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The impact of violence against women on severe acute maternal morbidity in the intensive care unit: a case-control study protocol

ForJournal: peerBMJ Open review only Manuscript ID bmjopen-2017-020147

Article Type: Protocol

Date Submitted by the Author: 16-Oct-2017

Complete List of Authors: Ayala Quintanilla, Beatriz; La Trobe University College of Science Health and Engineering, Judith Lumley Centre; Peruvian National Institute of Health, Lima Taft, Angela; La Trobe University, Mother and Child Health Research McDonald, SJ; Midwifery Professorial Unit, La Trobe University/Mercy Hospital for Women Pollock, Wendy; La Trobe University, The Judith Lumley Centre; Mercy Hospital for Women

Severe acute maternal morbidity, violence against women, intimate Keywords: partner violence, intensive care unit, social determinants, near miss

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1 2 3 4 Title Page 5 6 Study Protocol 7 8 9 The impact of violence against women on severe acute maternal 10 11 morbidity in the intensive care unit: a case-control study protocol 12 13 14 Corresponding autor: 15 16 Dr. Beatriz Paulina ForAyala Quintanilla. peer review only 17 18 Address: 215 Franklin Street, Melbourne, Vic 3000, Victoria, Australia. 19 20 Telephone: +61 3 9479 8800. Fax: +61 3 9479 8811. 21 22 Email: [email protected] 23

24 Authors: Beatriz Paulina Ayala Quintanilla1, 2, 4, Angela Taft1, Susan McDonald1, 2, Wendy 25 26 1, 2, 3 27 Pollock 28

29 30 Author affiliations 31 32 1 The Judith Lumley Centre, La Trobe University, Melbourne, Australia http://bmjopen.bmj.com/ 33 34 2 Mercy Hospital for Women, Melbourne, Australia 35 36 3 37 University of Melbourne, Melbourne, Australia 38 4 39 Peruvian National Institute of Health, Lima, Peru 40 on September 25, 2021 by guest. Protected copyright. 41 42 Keywords: Severe acute maternal morbidity, violence against women, intimate partner violence, 43 44 intensive care unit, social determinants, near miss. 45 46 47 Words in the abstract: 299 words. 48 49 Words in article: 3,276 words, excluding title page, abstract and references. 50 51 52 53 54 55 56 57 58 1 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 4 ABSTRACT 5 6 Introduction: Preventing and reducing violence against women (VAW) and maternal mortality 7 are Sustainable Development Goals. Worldwide, the maternal mortality ratio has fallen about 8 9 44% in the last 25 years; however, the majority of maternal deaths (99%) continue to occur in 10 developing countries. In addition, for one maternal death there are many women affected by 11 severe acute maternal morbidity (SAMM) requiring management in the intensive care unit 12 (ICU). These women represent the most critically ill obstetric patients of the maternal morbidity 13 spectrum and should be studied to complement the review of maternal mortality. Furthermore, 14 many women (30%) endure violence usually exerted by their intimate partners and VAW is 15 thought to be a contributory factor to maternal mortality; but, the impact on SAMM is unknown. 16 For peer review only 17 Thus, this study aims to investigate the impact of VAW on SAMM in the ICU. 18 19 Methods and analysis: This will be a prospective case-control study undertaken in a tertiary 20 healthcare facility in Lima-Peru. We calculated the sample size of 218 participants, 109 cases 21 (maternal ICU admissions) and 109 controls (non-maternal ICU admissions), considering a 22 confidence interval (CI) of 95% and a power of 80%. After obtaining individual written 23 24 informed consent, data on social determinants, medical and obstetric characteristics, VAW, 25 pregnancy and neonatal outcome will be collected through interviews and medical records. 26 VAW will be assessed by using the World Health Organization (WHO) instrument. Binary 27 logistic regression models will be developed to assess any association between VAW and 28 SAMM. 29 30 Ethics and dissemination: Ethical approval has been granted by the La Trobe University 31 32 Human Ethics committee, Melbourne, Australia and the tertiary healthcare facility in Lima-Peru. http://bmjopen.bmj.com/ 33 This research follows the WHO ethical and safety recommendations for research on VAW to 34 ensure the safety of the participants and interviewer. Findings will be presented at conferences, 35 and published in peer-reviewed journals. 36 37 38 39 40 Strengths and limitations of this study on September 25, 2021 by guest. Protected copyright. 41 42 • This prospective study will examine for the first time worldwide the influence of violence 43 against women (VAW) on severe acute maternal morbidity (SAMM). 44 • Studying the stage before maternal death (SAMM) can be considered as a complement to 45 46 maternal death review, and may provide evidence that gives useful insight into factors that 47 may prevent maternal deaths and improve the mother-baby dyad health. 48 • Assessing VAW can be challenging, because it is a sensitive issue and can be underestimated 49 due to recall and cultural bias. The sensitivity may have an impact on willingness to 50 participate in the study. This study will follow the ethical and safety recommendations for 51 research on VAW, and use standardised and pre-tested questions for the assessment of VAW 52 53 and other variables of interest to maximize participation. 54 • This study is within one very large tertiary hospital and further multi-centre studies are 55 needed, based on these replicable methods. 56 57 58 2 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 4 5 INTRODUCTION 6 Preventing and reducing violence against women (VAW) and maternal mortality are Sustainable 7 Development Goals (SDG).1 Worldwide, the maternal mortality ratio (MMR) has declined by 8 44% with a reduction from 385 to 216 maternal deaths per 100,000 live births between 1990 9 (532,000 maternal deaths) and 2015 (303,000 maternal deaths). This equates to approximately 10 2 11 830 women dying daily, of which 99% of maternal deaths occurred in developing countries. 12 However, maternal mortality is only a small proportion of the global burden of the maternal 3-5 13 morbidity spectrum. This is because for one maternal death there are many women affected by 14 severe acute maternal morbidity (SAMM) during pregnancy, childbirth and the postpartum 15 period5-11 including those obstetric patients who require multidisciplinary management in the 16 intensive care unit (ICU).For11-19 peer review only 17 18 13 15 20-25 19 ICU admission can be an alternative marker for defining SAMM, and SAMM can be 20 named as near miss; either term has been widely used to study this population of obstetric 15 17 21 25-28 21 patients. Although the World Health Organization (WHO) has developed a set of 22 (clinical, laboratory and management) criteria to facilitate the identification of near miss, taking 23 into account organ system dysfunction parameters;26 29 many researchers have argued the 24 applicability of using these criteria in both low-income and high-income countries.13 30-34 As a 25 result, in some studies, researchers have used an adapted version of the WHO criteria according 26 27 to the local context and characteristics of healthcare system resources, including the availability 31 32 35-38 28 of advanced laboratory measures and well-trained healthcare professionals. 29 30 Accordingly, there are no internationally accepted criteria for defining SAMM and its definition 31 could differ across studies.13 15 20 25 27 39-44 The use of ICU admission to identify severe maternal 32 22 morbidity has high sensitivity (86.4%), specificity (87.8%) and positive predicted value (0.85). http://bmjopen.bmj.com/ 33 27 45-48 34 This may not identify the wide range of severe obstetric complications because ICU 35 admission criteria may vary across setting and countries according to guidelines established by 26 49-51 36 the healthcare facility, hospital resources availability, among other factors. However, 37 women with SAMM in the ICU represent the most critically ill obstetric patients,11 15 52 whose 38 treatment requires timely managed care and involves unique challenges due to the physiologic 39 changes of pregnancy and the care of the mother-baby dyad.11 13 14 18 19 53-59 40 on September 25, 2021 by guest. Protected copyright. 41 The incidence of maternal ICU admission varies from 0.04 to 4.54%, and the common causes are 42 13 15 16 28 16 43 mainly direct obstetric clinical conditions. According to Pollock, et al., hypertensive 44 disorders were the leading cause of ICU admission (0.09% of deliveries), followed by obstetric 45 haemorrhage (0.07%), and sepsis (0.02%); and, although the ICU admission profile was similar 46 worldwide there were higher rates of maternal deaths in the ICUs of developing countries. 47 48 VAW is a global public health problem and many women of reproductive age endure violence 49 50 usually exerted by their intimate partners (IPV). Globally, 30% of women have experienced 60-62 51 partner abuse. However, the IPV rate varies across studies ranging from 15 to 71% and from 63 52 1 to 28% during pregnancy. Diverse studies have also reported a wide range of IPV rate during 53 pregnancy from 0.9 to 20.1% in developed countries,64 3 to 44% in Latin America and Caribbean 54 countries65 and 2 to 57% in African countries.66 55 56 57 58 3 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 Several studies have reported negative and mortal consequences of IPV on reproductive age 4 women.67-70 During pregnancy, these adverse health outcomes affect the mother-baby dyad; and, 5 can be augmented by consequent risky health behaviors (smoking, alcohol consumption, 6 70-72 7 substance abuse, poor nutrition, lack of seeking health care, among others) and physiological 8 mechanisms through neural, neuroendocrine, and immune responses to acute and/or chronic 9 stress originating from exposure to violence.68 73 All of this may exacerbate preexisting medical 10 conditions and/or lead to diverse pregnancy complications.65 68 74-76 Even though women could be 11 more vulnerable to IPV during the pregnancy and puerperium periods, no data on VAW of 12 obstetric patients in the ICU have been reported in Peru or elsewhere. Thus, further 13 14 investigations are urgently needed to fill this significant gap in understanding factor affecting the 15 burden of maternal morbidity. We are conducting this study in Peru, an upper-middle income 77 16 country with a lifetimeFor IPV peer rate of 68.2% review (emotional 64.2%,only physical 31.7% and sexual 17 6.6%).78 In Peru, there are about 9 cases of femicide monthly69 and a MMR of 68, which fell 18 72.9% from 251 between 1990 and 2015.2 19 20 VAW is also thought to contribute to maternal deaths, and there has been increased concern 21 74 79-82 22 about the negative influence of VAW on maternal mortality. This association was first 83 23 analysed in the 1997-1999 UK Confidential Enquiry into Maternal Death and then in the 2000– 24 2002 UK Confidential Enquiry into Maternal Death.84 However, there is a paucity of studies 25 evaluating this association and further studies are needed to investigate the role of VAW on 26 SAMM, which may be used as a complement to review maternal deaths.22 85-87 Therefore, this 27 research of the stage before maternal death (SAMM) will provide for the first time globally, a 28 29 better understanding about what potential factors, such as VAW, are affecting deterioration from 30 a healthy pregnancy to SAMM. This will make an important contribution to global knowledge of 31 causes of maternal morbidity to prevent and/or reduce maternal morbidity-mortality and improve 32 maternal health. http://bmjopen.bmj.com/ 33 34 35 36 37 HYPOTHESIS 38 We hypothesised that violence against women is significantly associated with severe acute 39 maternal morbidity in obstetric patients managed in the intensive care unit. 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 OBJECTIVES 45 46 47 • To investigate the impact of VAW on women with SAMM in the ICU of a tertiary 48 healthcare facility in Lima-Peru. 49 50 51 • To evaluate pregnancy and neonatal outcome of women with SAMM in the ICU of a 52 tertiary healthcare facility in Lima-Peru. 53 54 55 56 57 58 4 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 4 5 6 7 METHODS 8 This is a prospective case-control study protocol and follows the Strengthening the Reporting of 9 Observational studies in Epidemiology (STROBE) criteria.88 89 10 11 12 Study design 13 In this case-control study, cases will be obstetric patients experiencing SAMM in the ICU (s) 14 including miscarriage, therapeutic abortion, unsafe abortion, and ectopic pregnancy 15 prospectively identified from the ICU register. The inclusion criteria of cases include: i) a 16 woman with a maternalFor ICU peeradmission due review to a complication only (s) during pregnancy, delivery or 17 within 42 days of the ending of pregnancy, with favorable evolution and who fulfils eligibility 18 19 prior to hospital discharge; ii) 18-year-old or older; iii) Spanish speaker; and iv) gives written 20 informed consent. The exclusion criteria are: i) a woman with mental illness or disabilities or 21 other similar disabling pathologies; ii) not able to provide informed consent; iii) an obstetric 22 patient referred from other healthcare facilities for maternity care: iv) ICU stay less than 24 23 hours. Controls are non-maternal ICU admission with favorable evolution from the same source 24 population that gives rise to the cases, selected randomly by using allocated computer-generated 25 random numbers, and whose other criteria are consistent with all other inclusion and exclusion 26 27 criteria of the cases. 28 29 Setting 30 This study will be undertaken in a tertiary hospital located in the capital city of Peru (where 31 about one third of the Peruvian population live). This institution is the main national referral 32 hospital for high risk maternal and neonatal patients throughout Peru, where there are over http://bmjopen.bmj.com/ 33 90 34 22,000 deliveries yearly, which equates to approximately 1 delivery every 25 minutes. 35 36 Ethics 37 Ethical approval has been granted by the La Trobe University Human Ethics committee 38 (HEC15-023), Melbourne, Australia and the Institutional Review Board of the tertiary healthcare 39 40 hospital in Lima, Peru. Individual written informed consent will be obtained from participants on September 25, 2021 by guest. Protected copyright. 41 prior to data collection. The present research follows the WHO and other ethical and safety 42 recommendations for research on gender-based violence to ensure the safety of the participants 43 and the interviewer.63 91-95 44 45 Sample size 46 47 The sample size will comprise 218 participants (109 controls and 109 cases) which has been 48 calculated by using the Sample Size Calculation for Unmatched Case-Control Studies of the 96 49 software open EPi with a confidence level of 95% and a power of 80%. There are not 50 preceding studies assessing the prevalence of VAW among obstetric patients with SAMM in the 51 ICU. We estimated an IPV rate of 24.3% for controls and 43.1% for cases in accordance with 52 previous research investigating the relationship between IPV and preeclampsia in Peruvian 53 97 54 pregnant women at this maternity hospital. 55 56 57 58 5 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 6 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 4 5 6 Recruitment Method 7 Participants will be invited to participate and recruited during their hospital stay once their acute 8 medical condition (s) have been resolved (this will be after they were discharged from the ICU 9 10 for the case women), and before they are discharged from hospital to going home. Women in the 11 control group will be invited to participate within one week of a case woman being interviewed. 12 The interviewer, a Spanish speaking midwife, has been trained and has research experience 13 working on VAW studies and research ethics. She will ensure that the potential participants 14 understand the participant information statement and answer all their questions, and explain to 15 the participants that they can refuse or withdraw their participation at any time without affecting 16 their health care andFor rights. peer review only 17 18 19 Data Collection 20 Data collection commenced on 23rd October 2015 and is still ongoing. Currently, we are 21 collecting data from the medical records. Women who give consent will be interviewed once in 22 23 private using a structured questionnaire (Appendix 1). We will also extract information from 24 their medical records using a pretested form developed by the team members (Appendix 2). 25 26 Interview 27 The following information will be obtained during the face to face interview: socio-demographic 28 characteristics (age, place of residence, educational level, marital status, occupation and type of 29 30 health insurance) of the participant and her partner; behavioural factors (smoking, use of alcohol 31 or drugs); medical (previous and current diseases) and obstetric characteristics (number of 32 pregnancies, previous abortions, prenatal care visits, previous cesarean sections, and vaginal http://bmjopen.bmj.com/ 33 births; use of family planning methods; anemia during pregnancy and use of iron supplements 34 during pregnancy); and VAW evaluation. 35 36 VAW will be assessed by using the set of standardized questions of the WHO instrument.63 37 These questions were validated, translated and adapted rigorously, since Peru was one of the 38 63 39 countries selected in the WHO Multi-country study instrument. They have been also used by 40 other researchers for investigating VAW in Peru, and an adapted version was applied in the on September 25, 2021 by guest. Protected copyright. 41 Peruvian Demographic and Family Health Survey.78 42 43 VAW evaluation will comprise emotional (including controlling behaviours), physical and 44 sexual abuse exerted by intimate-partners and by non-intimate partners (relatives, friends or 45 46 others) assessed 12 months before and during pregnancy. The participants will answer the 47 frequency (once or twice or many) for each act of emotional, physical or sexual violence. VAW 48 will be examined in an empathetic, supportive and non-judgmental manner, giving the 49 participants the opportunity not to answer any questions that make them feel uncomfortable or to 50 reschedule or terminate the interview at any time. The interview will only be conducted with the 51 woman alone and in private. If the interview is interrupted, the interviewer will change the topic 52 53 or may terminate the interview correspondingly. It is expected that the interview will take 54 approximately 25 to 30 minutes. After the interview, information about free social support 55 services for domestic violence (available at this maternity hospital) will be offered to every 56 participant including a referral if they wish. There will be also debriefing sessions for the well- 57 58 6 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 7 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 being of the interviewer. Individual support/counselling can be arranged at the hospital for the 4 interviewer or participant if it is needed. 5 6 7 8 Extracting data from medical records 9 We will extract data from the medical reports of the mothers and newborns (if applicable) related 10 to SAMM, pregnancy outcome, fetal and neonatal characteristics and outcome. 11 12 SAMM data will include hospital admission date, clinical causes for hospitalization and/or ICU 13 14 admission, diagnoses after being discharged from the ICU and/or the hospital, number of 15 hospital stay days and ICU stay days, type of delivery, additional procedures, weeks of 16 pregnancy when SAMMFor occurs, peer organ review failure (s), use ofonly technologies, main delays, and 17 pregnancy outcome (Appendix 2). 18 19 Fetal and neonatal data will include: birth weight; birth age; sex; Apgar score (at 1 and 5 20 21 minutes); outcome at birth; clinical cause (s) for Neonatal ICU (NICU); number of days at the 22 NICU (if applicable) or at the hospital; use of technologies and/or antibiotics at the NICU; 23 feeding type (breastfeeding, formula or both); discharge status; and diagnoses from the hospital 24 and/or the NICU (Appendix 2). 25 26 27 Data entry and analysis 28 Data will be entered using SPSS V.24.0. Univariate analysis will be carried out to describe the 29 characteristics of SAMM, social determinants, VAW and pregnancy and neonatal outcomes. 30 Quantitative variables will be displayed as the mean ± SD and/or median (interquartile rate) after 31 verifying their normal or asymmetrical distribution. Difference of means analyses between 32 variables will be performed using appropriate statistical tests (Student's t-test or Mann–Whitney http://bmjopen.bmj.com/ 33 34 U test or other similar). Qualitative variables will be displayed as frequencies. 35 36 We will apply the following bivariate analysis: i) model 1 will include VAW (partner and non- 37 partner) as independent variable and evaluate its association with SAMM; ii) model 2 will 38 evaluate the association with partner violence only; iii) model 3 will evaluate the association 39 with non-partner violence only. 40 on September 25, 2021 by guest. Protected copyright. 41 42 We will fully assess VAW as a risk factor using multivariate logistic regression modeling 43 adjusted for important confounding variables (to the model 1, 2 and 3) and Odds Ratio with 95% 44 CI. Statistical significance will be set at p < 0.05. The final model will include all variables with 45 a probability of <0.25, those which were statically significant in the univariate analysis, and 46 socio-demographic characteristics (such as household income, partner’s educational level, 47 partner’s occupation, etc.) for SAMM according to literature review. The Hosmer-Lemeshow’s 48 goodness-of-fit test will be used to assess model adequacy and stepwise multiple regression 49 98 50 analysis performed to select and identify the predictive factors in the final models. 51 52 PRESENTING AND REPORTING RESULTS 53 This prospective case-control study will examine for the first time worldwide the influence of 54 55 VAW on women affected by severe acute maternal morbidity who require management in the 56 ICU, and evaluate their pregnancy and neonatal outcomes. We will present major findings in 57 58 7 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 8 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 tables and also describe results in narrative format outlining effect sizes and their parameters. 4 The findings and further publications will be reported following the Strengthening the Reporting 5 88 89 6 of Observational studies in Epidemiology (STROBE) criteria, which is part of the Enhancing 7 the quality and transparency of health research (EQUATOR) Network website. 8 9 DISCUSSION 10 Although, the negative contribution of VAW to maternal deaths has been described in the 1997- 11 1999 Confidential Enquiry into Maternal Death,83 and many studies have reported negative and 12 65 67-76 13 fatal repercussions of IPV on women’s health including during all stages of pregnancy, 14 there is a paucity of studies assessing the relationship between VAW and SAMM. Investigating 15 women affected by SAMM could complement the review of maternal deaths22 85-87 to understand 16 which underlying factorsFor are peer influencing review the sequence of only events from a healthy pregnancy 17 through minor complications to life threatening obstetric conditions and even death in 18 childbearing women.26 99 100 19 20 21 This case-control study will contribute to evidence about the potential negative consequences of 22 VAW of obstetric patients with SAMM in the ICU, who represent the most critically ill 23 patients11 15 52 and have been shown to be an important component of the maternal morbidity 24 spectrum requiring timely managed care.11-19 53-59 This may help to highlight that non-biological 25 factors (VAW), which are potentially modifiable, may be associated with SAMM and are 26 important to address to reduce maternal morbidity-mortality in Peru and in other low and middle- 27 income countries. Acute or chronic exposure to violence adversely affects both the mothers and 28 70-72 29 their babies and can be augmented by any risky health behaviors and through physiological 68 73 30 (neural, neuroendocrine, and immune) mechanisms in response to this abuse. All of this may 31 exacerbate preexisting medical conditions and/or lead to diverse pregnancy complications.65 68 74- 32 76

Thus, it would be important to know if VAW is a risk factor for SAMM in the ICU, and to http://bmjopen.bmj.com/ 33 understand the complete picture of the global burden of maternal morbidity-mortality to improve 34 35 mother-baby dyad health and womens’ well-being. 36 37 This study may also help participants affected by violence to disclose abuse in a safe and 38 supportive environment; and, give an opportunity for those abused women to understand that it is 39 possible to prevent violence and improve their and other women’s lives, since they will be 40 informed and/or referred to the free social support services available for domestic violence on September 25, 2021 by guest. Protected copyright. 41 provided by the Peruvian government. 42 43 44 We understand that the findings of this study should be interpreted cautiously and some 45 limitations should be noted. Firstly, this research will be undertaken in a single center. It will be 46 important to carry out further multi-centre and multi-country studies. Other limitations may 47 include recall, cultural and measurement bias.63 This is because the assessment of VAW is 48 complex and challenging. Accordingly, this research follows the ethical and safety 49 recommendations for research on VAW;63 91-95 and uses standardized questions for the 50 51 assessment of VAW (WHO instrument) and a pretested questionnaire for the evaluation of other 52 factors. Amendments to this protocol are not expected. However, if any are required, these 53 amendments will be reported transparently. 54 55 56 57 58 8 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 9 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 Notwithstanding these limitations, we hope that this study will contribute to the global effort 4 towards achieving SDGs by providing valuable information for a better understanding of SAMM 5 6 and VAW in Peru. This will make an important contribution to global knowledge of causes of 7 maternal mortality and morbidity by providing evidence of the relationship between VAW and 8 SAMM, which is important for preventing and/or reducing maternal morbidity-mortality and 9 improve maternal health. Therefore, we expect that this research will extend knowledge in an 10 identified research gap, and may provide direction for further studies in obstetric women affected 11 by SAMM in the ICU. 12 13 14 15 ETHICS AND DISSEMINATION 16 For peer review only 17 Ethical issues 18 19 Ethical approval has been granted by the La Trobe University Human Ethics Committee, 20 Melbourne, Australia (HEC15-023) and the Institutional Review Board of tertiary healthcare 21 facility in Lima, Peru. 22 23 Publication plan 24 It is planned that the findings of this case-control study will be presented at La Trobe University 25 and national and/or international conferences, and it will be also published in a peer review 26 27 journal. It is expected that these finding will inform policymakers, patients, and the public 28 through these presentations. 29 30 Authors’ contributions 31 BPAQ, AT, SMc and WP conceived and designed the study protocol. This study is part of the 32 first’s author PhD thesis. BPAQ drafted the manuscript and all authors edited following versions http://bmjopen.bmj.com/ 33 34 of the draft. BA, AT, SMc, and WP revised critically the methodological and clinical content of 35 the protocol to make contributions. All authors reviewed and approved the final manuscript. 36 37 Funding 38 This study is part of a doctoral study at La Trobe University funded by the Peruvian Government 39 through PRONABEC (National Program of Scholarship and Educational Loan) and with the 40 support of La Trobe University. on September 25, 2021 by guest. Protected copyright. 41 42 43 Disclaimer 44 No funding bodies will have any role in study design, collecting data, analysing data, interpreting 45 findings, and writing, reviewing or deciding to publish the manuscript. 46 47 Competing interest 48 The authors declare that they have no competing interest. 49 50 51 52 53 54 55 56 57 58 9 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 10 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 4 5 6 7 8 9 REFERENCES 10 11 1. United Nations. Transforming our world: the 2030 Agenda for Sustainable Development. Resolution 12 adopted by the General Assembly on 25 September 2015. 2015. 13 https://sustainabledevelopment.un.org/post2015/transformingourworld (accessed 6 May 2017). 14 2. World Health Organization. Trends in maternal mortality: 1990 to 2015. Estimates by WHO, UNICEF, 15 UNFPA, World Bank Group and the United Nations Population Division. Secondary Trends in maternal 16 mortality: 1990For to 2015. peer Estimates by WHO,review UNICEF, UNFPA, only World Bank Group and the United 17 Nations Population Division. 2015. http://www.who.int/classifications/icd/factsheet/en/ (accessed 15 Feb 18 2016). 19 3. Mantel GD, Buchmann E, Rees H, et al. Severe acute maternal morbidity: a pilot study of a definition for a 20 near-miss. Br J Obstet Gynaecol 1998;105:985-90. 21 4. Geller SE, Cox SM, Callaghan WM, et al. Morbidity and mortality in pregnancy: laying the groundwork 22 for safe motherhood. Womens Health Issues 2006;16:176-88. 23 5. Firoz T, Chou D, von Dadelszen P, et al. Measuring maternal health: focus on maternal morbidity. Bull 24 World Health Organ 2013;91:794-6. 25 6. Ashford L. Hidden suffering: disabilities from pregnancy and childbirth in less developed countries. Secondary Hidden suffering: disabilities from pregnancy and childbirth in less developed countries. 2002. 26 http://www.prb.org/pdf/hiddensufferingeng.pdf (accessed 23 Jul 2014). 27 7. Fottrell E, Kanhonou L, Goufodji S, et al. Risk of psychological distress following severe obstetric 28 complications in Benin: the role of economics, physical health and spousal abuse. Br J Psychiatry 29 2010;196:18-25. 30 8. Pacagnella RC, Cecatti JG, Camargo RP, et al. Rationale for a long-term evaluation of the consequences of 31 potentially life-threatening maternal conditions and maternal "near-miss" incidents using a 32

multidimensional approach. J Obstet Gynaecol Can 2010;32:730-8. http://bmjopen.bmj.com/ 33 9. Wilson RE, Salihu HM. The paradox of obstetric "near misses": converting maternal mortality into 34 morbidity. Int J Fertil Womens Med 2007;52:121-7. 35 10. Storeng KT, Drabo S, Ganaba R, et al. Mortality after near-miss obstetric complications in Burkina Faso: 36 medical, social and health-care factors. Bull World Health Organ 2012;90:418-25B. 37 11. Plaat F, Naik M. Critical care in pregnancy. Crit Care 2011;15:1014 doi: http://dx.doi.org/10.1186/cc10479 38 [published Online First: 22 December 2013]. 39 12. Oud L. Epidemiology of Pregnancy-Associated ICU Utilization in Texas: 2001 - 2010. J Clin Med Res 40 2017;9:143-53 doi: 10.14740/jocmr2854w [published Online First: 17 January 2017]. on September 25, 2021 by guest. Protected copyright. 41 13. Zieleskiewicz L, Chantry A, Duclos G, et al. Intensive care and pregnancy: Epidemiology and general 42 principles of management of obstetrics ICU patients during pregnancy. Anaesth Crit Care Pain Med 43 2016;35 (Suppl 1):S51-7 doi: 10.1016/j.accpm.2016.06.005 [published Online First: 5 July 2016]. 44 14. Guntupalli KK, Hall N, Karnad DR, et al. Critical illness in pregnancy Part I: an approach to a pregnant 45 patient in the ICU and common obstetric disorders. Chest 2015;148:1093-104. 46 15. Senanayake H, Dias T, Jayawardena A. Maternal mortality and morbidity: Epidemiology of intensive care 47 admissions in pregnancy. Best Pract Res Clin Obstet Gynaecol 2013;27:811-20. 48 16. Pollock W, Rose L, Dennis C. Pregnant and postpartum admissions to the intensive care unit: a systematic review. Intensive Care Med 2010;36:1465-74. 49 17. Baskett TF. Epidemiology of obstetric critical care. Best Pract Res Clin Obstet Gynaecol 2008;22:763-74. 50 18. Martin SR, Foley MR. Intensive care in obstetrics: an evidence-based review. Am J Obstet Gynecol 51 2006;195:673-89. 52 19. Germain S, Wyncoll D, Nelson-Piercy C. Management of the critically ill obstetric patient. Curr Obstet 53 Gynaecol 2006;16:125-33. 54 55 56 57 58 10 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 11 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

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1 2 3 69. Ayala Quintanilla BP, Taft A, McDonald S, et al. An examination of femicides in Peru between 2009 and 4 2014. Int J Gynaecol Obstet 2016;134:342-3 doi: 10.1016/j.ijgo.2016.03.020 [published Online First: 4 5 June 2016]. 6 70. Sugg N. Intimate partner violence: prevalence, health consequences, and intervention. Med Clin North Am 7 2015;99(3):629-49. 8 71. Sarkar NN. The impact of intimate partner violence on women's reproductive health and pregnancy 9 outcome. J Obstet Gynaecol 2008;28:266-71. 10 72. Chambliss LR. Intimate partner violence and its implication for pregnancy. Clin Obstet Gynecol 11 2008;51(2):385-97. 12 73. Chisholm CA, Bullock L, Ferguson JEJ, 2nd. Intimate partner violence and pregnancy: epidemiology and 13 impact. Am J Obstet Gynecol 2017;217(2):141-4. 14 74. Knight M, Tuffnell DJ, Kenyon S, et al. Saving Lives, Improving Mothers’ Care - Surveillance of maternal 15 deaths in the UK 2011-13 and lessons learned to inform maternity care from the UK and Ireland 16 Confidential Enquiries into Maternal Deaths and Morbidity 2009-13. Oxford: National Perinatal Epidemiology ForUnit, University peer of Oxford. review 2015. https://www.npeu.ox.ac.uk/ only (accessed 15 Apr 2016). 17 75. Alhusen JL, Ray E, Sharps P, et al. Intimate partner violence during pregnancy: maternal and neonatal 18 outcomes. J Womens Health (Larchmt) 2015;24:100-6. 19 76. Hill A, Pallitto C, McCleary-Sills J, et al. A systematic review and meta-analysis of intimate partner 20 violence during pregnancy and selected birth outcomes. Int J Gynaecol Obstet 2016; 133:269-76 21 doi:10.1016/j.ijgo.2015.10.023 [published Online First: 11 March 2013]. 22 77. World Bank. Data 2017. http://data.worldbank.org/about/country-and-lending-groups (accessed 4 Jun 23 2017). 24 78. INSTITUTO NACIONAL DE ESTADISTICA E INFORMATICA. Encuesta Demografica y de Salud 25 Familiar 2016 - Nacional y Regional 2016. 2017. 26 https://www.inei.gob.pe/media/MenuRecursivo/publicaciones_digitales/Est/Lib1356/. (accessed 12 Jun 27 2017). 28 79. United Nation, Every Woman Every Child. EVERY NEWBORN. An Action Plan To End Preventable 29 Deaths. Secondary EVERY NEWBORN. An Action Plan To End Preventable Deaths 2014. 30 http://apps.who.int/iris/bitstream/10665/127938/1/9789241507448_eng.pdf?ua=1 (accessed 14 Mar 2016). 31 80. Farquhar C, Sadler L, Masson V, et al. Beyond the numbers: classifying contributory factors and 32 potentially avoidable maternal deaths in New Zealand, 2006–2009. Am J Obstet Gynecol 2011;205:331.e1- http://bmjopen.bmj.com/ 33 31e-8 doi:10.1016/j.ajog.2011.07.044 [published Online First: 30 July 2011]. 34 81. Knight M., Kenyon S., Brocklehurst P., et al. Saving Lives, Improving Mothers’ Care - Lessons learned to 35 inform future maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and 36 Morbidity 2009 –12. Oxford: National Perinatal Epidemiology Unit, University of Oxford. 2014. 37 https://www.npeu.ox.ac.uk/downloads/files/mbrrace- 38 uk/reports/Saving%20Lives%20Improving%20Mothers%20Care%20report%202014%20Full.pdf 39 (accessed 27 Apr 2016). 40 82. Murphy NJ, Quinlan JD. Trauma in pregnancy: assessment, management, and prevention. Am Fam on September 25, 2021 by guest. Protected copyright. 41 Physician 2014;90(10):717-22. 42 83. The Confidential Enquiries into Maternal Deaths in the United Kingdom. 2001. Why mothers die 1997– 43 1999. The fifth report of the Confidential Enquiries into Maternal Deaths. http://www.hqip.org.uk/national- programmes/a-z-of-clinical-outcome-review-programmes/cmace-reports/ (accessed 2 Aug 2014). 44 84. The Confidential Enquiries into Maternal and Child Health in the United Kingdom. 2004. Why Mothers 45 Die 2000–2002. The Sixth Report of the Confidential Enquiries into Maternal Deaths. 46 http://www.hqip.org.uk/assets/NCAPOP-Library/CMACE-Reports/33.-2004-Why-Mothers-Die-2000- 47 2002-The-Sixth-Report-of-the-Confidential-Enquiries-into-Maternal-Deaths-in-the-UK.pdf (accessed 9 48 Aug 2014). 49 85. Knight M, Lewis G, Acosta CD, et al. Maternal near-miss case reviews: the UK approach. BJOG 2014;121 50 Suppl 4:112-6. 51 86. Ananth CV, Smulian JC. Chapter 1 Epidemiology of Critical Illness in Pregnancy. In Belfort MA, Saade G, 52 Foley MR, et al., eds. Critical Care Obstetrics Fifth Edition 2011:1-10. 53 87. Knight M, Acosta C, Brocklehurst P, et al. Beyond maternal death: improving the quality of maternal care 54 through national studies of 'near-miss' maternal morbidity. Programme Grants Appl Res 2016;4(9). 55 56 57 58 13 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 14 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 88. von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in 4 Epidemiology (STROBE) statement: guidelines for reporting observational studies. The Lancet 5 2007;370(9596):1453-57. 6 89. von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in 7 Epidemiology (STROBE) Statement: guidelines for reporting observational studies. Int J Surg 8 2014;12:1495-9. 9 90. Instituto Nacional Materno Perinatal. Boletín Estadístico 2015 - 2016. 2016. 10 http://www.inmp.gob.pe/institucional/boletines-estadisticos/1422371837 (accessed 28 May 2017). 11 91. Jewkes R, Dartnall E, Sikweyiya Y. Ethical and Safety Recommendations for Research on the Perpetration 12 of Sexual Violence. Sexual Violence Research Initiative Pretoria, South Africa: Medical Research Council. 13 2012. http://www.svri.org/EthicalRecommendations.pdf (accessed 28 May 2015). 14 92. Ellsberg M, Heise L. Researching Violence Against Women: A Practical Guide for Researchers and 15 Activists Washington DC, United States: World Health Organizationb PATH. 2005. 16 http://whqlibdoc.who.int/publications/2005/9241546476_eng.pdf?ua=1 (accessed 26 May 2015). 93. World Health ForOrganization. peer Putting Women review First: Ethical and onlySafety Recommendations for Research on 17 Domestic Violence Against Women. 2001. http://www.who.int/gender/violence/womenfirtseng.pdf 18 (accessed 27 May 2015). 19 94. Jansen HAFM, Watts C, Ellsberg M, et al. Interviewer Training in the WHO Multi-Country Study on 20 Women’s Health and Domestic Violence. 2004. 21 http://www.who.int/gender/documents/Interviewer_training.pdf (accessed 27 May 2015). 22 95. Garcia-Moreno C, Jansen HAFM, Ellsberg M, et al. WHO Multi-country Study on Women’s Health and 23 Domestic Violence Against Women. Initial results on prevalence, health outcomes and women’s responses. 24 2005. http://www.who.int/reproductivehealth/publications/violence/24159358X/en/ (accessed 2 Jul 2014). 25 96. Open Epi. Sample Size Calculation for Unmatched Case-Control Studies. Version 3.03.17. 2014. 26 http://web1.sph.emory.edu/cdckms/sample%20size%202%20grps%20case%20control.html (accessed 2 27 Jul 2015). 28 97. Sanchez SE, Qiu C, Perales MT, et al. Intimate partner violence (IPV) and preeclampsia among Peruvian 29 women. Eur J Obstet Gynecol Reprod Biol 2008;137:50-5 doi: 10.1016/j.ejogrb.2007.05.013 [published 30 Online First: 27 Jun 2007]. 31 98. Hosmer DV, Lemeshow S. Applied Logistic Regression. Second Edition ed. USA: A Wiley-Interscience 32 Publication. 2000:375. http://bmjopen.bmj.com/ 33 99. Karolinski A, Mercer R, Micone P, et al. The epidemiology of life-threatening complications associated 34 with reproductive process in public hospitals in Argentina. BJOG 2013;120:1685-95. 35 100. Filippi V, Chou D, Ronsmans C, et al. Levels and Causes of Maternal Mortality and Morbidity. In: Black 36 RE, Laxminarayan R, Temmerman M, et al., eds. 2016. Reproductive, Maternal, Newborn, and Child 37 Health. Disease Control Priorities, third edition, volume 2. Washington, DC: World Bank. 38 doi:10.1596/978-1-4648-0348-2. License: Creative Commons Attribution CC BY 3.0 IGO. 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 14 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 15 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 4 5 Appendix 1 6 7 Judith Lumley Centre for mother, infant and family health research 8 9 College of Science, Health and Engineering 10 11 La Trobe University 12 13 14 Maternal health research in a tertiary health care facility in Lima, Peru 15 Structured questionnaire for face to face interview 16 For peer review only 17

18 Code number: ______Interview Date: ______/ ______/______19 D D M M Y Y Y Y 20 Thank you for agreeing to participate in this study. 21 You are free to not answer any questions. If any of the questions are unclear, or you need more information the interviewer will be happy to provide 22 23 you with the information you need. 24 Before I start, do you have any questions? 25 26 SECTION A. GENERAL INFORMATION 27 WOMAN INFORMATION 28

29 First I would like to ask you some questions about your background. 30 31 A1.How old are you? ______(Years) 32 http://bmjopen.bmj.com/ 33 A2. Place of residence 34 1. Lima Norte (Ancón, Carabayllo, Comas, Independencia, Los Olivos, Puente Piedra, San Juan de Lurigancho, San Martin de Porres, Santa Rosa) 35 2. Lima Este 36 (Ate, Cieneguilla, Chaclacayo, El Agustino, Lurigancho, San Luis, Santa Anita) 37 3. Lima Sur 38 (Chorrillos, Lurín, Pachacamac, Pucusana, Punta Hermosa, Punta Negra, San Bartolo, San Juan de Miraflores, Santa María del Mar, Villa el Salvador, Villa María del Triunfo) 39 4. Residential Lima 40 (Barranco, Jesús María, La Molina, Lince, Magdalena, Miraflores, Pueblo Libre, San Borja, San Isidro, San Miguel, Santiago de Surco, Surquillo) on September 25, 2021 by guest. Protected copyright. 41 5. Callao 42 (Bellavista, Callao District, Carmen de la Legua Reynoso, La Perla, La Punta, Ventanilla District) 6. Central Lima 43 (Breña, La Victoria, Downtown Lima, Rimac) 44 45 A3. What is your level of education? Would you say? 46 1. Primary level 47 2. Secondary level 48 3. Technical studies 4. University level 49 5. Other (Specify)______50 9 Do not know / Not Sure 51 52 A4. What is your current marital status? 53 1. Single 54 2. Married 3. Cohabitant 55 4. Separated/Divorced 56 5. Widowed 57 9. Do not know / Not Sure 58 1 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 16 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 A5. What is your occupation? 2 1. Unemployed 3 2. Student 4 3. Employed 5 4. Selfemployed 6 5. Housewife 6. Other (specify) ______7 7. Do not know / Not Sure 8 9 A6. How hard is it for you (and your family) to pay for the very basics like food? 10 1 Very hard 11 2 Hard 12 3 Somewhat hard 4 Not very hard 13 9 Do not know / Not Sure 14 15 A7. How hard is it for you (and your family) to pay for medical care? 16 1 Very Hard For peer review only 17 2 Hard 18 3 Somewhat hard 4 Not very hard 19 9 Do not know / Not Sure 20 21 A8. How much is the estimated monthly income of your nuclear family? 22 23 24 25 A9. How many household members are dependent on this monthly income (specify)? 26 27 28 A10. Are you a SIS beneficiary? 29 1 No 30 2 Yes 31 9 Do not know / Declined to answer 32 http://bmjopen.bmj.com/ 33 A11. Can you tell me your SIS category? 34 1 Low risk 35 2 Medium risk 3 High risk 36 9 Do not know / Declined to answer 37 38 A12. If you do not have SIS, which health insurance do you have? 39 1 Private company 40 2 Other (specify)______on September 25, 2021 by guest. Protected copyright. 41 3 Do not have any health insurance 9 Do not know / Declined to answer 42 43 A13. What about smoking, do you smoke during this pregnancy? 44 1 No → Skip to A15 45 2 Yes → Continue to A14 46 9 Do not know / Declined to answer 47 A14. If yes, would you say? 1. Daily 48 2. Occasionally 49 3. Not at all 50 9 Do not know / Declined to answer 51 52 A15. What about alcohol use, do you drink alcohol during this pregnancy? 53 1 No → Skip to A17 2 Yes → Continue to A16 54 9 Do not know / Declined to answer 55 56 57 58 2 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 17 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 A16. If yes, would you say? 2 1. Every day or nearly every day 3 2. Once or twice a week 4 3. 1 – 3 times a month 5 4. Occasionally, less than once a month 6 5. Never 9 Do not know / Declined to answer 7 8 A17. What about drug use, do you use any illegal drugs during this pregnancy? 9 1. No 10 2. Yes 11 9. Do not know / Declined to answer 12

13 PARTNER INFORMATION 14 15 A18. What is the age of your partner ______(Years) 16 A19. What is the level of educationFor of your husband/partner? peer review only 17 18 1. Primary level 2. Secondary level 19 3. Technical studies 20 4. University level 21 5. Other (Specify)______22 9 Do not know / Declined to answer 23 A20. What is the occupation of your husband/partner? 24 1. Unemployed 25 2. Student 26 3. Employed 27 4. Selfemployed 5. Other (specify) ______28 9 Do not know / Declined to answer 29 30 A21. What about alcohol use, does/did your husband/partner drink alcohol during your pregnancy? 31 1 No → Skip to A25 32 2 Yes → Continue to A22 http://bmjopen.bmj.com/ 33 34 A22. If yes, would you say? 1. Every day or nearly every day 35 2. Once or twice a week 36 3. 1 – 3 times a month 37 4. Occasionally, less than once a month 38 5. Never 39 9 Do not know / Declined to answer 40 A23. Does/did your husband/partner get drunk during your pregnancy? on September 25, 2021 by guest. Protected copyright. 41 1. No → Skip to A25 42 2. Yes → Continue to A24 43 9. Do not know/Declined to answer 44 45 A24. If yes, would you say? 46 1. Most days 47 2. Weekly 3. Once a month 48 4. Less than once a month 49 5. Never 50 9 Do not know / Declined to answer 51 52 A25. What about drug use, does/did your partner use any illegal drugs during your pregnancy? 53 1. No 54 2. Yes 9. Do not know / Declined to answer 55 56 57 58 3 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 18 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 B. PREGNANCY AND PRENATAL CHARACTERISTICS 2 3 Now I would like to ask you some questions about your pregnancy history 4 5 B1. How many weeks of pregnancy were you at your first prenatal visit? ______(Weeks) 6 B2. Did you receive prenatal care during this pregnancy? 7 1. No → Skip to B4 8 2. Yes → Continue to B3 9 9 Do not know / Not sure 10 B3. How many antenatal care visits did you receive during pregnancy? ______times [999 = Do not know] 11 B4. How much was your weight before you became pregnant this time? ______Kilograms [999 = Do not know] 12 13 B5. How much weight did you gain since becoming pregnant? ______Kilograms [999 = Do not know] 14 B6. What is your height? ______Centimeters [999 = Do not know] 15 B7. GRAVIDITY = Number of pregnancies (including this pregnancy) ______16 For peer review only 17 B8. PARITY = Number of live births >22 weeks (including this pregnancy) ______18 B9. Number of vaginal deliveries (including this pregnancy) ______19 B10. Number of cesarean sections (including this pregnancy) ______20 B11. Number of total previous abortions ______21 22 B12. Miscarriages ______23 B13. Unsafe abortions ______24 B14. Therapeutic abortions ______25 26 B15. Number of Molas ______27 B16. Number of ectopic pregnancies ______28 B17. Number of alive children ______29 B18. Number of stillborns ______30 31 B19. Number of dead children ______32 B20. Did you plan to become pregnant this time? http://bmjopen.bmj.com/ 33 1 No 34 2 Yes 35 9 Do not know / Declined to answer 36 B21. Are you aware of family planning methods to avoid getting pregnant? 37 1. No → Skip to B24 38 2. Yes → Continue to B22 39 9 Do not know / Declined to answer 40 B22. Which family planning methods do you use to avoid getting pregnant (if it is more than one, only consider the main method)? on September 25, 2021 by guest. Protected copyright. 41 1 Pills/Tablets 42 2 Injectable 43 3 Diaphragm/foam/jelly 4 IUD 44 5 Condoms 45 6 Natural Method (calendar/mucus method) 46 7 Withdrawal 47 8 Other (specify)______48 B23. How often do you use family planning methods? 49 1. Often 50 2. Rarely 3. Never (because of) 51 3.1. Because of ignorance about them 52 3.2. Because of logistic/administrative issues 53 3.3. Because of unwillingness to use them 54 3.4. Because of partner unwillingness to use them 55 3.5. Because of the cost 56 3.6. Other (specify)______9. Do not know / Declined to answer 57 58 4 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 19 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 B24. Did you receive vaccination against tetanus in the last 10 years? 3 1. No 4 2. Yes 5 9 Do not know / Not sure 6 B25. Did a doctor ever tell you that you have anemia during this pregnancy? 7 1. No → Skip to B30 8 2. Yes → Continue to B26 9 9 Do not know / Not sure 10 11 B26. Which trimester, did a doctor tell you that you have anemia during this pregnancy? 12 1 I Trimester 13 2 II Trimester 3 III Trimester 14 9 Do not know / Not sure 15 16 B27. Did you takeFor any ferrous peer iron supplement duringreview this pregnancy? only 17 1. No → Skip to B30 18 2. Yes → Continue to B28 19 9 Do not know / Not sure 20 B28. If yes, how many pills/tablets per day? ______pills per day [99: Do not know / not sure] 21 B29. And, how many months did you drink these pills/tablets? ______months [99: Do not know / not sure] 22 23 B30. How many times did you visit the emergency room during this pregnancy? ______time/times [99: Do not know / not sure] 24 B31. Has a doctor ever told you that you have or do you have? 25 You have had You have 26 Diseases Do not know / Do not know / No Yes No Yes 27 not sure not sure 28 a Chronic hypertension 1 2 99 1 2 99 29 b Anemia 1 2 99 1 2 99 30 c Tuberculosis 1 2 99 1 2 99 31 d Diabetes Mellitus 1 2 99 1 2 99 32 e Heart disease 1 2 99 1 2 99 http://bmjopen.bmj.com/ 33 34 f Thyroid disease 1 2 99 1 2 99 35 g HIV infection 1 2 99 1 2 99 36 h Other (specify) ______1 2 99 1 2 99 37 38 39 40 B32. Did you ever have one or more of the following condition (s) during previous pregnancy (es)? Do not know / on September 25, 2021 by guest. Protected copyright. 41 Clinical conditions NO YES 42 not sure 43 1 Hypertensive related disease 1 2 99 44 a Severe Preeclampsia 1 2 99 45 b Eclampsia 1 2 99 46 c HELLP Syndrome 1 2 99 2 Antepartum hemorrhage in the second trimester of pregnancy because of (specify): 47 1 2 99 48 49 a Placenta previa 1 2 99 50 b Uterine rupture 1 2 99 51 c Abruptio placentae 52 d Other (specify) 1 2 99 53 54 3 Antepartum hemorrhage in the third trimester of pregnancy because of (specify): 1 2 99 55 a Placenta previa 1 2 99 56 b Uterine rupture 1 2 99 57 c Abruptio placentae 1 2 99 58 5 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 20 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 d Other (specify) 1 2 99 2 3 4 Postpartum hemorrhage complication 1 2 99 4 a Uterine atony 1 2 99 5 b Cervical laceration/tear 1 2 99 6 c Retained products/fetal membranes 1 2 99 7 d Ruptured uterus 1 2 99 8 e Accreta placenta 1 2 99 9 10 f Other (specify) 1 2 99 11 5 Sepsis (obstetric origin) 1 2 99 12 a Chorioamnionitis 1 2 99 13 b Surgical wound infection 1 2 99 14 c Endometritis 1 2 99 15 d Other (specify) 1 2 99 16 6 Sepsis (non-obstetric origin)For peer review only1 2 99 17 a Urine infection 1 2 99 18 b Other (specify) 1 2 99 19 7 Sepsis (pulmonary origin) 1 2 99 20 a Pneumonia 1 2 99 21 b Viral cause 1 2 99 22 b.1 H1N1 1 2 99 23 b.2 Varicella 1 2 99 24 b.3 Other (specify) 1 2 99 25 c Other (specify) 1 2 99 26 27 8 Clinical condition 1 2 99 28 a Oligohydramnios 1 2 99 29 b Intrauterine growth restriction 1 2 99 30 c Fetal macrosomy 1 2 99 31 d Other (specify) 1 2 99 32 http://bmjopen.bmj.com/ 33 9 Other associated pathologies 34 a Premature rupture of fetal membranes 1 2 99 35 b Disseminated intravascular coagulation (DIC) 1 2 99 36 c Maternal pulmonary edema 1 2 99 37 d Amniotic fluid embolism 1 2 99 38 e Retroplacental clot 1 2 99 39 f Septic shock. 1 2 99 40 g Hypovolemic Shock 1 2 99 on September 25, 2021 by guest. Protected copyright. 41 h Cervical cancer 1 2 99 42 43 i Other (specify) 1 2 99 44 45 46

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1 C. ASSESSMENT OF VAW (IPV AND NON-IPV) 2 3 When two people marry or live together, they usually share both good and bad moments. I would now like to ask you some questions about your current 4 and past relationships and how your husband / partner treats (treated) you. If anyone interrupts us I will change the topic of conversation. I would again 5 like to assure you that your answers will be kept secret, and that you do not have to answer any questions that you do not want to. May I continue?

6 7 BEFORE PREGNANCY DURING PREGNANCY Assessing IPV 8 (In the past 12 months before pregnancy) 9 10 (A) (B) (C) (D) (E) 11 (If YES continue Has this In the past 12 months before this Has this 12 with B. If NO, happened in pregnancy, would you say that this happened during During Pregnancy, would you say I am going to ask you about 13 ask during the past 12 has happened once, a few times or this pregnancy? that this has happened once, a few some situations that are true pregnancy and months before many times? (If YES ask E) times, or many times? 14 for many women. Would you if NO skip to this (after answering C, go to D) say it is generally true that he: 15 next item) pregnancy? 16 For peer(If YES ask C, review only 17 if NO ask D) 18

Many 19 Many YES NO YES NO One Few YES NO One Few (>5 times) (>5 times) 20 21 22 C1. Tries to keep you from 1 2 1 2 1 2 3 1 2 1 2 3 23 seeing your friends? 24 25 C2. Tries to restrict contact with 1 2 1 2 1 2 3 1 2 1 2 3 26 your family of birth? 27 C3. Insists on knowing where 28 1 2 1 2 1 2 3 1 2 1 2 3 29 you are at all times? 30 C4. Ignores you and treats you 31 1 2 1 2 1 2 3 1 2 1 2 3 32 indifferently? http://bmjopen.bmj.com/ 33 C5. Gets angry if you speak 34 1 2 1 2 1 2 3 1 2 1 2 3 35 with another man? 36 C6. Is often suspicious that you 37 1 2 1 2 1 2 3 1 2 1 2 3 38 are unfaithful? 39 40 C7. Expects you to ask his permission before seeking 1 2 1 2 1 2 3 1 2 1 2 3 on September 25, 2021 by guest. Protected copyright. 41 health care for yourself? 42 43

44 45 46

47 48 The next questions are about things that happen to many women, and that your current partner, or any other partner may have done to 49 you. 50

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1 2 3 BEFORE PREGNANCY DURING PREGNANCY 4 Assessing IPV 5 (In the past 12 months before pregnancy) 6 (A) (B) (C) (D) (E) 7 8 (If YES continue Has this In the past 12 months before Has this happened 9 Has your current with B. If NO, ask happened in the this pregnancy, would you say during this During Pregnancy would you say husband/partner or any other during pregnancy past 12 months that this has happened once, a pregnancy? that this has happened once, a few 10 partner ever …… and if NO skip to before this few times or many times? (If YES ask E) times, or many times? 11 next item) pregnancy? (after answering C, go to D) 12 (If YES ask C, if 13 NO ask D)

14 YES NO YES NO One Few Many YES NO One Few Many 15 (>5 times) (>5 times) 16 C8. Insulted you or made you 1 For2 peer 1 2 review1 2 3 only1 2 1 2 3 17 feel bad about yourself? 18 C9. Belittled or humiliated 1 2 1 2 1 2 3 1 2 1 2 3 19 you in front of other people? 20 C10. Done things to scare or 21 intimidate you on purpose 22 (e.g., by the way he looked at 1 2 1 2 1 2 3 1 2 1 2 3 you, by yelling and smashing 23 things)? 24 C11. Threatened to hurt you 1 2 1 2 1 2 3 1 2 1 2 3 25 or someone you care about 26

27 28 BEFORE PREGNANCY 29 DURING PREGNANCY Assessing IPV 30 31 (In the past 12 months before pregnancy) 32 (A) (B) (C) (D) (E) http://bmjopen.bmj.com/ 33 (If YES Has this In the past 12 months before this Has this 34 continue with happened in pregnancy, would you say that happened during During Pregnancy, would you say 35 Has your current B. If NO, ask the past 12 this has happened once, a few this pregnancy? that this has happened once, a few husband/partner or any other during months before times or many times? (If YES ask E) times, or many times? 36 partner ever …… pregnancy this (after answering C, go to D) 37 and if NO pregnancy? 38 skip to next (If YES ask C, item) if NO ask D) 39 40

Many Many on September 25, 2021 by guest. Protected copyright. YES NO YES NO One Few YES NO One Few 41 (>5 times) (>5 times) 42 C12. Slapped you or thrown 43 something at you that could 1 2 1 2 1 2 3 1 2 1 2 3 44 hurt you? 45 C13. Pushed you or shoved 1 2 1 2 1 2 3 1 2 1 2 3 46 you or pulled your hair? 47 C14. Hit you with his fist or 48 with something else that could 1 2 1 2 1 2 3 1 2 1 2 3 hurt you? 49 C15. Kicked you, dragged 50 1 2 1 2 1 2 3 1 2 1 2 3 you or beat you up? 51 52 C16. Choked or burnt you on 1 2 1 2 1 2 3 1 2 1 2 3 53 purpose? 54 C17. Threatened to use or 55 actually used a gun, knife or 1 2 1 2 1 2 3 1 2 1 2 3 56 other weapon against you? 57 58 8 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 23 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 4 BEFORE PREGNANCY DURING PREGNANCY 5 Assessing IPV 6 (In the past 12 months before pregnancy) 7 (A) (B) (C) (D) (E) 8 9 (If YES Has this In the past 12 months before Has this continue with happened in this pregnancy, would you say happened during During Pregnancy, would you 10 Has your current B. If NO ask the past 12 that this has happened once, a this pregnancy? say that this has happened husband/partner or any 11 during months before few times or many times? (If YES ask E) once, a few times, or many other partner ever …… 12 pregnancy, this pregnancy? (after answering C, go to D) times? 13 and if NO skip (If YES ask C, 14 to next item) if NO ask D)

15 Many Many 16 YES NO YES NO One Few (>5 times) YES NO One Few For peer review only (>5 times) 17 C18. Did your current 18 husband/partner or any 19 other partner ever physically 1 2 1 2 1 2 3 1 2 1 2 3 20 force you to have sexual 21 intercourse when you did not want to? 22 C19. Did you ever have 23 sexual intercourse you did not want to because you 24 1 2 1 2 1 2 3 1 2 1 2 3 were afraid of what your 25 partner or any other partner 26 might do? 27 C20. Did your partner or 28 any other partner ever force you to do something sexual 1 2 1 2 1 2 3 1 2 1 2 3 29 that you found degrading or 30 humiliating? 31 32 http://bmjopen.bmj.com/ 33 34 35 36 37 38

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1 NON-IPV 2 3 In their lives, may women experience different forms of violence from relatives, other people that they know, and/or from strangers. If you don’t mind. I 4 would like to briefly ask you about some of these situations. If anyone interrupts us I will change the topic of conversation. Everything that you say will be kept private. May I continue? 5 6 DURING PREGNANCY 7 BEFORE PREGNANCY

8 Assessing Non-IPV 9 10 (In the past 12 months before pregnancy) 11 12 (A) (B) (C) (D)

13 (If YES Has this happened in the past 12 In the past 12 months before this Has this happened during this pregnancy? 14 continue with months before this pregnancy? pregnancy, would you say that this (If YES ask Who was/were) Since the age of 15 B. If NO, ask (If YES ask C, if NO ask D) has happened once, a few times or 15 years, has during many times? 16 anyone (other pregnancy For peer(after answering review C, go to D) onlyAnd would you say that this has happened once, a few times, or many 17 than your and if NO times? partner/husband): 18 skip to next (in total from all the persons she (in total from all the persons she mentioned) item) mentioned) 19 (choose “one”, “few” or many” considering in total from all the persons 20 she mentioned) 21 Many Many Who did this to you? Who did this to you? YES NO YES No One Few (>5 YES No One Few (>5 22 (multiple responses) (multiple responses) times) times) 23 B Father B Father 24 C Mother C Mother D Father in law D Father in law 25 E Mother in law E Mother in law 26 C21. Insulted F Other family member F Other family member you or made you G Friend of family G Friend of family 27 1 2 1 2 1 2 3 1 2 1 2 3 feel bad about H Neighbor H Neighbor 28 yourself? I Someone at work I Someone at work J Stranger J Stranger 29 K Other (specify) K Other (specify) 30 ………………………………. ………………………… 31 ……….……………………… …….………………….. 32 B Father B Father

C Mother C Mother http://bmjopen.bmj.com/ 33 D Father in law D Father in law E Mother in law E Mother in law 34 C22. Belittled or F Other family member F Other family member 35 humiliated you in G Friend of family G Friend of family 1 2 1 2 1 2 3 1 2 1 2 3 36 front of other H Neighbor H Neighbor people? I Someone at work I Someone at work 37 J Stranger J Stranger K Other (specify) K Other (specify) 38 …………………………… ………………………… 39 ………….………………… …………….…………. 40 B Father B Father C23. Done C Mother C Mother on September 25, 2021 by guest. Protected copyright. 41 things to scare or D Father in law D Father in law 42 intimidate you on E Mother in law E Mother in law F Other family member F Other family member 43 purpose (e.g., by G Friend of family G Friend of family 44 the way he 1 2 1 H Neighbor 2 1 2 3 1 H Neighbor 2 1 2 3 looked at you, by I Someone at work I Someone at work 45 yelling and J Stranger J Stranger 46 smashing K Other (specify) K Other (specify) 47 things)? …………………………… ………………………… …….…….………………. …………….…………. 48 B Father B Father 49 C Mother C Mother D Father in law D Father in law 50 E Mother in law E Mother in law 51 C24. Threatened F Other family member F Other family member to hurt you or G Friend of family G Friend of family 1 2 1 2 1 2 3 1 2 1 2 3 52 someone you H Neighbor H Neighbor 53 care about? I Someone at work I Someone at work J Stranger J Stranger 54 K Other (specify) K Other (specify) 55 …………………………… ………………………… 56 …………………………… …….……….…………. 57 58 10 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 25 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 Continue with the following questions…………………………………… 2 3 4 5 BEFORE PREGNANCY DURING PREGNANCY 6 Assessing Non-IPV

7 (In the past 12 months before pregnancy) 8 9 (A) (B) (C) (D)

10 (If YES Has this happened in the past In the past 12 months before this Has this happened during this pregnancy? 11 continue with 12 months before this pregnancy, would you say that this (If YES ask Who was/were) B. If NO, ask pregnancy? has happened once, a few times or 12 Since the age of 15 during (If YES ask C, if NO ask D) many times? years, has anyone 13 pregnancy (after answering C, go to D) And would you say that this has happened once, a few times, or (other than your and if NO many times? 14 partner/husband): 15 skip to next (in total from all the persons she (in total from all the persons she mentioned) 16 item) mentioned) For peer review only(choose “one”, “few” or many” considering in total from all the 17 persons she mentioned) 18 Who did this Who did this 19 to you? Many to you? Many YES NO YES No One Few YES No One Few 20 (multiple (>5 times) (multiple (>5 times) 21 responses) responses) 22 B Father B Father 23 C Mother C Mother 24 D Father in law D Father in law E Mother in law E Mother in law 25 F Other family F Other family 26 C25. Ever beaten member member you or physically G Friend of G Friend of 1 2 1 2 1 2 3 1 2 1 2 3 27 mistreated you in family family 28 any way ? H Neighbor H Neighbor I Someone at I Someone at 29 work work 30 J Stranger J Stranger K Other (specify) K Other (specify) 31 ……………… ……………… 32 ……………… ……………… http://bmjopen.bmj.com/ 33 B Father B Father 34 C26. ¿forced you to C Mother C Mother 35 D Father in law D Father in law have sex or to E Mother in law E Mother in law 36 perform a sexual act F Other family F Other family 37 when did you not member member want or to do G Friend of G Friend of 1 2 1 2 1 2 3 1 2 1 2 3 38 something sexual family family 39 that you found H Neighbor H Neighbor degrading or I Someone at I Someone at 40 work work humiliating? on September 25, 2021 by guest. Protected copyright. 41 J Stranger J Stranger K Other (specify) K Other (specify) 42 ……………… ……………… 43 ……………… ……………… 44 45 46 C27. Have you ever been punched or kicked in the abdomen by anyone including your (ex or current) partner or other person(s) whilst you were pregnant? 47 1. No 48 2. Yes 49 C.28 When (indicate year and which pregnancy) Year………………Which pregnancy………………………...... 50 51 9. Don’t know / Decline to answer 52 C29. Have any health care professionals asked you if you were affected by IPV or nonpartner violence? 53 1 No 54 2 Yes 55 9 Do not know / Decline to answer 56 57 58 11 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 26 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 Continue with the questions C30, C31 and C32 for those participants who were affected by harm acts 4 5 Go to question C32 (Skip questions C29 and C30) for those participants who were NOT affected by harm acts 6 7 8 9

10 C30. Have you sought help to prevent or stop genderbased violence? 11 1 No 12 2 Yes 13 9 Do not know / Decline to answer 14 15 C31. Can you mention what type of help? 1 Family member 16 2 ForFriend peer review only 17 3 Community Social Services from the government 18 4 Police 19 5 Other (specify)………………………… 20 9 Do not know / Decline to answer 21

22 Ask the following question to each participant 23 24 25 C32. Is there anything else do you want to tell me? 26 (Write down the exact words expressed by the participant) 27 ______28 ______29 ______30 31 32 Now give the information about free social support services available for domestic violence at this Institution and which are free of cost and are http://bmjopen.bmj.com/ 33 provided by the Peruvian government. 34 35

36 37 Thank you for your participation¡¡¡¡ 38 39 40 on September 25, 2021 by guest. Protected copyright. 41

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1 2 3 4 5 6 7 Appendix 2 8 Judith Lumley Centre for mother, infant and family health research centre 9 10 College of Science, Health and Engineering 11 12 La Trobe University 13 14 15 Maternal health research in a tertiary health care facility in Lima, Peru 16 For peer review only 17 Form for data collection of medical records 18 19 20 Code number: ______Date: ______/ ______/______21 D D M M Y Y Y Y 22 23 D. MATERNAL MORBIDITY AND PREGNANCY OUTCOME INFORMATION S 24 Number______25 About previous pathologies during this pregnancy 26 In the First Trimester (< 13 weeks of gestation) 27 D1. Indicate which pathologies are described in the medical chart: 28 1. Anemia 29 2. Urine Infection 30 3. Threatened abortion 4. Other (specify)______31 5. No pathologies 32

6. No pathologies because first antenatal care was after 13 weeks of pregnancy http://bmjopen.bmj.com/ 33 34 In the Second Trimester (≥13 and <24 weeks of pregnancy) 35 D2. Indicate which pathologies are described in the medical chart: 36 1. Anemia 2. Urine Infection 37 3. Preeclampsia 38 4. Threatened abortion 39 5. Antepartum hemorrhage 40 6. Other (specify)______on September 25, 2021 by guest. Protected copyright. 41 7. No pathologies 42 8. No pathologies because first antenatal care was after 24 weeks of pregnancy

43 In the Third Trimester (≥24 weeks of pregnancy) 44 D3. Indicate which pathologies are described in the medical chart: 45 1. Anemia 46 2. Urine Infection 47 3. Preeclampsia 48 4. Antepartum hemorrhage 5. Other (specify)______49 6. No pathologies 50 51 About hospital stay of the participant (including Intensive Care Unit admission if applicable) 52 53 D4. 1st day of the last normal menstrual period __ __ / __ __ / ______54 D D / M M / Y Y Y Y 55 D5. Date of the first antenatal visit __ __ / __ __ / ______56 D D / M M / Y Y Y Y 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 28 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 D6 Gestational age at first antenatal visit ______weeks [999 = Not recorded] 4 D7. Number of antenatal visits______[999 = Not recorded] 5 6 D8 Prepregnancy weight (weight before the participant became pregnant this time) ______Kilograms [999 = Not recorded] 7 D9 Pregnancy weight before delivery ______Kilograms [999 = Not recorded] 8 D10. Weight gain during pregnant ______Kilograms [999 = Not recorded] 9 D11 Height ______Centimeters [999 = Not recorded] 10 11 D12. Date of admission at this hospital__ __ / __ __ / ______12 D D / M M / Y Y Y Y 13 D13. Indicate the diagnosis of the patient when she was hospitalized at this hospital: 14 1 ______15 2 ______16 3 ______4 ______For peer review only 17 5 ______18 19 D14 Socioeconomic level according to Social Services Department of this hospital: 1. Lower risk 20 2. Mediun risk 21 3. High risk 22 4. No category 23 D15. Was the participant admitted at the Intensive Care Unit? 24 1. No → Skip to D26 25 2. Yes → Continue to D16 26 27 D16. Date of admission at the Intensive Care Unit __ __ / __ __ / ______Time______(hour) 28 D D / M M / Y Y Y Y 29 D17. Indicate the diagnosis (ses) of the participant when she was admitted at the Intensive Care Unit: 30 1. ______31 2. ______32 3. ______4. ______http://bmjopen.bmj.com/ 33 5. ______34 35 D18. Weeks of pregnancy at the moment of the event (s) (SAMM) which cause(s) her admission at the Intensive Care Unit: 36 ______weeks 37 38 39 D19. Moment of such event (SAMM) in relation to the termination of pregnancy: 1. Before 40

2. During on September 25, 2021 by guest. Protected copyright. 41 3. After 42 D20. Did the woman received assistance with ventilation? 43 1. CPAP 44 2. Noninvasive ventilation (e.g. BiPAP) 45 3. Invasive mechanical ventilation 46 4. None of the above 47 D21. Which management did the woman receive in the ICU (multiple responses)? 48 1. Inotrope or vasopressor therapy 49 2. Renal replacement therapy (dialysis) 50 3. Central venous access 51 4. None of the above 52 D22. What was the severity of illness score on admission? ______Score (APACHE) 53 D23. Date of discharge of the Intensive Care Unit: __ __ / __ __ / ______54 D D / M M / Y Y Y Y 55 D24. Indicate the number of days in the Intensive Care Unit: _____days 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 29 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 D25. Indicate the diagnosis (ses) of the patient when she was discharged from the Intensive Care Unit: 4 1. ______5 2. ______6 3. ______7 4. ______8 5. ______9 6. ______

10 D26. Did the participant receive blood transfusion during her hospital stay? 11 1. No 12 2. Yes a. Indicate the numbers of red blood cell transfusion unit ______13 14 D27. Did the participant receive other blood product transfusions during her hospital stay? 15 1. No → Skip to D29 16 2. YesFor peer→ Continue to D28review only 17 D28. What were these other transfusions (multiple responses)? 18 1. Plasma 19 2. Platelet 20 3. Cryoprecipitate 21 4. Other (specify)______22 23 D29. Date of discharge of this hospital__ __ / __ __ / ______D D / M M / Y Y Y Y 24 D30. Diagnosis (ses) of the patient at discharge of this hospital: 25 1 ______26 2 ______27 3 ______28 4 ______29 5 ______6 ______30

31 D31. Indicate the number of hospital stay days ______days 32 http://bmjopen.bmj.com/ 33 34 About clinical conditions during this pregnancy 35 36 D32.Clinical conditions during this pregnancy (multiple responses)

37 Clinical conditions NO YES NOT RECORDED 38 1 Hypertensive related disease 1 2 99 39 a Severe Preeclampsia 1 2 99 40 Magnesium sulfate treatment 1 2 99 on September 25, 2021 by guest. Protected copyright. 41 b Eclampsia 1 2 99 42 Magnesium sulfate treatment 1 2 99 43 c HELLP Syndrome 1 2 99 44 2 Antepartum hemorrhage in the second trimester of pregnancy because of (specify): 1 2 99 45 a Placenta previa 1 2 99 b Uterine rupture 1 2 99 46 c Abruptio placentae 1 2 99 47 d Other (specify) 1 2 99 48 3 Antepartum hemorrhage in the third trimester of pregnancy because of (specify): 1 2 99 49 a Placenta previa 1 2 99 50 b Uterine rupture 1 2 99 51 c Abruptio placentae 1 2 99 52 d Other (specify) 1 2 99 53 4 Postpartum hemorrhage complication 1 2 99 54 a Uterine atony 1 2 99 55 b Cervical laceration/tear 1 2 99 c Retained products/fetal membranes 1 2 99 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 30 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 d Ruptured uterus 1 2 99 4 e Accreta/increta/percreta placenta 1 2 99 5 f Other (specify) 1 2 99 6 5 Miscarriage complication 1 2 99 7 8 a Uterine perforation 1 2 99 9 b Cervical laceration/tear 1 2 99 10 c Infection 1 2 99 11 d Other (specify) 1 2 99 12 6 Ectopic pregnancy 1 2 99 13 14 7 Sepsis (obstetric origin) 1 2 99 15 a Chorioamnionitis 1 2 99 b Surgical wound infection 1 2 99 16 c Endometritis For peer review only1 2 99 17 18 d Other (specify) 1 2 99 19 8 Sepsis (non-obstetric origin) 1 2 99 20 a Urine infection 1 2 99 21 b Other (specify) 1 2 99 22 9 Sepsis (pulmonary origin) 1 2 99 23 a Pneumonia 1 2 99 24 b Viral cause 1 2 99 25 b.1 Influenza (e.g. H1N1) 1 2 99 26 b.2 Varicella 1 2 99 27 b.3 Other (specify) 1 2 99 28 c Other (specify) 1 2 99 29 10 Clinical condition 1 2 99 30 31 a Oligohydramnios 1 2 99 32 b Intrauterine growth restriction 1 2 99 http://bmjopen.bmj.com/ 33 c Fetal macrosomy 1 2 99 34 d Other (specify) 1 2 99 35 11 Other associated pathologies 36 a Premature rupture of fetal membranes 1 2 99 37 b Disseminated intravascular coagulation (DIC) 1 2 99 38 c Maternal pulmonary edema 1 2 99 39 d Amniotic fluid embolism 1 2 99 40 e Retroplacental clot 1 2 99 on September 25, 2021 by guest. Protected copyright. 41 f Septic shock. 1 2 99 42 g Hypovolemic Shock 1 2 99 43 h Other (specify) 1 2 99 44 12 Complications of pre-existent diseases 1 2 99 45 a Tuberculosis 1 2 99 46 b Diabetes Mellitus 1 2 99 47 c Heart disease 1 2 99 48 d Thyroid crisis 1 2 99 49 e Chronic hypertension 1 2 99 50 f HIV infection 1 2 99 51 g Anemia 1 2 99 52 h Cervical cancer 1 2 99 53 i Ovarian cancer 1 2 99 54 j Other (specify) ______1 2 99 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 31 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 D33. Did the participant develop any organic dysfunctions? 4 1. No → Skip to D35 5 2. Yes → Continue to D34 6 7 D34. What were these organic dysfunctions? 8 (Information extracted from the epidemiological report, multiple responses) 1 Cardiovascular dysfunction 9 2 Respiratory dysfunction 10 3 Renal dysfunction 11 4 Coagulation/hematologic dysfunction 12 5 Hepatic dysfunction 13 6 Neurologic dysfunction 14 7 Uterine dysfunction/hysterectomy 8 Multiple organ dysfunction 15 16 About outcome of this pregnancyFor peer review only 17 18 D35. Type of pregnancy termination: 19 1 Abortion 20 i. Miscarriage ii. Therapeutic 21 iii. Unsafe 22 2 Delivery 23 3 Laparotomy for ectopic pregnancy 24 4 Still pregnant 25 D36. Date of pregnancy termination (delivery, abortion, ectopic pregnancy) __ __ / __ __ / ______Time ______(hour) 26 D D / M M / Y Y Y Y 27 28 D37. Indicate the number of hospital stay days before pregnancy termination______days 29 D38. Gestational age at delivery or abortion (including ectopic pregnancy): ______(Weeks) 30 D39. Mode of delivery or abortion 31 1 Vaginal, normal 32 a. Active management of the third stage of labor. http://bmjopen.bmj.com/ 33 i. No 34 ii. Yes 35 2 Vaginal, vacuum/forceps 36 a. Active management of the third stage of labor. i. No 37 ii. Yes 38 3 Emergency Csection 39 4 Scheduled Csection 40 5 Curettage (for a woman who had an abortion) on September 25, 2021 by guest. Protected copyright. 41 D40. Place of the delivery: 42 1. This hospital 43 2. Other hospital 44 3. Health Center 45 4. Home 5. Another (specify)______46 D41. Who attended the delivery? 47 1. Doctor 48 2. Midwifery 49 3. Another (specify)______50 51 About additional surgical treatment (s) performed during this pregnancy

52 D42. Was/were additional surgical treatment(s) performed? 53 1. No → Skip to D46 54 2. Yes → Continue to D43 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 32 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 D43. Report about additional first surgical treatment (s) performed (multiple responses): 4 1 Hysterectomy 5 2 Laparotomy 6 3 Curettage 4 Repair of cervical tears 7 5 Drainage of puerperal hematoma and repair of puerperal hematoma 8 6 Manual removal of placenta (after vaginal delivery) 9 7 Other (specify)______10 11 D44. Report about an additional second surgical treatment performed: 12 1 Hysterectomy 13 2 Laparotomy 3 Other (specify)______14 D45. Report about an additional third surgical treatment performed: 15 1 Hysterectomy 16 2 LaparotomyFor peer review only 17 3 Another (specify)______18 19 About surgical treatment (s) performed during this pregnancy, indicate the diagnosis (ses) for each procedures correspondingly:

20 21 D46. Uterine curettage indication: 22 1 ______2 ______23 3 ______24 4 ______25 D47. Cesarean indication: 26 1 ______27 2 ______28 3 ______29 4 ______30 D48. Laparotomy indication: 31 1 ______32 2 ______http://bmjopen.bmj.com/ 33 3 ______34 4 ______5 35 D49. Hysterectomy indication: 36 1 ______37 2 ______38 3 ______39 4 ______40 About main delays (Information extracted from the epidemiological report if the participant was admitted at the Intensive Care Unit). on September 25, 2021 by guest. Protected copyright. 41

42 Go to the Neonatal information (Skip item D50, D51, D52 and D53) if the participant was NOT admitted at the Intensive Care Unit. 43 44 D50. Qualitative analysis of Delay I 45 1 No 46 2 Yes 47 D51. Qualitative analysis of Delay II 1 No 48 2 Yes 49 D52. Qualitative analysis of Delay III 50 1 No 51 2 Yes 52 D53. Qualitative analysis of Delay IV 53 1 No 2 Yes 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 33 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

12 E2. Age at birth weeks weeks weeks 13 (according to Neonatologist) 14 1 Male 1 Male 1 Male 15 E3. Sex 2 Female 2 Female 2 Female 3 Ambiguous 3 Ambiguous 3 Ambiguous 16 E4. Apgar score (1 minute) For peer review only 17 18 E5. Apgar score (5 minutes) 19 E6. Baby outcome at birth: 1 Live birth 1 Live birth 1 Live birth 20 2 Stillborn 2 Stillborn 2 Stillborn 21 1 Stay with mom (Regular nursery) 1 Stay with mom (Regular nursery) 1 Stay with mom (Regular nursery) 22 E7. Nursery of baby 2 Other (specify) 2 Other (specify) 2 Other (specify) 23 24 1 Breastfeeding 1 Breastfeeding 1. Breastfeeding 25 2 Formula 2 Formula 2. Formula 26 E8. Breastfeeding 3 Both 3 Both 3. Both 27 4 Another(specify) 4 Another(specify) 4. Another(specify) 28 ______1 No 1. No 1. No 29 E9. Gross fetal/neonatal malformation 2 Yes 2. Yes 2. Yes 30 99 Do not know 99 Do not know 99 Do not know 1. No 1 No 31 E10. Neonatal Intensive Care Unit (NICU) 1. No 2. Yes 2 Yes 32 Admission 2. Yes http://bmjopen.bmj.com/ 33 1. ______1. ______1. ______34 2. ______2. ______2. ______35 E11. Indicate the diagnosis (ses) of the baby for NICU admission 3. ______3. ______3. ______36 37 4. ______4. ______4. ______1. CPAP 1. CPAP 38 1. CPAP 2. Noninvasive ventilation (e.g. 2. Noninvasive ventilation (e.g. 2. Noninvasive ventilation (e.g. 39 BiPAP) BiPAP) E12. Management of the baby at NICU BiPAP) 40 3. Invasive mechanical ventilation 3. Invasive mechanical ventilation (multiple responses) 3. Invasive mechanical ventilation on September 25, 2021 by guest. Protected copyright. 4. Inotrope or vasopressor therapy 4. Inotrope or vasopressor 41 4. Inotrope or vasopressor therapy 5. Blood transfusion therapy 5. None of the above 42 6. None of the above 5. None of the above 43 1. ______1 ______1. ______2. ______2 ______2. ______44 E13. Indicate the diagnosis (ses) of the 3. ______3 ______3. ______45 baby when was discharged from the 4. ______4 ______4. ______NICU 46 5. ______5 ______5. ______47 6. ______6 ______6. ______48 E14. Antibiotic use in NICU 1 No 1 No 1 No 49 2 Yes 2 Yes 2 Yes 50 51 E15. Days of stay at NICU ______days ______days ______days 52 53 E16. Days of stay at this hospital ______days ______days ______days 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 34 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 1. Alive 1 Alive 1. Alive 4 E17. Discharge status of baby from this 2. Dead 2 Dead 2. Dead hospital (Days after birth______) (Days after birth______) (Days after birth______) 5 6 1. ______1 ______1 ______7 2. ______2 ______2 ______E18. Indicate the diagnosis of the baby 3. ______3 ______3 ______8 when was discharged from this 4. ______4 ______4 ______9 hospital 5. ______5 ______5 ______10 6. ______6 ______6 ______11

12 13 14 15 The End 16 For peerThank review You!!!!!!!!!!!!!!! only 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

The impact of violence against women on severe acute maternal morbidity in the intensive care unit, including neonatal outcomes: a case-control study protocol in a tertiary healthcare facility in Lima-Peru

ForJournal: peerBMJ Open review only

Manuscript ID bmjopen-2017-020147.R1

Article Type: Protocol

Date Submitted by the Author: 22-Dec-2017

Primary Subject Public health Heading: http://bmjopen.bmj.com/ Secondary Subject Heading: Intensive care, Obstetrics and gynaecology

Severe acute maternal morbidity, violence against women, intimate Keywords: partner violence, intensive care unit, social determinants, near miss

on September 25, 2021 by guest. Protected copyright.

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 4 Title 5

6 7 The impact of violence against women on severe acute maternal 8 9 morbidity in the intensive care unit, including neonatal outcomes: a 10 11 case-control study protocol in a tertiary healthcare facility in Lima- 12 13 14 Peru

15 16 For peer review only 17 Corresponding author: 18 19 Dr. Beatriz Paulina Ayala Quintanilla. 20 Address: 215 Franklin Street, Melbourne, Vic 3000, Victoria, Australia. 21 22 Telephone: +61 3 9479 8800. Fax: +61 3 9479 8811. 23 24 Email: [email protected] 25

26 1, 2, 4 1 1, 2 27 Authors: Beatriz Paulina Ayala Quintanilla , Angela Taft , Susan McDonald , Wendy 28 1, 2, 3 29 Pollock 30

31 32 Author affiliations http://bmjopen.bmj.com/ 33 34 1 The Judith Lumley Centre, La Trobe University, Melbourne, Australia 35 36 2 37 Mercy Hospital for Women, Melbourne, Australia 38 3 39 University of Melbourne, Melbourne, Australia 40 on September 25, 2021 by guest. Protected copyright. 41 4 Peruvian National Institute of Health, Lima, Peru 42

43 44 Keywords: Severe acute maternal morbidity, violence against women, intimate partner violence, 45 46 47 intensive care unit, social determinants, near miss. 48 49 Words in the abstract: 290 words. 50 51 Words in article: 3,451 words, excluding title page, abstract, references, authors’ contributions, 52 53 funding and competing interest statement. 54 55 56 57 58 1 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 4 5 ABSTRACT 6 7 Introduction: Preventing and reducing violence against women (VAW) and maternal mortality 8 9 are Sustainable Development Goals. Worldwide, the maternal mortality ratio has fallen about 10 44% in the last 25 years, and for one maternal death there are many women affected by severe 11 acute maternal morbidity (SAMM) requiring management in the intensive care unit (ICU). These 12 women represent the most critically ill obstetric patients of the maternal morbidity spectrum and 13 should be studied to complement the review of maternal mortality. VAW has been associated 14 with all-cause maternal deaths, and since many women (30%) endure violence usually exerted by 15 their intimate partners and this abuse can be severe during pregnancy, it is important to 16 For peer review only 17 determine whether it impacts SAMM. Thus, this study aims to investigate the impact of VAW on 18 SAMM in the ICU. 19 20 Methods and analysis: This will be a prospective case-control study undertaken in a tertiary 21 healthcare facility in Lima-Peru, with a sample size of 109 cases (obstetric patients admitted to 22 the ICU) and 109 controls (obstetric patients not admitted to the ICU selected by systematic 23 24 random sampling). Data on social determinants, medical and obstetric characteristics, VAW, 25 pregnancy and neonatal outcome will be collected through interviews and by extracting 26 information from the medical records using a pretested form. Main outcome will be VAW rate 27 and neonatal mortality rate between cases and controls. VAW will be assessed by using the 28 World Health Organization (WHO) instrument. Binary logistic regression model will assess any 29 association between VAW and SAMM. 30 31 32 Ethics and dissemination: Ethical approval has been granted by the La Trobe University, http://bmjopen.bmj.com/ 33 Melbourne-Australia and the tertiary healthcare facility in Lima-Peru. This research follows the 34 WHO ethical and safety recommendations for research on VAW. Findings will be presented at 35 conferences, and published in peer-reviewed journals. 36 37 38 39 40 Strengths and limitations of this study on September 25, 2021 by guest. Protected copyright. 41 42 • This prospective study will examine for the first time the influence of violence against 43 women on severe acute maternal morbidity (SAMM). 44 • Studying the stage before maternal death (SAMM) complements the review of maternal 45 46 mortality. 47 • This study uses a standardised global instrument for the evaluation of violence against 48 women and a pre-tested form for the assessment of other variables of interest. 49 • Studying violence against women can be challenging and may underestimate the rate of 50 abuse due to recall and cultural bias. 51 52 • Findings should be interpreted cautiously because this study is within one very large tertiary 53 hospital and further multi-centre and multi-country studies may be needed, based on these 54 replicable methods. 55 56 57 58 2 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 4 5 INTRODUCTION 6 Preventing and reducing violence against women and maternal mortality are Sustainable 7 Development Goals (SDG).1 Worldwide, the maternal mortality ratio (MMR) has declined by 8 44% with a reduction from 385 to 216 maternal deaths per 100,000 live births between 1990 9 (532,000 maternal deaths) and 2015 (303,000 maternal deaths). This equates to approximately 10 2 11 830 women dying daily, of which 99% of maternal deaths occurred in developing countries. 12 However, maternal mortality is only a small proportion of the global burden of the maternal 3-5 13 morbidity spectrum. This is because for one maternal death there are many women affected by 14 severe acute maternal morbidity (SAMM) during pregnancy, childbirth and the postpartum 15 period5-11 including those obstetric patients who require multidisciplinary management in the 16 intensive care unit (ICU).For11-17 peer review only 17 18 ICU admission can be a marker for defining SAMM,12 18-25 and SAMM can be named as near 19 15 19 21 25-28 20 miss; either term has been widely used to study this population of obstetric patients. 21 There are no internationally accepted criteria for defining SAMM and its definition may differ 22 across studies,19 20 25-34 and the use of ICU admission to identify severe maternal morbidity has 23 high sensitivity (86.4%), specificity (87.8%) and positive predicted value (0.85).22 27 35-38 Women 24 with SAMM treated in the ICU represent the most critically ill obstetric patients,11 19 39 and 25 require timely managed care due to the physiologic changes of pregnancy and the care of the 26 11-17 40-46 27 mother-baby dyad. 28 29 The incidence of maternal ICU admission varies from 0.04 to 4.54%, and the common causes are 30 mainly direct obstetric clinical conditions.12 14 19 29 According to Pollock, et al.,14 hypertensive 31 disorders were the leading cause of ICU admission (0.09% of deliveries), followed by obstetric 32 haemorrhage (0.07%), and sepsis (0.02%); and, although the ICU admission profile was similar http://bmjopen.bmj.com/ 33 34 worldwide there were higher rates of maternal deaths in the ICUs of developing countries. 35 36 Violence against women is a global public health problem and many women of reproductive age 37 endure violence usually exerted by their intimate partners (IPV). Globally, 30% of women have 38 experienced partner abuse.47-49 However, the IPV rate varies across studies ranging from 15 to 39 71% and from 1 to 28% during pregnancy.50 Diverse studies have also reported a wide range of 40 51 IPV rate during pregnancy from 0.9 to 20.1% in high-income countries, 3 to 44% in Latin on September 25, 2021 by guest. Protected copyright. 41 52 53 42 America and Caribbean countries and 2 to 57% in African countries. 43 44 Several studies have reported negative and mortal consequences of IPV on reproductive age 45 women.54-57 During pregnancy, these adverse health outcomes affect the mother-baby dyad; and, 46 can be augmented by consequent risky health behaviours (smoking, alcohol consumption, 47 substance abuse, poor nutrition, lack of seeking health care, among others)57-60 and physiological 48 mechanisms through neural, neuroendocrine, and immune responses to acute and/or chronic 49 55 61 50 stress originating from exposure to violence. All of this may exacerbate pre-existing medical 52 55 61 62 51 conditions and/or lead to diverse pregnancy complications. Even though women could be 52 more vulnerable to IPV during the pregnancy and puerperium periods, no data on violence 53 against women of obstetric patients in the ICU have been reported in Peru or elsewhere63. Thus, 54 it is important to examine whether violence against women is a risk factor for women with 55 SAMM. We are conducting this study in Peru, an upper-middle income country64 with a lifetime 56 57 58 3 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 IPV rate of 68.2% (emotional 64.2%, physical 31.7% and sexual 6.6%).65 In Peru, there are 4 about 9 cases of femicide monthly56 and a MMR of 68, which fell 72.9% from 251 between 1990 5 2 6 and 2015. 7 8 9 There has been increased concern about the negative influence of violence against women on 10 maternal mortality,66-72 and violence against women has been associated with all-cause maternal 11 deaths.66 67 Although, this association was first analysed 16 years ago67 there is still a paucity of 12 studies investigating the influence of violence against women on SAMM63, which can be 13 15 22 29 36 73-75 14 considered as a complement to a review of maternal deaths. Thus, it is important to 15 determine whether violence against women impacts SAMM, since many women endure violence 16 usually exerted by For their intimate peer partners review and this abuse only can be severe during pregnancy. 17 Therefore, this research of the stage before maternal death (SAMM) will provide for the first 18 time, a better understanding about what potential factors, such as violence against women, are 19 affecting obstetric patients with SAMM in the ICU. This will make an important contribution to 20 21 global knowledge of causes of maternal morbidity. 22 23 24 HYPOTHESIS 25 We hypothesise that violence against women is significantly associated with severe acute 26 27 maternal morbidity in obstetric patients managed in the intensive care unit. 28 29 30 31 OBJECTIVES 32 http://bmjopen.bmj.com/ 33 • To investigate the impact of violence against women on obstetric patients with SAMM 34 treated in the ICU (cases) by comparing them with obstetric patients not admitted to the 35 36 ICU (controls), in a tertiary healthcare facility in Lima-Peru. 37 38 • To evaluate pregnancy and neonatal outcome of women with SAMM in the ICU of a 39 tertiary healthcare facility in Lima-Peru. 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 METHODS 45 This is a prospective case-control study protocol and follows the Strengthening the Reporting of 46 Observational studies in Epidemiology (STROBE) criteria.76 77 47 48 49 Study design 50 In this case-control study, cases will be obstetric patients experiencing SAMM in the ICU (s) 51 including miscarriage, therapeutic abortion, unsafe abortion, and ectopic pregnancy 52 prospectively identified from the ICU register. The inclusion criteria of cases include: i) a 53 woman with a maternal ICU admission due to a complication (s) during pregnancy, delivery or 54 within 42 days of the ending of pregnancy, with favourable evolution and who fulfils eligibility 55 56 prior to hospital discharge; ii) 18-year-old or older; iii) Spanish speaker; and iv) gives written 57 58 4 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 informed consent. The exclusion criteria are: i) a woman with mental illness or disabilities or 4 other similar disabling pathologies; ii) not able to provide informed consent; iii) an obstetric 5 6 patient referred from other healthcare facilities for maternity care; and iv) ICU stay less than 24 7 hours. The controls are from the same source population that gives rise to the cases and their 8 inclusion criteria consist of i) a woman admitted to this hospital during pregnancy, delivery or 9 within 42 days of the ending of pregnancy, with favourable evolution and who fulfils eligibility 10 prior to hospital discharge; ii) 18-year-old or older; iii) Spanish speaker; and iv) gives written 11 informed consent. The exclusion criteria are: i) a woman with mental illness or disabilities or 12 other similar disabling pathologies; ii) not able to provide informed consent; and iii) an obstetric 13 14 patient referred from other healthcare facilities for maternity care. Favourable evolution means 15 that an obstetric patient has received the required management for the condition responsible for 16 her admission to theFor hospital peer or the ICU, review is hemodynamically only stable without requiring strict 17 monitoring or specialized treatment, her life is not at risk, and is well enough to be discharge 18 from the hospital to home (it implies that the maternal morbidity has resolved for the cases). 19 20 21 We plan to include all cases who meet the selection criteria during the study period, until we 22 reach the estimated sample size of 109 obstetric patients admitted to the ICU. This is because 23 there were 263 ICU admissions (pregnant and non-pregnant women) in 2012, 230 in 2013 and 24 274 in 2014 according to the Department of Epidemiology of this hospital78; and, approximately 25 48% of the ICU admissions are referred from other healthcare facilities (as indicated by the 26 Chief of the ICU). We expect that cases will be recruited during a period of twelve (12) months, 27 though recruitment will continue for longer if necessary for the minimum sample sizes to be 28 29 achieved. Controls will be selected by using a probability sampling method, specifically a 30 systematic random sampling (without replacement) starting with 18 and with a value of k = 131 31 as the sampling interval. 32 http://bmjopen.bmj.com/ 33 Setting 34 This study is being undertaken in a tertiary hospital located in the capital city of Peru (where 35 36 about one third of the Peruvian population live). This institution is the main national referral 37 hospital for high risk maternal and neonatal patients throughout Peru, where there are over 79 38 22,000 deliveries yearly, which equates to approximately 1 delivery every 25 minutes. 39 40 Sample size on September 25, 2021 by guest. Protected copyright. 41 The sample size will comprise 218 participants (109 controls and 109 cases) which has been 42 calculated by using the Sample Size Calculation for Unmatched Case-Control Studies of the 43 80 44 software open Epi with a confidence level of 95% and a power of 80% to detect a (18.8%) 45 difference in the exposure of violence against women (rate) between cases and controls. There 46 are not preceding studies assessing the prevalence of violence against women among obstetric 47 patients with SAMM in the ICU. We estimated an IPV rate of 24.3% for controls and 43.1% for 48 cases in accordance with previous research investigating the relationship between IPV and 49 81 50 preeclampsia in Peruvian pregnant women at this maternity hospital. 51 52 Recruitment Method 53 Participants will be invited to participate and recruited during their hospital stay once their acute 54 medical condition (s) have been resolved (this will be after they were discharged from the ICU 55 56 for the case women), and before they are discharged from hospital to going home. Women in the 57 58 5 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 6 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 control group will be invited to participate within one week of a case woman being interviewed. 4 The researcher (interviewer), a Spanish speaking midwife, has been trained and has research 5 6 experience working on violence against women studies and research ethics. The researcher will 7 check with the hospital staff regarding eligibility (selection criteria, e.g. mental illness and 8 others), prior to approaching and inviting potential participants to the study. She will also ensure 9 that the potential participants understand the participant information statement and answer all 10 their questions, and explain to the participants that they can refuse or withdraw their participation 11 at any time without affecting their health care and rights. 12 13 14 15 Data Collection 16 Data collection commencedFor onpeer 23rd October review 2015 and is still only ongoing. We expect to finish by 17 18 the end of March 2018. Currently, we are collecting data from the medical records. Women who 19 give consent will be interviewed once in private using a structured questionnaire (Appendix 1). 20 We will also extract information from their medical records using a pretested form developed by 21 the team members (Appendix 2). 22 23 Interview 24 25 The following information will be obtained during the face to face interview: socio-demographic 26 characteristics (age, place of residence, educational level, marital status, occupation and type of 27 health insurance) of the participant and her partner; behavioural factors (smoking, use of alcohol 28 or drugs); medical (previous and current diseases) and obstetric characteristics (number of 29 pregnancies, previous abortions, prenatal care visits, previous caesarean sections, and vaginal 30 births; use of family planning methods; anaemia during pregnancy and use of iron supplements 31 during pregnancy); and violence against women evaluation. 32 http://bmjopen.bmj.com/ 33 34 Violence against women will be assessed by using questions from a standardised instrument of 50 35 the WHO. These questions were validated, translated and adapted rigorously, since Peru was 36 one of the countries selected in the WHO Multi-country study instrument.50 They have been also 37 used by other researchers for investigating violence against women in Peru, and an adapted 38 version was applied in the Peruvian Demographic and Family Health Survey.65 39 40 on September 25, 2021 by guest. Protected copyright. 41 Violence against women evaluation will comprise emotional (including controlling behaviours), 42 physical and sexual abuse exerted by intimate-partners and by non-intimate partners (relatives, 43 friends or others) assessed 12 months before and during pregnancy. The participants will answer 44 the frequency (once or twice or many) for each act of emotional, physical or sexual violence. 45 Violence against women will be examined in an empathetic, supportive and non-judgmental 46 manner, giving the participants the opportunity not to answer any questions that make them feel 47 48 uncomfortable or to reschedule or terminate the interview at any time. The interview will only be 49 conducted with the woman alone and in private. If the interview is interrupted, the interviewer 50 will change the topic or may terminate the interview correspondingly. It is expected that the 51 interview will take approximately 25 to 30 minutes. After the interview, information about free 52 social support services for domestic violence (available at this maternity hospital) will be offered 53 to every participant including a referral if they wish. There will be also debriefing sessions for 54 the well-being of the interviewer. Individual support/counselling can be arranged at the hospital 55 56 for the interviewer or participant if it is needed. 57 58 6 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 7 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 4 5 6 7 Extracting data from medical records 8 We will extract data from the medical reports of the mothers and newborns (if applicable) related 9 to SAMM, pregnancy outcome, fetal and neonatal characteristics and outcome. 10 11 SAMM data will include hospital admission date, clinical causes for hospitalisation and/or ICU 12 admission, diagnoses after being discharged from the ICU and/or the hospital, number of 13 14 hospital stay days and ICU stay days, type of delivery, additional procedures, weeks of 15 pregnancy when SAMM occurs, organ failure (s), use of technologies (mechanical ventilation, 16 transfusion, use of inotropicFor supportpeer and renalreview replacement therapies), only main delays (in relation to 17 the three delays model framework used to study maternal mortality82), and pregnancy outcome 18 (Appendix 2). 19 20 21 Fetal and neonatal data will include: birth weight; birth age; sex; Apgar score (at 1 and 5 22 minutes); outcome at birth; clinical cause (s) for Neonatal ICU (NICU); number of days at the 23 NICU (if applicable) or at the hospital; use of technologies and/or antibiotics at the NICU; 24 feeding type (breastfeeding, formula or both); discharge status; and diagnoses from the hospital 25 and/or the NICU (Appendix 2). 26 27 28 Data entry and analysis 29 Data will be entered using SPSS V.24.0. Univariate analysis will be carried out to describe the 30 characteristics of SAMM, social determinants, violence against women and pregnancy and 31 neonatal outcomes. Quantitative variables will be displayed as the mean ± SD and/or median 32 (interquartile rate) after verifying their normal or asymmetrical distribution. Difference of means http://bmjopen.bmj.com/ 33 34 analyses between variables will be performed using appropriate statistical tests (Student's t-test 35 or Mann–Whitney U test or other similar). Qualitative variables will be displayed as frequencies. 36 37 We will apply a bivariate analysis to evaluate the association of violence against women (partner 38 and non-partner) as an independent variable with SAMM; and we will also evaluate this 39 association with partner violence only; and, with non-partner violence only. 40 on September 25, 2021 by guest. Protected copyright. 41 42 We will fully assess violence against women as a risk factor by using a multivariate logistic 43 regression modelling considering an Odds Ratio (OR) with 95% CI. Crude ORs will also be 44 calculated. Statistical significance will be set at p < 0.05 for all analyses. We will identify effect 45 modification for age, level of education, alcohol consumption and use of drugs by performing a 46 47 stratified analysis of these variables that could potentially modify the effect of violence against 48 women on SAMM. This will be assessed by the calculation of crude ORs within every level of 49 each variable that is stratified. The final model will include the socio-demographic 50 characteristics of the participants, other variables of interest (such as household income, partner’s 51 52 educational level, partner’s occupation, etc.) according to the literature review, and modifiers 53 (we will remove the least significant modifiers one at a time until only those with p < 0.05 54 remain). Those variables with p values of < 0.25 will be initially chosen to be included in the 55 model,83 and the Hosmer-Lemeshow’s goodness-of-fit test will be used to assess model adequacy 56 57 58 7 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 8 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 and stepwise multiple regression analysis performed to select and identify the predictive factors 4 83 5 in the final model. 6 7 8 9 ETHICS AND DISSEMINATION 10 Ethical approval has been granted by the La Trobe University Human Ethics committee 11 (HEC15-023), Melbourne, Australia and the Institutional Review Board of the tertiary healthcare 12 13 hospital in Lima, Peru. Individual written informed consent will be obtained from participants 14 prior to data collection. The present research follows the WHO and other ethical and safety 15 recommendations for research on gender-based violence to ensure the safety of the participants 16 and the interviewer.For50 84-88 peer review only 17 It is planned that the findings of this case-control study will be presented at La Trobe University 18 and national and/or international conferences, and it will be also published in a peer review 19 journal. It is expected that these finding will inform policymakers, patients, and the public 20 21 through these presentations. 22 23 PRESENTING AND REPORTING RESULTS 24 This prospective case-control study will examine for the first time the influence of violence 25 against women on obstetric patients affected by severe acute maternal morbidity who require 26 27 management in the ICU, and evaluate their pregnancy and neonatal outcomes. We will present 28 major findings in tables and also describe results in narrative format outlining effect sizes and 29 their parameters. The findings and further publications will be reported following the 30 Strengthening the Reporting of Observational studies in Epidemiology (STROBE) criteria,76 77 31 which is part of the Enhancing the quality and transparency of health research (EQUATOR) 32 Network website. http://bmjopen.bmj.com/ 33 34 35 DISCUSSION 36 The influence of violence against pregnant women on the incidence of or type of SAMM is not 37 known and worthy of study. Although, the negative contribution of violence against women to 38 maternal deaths was described in the 1997-1999 Confidential Enquiry into Maternal Death,67 and 39 many studies have reported negative and fatal repercussions of IPV on women’s health including 40 52-62 during all stages of pregnancy, there is a paucity of studies assessing the relationship on September 25, 2021 by guest. Protected copyright. 41 63 42 between violence against women and SAMM . Investigating women affected by SAMM could 15 22 29 36 73-75 43 complement the review of maternal deaths to understand which underlying factors 44 are influencing the sequence of events from a healthy pregnancy through minor complications to 45 life threatening obstetric conditions and even death in childbearing women.26 89 90 46 47 This case-control study will contribute to evidence about the potential negative consequences of 48 violence against women of obstetric patients with SAMM in the ICU, who represent the most 49 11 19 39 50 critically ill patients and have been shown to be an important component of the maternal 11-17 40-46 51 morbidity spectrum requiring timely managed care. This may help to highlight that non- 52 biological factors (violence against women), which are potentially modifiable, may be associated 53 with SAMM and are important to address to reduce maternal morbidity-mortality in Peru and in 54 other low and middle-income countries. Acute or chronic exposure to violence adversely affects 55 both the mothers and their babies and can be augmented by any risky health behaviors57-60 and 56 57 58 8 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 9 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 through physiological (neural, neuroendocrine, and immune) mechanisms in response to this 4 abuse.55 61 All of this may exacerbate pre-existing medical conditions and/or lead to diverse 5 52 55 61 62 6 pregnancy complications. Thus, it would be important to know if violence against 7 women is a risk factor for SAMM in the ICU, and to understand the complete picture of the 8 global burden of maternal morbidity-mortality to improve mother-baby dyad health and 9 women’s well-being. 10 11 This study may also help participants affected by violence to disclose abuse in a safe and 12 supportive environment; and, provide an opportunity for those abused women to understand that 13 14 it is possible to prevent violence and improve their and other women’s lives, since they will be 15 informed and/or referred to the free social support services available for domestic violence 16 provided by the PeruvianFor government. peer review only 17 18 We understand that the findings of this study should be interpreted cautiously and some 19 limitations should be noted. Firstly, this research will be undertaken in a single centre. It will be 20 21 important to carry out further multi-centre and multi-country studies. Other limitations may 22 include recall, cultural and measurement bias which can underestimated or overestimate the 50 91 23 exposure. This is because the assessment of violence against women is complex and 24 challenging. Accordingly, this research follows the ethical and safety recommendations for 25 research on violence against women;50 84-88 and uses standardized questions for the assessment of 26 violence against women (WHO instrument) and a pretested questionnaire for the evaluation of 27 other factors. Amendments to this protocol are not expected. However, if any are required, these 28 29 amendments will be reported transparently. 30 31 Notwithstanding these limitations, we hope that this study will contribute to the global effort 32 towards achieving SDGs by providing valuable information for a better understanding of SAMM http://bmjopen.bmj.com/ 33 and violence against women in Peru. This will make an important contribution to global 34 knowledge of causes of maternal morbidity by providing evidence of the relationship between 35 violence against women and SAMM, which is important for preventing and/or reducing maternal 36 37 morbidity-mortality and improve maternal health. Therefore, we expect that this research will 38 extend knowledge in an identified research gap, and may provide direction for further studies in 39 obstetric women affected by SAMM in the ICU. 40

on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 9 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 10 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 4 5 6 7 8 9 10 REFERENCES 11 12 13 1. United Nations. Transforming our world: the 2030 Agenda for Sustainable Development. Resolution adopted 14 by the General Assembly on 25 September 2015. 2015. 15 https://sustainabledevelopment.un.org/post2015/transformingourworld (accessed 6 May 2017). 16 2. World Health Organization. Trends in maternal mortality: 1990 to 2015. Estimates by WHO, UNICEF, UNFPA, World For Bank Group peer and the United review Nations Population only Division. Secondary Trends in maternal 17 mortality: 1990 to 2015. Estimates by WHO, UNICEF, UNFPA, World Bank Group and the United Nations 18 Population Division. 2015. http://www.who.int/classifications/icd/factsheet/en/ (accessed 15 Feb 2016). 19 3. Mantel GD, Buchmann E, Rees H, et al. Severe acute maternal morbidity: a pilot study of a definition for a 20 near-miss. Br J Obstet Gynaecol 1998;105:985-90. 21 4. Geller SE, Cox SM, Callaghan WM, et al. Morbidity and mortality in pregnancy: laying the groundwork for 22 safe motherhood. Womens Health Issues 2006;16:176-88. 23 5. Firoz T, Chou D, von Dadelszen P, et al. Measuring maternal health: focus on maternal morbidity. Bull World 24 Health Organ 2013;91:794-6. 25 6. Ashford L. Hidden suffering: disabilities from pregnancy and childbirth in less developed countries. 26 Secondary Hidden suffering: disabilities from pregnancy and childbirth in less developed countries. 2002. 27 http://www.prb.org/pdf/hiddensufferingeng.pdf (accessed 23 Jul 2014). 28 7. Fottrell E, Kanhonou L, Goufodji S, et al. Risk of psychological distress following severe obstetric 29 complications in Benin: the role of economics, physical health and spousal abuse. Br J Psychiatry 30 2010;196:18-25. 31 8. Pacagnella RC, Cecatti JG, Camargo RP, et al. Rationale for a long-term evaluation of the consequences of 32 potentially life-threatening maternal conditions and maternal "near-miss" incidents using a multidimensional http://bmjopen.bmj.com/ 33 approach. J Obstet Gynaecol Can 2010;32:730-8. 34 9. Wilson RE, Salihu HM. The paradox of obstetric "near misses": converting maternal mortality into morbidity. 35 Int J Fertil Womens Med 2007;52:121-7. 36 10. Storeng KT, Drabo S, Ganaba R, et al. Mortality after near-miss obstetric complications in Burkina Faso: 37 medical, social and health-care factors. Bull World Health Organ 2012;90:418-25B. 38 11. Plaat F, Naik M. Critical care in pregnancy. Crit Care 2011;15:1014 doi: http://dx.doi.org/10.1186/cc10479 39 [published Online First: 22 December 2013]. 12. Zieleskiewicz L, Chantry A, Duclos G, et al. Intensive care and pregnancy: Epidemiology and general 40 principles of management of obstetrics ICU patients during pregnancy. Anaesth Crit Care Pain Med 2016;35 on September 25, 2021 by guest. Protected copyright. 41 (Suppl 1):S51-7 doi: 10.1016/j.accpm.2016.06.005 [published Online First: 5 July 2016]. 42 13. Guntupalli KK, Hall N, Karnad DR, et al. Critical illness in pregnancy Part I: an approach to a pregnant 43 patient in the ICU and common obstetric disorders. Chest 2015;148:1093-104. 44 14. Pollock W, Rose L, Dennis C. Pregnant and postpartum admissions to the intensive care unit: a systematic 45 review. Intensive Care Med 2010;36:1465-74. 46 15. Baskett TF. Epidemiology of obstetric critical care. Best Pract Res Clin Obstet Gynaecol 2008;22:763-74. 47 Complement to maternal deaths 48 16. Martin SR, Foley MR. Intensive care in obstetrics: an evidence-based review. Am J Obstet Gynecol 49 2006;195:673-89. 50 17. Germain S, Wyncoll D, Nelson-Piercy C. Management of the critically ill obstetric patient. Curr Obstet 51 Gynaecol 2006;16:125-33. 52 18. Oud L. Epidemiology of Pregnancy-Associated ICU Utilization in Texas: 2001 - 2010. J Clin Med Res 53 2017;9:143-53 doi: 10.14740/jocmr2854w [published Online First: 17 January 2017]. ICUprosxi of ICU 54 19. Senanayake H, Dias T, Jayawardena A. Maternal mortality and morbidity: Epidemiology of intensive care 55 admissions in pregnancy. Best Pract Res Clin Obstet Gynaecol 2013;27:811-20. ICUprosxi of ICU 56 57 58 10 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 11 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

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1 2 3 46. Munnur U, Bandi V, Guntupalli KK. Management Principles of the Critically Ill Obstetric Patient. Clin Chest 4 Med 2011;32:53-60. 5 47. World Health Organization. Global and regional estimates of violence against women: prevalence and health 6 effects of intimate partner violence and non-partner sexual violence. 2013. 7 http://apps.who.int/iris/bitstream/10665/85239/1/9789241564625_eng.pdf?ua=1 (accessed 13 Nov 2014). 8 48. Devries KM, Mak JY, Garcia-Moreno C, et al. Global health. The global prevalence of intimate partner 9 violence against women. Science 2013;340:1527-8 doi:10.1126/science.12409373042 [published Online 10 First: 28 June 2013]. 11 49. World Health Organization. The Global status report on violence prevention 2014. 2014. 12 http://www.who.int/violence_injury_prevention/violence/status_report/2014/en/ (accessed 28 May 2015). 13 50. Garcia-Moreno C, Jansen HAFM, Ellsberg M, et al. Prevalence of intimate partner violence: findings from 14 the WHO multi-country study on women's health and domestic violence. Lancet 2006;368:1260-9. 15 51. Gazmararian JA, Lazorick S, Spitz AM, et al. Prevalence of violence against pregnant women. JAMA 16 1996;275:1915-20. 52. Han A, Stewart DE.For Maternal peer and fetal outcomes review of intimate partner only violence associated with pregnancy in 17 the Latin American and Caribbean region. Int J Gynaecol Obstet 2014;124:6-11. 18 53. Shamu S, Abrahams N, Temmerman M, et al. A systematic review of African studies on intimate partner 19 violence against pregnant women: prevalence and risk factors. PloS One 2011;6(3):e17591 doi: 20 10.1371/journal.pone.0017591 [published Online First: 8 March 2011]. 21 54. Stockl H, Devries K, Rotstein A, et al. The global prevalence of intimate partner homicide: a systematic 22 review. Lancet 2013;382:859-65. 23 55. Black MC. Intimate Partner Violence and Adverse Health Consequences: Implications for Clinicians. J 24 Womens Health (Larchmt) 2011;5:428-39. 25 56. Ayala Quintanilla BP, Taft A, McDonald S, et al. An examination of femicides in Peru between 2009 and 26 2014. Int J Gynaecol Obstet 2016;134:342-3 doi: 10.1016/j.ijgo.2016.03.020 [published Online First: 4 June 27 2016]. 28 57. Sugg N. Intimate partner violence: prevalence, health consequences, and intervention. Med Clin North Am 29 2015;99(3):629-49. 30 58. Sarkar NN. The impact of intimate partner violence on women's reproductive health and pregnancy outcome. 31 J Obstet Gynaecol 2008;28:266-71. 32 59. Chambliss LR. Intimate partner violence and its implication for pregnancy. Clin Obstet Gynecol http://bmjopen.bmj.com/ 33 2008;51(2):385-97. 34 60. Chisholm CA, Bullock L, Ferguson JEJ, 2nd. Intimate partner violence and pregnancy: epidemiology and 35 impact. Am J Obstet Gynecol 2017;217(2):141-4. 36 61. Alhusen JL, Ray E, Sharps P, et al. Intimate partner violence during pregnancy: maternal and neonatal 37 outcomes. J Womens Health (Larchmt) 2015;24:100-6. 38 62. Hill A, Pallitto C, McCleary-Sills J, et al. A systematic review and meta-analysis of intimate partner violence 39 during pregnancy and selected birth outcomes. Int J Gynaecol Obstet 2016; 133:269-76 doi:10.1016/j.ijgo.2015.10.023 [published Online First: 11 March 2013]. 40 63. Ayala Quintanilla, B. P., Taft, A., McDonald, et al. Social determinants and maternal exposure to intimate on September 25, 2021 by guest. Protected copyright. 41 partner violence of obstetric patients with severe maternal morbidity in the intensive care unit: a systematic 42 review protocol BMJ Open 2016;6(11):e013270 doi:10.1136/bmjopen-2016-013270 [published Online First: 43 28 November 2016]. 44 64. World Bank. Data 2017. http://data.worldbank.org/about/country-and-lending-groups (accessed 4 Jun 2017). 45 65. INSTITUTO NACIONAL DE ESTADISTICA E INFORMATICA. Encuesta Demografica y de Salud 46 Familiar 2016 - Nacional y Regional 2016. 2017. 47 https://www.inei.gob.pe/media/MenuRecursivo/publicaciones_digitales/Est/Lib1356/. (accessed 12 Jun 48 2017). 49 66. Lewis G. (2007). The Confidential Enquiry into Maternal and Child Health (CEMACH). Saving Mothers’ 50 Lives: reviewing maternal deaths to make motherhood safer - 2003-2005. The Seventh Report on 51 Confidential Enquiries into Maternal Deaths in the United Kingdom. London: CEMACH. 52 http://www.publichealth.hscni.net/sites/default/files/Saving%20Mothers%27%20Lives%202003-05%20.pdf 53 (accessed 12 Dec 2017). 54 67. The Confidential Enquiries into Maternal Deaths in the United Kingdom. 2001. Why mothers die 1997–1999. 55 The fifth report of the Confidential Enquiries into Maternal Deaths. http://www.hqip.org.uk/national- 56 programmes/a-z-of-clinical-outcome-review-programmes/cmace-reports/ (accessed 2 Aug 2014). 57 58 12 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 13 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 68. Knight M, Tuffnell DJ, Kenyon S, et al. Saving Lives, Improving Mothers’ Care - Surveillance of maternal 4 deaths in the UK 2011-13 and lessons learned to inform maternity care from the UK and Ireland Confidential 5 Enquiries into Maternal Deaths and Morbidity 2009-13. Oxford: National Perinatal Epidemiology Unit, 6 University of Oxford. 2015. https://www.npeu.ox.ac.uk/ (accessed 15 Apr 2016). 7 69. Knight M., Kenyon S., Brocklehurst P., et al. Saving Lives, Improving Mothers’ Care - Lessons learned to 8 inform future maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and 9 Morbidity 2009 –12. Oxford: National Perinatal Epidemiology Unit, University of Oxford. 2014. 10 https://www.npeu.ox.ac.uk/downloads/files/mbrrace- 11 uk/reports/Saving%20Lives%20Improving%20Mothers%20Care%20report%202014%20Full.pdf (accessed 12 27 Apr 2016). 13 70. United Nation, Every Woman Every Child. EVERY NEWBORN. An Action Plan To End Preventable 14 Deaths. Secondary EVERY NEWBORN. An Action Plan To End Preventable Deaths 2014. 15 http://apps.who.int/iris/bitstream/10665/127938/1/9789241507448_eng.pdf?ua=1 (accessed 14 Mar 2016). 16 71. Farquhar C, Sadler L, Masson V, et al. Beyond the numbers: classifying contributory factors and potentially avoidable maternalFor deaths peer in New Zealand, review 2006–2009. Am Jonly Obstet Gynecol 2011;205:331.e1-31e-8 17 doi:10.1016/j.ajog.2011.07.044 [published Online First: 30 July 2011]. 18 72. Murphy NJ, Quinlan JD. Trauma in pregnancy: assessment, management, and prevention. Am Fam Physician 19 2014;90(10):717-22. 20 73. Knight M, Lewis G, Acosta CD, et al. Maternal near-miss case reviews: the UK approach. BJOG 2014;121 21 Suppl 4:112-6. 22 74. Ananth CV, Smulian JC. Chapter 1 Epidemiology of Critical Illness in Pregnancy. In Belfort MA, Saade G, 23 Foley MR, et al., eds. Critical Care Obstetrics Fifth Edition 2011:1-10. 24 75. Knight M, Acosta C, Brocklehurst P, et al. Beyond maternal death: improving the quality of maternal care 25 through national studies of 'near-miss' maternal morbidity. Programme Grants Appl Res 2016;4(9). 26 76. von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in 27 Epidemiology (STROBE) statement: guidelines for reporting observational studies. The Lancet 28 2007;370(9596):1453-57. 29 77. von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in 30 Epidemiology (STROBE) Statement: guidelines for reporting observational studies. Int J Surg 2014;12:1495- 31 9. 32 78. Instituto Nacional Materno Perinatal. Boletín Estadístico 2014. 2014. http://www.inmp.gob.pe/institucional/ http://bmjopen.bmj.com/ 33 /sala-situacional/1421334856 (accessed 28 Jan 2015). 34 79. Instituto Nacional Materno Perinatal. Boletín Estadístico 2015 - 2016. 2016. 35 http://www.inmp.gob.pe/institucional/boletines-estadisticos/1422371837 (accessed 28 May 2017). 36 80. Open Epi. Sample Size Calculation for Unmatched Case-Control Studies. Version 3.03.17. 2014. 37 http://web1.sph.emory.edu/cdckms/sample%20size%202%20grps%20case%20control.html (accessed 2 Jul 38 2015). 39 81. Sanchez SE, Qiu C, Perales MT, et al. Intimate partner violence (IPV) and preeclampsia among Peruvian women. Eur J Obstet Gynecol Reprod Biol 2008;137:50-5 doi: 10.1016/j.ejogrb.2007.05.013 [published 40 Online First: 27 Jun 2007]. on September 25, 2021 by guest. Protected copyright. 41 82. Thaddeus S, Maine D. Too far to walk: Maternal mortality in context. Soc Sci Med 1994;38:1091-110. 42 83. Hosmer DV, Lemeshow S. Applied Logistic Regression. Second Edition ed. USA: A Wiley-Interscience 43 Publication. 2000:375. 44 84. Jewkes R, Dartnall E, Sikweyiya Y. Ethical and Safety Recommendations for Research on the Perpetration of 45 Sexual Violence. Sexual Violence Research Initiative Pretoria, South Africa: Medical Research Council. 46 2012. http://www.svri.org/EthicalRecommendations.pdf (accessed 28 May 2015). 47 85. Ellsberg M, Heise L. Researching Violence Against Women: A Practical Guide for Researchers and Activists 48 Washington DC, United States: World Health Organizationb PATH. 2005. 49 http://whqlibdoc.who.int/publications/2005/9241546476_eng.pdf?ua=1 (accessed 26 May 2015). 50 86. World Health Organization. Putting Women First: Ethical and Safety Recommendations for Research on 51 Domestic Violence Against Women. 2001. http://www.who.int/gender/violence/womenfirtseng.pdf (accessed 52 27 May 2015). 53 87. Jansen HAFM, Watts C, Ellsberg M, et al. Interviewer Training in the WHO Multi-Country Study on 54 Women’s Health and Domestic Violence. 2004. 55 http://www.who.int/gender/documents/Interviewer_training.pdf (accessed 27 May 2015). 56 57 58 13 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 14 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 88. Garcia-Moreno C, Jansen HAFM, Ellsberg M, et al. WHO Multi-country Study on Women’s Health and 4 Domestic Violence Against Women. Initial results on prevalence, health outcomes and women’s responses. 5 2005. http://www.who.int/reproductivehealth/publications/violence/24159358X/en/ (accessed 2 Jul 2014). 6 89. Karolinski A, Mercer R, Micone P, et al. The epidemiology of life-threatening complications associated with 7 reproductive process in public hospitals in Argentina. BJOG 2013;120:1685-95. 8 90. Filippi V, Chou D, Ronsmans C, et al. Levels and Causes of Maternal Mortality and Morbidity. In: Black RE, 9 Laxminarayan R, Temmerman M, et al., eds. 2016. Reproductive, Maternal, Newborn, and Child Health. 10 Disease Control Priorities, third edition, volume 2. Washington, DC: World Bank. doi:10.1596/978-1-4648- 11 0348-2. License: Creative Commons Attribution CC BY 3.0 IGO. 12 91. Pandis, N. Case-control studies: part 2. Am J Orthod Dentofacial Orthop 2014;146:402-3. 13 14 15 Authors’ contributions 16 BPAQ, AT, SMc andFor WP conceived peer and reviewdesigned the study only protocol. This study is part of the 17 first’s author PhD thesis. BPAQ drafted the manuscript and all authors edited following versions 18 of the draft. BA, AT, SMc, and WP revised critically the methodological and clinical content of 19 the protocol to make contributions. All authors reviewed and approved the final manuscript. 20 21 22 23 Funding 24 This study is part of a doctoral study at La Trobe University was supported by the Peruvian 25 Government through PRONABEC (National Program of Scholarship and Educational Loan) and 26 La Trobe University. No funding bodies will have any role in study design, collecting data, 27 analysing data, interpreting findings, and writing, reviewing or deciding to publish the 28 29 manuscript. 30 31 32 Competing interest statement http://bmjopen.bmj.com/ 33 The authors declare that they have no competing interest. 34 35 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 14 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 15 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

47 48 49 50 51 52

44 45 46

47 48 The next questions are about things that happen to many women, and that your current partner, or any other partner may have done to 49 you. 50

51 52 53

on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45

46 47 48 49 50 51

8 Assessing Non-IPV 9 10 (In the past 12 months before pregnancy) 11 12 (A) (B) (C) (D)

1 Continue with the following questions…………………………………… 2 3 4 5 BEFORE PREGNANCY DURING PREGNANCY 6 Assessing Non-IPV

7 (In the past 12 months before pregnancy) 8 9 (A) (B) (C) (D)

36 37 Thank you for your participation¡¡¡¡ 38 39 40 on September 25, 2021 by guest. Protected copyright. 41

42 43 44 45 46 47

48 49 50 51 52 53

1 2 3 D25. Indicate the diagnosis (ses) of the patient when she was discharged from the Intensive Care Unit: 4 1. ______5 2. ______6 3. ______7 4. ______8 5. ______9 6. ______

ForJournal: peerBMJ Open review only

Manuscript ID bmjopen-2017-020147.R2

Article Type: Protocol

Date Submitted by the Author: 12-Feb-2018

Complete List of Authors: Ayala Quintanilla, Beatriz; La Trobe University College of Science Health and Engineering, Judith Lumley Centre; Peruvian National Institute of Health, Lima Pollock, Wendy; La Trobe University, The Judith Lumley Centre; Mercy Hospital for Women McDonald, SJ; Midwifery Professorial Unit, La Trobe University/Mercy Hospital for Women Taft, Angela; La Trobe University, Mother and Child Health Research

Primary Subject Public health Heading: http://bmjopen.bmj.com/ Secondary Subject Heading: Intensive care, Obstetrics and gynaecology

Severe acute maternal morbidity, violence against women, intimate Keywords: partner violence, intensive care unit, social determinants, near miss

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 4 Title 5

26 1, 2, 4 1, 2, 3 1, 2 27 Authors: Beatriz Paulina Ayala Quintanilla , Wendy Pollock , Susan McDonald , 28 1 29 Angela Taft 30

43 44 Keywords: Severe acute maternal morbidity, violence against women, intimate partner violence, 45 46 47 intensive care unit, social determinants, near miss. 48 49 Words in the abstract: 298 words. 50 51 Words in article: 3,451 words, excluding title page, abstract, references, authors’ contributions, 52 53 funding and competing interest statement. 54 55 56 57 58 1 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 4 5 ABSTRACT 6 7 Introduction: Preventing and reducing violence against women (VAW) and maternal mortality 8 9 are Sustainable Development Goals. Worldwide, the maternal mortality ratio has fallen about 10 44% in the last 25 years, and for one maternal death there are many women affected by severe 11 acute maternal morbidity (SAMM) requiring management in the intensive care unit (ICU). These 12 women represent the most critically ill obstetric patients of the maternal morbidity spectrum and 13 should be studied to complement the review of maternal mortality. VAW has been associated 14 with all-cause maternal deaths, and since many women (30%) endure violence usually exerted by 15 their intimate partners and this abuse can be severe during pregnancy, it is important to 16 For peer review only 17 determine whether it impacts SAMM. Thus, this study aims to investigate the impact of VAW on 18 SAMM in the ICU. 19 20 Methods and analysis: This will be a prospective case-control study undertaken in a tertiary 21 healthcare facility in Lima-Peru, with a sample size of 109 cases (obstetric patients admitted to 22 the ICU) and 109 controls (obstetric patients not admitted to the ICU selected by systematic 23 24 random sampling). Data on social determinants, medical and obstetric characteristics, VAW, 25 pregnancy and neonatal outcome will be collected through interviews and by extracting 26 information from the medical records using a pretested form. Main outcome will be VAW rate 27 and neonatal mortality rate between cases and controls. VAW will be assessed by using the 28 World Health Organization (WHO) instrument. Binary logistic followed by stepwise 29 multivariate regression and goodness of fit test will assess any association between VAW and 30 SAMM. 31 32 http://bmjopen.bmj.com/ 33 Ethics and dissemination: Ethical approval has been granted by the La Trobe University, 34 Melbourne-Australia and the tertiary healthcare facility in Lima-Peru. This research follows the 35 WHO ethical and safety recommendations for research on VAW. Findings will be presented at 36 conferences, and published in peer-reviewed journals. 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 Strengths and limitations of this study 42 43 • This prospective study will examine for the first time the influence of violence against 44 women on severe acute maternal morbidity (SAMM). 45 46 • Studying the stage before maternal death (SAMM) complements the review of maternal 47 mortality. 48 • This study uses a standardised global instrument for the evaluation of violence against 49 women and a pre-tested form for the assessment of other variables of interest. 50 • Studying violence against women can be challenging and may underestimate the rate of 51 abuse due to recall and cultural bias. 52 53 • Findings should be interpreted cautiously because this study is within one very large tertiary 54 hospital and further multi-centre and multi-country studies may be needed, based on these 55 replicable methods. 56 57 58 2 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 4 5 6 INTRODUCTION 7 Preventing and reducing violence against women and maternal mortality are Sustainable 8 Development Goals (SDG).1 Worldwide, the maternal mortality ratio (MMR) has declined by 9 44% with a reduction from 385 to 216 maternal deaths per 100,000 live births between 1990 10 (532,000 maternal deaths) and 2015 (303,000 maternal deaths). This equates to approximately 11 2 12 830 women dying daily, of which 99% of maternal deaths occurred in developing countries. 13 However, maternal mortality is only a small proportion of the global burden of the maternal 14 morbidity spectrum.3-5 This is because for one maternal death there are many women affected by 15 severe acute maternal morbidity (SAMM) during pregnancy, childbirth and the postpartum 16 period5-11 includingFor those obstetric peer patients review who require multidisciplinary only management in the 17 intensive care unit (ICU).11-17 18

19 12 18-25 20 ICU admission can be a marker for defining SAMM, and SAMM can be named as near 15 19 21 25-28 21 miss; either term has been widely used to study this population of obstetric patients. 22 There are no internationally accepted criteria for defining SAMM and its definition may differ 23 across studies,19 20 25-34 and the use of ICU admission to identify severe maternal morbidity has 24 high sensitivity (86.4%), specificity (87.8%) and positive predicted value (0.85).22 27 35-38 Women 25 with SAMM treated in the ICU represent the most critically ill obstetric patients,11 19 39 and 26 27 require timely managed care due to the physiologic changes of pregnancy and the care of the 11-17 40-46 28 mother-baby dyad. 29 30 The incidence of maternal ICU admission varies from 0.04 to 4.54%, and the common causes are 31 mainly direct obstetric clinical conditions.12 14 19 29 According to Pollock, et al.,14 hypertensive 32 disorders were the leading cause of ICU admission (0.09% of deliveries), followed by obstetric http://bmjopen.bmj.com/ 33 34 haemorrhage (0.07%), and sepsis (0.02%); and, although the ICU admission profile was similar 35 worldwide there were higher rates of maternal deaths in the ICUs of developing countries. 36 37 Violence against women is a global public health problem and many women of reproductive age 38 endure violence usually exerted by their intimate partners (IPV). Globally, 30% of women have 39 experienced partner abuse.47-49 However, the IPV rate varies across studies ranging from 15 to 40 50 71% and from 1 to 28% during pregnancy. Diverse studies have also reported a wide range of on September 25, 2021 by guest. Protected copyright. 41 IPV rate during pregnancy from 0.9 to 20.1% in high-income countries,51 3 to 44% in Latin 42 52 53 43 America and Caribbean countries and 2 to 57% in African countries. 44 45 Several studies have reported negative and mortal consequences of IPV on reproductive age 46 women.54-57 During pregnancy, these adverse health outcomes affect the mother-baby dyad; and, 47 can be augmented by consequent risky health behaviours (smoking, alcohol consumption, 48 substance abuse, poor nutrition, lack of seeking health care, among others)57-60 and physiological 49 50 mechanisms through neural, neuroendocrine, and immune responses to acute and/or chronic 55 61 51 stress originating from exposure to violence. All of this may exacerbate pre-existing medical 52 55 61 62 52 conditions and/or lead to diverse pregnancy complications. Even though women could be 53 more vulnerable to IPV during the pregnancy and puerperium periods, no data on violence 54 against women of obstetric patients in the ICU have been reported in Peru or elsewhere63. Thus, 55 it is important to examine whether violence against women is a risk factor for women with 56 57 58 3 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 SAMM. We are conducting this study in Peru, an upper-middle income country64 with a lifetime 4 IPV rate of 68.2% (emotional 64.2%, physical 31.7% and sexual 6.6%).65 In Peru, there are 5 about 9 cases of femicide monthly56 and a MMR of 68, which fell 72.9% from 251 between 1990 6 2 7 and 2015. 8 9 10 There has been increased concern about the negative influence of violence against women on 11 maternal mortality,66-72 and violence against women has been associated with all-cause maternal 12 deaths.66 67 Although, this association was first analysed 16 years ago67 there is still a paucity of 13 studies investigating the influence of violence against women on SAMM63, which can be 14 15 22 29 36 73-75 15 considered as a complement to a review of maternal deaths. Thus, it is important to 16 determine whether violenceFor againstpeer women review impacts SAMM, onlysince many women endure violence 17 usually exerted by their intimate partners and this abuse can be severe during pregnancy. 18 Therefore, this research of the stage before maternal death (SAMM) will provide for the first 19 time, a better understanding about what potential factors, such as violence against women, are 20 21 affecting obstetric patients with SAMM in the ICU. This will make an important contribution to 22 global knowledge of causes of maternal morbidity. 23 24 25 26 HYPOTHESIS 27 We hypothesise that violence against women is significantly associated with severe acute 28 maternal morbidity in obstetric patients managed in the intensive care unit. 29 30 31 32 OBJECTIVES http://bmjopen.bmj.com/ 33 34 • To investigate the impact of violence against women on obstetric patients with SAMM 35 36 treated in the ICU (cases) by comparing them with obstetric patients not admitted to the 37 ICU (controls), in a tertiary healthcare facility in Lima-Peru. 38 39 • To evaluate pregnancy and neonatal outcome of women with SAMM in the ICU of a 40

tertiary healthcare facility in Lima-Peru. on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 METHODS 46 This is a prospective case-control study protocol and follows the Strengthening the Reporting of 47 Observational studies in Epidemiology (STROBE) criteria.76 77 48 49 50 Study design 51 In this case-control study, cases will be obstetric patients experiencing SAMM in the ICU (s) 52 including miscarriage, therapeutic abortion, unsafe abortion, and ectopic pregnancy 53 prospectively identified from the ICU register. The inclusion criteria of cases include: i) a 54 woman with a maternal ICU admission due to a complication (s) during pregnancy, delivery or 55 56 within 42 days of the ending of pregnancy, with favourable evolution and who fulfils eligibility 57 58 4 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 prior to hospital discharge; ii) 18-year-old or older; iii) Spanish speaker; and iv) gives written 4 informed consent. The exclusion criteria are: i) a woman with mental illness or disabilities or 5 6 other similar disabling pathologies; ii) not able to provide informed consent; iii) an obstetric 7 patient referred from other healthcare facilities for maternity care; and iv) ICU stay less than 24 8 hours. The controls are from the same source population that gives rise to the cases and their 9 inclusion criteria consist of i) a woman admitted to this hospital during pregnancy, delivery or 10 within 42 days of the ending of pregnancy, with favourable evolution and who fulfils eligibility 11 prior to hospital discharge; ii) 18-year-old or older; iii) Spanish speaker; and iv) gives written 12 informed consent. The exclusion criteria are: i) a woman with mental illness or disabilities or 13 14 other similar disabling pathologies; ii) not able to provide informed consent; and iii) an obstetric 15 patient referred from other healthcare facilities for maternity care. Favourable evolution means 16 that an obstetric patientFor has receivedpeer the requiredreview management only for the condition responsible for 17 her admission to the hospital or the ICU, is hemodynamically stable without requiring strict 18 monitoring or specialized treatment, her life is not at risk, and is well enough to be discharge 19 from the hospital to home (it implies that the maternal morbidity has resolved for the cases). 20 21 22 We plan to include all cases who meet the selection criteria during the study period, until we 23 reach the estimated sample size of 109 obstetric patients admitted to the ICU. This is because 24 there were 263 ICU admissions (pregnant and non-pregnant women) in 2012, 230 in 2013 and 25 274 in 2014 according to the Department of Epidemiology of this hospital78; and, approximately 26 48% of the ICU admissions are referred from other healthcare facilities (as indicated by the 27 Chief of the ICU). We expect that cases will be recruited during a period of twelve (12) months, 28 29 though recruitment will continue for longer if necessary for the minimum sample sizes to be 30 achieved. Controls will be selected by using a probability sampling method, specifically a 31 systematic random sampling (without replacement) starting with 18 and with a value of k = 131 32 as the sampling interval. http://bmjopen.bmj.com/ 33 34 Setting 35 36 This study is being undertaken in a tertiary hospital located in the capital city of Peru (where 37 about one third of the Peruvian population live). This institution is the main national referral 38 hospital for high risk maternal and neonatal patients throughout Peru, where there are over 39 22,000 deliveries yearly, which equates to approximately 1 delivery every 25 minutes.79 40

on September 25, 2021 by guest. Protected copyright. 41 Sample size 42 43 The sample size will comprise 218 participants (109 controls and 109 cases) which has been 44 calculated by using the Sample Size Calculation for Unmatched Case-Control Studies of the 80 45 software open Epi with a confidence level of 95% and a power of 80% to detect a (18.8%) 46 difference in the exposure of violence against women (rate) between cases and controls. There 47 are not preceding studies assessing the prevalence of violence against women among obstetric 48 patients with SAMM in the ICU. We estimated an IPV rate of 24.3% for controls and 43.1% for 49 cases in accordance with previous research investigating the relationship between IPV and 50 81 51 preeclampsia in Peruvian pregnant women at this maternity hospital. 52 53 Recruitment Method 54 Participants will be invited to participate and recruited during their hospital stay once their acute 55 56 medical condition (s) have been resolved (this will be after they were discharged from the ICU 57 58 5 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 6 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 for the case women), and before they are discharged from hospital to going home. Women in the 4 control group will be invited to participate within one week of a case woman being interviewed. 5 6 The researcher (interviewer), a Spanish speaking midwife, has been trained and has research 7 experience working on violence against women studies and research ethics. The researcher will 8 check with the hospital staff regarding eligibility (selection criteria, e.g. mental illness and 9 others), prior to approaching and inviting potential participants to the study. She will also ensure 10 that the potential participants understand the participant information statement and answer all 11 their questions, and explain to the participants that they can refuse or withdraw their participation 12 at any time without affecting their health care and rights. 13 14 15 16 For peer review only 17 Data Collection 18 Data collection commenced on 23rd October 2015 and is still ongoing. We expect to finish by 19 the end of March 2018. Currently, we are collecting data from the medical records. Women who 20 give consent will be interviewed once in private using a structured questionnaire (Appendix 1). 21 We will also extract information from their medical records using a pretested form developed by 22 the team members (Appendix 2). 23 24 25 Interview 26 The following information will be obtained during the face to face interview: socio-demographic 27 characteristics (age, place of residence, educational level, marital status, occupation and type of 28 health insurance) of the participant and her partner; behavioural factors (smoking, use of alcohol 29 or drugs); medical (previous and current diseases) and obstetric characteristics (number of 30 pregnancies, previous abortions, prenatal care visits, previous caesarean sections, and vaginal 31 births; use of family planning methods; anaemia during pregnancy and use of iron supplements 32 http://bmjopen.bmj.com/ 33 during pregnancy); and violence against women evaluation. 34 35 Violence against women will be assessed by using questions from a standardised instrument of 36 the WHO.50 These questions were validated, translated and adapted rigorously, since Peru was 37 one of the countries selected in the WHO Multi-country study instrument.50 They have been also 38 used by other researchers for investigating violence against women in Peru, and an adapted 39 version was applied in the Peruvian Demographic and Family Health Survey.65 40 on September 25, 2021 by guest. Protected copyright. 41 42 Violence against women evaluation will comprise emotional (including controlling behaviours), 43 physical and sexual abuse exerted by intimate-partners and by non-intimate partners (relatives, 44 friends or others) assessed 12 months before and during pregnancy. The participants will answer 45 the frequency (once or twice or many) for each act of emotional, physical or sexual violence. 46 Violence against women will be examined in an empathetic, supportive and non-judgmental 47 48 manner, giving the participants the opportunity not to answer any questions that make them feel 49 uncomfortable or to reschedule or terminate the interview at any time. The interview will only be 50 conducted with the woman alone and in private. If the interview is interrupted, the interviewer 51 will change the topic or may terminate the interview correspondingly. It is expected that the 52 interview will take approximately 25 to 30 minutes. After the interview, information about free 53 social support services for domestic violence (available at this maternity hospital) will be offered 54 to every participant including a referral if they wish. There will be also debriefing sessions for 55 56 57 58 6 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 7 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 the well-being of the interviewer. Individual support/counselling can be arranged at the hospital 4 for the interviewer or participant if it is needed. 5 6 7 8 9 Extracting data from medical records 10 We will extract data from the medical reports of the mothers and newborns (if applicable) related 11 to SAMM, pregnancy outcome, fetal and neonatal characteristics and outcome. 12 13 14 SAMM data will include hospital admission date, clinical causes for hospitalisation and/or ICU 15 admission, diagnoses after being discharged from the ICU and/or the hospital, number of 16 hospital stay days For and ICU peer stay days, review type of delivery, only additional procedures, weeks of 17 pregnancy when SAMM occurs, organ failure (s), use of technologies (mechanical ventilation, 18 transfusion, use of inotropic support and renal replacement therapies), main delays (in relation to 19 the three delays model framework used to study maternal mortality82), and pregnancy outcome 20 21 (Appendix 2). 22 23 Fetal and neonatal data will include: birth weight; birth age; sex; Apgar score (at 1 and 5 24 minutes); outcome at birth; clinical cause (s) for Neonatal ICU (NICU); number of days at the 25 NICU (if applicable) or at the hospital; use of technologies and/or antibiotics at the NICU; 26 feeding type (breastfeeding, formula or both); discharge status; and diagnoses from the hospital 27 and/or the NICU (Appendix 2). 28 29 30 Data entry and analysis 31 Data will be entered using SPSS V.24.0. Univariate analysis will be carried out to describe the 32 characteristics of SAMM, social determinants, violence against women and pregnancy and http://bmjopen.bmj.com/ 33 34 neonatal outcomes. Quantitative variables will be displayed as the mean ± SD and/or median 35 (interquartile rate) after verifying their normal or asymmetrical distribution. Difference of means 36 analyses between variables will be performed using appropriate statistical tests (Student's t-test 37 or Mann–Whitney U test or other similar). Qualitative variables will be displayed as frequencies. 38 39 We will apply a bivariate analysis to evaluate the association of violence against women (partner 40 and non-partner) as an independent variable with SAMM; and we will also evaluate this on September 25, 2021 by guest. Protected copyright. 41 42 association with partner violence only; and, with non-partner violence only. 43 44 We will fully assess violence against women as a risk factor by using a multivariate logistic 45 regression modelling considering an Odds Ratio (OR) with 95% CI. Crude ORs will also be 46 calculated. Statistical significance will be set at p < 0.05 for all analyses. We will identify effect 47 48 modification for age, level of education, alcohol consumption and use of drugs by performing a 49 stratified analysis of these variables that could potentially modify the effect of violence against 50 women on SAMM. This will be assessed by the calculation of crude ORs within every level of 51 each variable that is stratified. The final model will include the socio-demographic 52 53 characteristics of the participants, other variables of interest (such as household income, partner’s 54 educational level, partner’s occupation, etc.) according to the literature review, and modifiers 55 (we will remove the least significant modifiers one at a time until only those with p < 0.05 56 57 58 7 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 8 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 remain). Those variables with p values of < 0.25 will be initially chosen to be included in the 4 83 ’ 5 model, and the Hosmer-Lemeshow s goodness-of-fit test will be used to assess model adequacy 6 and stepwise multiple regression analysis performed to select and identify the predictive factors 7 in the final model.83 8 9 10 11 12 ETHICS AND DISSEMINATION 13 Ethical approval has been granted by the La Trobe University Human Ethics committee 14 (HEC15-023), Melbourne, Australia and the Institutional Review Board of the tertiary healthcare 15 hospital in Lima, Peru. Individual written informed consent will be obtained from participants 16 prior to data collection.For The peer present research review follows the onlyWHO and other ethical and safety 17 recommendations for research on gender-based violence to ensure the safety of the participants 18 and the interviewer.50 84-88 19 20 It is planned that the findings of this case-control study will be presented at La Trobe University 21 and national and/or international conferences, and it will be also published in a peer review 22 journal. It is expected that these finding will inform policymakers, patients, and the public 23 through these presentations. 24 25 26 PRESENTING AND REPORTING RESULTS 27 This prospective case-control study will examine for the first time the influence of violence 28 against women on obstetric patients affected by severe acute maternal morbidity who require 29 management in the ICU, and evaluate their pregnancy and neonatal outcomes. We will present 30 major findings in tables and also describe results in narrative format outlining effect sizes and 31 their parameters. The findings and further publications will be reported following the 32 76 77 Strengthening the Reporting of Observational studies in Epidemiology (STROBE) criteria, http://bmjopen.bmj.com/ 33 34 which is part of the Enhancing the quality and transparency of health research (EQUATOR) 35 Network website. 36 37 DISCUSSION 38 The influence of violence against pregnant women on the incidence of or type of SAMM is not 39 40 known and worthy of study. Although, the negative contribution of violence against women to

67 on September 25, 2021 by guest. Protected copyright. 41 maternal deaths was described in the 1997-1999 Confidential Enquiry into Maternal Death, and 42 many studies have reported negative and fatal repercussions of IPV on women’s health including 43 during all stages of pregnancy,52-62 there is a paucity of studies assessing the relationship 44 between violence against women and SAMM63. Investigating women affected by SAMM could 45 complement the review of maternal deaths15 22 29 36 73-75 to understand which underlying factors 46 are influencing the sequence of events from a healthy pregnancy through minor complications to 47 26 89 90 48 life threatening obstetric conditions and even death in childbearing women. 49 50 This case-control study will contribute to evidence about the potential negative consequences of 51 violence against women of obstetric patients with SAMM in the ICU, who represent the most 52 critically ill patients11 19 39 and have been shown to be an important component of the maternal 53 morbidity spectrum requiring timely managed care. 11-17 40-46 This may help to highlight that non- 54 55 biological factors (violence against women), which are potentially modifiable, may be associated 56 with SAMM and are important to address to reduce maternal morbidity-mortality in Peru and in 57 58 8 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 9 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 other low and middle-income countries. Acute or chronic exposure to violence adversely affects 4 both the mothers and their babies and can be augmented by any risky health behaviors57-60 and 5 through physiological (neural, neuroendocrine, and immune) mechanisms in response to this 6 55 61 7 abuse. All of this may exacerbate pre-existing medical conditions and/or lead to diverse 52 55 61 62 8 pregnancy complications. Thus, it would be important to know if violence against 9 women is a risk factor for SAMM in the ICU, and to understand the complete picture of the 10 global burden of maternal morbidity-mortality to improve mother-baby dyad health and 11 women’s well-being. 12 13 14 This study may also help participants affected by violence to disclose abuse in a safe and 15 supportive environment; and, provide an opportunity for those abused women to understand that 16 it is possible to preventFor violence peer and improve review their and other only women’s lives, since they will be 17 informed and/or referred to the free social support services available for domestic violence 18 provided by the Peruvian government. 19 20 21 We understand that the findings of this study should be interpreted cautiously and some 22 limitations should be noted. Firstly, this research will be undertaken in a single centre. It will be 23 important to carry out further multi-centre and multi-country studies. Other limitations may 24 include recall, cultural and measurement bias which can underestimated or overestimate the 25 exposure.50 91 This is because the assessment of violence against women is complex and 26 challenging. Accordingly, this research follows the ethical and safety recommendations for 27 research on violence against women;50 84-88 and uses standardized questions for the assessment of 28 29 violence against women (WHO instrument) and a pretested questionnaire for the evaluation of 30 other factors. Amendments to this protocol are not expected. However, if any are required, these

31 amendments will be reported transparently. 32 http://bmjopen.bmj.com/ 33 Notwithstanding these limitations, we hope that this study will contribute to the global effort 34 towards achieving SDGs by providing valuable information for a better understanding of SAMM 35 and violence against women in Peru. This will make an important contribution to global 36 37 knowledge of causes of maternal morbidity by providing evidence of the relationship between 38 violence against women and SAMM, which is important for preventing and/or reducing maternal 39 morbidity-mortality and improve maternal health. Therefore, we expect that this research will 40 extend knowledge in an identified research gap, and may provide direction for further studies in on September 25, 2021 by guest. Protected copyright. 41 obstetric women affected by SAMM in the ICU. 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 9 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 10 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 4 5 6 7 8 9 10 11 12 13 14 REFERENCES 15 16 1. United Nations. TransformingFor peer our world: the review 2030 Agenda for Sustainable only Development. Resolution adopted 17 by the General Assembly on 25 September 2015. 2015. 18 https://sustainabledevelopment.un.org/post2015/transformingourworld (accessed 6 May 2017). 19 2. World Health Organization. Trends in maternal mortality: 1990 to 2015. Estimates by WHO, UNICEF, 20 UNFPA, World Bank Group and the United Nations Population Division. Secondary Trends in maternal 21 mortality: 1990 to 2015. Estimates by WHO, UNICEF, UNFPA, World Bank Group and the United Nations 22 Population Division. 2015. http://www.who.int/classifications/icd/factsheet/en/ (accessed 15 Feb 2016). 23 3. Mantel GD, Buchmann E, Rees H, et al. Severe acute maternal morbidity: a pilot study of a definition for a 24 near-miss. Br J Obstet Gynaecol 1998;105:985-90. 25 4. Geller SE, Cox SM, Callaghan WM, et al. Morbidity and mortality in pregnancy: laying the groundwork for 26 safe motherhood. Womens Health Issues 2006;16:176-88. 27 5. Firoz T, Chou D, von Dadelszen P, et al. Measuring maternal health: focus on maternal morbidity. Bull World 28 Health Organ 2013;91:794-6. 29 6. Ashford L. Hidden suffering: disabilities from pregnancy and childbirth in less developed countries. 30 Secondary Hidden suffering: disabilities from pregnancy and childbirth in less developed countries. 2002. http://www.prb.org/pdf/hiddensufferingeng.pdf (accessed 23 Jul 2014). 31 7. Fottrell E, Kanhonou L, Goufodji S, et al. Risk of psychological distress following severe obstetric 32 complications in Benin: the role of economics, physical health and spousal abuse. Br J Psychiatry http://bmjopen.bmj.com/ 33 2010;196:18-25. 34 8. Pacagnella RC, Cecatti JG, Camargo RP, et al. Rationale for a long-term evaluation of the consequences of 35 potentially life-threatening maternal conditions and maternal "near-miss" incidents using a multidimensional 36 approach. J Obstet Gynaecol Can 2010;32:730-8. 37 9. Wilson RE, Salihu HM. The paradox of obstetric "near misses": converting maternal mortality into morbidity. 38 Int J Fertil Womens Med 2007;52:121-7. 39 10. Storeng KT, Drabo S, Ganaba R, et al. Mortality after near-miss obstetric complications in Burkina Faso: 40 medical, social and health-care factors. Bull World Health Organ 2012;90:418-25B. on September 25, 2021 by guest. Protected copyright. 41 11. Plaat F, Naik M. Critical care in pregnancy. Crit Care 2011;15:1014 doi: http://dx.doi.org/10.1186/cc10479 42 [published Online First: 22 December 2013]. 43 12. Zieleskiewicz L, Chantry A, Duclos G, et al. Intensive care and pregnancy: Epidemiology and general 44 principles of management of obstetrics ICU patients during pregnancy. Anaesth Crit Care Pain Med 2016;35 45 (Suppl 1):S51-7 doi: 10.1016/j.accpm.2016.06.005 [published Online First: 5 July 2016]. 46 13. Guntupalli KK, Hall N, Karnad DR, et al. Critical illness in pregnancy Part I: an approach to a pregnant 47 patient in the ICU and common obstetric disorders. Chest 2015;148:1093-104. 48 14. Pollock W, Rose L, Dennis C. Pregnant and postpartum admissions to the intensive care unit: a systematic 49 review. Intensive Care Med 2010;36:1465-74. 50 15. Baskett TF. Epidemiology of obstetric critical care. Best Pract Res Clin Obstet Gynaecol 2008;22:763-74. 51 Complement to maternal deaths 52 16. Martin SR, Foley MR. Intensive care in obstetrics: an evidence-based review. Am J Obstet Gynecol 53 2006;195:673-89. 17. Germain S, Wyncoll D, Nelson-Piercy C. Management of the critically ill obstetric patient. Curr Obstet 54 Gynaecol 2006;16:125-33. 55 56 57 58 10 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 11 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

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Knight M, Lewis G, Acosta CD, et al. Maternal near-miss case reviews: the UK approach. BJOG 2014;121 24 Suppl 4:112-6. 25 74. Ananth CV, Smulian JC. Chapter 1 Epidemiology of Critical Illness in Pregnancy. In Belfort MA, Saade G, 26 Foley MR, et al., eds. Critical Care Obstetrics Fifth Edition 2011:1-10. 27 75. Knight M, Acosta C, Brocklehurst P, et al. Beyond maternal death: improving the quality of maternal care 28 through national studies of 'near-miss' maternal morbidity. Programme Grants Appl Res 2016;4(9). 29 76. von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in 30 Epidemiology (STROBE) statement: guidelines for reporting observational studies. The Lancet 31 2007;370(9596):1453-57. 32 77. von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in http://bmjopen.bmj.com/ 33 Epidemiology (STROBE) Statement: guidelines for reporting observational studies. Int J Surg 2014;12:1495- 34 9. 35 78. Instituto Nacional Materno Perinatal. Boletín Estadístico 2014. 2014. http://www.inmp.gob.pe/institucional/ 36 /sala-situacional/1421334856 (accessed 28 Jan 2015). 37 79. Instituto Nacional Materno Perinatal. Boletín Estadístico 2015 - 2016. 2016. 38 http://www.inmp.gob.pe/institucional/boletines-estadisticos/1422371837 (accessed 28 May 2017). 39 80. Open Epi. Sample Size Calculation for Unmatched Case-Control Studies. Version 3.03.17. 2014. http://web1.sph.emory.edu/cdckms/sample%20size%202%20grps%20case%20control.html (accessed 2 Jul 40 2015). on September 25, 2021 by guest. Protected copyright. 41 81. Sanchez SE, Qiu C, Perales MT, et al. Intimate partner violence (IPV) and preeclampsia among Peruvian 42 women. Eur J Obstet Gynecol Reprod Biol 2008;137:50-5 doi: 10.1016/j.ejogrb.2007.05.013 [published 43 Online First: 27 Jun 2007]. 44 82. Thaddeus S, Maine D. Too far to walk: Maternal mortality in context. Soc Sci Med 1994;38:1091-110. 45 83. Hosmer DV, Lemeshow S. Applied Logistic Regression. Second Edition ed. USA: A Wiley-Interscience 46 Publication. 2000:375. 47 84. Jewkes R, Dartnall E, Sikweyiya Y. Ethical and Safety Recommendations for Research on the Perpetration of 48 Sexual Violence. Sexual Violence Research Initiative Pretoria, South Africa: Medical Research Council. 49 2012. http://www.svri.org/EthicalRecommendations.pdf (accessed 28 May 2015). 50 85. Ellsberg M, Heise L. Researching Violence Against Women: A Practical Guide for Researchers and Activists 51 Washington DC, United States: World Health Organizationb PATH. 2005. 52 http://whqlibdoc.who.int/publications/2005/9241546476_eng.pdf?ua=1 (accessed 26 May 2015). 53 86. World Health Organization. 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1 2 3 87. Jansen HAFM, Watts C, Ellsberg M, et al. Interviewer Training in the WHO Multi-Country Study on 4 Women’s Health and Domestic Violence. 2004. 5 http://www.who.int/gender/documents/Interviewer_training.pdf (accessed 27 May 2015). 6 88. Garcia-Moreno C, Jansen HAFM, Ellsberg M, et al. WHO Multi-country Study on Women’s Health and 7 Domestic Violence Against Women. Initial results on prevalence, health outcomes and women’s responses. 8 2005. http://www.who.int/reproductivehealth/publications/violence/24159358X/en/ (accessed 2 Jul 2014). 9 89. Karolinski A, Mercer R, Micone P, et al. The epidemiology of life-threatening complications associated with 10 reproductive process in public hospitals in Argentina. BJOG 2013;120:1685-95. 11 90. Filippi V, Chou D, Ronsmans C, et al. Levels and Causes of Maternal Mortality and Morbidity. In: Black RE, 12 Laxminarayan R, Temmerman M, et al., eds. 2016. Reproductive, Maternal, Newborn, and Child Health. 13 Disease Control Priorities, third edition, volume 2. Washington, DC: World Bank. doi:10.1596/978-1-4648- 14 0348-2. License: Creative Commons Attribution CC BY 3.0 IGO. 15 91. Pandis, N. Case-control studies: part 2. Am J Orthod Dentofacial Orthop 2014;146:402-3. 16 For peer review only 17 18 Authors’ contributions 19 BPAQ, AT, SMc and WP conceived and designed the study protocol. This study is part of the 20 first’s author PhD thesis. BPAQ drafted the manuscript and all authors edited following versions 21 of the draft. BA, AT, SMc, and WP revised critically the methodological and clinical content of 22 the protocol to make contributions. All authors reviewed and approved the final manuscript. 23 24 25 26 Funding 27 This study is part of a doctoral study at La Trobe University was supported by the Peruvian 28 Government through PRONABEC (National Program of Scholarship and Educational Loan) and 29 La Trobe University. No funding bodies will have any role in study design, collecting data, 30 analysing data, interpreting findings, and writing, reviewing or deciding to publish the 31 manuscript. 32 http://bmjopen.bmj.com/ 33 34 35 Competing interest statement 36 The authors declare that they have no competing interest. 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 14 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 15 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 A5. What is your occupation? 2 1. Unemployed 3 2. Student 4 3. Employed 5 4. Self-employed 6 5. Housewife 6. Other (specify) ______7 7. Do not know / Not Sure 8 9 A6. How hard is it for you (and your family) to pay for the very basics like food? 10 1 Very hard 11 2 Hard 12 3 Somewhat hard 4 Not very hard 13 9 Do not know / Not Sure 14 15 A7. How hard is it for you (and your family) to pay for medical care? 16 1 Very Hard For peer review only 17 2 Hard 18 3 Somewhat hard 4 Not very hard 19 9 Do not know / Not Sure 20 21 A8. How much is the estimated monthly income of your nuclear family? 22 ------23 24 25 A9. How many household members are dependent on this monthly income (specify)? 26 ------27 28 A10. Are you a SIS beneficiary? 29 1 No 30 2 Yes 31 9 Do not know / Declined to answer 32 http://bmjopen.bmj.com/ 33 A11. Can you tell me your SIS category? 34 1 Low risk 35 2 Medium risk 3 High risk 36 9 Do not know / Declined to answer 37 38 A12. If you do not have SIS, which health insurance do you have? 39 1 Private company 40 2 Other (specify)______on September 25, 2021 by guest. Protected copyright. 41 3 Do not have any health insurance 9 Do not know / Declined to answer 42 43 A13. What about smoking, do you smoke during this pregnancy? 44 1 No → Skip to A15 45 2 Yes → Continue to A14 46 9 Do not know / Declined to answer 47 A14. If yes, would you say? 1. Daily 48 2. Occasionally 49 3. Not at all 50 9 Do not know / Declined to answer 51 52 A15. What about alcohol use, do you drink alcohol during this pregnancy? 53 1 No → Skip to A17 2 Yes → Continue to A16 54 9 Do not know / Declined to answer 55 56 57 58 2 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 17 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

13 PARTNER INFORMATION 14 15 A18. What is the age of your partner ______(Years) 16 A19. What is the level of educationFor of your husband/partner peer? review only 17 18 1. Primary level 2. Secondary level 19 3. Technical studies 20 4. University level 21 5. Other (Specify)______22 9 Do not know / Declined to answer 23 A20. What is the occupation of your husband/partner? 24 1. Unemployed 25 2. Student 26 3. Employed 27 4. Self-employed 5. Other (specify) ______28 9 Do not know / Declined to answer 29 30 A21. What about alcohol use, does/did your husband/partner drink alcohol during your pregnancy? 31 1 No → Skip to A25 32 2 Yes → Continue to A22 http://bmjopen.bmj.com/ 33 34 A22. If yes, would you say? 1. Every day or nearly every day 35 2. Once or twice a week 36 3. 1 – 3 times a month 37 4. Occasionally, less than once a month 38 5. Never 39 9 Do not know / Declined to answer 40 A23. Does/did your husband/partner get drunk during your pregnancy? on September 25, 2021 by guest. Protected copyright. 41 1. No → Skip to A25 42 2. Yes → Continue to A24 43 9. Do not know/Declined to answer 44 45 A24. If yes, would you say? 46 1. Most days 47 2. Weekly 3. Once a month 48 4. Less than once a month 49 5. Never 50 9 Do not know / Declined to answer 51 52 A25. What about drug use, does/did your partner use any illegal drugs during your pregnancy? 53 1. No 54 2. Yes 9. Do not know / Declined to answer 55 56 57 58 3 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 18 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 B24. Did you receive vaccination against tetanus in the last 10 years? 3 1. No 4 2. Yes 5 9 Do not know / Not sure 6 B25. Did a doctor ever tell you that you have anemia during this pregnancy? 7 1. No → Skip to B30 8 2. Yes → Continue to B26 9 9 Do not know / Not sure 10 11 B26. Which trimester, did a doctor tell you that you have anemia during this pregnancy? 12 1 I Trimester 13 2 II Trimester 3 III Trimester 14 9 Do not know / Not sure 15 16 B27. Did you takeFor any ferrous peer iron supplement duringreview this pregnancy? only 17 1. No → Skip to B30 18 2. Yes → Continue to B28 19 9 Do not know / Not sure 20 B28. If yes, how many pills/tablets per day? ______pills per day [99: Do not know / not sure] 21 B29. And, how many months did you drink these pills/tablets? ______months [99: Do not know / not sure] 22 23 B30. How many times did you visit the emergency room during this pregnancy? ______time/times [99: Do not know / not sure] 24 B31. Has a doctor ever told you that you have or do you have? 25 You have had You have 26 Diseases Do not know / Do not know / No Yes No Yes 27 not sure not sure 28 a Chronic hypertension 1 2 99 1 2 99 29 b Anemia 1 2 99 1 2 99 30 c Tuberculosis 1 2 99 1 2 99 31 d Diabetes Mellitus 1 2 99 1 2 99 32 e Heart disease 1 2 99 1 2 99 http://bmjopen.bmj.com/ 33 34 f Thyroid disease 1 2 99 1 2 99 35 g HIV infection 1 2 99 1 2 99 36 h Other (specify) ______1 2 99 1 2 99 37 38 39 40 B32. Did you ever have one or more of the following condition (s) during previous pregnancy (es)? Do not know / on September 25, 2021 by guest. Protected copyright. 41 Clinical conditions NO YES 42 not sure 43 1 Hypertensive related disease 1 2 99 44 a Severe Preeclampsia 1 2 99 45 b Eclampsia 1 2 99 46 c HELLP Syndrome 1 2 99 47 2 Antepartum hemorrhage in the second trimester of pregnancy because of (specify): 1 2 99 48 49 a Placenta previa 1 2 99 50 b Uterine rupture 1 2 99 51 c Abruptio placentae 52 d Other (specify) 1 2 99 53 54 3 Antepartum hemorrhage in the third trimester of pregnancy because of (specify): 1 2 99 55 a Placenta previa 1 2 99 56 b Uterine rupture 1 2 99 57 c Abruptio placentae 1 2 99 58 5 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 20 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

47 48 49 50 51 52

Many 19 Many YES NO YES NO One Few YES NO One Few (>5 times) (>5 times) 20 21 22 C1. Tries to keep you from 1 2 1 2 1 2 3 1 2 1 2 3 23 seeing your friends? 24 25 C2. Tries to restrict contact with 1 2 1 2 1 2 3 1 2 1 2 3 26 your family of birth? 27 28 C3. Insists on knowing where 1 2 1 2 1 2 3 1 2 1 2 3 29 you are at all times? 30 C4. Ignores you and treats you 31 1 2 1 2 1 2 3 1 2 1 2 3 32 indifferently? http://bmjopen.bmj.com/ 33 C5. Gets angry if you speak 34 1 2 1 2 1 2 3 1 2 1 2 3 35 with another man? 36 C6. Is often suspicious that you 37 1 2 1 2 1 2 3 1 2 1 2 3 38 are unfaithful? 39 40 C7. Expects you to ask his permission before seeking 1 2 1 2 1 2 3 1 2 1 2 3 on September 25, 2021 by guest. Protected copyright. 41 health care for yourself? 42 43

44 45 46

47 48 The next questions are about things that happen to many women, and that your current partner, or any other partner may have done to 49 you. 50

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14 YES NO YES NO One Few Many YES NO One Few Many 15 (>5 times) (>5 times) 16 C8. Insulted you or made you 1 For2 peer1 2 review1 2 3 only1 2 1 2 3 17 feel bad about yourself? 18 C9. Belittled or humiliated 1 2 1 2 1 2 3 1 2 1 2 3 19 you in front of other people? 20 C10. Done things to scare or 21 intimidate you on purpose 22 (e.g., by the way he looked at 1 2 1 2 1 2 3 1 2 1 2 3 you, by yelling and smashing 23 things)? 24 C11. Threatened to hurt you 1 2 1 2 1 2 3 1 2 1 2 3 25 or someone you care about 26

46 47 48 49 50 51

8 Assessing Non-IPV 9 10 (In the past 12 months before pregnancy) 11 12 (A) (B) (C) (D)

13 (If YES Has this happened in the past 12 In the past 12 months before this Has this happened during this pregnancy? 14 continue with months before this pregnancy? pregnancy, would you say that this (If YES ask Who was/were) Since the age of 15 B. If NO, ask (If YES ask C, if NO ask D) has happened once, a few times or 15 years, has during many times? 16 anyone (other pregnancy For peer(after answering review C, go to D) onlyAnd would you say that this has happened once, a few times, or many 17 than your and if NO times? partner/husband): 18 skip to next (in total from all the persons she (in total from all the persons she mentioned) item) mentioned) 19 (choose “one”, “few” or many” considering in total from all the persons 20 she mentioned) 21 Many Many Who did this to you? Who did this to you? YES NO YES No One Few (>5 YES No One Few (>5 22 (multiple responses) (multiple responses) times) times) 23 B Father B Father 24 C Mother C Mother D Father in law D Father in law 25 E Mother in law E Mother in law 26 C21. Insulted F Other family member F Other family member you or made you G Friend of family G Friend of family 27 1 2 1 2 1 2 3 1 2 1 2 3 feel bad about H Neighbor H Neighbor 28 yourself? I Someone at work I Someone at work 29 J Stranger J Stranger K Other (specify) K Other (specify) 30 ………………………………. ………………………… 31 ……….……………………… …….………………….. 32 B Father B Father

C Mother C Mother http://bmjopen.bmj.com/ 33 D Father in law D Father in law E Mother in law E Mother in law 34 C22. Belittled or F Other family member F Other family member 35 humiliated you in G Friend of family G Friend of family 1 2 1 2 1 2 3 1 2 1 2 3 36 front of other H Neighbor H Neighbor people? I Someone at work I Someone at work 37 J Stranger J Stranger K Other (specify) K Other (specify) 38 …………………………… ………………………… 39 ………….………………… …………….…………. 40 B Father B Father on September 25, 2021 by guest. Protected copyright. 41 C23. Done C Mother C Mother things to scare or D Father in law D Father in law 42 intimidate you on E Mother in law E Mother in law F Other family member F Other family member 43 purpose (e.g., by G Friend of family G Friend of family 44 the way he 1 2 1 H Neighbor 2 1 2 3 1 H Neighbor 2 1 2 3 looked at you, by I Someone at work I Someone at work 45 yelling and J Stranger J Stranger 46 smashing K Other (specify) K Other (specify) 47 things)? …………………………… ………………………… …….…….………………. …………….…………. 48 B Father B Father 49 C Mother C Mother D Father in law D Father in law 50 E Mother in law E Mother in law 51 C24. Threatened F Other family member F Other family member to hurt you or G Friend of family G Friend of family 1 2 1 2 1 2 3 1 2 1 2 3 52 someone you H Neighbor H Neighbor 53 care about? I Someone at work I Someone at work J Stranger J Stranger 54 K Other (specify) K Other (specify) 55 …………………………… ………………………… 56 …………………………… …….……….…………. 57 58 10 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 25 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 Continue with the following questions…………………………………… 2 3 4 5 BEFORE PREGNANCY DURING PREGNANCY 6 Assessing Non-IPV 7 (In the past 12 months before pregnancy) 8 9 (A) (B) (C) (D)

10 (If YES Has this happened in the past In the past 12 months before this Has this happened during this pregnancy? 11 continue with 12 months before this pregnancy, would you say that this (If YES ask Who was/were) B. If NO, ask pregnancy? has happened once, a few times or 12 Since the age of 15 during (If YES ask C, if NO ask D) many times? years, has anyone 13 pregnancy (after answering C, go to D) And would you say that this has happened once, a few times, or (other than your and if NO many times? 14 partner/husband): 15 skip to next (in total from all the persons she (in total from all the persons she mentioned) 16 item) mentioned) For peer review only(choose “one”, “few” or many” considering in total from all the 17 persons she mentioned) 18 Who did this Who did this 19 to you? Many to you? Many YES NO YES No One Few YES No One Few 20 (multiple (>5 times) (multiple (>5 times) 21 responses) responses) 22 B Father B Father 23 C Mother C Mother 24 D Father in law D Father in law E Mother in law E Mother in law 25 F Other family F Other family 26 C25. Ever beaten member member you or physically G Friend of G Friend of 1 2 1 2 1 2 3 1 2 1 2 3 27 mistreated you in family family 28 any way ? H Neighbor H Neighbor I Someone at I Someone at 29 work work 30 J Stranger J Stranger K Other (specify) K Other (specify) 31 ……………… ……………… 32 ……………… ……………… http://bmjopen.bmj.com/ 33 B Father B Father 34 C26. ¿forced you to C Mother C Mother 35 D Father in law D Father in law have sex or to E Mother in law E Mother in law 36 perform a sexual act F Other family F Other family 37 when did you not member member want or to do G Friend of G Friend of 1 2 1 2 1 2 3 1 2 1 2 3 38 something sexual family family 39 that you found H Neighbor H Neighbor degrading or I Someone at I Someone at 40 work work humiliating? on September 25, 2021 by guest. Protected copyright. 41 J Stranger J Stranger K Other (specify) K Other (specify) 42 ……………… ……………… 43 ……………… ……………… 44 45 46 C27. Have you ever been punched or kicked in the abdomen by anyone including your (ex or current) partner or other person(s) whilst you were pregnant? 47 1. No 48 2. Yes 49 C.28 When (indicate year and which pregnancy) Year………………Which pregnancy………………………...... 50 51 9. Don’t know / Decline to answer 52 C29. Have any health care professionals asked you if you were affected by IPV or non-partner violence? 53 1 No 54 2 Yes 55 9 Do not know / Decline to answer 56 57 58 11 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 26 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

10 C30. Have you sought help to prevent or stop gender-based violence? 11 1 No 12 2 Yes 13 9 Do not know / Decline to answer 14 15 C31. Can you mention what type of help? 1 Family member 16 2 ForFriend peer review only 17 3 Community Social Services from the government 18 4 Police 19 5 Other (specify)………………………… 20 9 Do not know / Decline to answer 21

36 37 Thank you for your participation¡¡¡¡ 38 39 40 on September 25, 2021 by guest. Protected copyright. 41

42 43 44 45 46 47

48 49 50 51 52 53

1 2 3 D6 Gestational age at first antenatal visit ______weeks [999 = Not recorded] 4 D7. Number of antenatal visits______[999 = Not recorded] 5 6 D8 Pre-pregnancy weight (weight before the participant became pregnant this time) ______Kilograms [999 = Not recorded] 7 D9 Pregnancy weight before delivery ______Kilograms [999 = Not recorded] 8 D10. Weight gain during pregnant ______Kilograms [999 = Not recorded] 9 D11 Height ______Centimeters [999 = Not recorded] 10 11 D12. Date of admission at this hospital__ __ / __ __ / ______12 D D / M M / Y Y Y Y 13 D13. Indicate the diagnosis of the patient when she was hospitalized at this hospital: 14 1 ______15 2 ______16 3 ______4 ______For peer review only 17 5 ______18 19 D14 Socioeconomic level according to Social Services Department of this hospital: 1. Lower risk 20 2. Mediun risk 21 3. High risk 22 4. No category 23 D15. Was the participant admitted at the Intensive Care Unit? 24 1. No → Skip to D26 25 2. Yes → Continue to D16 26 27 D16. Date of admission at the Intensive Care Unit __ __ / __ __ / ______Time______(hour) 28 D D / M M / Y Y Y Y 29 D17. Indicate the diagnosis (ses) of the participant when she was admitted at the Intensive Care Unit: 30 1. ______31 2. ______32 3. ______http://bmjopen.bmj.com/ 33 4. ______5. ______34 35 D18. Weeks of pregnancy at the moment of the event (s) (SAMM) which cause(s) her admission at the Intensive Care Unit: 36 ______weeks 37 38 39 D19. Moment of such event (SAMM) in relation to the termination of pregnancy: 1. Before 40

2. During on September 25, 2021 by guest. Protected copyright. 41 3. After 42 D20. Did the woman received assistance with ventilation? 43 1. CPAP 44 2. Non-invasive ventilation (e.g. BiPAP) 45 3. Invasive mechanical ventilation 46 4. None of the above 47 D21. Which management did the woman receive in the ICU (multiple responses)? 48 1. Inotrope or vasopressor therapy 49 2. Renal replacement therapy (dialysis) 50 3. Central venous access 51 4. None of the above 52 D22. What was the severity of illness score on admission? ______Score (APACHE) 53 D23. Date of discharge of the Intensive Care Unit: __ __ / __ __ / ______54 D D / M M / Y Y Y Y 55 D24. Indicate the number of days in the Intensive Care Unit: _____days 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 29 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 D25. Indicate the diagnosis (ses) of the patient when she was discharged from the Intensive Care Unit: 4 1. ______5 2. ______6 3. ______7 4. ______8 5. ______9 6. ______

1 2 3 d Ruptured uterus 1 2 99 4 e Accreta/increta/percreta placenta 1 2 99 5 f Other (specify) 1 2 99 6 5 Miscarriage complication 1 2 99 7 8 a Uterine perforation 1 2 99 9 b Cervical laceration/tear 1 2 99 10 c Infection 1 2 99 11 d Other (specify) 1 2 99 12 6 Ectopic pregnancy 1 2 99 13 14 7 Sepsis (obstetric origin) 1 2 99 15 a Chorioamnionitis 1 2 99 b Surgical wound infection 1 2 99 16 c Endometritis For peer review only1 2 99 17 18 d Other (specify) 1 2 99 19 8 Sepsis (non-obstetric origin) 1 2 99 20 a Urine infection 1 2 99 21 b Other (specify) 1 2 99 22 9 Sepsis (pulmonary origin) 1 2 99 23 a Pneumonia 1 2 99 24 b Viral cause 1 2 99 25 b.1 Influenza (e.g. H1N1) 1 2 99 26 b.2 Varicella 1 2 99 27 b.3 Other (specify) 1 2 99 28 c Other (specify) 1 2 99 29 10 Clinical condition 1 2 99 30 31 a Oligohydramnios 1 2 99 32 b Intrauterine growth restriction 1 2 99 http://bmjopen.bmj.com/ 33 c Fetal macrosomy 1 2 99 34 d Other (specify) 1 2 99 35 11 Other associated pathologies 36 a Premature rupture of fetal membranes 1 2 99 37 b Disseminated intravascular coagulation (DIC) 1 2 99 38 c Maternal pulmonary edema 1 2 99 39 d Amniotic fluid embolism 1 2 99 40 e Retroplacental clot 1 2 99 on September 25, 2021 by guest. Protected copyright. 41 f Septic shock. 1 2 99 42 g Hypovolemic Shock 1 2 99 43 h Other (specify) 1 2 99 44 12 Complications of pre-existent diseases 1 2 99 45 a Tuberculosis 1 2 99 46 b Diabetes Mellitus 1 2 99 47 c Heart disease 1 2 99 48 d Thyroid crisis 1 2 99 49 e Chronic hypertension 1 2 99 50 f HIV infection 1 2 99 51 g Anemia 1 2 99 52 h Cervical cancer 1 2 99 53 i Ovarian cancer 1 2 99 54 j Other (specify) ______1 2 99 55 56 D33. Did the participant develop any organic dysfunctions? 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 31 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 1. No → Skip to D35 4 2. Yes → Continue to D34 5 6 D34. What were these organic dysfunctions? 7 (Information extracted from the epidemiological report, multiple responses) 8 1 Cardiovascular dysfunction 2 Respiratory dysfunction 9 3 Renal dysfunction 10 4 Coagulation/hematologic dysfunction 11 5 Hepatic dysfunction 12 6 Neurologic dysfunction 13 7 Uterine dysfunction/hysterectomy 14 8 Multiple organ dysfunction

15 About outcome of this pregnancy 16 For peer review only 17 D35. Type of pregnancy termination: 18 1 Abortion 19 i. Miscarriage 20 ii. Therapeutic iii. Unsafe 21 2 Delivery 22 3 Laparotomy for ectopic pregnancy 23 4 Still pregnant 24 D36. Date of pregnancy termination (delivery, abortion, ectopic pregnancy) __ __ / __ __ / ______Time ______(hour) 25 26 D D / M M / Y Y Y Y 27 D37. Indicate the number of hospital stay days before pregnancy termination______days 28 D38. Gestational age at delivery or abortion (including ectopic pregnancy): ______(Weeks) 29 D39. Mode of delivery or abortion 30 1 Vaginal, normal 31 a. Active management of the third stage of labor. 32 i. No http://bmjopen.bmj.com/ 33 ii. Yes 34 2 Vaginal, vacuum/forceps 35 a. Active management of the third stage of labor. 36 i. No ii. Yes 37 3 Emergency C-section 38 4 Scheduled C-section 39 5 Curettage (for a woman who had an abortion) 40

D40. Place of the delivery: on September 25, 2021 by guest. Protected copyright. 41 1. This hospital 42 2. Other hospital 43 3. Health Center 44 4. Home 45 5. Another (specify)______D41. Who attended the delivery? 46 1. Doctor 47 2. Midwifery 48 3. Another (specify)______49 50 About additional surgical treatment (s) performed during this pregnancy 51 D42. Was/were additional surgical treatment(s) performed? 52 1. No → Skip to D46 53 2. Yes → Continue to D43 54 55 56 D43. Report about additional first surgical treatment (s) performed (multiple responses): 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 32 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 1 Hysterectomy 4 2 Laparotomy 5 3 Curettage 6 4 Repair of cervical tears 5 Drainage of puerperal hematoma and repair of puerperal hematoma 7 6 Manual removal of placenta (after vaginal delivery) 8 7 Other (specify)______9 10 D44. Report about an additional second surgical treatment performed: 11 1 Hysterectomy 12 2 Laparotomy 13 3 Other (specify)______D45. Report about an additional third surgical treatment performed: 14 1 Hysterectomy 15 2 Laparotomy 16 3 AnotherFor (specify)______peer review only 17 18 About surgical treatment (s) performed during this pregnancy, indicate the diagnosis (ses) for each procedures correspondingly: 19 20 D46. Uterine curettage indication: 21 1 ______22 2 ______3 ______23 4 ______24 25 D47. Cesarean indication: 1 ______26 2 ______27 3 ______28 4 ______29 D48. Laparotomy indication: 30 1 ______31 2 ______32 3 ______http://bmjopen.bmj.com/ 33 4 ______34 5 D49. Hysterectomy indication: 35 1 ______36 2 ______37 3 ______38 4 ______39 40 About main delays (Information extracted from the epidemiological report if the participant was admitted at the Intensive Care Unit). on September 25, 2021 by guest. Protected copyright. 41 Go to the Neonatal information (Skip item D50, D51, D52 and D53) if the participant was NOT admitted at the Intensive Care Unit. 42 43 D50. Qualitative analysis of Delay I 44 1 No 45 2 Yes 46 D51. Qualitative analysis of Delay II 47 1 No 2 Yes 48 D52. Qualitative analysis of Delay III 49 1 No 50 2 Yes 51 D53. Qualitative analysis of Delay IV 52 1 No 53 2 Yes

54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 33 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 E. NEONATAL INFORMATION 4 5 This information is excluded for those women who had an abortion or an ectopic pregnancy 6 7 Number ______8 9 Baby 1 Baby 2 (if applicable) Baby 3 (if applicable) E1. Birth weight ------grams ------grams ------grams 10 11 12 E2. Age at birth ------weeks ------weeks ------weeks (according to Neonatologist) 13 1 Male 1 Male 1 Male 14 E3. Sex 2 Female 2 Female 2 Female 15 3 Ambiguous 3 Ambiguous 3 Ambiguous 16 E4. Apgar score (1 minute) For peer------review only------17 E5. Apgar score (5 minutes) ------18 19 E6. Baby outcome at birth: 1 Live birth 1 Live birth 1 Live birth 20 2 Stillborn 2 Stillborn 2 Stillborn 21 1 Stay with mom (Regular nursery) 1 Stay with mom (Regular nursery) E7. Nursery of baby 1 Stay with mom (Regular nursery) 2 Other (specify) 2 Other (specify) 22 2 Other (specify) 23 1 Breastfeeding 1 Breastfeeding 1. Breastfeeding 24 2 Formula 2 Formula 2. Formula 25 E8. Breastfeeding 3 Both 3 Both 3. Both 26 4 Another(specify) 4 Another(specify) 4. Another(specify) ______27 1 No 1. No 1. No 28 E9. Gross fetal/neonatal malformation 2 Yes 2. Yes 2. Yes 29 99 Do not know 99 Do not know 99 Do not know 1. No 1 No 30 E10. Neonatal Intensive Care Unit (NICU) 1. No 2. Yes 2 Yes Admission 2. Yes 31 32 1. ______1. ______1. ______http://bmjopen.bmj.com/ 33 2. ______2. ______2. ______E11. Indicate the diagnosis (ses) of the 34 baby for NICU admission 3. ______3. ______3. ______35 4. ______4. ______4. ______36 1. CPAP 1. CPAP 37 1. CPAP 2. Non-invasive ventilation (e.g. 2. Non-invasive ventilation (e.g. 2. Non-invasive ventilation (e.g. 38 BiPAP) BiPAP) E12. Management of the baby at NICU BiPAP) 3. Invasive mechanical ventilation 3. Invasive mechanical ventilation 39 (multiple responses) 3. Invasive mechanical ventilation 4. Inotrope or vasopressor therapy 4. Inotrope or vasopressor 40 4. Inotrope or vasopressor therapy 5. Blood transfusion therapy on September 25, 2021 by guest. Protected copyright. 5. None of the above 41 6. None of the above 5. None of the above 42 1. ______1 ______1. ______2. ______2 ______2. ______43 E13. Indicate the diagnosis (ses) of the 3. ______3 ______3. ______baby when was discharged from the 44 4. ______4 ______4. ______NICU 45 5. ______5 ______5. ______46 6. ______6 ______6. ______47 E14. Antibiotic use in NICU 1 No 1 No 1 No 48 2 Yes 2 Yes 2 Yes 49

50 E15. Days of stay at NICU ______days ______days ______days 51 52 E16. Days of stay at this hospital ______days ______days ______days 53 1. Alive 1 Alive 1. Alive 54 E17. Discharge status of baby from this 2. Dead 2 Dead 2. Dead 55 hospital (Days after birth______) (Days after birth______) (Days after birth______) 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 34 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020147 on 14 March 2018. Downloaded from

1 2 3 1. ______1 ______1 ______4 2. ______2 ______2 ______E18. Indicate the diagnosis of the baby 3. ______3 ______3 ______5 when was discharged from this 4. ______4 ______4 ______6 hospital 5. ______5 ______5 ______7 6. ______6 ______6 ______8 9 10 11 12 The End 13 Thank You!!!!!!!!!!!!!!! 14 15 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml