimation of BMI among women36; b) a much smaller sample of 2,107 women, with fewer than 1% falling into their highest birth weight category; and c) participants born in the 1920s and early 1930s who were likely exposed to very different in utero and postnatal environments that could have differentially affected their long-term obesity risk.Our results are also consistent with the well-established association between high birth weight and an increased risk of obesity in later life18. Ponderal index at birth has been shown to predict total body fat in childhood better than birth weight alone16. However, in our study, we found that being too heavy at birth was associated with a greater risk of adult obesity than being born too large by ponderal index. This may be because ponderal index has only a weak association with body fat in neonates , and is not a direct proxy for corpulence as it is often assumed to be37. Thus, it is possible that the amount of fat mass at birth is a better predictor of adiposity later in life, rather than the ratio between weight and length at birth.Similarly to our findings, Rasmussen & Johansson found that a higher ponderal index at birth was associated with increased BMI in adulthoodper se; rather, it is a marker of events/stressors that occur before and/or during pregnancy. Babies are born LGA likely due to excessive nutrition in utero, which are associated with alterations in the developing fetus that will predispose them to obesity postnatally38. Both maternal obesity and gestational diabetes mellitus are associated with increased adiposity and greater BMI at birth40. Fetal secretion of insulin in response to increased maternal glucose levels drives fetal growth, and increased maternal nutrient supply to the fetus will result in higher insulin levels and greater adiposity, and subsequently to developmental programming of fetal adipose tissue41. In light of the increasing rates of obesity among women of reproductive age worldwide, preventive measures to address this problem and reduce the incidence of babies born in the upper end of the birth weight spectrum are likely to be beneficial in the long-term. These preventative measures should include appropriate lifestyle advice to those planning to conceive as well as women who are already pregnant15. For example, women with obesity may lower the risk of having a baby born LGA by limiting their weight gain during pregnancy15. Interventions aiming at assisting women to improve their health before pregnancy would have beneficial effects not only for their health, but also for future generations by breaking the intergenerational cycle of obesity42.Notably, it is important to highlight that being born LGA is not the cause of adult obesity 43. Interestingly, Goetz et al.44 found that children born LGA who were heavier at 7–12 months were more likely to have received proportionally less breast milk feedings from birth to 6 months compared to those born LGA who had normal weight at 7–12 months. Notably, there is evidence that even simple measures as reducing bottle size for those babies receiving formula may help prevent excessive weight gain, and consequently reduce the risk of obesity later in life46. In addition, fostering improvements in sleep47, diet, and physical activity early on the child’s life would likely play a role in reducing the risk of developing obesity.For babies already born LGA by weight (and thus with an increased risk of obesity later in life), there are measures that may prevent the onset of obesity. For example, two meta-analyses found that breastfeeding was associated with lower risk of overweight and/or obesity in childhood, and both observed a dose-dependent association, with the protective effect increasing with greater duration of breastfeeding18. Another limitation was the absence of data on pregnancy complications, particularly gestational diabetes. However, strengths of our study include our large sample size and our somewhat homogeneous population, with the latter likely to mitigate the potential effects of ethnicity on study outcomes. Importantly, our study accounted for maternal anthropometry, which is arguably the strongest predictor of offspring anthropometry and obesity risk, both at birth and in adulthood50. Of note, while we did not have data on paternal anthropometry, we have recently showed this to have no association with the likelihood of an LGA baby when maternal anthropometry was accounted for50. In addition, our multivariable models also adjusted for the smoking habit of the woman’s mother during pregnancy, which is also strongly associated with obesity risk in their adult daughters in Sweden31.A limitation of our study was the lack of information on the post-natal environment, particularly regarding factors such as socioeconomic status and education; for example, the odds of obesity in Swedish male conscripts were 2.3 times higher amongst the offspring of mothers with lower levels of educationWe showed that the LGA phenotype has a marked association with the risk of adult obesity. LGA by length is more likely to be genetically rather than nutritionally determined, and is therefore not associated with an increased risk of obesity in the long-term. Conversely, being LGA by weight is a major risk factor for adult obesity, and this holds true even if they were also born long for gestational age. When assessing the long-term health risks associated with being born LGA, it is therefore important to consider the specific phenotype. Our findings illustrate that it is essential that we address the problem of obesity early, and the best strategy to prevent adverse health outcomes in both shortterm and longterm is prevention. Interventions should aim to address the obesity issue before women decide to become pregnant, particularly through the promotion of better lifestyle choices, which would in turn likely reduce the risk of having an LGA infant that is too heavy. However, for those already born too heavy, understanding the risk is a tool to encourage behavioural changes that would help reduce the likelihood of adverse health outcomes, such as the development of obesity throughout the life span. These could include early feeding practices (e.g. breastfeeding) and lifestyle changes .Supplementary File.


To improve care for women going through trial of labor after cesarean (TOLAC), we need to understand their birth experience better. We investigated the association between mode of delivery on birth experience in second birth among women with a first cesarean.A population-based cohort study based on the Swedish Pregnancy Register with 808 women with a first cesarean and eligible for TOLAC in 2014–2017. Outcomes were mean birth experience measured by visual analogue scale (VAS) score from 1–10 and having a negative birth experience defined as VAS score ≤5. Linear and logistic regression analyses were performed with β-estimates and odds ratios (OR) with 95% confidence intervals (CI).Mean VAS score among women with an elective repeat cesarean (n = 251 (31%)), vaginal birth (n = 388 (48%)) or unplanned repeat cesarean (n = 169 (21%)) in second birth were 8.8 (standard deviation SD 1.4), 8.0 (SD 2.0) and 7.6 (SD 2.1), respectively. Compared to women having an elective repeat cesarean, women having an unplanned repeat cesarean delivery had five-fold higher odds of negative birth experience . Women having a first elective cesarean and a subsequent unplanned repeat cesarean delivery had the highest odds of negative birth experience .Most women with a first cesarean scored their second birth experience as positive irrespective of mode of delivery. However, the odds of a negative birth experience increased among women having an unplanned repeat cesarean delivery, especially when the first cesarean delivery was elective. Childbirth is an important life event in women´s life. Anticipating triumph and delight, most women accept the possible difficulties of labor as part of a process to achieve a positive outcome for them and their child . One in Birth experience is multidimensional, affected by maternal age, fear of childbirth, support from the midwife and partner during labor, induction of labor, labor duration, pain, expectations of giving birth, involvement and participation during labor, and surgical procedures , 7–13. MThe rate of CD is rising globally. Having a previous CD, as a reason for another CD, further increases CD rates , 17. TheThe knowledge about birth experience in subsequent delivery after a previous CD is sparse –25. PrevThe Swedish Pregnancy Register, founded in 2013, included in 2017 approximately 93% of all births in Sweden . The regAll Swedish citizens and immigrants with one-year or longer residence receive their unique personal identification number at birth or immigration. This together with our nationwide register enables a unique possibility for longitudinal research . All preIn this study, we included all women registered in the Swedish Pregnancy Register with a first cesarean delivery and a subsequent birth to a singleton, live-born infant in a cephalic presentation at or above 37 gestational weeks during 2014–2017. Women were classified as eligible for TOLAC when the presentation was cephalic and there was no placenta previa or other medical contraindication for trial of labor. The preliminary analysis showed that some regions had a lower rate of reporting birth experience, possibly due to differences in the evaluation of the VAS scale as an instrument to measure birth experience, however response rates did increase over time. To diminish confounding by organizational factors, we chose arbitrarily to exclude women giving birth in hospitals with a birth experience response rate of less than 80% in 2017 . A few hospitals (n = 7) in the southeast region of Sweden had until 2017 the opposite interpretation of the VAS score, and these hospitals were excluded since it was unclear the exact time point for reversing the VAS scale. We also excluded births with missing birth experience data, and a sensitivity analysis was performed comparing excluded and included women. In the end, the national sample gave us a population of 808 women with first and second birth in either of the remaining 12 hospitals . These rnd birth categorized into: 1) elective repeat cesarean delivery (ERCD), 2) vaginal birth after cesarean (VBAC) or 3) unplanned repeat cesarean delivery. Women with an ERCD were used as the reference. In a supplementary analysis, we also studied intended mode of delivery (TOLAC or ERCD) as the exposure.The main exposure of interest was mode of delivery in 2st and 2nd mode of delivery and birth experience, we further categorized the exposure of interest by the 1st mode of delivery, categorized into A) elective CD or B) unplanned CD. Women, where both 1st and 2nd birth was elective CD, were used as the reference.When studying 1nd delivery was the main outcome. Previous studies have shown that about 10% of women assessed their birth as negative when using a scoring tool similar to a VAS Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: YesReviewer #2: Yes**********2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: YesReviewer #2: Yes**********3. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #1: NoReviewer #2: Yes**********4. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: Yes**********5. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: This article aims to investigate the birth experience related to the mode of de delivery after a previous cesarean section.It’s an interesting point whereas there are only few data in the literature. The article is well written and provide relevant information.Here are several comments:In the abstract, the authors state that they included patients with a first cesarean and eligible for TOLAC. However, they don’t give any information in the methods section about what they consider being eligible for TOLAC. Indeed not every patients with a previous cesarean section are eligible for TOLAC, depending on different surgical and obstetrical parameters.The authors should provide details on the parameters which have leaded to the decision of TOLAC or ERCD. Did the patients have always the choice? In this kind of study, choice of the patients is a key-point since we can hypothesize that the birth experience might be better when the patients could actually choose the mode of delivery.Another important point is that it would be relevant to compare the birth experience regarding the intent mode of delivery, not only the actual mode of delivery, i.e. TOLAC vs ERCD, not only VBAC vs ERCD vs URCD. Indeed, at the time we counsel patients, we don’t know how TOLAC will work…VAS is a very poor tool to assess a complex feeling as birth experience. Even if the authors acknowledge limits of VAS in the discussion section, it should be more pointed out.The figures (flow-chart and histograms) are of poor quality.Reviewer #2: General comment:The article shows data from a population-based cohort of women registered in the Swedish Pregnancy register. The topic of this study is of interest. As described by the authors, few publications focus on women's experience in second birth among women with a first cesarean. I found the manuscript well written overall.AbstractThe abstract is clear. Minor comments: you may detail the number of women and frequencies in each categories for the exposure in the results section( n(%) for ERCD , URCD, VBAC). I would prefer using the terms of ‘odds’ instead of ‘risk’ when saying ‘URCD had five-fold …etc’.IntroductionVery clear, thank you.MethodsPlease be more precise, if possible, when describing how women usually report their experience: is the scoring is self-administered or is the question asked by / in presence of the midwife? Are the answers anonymous? It could be a point of discussion: women may be intimidated to answer the question honestly in the presence of the caregiver tending to bias the responses toward a positive experience. Is the question about childbirth’s experience standardized across maternity units?What do you mean by ‘organizational factors’ that could have an effect on the rate of reporting birth experience? Was the mean birth experience in these maternity units with birth experience response rate of less than 80% different from those with higher response rate ? Why choosing the cut off of 80% for exclusion?Please consider rephrasing the sentences explaining the cut-off of 5 for defining negative birth experience. Here is a suggestion (line 130-131): “Previous studies … […]. The tenth percentile of the distribution of birth experience was 5 in our study. Thereby, to find women …etc”.Do you have any information wether the decision of TOLAC or ERCD was shared with the women or decided only by the medical team? Many studies dealing with birth experience demonstrate the importance of shared-decision making process with the women; and that feeling of not having the choice was associated with lower satisfaction and experience, whatever the outcome.Do you also have information on why ERCD was performed instead of TOLAC ? Is there clinical factors that systematically contra-indicate TOLAC and are those standardized across hospitals? Was the rate of TOLAC homogeneous across hospitals?Statistical analysisBefore performing Student t test and linear regression, have you checked that hypothesizing a normal distribution seemed correct? Please consider justifying that somewhere.ResultsThe Table 1 is not very clear and in line with your method section. As your exposure variable is 1) ECRD ; 2) unplanned repeated CD ; 3) VBAC, I recommend not to compare ERCD with TOLAC but to compare ERCD with 2) and 3) (two-by-two), as described in the method. It will also be more in line with the way you analysed them in the multivariable models. The rate of TOLAC may just be detailed in the text. Perhaps the differences in women’s characteristics between ERCD and TOLAC might be added as supplemental data ?Line 178: the step-wise method for adjustment should be introduce in the method section and not in the results.Table 2: it’s not very clear how you selected the confounders for mode l1 and model 2. Please better explain that in the method section.Table 4: I’m not sure to clearly understand the table. What is the category of reference for the strata ‘unplanned CD in 1st birth, 2nd birth’? As far as I know, stratifying the results imply that the analyses of the effect of exposure on outcome are performed separately in each strata of a confounder (here elective or unplanned CD in first birth). Shouldn't the reference in stratum 2 be ERCD (but among women with 1st unplanned CD) as well?Line 198-9: I’m not sure you can conclude so strongly of a higher risk of negative second birth experience for women with unplanned CD in 1st birth given the very small number of women and the very wide confidence interval. Perhaps moderate the sentence with ‘it seems that …’?Table S1: it may be interesting to describe difference in hospital characteristics among women with and without missing data on childbirth experience (information as private maternity status and university status).DiscussionLine 18-19: same comment as above.Line 240-242: Couldn’t this assumption be easily verified?: were the scores of birth experience lower in hospitals were the scoring rate was lower than 80%?Line 249: it’s not clear on which studies you referred to: what kind of intervention programs do you mean? We understand it later in the section but detailed it briefly here for a better understanding.As commented before, I suggest that you discuss more about the importance of share decision making process and women’s involvement in this. It may be an element of explanation as to why the experience is high whatever the outcome of delivery.You also introduce the importance of postpartum counselling in the conclusion. It’s an important element of discussion that, in my view, merit to be mention in the discussion section.**********what does this mean?). If published, this will include your full peer review and any attached files.6. PLOS authors have the option to publish the peer review history of their article  digital diagnostic tool, AttachmentPlos_One_birth_experience.docxSubmitted filename: Click here for additional data file. 10 Jan 2020We have performed major revisions and answered the questions from the reviewers. We have incorporated all your suggestions into our revision. We are very thankful of your help.AttachmentResponse to Reviewers.docxSubmitted filename: Click here for additional data file. 4 Feb 2020Risk of negative birth experience in trial of labor after cesarean delivery: a population-based cohort studyPONE-D-19-19552R1Dear Dr. Lindblad Wollmann,We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. 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As noted by Reviewer 2 (Pauline Blanc-Petitjean), substantial modifications have been made by the authors, the answers are relevant, and presentation of the results is more clear.Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.Reviewer #1: All comments have been addressedReviewer #2: All comments have been addressed**********2. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: YesReviewer #2: Yes**********3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: YesReviewer #2: Yes**********4. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #1: YesReviewer #2: Yes**********5. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: Yes**********6. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: (No Response)Reviewer #2: Substantial modifications have been made by the authors and the answers are relevant. Presentation of the results is more clear. Thank you.**********what does this mean?). If published, this will include your full peer review and any attached files.7. PLOS authors have the option to publish the peer review history of their article (If you choose “no”, your identity will remain anonymous but your review may still be made public.Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.Reviewer #1: NoReviewer #2: Yes: Pauline Blanc-Petitjean 18 Feb 2020PONE-D-19-19552R1 Risk of negative birth experience in trial of labor after cesarean delivery: a population-based cohort study Dear Dr. Lindblad Wollmann:I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact plosone@plos.org. For any other questions or concerns, please email Thank you for submitting your work to PLOS ONE.With kind regards,PLOS ONE Editorial Office Staffon behalf ofDr. Guillaume Ducarme Academic EditorPLOS ONE


Objectives: To identify attributes  and levels  that would be included in a discrete choice experiment (DCE) questionnaire to evaluate women’s preferences for water immersion during labor and birth. Methods: A mixed-method approach, combining systematic reviews of the literature and patient focus groups to identify attributes and levels explaining women’s preferences. After the focus groups, preference exercises were conducted and led to the creation of the questionnaire, including the DCE. A qualitative validation of the questionnaire was conducted with women from the focus groups and with medical experts. Results: The literature reviews provided 26 attributes to be considered for childbirth in water, and focus groups identified 14 additional attributes. From these 40 attributes, preference exercises allowed us to select four for the DCE, in addition to the birth mode. Labor duration was also included, even if it was not well ranked, as it is the main clinical outcome in the literature. Validation with experts and women did not change the choice of attributes but slightly changed the levels selected. The final six attributes were: birth mode, duration of the labor phase, pain sensation, risk of severe tears in the perineum during the expulsion of the newborn, risk of death of the newborn, and general condition of the newborn (Apgar) score at 5 minutes. Conclusion: This study allowed us to detail all the stages for the design of a DCE questionnaire. To date, this is the first study of this kind in the context of women’s preferences for water immersion during labor and birth.  Considering patient preferences is crucial for shared decision-making that promotes greater satisfaction and better clinical outcomes ,2,3. IndOne intervention that has gained popularity in recent years is childbirth in water . DespiteA literature review conducted by our team leader and a more recent one published in 2018 provided similar results in regard to the benefits and risks of childbirth in water ,8. The lThe objective of this study was to use a mixed-method approach to identify attributes and levels that would be included in a discrete choice experiment (DCE) questionnaire to evaluate women’s preferences for water immersion during labor and birth.Using qualitative methods for the design of a DCE to define attributes and levels is highly recommended by experts ,29,30. IA systematic review of the literature was conducted by our team leader in 2013; details can be found elsewhere . The purFour different focus groups took place between 26 March and 5 April 2019. The criteria to be a participant were being a woman between 18 and 45 years of age and being able to understand French. We aimed to have equal representation by having participants who were nulliparous, primiparous, multiparous and pregnant women, in addition to women who had previously experienced giving birth in water. To recruit women from various socio-economic backgrounds, participants were solicited through the network of contacts of members of the research team, through the home-birth network and through the support network for single-parent and blended families in Eastern Township, QC, Canada. Although it was a convenient sample, more efforts were produced after the recruitment of the ten first participants to recruit new participants from groups that were less represented . Each focus group lasted about an hour. The objective was to determine those characteristics that have an impact on the choice of birth mode  to define the attributes and levels for the DCE. Each focus group was conducted in three steps. First, the consent of each woman was collected, followed by a description of the aim of the study and the DCE, and the history and definition of childbirth in water. Second, brainstorming conversations took place where each woman spontaneously indicated her personal advantages or disadvantages regarding giving birth in water. Third, the researcher presented the scientific evidence from the systematic literature reviews and asked participants if they thought they might change their minds based on this new information or if they had new advantages or disadvantages to add. A discussion was also conducted at this step to identify which characteristics were important and which were not in the decision-making process of choosing a birth mode.Following the focus groups, the research team identified all characteristics judged as important by women in their decision to consider water immersion during labor and birth. This was done during the analysis of the transcript of the focus groups where women clearly indicated which characteristics were important and which were not. A list of 22 characteristics/attributes (positive or negative) was established, and two ranking exercises were then proposed to the women by email. The first served to rank the 22 characteristics from one to 22 (from most to least important) that might influence their decision to give birth in water. An average for each item was calculated, and a ranking was established from smallest to largest. The second exercise was to complete a four-point Likert-type scale for each characteristic with the following values: very important (1), important (2), somewhat important (3), and of little importance (4). Two analyses were performed with these results. First, an average was identified using the Likert values and a ranking from smallest to largest was performed. Then, cumulative percentages for “very important” and “important” were identified, and the items were ranked from most important to least important.Considering the results from the preference exercises, the characteristics ranked the highest were selected to create the DCE attributes. Levels were defined by considering the literature review. The DCE included 12 choice cards; each card presents two scenarios according to the selected attributes and levels. For each choice card, following an orthogonal selection procedure, levels were randomly selected for each attribute. The respondent was asked to choose her preferred scenario or the option “none of these choices”. In order to test whether the responses of individuals are rational , one of the choice cards proposed a scenario that, initially, completely dominated the other. To test the consistency of responses over time, one of the choice cards was presented twice (consistency test). A series of socio-demographic questions, definitions of childbirth in water and birth phases, experience of past childbirth, and interest in giving birth in water preceded the DCE in the questionnaire. Other measures and questionnaires designed to assess quality-adjusted life year (QALY) followed the DCE ,32.The first version of the questionnaire was sent to all participants of the focus groups, a public health expert, a child development expert, a specialist in neonatal and perinatal medicine, and two general practitioners with a specialty in monitoring pregnancy. We asked them to complete the questionnaire online, to calculate the amount of time it took to complete, and to comment on the ease of completing it and on the clarity of the questions. Specifically, we asked them whether some sentences should be rephrased and if the attributes and levels selected for the DCE were appropriate. This study was approved by the ethics committee of the CIUSSS de l’Estrie—CHUS (Comité d’éthique de la recherche of the CIUSSS de l’Estrie—CHUS # 2019-3091). All participants signed a consent form and were informed that the results would be used to design a DCE that will inform decision-makers and that they may be published in a peer-reviewed journal.All details of the process of the mixed-method approach are presented step by step.The systematic review conducted by our team leader included not only randomized controlled trials, but also other designs . As a reThe main significant outcomes observed were the reduced duration of the labor phase with immersion ,15,16,17There is no evidence of increased adverse effects on the neonatal mortality rate ,20,22,25No differences were observed for the use of instruments during expulsion ,19 or foFinally, women who have experienced labor and delivery in water are mostly very satisfied and wish to repeat it for a future birth ,25,27. IThe focus groups included 17 women between 24 and 54 years old. Although one of the inclusion criteria was for participants to be between 18 and 45 years old, one was 54 years old. It is important to note that this older participant took part only in the focus group and not in the preference exercises. One group took place during a planned activity in the support group for single-parent and blended families. As the group was open to all women present, no one was excluded (including the older participant mentioned above). Three other focus groups took place in our hospital. Among the participants were three childless women, seven primiparous women including two who were pregnant, and seven multiparous women. Water immersion had been experienced by four of these participants, one at her home and three at a birthing house. In one of these cases, a woman had a hemorrhage while pulling on the umbilical cord, but she had no complications and did not require transfer to the hospital. The hemorrhage stopped when she emerged from the water. In all cases, the women were very satisfied with their experience.The first focus group was planned for five participants (Fleurimont), but only two attended. The second included seven women (Youville), the third had four women (community center) and, finally, the fourth group comprised four participants at the same site as the first focus group and included two participants who were unable to attend the first focus group. A total of 22 important characteristics identified as such by participants emerged from the brainstorming conversations, eight from the literature reviews, and 14 from the participants . The chaThe results of the preference exercises are provided in Considering that having more than seven attributes in a DCE is not recommended, the decision was made to keep the five most-preferred characteristics in addition to the birth mode. At first, it was decided to keep the attributes that were ranked in the top three among the three ranking results at least once, i.e., pain reduction, mortality risk of newborn is identical, risk of severe perineal tears is reduced, perineal injuries are reduced, and perineum remains intact. Since the last two characteristics were redundant, only one was kept . We then decided to keep the attribute that was ranked at least twice in the top five among the three ranking results, i.e., general condition of newborn slightly better (Apgar score). Finally, we also included active labor duration, even if it was ranked only seventh, since it is the clinical outcome most frequently reported in the literature, indicating a significant difference from land birth ,15,16,17The validation with medical experts  allowed us to better define conventional birth and water birth. They suggested several changes for the levels associated with the Apgar score in the DCE, as well as including a question asking the respondent who she would like to monitor her pregnancy  and where she may prefer to give birth . Women from the focus groups and other experts allowed the refining of several questions . For women who had previously experienced a water birth, a question asking whether or not they needed medical assistance was added. Following the questioning of two pregnant women for the SF-6Dv2 , a sentence was added indicating that pregnant women should describe their current health status and not their usual health status. For the first choice card in the DCE, one of the scenarios (the one with water birth) completely dominated the other  as it was initially set to be a rationality test. However, one woman thought that this forced the respondent to choose water birth even if it was not her preference. Therefore, we changed the first choice card to have the same levels (best one) for all attributes, except for the birth mode where, in scenario one, the conventional birth was presented and, in scenario two, the birth corresponding to water immersion in all phases  was presented. As many aspects of water birth could hardly be part of the DCE , a list of characteristics that might either encourage or discourage women from giving birth in water was added to the questionnaire. These characteristics were classified with a four-point Likert-type scale as in the preference exercise previously described: very important (1), important (2), somewhat important (3), and of little importance (4). Some participants found the DCE exercise difficult, but, in general, they found the questionnaire clear and concise, and noted that the choice of attributes and levels reflected the discussions in the focus groups well. The final selection of attributes and levels is described in The combination of literature reviews, focus groups, preference exercises, and comments from participants and medical experts aided in the selection of the most appropriate attributes and levels for the DCE questionnaire. These results will help to elicit women’s preferences for water birth within a larger DCE study to be conducted. The next step will be to conduct a survey using a large sample of women of childbearing age to define their preferences for water birth in order to inform healthcare institutions whether or not they should adapt their services to provide this mode of labor and delivery. Indeed, this information about women’s preferences is needed since there may be some barriers to implement water immersion in hospitals  ,7,27, alTo the best of our knowledge, no study has used a DCE method to evaluate women’s childbirth preferences by considering the aspect of immersion in water. Larkin et al. used mixed methods with qualitative analysis and DCE to assess women’s preferences for birth, but did not consider water immersion . The mosIn our study, the three main characteristics of interest in choosing or declining water birth were pain reduction; the mortality risk of the newborn, which was identical; and the risk of severe perineal tears, which was reduced. Several studies have shown a reduction in analgesic intake with water immersion ,12,13,14A reduction in the duration of the labor phase was considered in the attributes, although it did not emerge from the results. As this is one of the main effects observed in the literature, it was decided, with the experts, to add this aspect. With a larger sample, we will be able to determine whether or not this aspect is important during the survey.One limitation was that several potential attributes are related only to giving birth in water and are less applicable to the DCE that compares different alternatives . For example, we have seen that the distance between the hospital and the birthing house can reduce interest in giving birth in the water. In Quebec, only one hospital offers the possibility of delivery in water. Elsewhere, this mode is offered only at home or in a birthing house. In our region, there is a distance of 13 km between the birthing house and the hospital, which reduces interest in choosing this birth mode. Women in focus groups defined the majority of these attributes, which have also been observed in the literature but not measured. To compensate for the inability to include several attributes in the DCE, specific questions using Likert-type scales were added to the questionnaire to assess whether these characteristics would have a positive or negative impact on a woman’s choice to give birth in water. This additional information may complement the results of the DCE and possibly allow for the adaptation of services offered to women in hospitals. However, future research may be needed to specifically focus on these aspects, as well as on the barriers and facilitators that may guide the hospital decision-makers to implement water birth (or not) in specialized birth units.A strength of this study is the fact that we were able to collect the opinions of respondents including nulliparous, primiparous, multiparous and pregnant women, as well as women who had previously experienced giving birth in water. However, to be more representative, we would have liked to have more pregnant women in our sample. In addition, despite the diversity of women interviewed, it was still relatively easy to inquire about and obtain women’s preferences. In contrast, one limitation was that, in some very diverse focus groups, several women who had not had children did not feel comfortable about giving their opinions on conventional or water birth, especially in the presence of women who had experienced water birth. Another limitation was having to conduct several focus groups, since some groups were smaller than expected. Despite these limitations, from one focus group to another, the same preferences were usually highlighted, except in the group with women who had already experienced of giving birth in water, which further enriched the discussion. In addition, our selection of attributes is consistent with what was found in the literature.This study enabled the detailing of all the stages necessary to realize the design of a DCE questionnaire, from the process of identification through to the final choice of the attributes and levels. This is also, to the best of our knowledge, the first study to address the preferences of women for water birth. It will be interesting to analyze women’s preferences on a larger scale with the survey. These results will collect and elucidate women’s interests in two major birth modes and will help formulate recommendations to health care institutions, especially in Quebec. As such, implications of this study may support the need for a more patient-centered approach of care, as well as to show evidence in favor of alternatives initiated by patients and citizens .


Twin pregnancies account for 0.5–2.0% of all gestations worldwide. They have a negative impact on perinatal health indicators, mainly owing to the increased risk for preterm birth. However, population-based data from low/middle income countries are limited. The current paper aims to understand the health risks of twins, compared to singletons, amongst late preterms and early terms.Data is from “Birth in Brazil”, a national inquiry into childbirth care conducted in 2011/2012 in 266 maternity hospitals. We included women with a live birth or a stillborn, and excluded births of triplets or more, totalling 23,746 singletons and 554 twins. We used multiple logistic regressions and adjusted for potential confounders.Twins accounted for 1.2% of gestations and 2.3% of newborns. They had higher prevalence of low birth weight and intrauterine growth restriction, when compared to singletons, in all gestational age groups, except in the very premature ones (<34 weeks). Amongst late preterm’s, twins had higher odds of jaundice  and antibiotic use . Amongst early-terms, twins had higher odds of oxygen therapy , admission to neonatal intensive care unit , transient tachypnoea , jaundice  and antibiotic use . In relation to birth order, the second-born infant had an elevated likelihood of jaundice, antibiotic use and oxygen therapy, than the first-born infant.Although strongly mediated by gestational age, an independent risk remains for twins for most neonatal morbidities, when compared to singletons. These disadvantages seem to be more prominent in early-term newborns than in the late preterm ones. Twin births rates vary considerably around the world, according to country development, from less than 1% of all births in Asian South and Southeast  and FranIn Brazil, according to the National Live Births Database (SINASC), there is also an increasing trend in twin birth rates, from 1.7% to 2.0% in the sixteen years since 2000 . This trTwin births have a negative impact on perinatal health indicators, since twins have a higher risk of perinatal mortality –14, espeMoreover, maternal mortality and morbidity are higher in cases of twin births when compared with single pregnancies ,19,20. AIn Brazil, as in several developing countries, surveys of twin pregnancies with country-specific data are limited. Most studies are hospital-based and consider a limited number of hospitals , or theyThe objective of the current paper is to understand the health risks of giving birth to twins at different gestational ages. Subsequent analysis will explore the relationship between birth order and maternal and perinatal outcomes in cases of twin births.The present manuscript is based on data from ‘Birth in Brazil’, a nationwide population-based survey on gestation and delivery, performed between February 2011 and October 2012. The sample was selected in three stages. The first stage was to select hospitals with 500 or more births / year, stratified by the country's five macro-regions, location  and type of hospital . The second consisted of identifying the number of days needed to interview 90 puerperae . The third consisted of selecting appropriate puerperae. 266 hospitals were sampled in total. Further details of sample design are available in Vasconcellos et al (2014) .The study included 24,035 women who were admitted to maternity wards at the time of delivery, along with their newborns of any gestational age and weight, and stillbirths with birth weight ≥ 500 g and / or gestational age ≥ 22 weeks’ gestation. Of these, 23,746 had a single birth , 277 had twins (554 newborns) and 12 had triplets (36 newborns). For the present analysis, we have excluded deliveries of triplets. We thus sampled a total of 24,023 puerperae and 24,300 newborns.The main predictor variable was twin pregnancy, compared to single pregnancies, stratified into four gestational age groups: <34 weeks (preterm), 34–36 weeks (late preterm), 37 and 38 weeks (early term) and ≥39 weeks (full term). As a secondary predictor variable, we analysed the birth order of twin infants (first-born or second-born).th percentile as small for gestational age (SGA) and birth weight <3th percentile as intrauterine growth restriction (IUGR)  (below the tenth and third percentiles); resuscitation of the newborn in the delivery room ; oxygen therapy  or mechanical ventilation); use of antibiotics at any time during hospitalisation; admission to the Neonatal Intensive Care Unit (NICU); transient tachypnoea of the newborn; hypoglycaemia in the first 48 hours of life; phototherapy in the first 72 hours of life (jaundice); severe neonatal outcomes; and severe maternal outcomes. The severe neonatal outcome included neonatal near misses, according to the WHO classification . It also00g; intrn (IUGR) .We identified the following variables as potential confounding factors: macroregion , type of payment for childbirth (public or private); maternal age ; years of maternal schooling ; and gestational age upon delivery .We collected data on the socioeconomic characteristics of the women  through face-to-face interviews with puerperal women. Data on obstetric history and maternal medical conditions were collected from maternal hospital records and prenatal cards. We recorded all neonatal outcomes from hospital records of newborns.We gathered information on gestational age upon delivery primarily from results of ultrasound examinations, performed between seven and thirteen gestational weeks. We collected this information from both the original ultrasound examination and prenatal cards, maternal hospital and newborn records. 74% of women had gestational age at birth classified by this method and, in the absence of ultrasonographic estimates, gestational age was based on the information reported by the woman in the interview (23%) and, finally, on the date of the last menstrual period (1%) and the 50% percentile of weight for gestational age at birth (2%) .Post-hoc calculations show that with a significance level of 5%, the twin sample (554 newborns) would have 80% power to detect an increased risk corresponding to an OR of ≥2 for neonatal outcomes, with a prevalence of 5%. However, gestational age categories of 34–36 weeks (with 248 newborns) and 37–38 weeks (with 164 newborns) would have 80% power to detect an increased risk corresponding to an OR of ≥2.5 and ≥3.0, respectively, for neonatal outcomes with a prevalence of 5%.We analysed the differences in the characteristics of postpartum women, as well as absolute differences in neonatal outcomes according to twin births, using the χ2 test. Using multiple non-conditional logistic regressions, stratified by the four gestational age categories , we analysed neonatal outcomes associated with twin births in comparison to single births. We analysed neonatal outcomes associated with birth order by means of multiple non-conditional logistic regression. In both analyses, we estimated the odds ratios (OR), adjusted odds ratios (adj. OR) and their respective 95% confidence intervals.For all outcomes, macro-region, type of birth payment, maternal age, maternal schooling years and gestational age, we performed adjusted analysis. Gestational age at delivery was used as an adjustment variable in the model in complete gestational weeks, as there was a higher proportion of twins than single births at lower gestational ages, even within the pre-determined categories. We accounted for the complex sample design in all statistical analyses. We adopted a significance level of 5% for all analyses. For this research, we used the statistical programme SPSS V.20.0.This study was approved by the Research Ethics Committee of ENSP / FIOCRUZ under number 92/2010. Measures have been taken to ensure the privacy and confidentiality of data collected from participants. Informed consent was obtained prior to interviews with the use of an informed consent form.Women giving birth to twins shared several defining characteristics, including higher usage of private healthcare services, older age (≥ 35 years), and a greater prevalence of hypertensive disorders  when compared to single birth mothers.Among women giving birth to twins, the onset of labour was mostly provider-initiated, with almost no labour induction performed. Caesarean sections were performed in 84% of twin births and, amongst them, 61.5% were elective (antepartum) CS. Gestational age ranges in twin births also differed significantly from figures observed in single births . We detaNewborn twins showed lower birthweights and a higher prevalence of restricted intrauterine growth, when compared to newborn single births. The results were independent of which percentile was considered (either tenth or third percentile) . Of the Newborn twins presented a larger risk of presenting neonatal outcomes, such as oxygen therapy, admission to neonatal intensive care unit, transient tachypnoea, jaundice and antibiotic use. Nevertheless, the absolute difference between twin and single newborns was more noticeable in late preterm infants .Among late preterm infants, for every one-hundred infants born, around 48% of newborn twins showed neonatal near miss/foetal mortality/neonatal mortality, compared to 28% of the same outcomes among single newborns. Equally, 30% of twins showing signs of jaundice were subjected to phototherapy, compared to 11% in single newborns; 29% of twins were admitted to an intensive care unit (ICU), compared to 18% in single newborns; and antibiotics were used to treat 20% of newborn twins, compared to 12% in single newborns .For early term infants, absolute differences between newborn twins and single-births were of a lesser magnitude, varying between 0.9% and 6.5%. Yet statistical significance was noted in a greater number of outcomes .In cases of extreme prematurity, the difference in the application of supplemental oxygen between twins and single newborns was more telling: 91% vs. 76%, respectively. Meanwhile, the difference in levels of admission to an ICU was comparable to figures observed in late preterm infants. Although, the overall proportion of extremely premature infants admitted to an ICU was far greater .In adjusted analysis, late preterm newborn twins showed a greater likelihood of being admitted to an ICU, receiving treatment with antibiotics, neonatal near miss, and undergoing phototherapy, with OR varying between 1.6 (CI 1.0–2.7) and 4.1 (CI 1.2–3.8). For early term infants, newborn twins were more likely to receive antibiotics, supplemental oxygen, phototherapy, to be admitted to an ICU, and to suffer from transient tachypnoea and hypoglycaemia, with OR varying between 2.5 (CI 1.1–5.6) and 6.2 (CI 1.9–20.0). Twin births were neither associated with maternal near miss nor maternal mortality .When analysing birth order in twins, we found that the second-born twin showed a greater prevalence of the outcomes studied in this research, compared to the first-born twin. After adjusting for confounding factors, second-born twins showed an elevated likelihood of requiring supplemental oxygen, treatment with antibiotics and phototherapy, than first-born twin .The twin pregnancy rate has increased in the last three decades due to available technologies facilitating assisted reproduction, and because more women of advanced age (≥ 35 years old) are becoming pregnant –9. The pTwin pregnancies and births continue to present a challenge for health services. The risk of stillbirth is high, and the timing of delivery is important. Monochorionic twin pregnancies and dichorionic gestation, which often leads to early delivery, potentially increase the risk of neonatal complications –30. SincWe found that the absolute difference between severe perinatal outcomes in twins compared to single born infants is higher during the late preterm period. The magnitude of this outcome reaches almost 50% of infants. The proportion of spontaneous and provider-initiated twin births was similar to single births in the late preterm; spontaneous births represented 60% of the total number of births. Thus, a possible explanation for the disparities of outcomes between twins and single born infants could be due to the higher prevalence of intrauterine growth restriction. Weight is a defining criterion for neonatal near miss and IUGR infants had greater occurrence of stillbirths. As for early term births, there was no significant increase in the chances of adverse perinatal outcomes of twins relative to single born infants. However, other neonatal outcomes—with the exception of resuscitation—were more prevalent in twins. These differences can be explained, in part, by the fact that 66% of births were provider-initiated, mainly prelabour caesarean, which increases the risk of respiratory morbidity of the newborn .The optimal time of delivery for twin pregnancies is a highly debated topic –30,33. AEven though we collected our data before new recommendations regarding the timing of delivery of twins up to 38 weeks were emphasised in literature ,35, onlyIn our data, the non-significant difference in the odds of adverse perinatal outcomes between twins and early term single born infants suggests that early term delivery is more beneficial to infant and mother than late preterm delivery.The mode of delivery observed in this study was predominantly caesarean as an obstetric intervention. This procedure continues to draw controversy, especially when applied to a second twin not in the cephalic position ,18,36–38Unlike other studies ,19,20, wThe twin pregnancy rate was similar to that found in other studies in Brazil. The proportion of caesarean sections was high, with 75% of newborns classified as late preterm and early term. Along with this came the inevitable greater occurrence of neonatal complications associated with these gestational ages. However, all neonatal complications were more frequent in twins at all gestational ages, when compared to single births. Caesarean delivery may be the cause for poorer outcomes observed in early term twins.S1 Fig(TIF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S1 File(ZIP)Click here for additional data file. 13 Oct 2020PONE-D-20-23490Twin pregnancy and perinatal outcomes: data from ‘Birth in Brazil Study’PLOS ONEDear Dr. Esteves-Pereira,Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.Please submit your revised manuscript by 12/11/2020. 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The PLOS ONE style templates can be found athttps://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf andhttps://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdfhttp://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see In your revised cover letter, please address the following prompts:a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail  and who has imposed them . Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see We will update your Data Availability statement on your behalf to reflect the information you provide.3. Please amend your manuscript to include your abstract after the title page.Additional Editor Comments:A large cohort study of twins and singletons in brazil. The authors have attempted to compare the outcomes of twins to singletons at a variety of gestational age brackets.Likely, the increased age and hypertensive disorders are linked to assisted reproduction but the authors did not assess this. This would fit with others studies in twins. Likewise chorionicity was not assessed which is a common failing of large cohorts of twinsThe lack of detail about the incidence of preterm birth <34 weeks for twins is a shame as this is one of the highest risk groups. In addition, it is unclear which proportion of these babies in each group were delivered due to other clinical concerns or who laboured spontaneously. The approach to interpreting the data would be significantly different if the cause were not potentially preventable, i.e. delivering due to TTTS or severe IUGR in which case you would accept the risks of prematurity whatever they areOn page 5 please make the definition of IUGR and SGA clearer as <3rd and <10th respectively. You do this in the tables so I suspect you are using the Delphi criteria but the text does not make this clearPage 5 skin colour is an unusual term to use for ethnicity for this reviewer. I would suggest changing this to ethnicity to improve the translation to other readers.Table 1 can you split the mode of delivery into elective (no labour) CS and emergency CS. It is unclear at presentPlease add data for stillbirths and neonatal deaths to all relevant tables[Note: HTML markup is below. Please do not edit.]Reviewers' comments:https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool,  1 Dec 2020Manuscript “Twin pregnancy and perinatal outcomes: data from ‘Birth in Brazil Study” [PONE-D-20-23490].Each point raised has been answered as follows:1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. Response: The manuscript was amended to meet PLOS ONE's style requirements, including those for file naming.2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. Response: The authors have upload the minimal anonymized data set necessary to replicate the study findings as a Supporting Information file “NB1_GEMEOS_PLOSONE.sav”3. Please amend your manuscript to include your abstract after the title page.Response: The abstract (now page 2) was included in the manuscript after the title page.A large cohort study of twins and singletons in brazil. The authors have attempted to compare the outcomes of twins to singletons at a variety of gestational age brackets.4.1. Likely, the increased age and hypertensive disorders are linked to assisted reproduction but the authors did not assess this. This would fit with others studies in twins. Likewise chorionicity was not assessed which is a common failing of large cohorts of twins.Response: Since the main objective of “Birth in Brazil” study was not to study twin births, it was not possible to determine whether the twin pregnancy was monochorionic or dichorionic. Neither was it possible to discern which woman used assisted reproductive technologies (ART). This is a limitation of the study, addressed in the discussion section. However, we described that the proportion of twins was higher in the private sector and in women >39 years, which may be due, at least in some extent, to using ART more frequently than younger women from the public sector do. We will be able to fully address this hypothesis in Birth in Brazil 2, with data collection beginning in 2021.4.2.The lack of detail about the incidence of preterm birth <34 weeks for twins is a shame as this is one of the highest risk groups. In addition, it is unclear which proportion of these babies in each group were delivered due to other clinical concerns or who laboured spontaneously. The approach to interpreting the data would be significantly different if the cause were not potentially preventable, i.e. delivering due to TTTS or severe IUGR in which case you would accept the risks of prematurity whatever they are.Response: The authors have included two supporting files , which are described in the results section (page 9). These files show the detail about the incidence of preterm birth <34 weeks for twins and singletons, as well as the proportion of newborns with provider-initiated onset of labour (induction or elective caesarean) or who laboured spontaneously.4.3. On page 5 please make the definition of IUGR and SGA clearer as <3rd and <10th respectively. You do this in the tables so I suspect you are using the Delphi criteria but the text does not make this clear.Response: In now page 6, we changed the original text to: “Appropriate birth weight for gestational age was assessed by Intergrowth-21st intrauterine growth curves, considering birth weight <10th percentile as small for gestational age (SGA) and birth weight <3th percentile as intrauterine growth restriction (IUGR).”4.4. Page 5 skin colour is an unusual term to use for ethnicity for this reviewer. I would suggest changing this to ethnicity to improve the translation to other readers.Response: The term “skin colour” was changed for “ethnicity” in the text and tables.4.5. Table 1 can you split the mode of delivery into elective (no labour) CS and emergency CS. It is unclear at present.Response: Table 1 (page 10) and its results (page 9) were updated as suggested.4.6. Please add data for stillbirths and neonatal deaths to all relevant tablesResponse: The data for stillbirths and neonatal deaths were included in tables 2 and 4.AttachmentResponse_Review.docxSubmitted filename: Click here for additional data file. 23 Dec 2020Twin pregnancy and perinatal outcomes: data from ‘Birth in Brazil Study’PONE-D-20-23490R1Dear Dr. Esteves-Pereira,We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact Kind regards,Andrew Sharp, PhDAcademic EditorPLOS ONEAdditional Editor Comments :Reviewers' comments: 30 Dec 2020PONE-D-20-23490R1 Twin pregnancy and perinatal outcomes: data from ‘Birth in Brazil Study’ Dear Dr. Esteves-Pereira:I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact plosone@plos.org. If we can help with anything else, please email us at Thank you for submitting your work to PLOS ONE and supporting open access. 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Water immersion during labour and birth offers birthing women a means of non-pharmacological pain relief and a reduction in unnecessary and often routine intrapartum interventions . Women wIn New Zealand, the use of water immersion during labour and birth is predominantly at home or in primary maternity facilities (midwife-led birthing units) for low-risk women. Some secondary maternity units (for both uncomplicated and complicated pregnancies and births supported by multidisciplinary teams and access to operating theatres), and tertiary maternity units  provide access to birth pools or baths for ‘low risk’ women to utilise during labour and birth . For womThe New Zealand maternity system is an integrated system of primary, secondary and tertiary care that is free for most women. A Lead Maternity Carer (LMC) of the woman’s choice is responsible for care throughout pregnancy, labour and birth, and postnatally to 6 weeks. The LMC can be a midwife, a general practitioner (family physician) with a diploma in obstetrics or a private obstetrician (who can charge a fee for service). The majority (93.6%) of pregnant women in New Zealand choose a case-loading community-based LMC midwife who provides continuity-of-care in the woman’s home, a midwife-led unit, or a secondary or tertiary hospital . If the There is a dearth of data available from secondary and tertiary maternity units where water immersion for labour and birth are offered, particularly in New Zealand. The lack of data is likely to be due to a lack of capacity of the information technology (IT) systems to record water immersion and water births. No complete national data is reporting on water immersion and water births across all maternity settings . The onlThis study aimed to describe the maternal characteristics, intrapartum events, interventions, and maternal and neonatal outcomes of women who used water immersion during labour and birth at one New Zealand District Health Board (DHB). This paper presents the results from a prospective observational study of women who used water immersion for labour and birth across the three maternity facilities in the DHB from February 2009 to March 2014.The DHB maternity services include a tertiary-level maternity unit in a New Zealand city (average 3800 births per year) plus two midwife-led units (MLUs) . At the tertiary maternity unit, there are 12 birth rooms each with the same design features, including a birth pool or bath, included in the new hospital design commissioned in 2009. The room size and layout differ slightly. Five rooms have a purpose-built birth pool while the remaining seven rooms have baths permanently installed in the corner of the room. The birth pools are round, 1200 mm in diameter and 650 mm deep. There is access around 66% of the pool, a shower, two handrails and steps into the pool. The baths are five-sided and are bound on two sides by a wall. The sides alongside the wall measure 1480 mm, the two short slides measure 670 mm and the front access side measures 1080 mm. The depth of the bathtub is 510 mm. There is a hand-held mixer shower hose set plumbed in over the bath, four handrails, a sieve and thermometer and easy access to piped oxygen, suction and Entonox. At MLU 1 there is one bath measuring 1000 mm wide × 1840 mm long and 630 mm deep. The bath is in a separate room attached to two birth rooms. There is access around three sides of the bath, inner armrests and a headrest. All pools use a disposable liner. For comfort, a soft mat under the liner, and a floor mat are available for comfort for kneeling/laying on the floor around the bath. Equipment in the bathroom includes: a sieve, thermometer, a large mirror and an electric oil burner, portable oxygen, suction and Entonox are available. At MLU 2 there is one bathroom with a purpose-built birth pool permanently installed towards the corner of the room adjacent to the only birth room. The birth pool is rectangular, measuring 1020 mm wide, 1350 mm long and 740 mm deep. There is a built-in seat which can also be used as a step to get in and out, with access around three sides of the pool.Women who used the birth pool or bath during labour and birth across all three DHB maternity facilities, initiated at the time the new tertiary unit opened in February 2009 through to March 2014. Criteria for the use of water immersion for labour and birth usage, as outlined in the DHB guideline, as at least 37 weeks gestation, no adverse fetal or maternal factors in the pregnancy, an informed choice, established labour (judicious use for women with long latent labour is useful to promote relaxation) when there has been a diagnosis of labour dystocia (before using oxytocin). Ruptured membranes are not a contraindication for the use of the birth pool or bath.A paper-based data collection tool, included in the medical record of all women booked to birth at each of the three facilities, was adapted from the DHB water immersion guideline and the literature on water immersion. The form captured details of place of birth, type of caregiver and type of water facility as well as maternal characteristics (such as parity and gestation); and intrapartum events and interventions . Maternal outcomes  and neonatal outcomes (Apgar scores and NICU admission) were included see .Lead Maternity Care (LMC) midwives or core  midwives were asked to complete the form for each woman who used water immersion during labour or birth. Midwives could also enter the presence of any risk factors from the current or previous pregnancies. Data were manually entered in Excel spreadsheet by the primary investigator and research assistant and transferred to SPSS Version 23 for analysis. Where data was unclear or missing, a review of other DHB data sources such as the DHB Patient Information Management System (PIMS) and clinical records of women and neonates  post-birth) occurred. The denominator of some variables differs given missing data.Descriptive statistics describe the characteristics of women who used water immersion during labour and birth and to describe the women and infants’ birthing outcomes. Frequencies and percentages were calculated for categorical variables, mean and standard deviation for continuous variables.The New Zealand Health and Disability Ethics Committee  provided research ethics approval.There were 1517 data collection forms completed for women who used a birth-pool or bath during labour and birth between February 2009 and March 2014: 1188 from the tertiary maternity unit and 329 from two midwifery-led units (164 from MLU 1 and 165 from MLU 2). There were approximately 19,628 births at the DHB facilities during the study period, indicating approximately 7.7% of women used water immersion for labour and birth. As the data collection was reliant on midwives manually completing the data collection form, we cannot be sure this number (1517) fully represented all women who used water for labour and birth during the data collection period.Of the women for whom a data form was completed (1517) there were 584 (38.5%) who had a water birth, 1275 (84%) had a spontaneous vaginal birth, 242 (16%) had assisted births or caesarean sections. Midwives attending women during labour and birth were community-based LMCs (92.7%), core midwife/team (5.0%) and medical LMC/core midwife (2.3%).There were 284 18.7%) data sheets that recorded risk factors for women who used water immersion for labour and birth during the data collection period. Examples of the risk factors recorded are in Fig. 8.7% datan = 830, 54.7%). Most women had a gestational age at labour onset of more than 38 weeks up to 42 weeks gestation (94.3%). There were four women with a gestation of fewer than 36 weeks (0.3%) and ten women whose gestation was more than 42 weeks (0.7%) included in the analysis. Most (93.8%) women’s labour began spontaneously. The woman whose gestational age was less than 36 weeks and the three women whose gestational age were more than 42 weeks gestation had a water birth without any maternal and neonatal complications.A little over half of the women in this study were nulliparous , and the mean number of contractions on entry to water in 10 min was 3.4 (SD 0.7). Water temperature on entry to a birth pool or bath ranged from 23 °C to 44 °C , and the exit temperature was between 24 °C and 42 °C .Of the total 1517 women who used a birth pool or bath during labour, 677 women (44.6%) left the birth pool or bath before birth. Just over 40% of women left the water at their request as they felt fatigued/unwell/hot/cold. Others left due to a need for pharmacological pain relief (10.9%), assessment (9.5%), second stage (8.1%), slow progress (7.4%), fetal distress for cardiotocography , change of position (6.1%), and to use the toilet 3.2%)  (Table From the 1517 women who used water immersion for labour and birth there were 584 (38.5%) water births. More than half (53.7%) of the water births occurred in multiparous women whereas only a quarter (25.9%) of nulliparous had a water birth. Overall, the rate of spontaneous vaginal birth was 84% with 9.4% assisted deliveries and 6.5% caesarean sections. The proportion of assisted birth/CS was significantly higher in nulliparous (25.7%) than in multiparous (4.2%)  of women in this study used pain relief after leaving the pool or bath . More than a third (th Table . The phaThe mean duration of the first stage of labour was 330 mins (SD 238), the second stage of labour was 55 mins (SD 62) and the third stage of labour was 16 mins (SD 17)  or a hands and knees position (15.8%) for birth. Placental birth was actively managed in 917 (60.4%) women whilst 594 (39.2%) has a physiological third stage. Estimated blood loss below 500mls was recorded for 1322 (87.1%) women, with 13 .Nearly 43% of women had an intact perineum following birth with first- and second-degree perineal tears being most common (25.7 and 27.4% respectively). Severe perineal trauma (3rd and 4th degree tears combined) occurred for 35 (2.3%) women most during spontaneous vaginal birth, including the two 4th degree tears.Most neonates had an Apgar score greater than or equal to seven at both 1 min and 5 min post-birth (93.7 and 98.8% respectively). Only 37  chose the tertiary maternity unit for their birthplace over MLU 1 and MLU 2 , whereas more multiparous women chose MLU 1 and MLU 2  over the tertiary maternity unit . Midwifery-led units were more likely to adopt water birth than at the tertiary unit: approximately two-thirds of women who used water immersion during labour, both in MLU 1 and MLU 2, had a water birth  however less than a third of women using water immersion at the tertiary maternity unit had a water birth  . The gestational age at start of labour was similar across all settings. The use of pain relief during labour differed by place of birth: before entry to the pool/bath 493 (41%) of women in a tertiary maternity unit used pharmacological pain relief, whereas women in the midwife-led units used less (33 and 22% respectively) (Table n = 103) of women had a physiological third stage of labour at MLU 1 and 50% (n = 82) at MLU 2. In the tertiary maternity unit 65% (n = 775) of women had an actively managed third stage of labour even.In keeping with the strong association between water birth and physiological third stage of labour, 63% .This study described the maternal characteristics, intrapartum events, interventions, and maternal and neonatal outcomes of women who used water immersion during labour and birth at one New Zealand DHB during the period 2009–2014. The data revealed 84% of women who used water immersion for labour and birth across all three birth settings in this DHB had a spontaneous vaginal birth . This finding is important when compared with the DHB statistics reported in their 2009 annual clinical report that showed 41.3% (1643/3975) of all women who went to term, had a spontaneous labour then had a spontaneous vaginal birth (9). Of note, in this same report, only 34.5% (630/1826) of all primiparous women who went to term, had a spontaneous labour went on to have a spontaneous vaginal birth. The New Zealand national average for spontaneous vaginal birth was reported to be 65.2% in 2014 [The New Zealand Clinical Indicators report outcomes for the ‘standard primipara’ across all DHBs and facilities . They deThe rate of water immersion for labour and birth was very small overall. Despite the availability of a bath or birth pool in every birthing room at the tertiary unit, approximately 7.7% of women used this during labour and birth. The finding that more women have a water birth in the MLUs than at the tertiary unit is likely to be influenced by the philosophy of LMC led community-based care. A midwifery-led continuity of care model in New Zealand means midwives can support women to birth at home, primary birthing units or in the hospital . Most woThe 2009 systematic review  concluded that labouring in water reduces the need for pharmacological pain relief . This stIn the literature, outcomes related to perineal trauma are mixed. Nutter and colleagues 2014) report that there is a decreased likelihood of severe perineal trauma (3rd and 4th-degree tears) associated with water birth . In this report tBlood loss estimation is mainly subjective in most instances. The mean estimated blood loss over 1000mls low is low for all birth settings. While there were no other additional measures used in this study to determine the impact of blood loss such as haemoglobin estimation , 16, thiAs would be expected for this group of low-risk women, neonatal complications were few, with only 37 (2%) of babies admitted to the NICU. The low rate of neonatal admission is in keeping with the findings of the 2016 systematic review of neonatal outcomes following water birth .The results presented are from a sample of women who gave birth in one DHB in New Zealand, and as such, the findings are only indicative of the practice in these settings. The results might not represent all women who used water immersion for labour and birth at the DHB during the time frame of this study. Anecdotally, during the study period, we were aware that not all midwives completed documentation all the time, but were unable to establish the extent of this, nor to enforce it. No data for maternal age or ethnicity were collected. A further limitation is the lack of a control group of low-risk women who met the eligibility criteria but did not use the bath or birth pool during labour. To reduce the proportion of missing data, a review of the PIMS and the clinical records occurred.The differences in outcomes by place of birth should prompt a discussion around what else is happening to impact the decisions of women and midwives. Focused education on water immersion for labour and birth for all midwives and doctors is warranted as well as antenatal education that provides evidence for the impact of place of birth and caregiver on outcomes for women and babies.More research is required to explore factors impacting on women’s decision-making around the use of water immersion for labour and birth as well as women’s satisfaction. It would be beneficial to explore the factors influencing midwives to offer water immersion for labour and birth, and the barriers and facilitators to offering this service in the tertiary maternity environment.Water immersion for labour and birth is a positive intervention that benefits well women with uncomplicated pregnancies. This study shows that water immersion for labour and birth in a midwife-led unit with a community-based lead maternity care midwife results in excellent outcomes for women and infants. Water immersion for labour and birth also provides an essential option for women who have a desire to have a spontaneous vaginal birth. The positive outcomes generated from water birthing indicate that this simple intervention may be a useful solution to address the high intervention rates in New Zealand’s birthing population in tertiary and community settings. Midwives in both tertiary and community-based midwives should, therefore, campaign for improved accessibility to water immersion and water birth for women birthing in all birthing setting.Additional file 1: Supplementary File 1. Water immersion outcome data collection sheet.