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Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries: Protocol for a Multi-Centre, International, Prospective Cohort Study ForJournal: peerBMJ Open review only Manuscript ID bmjopen-2019-030452
Article Type: Protocol
Date Submitted by the 14-Mar-2019 Author:
Complete List of Authors: Wright, Naomi; King's College London, King's Centre for Global Health and Health Partnerships, School of Population Health and Environmental Sciences
PAEDIATRIC SURGERY, Paediatric anaesthesia < ANAESTHETICS, Paediatric intensive & critical care < INTENSIVE & CRITICAL CARE, Keywords: NEONATOLOGY, PAEDIATRICS, Neonatal intensive & critical care < INTENSIVE & CRITICAL CARE
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1 2 3 Management and Outcomes of Congenital Anomalies in Low-, BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 Middle- and High-Income Countries: Protocol for a Multi-Centre, 6 International, Prospective Cohort Study 7 8 9 10 11 Global PaedSurg Research Collaboration 12 13 Correspondence to: Naomi J. Wright, King’s Centre for Global Health and Health Partnerships, 14 School of Population Health and Environmental Sciences, King’s College London, Denmark Hill, SE5 15 9RJ, UK. Email: [email protected] 16 17 18 For peer review only 19 ABSTRACT 20 21 Introduction 22 23 th 24 Congenital anomalies are the 5 leading cause of death in children under 5-years of age globally, contributing an estimated half a million deaths per year. Very limited literature exists from low- and 25 middle-income countries (LMICs) where most of these deaths occur. The Global PaedSurg Research 26 Collaboration aims to undertake the first multi-centre, international, prospective cohort study of a 27 selection of common congenital anomalies, comparing management and outcomes between low-, 28 middle- and high-income countries (HICs) globally. 29 30 Methods and Analysis 31 32 33 The Global PaedSurg Research Collaboration consists of surgeons, paediatricians, anaesthetists and 34 allied healthcare professionals involved in the surgical care of children globally. Collaborators will prospectively collect observational data on consecutive patients presenting for the first time, with one 35 of seven common congenital anomalies (oesophageal atresia, congenital diaphragmatic hernia, 36 intestinal atresia, gastroschisis, exomphalos, anorectal malformation and Hirschsprung's disease).
37 http://bmjopen.bmj.com/ 38 39 Data collection will be for a minimum of one month from October 2018 to April 2019 with a 30-day post-primary intervention follow-up period. Anonymous data will be collected on patient 40 demographics, clinical status, interventions and outcomes using REDCap. Collaborators will complete 41 a survey regarding the resources and facilities for neonatal and paediatric surgery at their centre. 42 43 44 The primary outcome is all-cause in-hospital mortality. Secondary outcomes include the occurrence of post-operative complications. Chi-squared analysis will be used to compare mortality between LMICs
45 on September 23, 2021 by guest. Protected copyright. and HICs. Multilevel, multivariate logistic regression analysis will be undertaken to identify patient 46 level and hospital level factors affecting outcomes with adjustment for confounding factors. 47 48 49 Ethics and Dissemination 50 51 At the host centre this study is classified as an audit not requiring ethical approval. Participating 52 collaborators must gain local approval in accordance to their institutional ethical regulations. All 53 collaborators will be encouraged to present the results locally, nationally and internationally. The 54 results will be submitted for open access publication in a peer reviewed journal. 55 56 Registration Details 57 58 This study has been registered with ClinicalTrials.Gov, identifier: NCT03666767. The registration is 59 available to view via: https://goo.gl/ffXNMH 60
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3 Strengths and Limitations of this Study BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 This will be the first large-series, geographically comprehensive, multi-centre, international, 6 prospective cohort study to define the management and outcomes of a selection of common 7 congenital anomalies in low-, middle- and high-income countries across the globe. 8 The collaborative approach for this study allows a large series of high-quality data to be collected 9 in a timely manner without overburdening high-volume, low-resource centres. 10 11 The seven study conditions constitute a selection of the commonest life-threatening congenital 12 anomalies requiring emergency surgical care in the neonatal period (Box 1). 13 We recognise that some children may not reach a facility capable of providing acute paediatric 14 surgical care and hence the results obtained may be an underestimation of true morbidity and 15 mortality, especially in LMICs. 16 This study will only report on acute management and outcomes as follow up will be limited to 30- 17 days post-primary intervention. 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44
45 on September 23, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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3 INTRODUCTION BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 In 2015, the Global Burden of Disease study concluded congenital anomalies to be the 5th leading 6 cause of death in children under 5-years of age globally.1 This equates to approximately half a million 7 deaths from congenital anomalies each year, 97% of which occur in low- and middle-income countries 8 (LMICs) where the incidence and prevalence is higher compared to high-income countries (HICs).2,3 9 Indeed, this is likely to be an underestimation of the actual number of deaths due to under-diagnosis 10 of neonates with congenital anomalies who die in the community and a lack of death certification in 11 many LMICs.4 There is limited research and a lack of congenital anomaly registries in LMICs and 12 hence they have received very little global attention.5 13 14 The conditions forming the focus of this study (Box 1) constitute a selection of the most common life- 15 threatening congenital anomalies, which involve the gastrointestinal tract. They each have an 16 incidence of 1/2000 – 1/5000, they collectively form up to 40% of emergency neonatal surgery and 17 associated mortality can be in excess of 50% in many LMICs.6-9 Disparities in outcomes globally can 18 be stark; for exampleFor the mortality peer from gastroschisis review is 75-100% only in many LMICs compared to 4% or 12-14 19 less in HICs. Reasons for poor outcomes include a lack of antenatal diagnosis, delayed 20 presentation, limited neonatal transport and in-hospital resources, a dearth of trained support 9,15,16 21 personnel and a lack of intensive care and parenteral nutrition for neonates. In Uganda, it was 8 22 calculated that only 3.5% of the need for neonatal surgery was met by the healthcare system. 23 24 25 Box 1. Congenital Anomalies in the Global PaedSurg Study 26 27 Oesophageal atresia (OA) +/- tracheo-oesophageal fistula (TOF) 28 Congenital diaphragmatic hernia (CDH) 29 Intestinal atresia (IA) 30 Gastroschisis 31 Exomphalos 32 Anorectal malformation (ARM) 33 Hirschsprung’s disease 34 35 36
37 In 2010, the World Health Assembly passed a resolution recommending ‘prevention whenever http://bmjopen.bmj.com/ 38 possible, to implement screening programmes and to provide care and ongoing support to children 39 with birth defects and their families’.2 Prevention is paramount, however this is not yet possible for 40 many congenital anomalies and hence a focus on improving postnatal care and outcomes is vital. The 41 Sustainable Development Goal 3.2 aims to end preventable deaths of newborns and children under 6, 10,11 42 the age of 5-years by 2030. With a third of infant deaths being attributed to congenital 43 anomalies, clearly this will not be achievable without an accelerated effort towards the provision of 44 surgical care for children. It is estimated that two-thirds of deaths and disability from congenital anomalies can be avoided with the provision of neonatal and paediatric surgical care.6 Indeed, studies
45 on September 23, 2021 by guest. Protected copyright. have demonstrated such provision can be highly cost-effective in terms of disability adjusted life years 46 saved.5 Yet neonatal and paediatric surgical care remain a low priority on the global health agenda.5 47 48 A shift is needed to focus on the provision of surgical care for children within National Health Plans 49 and International Organisations and to elevate congenital anomalies on the global health agenda. 50 This large-scale, geographically comprehensive, multi-centre prospective cohort study aims to define 51 the current management and outcomes of a selection of common congenital anomalies globally and 52 identify factors affecting outcomes that can be modified to improve care. This is vital to aid advocacy 53 and global health prioritisation and inform future interventional studies aimed at improving outcomes. 54 55 56 AIM 57 58 To undertake the first large-scale, geographically comprehensive multi-centre, prospective cohort 59 study comparing the management and outcomes of a selection of common congenital anomalies in 60 low-, middle-, and high-income countries across the globe.
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3 OBJECTIVES BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 1. To compare the mortality and post-intervention complications of a selection of common congenital 6 anomalies in LMICs and HICs globally. 7 8 2. To identify patient level and hospital level factors affecting outcomes that be modified to improve 9 care. 10 11 3. To establish a research collaboration consisting of children’s surgical care providers across the 12 world to help enhance research capacity and to create a platform for ongoing collaborative research 13 and intervention studies aimed at improving outcomes. 14 15 4. To raise awareness and provide advocacy for neonatal and paediatric surgical care within global 16 health prioritisation, planning, policy and funding. 17 18 For peer review only 19 20 21 METHODS AND ANALYSIS 22 Study Design 23 24 This is an international, multi-centre, prospective observational cohort study. The Global PaedSurg 25 Research Collaboration consisting of children’s surgical care providers (collaborators) across the 26 world was established from November 2017 to facilitate data collection and continues to grow. 27 Collaborators are free to choose one or more months between 1st October 2018 to the 30th April 2019 28 (inclusive) to recruit consecutive patients to the study, with a 30-day post-primary intervention follow 29 up period. 30 31 Collaborators 32 33 International collaborators will have a variety of roles and responsibilities within the study. Local 34 collaborators will establish mini-teams locally, gain study approval, utilise the protocol criteria to 35 appropriately identify patients for study inclusion, collect prospective data and upload it to REDCap. 36 Each hospital will have a local study lead who will hold overall responsibility for ensuring the data is
37 accurate, complete and without duplications. Country-lead collaborators will help to recruit other http://bmjopen.bmj.com/ 38 collaborators from within their country and provide advice and support regarding gaining local study 39 approval and data collection. They may also help with translation of the study literature to the local 40 language if required. Continent and regional leads will help to recruit country leads, provide them with 41 advice regarding the study and also encourage and co-ordinate presentations of the protocol at 42 national and international meetings. Lead investigators will contribute to the study design through the 43 provision of feedback from the pilot studies undertaken in multiple languages. An organising 44 committee will help to co-ordinate all study activities and a steering committee will provide guidance throughout.
45 on September 23, 2021 by guest. Protected copyright. 46 47 There are a number of benefits for collaborators participating the study. Publishing journal(s) will be asked to make all collaborators PubMed citable co-authors. This is based on an equal partnership 48 model described by the Lancet and is used by a number of national and international collaboratives.17- 49 21 All collaborators will be listed as an author on resulting presentations. Collaborators will have the 50 opportunity to present the study locally, nationally and internationally, initially the study protocol and 51 later the results. This often provides collaborators, especially those who are junior or from LMICs, the 52 opportunity to apply for funding to attend, present and network at such meetings. Participation in the 53 study provides an easy route and insight into clinical research, which can be further established 54 through participation in the 2-year Research Training Fellowship which is running alongside the main 55 study free of charge for all interested collaborators. 56 57 Sample Selection 58 59 Collaborator and Hospital Inclusion Criteria: 60
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3 All hospitals and healthcare professionals providing surgical care for neonates and children, BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 presenting for the first time, with one or more of the study conditions can be included in the study. 5 Collaborators should gain permission from the senior surgeon or physician who oversees the care of 6 the children to be included in the study in order to participate. There can be up to three collaborators 7 in a mini-team per month of data collection. One mini-team can collect data over one or more months 8 or several mini-teams can collect data over a different month each. Each mini-team must contain at 9 least one senior surgeon or physician to oversee the data collection process. 10 11 Patient Inclusion and Exclusion Criteria: 12 13 Any neonate, infant or child under the age of 16-years, presenting acutely for the first time, with one 14 or more of the study conditions can be included in the study. Patients who have previously received 15 surgery for their presenting condition or those representing with a complication of surgery are 16 excluded. Patients presenting electively for surgery are excluded. Children who have received basic 17 resuscitative care for their condition at a different healthcare facility and are then transferred to the 18 study centre can be included.For Childrenpeer who onlyreview receive resuscitative only treatment at the study centre 19 and then are referred elsewhere for surgical care cannot be included since the outcome of the 20 surgical care will not be known and also to avoid the risk of duplicate patients in the study. Patients 21 who receive conservative treatment, palliative care, or no care must be included within the study to 22 reflect true outcomes. 23 24 If a patient presents with more than one of the study conditions, the details of each condition that they 25 present acutely with can be included, but not a previously managed condition. For example, a 26 newborn presenting with oesophageal atresia and anorectal malformation would have both conditions 27 included. A patient presenting for the first time with Hirschsprung’s disease at several months of age 28 who had a duodenal atresia repaired at birth would have the full details of the Hirschsprungs disease 29 included, but the duodenal atresia would simply be noted as an associated anomaly. 30 31 Outcome Measures 32 33 The primary outcome is all-cause, in-hospital mortality. 34 35 For patient’s hospitalised for over 30-days following primary intervention, a 30-day post-primary 36 intervention mortality rate will be utilised. Those who do not receive a primary intervention, but remain alive and hospitalised at 30-days following primary admission, will have this time point used for 37 http://bmjopen.bmj.com/ 38 recording their mortality status for the primary outcome. Primary outcome is defined in Table 1. 39 40 The secondary outcomes are the complications occurring within 30-days of primary intervention: 41 42 Surgical site-infection 43 Wound dehiscence 44 Need for re-intervention
45 Condition specific complications on September 23, 2021 by guest. Protected copyright. 46 Condition specific outcome variables 47 Length of hospital stay or time from admission to death in patients who do not survive 48 30-day post primary intervention mortality. 49 50 Secondary outcomes will not be collected on patients who do not receive a primary intervention within 51 30-days of hospital admission, with the exception of length of hospital stay or time from admission to 52 death. 30-day follow-up will be undertaken within the capacity of the collaborating team; no additional 53 funding will be provided. 54 55 Data Collection 56 57 Generic variables relating to the patient demographics, antenatal care, pre-hospital care, clinical 58 condition, surgical intervention and outcomes will be collected for all patients in the study (Table 1). 59 Specific variables will be collected for each individual condition (Supplementary File 1). 60
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3 Outcomes and variables have been chosen using published core outcome sets and commonly BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 collected outcomes in systematic reviews and meta-analyses.22-37 Collaborators will enter anonymous 5 data via the secure internet-based Research Electronic Data Capture (REDCap) system. This will be 6 stored on King’s College London REDCap server. No individual collaborator, institution or country will 7 be independently identifiable in the presented or published results. 8 9 A short survey will be completed by the local study lead and one other collaborating consultant or 10 registrar on the resources and facilities available for neonatal and paediatric surgical care at their 11 centre (Supplementary File 2). 12 13 14 Table 1. Generic Data Points 15 16 Generic questions Answers 17 During which month did the patient present to Please select the month that the patient presented to your hospital for the first time with this 18 your hospital? For peercongenital anomaly. review For example, if a babyonly was born with gastroschisis on the 29th September 19 and presented to your hospital on the 1st October you should select October. Has consent been provided to include this Yes / No / Patient consent is not required for this study at my institution 20 patient in the study? 21 If no, which condition did the patient present Oesophageal atresia / Congenital diaphragmatic hernia / Intestinal atresia / Gastroschisis / 22 with? Exomphalos / Omphalocele / Anorectal malformation / Hirschsprung's Disease. Please select all the conditions that the patient presented with. Do not select a condition which 23 the patient has already received surgical treatment for previously. 24 Demographics 25 Gestational age at birth Number of weeks from the first day of the women's last menstrual cycle until birth. Round up or 26 down to the nearest week. Age at presentation (in hours) We understand this information may be difficult to obtain - please be as accurate as you can. 27 Please round to the nearest hour. This number may be very large for patients who have a 28 delayed presentation - please still enter it. For neonates born within your centre please enter 0. 29 Enter unknown if unknown. Gender Male / Female/ Ambiguous/ Unknown 30 Weight at presentation In kilograms (kg) on the day of presentation. Please provide a value to 1 decimal place. 31 Does the patient have another anomaly in Yes, Cardiovascular, Yes, Respiratory, Yes: Gastrointestinal, Yes: Neurological, Yes: Genito- 32 addition to the study condition? urinary, Yes: Musculoskeletal, Yes: Down syndrome, Yes: Beckwith-Wiedemann syndrome, Yes: 33 Cystic fibrosis, Yes: Chromosomal, Yes: Other, No Select all that apply. Include all anomalies diagnosed at any stage up until 30-days post primary 34 intervention or 30-days following presentation for those who didn't receive an intervention. If you 35 suspect an associated anomaly, but it has yet to be diagnosed, select 'other'. 36 Distance from the patient's home to your In kilometres (km). Please round to the nearest kilometre. Please enter 0 if born in your hospital. hospital
37 http://bmjopen.bmj.com/ Antenatal Care and Delivery 38 Antenatal ultrasound undertaken? Yes: study condition diagnosed, Yes: problem identified but study condition not diagnosed, Yes: 39 no problem identified, No 40 If the condition was diagnosed antenatally, at Please round up to the nearest week. If the patient has more than one study condition, please what gestational age? note the gestational age at which one or more of the conditions was first diagnosed. 41 Mode of transport to hospital? Ambulance, Other transport provided by the health service, Patient's own transport, Born within 42 the hospital 43 Where did the patient present from? If other, Home / Community Clinic / General Practice / District Hospital / Other / Unknown 44 please specify. District hospital includes: secondary level healthcare, provincial hospital, general hospital, general mission hospital or regional hospital. It has general anaesthesia and can provide general
45 surgical care. on September 23, 2021 by guest. Protected copyright. 46 Type of delivery: Vaginal (spontaneous), Vaginal (induced), Caesarean section (elective), Caesarean section 47 (urgent/non-elective), Unknown. Vaginal delivery includes those requiring forceps and ventouse. Clinical condition and patient care 48 Was the patient septic on arrival? Yes, no 49 Sepsis is SIRS (Systemic Inflammatory Response Syndrome) with a suspected or confirmed 50 bacterial, viral, or fungal cause. SIRS is a response to a stimulus, which results in two or more of 51 the following: temperature > 38.5°C or < 36°C, tachycardia*, bradycardia* in children < 1 year old, tachypnoea*, leukopenia or leucocytosis*, hyperglycaemia*, altered mental status, 52 hyperlactaemia*, increased central capillary refill time >2 seconds. *Variables are defined as 53 values outside the normal range for age. Arrival is the time of birth for neonates born at your 54 hospital. If yes, were appropriate antibiotics Yes: within 1 hour of arrival, Yes: within the first day of arrival, No 55 administered? Appropriate antibiotics are defined as either broad spectrum covering gram negative, gram 56 positive and anaerobic bacteria OR antibiotics that are the standard empirical treatment for that 57 condition according to local guidelines OR are based on sensitivities provided by a microbiology sample. 58 Was the patient hypovolaemic on arrival? Yes/ No. Criteria for diagnosis include at least one of the following: prolonged central capillary 59 refill time > 2 seconds, *tachycardia, mottled skin, *reduced urine output, cyanosis, impaired 60 consciousness, *hypotension. *Variables are defined as values outside the normal range for age.
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3 If yes, was an intravenous fluid bolus given? Yes: within 1 hour of arrival, Yes: on the first day of arrival, No BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 If yes, how much intravenous fluid was given? 10 - 20mls/ kg, above 20mls/ kg 5 If less than 10mls/ kg was given please select 'no' for the question asking if intravenous fluid was given. 6 Was the patient hypothermic on arrival? Yes/ No. Defined as < 36.5 degrees Celsius core temperature. Arrival is the time of birth for 7 neonates born at your hospital. 8 If yes, was the patient warmed on arrival to Yes/ No. Only select yes if warming was commenced within 1 hour of arrival. Arrival is the time of within a normal temperature range? birth for neonates born at your hospital. 9 Did the patient receive central venous access? Yes: umbilical catheter, Yes: peripherally inserted central catheter (PICC), Yes: percutaneously 10 inserted central line with ultrasound guidance, Yes: surgically placed central line (open insertion), 11 No. Please select all that the patient received within 30-days of primary intervention or 30-days of 12 presentation if no intervention was undertaken. 13 If yes, did the patient acquire central line Yes: diagnosed clinically, Yes: confirmed on microbiology, No 14 sepsis? Within 30-days of primary intervention or 30-days of presentation if no intervention was 15 undertaken. Time from arrival at your hospital to primary (enter 0 if no intervention was undertaken) 16 intervention in hours Primary intervention for each condition is defined as: Oesophageal atresia; surgery, either 17 temporising or definitive, to manage the oesophageal atresia and/ or tracheo-oesophageal 18 For peerfistula. Congenital review diaphragmatic hernia only; surgery to reduce the hernia and close the defect. Intestinal atresia; surgery, either temporising or definitive, to manage the obstruction including 19 stoma formation and primary anastomosis. Gastroschisis; any procedure to either cover or 20 reduce the bowel and/ or close the defect. This includes application of a silo (regardless of 21 whether or not they go on to require surgery). It excludes initial covering of the bowel in a plastic covering (bag or cling film) prior to intervention. Exomphalos; surgery or application of topical 22 treatment to the sac in patients managed conservatively (regardless of whether or not they go on 23 to require surgery). Hirschsprung's disease; surgery, either temporising or definitive, or rectal/ 24 distal bowel irrigation, laxatives or digital stimulation in patients managed conservatively. This 25 does not include pre-operative washouts in patients planned to have surgery. Anorectal malformation; surgery, either temporising or definitive, or anal/ fistula dilatation in patients with a 26 low anorectal malformation managed conservatively. 27 American Society of Anesthesiologists (ASA) 1. Healthy person, 2. Mild systemic disease, 3. Severe systemic disease, 4. Severe systemic 28 Score at the time of primary intervention disease that is a constant threat to life, 5. A moribund patient who is not expected to survive without the operation, Not applicable - no intervention 29 What type of anaesthesia was used for the General anaesthesia with endotracheal tube, General anaesthesia with laryngeal airway, 30 primary intervention? Ketamine anaesthesia, Spinal/ caudal anaesthesia, Local anaesthesia only, No anaesthesia/ just 31 analgesia, No anaesthesia/ no analgesia, Not applicable: no surgery or intervention undertaken. 32 Who undertook the anaesthetic for the primary Anaesthetic doctor, Anaesthetic nurse, Medical officer, Surgeon, Other healthcare professional, intervention? No anaesthetic undertaken 33 If more than one of these personnel were present please select the most senior. 34 Who undertook the primary intervention? Paediatric surgeon (or junior with paediatric surgeon assisting/ in the room), General surgeon (or 35 junior with paediatric surgeon assisting/ in the room), Junior doctor, medical officer or other (without a paediatric or general surgeon assisting/ in the room), Trainee surgeon (without a 36 paediatric or general surgeon assisting or in the room), Not applicable - no surgery or primary
37 intervention undertaken. http://bmjopen.bmj.com/ 38 Was a Surgical Safety Checklist used at the Yes, No: but it was available, No: it was not available, Not applicable: a conservative primary 39 time of primary intervention? intervention was undertaken, Not applicable: no surgery or primary intervention undertaken Total duration of antibiotics following primary In days (including the day of surgery and the day antibiotics were stopped. Include intravenous 40 intervention and oral antibiotics). 41 Did the patient receive a blood transfusion? Yes: not cross-matched, Yes: cross-matched, No: not required, No: it was required but not 42 available. Within 30-days of primary intervention or 30-days of presentation if no intervention was 43 undertaken. Did the patient require ventilation? Yes: and it was given, Yes: but it was not available, No 44 Within 30-days of primary intervention or 30-days of presentation if no intervention was undertaken. Please include all types of ventilation. 45 on September 23, 2021 by guest. Protected copyright. 46 If yes, for how long did the patient remain on In days (include all days on ventilation within 30-days of primary intervention or 30-days of ventilation? presentation if no intervention was undertaken). 47 Time to first enteral feed (post-primary In days (include the day of primary intervention and the day of first enteral feed in the 48 intervention) calculation). Enter 0 if enteral feeds were not commenced. Enter 999 if feeds were not stopped, 49 for example in patients with Hirschsprung's Disease managed conservatively. Include all types of 50 enteral feeding - oral, nasogastric, gastrostomy and other. Time to full enteral feeds (post-primary In days (enter 0 if the patient died before reaching full enteral feeds or 30 if the patient had not 51 intervention) reached full enteral feeds at 30-days post primary intervention or 30-days following admission in 52 patients who did not receive a primary intervention). Include all types of enteral feeding - oral, 53 nasogastric, gastrostomy and other. Did the patient require parenteral nutrition? Yes and it was given, Yes and it was sometimes available but less than required, Yes but it was 54 not available, No 55 If yes, for how long did the patient receive In days. Include all days that the patient received parenteral nutrition (any volume) up until 30- 56 parenteral nutrition? days post primary intervention or 30-days following presentation in patients who do not receive an intervention. 57 Outcomes 58 Did the patient survive to discharge? Yes/ No 59 Select yes if the patient was still alive in your hospital 30-days after primary intervention or 30- 60 days after presentation in patients who do not receive a primary intervention.
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3 If the patient was discharged prior, were they Yes, No: not followed-up after discharge, Followed-up but not until 30-days post primary BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 still alive at 30-days following primary intervention 5 intervention? This can include all reliable communication with the patient/ patient's family including in person, via telephone and other. 6 If no, cause of death? Sepsis, Aspiration pneumonia, Respiratory failure, Cardiac failure, Malnutrition, Electrolyte 7 disturbance, Haemorrhage, Lack of intravenous access, Hypoglycaemia, Recurrent tracheo- 8 oesophageal fistula, Recurrent diaphragmatic hernia, Anastomotic leak, Ischaemic bowel, Ruptured exomphalos sac, Enterocolitis, Other. If other, please specify 9 Duration of hospital stay (days) Please include the day of admission and the day of discharge in your calculation. For example, if 10 a patient presented on 1st October and was discharged on the 5th October, their duration of 11 hospital stay would be 5 days. If the patient died, please record the number of days from admission to death. Only include the duration of the primary admission, not subsequent 12 admissions if the patient re-presented. 13 Did the patient have a surgical site infection? Yes, No, Not applicable: no surgical wound 14 This is defined as one or more of the following within 30-days of surgery: 1) purulent drainage 15 from the superficial or deep (fascia or muscle) incision, but not within the organ/ space component of the surgical site OR 2) at least two of: pain or tenderness; localised swelling; 16 redness; heat; fever; AND the incision is opened deliberately to manage infection, spontaneously 17 dehisces or the clinician diagnoses a SSI (negative culture swab excludes this criterion) OR 3) 18 For peerthere is an abscess review within the wound (clinically only or radiologically detected). Did the patient have a full thickness wound Yes, No, Not applicable - no surgical wound. 19 dehiscence? This is defined as all layers of the wound opening within 30-days of surgery 20 Did the patient require a further unplanned Yes - percutaneous intervention, Yes - surgical intervention, No, Not applicable - no primary 21 intervention? intervention undertaken. Within 30-days of primary intervention. This does not include routine 22 reduction and closure of the defect in neonates with gastroschisis receiving a preformed silo. Was the patient followed up at 30-days post Yes: reviewed in person, Yes: via telephone consultation, Yes: via other means, Yes: still an in- 23 primary surgery or intervention to assess for patient at 30-days, No: data is based on in-patient observations only, No: follow-up was done but 24 complications? prior to 30-days 25 If the patient had a complication, when was it During the primary admission, As an emergency re-attender, At routine follow-up as an out- diagnosed? patient, Not applicable: no complications 26 What study condition does this patient have? Oesophageal atresia, Congenital diaphragmatic hernia, Intestinal atresia, Gastroschisis, 27 Exomphalos/ Omphalocele, Anorectal malformation, Hirschsprung's Disease 28 If the patient has presented for the first time with more than one of these conditions please select 29 all that apply. If the patient presented on this occasion with one of these conditions, but previously had another condition managed then only select the condition they are presenting with 30 on this occasion and enter that they have another anomaly in the demographics section above. 31 For example, if the patient presents at 2-months with Hirschsprung's disease, but previously had 32 a duodenal atresia repair please select Hirschsprung's disease here (not intestinal atresia) and tick in the section above that they have another gastrointestinal anomaly. 33 34 35 Data Quality 36
37 To ensure high quality of data, a detailed protocol for collaborators has been produced and published http://bmjopen.bmj.com/ 38 on the study website (www.globalpaedsurg.com) in 12 languages: English, French, Spanish, 39 Portuguese, German, Italian, Chinese, Arabic, Korean, Lithuanian, Turkish and Russian. Clear and 40 concise definitions have been provided for all data points on the protocol, on the data collection forms 41 and within REDCap when entering the data. A study launch meeting was undertaken where the 42 principal investigator presented the data collection process in detail, demonstrated use of REDCap 43 and answered questions. This was recorded, circulated to all collaborators via email and placed on 44 the website. A frequently asked questions document has been circulated via email and placed on the website. A two separate meetings were held by the principal investigator to detail the study, data
45 on September 23, 2021 by guest. Protected copyright. 46 collection process and answer questions amongst the country leads so they in turn can provide 47 advice and support to local collaborators within their country. Again this was recorded, circulated and 48 placed on the website. 49 A pilot study of the patient data collection form and institutional survey was undertaken by lead 50 investigators to optimise the study design and to address any feasibility or other barriers to effective 51 data collection and study completion across participating sites. The pilot study commenced on 1st 52 August 2018 for 30 days in English, Spanish and French by 41 collaborator colleagues. The data 53 collection forms were amended following feedback to clarify terminology, add important missing 54 variables or descriptions and correct any translation errors. All translated data collection forms, 55 REDCap and study documentation has been checked and verified by a native speaker for accuracy. 56 57 Data Validation 58 59 Ten percent of collaborating centres will be selected at random for data validation by an independent 60 research collaborator. The aim will be to determine the numbers of patients eligible during the data
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3 collection period to check if any were missed and collect a selection of data again to cross-check for BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 accuracy. Validating questions have been built into the data collection tool. At least 90% of primary 5 and secondary outcomes must be completed for each patient. All collaborators within validating 6 centres will be asked to complete a brief survey regarding their experience with data collection to 7 identify any potential areas for error and to aid with data interpretation. 8 9 Sample Size Calculation 10 11 A sample size calculation was undertaken using Stata/IC 15.0 based on Bonferroni correction for 12 multiple testing, assuming 80% power and an overall type 1 error of 5%. The required sample size for 13 each condition has been calculated for the primary outcome of mortality in LMICs compared to HICs 14 and also low, middle and high-income countries separately (Table 2). Mortality estimations are based 15 on pooled data from published studies on these conditions in low-, middle- and high-income countries 16 respectively. 17 Based on the patient numbers included in the previously undertaken PaedSurg Africa study, which 18 utilised a similar studyFor design, thepeer estimated reviewsample sizes to detect only a significant difference between 19 LMICs and HICs in this study are achievable.13 20 21 Table 2. Estimated mortality and sample sizes for low, middle and high-income countries and 22 the mean number of cases per month per institution globally 23 24 Condition Mortality LIC Mortality MIC Mortality Mortality Sample Sample Sample Sample Mean no. 25 (%, n) (%, n) LMIC HIC size for size for size for size for cases/ month/ 26 combined (%, n) LIC MIC HIC LMIC vs institution 27 (%, n) HIC (per (L,M&HIC group) combined) 28 OA +/- TOF 79.5% 41.8% 43.7% 2.7% 34 34 23 21 1.02 29 (62/78) (623/1488) (685/1566) (6/221) 30 CDH - 47.4% 47.4% 20.4% - - - 63 0.54 31 (130/274) (130/274) (201/982) IA 42.9% 40.0% 41.0% 2.9% 6014 6014 25 24 0.63 32 (42/98) (97/241) (139/339) (12/407) 33 Gastroschisis 83.1% 42.6% 56.6% 3.7% 29 29 24 15 0.85 34 (211/254) (205/481) (416/735) (28/748) Exomphalos 25.5% 31.9% 30.1% 12.7% 1040 1040 196 115 0.63 35 (41/161) (132/414) (173/575) (40/316) 36 ARM 26.3% 17.5% 18.1% 3% 460 460 90 85 1.34 (26/99) (243/1391) (269/1490) (14/462) 37 http://bmjopen.bmj.com/ 38 Hirschsprung’s 19.1% 16.8% 17.6% 2.3% 5802 5802 85 79 2.21 39 Disease (33/173) (55/328) (88/501) (43/1897) 40 41 Estimated Study Population 42 43 The mean number of cases presenting to an institution per month for each study condition was 44 estimated from published studies across all income settings (Table 2). On average most institutions
45 caring for patients with these conditions receive 1-2 new cases per month; each participating on September 23, 2021 by guest. Protected copyright. 46 institution would expect approximately 7-14 new cases in the study per month although this can vary. 47 The aim is to include a minimum of 365 months of data; 183 months from LMICs and 183 months 48 from HICs. This should ensure enough cases of exomphalos to determine a significant difference 49 between LMICs and HICs; fewer months of data are required to determine significant differences 50 between other study conditions. An up-to-date total of patient numbers within the study will be 51 maintained on the study website. 52 53 54 Data Analysis 55 Patient and Institutional Data: 56 57 Data will be analysed using Stata and SAS 9.4 (Cary, NC; USA). Missing data for the covariates will 58 be analysed to determine whether it is related to the outcome and either complete-case analyses or 59 multiple imputation techniques will be used for analyses accordingly. 60
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3 Significant differences in mortality between LMICs and HICs will be determined for each of the study BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 conditions using Chi-squared analysis, or Fischer’s exact test if either group contains less than 10 5 patients. World Bank classification of low-, middle- and high-income countries during the fiscal year 6 2018 will be used.38 7 8 Univariate logistic regression analyses will be conducted between covariates and the primary 9 outcome of mortality. Based on the results, covariates with a p-value of <0.10 will be included in the 10 multivariate model. The final multi-level multivariate logistic model will be determined using stepwise 11 backward elimination to interventions and peri-operative factors affecting outcomes. Data will be 12 adjusted for confounding factors and effect modifiers. Potential confounders include: gestation age at 13 birth, weight, time from birth to presentation and ASA score at the time of primary intervention. 14 Potential effect modifiers include: administration of peri-operative antibiotics, fluid resuscitation, 15 thermal control and provision of other condition specific neonatal care such as parenteral nutrition in 16 neonates with gastroschisis. 17 Multi-level multivariate logistic regression analysis will also be undertaken to identify institutional 18 factors affecting mortalityFor with adjustmentpeer for review confounders. P< 0.05only will be deemed significant. 19 20 Data Validation: 21 22 A weighted kappa statistic will be utilised to determine the level of agreement between the patient 23 data in the main study and validation data. A weighted kappa statistic will be also utilised to determine 24 the level of agreement between institutional surveys independently completed by the local study lead 25 and one other consultant or registrar at each participating centre. Results will be presented as a 26 proportion of agreement for each variable being validated. 27 28 29 Patient and Public Involvement 30 31 CDH UK, a patient and family advisory group and charity, provided input into the design of the study 32 protocol and data collection tool. Their input will be sought on the findings and dissemination of the 33 results. 34 35 ETHICS AND DISSEMINATION 36
37 Research Ethics Approval http://bmjopen.bmj.com/ 38 39 The study has been classified as an audit at the host institution and hence did not require ethical 40 approval. The study fulfils the audit criteria as follows: 1) All data collected measures current practice. 41 The study does not involve any changes to patient management; 2) Current practice and outcomes in 42 low, middle and high-income countries will be compared to published standards in the literature. 43 Table 2 details the current mortality standards for each of the seven study conditions in high-income 44 countries; 3) All the study data is routinely collected information which should be known to the study
45 team without asking additional questions to the patients/parents; 4) All data to be entered into on September 23, 2021 by guest. Protected copyright. 46 REDCap is entirely anonymous; 5) No individual patient, collaborator, institution or country will be 47 independently identifiable in the study results; 6) All data will be stored securely and will be governed 48 by King’s College London data protection team. Research collaborators will be required to gain 49 approval for the study at their institution according to local ethical regulations. 50 51 Study Dissemination 52 53 The study concept and design will be presented at international conferences in order to recruit 54 collaborators. Following completion, the results will be presented at local, national and international 55 conferences globally. Both the promotional presentations of the study protocol and the study results 56 will be presented by study collaborators of all levels of training, disciplines and regions of the world. 57 The results will be submitted for open access publication in a peer reviewed journal. Following 58 publication, the full anonymous, de-identified dataset will be made publicly available via an online repository. Collaborators will have the opportunity to undertake sub-analyses of the data for their 59 country (if all collaborators from that country agree), region or continent. 60
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3 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 DISCUSSION 6 7 This study aims to define, for the first time, the management and outcomes of a selection of common 8 life-threatening congenital anomalies across the globe. This will help to raise awareness of the 9 unacceptable disparities in outcomes between low-, middle- and high-income countries and the need 10 to focus on improving access to quality surgical care for neonates with congenital anomalies within 11 national health plans and global health prioritisation. It is hoped that factors affecting mortality and 12 morbidity will be identified that can be modified to improve care. Establishment of the Global 13 PaedSurg Research Collaboration developed during this study will create a platform for ongoing 14 collaborative work and interventional studies aimed at improving outcomes in the future. 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44
45 on September 23, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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3 ADDITIONAL INFORMATION BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 Twitter: @GlobalPaedSurg 6 7 Website: http://globalpaedsurg.com 8 9 Author Contributions: The principal investigator conceived the idea for the study, gained study 10 funding, wrote the study protocol, designed the data collection tools, established the study team, co- 11 ordinated the pilot study, revised the study design/ data collection tools following feedback and made 12 critical revisions to the manuscript for publication. The steering committee contributed critical input 13 and revisions to the funding application, study design, protocol and manuscript for publication. The 14 writing committee drafted the protocol manuscript for publication and contributed as organising 15 committee members. The organising committee assisted in the recruitment of and communication 16 with collaborators to participate in the pilot study, helped to co-ordinate the pilot study and summarise 17 the feedback, made critical revisions to the data collection tools in multiple languages and contributed 18 to the study design. TheFor lead investigators peer contributed review to the study only design and content of the data 19 collection forms through feedback following participation in the pilot study. All contributed to the 20 content of this manuscript. 21 22 Funding Statement: Naomi Wright, Principal Investigator, is funded by the Wellcome Trust through a 23 Clinical PhD in Global Health undertaken at King’s College London (Funder Reference: 24 203905/Z/16/Z). The Wellcome Trust had no input into the study protocol other than to recommend 25 open-access publication in a peer-reviewed journal and to make the anonymised dataset publicly 26 available. Nick Sevdalis’ (NS) research is supported by the National Institute for Health Research 27 (NIHR) Collaboration for Leadership in Applied Health Research and Care South London at King’s 28 College Hospital NHS Foundation Trust. NS is a member of King’s Improvement Science, which is 29 part of the NIHR CLAHRC South London and comprises a specialist team of improvement scientists 30 and senior researchers based at King’s College London. Its work is funded by King’s Health Partners 31 (Guy’s and St Thomas’ NHS Foundation Trust, King’s College Hospital NHS Foundation Trust, King’s 32 College London and South London and Maudsley NHS Foundation Trust), Guy’s and St Thomas’ Charity, the Maudsley Charity and the Health Foundation. NS and Andrew Leather are also supported 33 by the NIHR Global Health Research Unit on Health System Strengthening in Sub-Saharan Africa, 34 King’s College London (GHRU 16/136/54) and by the ASPIRES research programme in LMICs 35 (Antibiotic use across Surgical Pathways - Investigating, Redesigning and Evaluating Systems), 36 funded by the Economic and Social Research Council. The views expressed are those of the authors
37 and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. http://bmjopen.bmj.com/ 38 39 40 Competing Interest’s Statement: Nick Sevdalis is the director of the London Safety and Training 41 Solutions Ltd, which offers training in patient safety, implementation solutions and human factors to 42 healthcare organisations. No other conflicts of interest are declared. 43 44 Patient Consent: Collaborators must follow their local ethical guidelines regarding patient consent.
45 on September 23, 2021 by guest. Protected copyright. 46 47 Ethics Approval: This study has been classified as a clinical audit with written confirmation from King’s College London Ethics Committee that it does not therefore require ethical approval. All 48 participating centres must gain local study approval to participate according to their institutional ethical 49 regulations. 50 51 52 Provenance and Peer Review: Not commissioned; externally peer reviewed. 53 54 Open Access: This is an Open Access article distributed in accordance with the terms of the Creative 55 Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build 56 upon this work, for commercial use, provided the original work is properly cited. 57 Licence Statement: I, the Submitting Author has the right to grant and does grant on behalf of all 58 authors of the Work (as defined in the below author licence), an exclusive licence and/or a non- 59 exclusive licence for contributions from authors who are: i) UK Crown employees; ii) where BMJ has 60
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3 agreed a CC-BY licence shall apply, and/or iii) in accordance with the terms applicable for US Federal BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Government officers or employees acting as part of their official duties; on a worldwide, perpetual, 5 irrevocable, royalty-free basis to BMJ Publishing Group Ltd (“BMJ”) its licensees and where the 6 relevant Journal is co-owned by BMJ to the co-owners of the Journal, to publish the Work in BMJ 7 Open and any other BMJ products and to exploit all rights, as set out in our licence. 8 9 The Submitting Author accepts and understands that any supply made under these terms is made by 10 BMJ to the Submitting Author unless you are acting as an employee on behalf of your employer or a 11 postgraduate student of an affiliated institution which is paying any applicable article publishing 12 charge (“APC”) for Open Access articles. Where the Submitting Author wishes to make the Work 13 available on an Open Access basis (and intends to pay the relevant APC), the terms of reuse of such 14 Open Access shall be governed by a Creative Commons licence – details of these licences and 15 which Creative Commons licence will apply to this Work are set out in our licence referred to above. 16 17 Acknowledgements: Thank you to Bolaji Coker for the REDCap administration and management. 18 Thank you to BeverleyFor Power (CDHpeer UK) for representingreview patients, only parents and families through your 19 feedback on the study design during the pilot study. Thank you to Xiya Ma and Dylan Goh for helping 20 with the Chinese translation of study documentation. 21 22 23 COLLABORATORS 24 25 26 Principal Investigator: Naomi Wright (King’s College London, UK) 27 28 Steering Committee: Niyi Ade-Ajayi (King’s College Hospital, UK), Adesoji Ademuyiwa (Lagos 29 University Teaching Hospital, Nigeria), Emmanuel Ameh (National Hospital, Abuja, Nigeria), Justine 30 Davies (University of Birmingham, UK), Kokila Lakhoo (University of Oxford and Oxford University 31 Hospitals, UK), Dan Poenaru (McGill University, Montreal, Canada), Nick Sevdalis (King’s College 32 London, UK), Emily Smith (Baylor University, Texas, USA), Andy Leather (King’s College London, UK) 33 34 35 Writing Committee: Harmony Ubhi (King’s College London, UK), Samuel Parker (Imperial College 36 London, UK), Godfrey Sama Philipo (Muhimbili University of Health and Allied Sciences, Tanzania)
37 http://bmjopen.bmj.com/ 38 Organising Committee: Sadi Abukhalaf (Al Quds University, Palestine), Nana Adofo-Ansong 39 (Mahikeng Provincial Hospital, South Africa), Melika Akhbari (King’s College London, UK), Ahmad 40 Alhamid (University of Aleppo, Syria), Osaid H. Alser (University of Oxford, UK), Emrah Aydin (Koc 41 University, Turkey), Yousra-Imane Benaskeur (Universite de Montreal, Canada), Shrouk M. Elghazaly 42 (Assiut University, Egypt), Safa abdal Elrais (University of Tripoli, Libya), Sophia Hashim (University College London, UK), Laura Herrera (Geisel School of Medicine, Dartmouth, USA), Gabriella Hyman 43 (University of Witwatersrand, South Africa), Henang Kwasau (College of Medicine and Allied Health 44 Sciences, University of Sierra Leone), Yang Liu (Children’s Hospital, Zhejiang University School of
45 on September 23, 2021 by guest. Protected copyright. Medicine, China), Bruno Martinez-Leo (Moctezuma Children’s Hospital, Mexico), Kelly Naranjo 46 (Columbia University Medical Centre, USA), Ibrahim Nour (Jordan University Hospital, Jordan), 47 Cristiana Riboni (University of Pavia, Italy), Mahmoud Saleh (University of Gezira, Sudan), Hosni 48 Khairy Salem (Cairo University, Egypt), Patricia Shinondo (University Teaching Hospital, Lusaka, 49 Zambia), Marcus Sim (Stepping Hill Hospital, UK), Hannah Thompson (King’s College Hospital, UK), 50 Agota Vaitkiene (Vilnius University Hospital Santaros Kliniko, Lithuania), Dominique Vervoort 51 (Harvard Medical School, USA), Isabelle Williams (Cambridge University, UK), Aayenah Yunus 52 (King’s College London, UK). 53 54 Lead Investigators: Muhammad Amjad Chaudhary, Adnan Ahmed Khan Khattak, Muhammad Bin 55 Amjad (Children’s Hospital, PIMS, Islamabad, Pakistan), Marlene Dominguez Anaya (Children’s 56 Hospital Manuel A.Villarroel Cochabamba, Bolivia), Samiul Hasan, Sabbir Karim, Ashrarur Rahman 57 Mitul (Dhaka Shishu (Children) Hospital, Bangladesh), Paolo Bragagnini, Segundo Rite (Hospital 58 Universitario Miguel Servent, Zaragoza), Hana Arbab, Lubna Samad, Aqil Soomro (Indus Hospital, 59 Pakistan), Niveshni Maistry (John Radcliffe Hospital, UK), Raed Nael Al-Taher, Ibrahim Rabi Nour, 60 Osama Abdul Kareem Sarhan (Jordan University Hospital, Jordan), Muhammad Arshad, Taimur
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3 Qureshi, Hina Yousaf (Liaquat National Hospital, Pakistan), Candy SC Choo, Doris Mae Dimatatac, BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Shireen Anne Nah (KK Women’s and Children’s Hospital, Singapore), Vijay Anand Ismavel, Ann 5 Miriam, Shajin T (Makunda Christian Leprosy and General Hospital, India), Monica Ivanov, 6 Andreea Serban (Marie Curie Hospital in Bucharest, Romania), Bruno Martinez-Leo (Moctezuma 7 Children’s Hospital, Mexico), Eva Blazquez-Gomez, Luis Garcia-Aparicio, Martí Iriondo, Jordi Prat, 8 Xavier Tarrado (Hospital Sant Joan de Deu, Spain), Lars Hagander, Emma Svensson (Skane 9 University Hospital’s Pediatric Care Hospital, Lund, Sweden), Alhassan Abdul-Mumin, Dominic 10 Bagbio, Sheila Owusu, Stephen Tabiri (Tamale Teaching Hospital, Ghana), Dayang Anita Abdul Aziz 11 (UKM Medical Centre, Kuala Lumpur, Malaysia). 12 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44
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3 REFERENCES BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 1. GBD Child Mortality Collaborators. Global, regional, national, and selected subnational levels 6 of stillbirths, neonatal, infant, and under-5 mortality, 1980-2015: a systematic analysis for the Global 7 Burden of Disease Study 2015. Lancet 2016; 388(10053): 1725-74. 8 2. Flores A, Valencia D, Sekkarie A, et al. Building capacity for birth defects surveillance in 9 Africa: Implementation of an intermediate birth defects surveillance workshop. J Glob Health Perspect 10 2015; 2015. 11 3. Sitkin NA, Ozgediz D, Donkor P, Farmer DL. Congenital anomalies in low- and middle-income 12 countries: the unborn child of global surgery. World J Surg 2015; 39(1): 36-40. 13 4. Boyle B, Addor MC, Arriola L, et al. Estimating Global Burden of Disease due to congenital 14 anomaly: an analysis of European data. Arch Dis Child Fetal Neonatal Ed 2017. 15 5. Ozgediz D, Langer M, Kisa P, Poenaru D. Pediatric surgery as an essential component of 16 global child health. Semin Pediatr Surg 2016; 25(1): 3-9. 17 6. Farmer D, Sitkin N, Lofberg K, Donkor P, Ozgediz D. Surgical Interventions for Congenital 18 Anomalies. In: DebasFor HT, Donkor peer P, Gawande review A, Jamison DT, Krukonly ME, Mock CN, eds. Essential 19 Surgery: Disease Control Priorities, Third Edition (Volume 1). Washington (DC); 2015. 20 7. Sakonidou S, Ali K, Farmer I, Hickey A, Greenough A. Mortality and short-term morbidity in 21 infants with exomphalos. Pediatr Int 2018. 22 8. Ameh EA, Seyi-Olajide JO, Sholadoye TT. Neonatal surgical care: a review of the burden, progress and challenges in sub-Saharan Africa. Paediatr Int Child Health 2015; 35(3): 243-51. 23 9. Ekenze SO, Ajuzieogu OV, Nwomeh BC. Challenges of management and outcome of 24 neonatal surgery in Africa: a systematic review. Pediatr Surg Int 2016; 32(3): 291-9. 25 10. United Nations. Sustainable Development Goals. 2015. 26 http://www.un.org/sustainabledevelopment/health/ (accessed 27th February 2018). 27 11. Wright NJ, Anderson JE, Ozgediz D, Farmer DL, Banu T. Addressing paediatric surgical care 28 on World Birth Defects Day. Lancet 2018; 391(10125): 1019. 29 12. Wright NJ, Zani A, Ade-Ajayi N. Epidemiology, management and outcome of gastroschisis in 30 Sub-Saharan Africa: Results of an international survey. Afr J Paediatr Surg 2015; 12(1): 1-6. 31 13. PaedSurg Africa Research Collaboration. Paediatric Surgery across Sub-Saharan Africa: A 32 Multi-Centre Prospective Cohort Study. https://clinicaltrials.gov/ct2/show/NCT03185637 (Accessed 33 26th January 2019). 34 14. Bradnock T, Marven S, Owen A, et al. Gastroschisis: one year outcomes from national cohort 35 study. BMJ 2011; 343(d6749). 36 15. Krishnaswami S, Nwomeh BC, Ameh AE. The pediatric surgery workforce in low- and middle-
37 income countries: problems and priorities. Semin Pediatr Surg 2016; 25(1): 32-42. http://bmjopen.bmj.com/ 38 16. Okoye MT, Ameh EA, Kushner AL, Nwomeh BC. A pilot survey of pediatric surgical capacity 39 in West Africa. World J Surg 2015; 39(3): 669-76. 40 17. GlobalSurg Collaborative. Mortality of emergency abdominal surgery in high-, middle- and 41 low-income countries. Br J Surg 2016; 103(8): 971-88 42 18. GlobalSurg Collaborative. Surgical site infection after gastrointestinal surgery in high-income, 43 middle-income, and low-income countries: a prospective, international, multi-centre cohort study. 44 Lancet Infect Dis 2018; 18(5): 516-25. 19. GlobalSurg Collaborative. Laparoscopy in management of appendicitis in high-, middle-, and
45 on September 23, 2021 by guest. Protected copyright. low-income countries: a multicenter, prospective, cohort study. Surg Endosc 2018. 46 20. GlobalSurg Collaborative. Determinants of morbidity and mortality following emergency 47 abdominal surgery in children in low-income and middle-income countries. BMJ Glob Health 2016; 48 1(4): e000091. 49 21. Bhangu A, Kolias AG, Pinkney T, Hall NJ, Fitzgerald JE. Surgical research collaboratives in 50 the UK. Lancet 2013; 382(9898): 1091-2. 51 22. Long AM, Bunch KJ, Knight M, Kurinczuk JJ, Losty PD, Baps C. Early population-based 52 outcomes of infants born with congenital diaphragmatic hernia. Arch Dis Child Fetal Neonatal Ed 53 2018. 54 23. Ruttenstock E, Wright N, Barrena S, et al. Best oxygenation index on day 1: a reliable marker 55 for outcome and survival in infants with congenital diaphragmatic hernia. Eur J Pediatr Surg 2015; 56 25(1): 3-8. 57 24. Burjonrappa S, Crete E, Bouchard S. Comparative outcomes in intestinal atresia: a clinical 58 outcome and pathophysiology analysis. Pediatr Surg Int 2011; 27(4): 437-42. 59 25. Forrester MB, Merz RD. Structural birth defects associated with omphalocele and 60 gastroschisis, Hawaii, 1986-2001. Congenit Anom (Kyoto) 2008; 48(2): 87-91.
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3 26. Kunz SN, Tieder JS, Whitlock KJ, Jackson C, Avansino JR. Primary fascial closure versus BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 staged closure with silo in patients with gastroschisis: a meta-analysis. J Pediatr Surg 2013; 48(4): 5 845-57. 6 27. Ross AR, Eaton S, Zani A, Ade-Ajayi N, Pierro A, Hall NJ. The role of preformed silos in the 7 management of infants with gastroschisis: a systematic review and meta-analysis. Pediatr Surg Int 8 2015; 31(5): 473-83. 9 28. Levitt MA, Pena A. Anorectal malformations. Orphanet J Rare Dis 2007; 2: 33. 10 29. Van der Steeg HJ, Schmiedeke E, Bagolan P, et al. European consensus meeting of ARM- 11 Net members concerning diagnosis and early management of newborns with anorectal 12 malformations. Tech Coloproctol 2015; 19(3): 181-5. 13 30. Holschneider A, Hutson J, Pena A, et al. Preliminary report on the International Conference 14 for the Development of Standards for the Treatment of Anorectal Malformations. J Pediatr Surg 2005; 15 40(10): 1521-6. 16 31. Bradnock TJ, Knight M, Kenny S, Nair M, Walker GM, British Association of Paediatric 17 Surgeons Congenital Anomalies Surveillance S. Hirschsprung's disease in the UK and Ireland: incidence and anomalies. Arch Dis Child 2017; 102(8): 722-7. 18 32. Ross AR, HallFor NJ. Outcome peer reporting review in randomized controlled only trials and systematic reviews 19 of gastroschisis treatment: a systematic review. J Pediatr Surg 2016; 51(8): 1385-9. 20 33. Allin BSR, Hall NJ, Ross AR, et al. Development of a gastroschisis core outcome set. Arch 21 Dis Child Fetal Neonatal Ed 2018. 22 34. Allin BS, Irvine A, Patni N, Knight M. Variability of outcome reporting in Hirschsprung's 23 Disease and gastroschisis: a systematic review. Sci Rep 2016; 6: 38969. 24 35. Watanabe S, Suzuki T, Hara F, Yasui T, Uga N, Naoe A. Omphalocele and Gastroschisis in 25 Newborns: Over 16 Years of Experience from a Single Clinic. J Neonatal Surg 2017; 6(2): 27. 26 36. Tan KB, Tan KH, Chew SK, Yeo GS. Gastroschisis and omphalocele in Singapore: a ten-year 27 series from 1993 to 2002. Singapore Med J 2008; 49(1): 31-6. 28 37. Schneider A, Blanc S, Bonnard A, et al. Results from the French National Esophageal Atresia 29 register: one-year outcome. Orphanet J Rare Dis 2014; 9: 206. 30 38. World Bank. World Bank Country and Lending Groups. 2018. 31 https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending- 32 groups (Accessed 26th January 2019). 33 34 35 36
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45 on September 23, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 Management and Outcomes of Congenital Anomalies in Low-, Middle- and BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 High-Income Countries: Protocol for a Multi-centre, International, Prospective 5 6 Cohort Study 7 8 9 SUPPLEMENTARY FILE 1: Condition Specific Data Points 10 11 12 Oesophageal Atresia (OA) +/- Tracheo-Oesophageal Fistula (TOF) 13 Question Answers 14 Type of OA +/- TOF (Gross classification) A, B, C, D, E 15 A: without a fistula, B: proximal TOF with distal OA, C: distal TOF with proximal 16 OA, D: proximal and distal TOF, E: H-type TOF without OA. 17 Long or short gap? Long, Short, Unknown Long gap OA: A gap of 4 vertebral bodies or more. Anatomically cases either 18 For peerhave noreview TOF or a gap of over only4 vertebral bodies following division of the distal 19 fistula making primary repair unfeasible. Short OA: A gap of less than 4 vertebral 20 bodies. Primary anastomosis typically feasible. Pneumonia at presentation? Yes: diagnosed clinically, Yes: diagnosed radiologically, Yes: other means of 21 diagnosis, No: patient born in the study centre, No: patient born outside the study 22 centre but no evidence of pneumonia on arrival 23 Pneumonia is defined as lung inflammation typically caused by bacterial or viral 24 infection, in which the air sacs fill with pus and may become solid. Primary intervention: TOF ligation, Oesophageal anastomosis, Oesophagostomy, Gastrostomy, 25 Ligation of the distal oesophagus, Gastro-oesophageal disconnection, Foker 26 technique, Fundoplication, Other (please specify), Palliative care 27 Select all that apply. If the patient had a primary oesophageal anastomosis, Yes, No. (At any stage) 28 was a post-operative oesophagogram undertaken? 29 If yes, routine or clinically indicated? Routine, Clinically indicated 30 If yes, when? Number of days after primary surgery If yes, what was the result? Leak, No leak 31 For patients diagnosed with a leak radiologically, was it Yes, No 32 associated with clinical symptoms? 33 Time to first oral feed post-operatively In days. Please include the day of surgery and the first day of oral feeds in the calculation. Enter 0 if oral feeds were not commenced within 30-days of primary 34 intervention. Do not include other types of enteral feeding such as nasogastric or 35 gastrostomy feeding. 36 Time to full oral feeds In days (enter 0 if the patient died before reaching full oral feeds or 30 if the patient had not reached full oral feeds at 30-days post primary intervention). Do
37 http://bmjopen.bmj.com/ not include other types of enteral feeding such as nasogastric or gastrostomy 38 feeding. 39 For patient's not receiving a primary oesophageal In months (enter unknown if not planned or enter not applicable if primary 40 anastomosis, at what age is definitive surgery planned? anastomosis was undertaken). For patient's not receiving a primary oesophageal Gap assessment, Primary oesophageal anastomosis if possible, Gastric pull-up, 41 anastomosis, what is the future planned procedure? Jejunal interposition, Colonic interposition, Not applicable: primary anastomosis 42 undertaken, Other, Unknown. Select all that apply. If other, please specify. 43 If the patient had surgery, what was the approach? Thoracotomy muscle cutting, Thoracotomy muscle splitting, Thoracoscopy, Laparotomy, Laparoscopy, Limited local incision, Other. 44 During primary surgery. If other, please specify.
45 If thoracoscopic or laparoscopic, was the surgery Yes, No on September 23, 2021 by guest. Protected copyright. 46 converted to open? 47 Did the patient have a condition specific complication Pneumonia, Mediastinitis, Pneumothorax, Chylothorax, Haemothorax, within 30-days of primary intervention? Anastomotic leak, Anastomotic stricture, Recurrent TOF, Other, None 48 Select all that apply. If other, please specify. 49 Did the patient have tracheomalacia? Yes: diagnosed clinically, Yes: diagnosed on bronchoscopy, Yes: diagnosed on 50 CT, Yes: diagnosed on bronchogram, Yes: other method of diagnosis, No If yes, was an intervention undertaken? If other, please Yes: aortopexy, Yes: tracheostomy, Yes: tracheal stent, Yes: supportive 51 specify management (oxygen +/- ventilation) only, Yes: other treatment, No 52 53 Congenital Diaphragmatic Hernia (CDH) 54 55 Question Answers 56 Type of CDH. Left posteriolateral (Bochdalek), Right posteriolateral (Bochdalek), Bilateral posteriolateral (Bochdalek), Central, Anterior (Morgagni), Other. If other, please 57 specify. 58 Type of Bochdalek CDH (CDH Study Group A, B, C, D, Other (specify), Unknown. 59 Classification) Defect A: smallest defect, usually "intramuscular" defect with >90% of the hemi- diaphragm present; this defect involves < 10% of the circumference of the chest 60 wall. Defect B: 50-75% hemi-diaphragm present; this defect involves < 50% of
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3 the chest wall. Defect C: < 50% hemi-diaphragm present; this defect involves BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 >50% of the chest wall. Defect D: largest defect (previously known as 5 "agenesis"); complete or near complete absence of the diaphragm with < 10% hemi-diaphragm present; this defect involves >90% of the chest wall. Surgically, 6 it is an absent posterior rim beyond the spine, absent posterior-lateral rim, and 7 an anterior/anterior-medial rim which is miniscule. As it is truly unusual to have 8 zero tissue at all, this is the CDHSG member consensus. "D" defects should all require a patch (or muscle flap) for repair. 9 If bilateral, what was the type of Bochdalek hernia on the A, B, C, D, Other, Unknown 10 left? If other, please specify. 11 If bilateral, what was the type of Bochdalek hernia on the A, B, C, D, Other, Unknown right? If other, please specify. 12 If antenatally diagnosed, what was the lung-to-head ratio Enter zero if not undertaken/ not known. 13 (LHR)? 14 Was foetal tracheal occlusion (FETO) undertaken? Yes, No 15 If yes, at what gestational age was it inserted? ______, unknown. If yes, at was gestational age was it removed? ______, at birth, unknown. 16 Liver position? Chest, Abdomen, Unknown 17 Did the patient have pulmonary hypertension (at any Yes: diagnosed clinically, Yes: diagnosis confirmed on echocardiography, Yes: 18 stage)? For peerother methodreview of confirming diagnosis, only No, Unknown 19 Persistent pulmonary hypertension of the newborn (PPHN) is defined as the failure of the normal circulatory transition that occurs after birth. It is a syndrome 20 characterised by marked pulmonary hypertension that causes hypoxemia 21 secondary to right-to-left extrapulmonary shunting of deoxygenated blood. It 22 should be suspected whenever the level of hypoxemia is out of proportion to the level of pulmonary disease. Echocardiography plays a major role in screening 23 and assisting in making the diagnosis of PPHN. 24 If yes, treatment given? If other, please specify. Nitric oxide, Prostacyclin, Alprostadil, Milrinone, Other, None: not required, 25 None: required but not available. Did the patient receive extracorporeal membrane Yes, No 26 oxygenation (ECMO)? 27 If yes, for how long? In days. Include the day the patient went onto ECMO and the day they were 28 taken off in the calculation. 29 Primary intervention Primary repair (absorbable sutures), Primary repair (non-absorbable sutures), Patch repair, Palliation, Discharged with planned elective repair, Other 30 If patch repair, material used? Permacol, PTFE, Alloderm, Dacron, Mesh plug, Muscle flap, Surgisis, Other. If 31 other, please specify. 32 Other procedures undertaken at the same time? Chest drain insertion, Abdominal wall patch, Fundoplication, Correction of malrotation, Appendicectomy, Other (specify), None 33 Select all that apply. If other, please specify. 34 Surgical approach: Laparotomy, Laparoscopy, Thoracotomy, Thoracoscopy, Other (please specify) 35 If laparoscopic or thoracoscopic, was the surgery Yes/No. converted to open? 36 Condition specific complication within 30-days of primary Air leak (not just redundant space in the pleural cavity which is common),
37 surgery? Chylothorax, Recurrence, Adhesional obstruction, Other, None. Select all that http://bmjopen.bmj.com/ 38 apply. If other, please specify. 39 40 Intestinal Atresia 41 42 Question Answers Type of intestinal atresia Duodenal, Jejuno-ileal, Colonic 43 Classification of duodenal or colonic atresia 1,2,3,4 44 1) intraluminal web with continuity of the muscular layer, 2) atretic segment without a mesenteric defect, 3) atretic segment with mesenteric defect, 4)
45 on September 23, 2021 by guest. Protected copyright. multiple atresias = string of sausages appearance. 46 Classification of jejuno-ileal atresia 1,2,3a,3b,4 47 1) intraluminal web with continuity of the muscular layer, 2) atretic segment 48 without a mesenteric defect, 3a) atretic segment with mesenteric defect, 3b) apple-peel (bowel wrapped around a single artery), 4) multiple atresias = string 49 of sausages appearance. 50 Primary intervention for duodenal atresia: Duodenoduodenostomy, Duodenojenunostomy, Web excision only, Palliation, 51 Other. If other, please specify. 52 Surgical approach Laparotomy, Laparoscopy, Endoscopy, Other Conversion to open procedure? Yes/ No 53 Type of anastomosis Kimura’s diamond shape, Side-to-side, End-to-end 54 Primary intervention for jejuno-ileal and colonic atresia: Primary anastomosis, Bowel resection, Division of web only, Loop stoma, 55 Divided stoma, Bishop-Koop stoma, Santulli stoma, Palliation, Other. Select all that apply. 56 If bowel was excised, what was the total length of bowel In centimetres (cm). Enter 0 if unknown 57 excised? 58 Surgical approach: Laparotomy, Laparoscopy, Endoscopy, Other Conversion to open procedure? Yes, No 59 Was the distal bowel flushed to check for patency? Yes, No 60
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3 If the patient underwent surgery, did they have a Anastomotic leak, Anastomotic stenosis, Short-gut, Missed additional atresia, BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 condition specific complication within 30-days of primary Adhesive bowel obstruction, Stoma prolapse, Stoma retraction, Parastomal 5 intervention? hernia, Parastomal skin breakdown, Other. If other, please specify. Select all that apply. For the purposes of this study short gut is defined as more 6 than 50% of the small intestine excised (when short bowel syndrome can occur). 7 8 Gastroschisis 9 10 Question Answers 11 Type of gastroschisis Simple, Complex: associated with atresia, Complex: associated with necrosis, Complex: associated with perforation, Complex: associated with closing 12 gastroschisis. Select all that apply. 13 Primary intervention: Primary closure in the operating room (OR), Primary closure at the cotside 14 (Bianchi technique), Staged closure using a preformed silo, Staged closure using an Alexis Wound Retractor and Protector, Staged closure using a surgical 15 silo (including improvised silo), Other method, No intervention undertaken. 16 If other, please specify. 17 Method of defect closure: Fascia and skin closed with sutures, Just skin closed with sutures: fascia left 18 For peeropen, reviewUmbilical cord sutured overonly the defect: fascia left open, Sutureless closure with skin edges opposed and dressing applied, Dressing applied: defect left 19 open to close by secondary intention, Other, Patient died before the defect was 20 closed. If other, please specify. 21 On what day following admission was abdominal wall In days. Please include the first day of admission and the day of closure in the closure achieved? calculation. For example, for a neonate admitted with gastroschisis on 2nd 22 October who had the defect closed on 4th October, please insert 3 days. 23 Did the neonate have any of these complications within Ischemic bowel, Abdominal compartment syndrome (ACS), Necrotising 24 30-days of primary intervention? enterocolitis, None of these Select all that apply. ACS is defined as respiratory insufficiency secondary to 25 compromised tidal volumes, decreased urine output caused by falling renal 26 perfusion or any other organ dysfunction caused by increased intra-abdominal 27 pressure. 28 If the patient has ACS, was the abdomen re-opened? Yes/ No 29 Exomphalos 30
31 Question Answers 32 Type of Exomphalos? Major, Minor 33 Major: >50% of the liver in the exomphalos sac and abdominal wall defect >5cm. 34 Minor: Infants with defects less than 5cm. Hypoglycaemic on arrival? Yes, No, Blood glucose not measured 35 Hypoglycaemia is defined as a blood glucose level below 4 mmol/L (72mg/dL). 36 Primary intervention Primary operative closure, Staged closure, Conservative management If the patient had a staged closure, what was the time In days. Please include the day of the primary intervention and the day of 37 http://bmjopen.bmj.com/ 38 from primary intervention to closure? closure in the calculation. Enter 30 if still not closed at 30-days after primary intervention. 39 If conservative management, was a topical treatment Yes: silver sulfadiazine, Yes: betadine, Yes: honey, Yes: merbromide tannage, 40 applied to the exomphalos sac? Yes: other, no. If other, please specify. 41 If conservative management was undertaken, what is the No further surgery planned, Delayed closure at this hospital, Delayed closure at plan for future management? another hospital, Other. If other, please specify. 42 Did the patient have a ruptured sac? Yes, No 43 44 Anorectal Malformation (ARM)
45 on September 23, 2021 by guest. Protected copyright. 46 Question Answers 47 Type of anorectal malformation (Krickenbeck Low ARM: Perineal (cutaneous) fistula, High ARM: Rectourethral fistula (bulbar), classification) High ARM: Rectourethral fistula (prostatic), High ARM: Rectovesical fistula, High 48 ARM: Vestibular fistula, High ARM: Cloaca, High ARM: No fistula, High ARM: 49 Type unknown at present, Rare variant: Pouch colon, Rare variant: Rectal atresia/ 50 stenosis, Rare variant: Rectovaginal fistula, Rare variant: H fistula, Other 51 Did the neonate have pre-operative bowel perforation? Yes, No What was the primary intervention undertaken? Fistula dilation: no surgery, Loop sigmoid colostomy, Divided sigmoid colostomy, 52 Loop transverse colostomy, Divided transverse colostomy, Other stoma, 53 Anoplasty, Posterior sagittal anorectoplasty (PSARP), Abdominosacroperineal 54 pull-through, Abdominoperineal pull-through, Laparoscopic-assisted pull-through, Palliative care, Other. If other, please specify. Select all that apply. 55 If primary anorectal reconstruction was undertaken, was Yes, no: equipment was not available, no: the equipment was available but not 56 a Peña stimulator or equivalent used to identify the used. Peña stimulator: Muscle locating stimulator commonly used to identify the 57 position of the muscle complex intra-operatively? anal sphincter muscles whilst undertaking a PSARP for patients with ARM. Did the patient have any of the following complications For each of the below answer: Yes, No, Not applicable 58 within 30-days of surgery? 59 - Electrolyte disturbance 60 - High output stoma (over 20mls/kg/day)
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3 - Stoma prolapse/ retraction/ herniation BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 - Peri-stoma skin breakdown (or perianal if primary 5 reconstructive surgery undertaken without a covering stoma) 6 - Anal stenosis in those undergoing primary anorectal 7 reconstruction without covering stoma. 8 What is the plan for future management? No further operative management, Anoplasty/ pull-through planned at your hospital, Anoplasty/ pull-through planned at another hospital, Stoma closure 9 planned at your hospital, Stoma closure planned at another hospital, Other 10 Please tick all that apply. If other, please specify. 11 12 Hirschsprung’s Disease 13 14 Question Answers Time to first passage of meconium after birth Less than 24 hours, 24-48 hours, Over 48 hours, Unknown 15 Features at presentation: Abdominal distension, Bilious vomiting, Non-bilious vomiting, Poor feeding, 16 Suspected enterocolitis, Perforation, Other. Select all that apply. 17 Source of diagnosis of Hirschsprung's disease Genetic, Mucosal biopsy, Full thickness biopsy, Anorectal manometry, Barium 18 For peerenema, review Not confirmed: suspected only only, Other. If on biopsy, what was the method of histology staining. Hemotoxilin and Eosin (H&E), Acetylcholinesterase, Calretinin, Other. 19 Select all that apply. If other, please specify. 20 Length of aganglionosis: Rectal, Sigmoid, Descending colon, Transverse colon, Ascending colon, Small 21 bowel, Unknown at present 22 Primary intervention Conservative: no treatment, Conservative: digital stimulation and laxatives, Conservative: regular rectal washouts/ enemas, Failed conservative management 23 followed by a stoma during the same hospital admission, Primary stoma (with or 24 without pre-operative washouts or enemas prior to a planned stoma placement), 25 Primary pull-through (Swenson), Primary pull-through (Duhamel), Primary pull- through (Soave), Primary pull-through (Other), Transanal posterior anorectal 26 myectomy, Palliative care, Other. 27 If primary pull-through was undertaken, did the patient Yes, No 28 have a covering stoma? Was it laparoscopic assisted? Yes, No 29 Did the patient have any condition specific complications Hirschsprung's associated enterocolitis (HAEC), Electrolyte disturbance, High 30 within 30-days of primary intervention? stoma output (over 20mls/kg/day), Stoma prolapse/ retraction/ herniation, Peri- 31 stoma skin breakdown (or perianal if primary pull-through was undertaken without a covering stoma), Anal stenosis, Post-operative obstruction, Anastomotic leak (if 32 primary pull-through was undertaken without a covering stoma), Other 33 HAEC is defined as inflammation of the small and or large bowel in patient's born 34 with Hirschsprung's disease. If the patient was managed conservatively, please 35 tick if they developed enterocolitis within 30-days of presentation. Select all that apply. 36 What is the plan for future management? No further surgery planned, Anorectal pull-through at your hospital, Anorectal pull-
37 through at a different hospital, Stoma closure, Other, Unknown http://bmjopen.bmj.com/ 38 39 40 41 42 43 44
45 on September 23, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 Management and Outcomes of Congenital Anomalies in Low-, Middle- and BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 High-Income Countries: Protocol for a Multi-centre, International, Prospective 5 6 Cohort Study 7 8 9 SUPPLEMENTARY FILE 2 10 Collaborator Survey: Resources and Facilities for Neonatal and Paediatric Surgery 11 12 13 Question Answers Title Professor, Dr, Mr, Mrs, Miss, Ms, Other 14 Surname 15 First Name 16 Professional Position Professor, Consultant or attending, Registrar or resident, Intern/ house 17 officer/ senior house officer, Medical Student, Nurse, Other 18 Are you the study lead at your centre?For peer reviewYes, No only Answers provided by the study lead will be used as the 'Gold Standard' to 19 which the other survey will be compared (this will remain anonymous). 20 Speciality General Surgery (adult and paediatric), Paediatric Surgery, Anaesthetics, 21 Paediatrics, Neonatology, Nursing, Not specialised yet, Other Full name of institution: 22 Address of institution: 23 Country Afghanistan, Albania, Algeria, Andorra, Angola, Antigua and Barbuda, 24 Argentina, Armenia, Aruba, Australia, Austria, Azerbaijan, Bahamas, 25 Bahrain, Bangladesh, Barbados, Belarus, Belgium, Belize, Benin, Bhutan, Bolivia, Bosnia and Herzegovina, Botswana, Brazil, Brunei, Bulgaria, 26 Burkina Faso, Burma, Burundi, Cambodia, Cameroon, Canada, Cabo 27 Verde, Central African Republic, Chad, Chile, China, Colombia, Comoros, 28 Republic of the Congo, Costa Rica, Cote d'Ivoire, Croatia, Cuba, Curacao, Cyprus, Czechia, Denmark, Djibouti, Dominica, Dominican Republic, 29 Ecuador, Egypt, El Salvador, Equatorial Guinea, Eritrea, Estonia, Eswatini, 30 Ethiopia, Fiji, Finland, France, Gabon, The Gambia, Georgia, Germany, 31 Ghana, Greece, Grenada, Guatemala, Guinea, Guinea-Bissau, Guyana, Haiti, Holy See, Honduras, Hong Kong, Hungary, Iceland, India, 32 Indonesia, Iran, Iraq, Ireland, Israel, Italy, Jamaica, Japan, Jordan, 33 Kazakhstan, Kenya, Kiribati, South Korea, Kosovo, Kuwait, Kyrgyzstan, 34 Laos, Latvia, Lebanon, Lesotho, Liberia, Libya, Liechtenstein, Lithuania, Luxembourg, Macau, Macedonia, Madagascar, Malawi, Malaysia, 35 Maldives, Mali, Malta, Marshall Islands, Mauritania, Mauritius, Mexico, 36 Micronesia, Moldova, Monaco, Mongolia, Montenegro, Morocco, Mozambique, Namibia, Nauru, Nepal, Netherlands, New Zealand, 37 http://bmjopen.bmj.com/ 38 Nicaragua, Niger, Nigeria, North Korea, Norway, Oman, Pakistan, Palau, Palestinian Territories, Panama, Papua New Guinea, Paraguay, Peru, 39 Philippines, Poland, Portugal, Qatar, Reunion Island, Romania, Russia, 40 Rwanda, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the 41 Grenadines, Samoa, San Marino, Sao Tome and Principe, Saudi Arabia, Senegal, Serbia, Seychelles, Sierra Leone, Singapore, Sint Maarten, 42 Slovakia, Slovenia, Solomon Islands, Somalia, Somaliland, South Africa, 43 South Korea, South Sudan, Spain, Sri Lanka, Sudan, Suriname, 44 Swaziland (See Eswatini), Sweden, Switzerland, Syria, Taiwan, Tajikistan, Tanzania, Thailand, Timor-Leste, Togo, Tonga, Trinidad and Tobago,
45 Tunisia, Turkey, Turkmenistan, Tuvalu, Uganda, Ukraine, United Arab on September 23, 2021 by guest. Protected copyright. 46 Emirates, United Kingdom, Uruguay, USA, Uzbekistan, Vanuatu, 47 Venezuela, Vietnam, Yemen, Zambia, Zimbabwe 48 Type of institution (WHO classification) - Specialised children's hospital (Provides highly specialised care dedicated to children) 49 - Referral hospital (WHO defined tertiary healthcare. Includes academic, 50 university, teaching, national, central and specialised 51 mission hospitals. Can provide specialised surgical services) - District hospital (WHO defined secondary healthcare. Includes 52 provincial, general, general mission or regional hospitals. Has general 53 anaesthesia and can provide general surgical care) 54 - Health centre (WHO defined primary healthcare. No general anaesthesia, can do minor local procedures, wound management, triage 55 and referral). 56 Institutional classification Government, Non-government 57 Institutional financial classification Not for profit, For profit 58 Population served by your institution (in millions, including children and adults) 59 Personnel 60 Number of Consultant Paediatric Surgeons undertaking ______(Excluding trainees)
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3 neonatal surgery at your institution: BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Number of Consultant General Surgeons (covering adults and 5 children) undertaking neonatal surgery independently at your ______(Excluding trainees) institution: 6 Number of medical officers or other non-surgeon healthcare 7 professionals undertaking neonatal surgery independently at ______(Without a consultant surgeon present at the time 8 your institution of surgery) 9 Infrastructure Please state whether the following facilities are available at your institution when required: 10 Running Water Always, Sometimes, Never 11 Electricity Always, Sometimes, Never 12 Electricity generator back-up Always, Sometimes, Never 13 Laboratory for biochemistry Always, Sometimes, Never Laboratory for haematology Always, Sometimes, Never 14 Blood bank Always, Sometimes, Never 15 Sterile gloves and gown Always, Sometimes, Never 16 Autoclave for sterilising surgical equipment Always, Sometimes, Never 17 Neonatal ventilation outside the operating room Always, Sometimes, Never Paediatric ventilation outside the operating room Always, Sometimes, Never 18 Neonatal intensive care unit for surgicalFor neonates peerpre and post reviewAlways, Sometimes, Never only 19 operatively (including if a stoma is present) 20 Paediatric intensive care unit for surgical paediatric patients pre Always, Sometimes, Never 21 and post operatively if required Parenteral nutrition for neonates Always, Sometimes, Never 22 Parenteral nutrition for adults and older children Always, Sometimes, Never 23 Extracorporeal membrane oxygenation (ECMO) Always, Sometimes, Never 24 Peña stimulator or equivalent device to identify the muscle Always, Sometimes, Never 25 complex during anorectal reconstruction Suction rectal biopsy gun to investigate for Hirschsprung's Always, Sometimes, Never 26 disease 27 Procedures 28 Please state whether the following procedures are available at your institution when clinically appropriate/ required: 29 Neonatal laparotomy Always, Sometimes, Never Neonatal laparoscopy Always, Sometimes, Never 30 Neonatal thoracotomy Always, Sometimes, Never 31 Neonatal thoracoscopy Always, Sometimes, Never 32 Neonatal central line insertion Always, Sometimes, Never 33 Paediatric central line insertion Always, Sometimes, Never Umbilical vein catheterisation Always, Sometimes, Never 34 Bedside primary reduction and closure of gastroschisis Always, Sometimes, Never 35 (Bianchi technique) 36 Preformed silo application, reduction and closure of Always, Sometimes, Never gastroschisis
37 http://bmjopen.bmj.com/ Surgical silo application, reduction and closure of Always, Sometimes, Never 38 gastroschisis 39 Primary closure of gastroschisis in the operating room Always, Sometimes, Never 40 Sigmoid colostomy Always, Sometimes, Never Posterior Sagittal Anorectoplasty (PSARP) for anorectal Always, Sometimes, Never 41 malformation 42 Foetal tracheal occlusion (FETO) for CDH Always, Sometimes, Never 43 Pull-through for Hirschsprung's disease Always, Sometimes, Never 44 Anaesthesia and resuscitation Please state whether the following facilities are available at your institution when required:
45 Neonatal bag, valve and mask Always, Sometimes, Never on September 23, 2021 by guest. Protected copyright. 46 Paediatric bag, valve and mask Always, Sometimes, Never 47 Bottled oxygen Always, Sometimes, Never 48 Piped oxygen Always, Sometimes, Never 49 Oxygen saturation monitor Always, Sometimes, Never Apnoea monitor Always, Sometimes, Never 50 Multi-parameter intra-operative monitoring Always, Sometimes, Never 51 Anaesthetic machine for neonates Always, Sometimes, Never 52 Anaesthetic machine for children Always, Sometimes, Never 53 Ketamine anaesthesia for neonates Always, Sometimes, Never Ketamine anaesthesia for children Always, Sometimes, Never 54 Spinal/ caudal anaesthesia for neonates Always, Sometimes, Never 55 Spinal/ caudal anaesthesia for children Always, Sometimes, Never 56 Anaesthetic doctor competent to perform neonatal anaesthesia Always, Sometimes, Never 57 Anaesthetic doctor competent to perform paediatric Always, Sometimes, Never anaesthesia 58 Anaesthetic nurse competent to perform neonatal anaesthesia Always, Sometimes, Never 59 Anaesthetic nurse competent to perform paediatric anaesthesia Always, Sometimes, Never 60
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3 Does your country have at least one specialised children's Yes, No BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 hospital that can provide neonatal and paediatric surgery? 5 Any other comments? 6 7 8 9 10 11 12 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44
45 on September 23, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
3 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
Management and Outcomes of Gastrointestinal Congenital Anomalies in Low-, Middle- and High-Income Countries: Protocol for a Multi-Centre, International, Prospective Cohort Study
ForJournal: peerBMJ Open review only Manuscript ID bmjopen-2019-030452.R1
Article Type: Protocol
Date Submitted by the 17-Jun-2019 Author:
Complete List of Authors: Wright, Naomi; King's College London, King's Centre for Global Health and Health Partnerships
Primary Subject Global health Heading:
Secondary Subject Heading: Paediatrics, Surgery
PAEDIATRIC SURGERY, Paediatric anaesthesia < ANAESTHETICS, Paediatric intensive & critical care < INTENSIVE & CRITICAL CARE, Keywords: NEONATOLOGY, PAEDIATRICS, Neonatal intensive & critical care <
INTENSIVE & CRITICAL CARE http://bmjopen.bmj.com/
on September 23, 2021 by guest. Protected copyright.
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1 2 3 Management and Outcomes of Gastrointestinal Congenital BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 Anomalies in Low-, Middle- and High-Income Countries: Protocol 6 for a Multi-Centre, International, Prospective Cohort Study 7 8 9 10 11 Global PaedSurg Research Collaboration 12 13 Correspondence to: Naomi J. Wright, King’s Centre for Global Health and Health Partnerships, 14 School of Population Health and Environmental Sciences, King’s College London, Denmark Hill, SE5 15 9RJ, UK. Email: [email protected] 16 17 18 For peer review only 19 ABSTRACT 20 21 Introduction 22 23 th 24 Congenital anomalies are the 5 leading cause of death in children under 5-years of age globally, contributing an estimated half a million deaths per year. Very limited literature exists from low- and 25 middle-income countries (LMICs) where most of these deaths occur. The Global PaedSurg Research 26 Collaboration aims to undertake the first multi-centre, international, prospective cohort study of a 27 selection of common congenital anomalies comparing management and outcomes between low-, 28 middle- and high-income countries (HICs) globally. 29 30 Methods and Analysis 31 32 33 The Global PaedSurg Research Collaboration consists of surgeons, paediatricians, anaesthetists and 34 allied healthcare professionals involved in the surgical care of children globally. Collaborators will prospectively collect observational data on consecutive patients presenting for the first time, with one 35 of seven common congenital anomalies (oesophageal atresia, congenital diaphragmatic hernia, 36 intestinal atresia, gastroschisis, exomphalos, anorectal malformation and Hirschsprung's disease).
37 http://bmjopen.bmj.com/ 38 39 Patient recruitment will be for a minimum of one month from October 2018 to April 2019 with a 30-day post-primary intervention follow-up period. Anonymous data will be collected on patient 40 demographics, clinical status, interventions and outcomes using REDCap. Collaborators will complete 41 a survey regarding the resources and facilities for neonatal and paediatric surgery at their centre. 42 43 44 The primary outcome is all-cause in-hospital mortality. Secondary outcomes include the occurrence of post-operative complications. Chi-squared analysis will be used to compare mortality between LMICs
45 on September 23, 2021 by guest. Protected copyright. and HICs. Multilevel, multivariate logistic regression analysis will be undertaken to identify patient 46 level and hospital level factors affecting outcomes with adjustment for confounding factors. 47 48 49 Ethics and Dissemination 50 51 At the host centre this study is classified as an audit not requiring ethical approval. All participating 52 collaborators have gained local approval in accordance with their institutional ethical regulations. 53 Collaborators will be encouraged to present the results locally, nationally and internationally. The 54 results will be submitted for open access publication in a peer reviewed journal. 55 56 Registration Details 57 58 This study has been registered with ClinicalTrials.Gov, identifier: NCT03666767. The registration is 59 available to view via: https://goo.gl/ffXNMH 60
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3 Strengths and Limitations of this Study BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 This will be the first large-series, geographically comprehensive, multi-centre, international, 6 prospective cohort study to define the management and outcomes of a selection of common 7 congenital anomalies in low-, middle- and high-income countries across the globe. 8 The collaborative approach for this study allows a large series of high-quality data to be collected 9 in a timely manner without overburdening high-volume, low-resource centres. 10 11 The seven study conditions constitute a selection of the commonest life-threatening congenital 12 anomalies requiring emergency surgical care in the neonatal period (Box 1). 13 We recognise that some children may not reach a facility capable of providing acute paediatric 14 surgical care and hence the results obtained may be an underestimation of true morbidity and 15 mortality, especially in LMICs. 16 The number of variables being collected per patient has been limited to those known to have the 17 greatest impact on outcomes to optimise the feasibility of the study; follow-up is limited to 30-days 18 post-primary intervention.For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44
45 on September 23, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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3 INTRODUCTION BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 In 2015, the Global Burden of Disease study concluded congenital anomalies (also known as 6 congenital malformations, congenital abnormalities or birth defects) to be the 5th leading cause of 7 death in children under 5-years of age globally.1 This equates to approximately half a million deaths 8 from congenital anomalies each year, 97% of which occur in low- and middle-income countries 9 (LMICs). Indeed, this is likely to be an underestimation of the actual number of deaths due to under- 10 diagnosis of neonates with congenital anomalies who die in the community and a lack of death 11 certification in many LMICs.2 Not only is the mortality rate higher in LMICs, the incidence and 12 prevalence are also higher due to micronutrient deficiencies, infections and teratogens during 13 pregnancy resulting in more cases and a lack of antenatal diagnosis prohibiting terminations.3,4 There 14 is limited research and a lack of congenital anomaly registries in LMICs and hence they have received 15 very little global attention.5 16 17 The conditions forming the focus of this study (Box 1) constitute a selection of the most common life- 18 threatening congenitalFor anomalies peer during the reviewneonatal period, which only involve the gastrointestinal tract. 19 They each have an incidence of 1/2000 – 1/5000, they collectively form up to 40% of emergency 6-9 20 neonatal surgery and associated mortality can be in excess of 50% in many LMICs. Disparities in 21 outcomes globally can be stark; for example the mortality from gastroschisis is 75-100% in many 10-12 22 LMICs compared to 4% or less in HICs. Reasons for poor outcomes include a lack of antenatal diagnosis, delayed presentation, limited neonatal transport and in-hospital resources, a dearth of 23 trained support personnel and a lack of intensive care and parenteral nutrition for neonates.9,13,14 In 24 Uganda, it was calculated that only 3.5% of the need for neonatal surgery was met by the healthcare 25 system.8 26 27 28 29 Box 1. Congenital Anomalies in the Global PaedSurg Study 30 31 Oesophageal atresia (OA) +/- tracheo-oesophageal fistula (TOF) 32 Congenital diaphragmatic hernia (CDH) 33 Intestinal atresia (IA) 34 Gastroschisis 35 Exomphalos 36 Anorectal malformation (ARM)
37 Hirschsprung’s disease http://bmjopen.bmj.com/ 38 39 40 41 In 2010, the World Health Assembly passed a resolution recommending ‘prevention whenever 42 possible, to implement screening programmes and to provide care and ongoing support to children 2 43 with birth defects and their families’. Prevention is paramount, however this is not yet possible for 44 many congenital anomalies and hence a focus on improving postnatal care and outcomes is vital. The Sustainable Development Goal 3.2 aims to end preventable deaths of newborns and children under
45 on September 23, 2021 by guest. Protected copyright. the age of 5-years by 2030.6, 15,16 With a third of infant deaths being attributed to congenital 46 anomalies, clearly this will not be achievable without an accelerated effort towards the provision of 47 surgical care for children. It is estimated that two-thirds of deaths and disability from congenital 48 anomalies can be avoided with the provision of neonatal and paediatric surgical care.6 Indeed, studies 49 have demonstrated such provision can be highly cost-effective in terms of disability adjusted life years 50 saved.5 Yet neonatal and paediatric surgical care remain a low priority on the global health agenda.5 51 52 A shift is needed to focus on the provision of surgical care for children within National Health Plans 53 and International Organisations and to elevate congenital anomalies on the global health agenda. 54 This large-scale, geographically comprehensive, multi-centre prospective cohort study aims to define 55 the current management and outcomes of a selection of common congenital anomalies globally and 56 identify factors affecting outcomes that can be modified to improve care. This is vital to aid advocacy 57 and global health prioritisation and inform future interventional studies aimed at improving outcomes. 58 59 60 AIM
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3 To undertake the first large-scale, geographically comprehensive multi-centre, prospective cohort BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 study comparing the management and outcomes of a selection of common congenital anomalies in 5 low-, middle-, and high-income countries across the globe. 6 7 OBJECTIVES 8 9 1. To compare the mortality and post-intervention complications of a selection of common congenital 10 anomalies involving the gastrointestinal tract in LMICs and HICs globally. 11 12 2. To identify patient level and hospital level factors affecting outcomes that be modified to improve 13 care. 14 15 3. To establish a research collaboration consisting of children’s surgical care providers across the 16 world to help enhance research capacity and to create a platform for ongoing collaborative research 17 and intervention studies aimed at improving outcomes. 18 For peer review only 19 4. To raise awareness and provide advocacy for neonatal and paediatric surgical care within global 20 health prioritisation, planning, policy and funding. 21 22 23 24 25 METHODS AND ANALYSIS 26 Study Design 27 28 29 This is an international, multi-centre, prospective observational cohort study. The Global PaedSurg Research Collaboration consisting of children’s surgical care providers (collaborators) across the 30 world was established from November 2017 to co-ordinate the study at an institutional level and 31 facilitate data collection. Collaborators are free to choose one or more months between 1st October 32 2018 to the 30th April 2019 (inclusive) to recruit consecutive patients to the study, with a 30-day post- 33 primary intervention follow up period. The primary intervention must occur within 30-days of 34 presentation to be included in the study. Hence, the last date for primary data collection is 29th June 35 2019. Following this there will be a period of data collection for the data validation process continuing 36 until the end of July 2019.
37 http://bmjopen.bmj.com/ 38 Collaborators 39 40 International collaborators will have a variety of roles and responsibilities within the study. Local 41 collaborators will establish mini-teams locally, gain study approval, utilise the protocol criteria to 42 appropriately identify patients for study inclusion, collect prospective data and upload it to REDCap. 43 Each hospital will have a local study lead who will hold overall responsibility for ensuring the data is 44 accurate, complete and without duplications. Country-lead collaborators will help to recruit other collaborators from within their country and provide advice and support regarding gaining local study 45 on September 23, 2021 by guest. Protected copyright. 46 approval and data collection. They may also help with translation of the study literature to the local 47 language if required. Continent and regional leads will help to recruit country leads, provide them with 48 advice regarding the study and also encourage and co-ordinate presentations of the protocol at 49 national and international meetings. Lead investigators will contribute to the study design through the 50 provision of feedback from the pilot studies undertaken in multiple languages. An organising 51 committee will help to co-ordinate all study activities and a steering committee will provide guidance 52 throughout. 53 There are a number of benefits for collaborators participating the study. Publishing journal(s) will be 54 asked to make all collaborators PubMed citable co-authors. This is based on an equal partnership 55 model described by the Lancet and is used by a number of national and international collaboratives.17- 56 21 All collaborators will be listed as an author on resulting presentations. Collaborators will have the 57 opportunity to present the study locally, nationally and internationally, initially the study protocol and 58 later the results. This often provides collaborators, especially those who are junior or from LMICs, the 59 opportunity to apply for funding to attend, present and network at such meetings. Participation in the 60 study provides an easy route and insight into clinical research, which can be further established
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3 through participation in the 2-year Research Training Fellowship which is running alongside the main BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 study free of charge for all interested collaborators. 5 6 Sample Selection 7 8 Collaborator and Hospital Inclusion Criteria: 9 10 All hospitals and healthcare professionals providing surgical care for neonates and children, 11 presenting for the first time, with one or more of the study conditions can be included in the study. 12 Collaborators should gain permission from the senior surgeon or physician who oversees the care of 13 the children to be included in the study in order to participate. There can be up to three collaborators 14 in a mini-team per month of data collection. One mini-team can collect data over one or more months 15 or several mini-teams can collect data over a different month each. Each mini-team must contain at 16 least one senior surgeon or physician to oversee the data collection process. 17 18 Patient Inclusion andFor Exclusion peer Criteria: review only 19 20 Any neonate, infant or child under the age of 16-years, presenting acutely for the first time, with one 21 or more of the study conditions can be included in the study. Patients who have previously received 22 surgery for their presenting condition or those representing with a complication of surgery are 23 excluded. Patients presenting electively for surgery are excluded. Children who have received basic 24 resuscitative care for their condition at a different healthcare facility and are then transferred to the 25 study centre for their primary surgical intervention can be included. Children who only receive 26 resuscitative treatment at the study centre and are then referred elsewhere for their primary surgical 27 intervention cannot be included since the outcome of the surgical care will not be known and also to 28 avoid the risk of duplicate patients in the study. Patients who receive conservative treatment as their 29 primary intervention, palliative care, or no care must be included within the study to accurately reflect 30 the management and outcomes of all presenting cases. 31 32 If a patient presents with more than one of the study conditions, the details of each condition that they 33 present acutely with can be included, but not a previously managed condition. For example, a 34 newborn presenting with oesophageal atresia and anorectal malformation would have both conditions 35 included. A patient presenting for the first time with Hirschsprung’s disease at several months of age 36 who had a duodenal atresia repaired at birth would have the full details of the Hirschsprungs disease
37 included, but the duodenal atresia would simply be noted as an associated anomaly. http://bmjopen.bmj.com/ 38 39 Outcome Measures 40 41 The primary outcome is all-cause, in-hospital mortality. 42 43 For patient’s hospitalised for over 30-days following primary intervention, a 30-day post-primary 44 intervention mortality rate will be utilised. Those who do not receive a primary intervention, but remain
45 alive and hospitalised at 30-days following primary admission, will have this time point used for on September 23, 2021 by guest. Protected copyright. 46 recording their mortality status for the primary outcome. Primary outcome is defined in Table 1. 47 48 The secondary outcomes include complications occurring within 30-days of primary intervention: 49 50 Surgical site-infection 51 Wound dehiscence 52 Need for re-intervention 53 Condition specific complications 54 Condition specific outcome variables 55 Length of hospital stay or time from admission to death in patients who do not survive 56 30-day post primary intervention mortality. 57 58 Secondary outcomes will not be collected on patients who do not receive a primary intervention within 59 30-days of hospital admission, with the exception of length of hospital stay or time from admission to 60
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3 death. 30-day follow-up will be undertaken within the capacity of the collaborating team; no additional BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 funding will be provided. 5 6 Data Collection 7 8 Generic variables relating to the patient demographics, antenatal care, pre-hospital care, clinical 9 condition, surgical intervention and outcomes will be collected for all patients in the study (Table 1). 10 Specific variables will be collected for each individual condition (Supplementary File 1). 11 12 Outcomes and variables have been chosen using published core outcome sets and commonly 13 collected outcomes in systematic reviews and meta-analyses.22-37 Collaborators will enter anonymous, 14 de-identified data via the secure internet-based Research Electronic Data Capture (REDCap) system. 15 This will be stored on King’s College London REDCap server. 16 17 A short survey will be completed by the local study lead and one other collaborating consultant or 18 registrar on the resourcesFor and facilitiespeer available review for neonatal and only paediatric surgical care at their 19 centre (Supplementary File 2). 20 21 22 Table 1. Generic Data Points 23 24 Generic questions Answers 25 During which month did the patient present to Please select the month that the patient presented to your hospital for the first time with this 26 your hospital? congenital anomaly. For example, if a baby was born with gastroschisis on the 29th September 27 and presented to your hospital on the 1st October you should select October. Has consent been provided to include this Yes / No / Patient consent is not required for this study at my institution 28 patient in the study? 29 If no, which condition did the patient present Oesophageal atresia / Congenital diaphragmatic hernia / Intestinal atresia / Gastroschisis / 30 with? Exomphalos / Omphalocele / Anorectal malformation / Hirschsprung's Disease. Please select all the conditions that the patient presented with. Do not select a condition which 31 the patient has already received surgical treatment for previously. 32 Demographics 33 Gestational age at birth Number of weeks from the first day of the women's last menstrual cycle until birth. Round up or 34 down to the nearest week. Age at presentation (in hours) We understand this information may be difficult to obtain - please be as accurate as you can. 35 Please round to the nearest hour. This number may be very large for patients who have a 36 delayed presentation - please still enter it. For neonates born within your centre please enter 0. Enter unknown if unknown. 37 http://bmjopen.bmj.com/ 38 Gender Male / Female/ Ambiguous/ Unknown Weight at presentation In kilograms (kg) on the day of presentation. Please provide a value to 1 decimal place. 39 Does the patient have another anomaly in Yes, Cardiovascular, Yes, Respiratory, Yes: Gastrointestinal, Yes: Neurological, Yes: Genito- 40 addition to the study condition? urinary, Yes: Musculoskeletal, Yes: Down syndrome, Yes: Beckwith-Wiedemann syndrome, Yes: 41 Cystic fibrosis, Yes: Chromosomal, Yes: Other, No Select all that apply. Include all anomalies diagnosed at any stage up until 30-days post primary 42 intervention or 30-days following presentation for those who didn't receive an intervention. If you 43 suspect an associated anomaly, but it has yet to be diagnosed, select 'other'. 44 Distance from the patient's home to your In kilometres (km). Please round to the nearest kilometre. Please enter 0 if born in your hospital. hospital
45 on September 23, 2021 by guest. Protected copyright. Antenatal Care and Delivery 46 Antenatal ultrasound undertaken? Yes: study condition diagnosed, Yes: problem identified but study condition not diagnosed, Yes: 47 no problem identified, No 48 If the condition was diagnosed antenatally, at Please round up to the nearest week. If the patient has more than one study condition, please 49 what gestational age? note the gestational age at which one or more of the conditions was first diagnosed. Mode of transport to hospital? Ambulance, Other transport provided by the health service, Patient's own transport, Born within 50 the hospital 51 Where did the patient present from? If other, Home / Community Clinic / General Practice / District Hospital / Other / Unknown 52 please specify. District hospital includes: secondary level healthcare, provincial hospital, general hospital, general mission hospital or regional hospital. It has general anaesthesia and can provide general 53 surgical care. 54 Type of delivery: Vaginal (spontaneous), Vaginal (induced), Caesarean section (elective), Caesarean section 55 (urgent/non-elective), Unknown. Vaginal delivery includes those requiring forceps and ventouse. 56 Clinical condition and patient care Was the patient septic on arrival? Yes, no 57 Sepsis is SIRS (Systemic Inflammatory Response Syndrome) with a suspected or confirmed 58 bacterial, viral, or fungal cause. SIRS is a response to a stimulus, which results in two or more of 59 the following: temperature > 38.5°C or < 36°C, tachycardia*, bradycardia* in children < 1 year old, tachypnoea*, leukopenia or leucocytosis*, hyperglycaemia*, altered mental status, 60 hyperlactaemia*, increased central capillary refill time >2 seconds. *Variables are defined as
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3 values outside the normal range for age. Arrival is the time of birth for neonates born at your BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 hospital. 5 If yes, were appropriate antibiotics Yes: within 1 hour of arrival, Yes: within the first day of arrival, No administered? Appropriate antibiotics are defined as either broad spectrum covering gram negative, gram 6 positive and anaerobic bacteria OR antibiotics that are the standard empirical treatment for that 7 condition according to local guidelines OR are based on sensitivities provided by a microbiology 8 sample. Was the patient hypovolaemic on arrival? Yes/ No. Criteria for diagnosis include at least one of the following: prolonged central capillary 9 refill time > 2 seconds, *tachycardia, mottled skin, *reduced urine output, cyanosis, impaired 10 consciousness, *hypotension. *Variables are defined as values outside the normal range for age. 11 If yes, was an intravenous fluid bolus given? Yes: within 1 hour of arrival, Yes: on the first day of arrival, No If yes, how much intravenous fluid was given? 10 - 20mls/ kg, above 20mls/ kg 12 If less than 10mls/ kg was given please select 'no' for the question asking if intravenous fluid was 13 given. 14 Was the patient hypothermic on arrival? Yes/ No. Defined as < 36.5 degrees Celsius core temperature. Arrival is the time of birth for 15 neonates born at your hospital. If yes, was the patient warmed on arrival to Yes/ No. Only select yes if warming was commenced within 1 hour of arrival. Arrival is the time of 16 within a normal temperature range? birth for neonates born at your hospital. 17 Did the patient receive central venous access? Yes: umbilical catheter, Yes: peripherally inserted central catheter (PICC), Yes: percutaneously 18 For peerinserted central reviewline with ultrasound guidance, only Yes: surgically placed central line (open insertion), No. 19 Please select all that the patient received within 30-days of primary intervention or 30-days of 20 presentation if no intervention was undertaken. 21 If yes, did the patient acquire central line Yes: diagnosed clinically, Yes: confirmed on microbiology, No sepsis? Within 30-days of primary intervention or 30-days of presentation if no intervention was 22 undertaken. 23 Time from arrival at your hospital to primary (enter 0 if no intervention was undertaken) 24 intervention in hours Primary intervention for each condition is defined as: Oesophageal atresia; surgery, either 25 temporising or definitive, to manage the oesophageal atresia and/ or tracheo-oesophageal fistula. Congenital diaphragmatic hernia; surgery to reduce the hernia and close the defect. 26 Intestinal atresia; surgery, either temporising or definitive, to manage the obstruction including 27 stoma formation and primary anastomosis. Gastroschisis; any procedure to either cover or 28 reduce the bowel and/ or close the defect. This includes application of a silo (regardless of whether or not they go on to require surgery). It excludes initial covering of the bowel in a plastic 29 covering (bag or cling film) prior to intervention. Exomphalos; surgery or application of topical 30 treatment to the sac in patients managed conservatively (regardless of whether or not they go on 31 to require surgery). Hirschsprung's disease; surgery, either temporising or definitive, or rectal/ 32 distal bowel irrigation, laxatives or digital stimulation in patients managed conservatively. This does not include pre-operative washouts in patients planned to have surgery. Anorectal 33 malformation; surgery, either temporising or definitive, or anal/ fistula dilatation in patients with a 34 low anorectal malformation managed conservatively. 35 American Society of Anesthesiologists (ASA) 1. Healthy person, 2. Mild systemic disease, 3. Severe systemic disease, 4. Severe systemic Score at the time of primary intervention disease that is a constant threat to life, 5. A moribund patient who is not expected to survive 36 without the operation, Not applicable - no intervention
37 What type of anaesthesia was used for the General anaesthesia with endotracheal tube, General anaesthesia with laryngeal airway, http://bmjopen.bmj.com/ 38 primary intervention? Ketamine anaesthesia, Spinal/ caudal anaesthesia, Local anaesthesia only, No anaesthesia/ just 39 analgesia, No anaesthesia/ no analgesia, Not applicable: no surgery or intervention undertaken. Who undertook the anaesthetic for the primary Anaesthetic doctor, Anaesthetic nurse, Medical officer, Surgeon, Other healthcare professional, 40 intervention? No anaesthetic undertaken 41 If more than one of these personnel were present please select the most senior. 42 Who undertook the primary intervention? Paediatric surgeon (or junior with paediatric surgeon assisting/ in the room), General surgeon (or junior with paediatric surgeon assisting/ in the room), Junior doctor, medical officer or other 43 (without a paediatric or general surgeon assisting/ in the room), Trainee surgeon (without a 44 paediatric or general surgeon assisting or in the room), Not applicable - no surgery or primary intervention undertaken.
45 on September 23, 2021 by guest. Protected copyright. 46 Was a Surgical Safety Checklist used at the Yes, No: but it was available, No: it was not available, Not applicable: a conservative primary time of primary intervention? intervention was undertaken, Not applicable: no surgery or primary intervention undertaken 47 Total duration of antibiotics following primary In days (including the day of surgery and the day antibiotics were stopped. Include intravenous 48 intervention and oral antibiotics). 49 Did the patient receive a blood transfusion? Yes: not cross-matched, Yes: cross-matched, No: not required, No: it was required but not available. Within 30-days of primary intervention or 30-days of presentation if no intervention was 50 undertaken. 51 Did the patient require ventilation? Yes: and it was given, Yes: but it was not available, No 52 Within 30-days of primary intervention or 30-days of presentation if no intervention was 53 undertaken. Please include all types of ventilation. If yes, for how long did the patient remain on In days (include all days on ventilation within 30-days of primary intervention or 30-days of 54 ventilation? presentation if no intervention was undertaken). 55 Time to first enteral feed (post-primary In days (include the day of primary intervention and the day of first enteral feed in the 56 intervention) calculation). Enter 0 if enteral feeds were not commenced. Enter 999 if feeds were not stopped, for example in patients with Hirschsprung's Disease managed conservatively. Include all types of 57 enteral feeding - oral, nasogastric, gastrostomy and other. 58 Time to full enteral feeds (post-primary In days (enter 0 if the patient died before reaching full enteral feeds or 30 if the patient had not 59 intervention) reached full enteral feeds at 30-days post primary intervention or 30-days following admission in 60
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3 patients who did not receive a primary intervention). Include all types of enteral feeding - oral, BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 nasogastric, gastrostomy and other. 5 Did the patient require parenteral nutrition? Yes and it was given, Yes and it was sometimes available but less than required, Yes but it was not available, No 6 If yes, for how long did the patient receive In days. Include all days that the patient received parenteral nutrition (any volume) up until 30- 7 parenteral nutrition? days post primary intervention or 30-days following presentation in patients who do not receive 8 an intervention. Outcomes 9 Did the patient survive to discharge? Yes/ No 10 Select yes if the patient was still alive in your hospital 30-days after primary intervention or 30- 11 days after presentation in patients who do not receive a primary intervention. 12 If the patient was discharged prior, were they Yes, No: not followed-up after discharge, Followed-up but not until 30-days post primary still alive at 30-days following primary intervention 13 intervention? This can include all reliable communication with the patient/ patient's family including in person, 14 via telephone and other. 15 If no, cause of death? Sepsis, Aspiration pneumonia, Respiratory failure, Cardiac failure, Malnutrition, Electrolyte disturbance, Haemorrhage, Lack of intravenous access, Hypoglycaemia, Recurrent tracheo- 16 oesophageal fistula, Recurrent diaphragmatic hernia, Anastomotic leak, Ischaemic bowel, 17 Ruptured exomphalos sac, Enterocolitis, Other. If other, please specify 18 Duration of hospital stay (days) For peerPlease include thereview day of admission and only the day of discharge in your calculation. For example, if a patient presented on 1st October and was discharged on the 5th October, their duration of 19 hospital stay would be 5 days. If the patient died, please record the number of days from 20 admission to death. Only include the duration of the primary admission, not subsequent 21 admissions if the patient re-presented. 22 Did the patient have a surgical site infection? Yes, No, Not applicable: no surgical wound This is defined as one or more of the following within 30-days of surgery: 1) purulent drainage 23 from the superficial or deep (fascia or muscle) incision, but not within the organ/ space 24 component of the surgical site OR 2) at least two of: pain or tenderness; localised swelling; 25 redness; heat; fever; AND the incision is opened deliberately to manage infection, spontaneously dehisces or the clinician diagnoses a SSI (negative culture swab excludes this criterion) OR 3) 26 there is an abscess within the wound (clinically or radiologically detected). 27 Did the patient have a full thickness wound Yes, No, Not applicable - no surgical wound. 28 dehiscence? This is defined as all layers of the wound opening within 30-days of surgery 29 Did the patient require a further unplanned Yes - percutaneous intervention, Yes - surgical intervention, No, Not applicable - no primary intervention? intervention undertaken. Within 30-days of primary intervention. This does not include routine 30 reduction and closure of the defect in neonates with gastroschisis receiving a preformed silo. 31 Was the patient followed up at 30-days post Yes: reviewed in person, Yes: via telephone consultation, Yes: via other means, Yes: still an in- 32 primary surgery or intervention to assess for patient at 30-days, No: data is based on in-patient observations only, No: follow-up was done but complications? prior to 30-days 33 If the patient had a complication, when was it During the primary admission, As an emergency re-attender, At routine follow-up as an out- 34 diagnosed? patient, Not applicable: no complications 35 What study condition does this patient have? Oesophageal atresia, Congenital diaphragmatic hernia, Intestinal atresia, Gastroschisis, 36 Exomphalos/ Omphalocele, Anorectal malformation, Hirschsprung's Disease If the patient has presented for the first time with more than one of these conditions please select
37 all that apply. If the patient presented on this occasion with one of these conditions, but http://bmjopen.bmj.com/ 38 previously had another condition managed then only select the condition they are presenting with 39 on this occasion and enter that they have another anomaly in the demographics section above. For example, if the patient presents at 2-months with Hirschsprung's disease, but previously had 40 a duodenal atresia repair please select Hirschsprung's disease here (not intestinal atresia) and 41 tick in the section above that they have another gastrointestinal anomaly. 42 43 44 Data Quality
45 on September 23, 2021 by guest. Protected copyright. 46 To ensure high quality of data, a detailed protocol for collaborators has been produced and published 47 on the study website (www.globalpaedsurg.com) in 12 languages: English, French, Spanish, Portuguese, German, Italian, Chinese, Arabic, Korean, Lithuanian, Turkish and Russian. Clear and 48 concise definitions have been provided for all data points on the protocol, on the data collection forms 49 and within REDCap when entering the data. A study launch meeting was undertaken where the 50 principal investigator presented the data collection process in detail, demonstrated use of REDCap 51 and answered questions. This was recorded, circulated to all collaborators via email and placed on 52 the website. A frequently asked questions document has been circulated via email and placed on the 53 website. Two meetings were held by the principal investigator to detail the study, data collection 54 process and answer questions amongst the country leads so they in turn can provide advice and 55 support to local collaborators within their country. Again this was recorded, circulated and placed on 56 the website. 57 58 A pilot study of the patient data collection form and institutional survey was undertaken by lead 59 investigators to optimise the study design and to address any feasibility or other barriers to effective 60 data collection and study completion across participating sites. The pilot study commenced on 1st
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3 August 2018 for 30 days in English, Spanish and French by 41 collaborator colleagues. The data BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 collection forms were amended following feedback to clarify terminology, add important missing 5 variables or descriptions and correct any translation errors. All translated data collection forms, 6 REDCap and study documentation has been checked and verified by a native speaker for accuracy. 7 8 Data Validation 9 10 Ten percent of collaborating centres will be selected at random for data validation by an independent 11 research collaborator. The aim will be to determine the numbers of patients eligible during the data 12 collection period to check if any were missed and collect a selection of data again to cross-check for 13 accuracy. Validating questions have been built into the data collection tool. At least 90% of primary 14 and secondary outcomes must be completed for each patient. All collaborators within validating 15 centres will be asked to complete a brief survey regarding their experience with data collection to 16 identify any potential errors and to aid with data interpretation. 17 18 Sample Size CalculationFor peer review only 19 20 A sample size calculation was undertaken using Stata/IC 15.0 based on Bonferroni correction for 21 multiple testing, assuming 80% power and an overall type 1 error of 5%. The required sample size for 22 each condition has been calculated for the primary outcome of mortality in LMICs compared to HICs and also low, middle and high-income countries separately (Table 2). Mortality estimations are based 23 on pooled data from published studies on these conditions in low-, middle- and high-income countries 24 respectively. 25 26 Based on the patient numbers included in the previously undertaken PaedSurg Africa study, which 27 utilised a similar study design, the estimated sample sizes to detect a significant difference between 28 LMICs and HICs in this study are achievable.13 29 30 Table 2. Estimated mortality and sample sizes for low, middle and high-income countries and 31 the mean number of cases per month per institution globally 32 33 Condition Mortality LIC Mortality MIC Mortality Mortality Sample Sample Sample Sample Mean no. 34 (%, n) (%, n) LMIC HIC size for size for size for size for cases/ month/ 35 combined (%, n) LIC MIC HIC LMIC vs institution (%, n) HIC (per (L,M&HIC 36 group) combined)
37 OA +/- TOF 79.5% 41.8% 43.7% 2.7% 34 34 23 21 1.02 http://bmjopen.bmj.com/ 38 (62/78) (623/1488) (685/1566) (6/221) 39 CDH - 47.4% 47.4% 20.4% - - - 63 0.54 (130/274) (130/274) (201/982) 40 IA 42.9% 40.0% 41.0% 2.9% 6014 6014 25 24 0.63 41 (42/98) (97/241) (139/339) (12/407) 42 Gastroschisis 83.1% 42.6% 56.6% 3.7% 29 29 24 15 0.85 43 (211/254) (205/481) (416/735) (28/748) Exomphalos 25.5% 31.9% 30.1% 12.7% 1040 1040 196 115 0.63 44 (41/161) (132/414) (173/575) (40/316)
45 ARM 26.3% 17.5% 18.1% 3% 460 460 90 85 1.34 on September 23, 2021 by guest. Protected copyright. 46 (26/99) (243/1391) (269/1490) (14/462) 47 Hirschsprung’s 19.1% 16.8% 17.6% 2.3% 5802 5802 85 79 2.21 48 Disease (33/173) (55/328) (88/501) (43/1897) 49 50 Estimated Study Population 51 52 The mean number of cases presenting to an institution per month for each study condition was 53 estimated from published studies across all income settings (Table 2). On average most institutions 54 caring for patients with these conditions receive 1-2 new cases per month; each participating 55 institution would expect approximately 7-14 new cases in the study per month although this can vary. 56 The aim is to include a minimum of 365 months of data; 183 months from LMICs and 183 months 57 from HICs. This should ensure enough cases of exomphalos to determine a significant difference 58 between LMICs and HICs; fewer months of data are required to determine significant differences 59 between other study conditions. An up-to-date total of patient numbers within the study will be maintained on the study website. 60
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3 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 Data Analysis 6 7 Patient and Institutional Data: 8 9 Data will be analysed using Stata and SAS 9.4 (Cary, NC; USA). Missing data for the covariates will 10 be analysed to determine whether it is related to the outcome and either complete-case analyses or 11 multiple imputation techniques will be used for analyses accordingly. 12 13 Significant differences in mortality between LMICs and HICs will be determined for each of the study 14 conditions using Chi-squared analysis, or Fischer’s exact test if either group contains less than 10 15 patients. World Bank classification of low-, middle- and high-income countries during the fiscal year 38 16 2018 will be used. 17 Univariate logistic regression analyses will be conducted between covariates and the primary 18 outcome of mortality. ForBased on peer the results, covariatesreview with a p-value only of <0.10 will be included in the 19 multivariate model. The final multi-level multivariate logistic model will be determined using stepwise 20 backward elimination to interventions and peri-operative factors affecting outcomes. Data will be 21 adjusted for confounding factors and effect modifiers. Potential confounders include: gestation age at 22 birth, weight, time from birth to presentation and ASA score at the time of primary intervention. 23 Potential effect modifiers include: administration of peri-operative antibiotics, fluid resuscitation, 24 thermal control and provision of other condition specific neonatal care such as parenteral nutrition in 25 neonates with gastroschisis. 26 27 Multi-level multivariate logistic regression analysis will also be undertaken to identify institutional 28 factors affecting mortality with adjustment for confounders. P< 0.05 will be deemed significant. 29 30 Data Validation: 31 32 A weighted kappa statistic will be utilised to determine the level of agreement between the patient 33 data in the main study and the validation data. A weighted kappa statistic will be also utilised to 34 determine the level of agreement between institutional surveys independently completed by the local 35 study lead and one other consultant or registrar at each participating centre. Results will be presented 36 as a proportion of agreement for each variable being validated.
37 http://bmjopen.bmj.com/ 38 39 Patient and Public Involvement 40 CDH UK, a patient and family advisory group and charity, provided input into the design of the study 41 protocol and data collection tool. Their input will be sought on the findings and dissemination of the 42 results. 43 44
45 ETHICS AND DISSEMINATION on September 23, 2021 by guest. Protected copyright. 46 47 Research Ethics Approval 48 49 The study has been classified as an audit at the host institution and hence did not require ethical 50 approval. The study fulfils the audit criteria as follows: 1) All data collected measures current practice. 51 The study does not involve any changes to patient management; 2) Current practice and outcomes in 52 low, middle and high-income countries will be compared to published standards in the literature. 53 Table 2 details the current mortality standards for each of the seven study conditions in high-income countries; 3) All the study data is routinely collected information which should be known to the study 54 team without asking additional questions to the patients/parents; 4) All data to be entered into 55 REDCap is entirely anonymous; 5) No individual patient, collaborator, institution or country will be 56 independently identifiable in the study results; 6) All data will be stored securely and will be governed 57 by King’s College London data protection team. 58 59 60
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3 Research collaborators were required to gain approval to participate in the study at their institution BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 according to their local ethical regulations. Data transfer agreements were legally signed between 5 institutions where required. The participating institutions, type of study approval and study approval 6 reference numbers are detailed in Supplementary File 3. It was not mandated for study approvals to 7 be translated into English. Hence, some reference numbers are in the local scripture of the 8 participating country and have therefore not been incorporated into the table. 9 10 Study Dissemination 11 12 The study concept and design will be presented at international conferences in order to recruit 13 collaborators. Following completion, the results will be presented at local, national and international 14 conferences globally. Both the promotional presentations of the study protocol and the study results 15 will be presented by study collaborators of all levels of training, disciplines and regions of the world. 16 The results will be submitted for open access publication in a peer reviewed journal. Following 17 publication, the full anonymous, de-identified dataset will be made publicly available via an online 18 repository. CollaboratorsFor will have peer the opportunity review to undertake sub-analysesonly of the data for their 19 country (if all collaborators from that country agree), region or continent. 20 21 22 DISCUSSION 23 This study aims to define, for the first time, the management and outcomes of a selection of common 24 life-threatening congenital anomalies across the globe. This will help to raise awareness of the 25 unacceptable disparities in outcomes between low-, middle- and high-income countries and the need 26 to focus on improving access to quality surgical care for neonates with congenital anomalies within 27 national health plans and global health prioritisation. It is hoped that factors affecting mortality and 28 morbidity will be identified that can be modified to improve care. Establishment of the Global 29 PaedSurg Research Collaboration developed during this study will create a platform for ongoing 30 collaborative work and interventional studies aimed at improving outcomes in the future. 31 32 33 34 35 36
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3 ADDITIONAL INFORMATION BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 Twitter: @GlobalPaedSurg 6 7 Website: http://globalpaedsurg.com 8 9 Author Contributions: The principal investigator conceived the idea for the study, gained study 10 funding, wrote the study protocol, designed the data collection tools, established the study team, co- 11 ordinated the pilot study, revised the study design/ data collection tools following feedback and made 12 critical revisions to the manuscript for publication. The steering committee contributed critical input 13 and revisions to the funding application, study design, protocol and manuscript for publication. The 14 writing committee drafted the protocol manuscript for publication and contributed as organising 15 committee members. The organising committee assisted in the recruitment of and communication 16 with collaborators to participate in the pilot study, helped to co-ordinate the pilot study and summarise 17 the feedback, made critical revisions to the data collection tools in multiple languages and contributed 18 to the study design. TheFor lead investigators peer contributed review to the study only design and content of the data 19 collection forms through feedback following participation in the pilot study. All contributed to the 20 content of this manuscript. 21 22 Funding Statement: Naomi Wright, Principal Investigator, is funded by the Wellcome Trust through a 23 Clinical PhD in Global Health undertaken at King’s College London (Funder Reference: 24 203905/Z/16/Z). The Wellcome Trust had no input into the study protocol other than to recommend 25 open-access publication in a peer-reviewed journal and to make the anonymised dataset publicly 26 available. Nick Sevdalis’ (NS) research is supported by the National Institute for Health Research 27 (NIHR) Collaboration for Leadership in Applied Health Research and Care South London at King’s 28 College Hospital NHS Foundation Trust. NS is a member of King’s Improvement Science, which is 29 part of the NIHR CLAHRC South London and comprises a specialist team of improvement scientists 30 and senior researchers based at King’s College London. Its work is funded by King’s Health Partners 31 (Guy’s and St Thomas’ NHS Foundation Trust, King’s College Hospital NHS Foundation Trust, King’s 32 College London and South London and Maudsley NHS Foundation Trust), Guy’s and St Thomas’ Charity, the Maudsley Charity and the Health Foundation. NS and Andrew Leather are also supported 33 by the NIHR Global Health Research Unit on Health System Strengthening in Sub-Saharan Africa, 34 King’s College London (GHRU 16/136/54) and by the ASPIRES research programme in LMICs 35 (Antibiotic use across Surgical Pathways - Investigating, Redesigning and Evaluating Systems), 36 funded by the Economic and Social Research Council. The views expressed are those of the authors
37 and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. http://bmjopen.bmj.com/ 38 39 40 Competing Interest’s Statement: Nick Sevdalis is the director of the London Safety and Training 41 Solutions Ltd, which offers training in patient safety, implementation solutions and human factors to 42 healthcare organisations. No other conflicts of interest are declared. 43 44 Patient Consent: Collaborators must follow their local ethical guidelines regarding patient consent.
45 on September 23, 2021 by guest. Protected copyright. 46 47 Ethics Approval: This study has been classified as a clinical audit with written confirmation from King’s College London Ethics Committee that it does not therefore require ethical approval. All 48 participating centres have gained study approval to participate according to their local institutional 49 ethical regulations (Supplementary File 3). 50 51 52 Provenance and Peer Review: Not commissioned; externally peer reviewed. 53 54 Open Access: This is an Open Access article distributed in accordance with the terms of the Creative 55 Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build 56 upon this work, for commercial use, provided the original work is properly cited. 57 Licence Statement: I, the Submitting Author has the right to grant and does grant on behalf of all 58 authors of the Work (as defined in the below author licence), an exclusive licence and/or a non- 59 exclusive licence for contributions from authors who are: i) UK Crown employees; ii) where BMJ has 60
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3 agreed a CC-BY licence shall apply, and/or iii) in accordance with the terms applicable for US Federal BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Government officers or employees acting as part of their official duties; on a worldwide, perpetual, 5 irrevocable, royalty-free basis to BMJ Publishing Group Ltd (“BMJ”) its licensees and where the 6 relevant Journal is co-owned by BMJ to the co-owners of the Journal, to publish the Work in BMJ 7 Open and any other BMJ products and to exploit all rights, as set out in our licence. 8 9 The Submitting Author accepts and understands that any supply made under these terms is made by 10 BMJ to the Submitting Author unless you are acting as an employee on behalf of your employer or a 11 postgraduate student of an affiliated institution which is paying any applicable article publishing 12 charge (“APC”) for Open Access articles. Where the Submitting Author wishes to make the Work 13 available on an Open Access basis (and intends to pay the relevant APC), the terms of reuse of such 14 Open Access shall be governed by a Creative Commons licence – details of these licences and 15 which Creative Commons licence will apply to this Work are set out in our licence referred to above. 16 17 Acknowledgements: Thank you to Bolaji Coker for the REDCap administration and management. 18 Thank you to BeverleyFor Power (CDHpeer UK) for representingreview patients, only parents and families through your 19 feedback on the study design during the pilot study. Thank you to Xiya Ma and Dylan Goh for helping 20 with the Chinese translation of study documentation. 21 22 23 COLLABORATORS 24 25 26 Principal Investigator: Naomi Wright (King’s College London, UK) 27 28 Steering Committee: Niyi Ade-Ajayi (King’s College Hospital, UK), Adesoji Ademuyiwa (Lagos 29 University Teaching Hospital, Nigeria), Emmanuel Ameh (National Hospital, Abuja, Nigeria), Justine 30 Davies (University of Birmingham, UK), Kokila Lakhoo (University of Oxford and Oxford University 31 Hospitals, UK), Dan Poenaru (McGill University, Montreal, Canada), Nick Sevdalis (King’s College 32 London, UK), Emily Smith (Baylor University, Texas, USA), Andy Leather (King’s College London, UK) 33 34 35 Writing Committee: Harmony Ubhi (King’s College London, UK), Samuel Parker (Imperial College 36 London, UK), Godfrey Sama Philipo (Muhimbili University of Health and Allied Sciences, Tanzania)
37 http://bmjopen.bmj.com/ 38 Organising Committee: Sadi Abukhalaf (Al Quds University, Palestine), Nana Adofo-Ansong 39 (Mahikeng Provincial Hospital, South Africa), Melika Akhbari (King’s College London, UK), Ahmad 40 Alhamid (University of Aleppo, Syria), Osaid H. Alser (University of Oxford, UK), Emrah Aydin (Koc 41 University, Turkey), Yousra-Imane Benaskeur (Universite de Montreal, Canada), Shrouk M. Elghazaly 42 (Assiut University, Egypt), Safa abdal Elrais (University of Tripoli, Libya), Sophia Hashim (University College London, UK), Laura Herrera (Geisel School of Medicine, Dartmouth, USA), Gabriella Hyman 43 (University of Witwatersrand, South Africa), Henang Kwasau (College of Medicine and Allied Health 44 Sciences, University of Sierra Leone), Yang Liu (Children’s Hospital, Zhejiang University School of
45 on September 23, 2021 by guest. Protected copyright. Medicine, China), Bruno Martinez-Leo (Moctezuma Children’s Hospital, Mexico), Kelly Naranjo 46 (Columbia University Medical Centre, USA), Ibrahim Nour (Jordan University Hospital, Jordan), 47 Cristiana Riboni (University of Pavia, Italy), Mahmoud Saleh (University of Gezira, Sudan), Hosni 48 Khairy Salem (Cairo University, Egypt), Patricia Shinondo (University Teaching Hospital, Lusaka, 49 Zambia), Marcus Sim (Stepping Hill Hospital, UK), Hannah Thompson (King’s College Hospital, UK), 50 Agota Vaitkiene (Vilnius University Hospital Santaros Kliniko, Lithuania), Dominique Vervoort 51 (Harvard Medical School, USA), Isabelle Williams (Cambridge University, UK), Aayenah Yunus 52 (King’s College London, UK). 53 54 Lead Investigators: Muhammad Amjad Chaudhary, Adnan Ahmed Khan Khattak, Muhammad Bin 55 Amjad (Children’s Hospital, PIMS, Islamabad, Pakistan), Marlene Dominguez Anaya (Children’s 56 Hospital Manuel A.Villarroel Cochabamba, Bolivia), Samiul Hasan, Sabbir Karim, Ashrarur Rahman 57 Mitul (Dhaka Shishu (Children) Hospital, Bangladesh), Paolo Bragagnini, Segundo Rite (Hospital 58 Universitario Miguel Servent, Zaragoza), Hana Arbab, Lubna Samad, Aqil Soomro (Indus Hospital, 59 Pakistan), Niveshni Maistry (John Radcliffe Hospital, UK), Raed Nael Al-Taher, Ibrahim Rabi Nour, 60 Osama Abdul Kareem Sarhan (Jordan University Hospital, Jordan), Muhammad Arshad, Taimur
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3 Qureshi, Hina Yousaf (Liaquat National Hospital, Pakistan), Candy SC Choo, Doris Mae Dimatatac, BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Shireen Anne Nah (KK Women’s and Children’s Hospital, Singapore), Vijay Anand Ismavel, Ann 5 Miriam, Shajin T (Makunda Christian Leprosy and General Hospital, India), Monica Ivanov, 6 Andreea Serban (Marie Curie Hospital in Bucharest, Romania), Bruno Martinez-Leo (Moctezuma 7 Children’s Hospital, Mexico), Eva Blazquez-Gomez, Luis Garcia-Aparicio, Martí Iriondo, Jordi Prat, 8 Xavier Tarrado (Hospital Sant Joan de Deu, Spain), Lars Hagander, Emma Svensson (Skane 9 University Hospital’s Pediatric Care Hospital, Lund, Sweden), Alhassan Abdul-Mumin, Dominic 10 Bagbio, Sheila Owusu, Stephen Tabiri (Tamale Teaching Hospital, Ghana), Dayang Anita Abdul Aziz 11 (UKM Medical Centre, Kuala Lumpur, Malaysia). 12 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44
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3 REFERENCES BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 1. GBD Child Mortality Collaborators. Global, regional, national, and selected subnational levels 6 of stillbirths, neonatal, infant, and under-5 mortality, 1980-2015: a systematic analysis for the Global 7 Burden of Disease Study 2015. Lancet 2016; 388(10053): 1725-74. 8 2. Boyle B, Addor MC, Arriola L, et al. Estimating Global Burden of Disease due to congenital 9 anomaly: an analysis of European data. Arch Dis Child Fetal Neonatal Ed 2017. 10 3. Flores A, Valencia D, Sekkarie A, et al. Building capacity for birth defects surveillance in 11 Africa: Implementation of an intermediate birth defects surveillance workshop. J Glob Health Perspect 12 2015; 2015. 13 4. Sitkin NA, Ozgediz D, Donkor P, Farmer DL. Congenital anomalies in low- and middle-income 14 countries: the unborn child of global surgery. World J Surg 2015; 39(1): 36-40. 15 5. Ozgediz D, Langer M, Kisa P, Poenaru D. Pediatric surgery as an essential component of 16 global child health. Semin Pediatr Surg 2016; 25(1): 3-9. 17 6. Farmer D, Sitkin N, Lofberg K, Donkor P, Ozgediz D. Surgical Interventions for Congenital 18 Anomalies. In: DebasFor HT, Donkor peer P, Gawande review A, Jamison DT, Krukonly ME, Mock CN, eds. Essential 19 Surgery: Disease Control Priorities, Third Edition (Volume 1). Washington (DC); 2015. 20 7. Sakonidou S, Ali K, Farmer I, Hickey A, Greenough A. Mortality and short-term morbidity in 21 infants with exomphalos. Pediatr Int 2018. 22 8. Ameh EA, Seyi-Olajide JO, Sholadoye TT. Neonatal surgical care: a review of the burden, progress and challenges in sub-Saharan Africa. Paediatr Int Child Health 2015; 35(3): 243-51. 23 9. Ekenze SO, Ajuzieogu OV, Nwomeh BC. Challenges of management and outcome of 24 neonatal surgery in Africa: a systematic review. Pediatr Surg Int 2016; 32(3): 291-9. 25 10. Wright NJ, Zani A, Ade-Ajayi N. Epidemiology, management and outcome of gastroschisis in 26 Sub-Saharan Africa: Results of an international survey. Afr J Paediatr Surg 2015; 12(1): 1-6. 27 11. PaedSurg Africa Research Collaboration. Paediatric Surgery across Sub-Saharan Africa: A 28 Multi-Centre Prospective Cohort Study. https://clinicaltrials.gov/ct2/show/NCT03185637 (Accessed 29 26th January 2019). 30 12. Bradnock T, Marven S, Owen A, et al. Gastroschisis: one year outcomes from national cohort 31 study. BMJ 2011; 343(d6749). 32 13. Krishnaswami S, Nwomeh BC, Ameh AE. The pediatric surgery workforce in low- and middle- 33 income countries: problems and priorities. Semin Pediatr Surg 2016; 25(1): 32-42. 34 14. Okoye MT, Ameh EA, Kushner AL, Nwomeh BC. A pilot survey of pediatric surgical capacity 35 in West Africa. World J Surg 2015; 39(3): 669-76. 36 15. United Nations. Sustainable Development Goals. 2015.
37 http://www.un.org/sustainabledevelopment/health/ (accessed 27th February 2018). http://bmjopen.bmj.com/ 38 16. Wright NJ, Anderson JE, Ozgediz D, Farmer DL, Banu T. Addressing paediatric surgical care 39 on World Birth Defects Day. Lancet 2018; 391(10125): 1019. 40 17. GlobalSurg Collaborative. Mortality of emergency abdominal surgery in high-, middle- and 41 low-income countries. Br J Surg 2016; 103(8): 971-88 42 18. GlobalSurg Collaborative. Surgical site infection after gastrointestinal surgery in high-income, 43 middle-income, and low-income countries: a prospective, international, multi-centre cohort study. 44 Lancet Infect Dis 2018; 18(5): 516-25. 19. GlobalSurg Collaborative. Laparoscopy in management of appendicitis in high-, middle-, and
45 on September 23, 2021 by guest. Protected copyright. low-income countries: a multicenter, prospective, cohort study. Surg Endosc 2018. 46 20. GlobalSurg Collaborative. Determinants of morbidity and mortality following emergency 47 abdominal surgery in children in low-income and middle-income countries. BMJ Glob Health 2016; 48 1(4): e000091. 49 21. Bhangu A, Kolias AG, Pinkney T, Hall NJ, Fitzgerald JE. Surgical research collaboratives in 50 the UK. Lancet 2013; 382(9898): 1091-2. 51 22. Long AM, Bunch KJ, Knight M, Kurinczuk JJ, Losty PD, Baps C. Early population-based 52 outcomes of infants born with congenital diaphragmatic hernia. Arch Dis Child Fetal Neonatal Ed 53 2018. 54 23. Ruttenstock E, Wright N, Barrena S, et al. Best oxygenation index on day 1: a reliable marker 55 for outcome and survival in infants with congenital diaphragmatic hernia. Eur J Pediatr Surg 2015; 56 25(1): 3-8. 57 24. Burjonrappa S, Crete E, Bouchard S. Comparative outcomes in intestinal atresia: a clinical 58 outcome and pathophysiology analysis. Pediatr Surg Int 2011; 27(4): 437-42. 59 25. Forrester MB, Merz RD. Structural birth defects associated with omphalocele and 60 gastroschisis, Hawaii, 1986-2001. Congenit Anom (Kyoto) 2008; 48(2): 87-91.
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3 26. Kunz SN, Tieder JS, Whitlock KJ, Jackson C, Avansino JR. Primary fascial closure versus BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 staged closure with silo in patients with gastroschisis: a meta-analysis. J Pediatr Surg 2013; 48(4): 5 845-57. 6 27. Ross AR, Eaton S, Zani A, Ade-Ajayi N, Pierro A, Hall NJ. The role of preformed silos in the 7 management of infants with gastroschisis: a systematic review and meta-analysis. Pediatr Surg Int 8 2015; 31(5): 473-83. 9 28. Levitt MA, Pena A. Anorectal malformations. Orphanet J Rare Dis 2007; 2: 33. 10 29. Van der Steeg HJ, Schmiedeke E, Bagolan P, et al. European consensus meeting of ARM- 11 Net members concerning diagnosis and early management of newborns with anorectal 12 malformations. Tech Coloproctol 2015; 19(3): 181-5. 13 30. Holschneider A, Hutson J, Pena A, et al. Preliminary report on the International Conference 14 for the Development of Standards for the Treatment of Anorectal Malformations. J Pediatr Surg 2005; 15 40(10): 1521-6. 16 31. Bradnock TJ, Knight M, Kenny S, Nair M, Walker GM, British Association of Paediatric 17 Surgeons Congenital Anomalies Surveillance S. Hirschsprung's disease in the UK and Ireland: incidence and anomalies. Arch Dis Child 2017; 102(8): 722-7. 18 32. Ross AR, HallFor NJ. Outcome peer reporting review in randomized controlled only trials and systematic reviews 19 of gastroschisis treatment: a systematic review. J Pediatr Surg 2016; 51(8): 1385-9. 20 33. Allin BSR, Hall NJ, Ross AR, et al. Development of a gastroschisis core outcome set. Arch 21 Dis Child Fetal Neonatal Ed 2018. 22 34. Allin BS, Irvine A, Patni N, Knight M. Variability of outcome reporting in Hirschsprung's 23 Disease and gastroschisis: a systematic review. Sci Rep 2016; 6: 38969. 24 35. Watanabe S, Suzuki T, Hara F, Yasui T, Uga N, Naoe A. Omphalocele and Gastroschisis in 25 Newborns: Over 16 Years of Experience from a Single Clinic. J Neonatal Surg 2017; 6(2): 27. 26 36. Tan KB, Tan KH, Chew SK, Yeo GS. Gastroschisis and omphalocele in Singapore: a ten-year 27 series from 1993 to 2002. Singapore Med J 2008; 49(1): 31-6. 28 37. Schneider A, Blanc S, Bonnard A, et al. Results from the French National Esophageal Atresia 29 register: one-year outcome. Orphanet J Rare Dis 2014; 9: 206. 30 38. World Bank. World Bank Country and Lending Groups. 2018. 31 https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending- 32 groups (Accessed 26th January 2019). 33 34 35 36
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1 2 3 Management and Outcomes of Gastrointestinal Congenital Anomalies in Low-, BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Middle- and High-Income Countries: Protocol for a Multi-Centre, International, 5 6 Prospective Cohort Study 7 8 9 SUPPLEMENTARY FILE 1: Condition Specific Data Points 10 11 12 Oesophageal Atresia (OA) +/- Tracheo-Oesophageal Fistula (TOF) 13 Question Answers 14 Type of OA +/- TOF (Gross classification) A, B, C, D, E 15 A: without a fistula, B: proximal TOF with distal OA, C: distal TOF with proximal 16 OA, D: proximal and distal TOF, E: H-type TOF without OA. 17 Long or short gap? Long, Short, Unknown Long gap OA: A gap of 4 vertebral bodies or more. Anatomically cases either 18 For peerhave noreview TOF or a gap of over only4 vertebral bodies following division of the distal 19 fistula making primary repair unfeasible. Short OA: A gap of less than 4 vertebral 20 bodies. Primary anastomosis typically feasible. Pneumonia at presentation? Yes: diagnosed clinically, Yes: diagnosed radiologically, Yes: other means of 21 diagnosis, No: patient born in the study centre, No: patient born outside the study 22 centre but no evidence of pneumonia on arrival 23 Pneumonia is defined as lung inflammation typically caused by bacterial or viral 24 infection, in which the air sacs fill with pus and may become solid. Primary intervention: TOF ligation, Oesophageal anastomosis, Oesophagostomy, Gastrostomy, 25 Ligation of the distal oesophagus, Gastro-oesophageal disconnection, Foker 26 technique, Fundoplication, Other (please specify), Palliative care 27 Select all that apply. If the patient had a primary oesophageal anastomosis, Yes, No. (At any stage) 28 was a post-operative oesophagogram undertaken? 29 If yes, routine or clinically indicated? Routine, Clinically indicated 30 If yes, when? Number of days after primary surgery If yes, what was the result? Leak, No leak 31 For patients diagnosed with a leak radiologically, was it Yes, No 32 associated with clinical symptoms? 33 Time to first oral feed post-operatively In days. Please include the day of surgery and the first day of oral feeds in the calculation. Enter 0 if oral feeds were not commenced within 30-days of primary 34 intervention. Do not include other types of enteral feeding such as nasogastric or 35 gastrostomy feeding. 36 Time to full oral feeds In days (enter 0 if the patient died before reaching full oral feeds or 30 if the patient had not reached full oral feeds at 30-days post primary intervention). Do
37 http://bmjopen.bmj.com/ not include other types of enteral feeding such as nasogastric or gastrostomy 38 feeding. 39 For patient's not receiving a primary oesophageal In months (enter unknown if not planned or enter not applicable if primary 40 anastomosis, at what age is definitive surgery planned? anastomosis was undertaken). For patient's not receiving a primary oesophageal Gap assessment, Primary oesophageal anastomosis if possible, Gastric pull-up, 41 anastomosis, what is the future planned procedure? Jejunal interposition, Colonic interposition, Not applicable: primary anastomosis 42 undertaken, Other, Unknown. Select all that apply. If other, please specify. 43 If the patient had surgery, what was the approach? Thoracotomy muscle cutting, Thoracotomy muscle splitting, Thoracoscopy, Laparotomy, Laparoscopy, Limited local incision, Other. 44 During primary surgery. If other, please specify.
45 If thoracoscopic or laparoscopic, was the surgery Yes, No on September 23, 2021 by guest. Protected copyright. 46 converted to open? 47 Did the patient have a condition specific complication Pneumonia, Mediastinitis, Pneumothorax, Chylothorax, Haemothorax, within 30-days of primary intervention? Anastomotic leak, Anastomotic stricture, Recurrent TOF, Other, None 48 Select all that apply. If other, please specify. 49 Did the patient have tracheomalacia? Yes: diagnosed clinically, Yes: diagnosed on bronchoscopy, Yes: diagnosed on 50 CT, Yes: diagnosed on bronchogram, Yes: other method of diagnosis, No If yes, was an intervention undertaken? If other, please Yes: aortopexy, Yes: tracheostomy, Yes: tracheal stent, Yes: supportive 51 specify management (oxygen +/- ventilation) only, Yes: other treatment, No 52 53 Congenital Diaphragmatic Hernia (CDH) 54 55 Question Answers 56 Type of CDH. Left posteriolateral (Bochdalek), Right posteriolateral (Bochdalek), Bilateral posteriolateral (Bochdalek), Central, Anterior (Morgagni), Other. If other, please 57 specify. 58 Type of Bochdalek CDH (CDH Study Group A, B, C, D, Other (specify), Unknown. 59 Classification) Defect A: smallest defect, usually "intramuscular" defect with >90% of the hemi- diaphragm present; this defect involves < 10% of the circumference of the chest 60 wall. Defect B: 50-75% hemi-diaphragm present; this defect involves < 50% of
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3 the chest wall. Defect C: < 50% hemi-diaphragm present; this defect involves BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 >50% of the chest wall. Defect D: largest defect (previously known as 5 "agenesis"); complete or near complete absence of the diaphragm with < 10% hemi-diaphragm present; this defect involves >90% of the chest wall. Surgically, 6 it is an absent posterior rim beyond the spine, absent posterior-lateral rim, and 7 an anterior/anterior-medial rim which is miniscule. As it is truly unusual to have 8 zero tissue at all, this is the CDHSG member consensus. "D" defects should all require a patch (or muscle flap) for repair. 9 If bilateral, what was the type of Bochdalek hernia on the A, B, C, D, Other, Unknown 10 left? If other, please specify. 11 If bilateral, what was the type of Bochdalek hernia on the A, B, C, D, Other, Unknown right? If other, please specify. 12 If antenatally diagnosed, what was the lung-to-head ratio Enter zero if not undertaken/ not known. 13 (LHR)? 14 Was foetal tracheal occlusion (FETO) undertaken? Yes, No 15 If yes, at what gestational age was it inserted? ______, unknown. If yes, at was gestational age was it removed? ______, at birth, unknown. 16 Liver position? Chest, Abdomen, Unknown 17 Did the patient have pulmonary hypertension (at any Yes: diagnosed clinically, Yes: diagnosis confirmed on echocardiography, Yes: 18 stage)? For peerother methodreview of confirming diagnosis, only No, Unknown 19 Persistent pulmonary hypertension of the newborn (PPHN) is defined as the failure of the normal circulatory transition that occurs after birth. It is a syndrome 20 characterised by marked pulmonary hypertension that causes hypoxemia 21 secondary to right-to-left extrapulmonary shunting of deoxygenated blood. It 22 should be suspected whenever the level of hypoxemia is out of proportion to the level of pulmonary disease. Echocardiography plays a major role in screening 23 and assisting in making the diagnosis of PPHN. 24 If yes, treatment given? If other, please specify. Nitric oxide, Prostacyclin, Alprostadil, Milrinone, Other, None: not required, 25 None: required but not available. Did the patient receive extracorporeal membrane Yes, No 26 oxygenation (ECMO)? 27 If yes, for how long? In days. Include the day the patient went onto ECMO and the day they were 28 taken off in the calculation. 29 Primary intervention Primary repair (absorbable sutures), Primary repair (non-absorbable sutures), Patch repair, Palliation, Discharged with planned elective repair, Other 30 If patch repair, material used? Permacol, PTFE, Alloderm, Dacron, Mesh plug, Muscle flap, Surgisis, Other. If 31 other, please specify. 32 Other procedures undertaken at the same time? Chest drain insertion, Abdominal wall patch, Fundoplication, Correction of malrotation, Appendicectomy, Other (specify), None 33 Select all that apply. If other, please specify. 34 Surgical approach: Laparotomy, Laparoscopy, Thoracotomy, Thoracoscopy, Other (please specify) 35 If laparoscopic or thoracoscopic, was the surgery Yes/No. converted to open? 36 Condition specific complication within 30-days of primary Air leak (not just redundant space in the pleural cavity which is common),
37 surgery? Chylothorax, Recurrence, Adhesional obstruction, Other, None. Select all that http://bmjopen.bmj.com/ 38 apply. If other, please specify. 39 40 Intestinal Atresia 41 42 Question Answers Type of intestinal atresia Duodenal, Jejuno-ileal, Colonic 43 Classification of duodenal or colonic atresia 1,2,3,4 44 1) intraluminal web with continuity of the muscular layer, 2) atretic segment without a mesenteric defect, 3) atretic segment with mesenteric defect, 4)
45 on September 23, 2021 by guest. Protected copyright. multiple atresias = string of sausages appearance. 46 Classification of jejuno-ileal atresia 1,2,3a,3b,4 47 1) intraluminal web with continuity of the muscular layer, 2) atretic segment 48 without a mesenteric defect, 3a) atretic segment with mesenteric defect, 3b) apple-peel (bowel wrapped around a single artery), 4) multiple atresias = string 49 of sausages appearance. 50 Primary intervention for duodenal atresia: Duodenoduodenostomy, Duodenojenunostomy, Web excision only, Palliation, 51 Other. If other, please specify. 52 Surgical approach Laparotomy, Laparoscopy, Endoscopy, Other Conversion to open procedure? Yes/ No 53 Type of anastomosis Kimura’s diamond shape, Side-to-side, End-to-end 54 Primary intervention for jejuno-ileal and colonic atresia: Primary anastomosis, Bowel resection, Division of web only, Loop stoma, 55 Divided stoma, Bishop-Koop stoma, Santulli stoma, Palliation, Other. Select all that apply. 56 If bowel was excised, what was the total length of bowel In centimetres (cm). Enter 0 if unknown 57 excised? 58 Surgical approach: Laparotomy, Laparoscopy, Endoscopy, Other Conversion to open procedure? Yes, No 59 Was the distal bowel flushed to check for patency? Yes, No 60
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3 If the patient underwent surgery, did they have a Anastomotic leak, Anastomotic stenosis, Short-gut, Missed additional atresia, BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 condition specific complication within 30-days of primary Adhesive bowel obstruction, Stoma prolapse, Stoma retraction, Parastomal 5 intervention? hernia, Parastomal skin breakdown, Other. If other, please specify. Select all that apply. For the purposes of this study short gut is defined as more 6 than 50% of the small intestine excised (when short bowel syndrome can occur). 7 8 Gastroschisis 9 10 Question Answers 11 Type of gastroschisis Simple, Complex: associated with atresia, Complex: associated with necrosis, Complex: associated with perforation, Complex: associated with closing 12 gastroschisis. Select all that apply. 13 Primary intervention: Primary closure in the operating room (OR), Primary closure at the cotside 14 (Bianchi technique), Staged closure using a preformed silo, Staged closure using an Alexis Wound Retractor and Protector, Staged closure using a surgical 15 silo (including improvised silo), Other method, No intervention undertaken. 16 If other, please specify. 17 Method of defect closure: Fascia and skin closed with sutures, Just skin closed with sutures: fascia left 18 For peeropen, reviewUmbilical cord sutured overonly the defect: fascia left open, Sutureless closure with skin edges opposed and dressing applied, Dressing applied: defect left 19 open to close by secondary intention, Other, Patient died before the defect was 20 closed. If other, please specify. 21 On what day following admission was abdominal wall In days. Please include the first day of admission and the day of closure in the closure achieved? calculation. For example, for a neonate admitted with gastroschisis on 2nd 22 October who had the defect closed on 4th October, please insert 3 days. 23 Did the neonate have any of these complications within Ischemic bowel, Abdominal compartment syndrome (ACS), Necrotising 24 30-days of primary intervention? enterocolitis, None of these Select all that apply. ACS is defined as respiratory insufficiency secondary to 25 compromised tidal volumes, decreased urine output caused by falling renal 26 perfusion or any other organ dysfunction caused by increased intra-abdominal 27 pressure. 28 If the patient has ACS, was the abdomen re-opened? Yes/ No 29 Exomphalos 30
31 Question Answers 32 Type of Exomphalos? Major, Minor 33 Major: >50% of the liver in the exomphalos sac and abdominal wall defect >5cm. 34 Minor: Infants with defects less than 5cm. Hypoglycaemic on arrival? Yes, No, Blood glucose not measured 35 Hypoglycaemia is defined as a blood glucose level below 4 mmol/L (72mg/dL). 36 Primary intervention Primary operative closure, Staged closure, Conservative management If the patient had a staged closure, what was the time In days. Please include the day of the primary intervention and the day of 37 http://bmjopen.bmj.com/ 38 from primary intervention to closure? closure in the calculation. Enter 30 if still not closed at 30-days after primary intervention. 39 If conservative management, was a topical treatment Yes: silver sulfadiazine, Yes: betadine, Yes: honey, Yes: merbromide tannage, 40 applied to the exomphalos sac? Yes: other, no. If other, please specify. 41 If conservative management was undertaken, what is the No further surgery planned, Delayed closure at this hospital, Delayed closure at plan for future management? another hospital, Other. If other, please specify. 42 Did the patient have a ruptured sac? Yes, No 43 44 Anorectal Malformation (ARM)
45 on September 23, 2021 by guest. Protected copyright. 46 Question Answers 47 Type of anorectal malformation (Krickenbeck Low ARM: Perineal (cutaneous) fistula, High ARM: Rectourethral fistula (bulbar), classification) High ARM: Rectourethral fistula (prostatic), High ARM: Rectovesical fistula, High 48 ARM: Vestibular fistula, High ARM: Cloaca, High ARM: No fistula, High ARM: 49 Type unknown at present, Rare variant: Pouch colon, Rare variant: Rectal atresia/ 50 stenosis, Rare variant: Rectovaginal fistula, Rare variant: H fistula, Other 51 Did the neonate have pre-operative bowel perforation? Yes, No What was the primary intervention undertaken? Fistula dilation: no surgery, Loop sigmoid colostomy, Divided sigmoid colostomy, 52 Loop transverse colostomy, Divided transverse colostomy, Other stoma, 53 Anoplasty, Posterior sagittal anorectoplasty (PSARP), Abdominosacroperineal 54 pull-through, Abdominoperineal pull-through, Laparoscopic-assisted pull-through, Palliative care, Other. If other, please specify. Select all that apply. 55 If primary anorectal reconstruction was undertaken, was Yes, no: equipment was not available, no: the equipment was available but not 56 a Peña stimulator or equivalent used to identify the used. Peña stimulator: Muscle locating stimulator commonly used to identify the 57 position of the muscle complex intra-operatively? anal sphincter muscles whilst undertaking a PSARP for patients with ARM. Did the patient have any of the following complications For each of the below answer: Yes, No, Not applicable 58 within 30-days of surgery? 59 - Electrolyte disturbance 60 - High output stoma (over 20mls/kg/day)
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3 - Stoma prolapse/ retraction/ herniation BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 - Peri-stoma skin breakdown (or perianal if primary 5 reconstructive surgery undertaken without a covering stoma) 6 - Anal stenosis in those undergoing primary anorectal 7 reconstruction without covering stoma. 8 What is the plan for future management? No further operative management, Anoplasty/ pull-through planned at your hospital, Anoplasty/ pull-through planned at another hospital, Stoma closure 9 planned at your hospital, Stoma closure planned at another hospital, Other 10 Please tick all that apply. If other, please specify. 11 12 Hirschsprung’s Disease 13 14 Question Answers Time to first passage of meconium after birth Less than 24 hours, 24-48 hours, Over 48 hours, Unknown 15 Features at presentation: Abdominal distension, Bilious vomiting, Non-bilious vomiting, Poor feeding, 16 Suspected enterocolitis, Perforation, Other. Select all that apply. 17 Source of diagnosis of Hirschsprung's disease Genetic, Mucosal biopsy, Full thickness biopsy, Anorectal manometry, Barium 18 For peerenema, review Not confirmed: suspected only only, Other. If on biopsy, what was the method of histology staining. Hemotoxilin and Eosin (H&E), Acetylcholinesterase, Calretinin, Other. 19 Select all that apply. If other, please specify. 20 Length of aganglionosis: Rectal, Sigmoid, Descending colon, Transverse colon, Ascending colon, Small 21 bowel, Unknown at present 22 Primary intervention Conservative: no treatment, Conservative: digital stimulation and laxatives, Conservative: regular rectal washouts/ enemas, Failed conservative management 23 followed by a stoma during the same hospital admission, Primary stoma (with or 24 without pre-operative washouts or enemas prior to a planned stoma placement), 25 Primary pull-through (Swenson), Primary pull-through (Duhamel), Primary pull- through (Soave), Primary pull-through (Other), Transanal posterior anorectal 26 myectomy, Palliative care, Other. 27 If primary pull-through was undertaken, did the patient Yes, No 28 have a covering stoma? Was it laparoscopic assisted? Yes, No 29 Did the patient have any condition specific complications Hirschsprung's associated enterocolitis (HAEC), Electrolyte disturbance, High 30 within 30-days of primary intervention? stoma output (over 20mls/kg/day), Stoma prolapse/ retraction/ herniation, Peri- 31 stoma skin breakdown (or perianal if primary pull-through was undertaken without a covering stoma), Anal stenosis, Post-operative obstruction, Anastomotic leak (if 32 primary pull-through was undertaken without a covering stoma), Other 33 HAEC is defined as inflammation of the small and or large bowel in patient's born 34 with Hirschsprung's disease. If the patient was managed conservatively, please 35 tick if they developed enterocolitis within 30-days of presentation. Select all that apply. 36 What is the plan for future management? No further surgery planned, Anorectal pull-through at your hospital, Anorectal pull-
37 through at a different hospital, Stoma closure, Other, Unknown http://bmjopen.bmj.com/ 38 39 40 41 42 43 44
45 on September 23, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 Management and Outcomes of Gastrointestinal Congenital Anomalies in Low-, BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Middle- and High-Income Countries: Protocol for a Multi-Centre, International, 5 6 Prospective Cohort Study 7 8 9 SUPPLEMENTARY FILE 2 10 Collaborator Survey: Resources and Facilities for Neonatal and Paediatric Surgery 11 12 13 Question Answers Title Professor, Dr, Mr, Mrs, Miss, Ms, Other 14 Surname 15 First Name 16 Professional Position Professor, Consultant or attending, Registrar or resident, Intern/ house 17 officer/ senior house officer, Medical Student, Nurse, Other 18 Are you the study lead at your centre?For peer reviewYes, No only Answers provided by the study lead will be used as the 'Gold Standard' to 19 which the other survey will be compared (this will remain anonymous). 20 Speciality General Surgery (adult and paediatric), Paediatric Surgery, Anaesthetics, 21 Paediatrics, Neonatology, Nursing, Not specialised yet, Other Full name of institution: 22 Address of institution: 23 Country Afghanistan, Albania, Algeria, Andorra, Angola, Antigua and Barbuda, 24 Argentina, Armenia, Aruba (Kingdom of the Netherlands), Australia, 25 Austria, Azerbaijan, Bahamas, Bahrain, Bangladesh, Barbados, Belarus, Belgium, Belize, Benin, Bhutan, Bolivia, Bosnia and Herzegovina, 26 Botswana, Brazil, Brunei Darussalam, Bulgaria, Burkina Faso, Burundi, 27 Cambodia, Cameroon, Canada, Cape Verde, Central African Republic, 28 Chad, Chile, China, Colombia, Comoros, Congo, Costa Rica, Cote d'Ivoire, Croatia, Cuba, Curacao (Kingdom of the Netherlands), Cyprus, 29 Czech Republic, Democratic Peoples Republic of Korea, Democratic 30 Republic of the Congo, Denmark, Djibouti, Dominica, Dominican Republic, 31 Ecuador, Egypt, El Salvador, Equatorial Guinea, Eritrea, Estonia, Eswatini (Swaziland), Ethiopia, Fiji, Finland, France, Gabon, Gambia, Georgia, 32 Germany, Ghana, Greece, Grenada, Guatemala, Guinea, Guinea-Bissau, 33 Guyana, Haiti, Holy See (Vatican City State), Honduras, Hong Kong 34 (China), Hungary, Iceland, India, Indonesia, Iran (Islamic Republic of), Iraq, Ireland, Israel, Italy, Jamaica, Japan, Jordan, Kazakhstan, Kenya, 35 Kiribati, Korea (Republic of), , Kuwait, Kyrgyzstan, Lao People’s 36 Democratic Republic, Latvia, Lebanon, Lesotho, Liberia, Libya, Liechtenstein, Lithuania, Luxembourg, Macau (China), Macedonia (the 37 http://bmjopen.bmj.com/ 38 former Yugoslav Republic of), Madagascar, Malawi, Malaysia, Maldives, Mali, Malta, Marshall Islands, Mauritania, Mauritius, Mexico, Micronesia 39 (Federated States of), Moldova (Republic of), Monaco, Mongolia, 40 Montenegro, Morocco, Mozambique, Myanmar, Namibia, Nauru, Nepal, 41 Netherlands, New Zealand, Nicaragua, Niger, Nigeria, Niue, Norway, Oman, Pakistan, Palau, Palestinian Territories, Panama, Papua New 42 Guinea, Paraguay, Peru, Philippines, Poland, Portugal, Qatar, Republic of 43 Kosovo, Reunion Island, Romania, Russian Federation, Rwanda, Saint 44 Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Samoa, San Marino, Sao Tome and Principe, Saudi Arabia, Senegal, Serbia,
45 Seychelles, Sierra Leone, Singapore, Sint Maarten (Kingdom of the on September 23, 2021 by guest. Protected copyright. 46 Netherlands), Slovakia, Slovenia, Solomon Islands, Somalia, Somaliland, 47 South Africa, South Sudan, Spain, Sri Lanka, Sudan, Suriname, 48 Swaziland (See Eswatini), Sweden, Switzerland, Syrian Arab Republic, Taiwan, Tajikistan, Tanzania (United Republic of), Thailand, Timor-Leste, 49 Togo, Tonga, Trinidad and Tobago, Tunisia, Turkey, Turkmenistan, 50 Tuvalu, Uganda, Ukraine, United Arab Emirates, United Kingdom, 51 Uruguay, USA, Uzbekistan, Vanuatu, Venezuela, Viet Nam, Yemen, Zambia, Zimbabwe 52 Type of institution (WHO classification) - Specialised children's hospital (Provides highly specialised care 53 dedicated to children) 54 - Referral hospital (WHO defined tertiary healthcare. Includes academic, university, teaching, national, central and specialised 55 mission hospitals. Can provide specialised surgical services) 56 - District hospital (WHO defined secondary healthcare. Includes 57 provincial, general, general mission or regional hospitals. Has general 58 anaesthesia and can provide general surgical care) - Health centre (WHO defined primary healthcare. No general 59 anaesthesia, can do minor local procedures, wound management, triage 60 and referral).
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3 Institutional classification Government, Non-government BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Institutional financial classification Not for profit, For profit 5 Population served by your institution (in millions, including children and adults) 6 Personnel 7 Number of Consultant Paediatric Surgeons undertaking ______(Excluding trainees) 8 neonatal surgery at your institution: 9 Number of Consultant General Surgeons (covering adults and children) undertaking neonatal surgery independently at your ______(Excluding trainees) 10 institution: 11 Number of medical officers or other non-surgeon healthcare 12 professionals undertaking neonatal surgery independently at ______(Without a consultant surgeon present at the time 13 your institution of surgery) Infrastructure 14 Please state whether the following facilities are available at your institution when required: 15 Running Water Always, Sometimes, Never 16 Electricity Always, Sometimes, Never 17 Electricity generator back-up Always, Sometimes, Never Laboratory for biochemistry Always, Sometimes, Never 18 Laboratory for haematology For peer reviewAlways, Sometimes, Never only 19 Blood bank Always, Sometimes, Never 20 Sterile gloves and gown Always, Sometimes, Never 21 Autoclave for sterilising surgical equipment Always, Sometimes, Never Neonatal ventilation outside the operating room Always, Sometimes, Never 22 Paediatric ventilation outside the operating room Always, Sometimes, Never 23 Neonatal intensive care unit for surgical neonates pre and post Always, Sometimes, Never 24 operatively (including if a stoma is present) 25 Paediatric intensive care unit for surgical paediatric patients pre Always, Sometimes, Never and post operatively if required 26 Parenteral nutrition for neonates Always, Sometimes, Never 27 Parenteral nutrition for adults and older children Always, Sometimes, Never 28 Extracorporeal membrane oxygenation (ECMO) Always, Sometimes, Never 29 Peña stimulator or equivalent device to identify the muscle Always, Sometimes, Never complex during anorectal reconstruction 30 Suction rectal biopsy gun to investigate for Hirschsprung's Always, Sometimes, Never 31 disease 32 Procedures Please state whether the following procedures are available at your institution when clinically appropriate/ required: 33 Neonatal laparotomy Always, Sometimes, Never 34 Neonatal laparoscopy Always, Sometimes, Never 35 Neonatal thoracotomy Always, Sometimes, Never 36 Neonatal thoracoscopy Always, Sometimes, Never Neonatal central line insertion Always, Sometimes, Never
37 http://bmjopen.bmj.com/ Paediatric central line insertion Always, Sometimes, Never 38 Umbilical vein catheterisation Always, Sometimes, Never 39 Bedside primary reduction and closure of gastroschisis Always, Sometimes, Never 40 (Bianchi technique) Preformed silo application, reduction and closure of Always, Sometimes, Never 41 gastroschisis 42 Surgical silo application, reduction and closure of Always, Sometimes, Never 43 gastroschisis 44 Primary closure of gastroschisis in the operating room Always, Sometimes, Never Sigmoid colostomy Always, Sometimes, Never
45 Posterior Sagittal Anorectoplasty (PSARP) for anorectal Always, Sometimes, Never on September 23, 2021 by guest. Protected copyright. 46 malformation 47 Foetal tracheal occlusion (FETO) for CDH Always, Sometimes, Never 48 Pull-through for Hirschsprung's disease Always, Sometimes, Never Anaesthesia and resuscitation 49 Please state whether the following facilities are available at your institution when required: 50 Neonatal bag, valve and mask Always, Sometimes, Never 51 Paediatric bag, valve and mask Always, Sometimes, Never 52 Bottled oxygen Always, Sometimes, Never Piped oxygen Always, Sometimes, Never 53 Oxygen saturation monitor Always, Sometimes, Never 54 Apnoea monitor Always, Sometimes, Never 55 Multi-parameter intra-operative monitoring Always, Sometimes, Never 56 Anaesthetic machine for neonates Always, Sometimes, Never 57 Anaesthetic machine for children Always, Sometimes, Never Ketamine anaesthesia for neonates Always, Sometimes, Never 58 Ketamine anaesthesia for children Always, Sometimes, Never 59 Spinal/ caudal anaesthesia for neonates Always, Sometimes, Never 60 Spinal/ caudal anaesthesia for children Always, Sometimes, Never
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3 Anaesthetic doctor competent to perform neonatal anaesthesia Always, Sometimes, Never BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Anaesthetic doctor competent to perform paediatric Always, Sometimes, Never 5 anaesthesia Anaesthetic nurse competent to perform neonatal anaesthesia Always, Sometimes, Never 6 Anaesthetic nurse competent to perform paediatric anaesthesia Always, Sometimes, Never 7 Does your country have at least one specialised children's Yes, No 8 hospital that can provide neonatal and paediatric surgery? 9 Any other comments? 10 11 12 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
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1 2 3 Management and Outcomes of Gastrointestinal Congenital Anomalies in Low-, Middle- and High-Income Countries: 4 Protocol for a Multi-Centre, International, Prospective Cohort Study 5 6 7 8 SUPPLEMENTARY FILE 3: Study approval details of participating centres 9 10 Number Country Institution Name Ethical/Audit Review Board Name Approval Type Approval Reference Number Low-Income Countries (LICs) 11 Afghanistan Ataturk National Children’s Hospital Islamic Republic of Afghanistan Ministry of Public Local (Ethical) 444738 12 For peerHealth, review Afghanistan National Public Health only Institute, 13 1 Institutional Review Board 14 Afghanistan French Medical Institute for Mothers and Institutional Review Board Local (Ethical) - 2 Children (FMIC) 15 3 Afghanistan Ghalib University Hospital Ministry of Higher Education, Ghalib Cadre Hospital Local (Ethical) - 16 Afghanistan Ghor Provincial Hospital EPHS Directorate, GD of Curative Medicine, Ministry of Local (Ethical) - 17 4 Public Health http://bmjopen.bmj.com/ 18 5 Afghanistan Indra Ghandi Institute of Child Health (IGICH) Institutional Review Board Local (Ethical) - 6 Afghanistan Irena Salimi Children Hospital (ISCH) Institutional Review Board Local (Ethical) - 19 7 Burundi Bujumbura, Kamenge Military Hospital Head of Department Surgery Local (Departmental) - 20 8 Burundi District Hospital Kibimba, Gitega Medical Director of Kibimba Hospital Local (Hospital) 4000342958 21 9 Burundi Gitega Hospital Mutoyi Hospital Director Local (Hospital) - 22 Burundi Kibuye Hope Hospital, Hope Africa Head of Surgery and Ethics Team Local (Ethical and - 10 University, Gitega Hospital) 23 11 Burundi King Khaled Teaching Hospital Medical Director General Local (Hospital) 2019|DECHUK.359|11.5 24 12 Burundi Teaching Hospital University of Kamenge Medical Director General Local (Hospital) 2019|DECHUK.271|11.5 25 13 Burundi Van Norman Clinic Bjumbura Medical Director of Kibimba Hospital Local on September 23, 2021 by guest. Protected copyright. (Hospital) - 26 Democratic Republic of HEAL Africa Hospital, Goma Institutional Review Board at HEAL Africa Local (Ethical) - 14 Congo 27 15 Ethiopia Addis Ababa University Deputy Head of Department of Surgery Local (Departmental) - 28 Gambia Edward Francis Small Teaching Hospital, Chair of Gambia Government/MRCG Joint Ethics Local (Ethical) - 29 16 Banjul Committee 30 17 Gambia Kanifing General Hospital, Kanifing Gambia Government / MRCG Joint Ethics Committee Regional (Ethical) - 18 Nepal Annapurna Children and Women’s Hospital Medical Director Local (Hospital) - 31 19 Niger National Hospital Lamorde, Niamey Hospital Director General Local (Hospital) 000306 32 Rwanda Centre Hospitalier Universitaire de Butare College of Medicine and Health Science Institutional Local (Ethical) 301/CMHS IRB/2018 33 20 Review Board 34 Rwanda Rwanda Military Hospital College of Medicine and Health Science Institutional Local (Ethical) 301/CMHS IRB/2018 21 Review Board 35 Rwanda University Teaching Hospital of Kigali College of Medicine and Health Science Institutional Local (Ethical) 301/CMHS IRB/2018 36 22 Review Board 37 23 Somaliland Hargeisa Group Hospital Director of Hargeisa Group Hospital Local (Hospital) HGH/800/0.1/18 38 24 Tanzania Kilimanjaro Christian Medical Centre Executive Director Local (Hospital) - 25 Zimbabwe Mpilo Hospital Clinical Director of Mpilo Central Hospital Local (Hospital) - 39 TOTAL LICs: 25 40 41 42 1 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 Middle-Income Countries (MICs) 4 26 Algeria Hôpital Mère-Enfant EHS EL EULMA Institutional Ethical Committee of Ferhat ABBAS Local (Ethical) - 5 University SETIF 27 Algeria Hospital Chu Tizi-ouzou Ethical Committee of the University Mouloud Maameri Local (Ethical) - 6 de Tizi-ouzou 7 28 Algeria Le Nefissa Hamoud University Hospital Institutional Ethics Comittee Local (Ethical) - 8 29 Angola Pediatric Hospital David Bernardino Hospital Director Local (Hospital) 55/09/DIRPED/HPDB/018 9 30 Argentina Children’s Hospital of Santa Fe Associate Director of Teaching and Research Local (Hospital) - 31 Argentina Clinica Pueyrredon Medical Director Local (Hospital) - 10 32 Argentina Dr Humberto Notti Pediatric Hospital of Executive Director Local (Hospital) 3542-D-2018-04238-E-0-6 11 Mendoza 12 33 Argentina Fundación Dr JR Villavicencio Clinical Investigation Ethical Committee Local (Ethical) - 34 Argentina Fundacion HospitalariaFor peerChief ofreview Department of Paediatric Surgery only Local (Departmental) - 13 35 Argentina Hospital de Niños Victor J. Vilela, Rosario, President of the Ethics Committee in Research Local (Ethical) - 14 Santa Fe 15 36 Argentina Hospital Escuela Eva Perón, Rosario Medical Director Local (Hospital) 30630225 16 37 Argentina Hospital Italiano de Buenos Aires, Buenos Ethical Committee Local (Ethical) 139/DGDOIN/14 Anexo 1 17 Aires http://bmjopen.bmj.com/ 38 Argentina Hospital Provincial de Rosario Research Ethics Committee (CEI) Local (Ethical) - 18 39 Argentina Hospital Público Materno Infantil President of the Advisory Commission on Teaching and Local (Hospital) - 19 Investigation 20 40 Argentina Hospital Rawson, San Juan Ethics committee in research Local (Ethical) 33/18 21 41 Argentina Maternidad Martin, Rosario, Santa Fe President of the Ethics Committee in Research Local (Ethical) - 42 Argentina Maternity Clinic Colón Teaching and Research committee Local (Hospital) - 22 43 Argentina Materno Provincial Health Minister, Training, Teaching and Investigation Local (Hospital) - 23 Committee 24 44 Argentina Maternoneonatal, Córdoba Surgical Director Local (Departmental) - 25 45 Argentina Pediatric Hospital of Santiago del Estero Deputy Medical Director Local on September 23, 2021 by guest. Protected copyright. (Hospital) - 46 Argentina Zona Norte Children Hospital Medical Director Local (Hospital) - 26 47 Bangladesh Bangabandhu Sheik Mujib Medical University Chairman, Department of Paediatric Surgery Local (Departmental) - 27 (BSMMU), Dhaka 28 48 Bangladesh Dhaka Medical College Hospital Ethical Committee Local (Ethical) MEU-DMC/ECC/2018/249 29 49 Bangladesh Dhaka Shishu Hospital Hospital Authority Local (Hospital) - 30 50 Belarus Republican Scientific Practical Centre of Ethical Council Local (Ethical) 1-18/394 31 Pediatric Surgery, Minsk 32 51 Bolivia Children's Hospital Manuel A.Villarroel Medical Director Local (Hospital) - 33 Cochabamba 52 Bolivia Hospital Hernandez Vera, Santa Cruz Medical Director Local (Hospital) - 34 53 Bolivia Hospital San Juan de Dios, Tarija Medical Director Local (Hospital) - 35 54 Bolivia Mario Ortiz Children's Hospital Suarez, Santa Medical Director Local (Hospital) - 36 Cruz 55 Bolivia Women’s Hospital Percy Boland Rodriguez Medical Director Local (Hospital) - 37 Santa Cruz 38 56 Bosnia and Herzegovnia Clinic of Paediatric Surgery, Clinical Centre Ethical Committee Local (Ethical) 03-02-47488 (Protocol: 0602- 39 University of Sarajevo, Sarajevo 40400) 40 57 Brazil Associação de Ensino Superior de Nova Iguaçu National Ethical Committee National (Ethical) 3.130.042 41 42 2 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 58 Brazil Associação Hospitalar de Prot Infancia Dr. Raul National Ethical Committee National (Ethical) 3.130.042 4 Carneiro 5 59 Brazil Botucatu Medical School, State of Sao Paulo National Ethical Committee National (Ethical) 3.130.042 University 6 60 Brazil Centro de Ensino São Lucas Ltda/ RO National Ethical Committee National (Ethical) 3.130.042 7 61 Brazil Clinical Hospital from Federal University of National Ethical Committee National (Ethical) 3.130.042 8 Uberlandia 9 62 Brazil Federal University of Minas Gerais National Ethical Committee National (Ethical) 3.130.042 63 Brazil Federal University of Parana National Ethical Committee National (Ethical) 3.130.042 10 64 Brazil Fundação Facudade Regional de Medicina S J National Ethical Committee National (Ethical) 3.130.042 11 Rio Preto 12 65 Brazil Fundação Hospitalar Blumenau: Hospital Santo National Ethical Committee National (Ethical) 3.130.042 Antoni For peer review only 13 66 Brazil Hospital da Criança Santo Antônio – Santa National Ethical Committee National (Ethical) 3.130.042 14 Casa/RS 15 67 Brazil Hospital da Luz/ São Paulo – SP National Ethical Committee National (Ethical) 3.130.042 16 68 Brazil Hospital de Base Dr. Ary Pinheiro, Porto Velho National Ethical Committee National (Ethical) 3.130.042 17 69 Brazil Hospital do Rocio National Ethical Committee Nationalhttp://bmjopen.bmj.com/ (Ethical) 3.130.042 70 Brazil Hospital Federal de Bonsucesso National Ethical Committee National (Ethical) 3.130.042 18 71 Brazil Hospital Infantil Jona de Gusmão/ SES – SC National Ethical Committee National (Ethical) 3.130.042 19 72 Brazil Hospital Jorge Valente/ Salvador - BA National Ethical Committee National (Ethical) 3.130.042 20 73 Brazil Hospital Materno Infantil de Brasília – HMIB National Ethical Committee National (Ethical) 3.130.042 21 74 Brazil Hospital Nossa Senhora da Conceição SA National Ethical Committee National (Ethical) 3.130.042 75 Brazil Hospital Santo Antônio Blumenau Santa National Ethical Committee National (Ethical) 3.130.042 22 Catarina 23 76 Brazil Hospital Universitário de Santa Maria National Ethical Committee National (Ethical) 3.130.042 24 77 Brazil Hospital Universitário do Oeste do Paraná National Ethical Committee National (Ethical) 3.130.042 25 78 Brazil Hospitalar Municipal do M’boi Mirim/ São Paulo National Ethical Committee National on September 23, 2021 by guest. Protected copyright. (Ethical) 3.130.042 - SP 26 79 Brazil Instituto de Medicina Integral Professor National Ethical Committee National (Ethical) 3.130.042 27 Fernando Figueira 28 80 Brazil Instituto Fernandes Figueira, Rio de Janeiro National Ethical Committee National (Ethical) 3.130.042 29 81 Brazil Irmandade da Santa Casa de Misericórdia de National Ethical Committee National (Ethical) 3.130.042 Santos 30 82 Brazil Irmandade Nossa Senhora das Merces de National Ethical Committee National (Ethical) 3.130.042 31 Montes Claros 32 83 Brazil Instituto Fernandes Figueira, Rio de Janeiro National Ethical Committee National (Ethical) 3.130.042 84 Brazil SPDM – Associação Paulista para o National Ethical Committee National (Ethical) 3.130.042 33 Desenvolvimento da Medicina 34 85 Brazil Universidade Estadual de Montes Claros - National Ethical Committee National (Ethical) 3.130.042 35 UNIMONTES 36 86 Brazil Universidade Federal de São Paulo – National Ethical Committee National (Ethical) 3.130.042 UNIFESP/EPM 37 87 Brazil University Hospital, Porto Alegre National Ethical Committee National (Ethical) 3.130.042 38 88 Cameroon Mbingo Hospital in North West Cameroon Institutional Review Board Local (Ethical) - 39 89 China Bayi Children’s Hospital Research Ethics Criteria Local (Ethical) - 40 90 China Children's Hospital of Shanghai In Chinese script Local (Ethical) - 41 42 3 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 91 China Children’s Hospital of Soochow University President of the Seventh Medical Center of PLA Local (Ethical) - 4 General Hospital 5 92 China Children’s Hospital, Zhejiang University School Hospital President and Ethics Committee Local (Ethical) - of Medicine, Binjiang District, Hangzhou 6 93 China First Affiliated Hospital of Xinjiang Medical Research Ethics Criteria Local (Ethical) - 7 University 8 94 China Hunan Children’s Hospital In Chinese script Local (Ethical) - 9 95 China Jinhua Municipal Central Hospital Research Ethics Committee Local (Ethical) - 96 China Kunming Children’s Hospital Medical Ethics Committee Local (Ethical) - 10 97 China Nanjing Children’s Hospital Research Ethics Criteria Local (Ethical) - 11 98 China Ningbo Women Children’s Hospital Research Ethics Criteria Local (Ethical) - 12 99 China Shengjing Hospital In Chinese script Local (Ethical) - 100 China Wenzhou MedicalFor University Affiliate peer 2nd Research review Ethics Criteria onlyLocal (Ethical) - 13 Hospital and Yuying Children Hospital 14 101 China Wuhan Children’s Hospital In Chinese script Local (Ethical) - 15 102 Colombia Bogota Hospital Militar Central Director General Local (Hospital) 2018046 16 103 Colombia Bogota Hospital San Jose Centro Society for President of Society Local (Departmental) - 17 Surgery http://bmjopen.bmj.com/ 104 Colombia Fundacion Valle de Lili Cali Colombia Research and Biomedical Ethics Committee Local (Ethical) 234-2018 18 105 Colombia Materno Infantil Saludcoop, Villavicencio Medical Director Local (Hospital) - 19 106 Dominican Republic Hospital Infantil Dr. Robert Reid Cabral, Santa Investigational Committee Local (Hospital) 20 Domingo 21 107 Ecuador Hospital Especialidades Carlos Andrade Martin, Technical Director Local (Hospital) IESS-HJCA-DT-2018-5098-M Quito 22 108 Ecuador Hospital de Especialidades José Carrasco Hospital Director Local (Hospital) - 23 Arteaga, Cuenca 24 109 Ecuador Hospital de Los Valles Medical Director Local (Hospital) - 25 110 Ecuador Hospital General del Norte de Guayaquil Deputy Director of Teaching Local on September 23, 2021 by guest. Protected copyright. (Hospital) IESS-HG-NGC-DO-2018-0008-O 111 Ecuador Omni Hospital, Gayaquil Director of Teaching Local (Hospital) - 26 112 Egypt Al Zahra Hospital In Arabic script Local (Ethical) - 27 113 Egypt Alexandria University Children’s Hospital Ethics Committee Local (ethical) 0304041 28 114 Egypt Assiut University Hospital In Arabic script Local (Ethical) - 29 115 Egypt Mansoura University Children’s Hospital Head of Department of Pediatric Surgery Council Local (Departmental) 0032610/2020/81A
30 116 Egypt Nasser Institution for Research and Treatment, Hospital Director Letter Local (Ethical) - 31 Cairo 32 117 Egypt Tanta University Hospital In Arabic script Local (Ethical) - 33 118 Gabon Bongolo Hospital, Lebamba Institutional Review Board at Bongolo Hospital Local (Ethical) - 119 Ghana Korle-Bu Teaching Hospital Scientific and Technical Committee & KBTH Local (Ethical) KBTH/MIS/G3/19 34 Institutional Review Board 35 120 Ghana Tamale Teaching Hospital Head of Research and Development Local (Ethical) TTH/R&D/SR/18/8 36 121 India Bazaricherra, Karimganj District Chairman Research Committee Local (Ethical) - 37 122 India Christian Medical college Ludhiana, Punjab Institutional Research Committee Local (Ethical) - 123 India Kasturba Medical College (Kasturba Hospital) Institutional Ethics Committee Local (Ethical) ECR/146/Inst/KA/2013/RR-16 38 Manipal 39 124 India Makunda Christian Leprosy and General Chairman of Research Committee Local (Ethical) - 40 Hospital, Bazaricherra, Karimganj District 41 42 4 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 125 Indonesia Dr Soetomo Hospital, Surabaya President of Indonesian Association of Pediatric Local (Association and 83/PERBANI/XI/2018 4 Surgeons and Head of Institutional Review Board Ethical) IRB/22/04/ETIK/2019 5 126 Indonesia Rumah Sakit Anak dan Bunda Harapan Kita Indonesian Association of Pediatric Surgeons president Local and Regional - Jakarta approval 6 127 Iran Mofid Children’s Hospital (MCH) Research Council of Research Institute for Children Local (Ethical) 0477, 162 7 Health 8 128 Iraq Al-Mustansiriyah University Central Ministry of Higher Education and Scientific Research Local (Ethical) 239 9 129 Iraq Child's Central Teaching Hospital, Ethical Committee Local (Ethical) - Baghdad/Mustansiriyah Medical College 10 130 Iraq University of Kufa Medical Ethics Committee for University Local (Ethical) MEC-035 11 131 Jordan Al-Basheer Hospital Al-Basheer Hospital and Chairman of Pediatric Surgery Local (Departmental, 15999 12 Hospital) 132 Jordan Jordon UniversityFor Hospital of Medicine peer Institutional review Review Board onlyLocal (Ethical) 10/2018/2448 13 133 Jordan JUST King Abdallah University Hospital Institutional Review Board Local (Ethical) 4/118/2018 14 134 Kenya Aga Khan University Hospital Research Ethics Committee, Aga Khan University Local (Ethical) 2018/REC-138 (v1) 15 135 Kenya Joromongi Oginga Odinga Teaching & Referral JOOTRH Institutional Ethics and Research Committee Local (Ethical) ERC.IB/VOL.1/475 16 Hospital, Kisumu 17 136 Kenya University of Nairobi and Kenyatta National Kenyatta National Hospital – University of Nairobi Local http://bmjopen.bmj.com/ (Ethical) KNH-ERC/A/6 Hospital Ethics and Research Committee 18 137 Libya Al Fardous Clinic Ethical Approval from Head of Medical Services Local (Ethical) 2/018 P. 19 138 Libya Alaml Specialised Hospital, Misurata Ethical Approval from Head Director of Alaml Local (Ethical) - 20 Specialized Hospital 21 139 Libya Asalam, Misurata In local script Local (Ethical) - 140 Libya Assafwa international hospital, Misurata Ethical Approval from Head of Medical Service Local (Ethical) - 22 141 Libya Dar Alhekma Hospital Head Director of Dar Alhekma Specialized Hospital Local (Ethical) - 23 142 Libya Ghout El-Shaal Specialized Hospital In local script Local (Ethical) - 24 143 Libya Misarata Cancer Centre Director of Medical Affairs, Chief of Medical Ethics Local (Ethical) 708/42. 25 144 Libya Misurata Medical Centre Medical Director Local on September 23, 2021 by guest. Protected copyright. (Ethical) - 26 145 Libya Tripoli Children’s Hospital Ethical Committee Local (Ethical) NCDC:E17:2018. 146 Libya Tripoli Medical Centre Hospital Director Local (Hospital) - 27 147 Macedonia University Clinic for Paediatric Surgery Ethical Committee Local (Ethical) - 28 148 Malaysia Hospital Canselor Tuanku Muhriz, UKM Research Ethics Committee Local (Ethical) UKM PPI/111/8/JEP-2018-464 29 Medical Centre 149 Malaysia Hospital Kuala Lumpar Medical Research and Ethics Committee of Ministry of Regional (Ethical) KKM/NIHSEC/ P18-1816 (14) 30 Health Malaysia 31 150 Malaysia Hospital Pulau Pinang Medical Research and Ethics Committee of Ministry of Regional (Ethical) KKM/NIHSEC/ P18-1816 (14) 32 Health Malaysia 33 151 Malaysia Hospital Raja Perempuan Zainab II, Kota Medical Research and Ethics Committee of Ministry of Regional (Ethical) KKM/NIHSEC/ P18-1816 (14) Bharu, Kelantan Health Malaysia 34 152 Malaysia Hospital Sultanah Aminah, Johor Bharu, Johor Medical Research and Ethics Committee of Ministry of Regional (Ethical) KKM/NIHSEC/ P18-1816 (14) 35 Health Malaysia 36 153 Malaysia Hospital Sultanah Nur Zahirah, Kuala Medical Research and Ethics Committee of Ministry of Regional (Ethical) KKM/NIHSEC/ P18-1816 (14) 37 Terengganu, Terengganu Health Malaysia 154 Malaysia Hospital Tengku Ampuan Afzan, Kuantan Medical Research and Ethics Committee of Ministry of Regional (Ethical) KKM/NIHSEC/ P18-1816 (14) 38 Health Malaysia 39 155 Malaysia Hospital Wanita dan Kanak-Kanak, Likas, Medical Research and Ethics Committee of Ministry of Regional (Ethical) KKM/NIHSEC/ P18-1816 (14) 40 Sabah Health Malaysia 41 42 5 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 156 Malaysia Penang General Hospital Ethics & Medical research Committee Local (Ethical) KKM/NIHSEC/P18-1816(11) 4 157 Mexico Hospital General Tijuana, Baja California Research and Ethics Committee Local (Ethical) - 5 158 Mexico Hospital Civil de Guadalajara Research Committee and Ethics Committee Local (Ethical) 0247/18 HCJIM/2018 and HCG/CEI-0913/18 6 159 Mexico Hospital de Especialidades del Nino y Mujer de Research Committee Local (Hospital) 135/10-10-2018/CIR.PED / HENM 7 Queretaro 8 160 Mexico Hospital del Niño Poblano Research Committee Local (Hospital) HNP 2018-16 9 161 Mexico Hospital Infantil de Mexico Federico Gomez Committee of Research, Ethics and Biosecurity Local (Ethical) HIM 2018-043 162 Mexico Hospital Regional de Alta Especialidad del Niño Research and Ethics Committee Local (Ethical) DI/051/18 10 “Dr. Rodolfo Nieto Padrón” 11 163 Mexico Moctezuma Children’s Hospital Research and Ethics Committee Local (Ethical) 09-CEI-006-20180328 12 164 Mexico Pediatric Hospital, Western Medical Center, SIRELCIS Administration Local (Hospital) F-CNNIC-2018-209 Mexican InstituteFor of Social Security peer review only 13 165 Morocco Centre Hospitalier Universaitaire IBN Sina de Chief of Paediatric Emergency Services Local (Departmental) - 14 Rabat, Rabat 15 166 Nigeria Amino Kano Teaching Hospital Research Ethics Committee Local (Ethical) LAKTH/MAC/SUB/12A/ P- 16 3/VI/2402 17 167 Nigeria Bowen University Teaching Hospital Ethics Committee Local http://bmjopen.bmj.com/ (Ethical) NHREC/12/04/2012 168 Nigeria Federal Medical Centre Abeokuta Health Research Ethics Committee Local (Ethical) FMCA/470/19 18 169 Nigeria Federal Medical Centre Umuahia Health Research Ethics Committee Local (Ethical) FMC/QEH/G.596/Vol.10/ 371 19 170 Nigeria Federal Medical Centre Yola Research and Ethics Committee Local (Ethical) FMCY/SUB/S.128/042 20 171 Nigeria Federal Teaching Hospital Gombe Health Research Ethics Committee Local (Ethical) NHREC/25/10/2013 21 172 Nigeria Lagos State University Teaching Hospital Health Research Ethics Committee of LASUTH (LREC) Local (Ethical) NHREC04/04/2008 173 Nigeria Lagos University Teaching Hospital Lagos University Teaching Hospital Health Research Local (Ethical) NHREC 19/12/2008a 22 Ethics Committee (LUTHHREC) 23 174 Nigeria National Hospital Abuja Institute Review Board Committee Local (Ethical) NHA/EC/054/2018 24 175 Nigeria Nnamdi Azikiwe University Teaching hospital Ethics Committee Local (Ethical) NAUTH/CS/668/VOL.2 /024 and 25 on September 23, 2021 by guest. Protected copyright. NAUTH/CS/66/VOL.11/ 171/2018/107 26 176 Nigeria Olabisi Onabanjo University Teaching Hospital Health Research Ethics Committee Local (Ethical) NHREC/28/11/2017 27 177 Nigeria University College Hospital, Ibadan Ethics Committee and Head of Department of Surgery Local (Ethical) UI/EC/18/0432 28 178 Nigeria University of Abuja Teaching Hospital Health Research Ethics Committee Local (Ethical) UATH/HREC/PR/2019/001 29 179 Nigeria University of Nigeria Teaching Hospital Health Research Ethics Committee Local (Ethical) UNTH/CSA/329/OL5 180 Pakistan Aga Khan University Ethics Review Committee Local (Ethical) 2019-0454-2658 30 181 Pakistan Children's Hospital, PIMS, and Shaheed Ethical Review Board Local (Ethical) 1-1 /2015 /ERB /SZABMU /274 31 Zulfiqar Ali Bhutto Medical University, 32 Islamabad 182 Pakistan Karachi Indus hospital Interactive Research and Development Institute Review Local (Ethical) IRD_IRB_2018_07_012 33 Board 34 183 Pakistan Lahore King Edward Medical University Institute Review Board Local (Ethical) 109/RC/KEMU 35 184 Pakistan Liaquat National Hospital Ethics Review Committee Local (Ethical) 0434-2018 LNH-ERC 36 185 Pakistan The Children’s Hospital and the Institute of Institute Review Board Local (Ethical) 45868 Child Health 37 186 Palestine, Gaza Al-Aqsa Hospital, Gaza Strip Helsinki Committee for Ethical Approval National (ethical) PHRC/HC/41//18 38 187 Palestine, Gaza Al-Shifa Hospital, Gaza Strip Helsinki Committee for Ethical Approval National (ethical) PHRC/HC/41//18 39 188 Palestine, Gaza European Gaza Hospital, Gaza Strip Helsinki Committee for Ethical Approval National (ethical) PHRC/HC/41//18 40 189 Palestine, West Bank Ahli Hospital, Hebron In Arabic script National/Local (ethical) - 41 42 6 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 190 Palestine, West Bank Jenin Government Hospital, Jenin In Arabic script National/Local (ethical) - 4 191 Palestine, West Bank Mount of Olives/Makassed, Jerusalem In Arabic script National/Local (ethical) - 5 192 Palestine, West Bank Palestinian Medical Complex ( PMC), Ramallah In Arabic script National/Local (ethical) - 6 193 Palestine, West Bank Rafidia Surgery Hospital, Nablus In Arabic script National/Local (ethical) - 7 194 Palestine, West Bank Red Crescent Society, Hebron In Arabic script National/Local (ethical) - 195 Papua New Guinea Mount Hagen General Hospital Director Clinical Excellence Local (Hospital) - 8 196 Papua New Guinea Port Moresby General Hospital Director Medical Services and Ethical Committee Local (Ethical) - 9 197 Peru Cayetano Heredia Hospital Institutional Committee of Ethics and Investigation Local (Ethical) - 10 198 Peru Guillermo Almenara National Hospital, Lima Ethical Committee Local (Ethical) 174-2018 11 199 Peru Hospital Dos de Mayo Ethics committee in biomedical research Local (Ethical) 085-2018-CEIB-HNDM 12 200 Peru Hospital Nacional Alberto Sabogal Sologuren Institutional committee on ethics in research Local (Ethical) 549-OAIyD-HNASS-ESSALUD- For peer review only 2018 13 79-UCP-DC-GQ-HNASS- 14 ESSALUD-2018 15 201 Peru Hospital Nacional Docente Madre Niño San Committee of Institutional Ethics and Research Local (Ethical) 12200-18 Bartolomé 16 202 Peru Hospital Nacional Edgardo Rebagliati Martins Ethics Committee Local (Ethical) 943-OCIYD-GHNERM-GRPR- http://bmjopen.bmj.com/ 17 ESSALUD-2018 18 19 203 Peru Hospital Regional Del Cusco Research committee and training unit Local (Hospital) 8868-18. 204 Peru Instituto Nacional de Salud Del Niño Institutional Committee of Ethics and Investigation Local (Ethical) PI-64/18 20 205 Peru Instituto Nacional de Salud de Nino de San Institutional Committee of Ethics and Investigation Local (Ethical) PI-2018-246 21 Borja 22 206 Peru Instituto Nacional Materno Perinatal Health Minister Local (Hospital) 699-2018-DEN/INMP 23 207 Peru Pediatric Emergencies Hospital Head of the Teaching and Research Support Office Local (Hospital) 065-2018-OADI-HEP/MINSA 208 Philippines Philippines Children’s Medical Center Institutional Review Board – Ethics Committee Local (Ethical) PCMC IRB-EC 2018-040 24 209 Romania Children Clinical Hospital of Brasov, Ethical Committee Local (Ethical) - 25 Brasov/University of Brasov on September 23, 2021 by guest. Protected copyright. 26 210 Romania Marie Curie Hospital in Bucharest Ethical Committee Local (Ethical) - 27 211 Serbia Clinical Centre for Paediatric Surgery and Ethics Committee of the Faculty of Medicine University Local (Ethical) 12-3182-2/11 Orthopaedics, Clinical Center Niš of Niš President 28 212 Serbia University Children’s Hospital Ethics Committee Local (Ethical) 14/390 29 213 South Africa Frere Hospital Clinical Governance Committee and Frere and Cecilia Local (Ethical) FCMHREC/013/2019 30 Makiwane Hospitals Research Ethics Committee 214 South Africa Greys Hospital, Pietermaritzburg Subcommittee of Biomedical Research Ethics Local (Ethical) BCA221/13 31 Committee 32 215 South Africa Grootte Schurr Hospital Human Research Ethics Committee and Medical Local (Ethical) 572/2018 and RCC158 33 Services Manager 34 216 South Africa Red Cross War Memorial Human Research Ethics Committee and Medical Local (Ethical) 572/2018 and RCC158 Services Manager 35 217 South Africa Tygerberg Children’s Hospital Human Research Ethics Committee and Medical Local (Ethical) N18/09/101 36 Services Manager 37 218 Sri Lanka Lady Ridgeway Hospital for Children Ethical Committee Local (Ethical) - 38 219 Sudan Khartoum University Hospital Head of Department of Paediatric Surgery Local (Departmental) - 220 Syria Aleppo University Hospital Dean of Faculty of Medicine Local (Dean) - 39 221 Syria AlShahbaa Hospital, Aleppo city Head of Alshahbaa Private Hospital Local (Hospital) - 40 41 42 7 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 222 Syria Tishreen University Hospital In Arabic Local (Ethical) - 4 223 Thailand Bangkok Ramathibodi Hospital Institutional Review Board Local (Ethical) 07-61-17 5 224 Thailand Chiangmai Jiraporn Khorana Ethics Committee Local (Ethical) SUR-2561-05619 225 Thailand Hatyai Hospital Research Ethics Committee Local (Ethical) 80/2561 6 226 Thailand Khon Kaen University Ethics Committee for Human Research Local (Ethical) HE611526 7 227 Thailand National Institute of Child Health (QSNICH) Research Ethics Review Committee Local (Ethical) 61-065 8 228 Thailand Siriraj Hospital Institutional Review Board Local (Ethical) 687/2561(EC2) 9 229 Thailand Sisaket Hospital Research Ethics Committee Local (Ethical) 071/2561. 10 230 Tunisia CHU Hedi Chaker Hospital President of the Ethical Committee Local (Ethical) - 231 Tunisia Fattouma Bourguiba Hospital President of the Ethical Committee Local (Ethical) - 11 232 Turkey Adana State Training Hospital Head Physician Local (Hospital) 60247264-799-41 12 233 Turkey Amerikan Hospital,For Istanbul peerEthics Committeereview Chairman onlyLocal (Ethical) 2018.235.irbi.028. 13 234 Turkey Bezmialem University School of Medicine Hospital President Local (Hospital) 54022451-050.05.04 14 235 Turkey Biruni University Hospital University Ethics Committee Local (Ethical) - 236 Turkey Gazi University School of Medicine University Dean Local (Dean) 24074710-604.01.01-47 15 237 Turkey Karadeniz technical University Head Physician Local (Hospital) E.10031 16 238 Turkey Koç University Ethics Committee Chairman Local (Ethical) 2018.235.irbi.028 17 239 Turkey Muğla Education and Research Hospital Chief of Staff Local http://bmjopen.bmj.com/ (Hospital) 2018.235.IRB1.028 18 240 Uzbekistan Republican Perinatal Center In local script Local (Ethical) 000174 241 Uzbekistan Republican Specialized Scientific Practical In local script Local (Ethical) - 19 Medical Center of Pediatrics, Tashkent 20 242 Zambia University Teaching Hospital, Lusaka ERES Converge I Institutional Review Board Local (Ethical) 2018-Sept-001 21 TOTAL MICs: 217 22 High-Income Countries (HICs) 243 Australia Children’s Hospital at Westmead, Sydney Research Governance Officer and Human Research Local (Ethical) LNR/18/SCHN/347 23 Ethics Committee 24 244 Australia Gold Coast University Hospital Human Research Ethics Committee Local (Ethical) HREC/18/QGC/47042 25 245 Australia Monash Children’s Hospital, Victoria Human Research Ethics Committees Local on September 23, 2021 by guest. Protected copyright. (Ethical) HREC/43418/MonH-2018- 26 67965(v1) 246 Australia The Royal Children’s Hospital, Melbourne Murdoch Children’s Research Institute and Research Local (Ethical) QA/50138/RCHM-2018 27 Ethics and Governance Officer 28 247 Austria Medical University of Graz Ethics Committee Local (Ethical) 31-157 ex. 18/19 29 248 Austria Medical University of Vienna, Spitalgasse Ethics Committee Local (Ethical) 2006/2018 30 249 Belgium Queen Fabiola University Children's Hospital Ethics Committee Local (Ethical) B406201837832 250 Brunei Darussalam RIPAS Hospital, Bandar Seri Begawan Medical and Health Research and Ethics Committee Local (Ethical) MHREC/MOH/2018/7 31 251 Canada Ste-Justine Children’s Hospital Scientific Research Committee and Research Ethics Local (Ethical) 2019-2158 32 Board for Ethical Review 33 252 Chile San Juan de Dios Hospital Ethics Committee for Scientific Investigation Local (Ethical) 47/2018 34 253 Czech Republic Fakultni Nemocnice BRNO Ethics Committee Local (Ethical) 13-130219/EK 254 Czech Republic University Hospital Hradec Kralove Ethics Committee Local (Ethical) 201812 s17p 35 255 Czech Republic University Hospital Motol Ethics Committee Local (Ethical) - 36 256 England Alder Hey Children’s Hospital Governance and Quality Assurance Team Local (Hospital) 5714 37 257 England Birmingham Children’s Hospital Clinical Audit Registration and Management System Local (Hospital) CARMS-30164 38 258 England Bristol Royal Hospital for Children Audit Governor Local (Hospital) - 259 England Evelina Children's Hospital, Guy's & St.Thomas' Audit Team Local (Hospital) 8956 39 NHS Trust 40 41 42 8 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 260 England John Radcliffe Hospital, Oxford Clinical Effectiveness Committee Local (Hospital) 5150 4 261 England King’s College Hospital Governance Manager Local (Hospital) CH011 5 262 England Leeds General Infirmary Clinical Director and Deputy Caldicott Guardian Local (Hospital) Globalpaedsurg 263 England Leicester and Kettering Hospitals Clinical Audit Facilitator Local (Hospital) 9482e 6 264 England Nottingham Hospital Audit Department Local (Hospital) 18-350C 7 265 England Southampton General Hospital Audit Department Local (Hospital) SEV/0049 8 266 England St Georges Hospital Audit Department Local (Hospital) AUD1000163 9 267 France CHU Amiens Ethical Review Board National (Ethical) 18.105 10 268 France CHU Amiens-Picardie, Amiens Ethical Review Board National (Ethical) 18.105 269 France CHU Angers Ethical Review Board National (Ethical) 18.105 11 270 France CHU APHM-Marseille Ethical Review Board National (Ethical) 18.105 12 271 France CHU APHP-BicêtreFor peerEthical reviewReview Board onlyNational (Ethical) 18.105 13 272 France CHU APHP-Necker Ethical Review Board National (Ethical) 18.105 14 273 France CHU APHP-Robert Debré Ethical Review Board National (Ethical) 18.105 274 France CHU Bordeaux Ethical Review Board National (Ethical) 18.105 15 275 France CHU Limoges Ethical Review Board National (Ethical) 18.105 16 276 France CHU Poitiers Ethical Review Board National (Ethical) 18.105 17 277 France CHU Rennes Ethical Review Board Nationalhttp://bmjopen.bmj.com/ (Ethical) 18.105 18 278 France CHU Rouen Ethical Review Board National (Ethical) 18.105 279 France CHU StEtienne Ethical Review Board National (Ethical) 18.105 19 280 France CHU Toulouse Ethical Review Board National (Ethical) 18.105 20 281 Germany Frankfurt University Hospital Ethics Committee Local (Ethical) 346/18 21 282 Germany Hospital St. Barbara Elisabeth Halle Ethics Committee Local (Ethical) - 22 283 Germany Krankenhaus Barmherzige Brüder Regensburg Ethics Committee Local (Ethical) 19-1263-101 284 Germany Kinderchirurgie Vivantes Neukölln, Berlin Coordinator of Clinical Research and Academic Local (Hospital) - 23 Teaching 24 285 Germany Medical Faculty Otto-von-Guericke University Executive Director of Ethics Committee Local (Ethical) 151/18 25 Magdeburg on September 23, 2021 by guest. Protected copyright. 26 286 Germany Universitat zu Lubeck Ethics Committee Local (Ethical) 18-249 287 Italy San Matteo Hospital Secretary to the Head of Science Technology Local (Hospital) 20180097159 27 288 Hungary Albert Szent-Györgyi Clinical Centre, Szeged Human Investigation Review Board Local (Ethical) 4413 28 289 Lithuania Children‘s Hospital, Affiliate of Vilnius University Chairman Local (Hospital) 18VSR-1735 29 Hospital SK 158200-18/9-1061-562 30 290 Lithuania Lithuanian University of Health Sciences Chairman of Kaunas RBTEK Local (Hospital) - 291 New Zealand Christchurch Hospital Quality Co-ordinator Childs Health and Audit Group Local (Hospital) BE-2-82 31 292 New Zealand Starship Children's Hospital, NZ Southern health and Disability Ethics Committee Local (Ethical) 18/STH/143 32 293 New Zealand Waikato Hospital Director of Quality and Patient Safety Local (Hospital) RD018104 33 294 New Zealand Wellington Hospital Operations Manager Child Health Service Local (Hospital) - 34 295 Poland Department of Children’s Developmental Bioethical Commission Local (Ethical) KNW/0022/KB/204/I/18 Defects Surgery and Traumatology 35 296 Poland Medical University of Gdańsk Bioethical Committee for Research Local (Ethical) NKBBN/456/2018 36 297 Poland Medical University of Silesia, Katowice Bioethical Commission Local (Ethical) KNW/0022/KB/172/18 37 298 Poland Warsaw Children’s Memorial Health Institute Bioethical Commission and Ethical Committee Local (Ethical) 20/KBE/2018 38 Assembly 299 Poland Wladyslaw Buskowski Children’s Hospital Bioethical Commission Local (Ethical) 44/2018 39 300 Poland Wroclaw University Bioethical Commission Local (Ethical) 133/XV R/2017 40 41 42 9 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 301 Qatar Sidra Medecine, Doha Institutional Review Board Local (Ethical) 1808029580 4 302 Saudi Arabia King Fahd Armed Forces Hospital Director of the Research Center, Research and Ethics Local (Ethical) REC 261 5 Committee 303 Saudi Arabia King Saud University College of Medicine Institutional Review Board Local (Ethical) E-18-3427 6 304 Scotland Glasgow Children’s Hospital, NHS Greater Caldicott Guardian Local (Hospital) - 7 Glasgow and Clyde 8 305 Scotland Royal Hospital for Sick Children Associate Medical Director Local (Hospital) - 9 306 Singapore KK Women’s and Children’s Hospital, Little Head of Department Local (Departmental) - India 10 307 South Korea Cheonnam National University Hospital, Dong- Chonnam National University Hospital Biomedical Local (Ethical) - 11 gu, Gwangju Research Ethics Review Committee Chairperson 12 308 South Korea Samsung Medical Centre Institutional Review Board Local (Ethical) 2018-09-110 309 South Korea Seoul National UniversityFor Children’s peer Hospital Institutional review Review Board onlyLocal (Ethical) H-1810-050-977 13 310 South Korea Seoul St. Marys Hospital Institutional Review Board Local (Ethical) KC18OCGI0669 14 311 Spain Barcelona Sant Joan de Déu Hospital Secretary of CEIM Sant Joan de Déu Local (Hospital) - 15 312 Spain Complejo Hospitalario Universitario de a Head of Paediatric Surgery Unit Local (Departmental) - 16 Coruña (CHUAC) 17 313 Spain Hospital Clinico Universitario de Valladolid Director Manager and CEIM of Valladoid Health Area Local http://bmjopen.bmj.com/ (Hospital) - 314 Spain Maternal Hospital Infantil de Badajoz Secretary of the Ethical Investigation Committee of Local (Ethical) - 18 Badajoz Clinic 19 315 Spain Zaragoza Hospital Universitario Miguel Favourable Report Project of Biomedical Research a Local (Hospital) - 20 Secretary of the CEIC Aragón (CEICA) 21 316 Sweden Lund Skåne University Hospital Pediatric Care Consultation group for quality registers Local (Hospital) - Hospital 22 317 Sweden Queen Silvia Children’s Hospital Area Manager of QSCH and Head of operations or unit Local (Hospital) - 23 manager 24 318 Sweden Sachs Children’s Hospital Patient Area Director Local (Hospital) - 25 319 Sweden Uppsala University Children’s Hospital Section Chief, Paediatric Surgery Clinician Local on September 23, 2021 by guest. Protected copyright. (Departmental) - 320 Switzerland Inselspital/University Hospital, Bern Kantonale Ethics Committee Local (Ethical) - 26 321 UAE Danat Al Emarat Hospital Head of Surgery Local (Departmental) - 27 322 Uruguay University De La Republica Facultad de Service Chief for the Neonatal Department Local (Departmental) - 28 Medicina 29 323 Uruguay Centro Hospitalario Pereira Rossell Audit Team Local (Hospital) - 324 USA Ann and Robert H. Lurie Children’s Hospital of Institutional Review Board Local (Ethical) IRB 2019-2334 30 Chicago 31 325 USA Beaumont’s Children’s Hospital in Royal Oak Institutional Review Board Local (Ethical) IRB 2018-402 32 326 USA Children’s Hospital of Wisconsin Institutional Review Board Local (Ethical) 1352795-2 33 327 USA Dartmouth-Hitchcock Medical Center Committee for the Protection of Human Subjects Local (Ethical) STUDY00031666 328 USA Le Bonheur Children’s Hospital Memphis UTHSC Institutional Review Board Local (Ethical) 18-06176-XP 34 329 USA Nationwide Children’s Hospital Institutional Review Board Office Local (Ethical) IRB18-01005 35 330 USA New York Presbyterian Morgan Stanley Institutional Review Board Local (Ethical) IRB-AAAS0645 36 Children’s Hospital 37 331 USA Oregon Health and Science University Institutional Review Board Local (Ethical) STUDY00018665 332 USA Phoenix Children’s Hospital Institutional Review Board Local (Ethical) PCH IRB #18-100 38 333 USA University of Miami Institutional Review Board Local (Ethical) 20181054 39 334 USA University of Michigan Co-chairs of Institutional Review Board MED Local (Ethical) HUM 00151299 40 335 USA University of Texas Medical Branch Institutional Review Board Vice Chairman Local (Ethical) IRB18-0318 41 42 10 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 336 USA UT Southwestern Medical Center Children’s Institutional Review Board Local (Ethical) STU 072018-058 4 Hospital 5 337 USA Yale New Haven Hospital Institutional Review Board Local (Ethical) 2000024339 TOTAL HICs: 95 6 OVERALL TOTAL: 337 7 8 9 10 11 12 For peer review only 13 14 15 16 17 http://bmjopen.bmj.com/ 18 19 20 21 22 23 24 25 on September 23, 2021 by guest. Protected copyright. 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 11 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Page 35 of 36 BMJ Open
1 2 3 Management and Outcomes of Gastrointestinal Congenital Anomalies in Low-, BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Middle- and High-Income Countries: Protocol for a Multi-Centre, International, 5 6 Prospective Cohort Study 7 8 9 STROBE checklist detailing where each item is addressed in the protocol 10
11 Section where this is 12 Item covered in the 13 No Recommendation manuscript 14 Title and abstract 1 (a) Indicate the study’s design with a commonly used term in the title or the abstract Title, abstract 15 (b) Provide in the abstract an informative and balanced summary of what was done Abstract and what was found 16 Introduction 17 18 Background/rationale 2 ExplainFor the scientific peer background andreview rationale for the investigation only being reported Introduction Objectives 3 State specific objectives, including any prespecified hypotheses Objective 19 Methods 20 Study design 4 Present key elements of study design early in the paper Abstract, Methods - 21 Study Design 22 Setting 5 Describe the setting, locations, and relevant dates, including periods of recruitment, Methods 23 exposure, follow-up, and data collection 24 Participants 6 (a) Give the eligibility criteria, and the sources and methods of selection of participants. Methods – inclusion/ Describe methods of follow-up exclusion criteria, 25 outcome measures 26 (b) For matched studies, give matching criteria and number of exposed and unexposed Not Applicable 27 Variables 7 Clearly define all outcomes, exposures, predictors, potential confounders, and effect Methods – Outcomes, modifiers. Give diagnostic criteria, if applicable Data Collection, Data 28 Analysis, Appendix 29 Data sources/ 8* For each variable of interest, give sources of data and details of methods of Table 1, Methods – 30 measurement assessment (measurement). Describe comparability of assessment methods if there is sample selection, 31 more than one group Appendix 1 and 2 Bias 9 Describe any efforts to address potential sources of bias Data quality, data 32 validation 33 Study size 10 Explain how the study size was arrived at Sample size calculation 34 Quantitative 11 Explain how quantitative variables were handled in the analyses. If applicable, describe Not applicable 35 variables which groupings were chosen and why Statistical methods 12 (a) Describe all statistical methods, including those used to control for confounding Data Analysis 36 (b) Describe any methods used to examine subgroups and interactions Data Analysis
37 (c) Explain how missing data were addressed Data Analysis http://bmjopen.bmj.com/ 38 (d) If applicable, explain how loss to follow-up was addressed Data Analysis 39 (e) Describe any sensitivity analyses Data Analysis Results 40 41 Participants 13* (a) Report numbers of individuals at each stage of study—eg numbers potentially Estimated Study eligible, examined for eligibility, confirmed eligible, included in the study, completing Population 42 follow-up, and analysed 43 (b) Give reasons for non-participation at each stage Not applicable 44 (c) Consider use of a flow diagram Not applicable Descriptive data 14* (a) Give characteristics of study participants (eg demographic, clinical, social) and Not applicable
45 on September 23, 2021 by guest. Protected copyright. information on exposures and potential confounders 46 (b) Indicate number of participants with missing data for each variable of interest Not applicable 47 (c) Summarise follow-up time (eg, average and total amount) Not applicable 48 Outcome data 15* Report numbers of outcome events or summary measures over time Not applicable 49 Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and Not applicable 50 their precision (eg, 95% confidence interval). Make clear which confounders were 51 adjusted for and why they were included 52 (b) Report category boundaries when continuous variables were categorized Not applicable (c) If relevant, consider translating estimates of relative risk into absolute risk for a Not applicable 53 meaningful time period 54 Other analyses 17 Report other analyses done—eg analyses of subgroups and interactions, and Data Analysis 55 sensitivity analyses Discussion 56 57 Key results 18 Summarise key results with reference to study objectives Not applicable 58 Limitations 19 Discuss limitations of the study, taking into account sources of potential bias or Strengths and imprecision. Discuss both direction and magnitude of any potential bias Limitations 59 Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations, Not applicable 60 multiplicity of analyses, results from similar studies, and other relevant evidence
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3 Generalisability 21 Discuss the generalisability (external validity) of the study results Not applicable BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Other information
5 Funding 22 Give the source of funding and the role of the funders for the present study and, if Additional Information 6 applicable, for the original study on which the present article is based 7 8 9 10 11 12 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44
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Management and Outcomes of Gastrointestinal Congenital Anomalies in Low-, Middle- and High-Income Countries: Protocol for a Multi-Centre, International, Prospective Cohort Study
ForJournal: peerBMJ Open review only Manuscript ID bmjopen-2019-030452.R2
Article Type: Protocol
Date Submitted by the 10-Jul-2019 Author:
Complete List of Authors: Wright, Naomi; King's College London, King's Centre for Global Health and Health Partnerships
Primary Subject Global health Heading:
Secondary Subject Heading: Paediatrics, Surgery
PAEDIATRIC SURGERY, Paediatric anaesthesia < ANAESTHETICS, Paediatric intensive & critical care < INTENSIVE & CRITICAL CARE, Keywords: NEONATOLOGY, PAEDIATRICS, Neonatal intensive & critical care <
INTENSIVE & CRITICAL CARE http://bmjopen.bmj.com/
on September 23, 2021 by guest. Protected copyright.
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1 2 3 Management and Outcomes of Gastrointestinal Congenital BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 Anomalies in Low-, Middle- and High-Income Countries: Protocol 6 for a Multi-Centre, International, Prospective Cohort Study 7 8 9 10 11 Global PaedSurg Research Collaboration 12 13 Correspondence to: Naomi J. Wright, King’s Centre for Global Health and Health Partnerships, 14 School of Population Health and Environmental Sciences, King’s College London, Denmark Hill, SE5 15 9RJ, UK. Email: [email protected] 16 17 18 For peer review only 19 ABSTRACT 20 21 Introduction 22 23 th 24 Congenital anomalies are the 5 leading cause of death in children under 5-years of age globally, contributing an estimated half a million deaths per year. Very limited literature exists from low- and 25 middle-income countries (LMICs) where most of these deaths occur. The Global PaedSurg Research 26 Collaboration aims to undertake the first multi-centre, international, prospective cohort study of a 27 selection of common congenital anomalies comparing management and outcomes between low-, 28 middle- and high-income countries (HICs) globally. 29 30 Methods and Analysis 31 32 33 The Global PaedSurg Research Collaboration consists of surgeons, paediatricians, anaesthetists and 34 allied healthcare professionals involved in the surgical care of children globally. Collaborators will prospectively collect observational data on consecutive patients presenting for the first time, with one 35 of seven common congenital anomalies (oesophageal atresia, congenital diaphragmatic hernia, 36 intestinal atresia, gastroschisis, exomphalos, anorectal malformation and Hirschsprung's disease).
37 http://bmjopen.bmj.com/ 38 39 Patient recruitment will be for a minimum of one month from October 2018 to April 2019 with a 30-day post-primary intervention follow-up period. Anonymous data will be collected on patient 40 demographics, clinical status, interventions and outcomes using REDCap. Collaborators will complete 41 a survey regarding the resources and facilities for neonatal and paediatric surgery at their centre. 42 43 44 The primary outcome is all-cause in-hospital mortality. Secondary outcomes include the occurrence of post-operative complications. Chi-squared analysis will be used to compare mortality between LMICs
45 on September 23, 2021 by guest. Protected copyright. and HICs. Multilevel, multivariate logistic regression analysis will be undertaken to identify patient 46 level and hospital level factors affecting outcomes with adjustment for confounding factors. 47 48 49 Ethics and Dissemination 50 51 At the host centre this study is classified as an audit not requiring ethical approval. All participating 52 collaborators have gained local approval in accordance with their institutional ethical regulations. 53 Collaborators will be encouraged to present the results locally, nationally and internationally. The 54 results will be submitted for open access publication in a peer reviewed journal. 55 56 Registration Details 57 58 This study has been registered with ClinicalTrials.Gov, identifier: NCT03666767. The registration is 59 available to view via: https://goo.gl/ffXNMH 60
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3 Strengths and Limitations of this Study BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 This will be the first large-series, geographically comprehensive, multi-centre, international, 6 prospective cohort study to define the management and outcomes of a selection of common 7 congenital anomalies in low-, middle- and high-income countries across the globe. 8 The collaborative approach for this study allows a large series of high-quality data to be collected 9 in a timely manner without overburdening high-volume, low-resource centres. 10 11 The seven study conditions constitute a selection of the commonest life-threatening congenital 12 anomalies requiring emergency surgical care in the neonatal period (Box 1). 13 We recognise that some children may not reach a facility capable of providing acute paediatric 14 surgical care and hence the results obtained may be an underestimation of true morbidity and 15 mortality, especially in LMICs. 16 The number of variables being collected per patient has been limited to those known to have the 17 greatest impact on outcomes to optimise the feasibility of the study; follow-up is limited to 30-days 18 post-primary intervention.For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
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3 INTRODUCTION BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 In 2015, the Global Burden of Disease study concluded congenital anomalies (also known as 6 congenital malformations, congenital abnormalities or birth defects) to be the 5th leading cause of 7 death in children under 5-years of age globally.1 This equates to approximately half a million deaths 8 from congenital anomalies each year, 97% of which occur in low- and middle-income countries 9 (LMICs). Indeed, this is likely to be an underestimation of the actual number of deaths due to under- 10 diagnosis of neonates with congenital anomalies who die in the community and a lack of death 11 certification in many LMICs.2 Not only is the mortality rate higher in LMICs, the prevalence is also 12 higher due to micronutrient deficiencies, infections and teratogens during pregnancy resulting in more 13 cases and a lack of antenatal diagnosis prohibiting terminations.3,4 There is limited research and a 14 lack of congenital anomaly registries in LMICs and hence they have received very little global 15 attention.5 16 17 The conditions forming the focus of this study (Box 1) constitute a selection of the most common life- 18 threatening congenitalFor anomalies peer during the reviewneonatal period, which only involve the gastrointestinal tract. 19 They each have an incidence of 1/2000 – 1/5000, they collectively form up to 40% of emergency 6-9 20 neonatal surgery and associated mortality can be in excess of 50% in many LMICs. Disparities in 21 outcomes globally can be stark; for example the mortality from gastroschisis is 75-100% in many 10-12 22 LMICs compared to 4% or less in HICs. Reasons for poor outcomes include a lack of antenatal diagnosis, delayed presentation, limited neonatal transport and in-hospital resources, a dearth of 23 trained support personnel and a lack of intensive care and parenteral nutrition for neonates.9,13,14 In 24 Uganda, it was calculated that only 3.5% of the need for neonatal surgery was met by the healthcare 25 system.8 26 27 28 29 Box 1. Congenital Anomalies in the Global PaedSurg Study 30 31 Oesophageal atresia (OA) +/- tracheo-oesophageal fistula (TOF) 32 Congenital diaphragmatic hernia (CDH) 33 Intestinal atresia (IA) 34 Gastroschisis 35 Exomphalos 36 Anorectal malformation (ARM)
37 Hirschsprung’s disease http://bmjopen.bmj.com/ 38 39 40 41 In 2010, the World Health Assembly passed a resolution recommending ‘prevention whenever 42 possible, to implement screening programmes and to provide care and ongoing support to children 2 43 with birth defects and their families’. Prevention is paramount, however this is not yet possible for 44 many congenital anomalies and hence a focus on improving postnatal care and outcomes is vital. The Sustainable Development Goal 3.2 aims to end preventable deaths of newborns and children under
45 on September 23, 2021 by guest. Protected copyright. the age of 5-years by 2030.6, 15,16 With a third of infant deaths being attributed to congenital 46 anomalies, clearly this will not be achievable without an accelerated effort towards the provision of 47 surgical care for children. It is estimated that two-thirds of deaths and disability from congenital 48 anomalies can be avoided with the provision of neonatal and paediatric surgical care.6 Indeed, studies 49 have demonstrated such provision can be highly cost-effective in terms of disability adjusted life years 50 saved.5 Yet neonatal and paediatric surgical care remain a low priority on the global health agenda.5 51 52 A shift is needed to focus on the provision of surgical care for children within National Health Plans 53 and International Organisations and to elevate congenital anomalies on the global health agenda. 54 This large-scale, geographically comprehensive, multi-centre prospective cohort study aims to define 55 the current management and outcomes of a selection of common congenital anomalies globally and 56 identify factors affecting outcomes that can be modified to improve care. This is vital to aid advocacy 57 and global health prioritisation and inform future interventional studies aimed at improving outcomes. 58 59 60 AIM
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3 To undertake the first large-scale, geographically comprehensive multi-centre, prospective cohort BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 study comparing the management and outcomes of a selection of common congenital anomalies in 5 low-, middle-, and high-income countries across the globe. 6 7 OBJECTIVES 8 9 1. To compare the mortality and post-intervention complications of a selection of common congenital 10 anomalies involving the gastrointestinal tract in LMICs and HICs globally. 11 12 2. To identify patient level and hospital level factors affecting outcomes that be modified to improve 13 care. 14 15 3. To establish a research collaboration consisting of children’s surgical care providers across the 16 world to help enhance research capacity and to create a platform for ongoing collaborative research 17 and intervention studies aimed at improving outcomes. 18 For peer review only 19 4. To raise awareness and provide advocacy for neonatal and paediatric surgical care within global 20 health prioritisation, planning, policy and funding. 21 22 23 24 25 METHODS AND ANALYSIS 26 Study Design 27 28 29 This is an international, multi-centre, prospective observational cohort study. The Global PaedSurg Research Collaboration consisting of children’s surgical care providers (collaborators) across the 30 world was established from November 2017 to co-ordinate the study at an institutional level and 31 facilitate data collection. Collaborators are free to choose one or more months between 1st October 32 2018 to the 30th April 2019 (inclusive) to recruit consecutive patients to the study, with a 30-day post- 33 primary intervention follow up period. The primary intervention must occur within 30-days of 34 presentation to be included in the study. Hence, the last date for primary data collection is 29th June 35 2019. Following this there will be a period of data collection for the data validation process continuing 36 until the end of August 2019.
37 http://bmjopen.bmj.com/ 38 Collaborators 39 40 International collaborators will have a variety of roles and responsibilities within the study. Local 41 collaborators will establish mini-teams locally, gain study approval, utilise the protocol criteria to 42 appropriately identify patients for study inclusion, collect prospective data and upload it to REDCap. 43 Each hospital will have a local study lead who will hold overall responsibility for ensuring the data is 44 accurate, complete and without duplications. Country-lead collaborators will help to recruit other collaborators from within their country and provide advice and support regarding gaining local study 45 on September 23, 2021 by guest. Protected copyright. 46 approval and data collection. They may also help with translation of the study literature to the local 47 language if required. Continent and regional leads will help to recruit country leads, provide them with 48 advice regarding the study and also encourage and co-ordinate presentations of the protocol at 49 national and international meetings. Lead investigators will contribute to the study design through the 50 provision of feedback from the pilot studies undertaken in multiple languages. An organising 51 committee will help to co-ordinate all study activities and a steering committee will provide guidance 52 throughout. 53 There are a number of benefits for collaborators participating the study. Publishing journal(s) will be 54 asked to make all collaborators PubMed citable co-authors. This is based on an equal partnership 55 model described by the Lancet and is used by a number of national and international collaboratives.17- 56 21 All collaborators will be listed as an author on resulting presentations. Collaborators will have the 57 opportunity to present the study locally, nationally and internationally, initially the study protocol and 58 later the results. This often provides collaborators, especially those who are junior or from LMICs, the 59 opportunity to apply for funding to attend, present and network at such meetings. Participation in the 60 study provides an easy route and insight into clinical research, which can be further established
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3 through participation in the 2-year Research Training Fellowship which is running alongside the main BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 study free of charge for all interested collaborators. 5 6 Sample Selection 7 8 Collaborator and Hospital Inclusion Criteria: 9 10 All hospitals and healthcare professionals providing surgical care for neonates and children, 11 presenting for the first time, with one or more of the study conditions can be included in the study. 12 Collaborators should gain permission from the senior surgeon or physician who oversees the care of 13 the children to be included in the study in order to participate. There can be up to three collaborators 14 in a mini-team per month of data collection. One mini-team can collect data over one or more months 15 or several mini-teams can collect data over a different month each. Each mini-team must contain at 16 least one senior surgeon or physician to oversee the data collection process. 17 18 Patient Inclusion andFor Exclusion peer Criteria: review only 19 20 Any neonate, infant or child under the age of 16-years, presenting acutely for the first time, with one 21 or more of the study conditions can be included in the study. Patients who have previously received 22 surgery for their presenting condition or those representing with a complication of surgery are 23 excluded. Patients presenting electively for surgery are excluded. Children who have received basic 24 resuscitative care for their condition at a different healthcare facility and are then transferred to the 25 study centre for their primary surgical intervention can be included. Children who only receive 26 resuscitative treatment at the study centre and are then referred elsewhere for their primary surgical 27 intervention cannot be included since the outcome of the surgical care will not be known and also to 28 avoid the risk of duplicate patients in the study. Patients who receive conservative treatment as their 29 primary intervention, palliative care, or no care must be included within the study to accurately reflect 30 the management and outcomes of all presenting cases. 31 32 If a patient presents with more than one of the study conditions, the details of each condition that they 33 present acutely with can be included, but not a previously managed condition. For example, a 34 newborn presenting with oesophageal atresia and anorectal malformation would have both conditions 35 included. A patient presenting for the first time with Hirschsprung’s disease at several months of age 36 who had a duodenal atresia repaired at birth would have the full details of the Hirschsprungs disease
37 included, but the duodenal atresia would simply be noted as an associated anomaly. http://bmjopen.bmj.com/ 38 39 Outcome Measures 40 41 The primary outcome is all-cause, in-hospital mortality. 42 43 For patient’s hospitalised for over 30-days following primary intervention, a 30-day post-primary 44 intervention mortality rate will be utilised. Those who do not receive a primary intervention, but remain
45 alive and hospitalised at 30-days following primary admission, will have this time point used for on September 23, 2021 by guest. Protected copyright. 46 recording their mortality status for the primary outcome. Primary outcome is defined in Table 1. 47 48 The secondary outcomes include complications occurring within 30-days of primary intervention: 49 50 Surgical site-infection 51 Wound dehiscence 52 Need for re-intervention 53 Condition specific complications 54 Condition specific outcome variables 55 Length of hospital stay or time from admission to death in patients who do not survive 56 30-day post primary intervention mortality. 57 58 Secondary outcomes will not be collected on patients who do not receive a primary intervention within 59 30-days of hospital admission, with the exception of length of hospital stay or time from admission to 60
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3 death. 30-day follow-up will be undertaken within the capacity of the collaborating team; no additional BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 funding will be provided. 5 6 Data Collection 7 8 Generic variables relating to the patient demographics, antenatal care, pre-hospital care, clinical 9 condition, surgical intervention and outcomes will be collected for all patients in the study (Table 1). 10 Specific variables will be collected for each individual condition (Supplementary File 1). 11 12 Outcomes and variables have been chosen using published core outcome sets and commonly 13 collected outcomes in systematic reviews and meta-analyses.22-37 Collaborators will enter anonymous, 14 de-identified data via the secure internet-based Research Electronic Data Capture (REDCap) system. 15 This will be stored on King’s College London REDCap server. 16 17 A short survey will be completed by the local study lead and one other collaborating consultant or 18 registrar on the resourcesFor and facilitiespeer available review for neonatal and only paediatric surgical care at their 19 centre (Supplementary File 2). 20 21 22 Table 1. Generic Data Points 23 24 Generic questions Answers 25 During which month did the patient present to Please select the month that the patient presented to your hospital for the first time with this 26 your hospital? congenital anomaly. For example, if a baby was born with gastroschisis on the 29th September 27 and presented to your hospital on the 1st October you should select October. Has consent been provided to include this Yes / No / Patient consent is not required for this study at my institution 28 patient in the study? 29 If no, which condition did the patient present Oesophageal atresia / Congenital diaphragmatic hernia / Intestinal atresia / Gastroschisis / 30 with? Exomphalos / Omphalocele / Anorectal malformation / Hirschsprung's Disease. Please select all the conditions that the patient presented with. Do not select a condition which 31 the patient has already received surgical treatment for previously. 32 Demographics 33 Gestational age at birth Number of weeks from the first day of the women's last menstrual cycle until birth. Round up or 34 down to the nearest week. Age at presentation (in hours) We understand this information may be difficult to obtain - please be as accurate as you can. 35 Please round to the nearest hour. This number may be very large for patients who have a 36 delayed presentation - please still enter it. For neonates born within your centre please enter 0. Enter unknown if unknown. 37 http://bmjopen.bmj.com/ 38 Gender Male / Female/ Ambiguous/ Unknown Weight at presentation In kilograms (kg) on the day of presentation. Please provide a value to 1 decimal place. 39 Does the patient have another anomaly in Yes, Cardiovascular, Yes, Respiratory, Yes: Gastrointestinal, Yes: Neurological, Yes: Genito- 40 addition to the study condition? urinary, Yes: Musculoskeletal, Yes: Down syndrome, Yes: Beckwith-Wiedemann syndrome, Yes: 41 Cystic fibrosis, Yes: Chromosomal, Yes: Other, No Select all that apply. Include all anomalies diagnosed at any stage up until 30-days post primary 42 intervention or 30-days following presentation for those who didn't receive an intervention. If you 43 suspect an associated anomaly, but it has yet to be diagnosed, select 'other'. 44 Distance from the patient's home to your In kilometres (km). Please round to the nearest kilometre. Please enter 0 if born in your hospital. hospital
45 on September 23, 2021 by guest. Protected copyright. Antenatal Care and Delivery 46 Antenatal ultrasound undertaken? Yes: study condition diagnosed, Yes: problem identified but study condition not diagnosed, Yes: 47 no problem identified, No 48 If the condition was diagnosed antenatally, at Please round up to the nearest week. If the patient has more than one study condition, please 49 what gestational age? note the gestational age at which one or more of the conditions was first diagnosed. Mode of transport to hospital? Ambulance, Other transport provided by the health service, Patient's own transport, Born within 50 the hospital 51 Where did the patient present from? If other, Home / Community Clinic / General Practice / District Hospital / Other / Unknown 52 please specify. District hospital includes: secondary level healthcare, provincial hospital, general hospital, general mission hospital or regional hospital. It has general anaesthesia and can provide general 53 surgical care. 54 Type of delivery: Vaginal (spontaneous), Vaginal (induced), Caesarean section (elective), Caesarean section 55 (urgent/non-elective), Unknown. Vaginal delivery includes those requiring forceps and ventouse. 56 Clinical condition and patient care Was the patient septic on arrival? Yes, no 57 Sepsis is SIRS (Systemic Inflammatory Response Syndrome) with a suspected or confirmed 58 bacterial, viral, or fungal cause. SIRS is a response to a stimulus, which results in two or more of 59 the following: temperature > 38.5°C or < 36°C, tachycardia*, bradycardia* in children < 1 year old, tachypnoea*, leukopenia or leucocytosis*, hyperglycaemia*, altered mental status, 60 hyperlactaemia*, increased central capillary refill time >2 seconds. *Variables are defined as
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3 values outside the normal range for age. Arrival is the time of birth for neonates born at your BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 hospital. 5 If yes, were appropriate antibiotics Yes: within 1 hour of arrival, Yes: within the first day of arrival, No administered? Appropriate antibiotics are defined as either broad spectrum covering gram negative, gram 6 positive and anaerobic bacteria OR antibiotics that are the standard empirical treatment for that 7 condition according to local guidelines OR are based on sensitivities provided by a microbiology 8 sample. Was the patient hypovolaemic on arrival? Yes/ No. Criteria for diagnosis include at least one of the following: prolonged central capillary 9 refill time > 2 seconds, *tachycardia, mottled skin, *reduced urine output, cyanosis, impaired 10 consciousness, *hypotension. *Variables are defined as values outside the normal range for age. 11 If yes, was an intravenous fluid bolus given? Yes: within 1 hour of arrival, Yes: on the first day of arrival, No If yes, how much intravenous fluid was given? 10 - 20mls/ kg, above 20mls/ kg 12 If less than 10mls/ kg was given please select 'no' for the question asking if intravenous fluid was 13 given. 14 Was the patient hypothermic on arrival? Yes/ No. Defined as < 36.5 degrees Celsius core temperature. Arrival is the time of birth for 15 neonates born at your hospital. If yes, was the patient warmed on arrival to Yes/ No. Only select yes if warming was commenced within 1 hour of arrival. Arrival is the time of 16 within a normal temperature range? birth for neonates born at your hospital. 17 Did the patient receive central venous access? Yes: umbilical catheter, Yes: peripherally inserted central catheter (PICC), Yes: percutaneously 18 For peerinserted central reviewline with ultrasound guidance, only Yes: surgically placed central line (open insertion), No. 19 Please select all that the patient received within 30-days of primary intervention or 30-days of 20 presentation if no intervention was undertaken. 21 If yes, did the patient acquire central line Yes: diagnosed clinically, Yes: confirmed on microbiology, No sepsis? Within 30-days of primary intervention or 30-days of presentation if no intervention was 22 undertaken. 23 Time from arrival at your hospital to primary (enter 0 if no intervention was undertaken) 24 intervention in hours Primary intervention for each condition is defined as: Oesophageal atresia; surgery, either 25 temporising or definitive, to manage the oesophageal atresia and/ or tracheo-oesophageal fistula. Congenital diaphragmatic hernia; surgery to reduce the hernia and close the defect. 26 Intestinal atresia; surgery, either temporising or definitive, to manage the obstruction including 27 stoma formation and primary anastomosis. Gastroschisis; any procedure to either cover or 28 reduce the bowel and/ or close the defect. This includes application of a silo (regardless of whether or not they go on to require surgery). It excludes initial covering of the bowel in a plastic 29 covering (bag or cling film) prior to intervention. Exomphalos; surgery or application of topical 30 treatment to the sac in patients managed conservatively (regardless of whether or not they go on 31 to require surgery). Hirschsprung's disease; surgery, either temporising or definitive, or rectal/ 32 distal bowel irrigation, laxatives or digital stimulation in patients managed conservatively. This does not include pre-operative washouts in patients planned to have surgery. Anorectal 33 malformation; surgery, either temporising or definitive, or anal/ fistula dilatation in patients with a 34 low anorectal malformation managed conservatively. 35 American Society of Anesthesiologists (ASA) 1. Healthy person, 2. Mild systemic disease, 3. Severe systemic disease, 4. Severe systemic Score at the time of primary intervention disease that is a constant threat to life, 5. A moribund patient who is not expected to survive 36 without the operation, Not applicable - no intervention
37 What type of anaesthesia was used for the General anaesthesia with endotracheal tube, General anaesthesia with laryngeal airway, http://bmjopen.bmj.com/ 38 primary intervention? Ketamine anaesthesia, Spinal/ caudal anaesthesia, Local anaesthesia only, No anaesthesia/ just 39 analgesia, No anaesthesia/ no analgesia, Not applicable: no surgery or intervention undertaken. Who undertook the anaesthetic for the primary Anaesthetic doctor, Anaesthetic nurse, Medical officer, Surgeon, Other healthcare professional, 40 intervention? No anaesthetic undertaken 41 If more than one of these personnel were present please select the most senior. 42 Who undertook the primary intervention? Paediatric surgeon (or junior with paediatric surgeon assisting/ in the room), General surgeon (or junior with paediatric surgeon assisting/ in the room), Junior doctor, medical officer or other 43 (without a paediatric or general surgeon assisting/ in the room), Trainee surgeon (without a 44 paediatric or general surgeon assisting or in the room), Not applicable - no surgery or primary intervention undertaken.
45 on September 23, 2021 by guest. Protected copyright. 46 Was a Surgical Safety Checklist used at the Yes, No: but it was available, No: it was not available, Not applicable: a conservative primary time of primary intervention? intervention was undertaken, Not applicable: no surgery or primary intervention undertaken 47 Total duration of antibiotics following primary In days (including the day of surgery and the day antibiotics were stopped. Include intravenous 48 intervention and oral antibiotics). 49 Did the patient receive a blood transfusion? Yes: not cross-matched, Yes: cross-matched, No: not required, No: it was required but not available. Within 30-days of primary intervention or 30-days of presentation if no intervention was 50 undertaken. 51 Did the patient require ventilation? Yes: and it was given, Yes: but it was not available, No 52 Within 30-days of primary intervention or 30-days of presentation if no intervention was 53 undertaken. Please include all types of ventilation. If yes, for how long did the patient remain on In days (include all days on ventilation within 30-days of primary intervention or 30-days of 54 ventilation? presentation if no intervention was undertaken). 55 Time to first enteral feed (post-primary In days (include the day of primary intervention and the day of first enteral feed in the 56 intervention) calculation). Enter 0 if enteral feeds were not commenced. Enter 999 if feeds were not stopped, for example in patients with Hirschsprung's Disease managed conservatively. Include all types of 57 enteral feeding - oral, nasogastric, gastrostomy and other. 58 Time to full enteral feeds (post-primary In days (enter 0 if the patient died before reaching full enteral feeds or 30 if the patient had not 59 intervention) reached full enteral feeds at 30-days post primary intervention or 30-days following admission in 60
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3 patients who did not receive a primary intervention). Include all types of enteral feeding - oral, BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 nasogastric, gastrostomy and other. 5 Did the patient require parenteral nutrition? Yes and it was given, Yes and it was sometimes available but less than required, Yes but it was not available, No 6 If yes, for how long did the patient receive In days. Include all days that the patient received parenteral nutrition (any volume) up until 30- 7 parenteral nutrition? days post primary intervention or 30-days following presentation in patients who do not receive 8 an intervention. Outcomes 9 Did the patient survive to discharge? Yes/ No 10 Select yes if the patient was still alive in your hospital 30-days after primary intervention or 30- 11 days after presentation in patients who do not receive a primary intervention. 12 If the patient was discharged prior, were they Yes, No: not followed-up after discharge, Followed-up but not until 30-days post primary still alive at 30-days following primary intervention 13 intervention? This can include all reliable communication with the patient/ patient's family including in person, 14 via telephone and other. 15 If no, cause of death? Sepsis, Aspiration pneumonia, Respiratory failure, Cardiac failure, Malnutrition, Electrolyte disturbance, Haemorrhage, Lack of intravenous access, Hypoglycaemia, Recurrent tracheo- 16 oesophageal fistula, Recurrent diaphragmatic hernia, Anastomotic leak, Ischaemic bowel, 17 Ruptured exomphalos sac, Enterocolitis, Other. If other, please specify 18 Duration of hospital stay (days) For peerPlease include thereview day of admission and only the day of discharge in your calculation. For example, if a patient presented on 1st October and was discharged on the 5th October, their duration of 19 hospital stay would be 5 days. If the patient died, please record the number of days from 20 admission to death. Only include the duration of the primary admission, not subsequent 21 admissions if the patient re-presented. 22 Did the patient have a surgical site infection? Yes, No, Not applicable: no surgical wound This is defined as one or more of the following within 30-days of surgery: 1) purulent drainage 23 from the superficial or deep (fascia or muscle) incision, but not within the organ/ space 24 component of the surgical site OR 2) at least two of: pain or tenderness; localised swelling; 25 redness; heat; fever; AND the incision is opened deliberately to manage infection, spontaneously dehisces or the clinician diagnoses a SSI (negative culture swab excludes this criterion) OR 3) 26 there is an abscess within the wound (clinically or radiologically detected). 27 Did the patient have a full thickness wound Yes, No, Not applicable - no surgical wound. 28 dehiscence? This is defined as all layers of the wound opening within 30-days of surgery 29 Did the patient require a further unplanned Yes - percutaneous intervention, Yes - surgical intervention, No, Not applicable - no primary intervention? intervention undertaken. Within 30-days of primary intervention. This does not include routine 30 reduction and closure of the defect in neonates with gastroschisis receiving a preformed silo. 31 Was the patient followed up at 30-days post Yes: reviewed in person, Yes: via telephone consultation, Yes: via other means, Yes: still an in- 32 primary surgery or intervention to assess for patient at 30-days, No: data is based on in-patient observations only, No: follow-up was done but complications? prior to 30-days 33 If the patient had a complication, when was it During the primary admission, As an emergency re-attender, At routine follow-up as an out- 34 diagnosed? patient, Not applicable: no complications 35 What study condition does this patient have? Oesophageal atresia, Congenital diaphragmatic hernia, Intestinal atresia, Gastroschisis, 36 Exomphalos/ Omphalocele, Anorectal malformation, Hirschsprung's Disease If the patient has presented for the first time with more than one of these conditions please select
37 all that apply. If the patient presented on this occasion with one of these conditions, but http://bmjopen.bmj.com/ 38 previously had another condition managed then only select the condition they are presenting with 39 on this occasion and enter that they have another anomaly in the demographics section above. For example, if the patient presents at 2-months with Hirschsprung's disease, but previously had 40 a duodenal atresia repair please select Hirschsprung's disease here (not intestinal atresia) and 41 tick in the section above that they have another gastrointestinal anomaly. 42 43 44 Data Quality
45 on September 23, 2021 by guest. Protected copyright. 46 To ensure high quality of data, a detailed protocol for collaborators has been produced and published 47 on the study website (www.globalpaedsurg.com) in 12 languages: English, French, Spanish, Portuguese, German, Italian, Chinese, Arabic, Korean, Lithuanian, Turkish and Russian. Clear and 48 concise definitions have been provided for all data points on the protocol, on the data collection forms 49 and within REDCap when entering the data. A study launch meeting was undertaken where the 50 principal investigator presented the data collection process in detail, demonstrated use of REDCap 51 and answered questions. This was recorded, circulated to all collaborators via email and placed on 52 the website. A frequently asked questions document has been circulated via email and placed on the 53 website. Two meetings were held by the principal investigator to detail the study, data collection 54 process and answer questions amongst the country leads so they in turn can provide advice and 55 support to local collaborators within their country. Again this was recorded, circulated and placed on 56 the website. 57 58 A pilot study of the patient data collection form and institutional survey was undertaken by lead 59 investigators to optimise the study design and to address any feasibility or other barriers to effective 60 data collection and study completion across participating sites. The pilot study commenced on 1st
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3 August 2018 for 30 days in English, Spanish and French by 41 collaborator colleagues. The data BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 collection forms were amended following feedback to clarify terminology, add important missing 5 variables or descriptions and correct any translation errors. All translated data collection forms, 6 REDCap and study documentation has been checked and verified by a native speaker for accuracy. 7 8 Data Validation 9 10 Ten percent of collaborating centres will be selected at random for data validation by an independent 11 research collaborator. The aim will be to determine the numbers of patients eligible during the data 12 collection period to check if any were missed and collect a selection of data again to cross-check for 13 accuracy. Validating questions have been built into the data collection tool. At least 90% of primary 14 and secondary outcomes must be completed for each patient. All collaborators within validating 15 centres will be asked to complete a brief survey regarding their experience with data collection to 16 identify any potential errors and to aid with data interpretation. 17 18 Sample Size CalculationFor peer review only 19 20 A sample size calculation was undertaken using Stata/IC 15.0 based on Bonferroni correction for 21 multiple testing, assuming 80% power and an overall type 1 error of 5%. The required sample size for 22 each condition has been calculated for the primary outcome of mortality in LMICs compared to HICs and also low, middle and high-income countries separately (Table 2). Mortality estimations are based 23 on pooled data from published studies on these conditions in low-, middle- and high-income countries 24 respectively. 25 26 Based on the patient numbers included in the previously undertaken PaedSurg Africa study, which 27 utilised a similar study design, the estimated sample sizes to detect a significant difference between 28 LMICs and HICs in this study are achievable.13 29 30 Table 2. Estimated mortality and sample sizes for low, middle and high-income countries and 31 the mean number of cases per month per institution globally 32 33 Condition Mortality LIC Mortality MIC Mortality Mortality Sample Sample Sample Sample Mean no. 34 (%, n) (%, n) LMIC HIC size for size for size for size for cases/ month/ 35 combined (%, n) LIC MIC HIC LMIC vs institution (%, n) HIC (per (L,M&HIC 36 group) combined)
37 OA +/- TOF 79.5% 41.8% 43.7% 2.7% 34 34 23 21 1.02 http://bmjopen.bmj.com/ 38 (62/78) (623/1488) (685/1566) (6/221) 39 CDH - 47.4% 47.4% 20.4% - - - 63 0.54 (130/274) (130/274) (201/982) 40 IA 42.9% 40.0% 41.0% 2.9% 6014 6014 25 24 0.63 41 (42/98) (97/241) (139/339) (12/407) 42 Gastroschisis 83.1% 42.6% 56.6% 3.7% 29 29 24 15 0.85 43 (211/254) (205/481) (416/735) (28/748) Exomphalos 25.5% 31.9% 30.1% 12.7% 1040 1040 196 115 0.63 44 (41/161) (132/414) (173/575) (40/316)
45 ARM 26.3% 17.5% 18.1% 3% 460 460 90 85 1.34 on September 23, 2021 by guest. Protected copyright. 46 (26/99) (243/1391) (269/1490) (14/462) 47 Hirschsprung’s 19.1% 16.8% 17.6% 2.3% 5802 5802 85 79 2.21 48 Disease (33/173) (55/328) (88/501) (43/1897) 49 50 Estimated Study Population 51 52 The mean number of cases presenting to an institution per month for each study condition was 53 estimated from published studies across all income settings (Table 2). On average most institutions 54 caring for patients with these conditions receive 1-2 new cases per month; each participating 55 institution would expect approximately 7-14 new cases in the study per month although this can vary. 56 The aim is to include a minimum of 365 months of data; 183 months from LMICs and 183 months 57 from HICs. This should ensure enough cases of exomphalos to determine a significant difference 58 between LMICs and HICs; fewer months of data are required to determine significant differences 59 between other study conditions. An up-to-date total of patient numbers within the study will be maintained on the study website. 60
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3 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 Data Analysis 6 7 Patient and Institutional Data: 8 9 Data will be analysed using Stata and SAS 9.4 (Cary, NC; USA). Missing data for the covariates will 10 be analysed to determine whether it is related to the outcome and either complete-case analyses or 11 multiple imputation techniques will be used for analyses accordingly. 12 13 Significant differences in mortality between LMICs and HICs will be determined for each of the study 14 conditions using Chi-squared analysis, or Fischer’s exact test if either group contains less than 10 15 patients. World Bank classification of low-, middle- and high-income countries during the fiscal year 38 16 2018 will be used. 17 Univariate logistic regression analyses will be conducted between covariates and the primary 18 outcome of mortality. ForBased on peer the results, covariatesreview with a p-value only of <0.10 will be included in the 19 multivariate model. The final multi-level multivariate logistic model will be determined using stepwise 20 backward elimination to interventions and peri-operative factors affecting outcomes. Data will be 21 adjusted for confounding factors and effect modifiers. Potential confounders include: gestation age at 22 birth, weight, time from birth to presentation and ASA score at the time of primary intervention. 23 Potential effect modifiers include: administration of peri-operative antibiotics, fluid resuscitation, 24 thermal control and provision of other condition specific neonatal care such as parenteral nutrition in 25 neonates with gastroschisis. 26 27 Multi-level multivariate logistic regression analysis will also be undertaken to identify institutional 28 factors affecting mortality with adjustment for confounders. P< 0.05 will be deemed significant. 29 30 Data Validation: 31 32 A weighted kappa statistic will be utilised to determine the level of agreement between the patient 33 data in the main study and the validation data. A weighted kappa statistic will be also utilised to 34 determine the level of agreement between institutional surveys independently completed by the local 35 study lead and one other consultant or registrar at each participating centre. Results will be presented 36 as a proportion of agreement for each variable being validated.
37 http://bmjopen.bmj.com/ 38 39 Patient and Public Involvement 40 CDH UK, a patient and family advisory group and charity, provided input into the design of the study 41 protocol and data collection tool. Their input will be sought on the findings and dissemination of the 42 results. 43 44
45 ETHICS AND DISSEMINATION on September 23, 2021 by guest. Protected copyright. 46 47 Research Ethics Approval 48 49 The study has been classified as an audit at the host institution and hence did not require ethical 50 approval. The study fulfils the audit criteria as follows: 1) All data collected measures current practice. 51 The study does not involve any changes to patient management; 2) Current practice and outcomes in 52 low, middle and high-income countries will be compared to published standards in the literature. 53 Table 2 details the current mortality standards for each of the seven study conditions in high-income countries; 3) All the study data is routinely collected information which should be known to the study 54 team without asking additional questions to the patients/parents; 4) All data to be entered into 55 REDCap is entirely anonymous; 5) No individual patient, collaborator, institution or country will be 56 independently identifiable in the study results; 6) All data will be stored securely and will be governed 57 by King’s College London data protection team. 58 59 60
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3 Research collaborators were required to gain approval to participate in the study at their institution BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 according to their local ethical regulations. Data transfer agreements were legally signed between 5 institutions where required. The participating institutions, type of study approval and study approval 6 reference numbers are detailed in Supplementary File 3. It was not mandated for study approvals to 7 be translated into English. Hence, some reference numbers are in the local scripture of the 8 participating country and have therefore not been incorporated into the table. 9 10 Study Dissemination 11 12 The study concept and design will be presented at international conferences in order to recruit 13 collaborators. Following completion, the results will be presented at local, national and international 14 conferences globally. Both the promotional presentations of the study protocol and the study results 15 will be presented by study collaborators of all levels of training, disciplines and regions of the world. 16 The results will be submitted for open access publication in a peer reviewed journal. Following 17 publication, the full anonymous, de-identified dataset will be made publicly available via an online 18 repository. CollaboratorsFor will have peer the opportunity review to undertake sub-analysesonly of the data for their 19 country (if all collaborators from that country agree), region or continent. 20 21 22 DISCUSSION 23 This study aims to define, for the first time, the management and outcomes of a selection of common 24 life-threatening congenital anomalies across the globe. This will help to raise awareness of the 25 unacceptable disparities in outcomes between low-, middle- and high-income countries and the need 26 to focus on improving access to quality surgical care for neonates with congenital anomalies within 27 national health plans and global health prioritisation. It is hoped that factors affecting mortality and 28 morbidity will be identified that can be modified to improve care. Establishment of the Global 29 PaedSurg Research Collaboration developed during this study will create a platform for ongoing 30 collaborative work and interventional studies aimed at improving outcomes in the future. 31 32 33 34 35 36
37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44
45 on September 23, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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3 ADDITIONAL INFORMATION BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 Twitter: @GlobalPaedSurg 6 7 Website: http://globalpaedsurg.com 8 9 Author Contributions: The principal investigator conceived the idea for the study, gained study 10 funding, wrote the study protocol, designed the data collection tools, established the study team, co- 11 ordinated the pilot study, revised the study design/ data collection tools following feedback and made 12 critical revisions to the manuscript for publication. The steering committee contributed critical input 13 and revisions to the funding application, study design, protocol and manuscript for publication. The 14 writing committee drafted the protocol manuscript for publication and contributed as organising 15 committee members. The organising committee assisted in the recruitment of and communication 16 with collaborators to participate in the pilot study, helped to co-ordinate the pilot study and summarise 17 the feedback, made critical revisions to the data collection tools in multiple languages and contributed 18 to the study design. TheFor lead investigators peer contributed review to the study only design and content of the data 19 collection forms through feedback following participation in the pilot study. All contributed to the 20 content of this manuscript. 21 22 Funding Statement: Naomi Wright, Principal Investigator, is funded by the Wellcome Trust through a 23 Clinical PhD in Global Health undertaken at King’s College London (Funder Reference: 24 203905/Z/16/Z). The Wellcome Trust had no input into the study protocol other than to recommend 25 open-access publication in a peer-reviewed journal and to make the anonymised dataset publicly 26 available. Nick Sevdalis’ (NS) research is supported by the National Institute for Health Research 27 (NIHR) Collaboration for Leadership in Applied Health Research and Care South London at King’s 28 College Hospital NHS Foundation Trust. NS is a member of King’s Improvement Science, which is 29 part of the NIHR CLAHRC South London and comprises a specialist team of improvement scientists 30 and senior researchers based at King’s College London. Its work is funded by King’s Health Partners 31 (Guy’s and St Thomas’ NHS Foundation Trust, King’s College Hospital NHS Foundation Trust, King’s 32 College London and South London and Maudsley NHS Foundation Trust), Guy’s and St Thomas’ Charity, the Maudsley Charity and the Health Foundation. NS and Andrew Leather are also supported 33 by the NIHR Global Health Research Unit on Health System Strengthening in Sub-Saharan Africa, 34 King’s College London (GHRU 16/136/54) and by the ASPIRES research programme in LMICs 35 (Antibiotic use across Surgical Pathways - Investigating, Redesigning and Evaluating Systems), 36 funded by the Economic and Social Research Council. The views expressed are those of the authors
37 and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. http://bmjopen.bmj.com/ 38 39 40 Competing Interest’s Statement: Nick Sevdalis is the director of the London Safety and Training 41 Solutions Ltd, which offers training in patient safety, implementation solutions and human factors to 42 healthcare organisations. No other conflicts of interest are declared. 43 44 Patient Consent: Collaborators must follow their local ethical guidelines regarding patient consent.
45 on September 23, 2021 by guest. Protected copyright. 46 47 Ethics Approval: This study has been classified as a clinical audit with written confirmation from King’s College London Ethics Committee that it does not therefore require ethical approval. All 48 participating centres have gained study approval to participate according to their local institutional 49 ethical regulations (Supplementary File 3). 50 51 52 Provenance and Peer Review: Not commissioned; externally peer reviewed. 53 54 Open Access: This is an Open Access article distributed in accordance with the terms of the Creative 55 Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build 56 upon this work, for commercial use, provided the original work is properly cited. 57 Licence Statement: I, the Submitting Author has the right to grant and does grant on behalf of all 58 authors of the Work (as defined in the below author licence), an exclusive licence and/or a non- 59 exclusive licence for contributions from authors who are: i) UK Crown employees; ii) where BMJ has 60
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3 agreed a CC-BY licence shall apply, and/or iii) in accordance with the terms applicable for US Federal BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Government officers or employees acting as part of their official duties; on a worldwide, perpetual, 5 irrevocable, royalty-free basis to BMJ Publishing Group Ltd (“BMJ”) its licensees and where the 6 relevant Journal is co-owned by BMJ to the co-owners of the Journal, to publish the Work in BMJ 7 Open and any other BMJ products and to exploit all rights, as set out in our licence. 8 9 The Submitting Author accepts and understands that any supply made under these terms is made by 10 BMJ to the Submitting Author unless you are acting as an employee on behalf of your employer or a 11 postgraduate student of an affiliated institution which is paying any applicable article publishing 12 charge (“APC”) for Open Access articles. Where the Submitting Author wishes to make the Work 13 available on an Open Access basis (and intends to pay the relevant APC), the terms of reuse of such 14 Open Access shall be governed by a Creative Commons licence – details of these licences and 15 which Creative Commons licence will apply to this Work are set out in our licence referred to above. 16 17 Acknowledgements: Thank you to Bolaji Coker for the REDCap administration and management. 18 Thank you to BeverleyFor Power (CDHpeer UK) for representingreview patients, only parents and families through your 19 feedback on the study design during the pilot study. Thank you to Xiya Ma and Dylan Goh for helping 20 with the Chinese translation of study documentation. 21 22 23 COLLABORATORS 24 25 26 Principal Investigator: Naomi Wright (King’s College London, UK) 27 28 Steering Committee: Niyi Ade-Ajayi (King’s College Hospital, UK), Adesoji Ademuyiwa (Lagos 29 University Teaching Hospital, Nigeria), Emmanuel Ameh (National Hospital, Abuja, Nigeria), Justine 30 Davies (University of Birmingham, UK), Kokila Lakhoo (University of Oxford and Oxford University 31 Hospitals, UK), Dan Poenaru (McGill University, Montreal, Canada), Nick Sevdalis (King’s College 32 London, UK), Emily Smith (Baylor University, Texas, USA), Andy Leather (King’s College London, UK) 33 34 35 Writing Committee: Harmony Ubhi (King’s College London, UK), Samuel Parker (Imperial College 36 London, UK), Godfrey Sama Philipo (Muhimbili University of Health and Allied Sciences, Tanzania)
37 http://bmjopen.bmj.com/ 38 Organising Committee: Sadi Abukhalaf (Al Quds University, Palestine), Nana Adofo-Ansong 39 (Mahikeng Provincial Hospital, South Africa), Melika Akhbari (King’s College London, UK), Ahmad 40 Alhamid (University of Aleppo, Syria), Osaid H. Alser (University of Oxford, UK), Emrah Aydin (Koc 41 University, Turkey), Yousra-Imane Benaskeur (Universite de Montreal, Canada), Shrouk M. Elghazaly 42 (Assiut University, Egypt), Safa abdal Elrais (University of Tripoli, Libya), Sophia Hashim (University College London, UK), Laura Herrera (Geisel School of Medicine, Dartmouth, USA), Gabriella Hyman 43 (University of Witwatersrand, South Africa), Henang Kwasau (College of Medicine and Allied Health 44 Sciences, University of Sierra Leone), Yang Liu (Children’s Hospital, Zhejiang University School of
45 on September 23, 2021 by guest. Protected copyright. Medicine, China), Bruno Martinez-Leo (Moctezuma Children’s Hospital, Mexico), Kelly Naranjo 46 (Columbia University Medical Centre, USA), Ibrahim Nour (Jordan University Hospital, Jordan), 47 Cristiana Riboni (University of Pavia, Italy), Mahmoud Saleh (University of Gezira, Sudan), Hosni 48 Khairy Salem (Cairo University, Egypt), Patricia Shinondo (University Teaching Hospital, Lusaka, 49 Zambia), Marcus Sim (Stepping Hill Hospital, UK), Hannah Thompson (King’s College Hospital, UK), 50 Agota Vaitkiene (Vilnius University Hospital Santaros Kliniko, Lithuania), Dominique Vervoort 51 (Harvard Medical School, USA), Isabelle Williams (Cambridge University, UK), Aayenah Yunus 52 (King’s College London, UK). 53 54 Lead Investigators: Muhammad Amjad Chaudhary, Adnan Ahmed Khan Khattak, Muhammad Bin 55 Amjad (Children’s Hospital, PIMS, Islamabad, Pakistan), Marlene Dominguez Anaya (Children’s 56 Hospital Manuel A.Villarroel Cochabamba, Bolivia), Samiul Hasan, Sabbir Karim, Ashrarur Rahman 57 Mitul (Dhaka Shishu (Children) Hospital, Bangladesh), Paolo Bragagnini, Segundo Rite (Hospital 58 Universitario Miguel Servent, Zaragoza), Hana Arbab, Lubna Samad, Aqil Soomro (Indus Hospital, 59 Pakistan), Niveshni Maistry (John Radcliffe Hospital, UK), Raed Nael Al-Taher, Ibrahim Rabi Nour, 60 Osama Abdul Kareem Sarhan (Jordan University Hospital, Jordan), Muhammad Arshad, Taimur
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3 Qureshi, Hina Yousaf (Liaquat National Hospital, Pakistan), Candy SC Choo, Doris Mae Dimatatac, BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Shireen Anne Nah (KK Women’s and Children’s Hospital, Singapore), Vijay Anand Ismavel, Ann 5 Miriam, Shajin T (Makunda Christian Leprosy and General Hospital, India), Monica Ivanov, 6 Andreea Serban (Marie Curie Hospital in Bucharest, Romania), Bruno Martinez-Leo (Moctezuma 7 Children’s Hospital, Mexico), Eva Blazquez-Gomez, Luis Garcia-Aparicio, Martí Iriondo, Jordi Prat, 8 Xavier Tarrado (Hospital Sant Joan de Deu, Spain), Lars Hagander, Emma Svensson (Skane 9 University Hospital’s Pediatric Care Hospital, Lund, Sweden), Alhassan Abdul-Mumin, Dominic 10 Bagbio, Sheila Owusu, Stephen Tabiri (Tamale Teaching Hospital, Ghana), Dayang Anita Abdul Aziz 11 (UKM Medical Centre, Kuala Lumpur, Malaysia). 12 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44
45 on September 23, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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3 REFERENCES BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 5 1. GBD Child Mortality Collaborators. Global, regional, national, and selected subnational levels 6 of stillbirths, neonatal, infant, and under-5 mortality, 1980-2015: a systematic analysis for the Global 7 Burden of Disease Study 2015. Lancet 2016; 388(10053): 1725-74. 8 2. Boyle B, Addor MC, Arriola L, et al. Estimating Global Burden of Disease due to congenital 9 anomaly: an analysis of European data. Arch Dis Child Fetal Neonatal Ed 2017. 10 3. Flores A, Valencia D, Sekkarie A, et al. Building capacity for birth defects surveillance in 11 Africa: Implementation of an intermediate birth defects surveillance workshop. J Glob Health Perspect 12 2015; 2015. 13 4. Sitkin NA, Ozgediz D, Donkor P, Farmer DL. Congenital anomalies in low- and middle-income 14 countries: the unborn child of global surgery. World J Surg 2015; 39(1): 36-40. 15 5. Ozgediz D, Langer M, Kisa P, Poenaru D. Pediatric surgery as an essential component of 16 global child health. Semin Pediatr Surg 2016; 25(1): 3-9. 17 6. Farmer D, Sitkin N, Lofberg K, Donkor P, Ozgediz D. Surgical Interventions for Congenital 18 Anomalies. In: DebasFor HT, Donkor peer P, Gawande review A, Jamison DT, Krukonly ME, Mock CN, eds. Essential 19 Surgery: Disease Control Priorities, Third Edition (Volume 1). Washington (DC); 2015. 20 7. Sakonidou S, Ali K, Farmer I, Hickey A, Greenough A. Mortality and short-term morbidity in 21 infants with exomphalos. Pediatr Int 2018. 22 8. Ameh EA, Seyi-Olajide JO, Sholadoye TT. Neonatal surgical care: a review of the burden, progress and challenges in sub-Saharan Africa. Paediatr Int Child Health 2015; 35(3): 243-51. 23 9. Ekenze SO, Ajuzieogu OV, Nwomeh BC. Challenges of management and outcome of 24 neonatal surgery in Africa: a systematic review. Pediatr Surg Int 2016; 32(3): 291-9. 25 10. Wright NJ, Zani A, Ade-Ajayi N. Epidemiology, management and outcome of gastroschisis in 26 Sub-Saharan Africa: Results of an international survey. Afr J Paediatr Surg 2015; 12(1): 1-6. 27 11. PaedSurg Africa Research Collaboration. Paediatric Surgery across Sub-Saharan Africa: A 28 Multi-Centre Prospective Cohort Study. https://clinicaltrials.gov/ct2/show/NCT03185637 (Accessed 29 26th January 2019). 30 12. Bradnock T, Marven S, Owen A, et al. Gastroschisis: one year outcomes from national cohort 31 study. BMJ 2011; 343(d6749). 32 13. Krishnaswami S, Nwomeh BC, Ameh AE. The pediatric surgery workforce in low- and middle- 33 income countries: problems and priorities. Semin Pediatr Surg 2016; 25(1): 32-42. 34 14. Okoye MT, Ameh EA, Kushner AL, Nwomeh BC. A pilot survey of pediatric surgical capacity 35 in West Africa. World J Surg 2015; 39(3): 669-76. 36 15. United Nations. Sustainable Development Goals. 2015.
37 http://www.un.org/sustainabledevelopment/health/ (accessed 27th February 2018). http://bmjopen.bmj.com/ 38 16. Wright NJ, Anderson JE, Ozgediz D, Farmer DL, Banu T. Addressing paediatric surgical care 39 on World Birth Defects Day. Lancet 2018; 391(10125): 1019. 40 17. GlobalSurg Collaborative. Mortality of emergency abdominal surgery in high-, middle- and 41 low-income countries. Br J Surg 2016; 103(8): 971-88 42 18. GlobalSurg Collaborative. Surgical site infection after gastrointestinal surgery in high-income, 43 middle-income, and low-income countries: a prospective, international, multi-centre cohort study. 44 Lancet Infect Dis 2018; 18(5): 516-25. 19. GlobalSurg Collaborative. Laparoscopy in management of appendicitis in high-, middle-, and
45 on September 23, 2021 by guest. Protected copyright. low-income countries: a multicenter, prospective, cohort study. Surg Endosc 2018. 46 20. GlobalSurg Collaborative. Determinants of morbidity and mortality following emergency 47 abdominal surgery in children in low-income and middle-income countries. BMJ Glob Health 2016; 48 1(4): e000091. 49 21. Bhangu A, Kolias AG, Pinkney T, Hall NJ, Fitzgerald JE. Surgical research collaboratives in 50 the UK. Lancet 2013; 382(9898): 1091-2. 51 22. Long AM, Bunch KJ, Knight M, Kurinczuk JJ, Losty PD, Baps C. Early population-based 52 outcomes of infants born with congenital diaphragmatic hernia. Arch Dis Child Fetal Neonatal Ed 53 2018. 54 23. Ruttenstock E, Wright N, Barrena S, et al. Best oxygenation index on day 1: a reliable marker 55 for outcome and survival in infants with congenital diaphragmatic hernia. Eur J Pediatr Surg 2015; 56 25(1): 3-8. 57 24. Burjonrappa S, Crete E, Bouchard S. Comparative outcomes in intestinal atresia: a clinical 58 outcome and pathophysiology analysis. Pediatr Surg Int 2011; 27(4): 437-42. 59 25. Forrester MB, Merz RD. Structural birth defects associated with omphalocele and 60 gastroschisis, Hawaii, 1986-2001. Congenit Anom (Kyoto) 2008; 48(2): 87-91.
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3 26. Kunz SN, Tieder JS, Whitlock KJ, Jackson C, Avansino JR. Primary fascial closure versus BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 staged closure with silo in patients with gastroschisis: a meta-analysis. J Pediatr Surg 2013; 48(4): 5 845-57. 6 27. Ross AR, Eaton S, Zani A, Ade-Ajayi N, Pierro A, Hall NJ. The role of preformed silos in the 7 management of infants with gastroschisis: a systematic review and meta-analysis. Pediatr Surg Int 8 2015; 31(5): 473-83. 9 28. Levitt MA, Pena A. Anorectal malformations. Orphanet J Rare Dis 2007; 2: 33. 10 29. Van der Steeg HJ, Schmiedeke E, Bagolan P, et al. European consensus meeting of ARM- 11 Net members concerning diagnosis and early management of newborns with anorectal 12 malformations. Tech Coloproctol 2015; 19(3): 181-5. 13 30. Holschneider A, Hutson J, Pena A, et al. Preliminary report on the International Conference 14 for the Development of Standards for the Treatment of Anorectal Malformations. J Pediatr Surg 2005; 15 40(10): 1521-6. 16 31. Bradnock TJ, Knight M, Kenny S, Nair M, Walker GM, British Association of Paediatric 17 Surgeons Congenital Anomalies Surveillance S. Hirschsprung's disease in the UK and Ireland: incidence and anomalies. Arch Dis Child 2017; 102(8): 722-7. 18 32. Ross AR, HallFor NJ. Outcome peer reporting review in randomized controlled only trials and systematic reviews 19 of gastroschisis treatment: a systematic review. J Pediatr Surg 2016; 51(8): 1385-9. 20 33. Allin BSR, Hall NJ, Ross AR, et al. Development of a gastroschisis core outcome set. Arch 21 Dis Child Fetal Neonatal Ed 2018. 22 34. Allin BS, Irvine A, Patni N, Knight M. Variability of outcome reporting in Hirschsprung's 23 Disease and gastroschisis: a systematic review. Sci Rep 2016; 6: 38969. 24 35. Watanabe S, Suzuki T, Hara F, Yasui T, Uga N, Naoe A. Omphalocele and Gastroschisis in 25 Newborns: Over 16 Years of Experience from a Single Clinic. J Neonatal Surg 2017; 6(2): 27. 26 36. Tan KB, Tan KH, Chew SK, Yeo GS. Gastroschisis and omphalocele in Singapore: a ten-year 27 series from 1993 to 2002. Singapore Med J 2008; 49(1): 31-6. 28 37. Schneider A, Blanc S, Bonnard A, et al. Results from the French National Esophageal Atresia 29 register: one-year outcome. Orphanet J Rare Dis 2014; 9: 206. 30 38. World Bank. World Bank Country and Lending Groups. 2018. 31 https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending- 32 groups (Accessed 26th January 2019). 33 34 35 36
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1 2 3 Management and Outcomes of Gastrointestinal Congenital Anomalies in Low-, BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Middle- and High-Income Countries: Protocol for a Multi-Centre, International, 5 6 Prospective Cohort Study 7 8 9 SUPPLEMENTARY FILE 1: Condition Specific Data Points 10 11 12 Oesophageal Atresia (OA) +/- Tracheo-Oesophageal Fistula (TOF) 13 Question Answers 14 Type of OA +/- TOF (Gross classification) A, B, C, D, E 15 A: without a fistula, B: proximal TOF with distal OA, C: distal TOF with proximal 16 OA, D: proximal and distal TOF, E: H-type TOF without OA. 17 Long or short gap? Long, Short, Unknown Long gap OA: A gap of 4 vertebral bodies or more. Anatomically cases either 18 For peerhave noreview TOF or a gap of over only4 vertebral bodies following division of the distal 19 fistula making primary repair unfeasible. Short OA: A gap of less than 4 vertebral 20 bodies. Primary anastomosis typically feasible. Pneumonia at presentation? Yes: diagnosed clinically, Yes: diagnosed radiologically, Yes: other means of 21 diagnosis, No: patient born in the study centre, No: patient born outside the study 22 centre but no evidence of pneumonia on arrival 23 Pneumonia is defined as lung inflammation typically caused by bacterial or viral 24 infection, in which the air sacs fill with pus and may become solid. Primary intervention: TOF ligation, Oesophageal anastomosis, Oesophagostomy, Gastrostomy, 25 Ligation of the distal oesophagus, Gastro-oesophageal disconnection, Foker 26 technique, Fundoplication, Other (please specify), Palliative care 27 Select all that apply. If the patient had a primary oesophageal anastomosis, Yes, No. (At any stage) 28 was a post-operative oesophagogram undertaken? 29 If yes, routine or clinically indicated? Routine, Clinically indicated 30 If yes, when? Number of days after primary surgery If yes, what was the result? Leak, No leak 31 For patients diagnosed with a leak radiologically, was it Yes, No 32 associated with clinical symptoms? 33 Time to first oral feed post-operatively In days. Please include the day of surgery and the first day of oral feeds in the calculation. Enter 0 if oral feeds were not commenced within 30-days of primary 34 intervention. Do not include other types of enteral feeding such as nasogastric or 35 gastrostomy feeding. 36 Time to full oral feeds In days (enter 0 if the patient died before reaching full oral feeds or 30 if the patient had not reached full oral feeds at 30-days post primary intervention). Do
37 http://bmjopen.bmj.com/ not include other types of enteral feeding such as nasogastric or gastrostomy 38 feeding. 39 For patient's not receiving a primary oesophageal In months (enter unknown if not planned or enter not applicable if primary 40 anastomosis, at what age is definitive surgery planned? anastomosis was undertaken). For patient's not receiving a primary oesophageal Gap assessment, Primary oesophageal anastomosis if possible, Gastric pull-up, 41 anastomosis, what is the future planned procedure? Jejunal interposition, Colonic interposition, Not applicable: primary anastomosis 42 undertaken, Other, Unknown. Select all that apply. If other, please specify. 43 If the patient had surgery, what was the approach? Thoracotomy muscle cutting, Thoracotomy muscle splitting, Thoracoscopy, Laparotomy, Laparoscopy, Limited local incision, Other. 44 During primary surgery. If other, please specify.
45 If thoracoscopic or laparoscopic, was the surgery Yes, No on September 23, 2021 by guest. Protected copyright. 46 converted to open? 47 Did the patient have a condition specific complication Pneumonia, Mediastinitis, Pneumothorax, Chylothorax, Haemothorax, within 30-days of primary intervention? Anastomotic leak, Anastomotic stricture, Recurrent TOF, Other, None 48 Select all that apply. If other, please specify. 49 Did the patient have tracheomalacia? Yes: diagnosed clinically, Yes: diagnosed on bronchoscopy, Yes: diagnosed on 50 CT, Yes: diagnosed on bronchogram, Yes: other method of diagnosis, No If yes, was an intervention undertaken? If other, please Yes: aortopexy, Yes: tracheostomy, Yes: tracheal stent, Yes: supportive 51 specify management (oxygen +/- ventilation) only, Yes: other treatment, No 52 53 Congenital Diaphragmatic Hernia (CDH) 54 55 Question Answers 56 Type of CDH. Left posteriolateral (Bochdalek), Right posteriolateral (Bochdalek), Bilateral posteriolateral (Bochdalek), Central, Anterior (Morgagni), Other. If other, please 57 specify. 58 Type of Bochdalek CDH (CDH Study Group A, B, C, D, Other (specify), Unknown. 59 Classification) Defect A: smallest defect, usually "intramuscular" defect with >90% of the hemi- diaphragm present; this defect involves < 10% of the circumference of the chest 60 wall. Defect B: 50-75% hemi-diaphragm present; this defect involves < 50% of
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3 the chest wall. Defect C: < 50% hemi-diaphragm present; this defect involves BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 >50% of the chest wall. Defect D: largest defect (previously known as 5 "agenesis"); complete or near complete absence of the diaphragm with < 10% hemi-diaphragm present; this defect involves >90% of the chest wall. Surgically, 6 it is an absent posterior rim beyond the spine, absent posterior-lateral rim, and 7 an anterior/anterior-medial rim which is miniscule. As it is truly unusual to have 8 zero tissue at all, this is the CDHSG member consensus. "D" defects should all require a patch (or muscle flap) for repair. 9 If bilateral, what was the type of Bochdalek hernia on the A, B, C, D, Other, Unknown 10 left? If other, please specify. 11 If bilateral, what was the type of Bochdalek hernia on the A, B, C, D, Other, Unknown right? If other, please specify. 12 If antenatally diagnosed, what was the lung-to-head ratio Enter zero if not undertaken/ not known. 13 (LHR)? 14 Was foetal tracheal occlusion (FETO) undertaken? Yes, No 15 If yes, at what gestational age was it inserted? ______, unknown. If yes, at was gestational age was it removed? ______, at birth, unknown. 16 Liver position? Chest, Abdomen, Unknown 17 Did the patient have pulmonary hypertension (at any Yes: diagnosed clinically, Yes: diagnosis confirmed on echocardiography, Yes: 18 stage)? For peerother methodreview of confirming diagnosis, only No, Unknown 19 Persistent pulmonary hypertension of the newborn (PPHN) is defined as the failure of the normal circulatory transition that occurs after birth. It is a syndrome 20 characterised by marked pulmonary hypertension that causes hypoxemia 21 secondary to right-to-left extrapulmonary shunting of deoxygenated blood. It 22 should be suspected whenever the level of hypoxemia is out of proportion to the level of pulmonary disease. Echocardiography plays a major role in screening 23 and assisting in making the diagnosis of PPHN. 24 If yes, treatment given? If other, please specify. Nitric oxide, Prostacyclin, Alprostadil, Milrinone, Other, None: not required, 25 None: required but not available. Did the patient receive extracorporeal membrane Yes, No 26 oxygenation (ECMO)? 27 If yes, for how long? In days. Include the day the patient went onto ECMO and the day they were 28 taken off in the calculation. 29 Primary intervention Primary repair (absorbable sutures), Primary repair (non-absorbable sutures), Patch repair, Palliation, Discharged with planned elective repair, Other 30 If patch repair, material used? Permacol, PTFE, Alloderm, Dacron, Mesh plug, Muscle flap, Surgisis, Other. If 31 other, please specify. 32 Other procedures undertaken at the same time? Chest drain insertion, Abdominal wall patch, Fundoplication, Correction of malrotation, Appendicectomy, Other (specify), None 33 Select all that apply. If other, please specify. 34 Surgical approach: Laparotomy, Laparoscopy, Thoracotomy, Thoracoscopy, Other (please specify) 35 If laparoscopic or thoracoscopic, was the surgery Yes/No. converted to open? 36 Condition specific complication within 30-days of primary Air leak (not just redundant space in the pleural cavity which is common),
37 surgery? Chylothorax, Recurrence, Adhesional obstruction, Other, None. Select all that http://bmjopen.bmj.com/ 38 apply. If other, please specify. 39 40 Intestinal Atresia 41 42 Question Answers Type of intestinal atresia Duodenal, Jejuno-ileal, Colonic 43 Classification of duodenal or colonic atresia 1,2,3,4 44 1) intraluminal web with continuity of the muscular layer, 2) atretic segment without a mesenteric defect, 3) atretic segment with mesenteric defect, 4)
45 on September 23, 2021 by guest. Protected copyright. multiple atresias = string of sausages appearance. 46 Classification of jejuno-ileal atresia 1,2,3a,3b,4 47 1) intraluminal web with continuity of the muscular layer, 2) atretic segment 48 without a mesenteric defect, 3a) atretic segment with mesenteric defect, 3b) apple-peel (bowel wrapped around a single artery), 4) multiple atresias = string 49 of sausages appearance. 50 Primary intervention for duodenal atresia: Duodenoduodenostomy, Duodenojenunostomy, Web excision only, Palliation, 51 Other. If other, please specify. 52 Surgical approach Laparotomy, Laparoscopy, Endoscopy, Other Conversion to open procedure? Yes/ No 53 Type of anastomosis Kimura’s diamond shape, Side-to-side, End-to-end 54 Primary intervention for jejuno-ileal and colonic atresia: Primary anastomosis, Bowel resection, Division of web only, Loop stoma, 55 Divided stoma, Bishop-Koop stoma, Santulli stoma, Palliation, Other. Select all that apply. 56 If bowel was excised, what was the total length of bowel In centimetres (cm). Enter 0 if unknown 57 excised? 58 Surgical approach: Laparotomy, Laparoscopy, Endoscopy, Other Conversion to open procedure? Yes, No 59 Was the distal bowel flushed to check for patency? Yes, No 60
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3 If the patient underwent surgery, did they have a Anastomotic leak, Anastomotic stenosis, Short-gut, Missed additional atresia, BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 condition specific complication within 30-days of primary Adhesive bowel obstruction, Stoma prolapse, Stoma retraction, Parastomal 5 intervention? hernia, Parastomal skin breakdown, Other. If other, please specify. Select all that apply. For the purposes of this study short gut is defined as more 6 than 50% of the small intestine excised (when short bowel syndrome can occur). 7 8 Gastroschisis 9 10 Question Answers 11 Type of gastroschisis Simple, Complex: associated with atresia, Complex: associated with necrosis, Complex: associated with perforation, Complex: associated with closing 12 gastroschisis. Select all that apply. 13 Primary intervention: Primary closure in the operating room (OR), Primary closure at the cotside 14 (Bianchi technique), Staged closure using a preformed silo, Staged closure using an Alexis Wound Retractor and Protector, Staged closure using a surgical 15 silo (including improvised silo), Other method, No intervention undertaken. 16 If other, please specify. 17 Method of defect closure: Fascia and skin closed with sutures, Just skin closed with sutures: fascia left 18 For peeropen, reviewUmbilical cord sutured overonly the defect: fascia left open, Sutureless closure with skin edges opposed and dressing applied, Dressing applied: defect left 19 open to close by secondary intention, Other, Patient died before the defect was 20 closed. If other, please specify. 21 On what day following admission was abdominal wall In days. Please include the first day of admission and the day of closure in the closure achieved? calculation. For example, for a neonate admitted with gastroschisis on 2nd 22 October who had the defect closed on 4th October, please insert 3 days. 23 Did the neonate have any of these complications within Ischemic bowel, Abdominal compartment syndrome (ACS), Necrotising 24 30-days of primary intervention? enterocolitis, None of these Select all that apply. ACS is defined as respiratory insufficiency secondary to 25 compromised tidal volumes, decreased urine output caused by falling renal 26 perfusion or any other organ dysfunction caused by increased intra-abdominal 27 pressure. 28 If the patient has ACS, was the abdomen re-opened? Yes/ No 29 Exomphalos 30
31 Question Answers 32 Type of Exomphalos? Major, Minor 33 Major: >50% of the liver in the exomphalos sac and abdominal wall defect >5cm. 34 Minor: Infants with defects less than 5cm. Hypoglycaemic on arrival? Yes, No, Blood glucose not measured 35 Hypoglycaemia is defined as a blood glucose level below 4 mmol/L (72mg/dL). 36 Primary intervention Primary operative closure, Staged closure, Conservative management If the patient had a staged closure, what was the time In days. Please include the day of the primary intervention and the day of 37 http://bmjopen.bmj.com/ 38 from primary intervention to closure? closure in the calculation. Enter 30 if still not closed at 30-days after primary intervention. 39 If conservative management, was a topical treatment Yes: silver sulfadiazine, Yes: betadine, Yes: honey, Yes: merbromide tannage, 40 applied to the exomphalos sac? Yes: other, no. If other, please specify. 41 If conservative management was undertaken, what is the No further surgery planned, Delayed closure at this hospital, Delayed closure at plan for future management? another hospital, Other. If other, please specify. 42 Did the patient have a ruptured sac? Yes, No 43 44 Anorectal Malformation (ARM)
45 on September 23, 2021 by guest. Protected copyright. 46 Question Answers 47 Type of anorectal malformation (Krickenbeck Low ARM: Perineal (cutaneous) fistula, High ARM: Rectourethral fistula (bulbar), classification) High ARM: Rectourethral fistula (prostatic), High ARM: Rectovesical fistula, High 48 ARM: Vestibular fistula, High ARM: Cloaca, High ARM: No fistula, High ARM: 49 Type unknown at present, Rare variant: Pouch colon, Rare variant: Rectal atresia/ 50 stenosis, Rare variant: Rectovaginal fistula, Rare variant: H fistula, Other 51 Did the neonate have pre-operative bowel perforation? Yes, No What was the primary intervention undertaken? Fistula dilation: no surgery, Loop sigmoid colostomy, Divided sigmoid colostomy, 52 Loop transverse colostomy, Divided transverse colostomy, Other stoma, 53 Anoplasty, Posterior sagittal anorectoplasty (PSARP), Abdominosacroperineal 54 pull-through, Abdominoperineal pull-through, Laparoscopic-assisted pull-through, Palliative care, Other. If other, please specify. Select all that apply. 55 If primary anorectal reconstruction was undertaken, was Yes, no: equipment was not available, no: the equipment was available but not 56 a Peña stimulator or equivalent used to identify the used. Peña stimulator: Muscle locating stimulator commonly used to identify the 57 position of the muscle complex intra-operatively? anal sphincter muscles whilst undertaking a PSARP for patients with ARM. Did the patient have any of the following complications For each of the below answer: Yes, No, Not applicable 58 within 30-days of surgery? 59 - Electrolyte disturbance 60 - High output stoma (over 20mls/kg/day)
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3 - Stoma prolapse/ retraction/ herniation BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 - Peri-stoma skin breakdown (or perianal if primary 5 reconstructive surgery undertaken without a covering stoma) 6 - Anal stenosis in those undergoing primary anorectal 7 reconstruction without covering stoma. 8 What is the plan for future management? No further operative management, Anoplasty/ pull-through planned at your hospital, Anoplasty/ pull-through planned at another hospital, Stoma closure 9 planned at your hospital, Stoma closure planned at another hospital, Other 10 Please tick all that apply. If other, please specify. 11 12 Hirschsprung’s Disease 13 14 Question Answers Time to first passage of meconium after birth Less than 24 hours, 24-48 hours, Over 48 hours, Unknown 15 Features at presentation: Abdominal distension, Bilious vomiting, Non-bilious vomiting, Poor feeding, 16 Suspected enterocolitis, Perforation, Other. Select all that apply. 17 Source of diagnosis of Hirschsprung's disease Genetic, Mucosal biopsy, Full thickness biopsy, Anorectal manometry, Barium 18 For peerenema, review Not confirmed: suspected only only, Other. If on biopsy, what was the method of histology staining. Hemotoxilin and Eosin (H&E), Acetylcholinesterase, Calretinin, Other. 19 Select all that apply. If other, please specify. 20 Length of aganglionosis: Rectal, Sigmoid, Descending colon, Transverse colon, Ascending colon, Small 21 bowel, Unknown at present 22 Primary intervention Conservative: no treatment, Conservative: digital stimulation and laxatives, Conservative: regular rectal washouts/ enemas, Failed conservative management 23 followed by a stoma during the same hospital admission, Primary stoma (with or 24 without pre-operative washouts or enemas prior to a planned stoma placement), 25 Primary pull-through (Swenson), Primary pull-through (Duhamel), Primary pull- through (Soave), Primary pull-through (Other), Transanal posterior anorectal 26 myectomy, Palliative care, Other. 27 If primary pull-through was undertaken, did the patient Yes, No 28 have a covering stoma? Was it laparoscopic assisted? Yes, No 29 Did the patient have any condition specific complications Hirschsprung's associated enterocolitis (HAEC), Electrolyte disturbance, High 30 within 30-days of primary intervention? stoma output (over 20mls/kg/day), Stoma prolapse/ retraction/ herniation, Peri- 31 stoma skin breakdown (or perianal if primary pull-through was undertaken without a covering stoma), Anal stenosis, Post-operative obstruction, Anastomotic leak (if 32 primary pull-through was undertaken without a covering stoma), Other 33 HAEC is defined as inflammation of the small and or large bowel in patient's born 34 with Hirschsprung's disease. If the patient was managed conservatively, please 35 tick if they developed enterocolitis within 30-days of presentation. Select all that apply. 36 What is the plan for future management? No further surgery planned, Anorectal pull-through at your hospital, Anorectal pull-
37 through at a different hospital, Stoma closure, Other, Unknown http://bmjopen.bmj.com/ 38 39 40 41 42 43 44
45 on September 23, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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1 2 3 Management and Outcomes of Gastrointestinal Congenital Anomalies in Low-, BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Middle- and High-Income Countries: Protocol for a Multi-Centre, International, 5 6 Prospective Cohort Study 7 8 9 SUPPLEMENTARY FILE 2 10 Collaborator Survey: Resources and Facilities for Neonatal and Paediatric Surgery 11 12 13 Question Answers Title Professor, Dr, Mr, Mrs, Miss, Ms, Other 14 Surname 15 First Name 16 Professional Position Professor, Consultant or attending, Registrar or resident, Intern/ house 17 officer/ senior house officer, Medical Student, Nurse, Other 18 Are you the study lead at your centre?For peer reviewYes, No only Answers provided by the study lead will be used as the 'Gold Standard' to 19 which the other survey will be compared (this will remain anonymous). 20 Speciality General Surgery (adult and paediatric), Paediatric Surgery, Anaesthetics, 21 Paediatrics, Neonatology, Nursing, Not specialised yet, Other Full name of institution: 22 Address of institution: 23 Country Afghanistan, Albania, Algeria, Andorra, Angola, Antigua and Barbuda, 24 Argentina, Armenia, Aruba (Kingdom of the Netherlands), Australia, 25 Austria, Azerbaijan, Bahamas, Bahrain, Bangladesh, Barbados, Belarus, Belgium, Belize, Benin, Bhutan, Bolivia, Bosnia and Herzegovina, 26 Botswana, Brazil, Brunei Darussalam, Bulgaria, Burkina Faso, Burundi, 27 Cambodia, Cameroon, Canada, Cape Verde, Central African Republic, 28 Chad, Chile, China, Colombia, Comoros, Congo, Costa Rica, Cote d'Ivoire, Croatia, Cuba, Curacao (Kingdom of the Netherlands), Cyprus, 29 Czech Republic, Democratic Peoples Republic of Korea, Democratic 30 Republic of the Congo, Denmark, Djibouti, Dominica, Dominican Republic, 31 Ecuador, Egypt, El Salvador, Equatorial Guinea, Eritrea, Estonia, Eswatini (Swaziland), Ethiopia, Fiji, Finland, France, Gabon, Gambia, Georgia, 32 Germany, Ghana, Greece, Grenada, Guatemala, Guinea, Guinea-Bissau, 33 Guyana, Haiti, Holy See (Vatican City State), Honduras, Hong Kong 34 (China), Hungary, Iceland, India, Indonesia, Iran (Islamic Republic of), Iraq, Ireland, Israel, Italy, Jamaica, Japan, Jordan, Kazakhstan, Kenya, 35 Kiribati, Korea (Republic of), , Kuwait, Kyrgyzstan, Lao People’s 36 Democratic Republic, Latvia, Lebanon, Lesotho, Liberia, Libya, Liechtenstein, Lithuania, Luxembourg, Macau (China), Macedonia (the 37 http://bmjopen.bmj.com/ 38 former Yugoslav Republic of), Madagascar, Malawi, Malaysia, Maldives, Mali, Malta, Marshall Islands, Mauritania, Mauritius, Mexico, Micronesia 39 (Federated States of), Moldova (Republic of), Monaco, Mongolia, 40 Montenegro, Morocco, Mozambique, Myanmar, Namibia, Nauru, Nepal, 41 Netherlands, New Zealand, Nicaragua, Niger, Nigeria, Niue, Norway, Oman, Pakistan, Palau, Palestinian Territories, Panama, Papua New 42 Guinea, Paraguay, Peru, Philippines, Poland, Portugal, Qatar, Republic of 43 Kosovo, Reunion Island, Romania, Russian Federation, Rwanda, Saint 44 Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Samoa, San Marino, Sao Tome and Principe, Saudi Arabia, Senegal, Serbia,
45 Seychelles, Sierra Leone, Singapore, Sint Maarten (Kingdom of the on September 23, 2021 by guest. Protected copyright. 46 Netherlands), Slovakia, Slovenia, Solomon Islands, Somalia, Somaliland, 47 South Africa, South Sudan, Spain, Sri Lanka, Sudan, Suriname, 48 Swaziland (See Eswatini), Sweden, Switzerland, Syrian Arab Republic, Taiwan, Tajikistan, Tanzania (United Republic of), Thailand, Timor-Leste, 49 Togo, Tonga, Trinidad and Tobago, Tunisia, Turkey, Turkmenistan, 50 Tuvalu, Uganda, Ukraine, United Arab Emirates, United Kingdom, 51 Uruguay, USA, Uzbekistan, Vanuatu, Venezuela, Viet Nam, Yemen, Zambia, Zimbabwe 52 Type of institution (WHO classification) - Specialised children's hospital (Provides highly specialised care 53 dedicated to children) 54 - Referral hospital (WHO defined tertiary healthcare. Includes academic, university, teaching, national, central and specialised 55 mission hospitals. Can provide specialised surgical services) 56 - District hospital (WHO defined secondary healthcare. Includes 57 provincial, general, general mission or regional hospitals. Has general 58 anaesthesia and can provide general surgical care) - Health centre (WHO defined primary healthcare. No general 59 anaesthesia, can do minor local procedures, wound management, triage 60 and referral).
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3 Institutional classification Government, Non-government BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Institutional financial classification Not for profit, For profit 5 Population served by your institution (in millions, including children and adults) 6 Personnel 7 Number of Consultant Paediatric Surgeons undertaking ______(Excluding trainees) 8 neonatal surgery at your institution: 9 Number of Consultant General Surgeons (covering adults and children) undertaking neonatal surgery independently at your ______(Excluding trainees) 10 institution: 11 Number of medical officers or other non-surgeon healthcare 12 professionals undertaking neonatal surgery independently at ______(Without a consultant surgeon present at the time 13 your institution of surgery) Infrastructure 14 Please state whether the following facilities are available at your institution when required: 15 Running Water Always, Sometimes, Never 16 Electricity Always, Sometimes, Never 17 Electricity generator back-up Always, Sometimes, Never Laboratory for biochemistry Always, Sometimes, Never 18 Laboratory for haematology For peer reviewAlways, Sometimes, Never only 19 Blood bank Always, Sometimes, Never 20 Sterile gloves and gown Always, Sometimes, Never 21 Autoclave for sterilising surgical equipment Always, Sometimes, Never Neonatal ventilation outside the operating room Always, Sometimes, Never 22 Paediatric ventilation outside the operating room Always, Sometimes, Never 23 Neonatal intensive care unit for surgical neonates pre and post Always, Sometimes, Never 24 operatively (including if a stoma is present) 25 Paediatric intensive care unit for surgical paediatric patients pre Always, Sometimes, Never and post operatively if required 26 Parenteral nutrition for neonates Always, Sometimes, Never 27 Parenteral nutrition for adults and older children Always, Sometimes, Never 28 Extracorporeal membrane oxygenation (ECMO) Always, Sometimes, Never 29 Peña stimulator or equivalent device to identify the muscle Always, Sometimes, Never complex during anorectal reconstruction 30 Suction rectal biopsy gun to investigate for Hirschsprung's Always, Sometimes, Never 31 disease 32 Procedures Please state whether the following procedures are available at your institution when clinically appropriate/ required: 33 Neonatal laparotomy Always, Sometimes, Never 34 Neonatal laparoscopy Always, Sometimes, Never 35 Neonatal thoracotomy Always, Sometimes, Never 36 Neonatal thoracoscopy Always, Sometimes, Never Neonatal central line insertion Always, Sometimes, Never
37 http://bmjopen.bmj.com/ Paediatric central line insertion Always, Sometimes, Never 38 Umbilical vein catheterisation Always, Sometimes, Never 39 Bedside primary reduction and closure of gastroschisis Always, Sometimes, Never 40 (Bianchi technique) Preformed silo application, reduction and closure of Always, Sometimes, Never 41 gastroschisis 42 Surgical silo application, reduction and closure of Always, Sometimes, Never 43 gastroschisis 44 Primary closure of gastroschisis in the operating room Always, Sometimes, Never Sigmoid colostomy Always, Sometimes, Never
45 Posterior Sagittal Anorectoplasty (PSARP) for anorectal Always, Sometimes, Never on September 23, 2021 by guest. Protected copyright. 46 malformation 47 Foetal tracheal occlusion (FETO) for CDH Always, Sometimes, Never 48 Pull-through for Hirschsprung's disease Always, Sometimes, Never Anaesthesia and resuscitation 49 Please state whether the following facilities are available at your institution when required: 50 Neonatal bag, valve and mask Always, Sometimes, Never 51 Paediatric bag, valve and mask Always, Sometimes, Never 52 Bottled oxygen Always, Sometimes, Never Piped oxygen Always, Sometimes, Never 53 Oxygen saturation monitor Always, Sometimes, Never 54 Apnoea monitor Always, Sometimes, Never 55 Multi-parameter intra-operative monitoring Always, Sometimes, Never 56 Anaesthetic machine for neonates Always, Sometimes, Never 57 Anaesthetic machine for children Always, Sometimes, Never Ketamine anaesthesia for neonates Always, Sometimes, Never 58 Ketamine anaesthesia for children Always, Sometimes, Never 59 Spinal/ caudal anaesthesia for neonates Always, Sometimes, Never 60 Spinal/ caudal anaesthesia for children Always, Sometimes, Never
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3 Anaesthetic doctor competent to perform neonatal anaesthesia Always, Sometimes, Never BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Anaesthetic doctor competent to perform paediatric Always, Sometimes, Never 5 anaesthesia Anaesthetic nurse competent to perform neonatal anaesthesia Always, Sometimes, Never 6 Anaesthetic nurse competent to perform paediatric anaesthesia Always, Sometimes, Never 7 Does your country have at least one specialised children's Yes, No 8 hospital that can provide neonatal and paediatric surgery? 9 Any other comments? 10 11 12 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44
45 on September 23, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
3 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 Management and Outcomes of Gastrointestinal Congenital Anomalies in Low-, Middle- and High-Income Countries: 4 Protocol for a Multi-Centre, International, Prospective Cohort Study 5 6 7 8 SUPPLEMENTARY FILE 3: Study approval details of participating centres 9 10 Number Country Institution Name Ethical/Audit Review Board Name Approval Type Approval Reference Number Low-Income Countries (LICs) 11 Afghanistan Ataturk National Children’s Hospital Islamic Republic of Afghanistan Ministry of Public Local (Ethical) 444738 12 For peerHealth, review Afghanistan National Public Health only Institute, 13 1 Institutional Review Board 14 Afghanistan French Medical Institute for Mothers and Institutional Review Board Local (Ethical) - 2 Children (FMIC) 15 3 Afghanistan Ghalib University Hospital Ministry of Higher Education, Ghalib Cadre Hospital Local (Ethical) - 16 Afghanistan Ghor Provincial Hospital EPHS Directorate, GD of Curative Medicine, Ministry of Local (Ethical) - 17 4 Public Health http://bmjopen.bmj.com/ 18 5 Afghanistan Indra Ghandi Institute of Child Health (IGICH) Institutional Review Board Local (Ethical) - 6 Afghanistan Irena Salimi Children Hospital (ISCH) Institutional Review Board Local (Ethical) - 19 7 Burundi Bujumbura, Kamenge Military Hospital Head of Department Surgery Local (Departmental) - 20 8 Burundi District Hospital Kibimba, Gitega Medical Director of Kibimba Hospital Local (Hospital) 4000342958 21 9 Burundi Gitega Hospital Mutoyi Hospital Director Local (Hospital) - 22 Burundi Kibuye Hope Hospital, Hope Africa Head of Surgery and Ethics Team Local (Ethical and - 10 University, Gitega Hospital) 23 11 Burundi King Khaled Teaching Hospital Medical Director General Local (Hospital) 2019|DECHUK.359|11.5 24 12 Burundi Teaching Hospital University of Kamenge Medical Director General Local (Hospital) 2019|DECHUK.271|11.5 25 13 Burundi Van Norman Clinic Bjumbura Medical Director of Kibimba Hospital Local on September 23, 2021 by guest. Protected copyright. (Hospital) - 26 Democratic Republic of HEAL Africa Hospital, Goma Institutional Review Board at HEAL Africa Local (Ethical) - 14 Congo 27 15 Ethiopia Addis Ababa University Deputy Head of Department of Surgery Local (Departmental) - 28 Gambia Edward Francis Small Teaching Hospital, Chair of Gambia Government/MRCG Joint Ethics Local (Ethical) - 29 16 Banjul Committee 30 17 Gambia Kanifing General Hospital, Kanifing Gambia Government / MRCG Joint Ethics Committee Regional (Ethical) - 18 Nepal Annapurna Children and Women’s Hospital Medical Director Local (Hospital) - 31 19 Niger National Hospital Lamorde, Niamey Hospital Director General Local (Hospital) 000306 32 Rwanda Centre Hospitalier Universitaire de Butare College of Medicine and Health Science Institutional Local (Ethical) 301/CMHS IRB/2018 33 20 Review Board 34 Rwanda Rwanda Military Hospital College of Medicine and Health Science Institutional Local (Ethical) 301/CMHS IRB/2018 21 Review Board 35 Rwanda University Teaching Hospital of Kigali College of Medicine and Health Science Institutional Local (Ethical) 301/CMHS IRB/2018 36 22 Review Board 37 23 Somaliland Hargeisa Group Hospital Director of Hargeisa Group Hospital Local (Hospital) HGH/800/0.1/18 38 24 Tanzania Kilimanjaro Christian Medical Centre Executive Director Local (Hospital) - 25 Zimbabwe Mpilo Hospital Clinical Director of Mpilo Central Hospital Local (Hospital) - 39 TOTAL LICs: 25 40 41 42 1 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 Middle-Income Countries (MICs) 4 26 Algeria Hôpital Mère-Enfant EHS EL EULMA Institutional Ethical Committee of Ferhat ABBAS Local (Ethical) - 5 University SETIF 27 Algeria Hospital Chu Tizi-ouzou Ethical Committee of the University Mouloud Maameri Local (Ethical) - 6 de Tizi-ouzou 7 28 Algeria Le Nefissa Hamoud University Hospital Institutional Ethics Comittee Local (Ethical) - 8 29 Angola Pediatric Hospital David Bernardino Hospital Director Local (Hospital) 55/09/DIRPED/HPDB/018 9 30 Argentina Children’s Hospital of Santa Fe Associate Director of Teaching and Research Local (Hospital) - 31 Argentina Clinica Pueyrredon Medical Director Local (Hospital) - 10 32 Argentina Dr Humberto Notti Pediatric Hospital of Executive Director Local (Hospital) 3542-D-2018-04238-E-0-6 11 Mendoza 12 33 Argentina Fundación Dr JR Villavicencio Clinical Investigation Ethical Committee Local (Ethical) - 34 Argentina Fundacion HospitalariaFor peerChief ofreview Department of Paediatric Surgery only Local (Departmental) - 13 35 Argentina Hospital de Niños Victor J. Vilela, Rosario, President of the Ethics Committee in Research Local (Ethical) - 14 Santa Fe 15 36 Argentina Hospital Escuela Eva Perón, Rosario Medical Director Local (Hospital) 30630225 16 37 Argentina Hospital Italiano de Buenos Aires, Buenos Ethical Committee Local (Ethical) 139/DGDOIN/14 Anexo 1 17 Aires http://bmjopen.bmj.com/ 38 Argentina Hospital Provincial de Rosario Research Ethics Committee (CEI) Local (Ethical) - 18 39 Argentina Hospital Público Materno Infantil President of the Advisory Commission on Teaching and Local (Hospital) - 19 Investigation 20 40 Argentina Hospital Rawson, San Juan Ethics committee in research Local (Ethical) 33/18 21 41 Argentina Maternidad Martin, Rosario, Santa Fe President of the Ethics Committee in Research Local (Ethical) - 42 Argentina Maternity Clinic Colón Teaching and Research committee Local (Hospital) - 22 43 Argentina Materno Provincial Health Minister, Training, Teaching and Investigation Local (Hospital) - 23 Committee 24 44 Argentina Maternoneonatal, Córdoba Surgical Director Local (Departmental) - 25 45 Argentina Pediatric Hospital of Santiago del Estero Deputy Medical Director Local on September 23, 2021 by guest. Protected copyright. (Hospital) - 46 Argentina Zona Norte Children Hospital Medical Director Local (Hospital) - 26 47 Bangladesh Bangabandhu Sheik Mujib Medical University Chairman, Department of Paediatric Surgery Local (Departmental) - 27 (BSMMU), Dhaka 28 48 Bangladesh Dhaka Medical College Hospital Ethical Committee Local (Ethical) MEU-DMC/ECC/2018/249 29 49 Bangladesh Dhaka Shishu Hospital Hospital Authority Local (Hospital) - 30 50 Belarus Republican Scientific Practical Centre of Ethical Council Local (Ethical) 1-18/394 31 Pediatric Surgery, Minsk 32 51 Bolivia Children's Hospital Manuel A.Villarroel Medical Director Local (Hospital) - 33 Cochabamba 52 Bolivia Hospital Hernandez Vera, Santa Cruz Medical Director Local (Hospital) - 34 53 Bolivia Hospital San Juan de Dios, Tarija Medical Director Local (Hospital) - 35 54 Bolivia Mario Ortiz Children's Hospital Suarez, Santa Medical Director Local (Hospital) - 36 Cruz 55 Bolivia Women’s Hospital Percy Boland Rodriguez Medical Director Local (Hospital) - 37 Santa Cruz 38 56 Bosnia and Herzegovnia Clinic of Paediatric Surgery, Clinical Centre Ethical Committee Local (Ethical) 03-02-47488 (Protocol: 0602- 39 University of Sarajevo, Sarajevo 40400) 40 57 Brazil Associação de Ensino Superior de Nova Iguaçu National Ethical Committee National (Ethical) 3.130.042 41 42 2 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 58 Brazil Associação Hospitalar de Prot Infancia Dr. Raul National Ethical Committee National (Ethical) 3.130.042 4 Carneiro 5 59 Brazil Botucatu Medical School, State of Sao Paulo National Ethical Committee National (Ethical) 3.130.042 University 6 60 Brazil Centro de Ensino São Lucas Ltda/ RO National Ethical Committee National (Ethical) 3.130.042 7 61 Brazil Clinical Hospital from Federal University of National Ethical Committee National (Ethical) 3.130.042 8 Uberlandia 9 62 Brazil Federal University of Minas Gerais National Ethical Committee National (Ethical) 3.130.042 63 Brazil Federal University of Parana National Ethical Committee National (Ethical) 3.130.042 10 64 Brazil Fundação Facudade Regional de Medicina S J National Ethical Committee National (Ethical) 3.130.042 11 Rio Preto 12 65 Brazil Fundação Hospitalar Blumenau: Hospital Santo National Ethical Committee National (Ethical) 3.130.042 Antoni For peer review only 13 66 Brazil Hospital da Criança Santo Antônio – Santa National Ethical Committee National (Ethical) 3.130.042 14 Casa/RS 15 67 Brazil Hospital da Luz/ São Paulo – SP National Ethical Committee National (Ethical) 3.130.042 16 68 Brazil Hospital de Base Dr. Ary Pinheiro, Porto Velho National Ethical Committee National (Ethical) 3.130.042 17 69 Brazil Hospital do Rocio National Ethical Committee Nationalhttp://bmjopen.bmj.com/ (Ethical) 3.130.042 70 Brazil Hospital Federal de Bonsucesso National Ethical Committee National (Ethical) 3.130.042 18 71 Brazil Hospital Infantil Jona de Gusmão/ SES – SC National Ethical Committee National (Ethical) 3.130.042 19 72 Brazil Hospital Jorge Valente/ Salvador - BA National Ethical Committee National (Ethical) 3.130.042 20 73 Brazil Hospital Materno Infantil de Brasília – HMIB National Ethical Committee National (Ethical) 3.130.042 21 74 Brazil Hospital Nossa Senhora da Conceição SA National Ethical Committee National (Ethical) 3.130.042 75 Brazil Hospital Santo Antônio Blumenau Santa National Ethical Committee National (Ethical) 3.130.042 22 Catarina 23 76 Brazil Hospital Universitário de Santa Maria National Ethical Committee National (Ethical) 3.130.042 24 77 Brazil Hospital Universitário do Oeste do Paraná National Ethical Committee National (Ethical) 3.130.042 25 78 Brazil Hospitalar Municipal do M’boi Mirim/ São Paulo National Ethical Committee National on September 23, 2021 by guest. Protected copyright. (Ethical) 3.130.042 - SP 26 79 Brazil Instituto de Medicina Integral Professor National Ethical Committee National (Ethical) 3.130.042 27 Fernando Figueira 28 80 Brazil Instituto Fernandes Figueira, Rio de Janeiro National Ethical Committee National (Ethical) 3.130.042 29 81 Brazil Irmandade da Santa Casa de Misericórdia de National Ethical Committee National (Ethical) 3.130.042 Santos 30 82 Brazil Irmandade Nossa Senhora das Merces de National Ethical Committee National (Ethical) 3.130.042 31 Montes Claros 32 83 Brazil Instituto Fernandes Figueira, Rio de Janeiro National Ethical Committee National (Ethical) 3.130.042 84 Brazil SPDM – Associação Paulista para o National Ethical Committee National (Ethical) 3.130.042 33 Desenvolvimento da Medicina 34 85 Brazil Universidade Estadual de Montes Claros - National Ethical Committee National (Ethical) 3.130.042 35 UNIMONTES 36 86 Brazil Universidade Federal de São Paulo – National Ethical Committee National (Ethical) 3.130.042 UNIFESP/EPM 37 87 Brazil University Hospital, Porto Alegre National Ethical Committee National (Ethical) 3.130.042 38 88 Cameroon Mbingo Hospital in North West Cameroon Institutional Review Board Local (Ethical) - 39 89 China Bayi Children’s Hospital Research Ethics Criteria Local (Ethical) - 40 90 China Children's Hospital of Shanghai In Chinese script Local (Ethical) - 41 42 3 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 91 China Children’s Hospital of Soochow University President of the Seventh Medical Center of PLA Local (Ethical) - 4 General Hospital 5 92 China Children’s Hospital, Zhejiang University School Hospital President and Ethics Committee Local (Ethical) - of Medicine, Binjiang District, Hangzhou 6 93 China First Affiliated Hospital of Xinjiang Medical Research Ethics Criteria Local (Ethical) - 7 University 8 94 China Hunan Children’s Hospital In Chinese script Local (Ethical) - 9 95 China Jinhua Municipal Central Hospital Research Ethics Committee Local (Ethical) - 96 China Kunming Children’s Hospital Medical Ethics Committee Local (Ethical) - 10 97 China Nanjing Children’s Hospital Research Ethics Criteria Local (Ethical) - 11 98 China Ningbo Women Children’s Hospital Research Ethics Criteria Local (Ethical) - 12 99 China Shengjing Hospital In Chinese script Local (Ethical) - 100 China Wenzhou MedicalFor University Affiliate peer 2nd Research review Ethics Criteria onlyLocal (Ethical) - 13 Hospital and Yuying Children Hospital 14 101 China Wuhan Children’s Hospital In Chinese script Local (Ethical) - 15 102 Colombia Bogota Hospital Militar Central Director General Local (Hospital) 2018046 16 103 Colombia Bogota Hospital San Jose Centro Society for President of Society Local (Departmental) - 17 Surgery http://bmjopen.bmj.com/ 104 Colombia Fundacion Valle de Lili Cali Colombia Research and Biomedical Ethics Committee Local (Ethical) 234-2018 18 105 Colombia Materno Infantil Saludcoop, Villavicencio Medical Director Local (Hospital) - 19 106 Dominican Republic Hospital Infantil Dr. Robert Reid Cabral, Santa Investigational Committee Local (Hospital) 20 Domingo 21 107 Ecuador Hospital Especialidades Carlos Andrade Martin, Technical Director Local (Hospital) IESS-HJCA-DT-2018-5098-M Quito 22 108 Ecuador Hospital de Especialidades José Carrasco Hospital Director Local (Hospital) - 23 Arteaga, Cuenca 24 109 Ecuador Hospital de Los Valles Medical Director Local (Hospital) - 25 110 Ecuador Hospital General del Norte de Guayaquil Deputy Director of Teaching Local on September 23, 2021 by guest. Protected copyright. (Hospital) IESS-HG-NGC-DO-2018-0008-O 111 Ecuador Omni Hospital, Gayaquil Director of Teaching Local (Hospital) - 26 112 Egypt Al Zahra Hospital In Arabic script Local (Ethical) - 27 113 Egypt Alexandria University Children’s Hospital Ethics Committee Local (ethical) 0304041 28 114 Egypt Assiut University Hospital In Arabic script Local (Ethical) - 29 115 Egypt Mansoura University Children’s Hospital Head of Department of Pediatric Surgery Council Local (Departmental) 0032610/2020/81A
30 116 Egypt Nasser Institution for Research and Treatment, Hospital Director Letter Local (Ethical) - 31 Cairo 32 117 Egypt Tanta University Hospital In Arabic script Local (Ethical) - 33 118 Gabon Bongolo Hospital, Lebamba Institutional Review Board at Bongolo Hospital Local (Ethical) - 119 Ghana Korle-Bu Teaching Hospital Scientific and Technical Committee & KBTH Local (Ethical) KBTH/MIS/G3/19 34 Institutional Review Board 35 120 Ghana Tamale Teaching Hospital Head of Research and Development Local (Ethical) TTH/R&D/SR/18/8 36 121 India Bazaricherra, Karimganj District Chairman Research Committee Local (Ethical) - 37 122 India Christian Medical college Ludhiana, Punjab Institutional Research Committee Local (Ethical) - 123 India Kasturba Medical College (Kasturba Hospital) Institutional Ethics Committee Local (Ethical) ECR/146/Inst/KA/2013/RR-16 38 Manipal 39 124 India Makunda Christian Leprosy and General Chairman of Research Committee Local (Ethical) - 40 Hospital, Bazaricherra, Karimganj District 41 42 4 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 125 Indonesia Dr Soetomo Hospital, Surabaya President of Indonesian Association of Pediatric Local (Association and 83/PERBANI/XI/2018 4 Surgeons and Head of Institutional Review Board Ethical) IRB/22/04/ETIK/2019 5 126 Indonesia Rumah Sakit Anak dan Bunda Harapan Kita Indonesian Association of Pediatric Surgeons president Local and Regional - Jakarta approval 6 127 Iran Mofid Children’s Hospital (MCH) Research Council of Research Institute for Children Local (Ethical) 0477, 162 7 Health 8 128 Iraq Al-Mustansiriyah University Central Ministry of Higher Education and Scientific Research Local (Ethical) 239 9 129 Iraq Child's Central Teaching Hospital, Ethical Committee Local (Ethical) - Baghdad/Mustansiriyah Medical College 10 130 Iraq University of Kufa Medical Ethics Committee for University Local (Ethical) MEC-035 11 131 Jordan Al-Basheer Hospital Al-Basheer Hospital and Chairman of Pediatric Surgery Local (Departmental, 15999 12 Hospital) 132 Jordan Jordon UniversityFor Hospital of Medicine peer Institutional review Review Board onlyLocal (Ethical) 10/2018/2448 13 133 Jordan JUST King Abdallah University Hospital Institutional Review Board Local (Ethical) 4/118/2018 14 134 Kenya Aga Khan University Hospital Research Ethics Committee, Aga Khan University Local (Ethical) 2018/REC-138 (v1) 15 135 Kenya Joromongi Oginga Odinga Teaching & Referral JOOTRH Institutional Ethics and Research Committee Local (Ethical) ERC.IB/VOL.1/475 16 Hospital, Kisumu 17 136 Kenya University of Nairobi and Kenyatta National Kenyatta National Hospital – University of Nairobi Local http://bmjopen.bmj.com/ (Ethical) KNH-ERC/A/6 Hospital Ethics and Research Committee 18 137 Libya Al Fardous Clinic Ethical Approval from Head of Medical Services Local (Ethical) 2/018 P. 19 138 Libya Alaml Specialised Hospital, Misurata Ethical Approval from Head Director of Alaml Local (Ethical) - 20 Specialized Hospital 21 139 Libya Asalam, Misurata In local script Local (Ethical) - 140 Libya Assafwa international hospital, Misurata Ethical Approval from Head of Medical Service Local (Ethical) - 22 141 Libya Dar Alhekma Hospital Head Director of Dar Alhekma Specialized Hospital Local (Ethical) - 23 142 Libya Ghout El-Shaal Specialized Hospital In local script Local (Ethical) - 24 143 Libya Misarata Cancer Centre Director of Medical Affairs, Chief of Medical Ethics Local (Ethical) 708/42. 25 144 Libya Misurata Medical Centre Medical Director Local on September 23, 2021 by guest. Protected copyright. (Ethical) - 26 145 Libya Tripoli Children’s Hospital Ethical Committee Local (Ethical) NCDC:E17:2018. 146 Libya Tripoli Medical Centre Hospital Director Local (Hospital) - 27 147 Macedonia University Clinic for Paediatric Surgery Ethical Committee Local (Ethical) - 28 148 Malaysia Hospital Canselor Tuanku Muhriz, UKM Research Ethics Committee Local (Ethical) UKM PPI/111/8/JEP-2018-464 29 Medical Centre 149 Malaysia Hospital Kuala Lumpar Medical Research and Ethics Committee of Ministry of Regional (Ethical) KKM/NIHSEC/ P18-1816 (14) 30 Health Malaysia 31 150 Malaysia Hospital Pulau Pinang Medical Research and Ethics Committee of Ministry of Regional (Ethical) KKM/NIHSEC/ P18-1816 (14) 32 Health Malaysia 33 151 Malaysia Hospital Raja Perempuan Zainab II, Kota Medical Research and Ethics Committee of Ministry of Regional (Ethical) KKM/NIHSEC/ P18-1816 (14) Bharu, Kelantan Health Malaysia 34 152 Malaysia Hospital Sultanah Aminah, Johor Bharu, Johor Medical Research and Ethics Committee of Ministry of Regional (Ethical) KKM/NIHSEC/ P18-1816 (14) 35 Health Malaysia 36 153 Malaysia Hospital Sultanah Nur Zahirah, Kuala Medical Research and Ethics Committee of Ministry of Regional (Ethical) KKM/NIHSEC/ P18-1816 (14) 37 Terengganu, Terengganu Health Malaysia 154 Malaysia Hospital Tengku Ampuan Afzan, Kuantan Medical Research and Ethics Committee of Ministry of Regional (Ethical) KKM/NIHSEC/ P18-1816 (14) 38 Health Malaysia 39 155 Malaysia Hospital Wanita dan Kanak-Kanak, Likas, Medical Research and Ethics Committee of Ministry of Regional (Ethical) KKM/NIHSEC/ P18-1816 (14) 40 Sabah Health Malaysia 41 42 5 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 156 Malaysia Penang General Hospital Ethics & Medical research Committee Local (Ethical) KKM/NIHSEC/P18-1816(11) 4 157 Mexico Hospital General Tijuana, Baja California Research and Ethics Committee Local (Ethical) - 5 158 Mexico Hospital Civil de Guadalajara Research Committee and Ethics Committee Local (Ethical) 0247/18 HCJIM/2018 and HCG/CEI-0913/18 6 159 Mexico Hospital de Especialidades del Nino y Mujer de Research Committee Local (Hospital) 135/10-10-2018/CIR.PED / HENM 7 Queretaro 8 160 Mexico Hospital del Niño Poblano Research Committee Local (Hospital) HNP 2018-16 9 161 Mexico Hospital Infantil de Mexico Federico Gomez Committee of Research, Ethics and Biosecurity Local (Ethical) HIM 2018-043 162 Mexico Hospital Regional de Alta Especialidad del Niño Research and Ethics Committee Local (Ethical) DI/051/18 10 “Dr. Rodolfo Nieto Padrón” 11 163 Mexico Moctezuma Children’s Hospital Research and Ethics Committee Local (Ethical) 09-CEI-006-20180328 12 164 Mexico Pediatric Hospital, Western Medical Center, SIRELCIS Administration Local (Hospital) F-CNNIC-2018-209 Mexican InstituteFor of Social Security peer review only 13 165 Morocco Centre Hospitalier Universaitaire IBN Sina de Chief of Paediatric Emergency Services Local (Departmental) - 14 Rabat, Rabat 15 166 Nigeria Amino Kano Teaching Hospital Research Ethics Committee Local (Ethical) LAKTH/MAC/SUB/12A/ P- 16 3/VI/2402 17 167 Nigeria Bowen University Teaching Hospital Ethics Committee Local http://bmjopen.bmj.com/ (Ethical) NHREC/12/04/2012 168 Nigeria Federal Medical Centre Abeokuta Health Research Ethics Committee Local (Ethical) FMCA/470/19 18 169 Nigeria Federal Medical Centre Umuahia Health Research Ethics Committee Local (Ethical) FMC/QEH/G.596/Vol.10/ 371 19 170 Nigeria Federal Medical Centre Yola Research and Ethics Committee Local (Ethical) FMCY/SUB/S.128/042 20 171 Nigeria Federal Teaching Hospital Gombe Health Research Ethics Committee Local (Ethical) NHREC/25/10/2013 21 172 Nigeria Lagos State University Teaching Hospital Health Research Ethics Committee of LASUTH (LREC) Local (Ethical) NHREC04/04/2008 173 Nigeria Lagos University Teaching Hospital Lagos University Teaching Hospital Health Research Local (Ethical) NHREC 19/12/2008a 22 Ethics Committee (LUTHHREC) 23 174 Nigeria National Hospital Abuja Institute Review Board Committee Local (Ethical) NHA/EC/054/2018 24 175 Nigeria Nnamdi Azikiwe University Teaching hospital Ethics Committee Local (Ethical) NAUTH/CS/668/VOL.2 /024 and 25 on September 23, 2021 by guest. Protected copyright. NAUTH/CS/66/VOL.11/ 171/2018/107 26 176 Nigeria Olabisi Onabanjo University Teaching Hospital Health Research Ethics Committee Local (Ethical) NHREC/28/11/2017 27 177 Nigeria University College Hospital, Ibadan Ethics Committee and Head of Department of Surgery Local (Ethical) UI/EC/18/0432 28 178 Nigeria University of Abuja Teaching Hospital Health Research Ethics Committee Local (Ethical) UATH/HREC/PR/2019/001 29 179 Nigeria University of Nigeria Teaching Hospital Health Research Ethics Committee Local (Ethical) UNTH/CSA/329/OL5 180 Pakistan Aga Khan University Ethics Review Committee Local (Ethical) 2019-0454-2658 30 181 Pakistan Children's Hospital, PIMS, and Shaheed Ethical Review Board Local (Ethical) 1-1 /2015 /ERB /SZABMU /274 31 Zulfiqar Ali Bhutto Medical University, 32 Islamabad 182 Pakistan Karachi Indus hospital Interactive Research and Development Institute Review Local (Ethical) IRD_IRB_2018_07_012 33 Board 34 183 Pakistan Lahore King Edward Medical University Institute Review Board Local (Ethical) 109/RC/KEMU 35 184 Pakistan Liaquat National Hospital Ethics Review Committee Local (Ethical) 0434-2018 LNH-ERC 36 185 Pakistan The Children’s Hospital and the Institute of Institute Review Board Local (Ethical) 45868 Child Health 37 186 Palestine, Gaza Al-Aqsa Hospital, Gaza Strip Helsinki Committee for Ethical Approval National (ethical) PHRC/HC/41//18 38 187 Palestine, Gaza Al-Shifa Hospital, Gaza Strip Helsinki Committee for Ethical Approval National (ethical) PHRC/HC/41//18 39 188 Palestine, Gaza European Gaza Hospital, Gaza Strip Helsinki Committee for Ethical Approval National (ethical) PHRC/HC/41//18 40 189 Palestine, West Bank Ahli Hospital, Hebron In Arabic script National/Local (ethical) - 41 42 6 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 190 Palestine, West Bank Jenin Government Hospital, Jenin In Arabic script National/Local (ethical) - 4 191 Palestine, West Bank Mount of Olives/Makassed, Jerusalem In Arabic script National/Local (ethical) - 5 192 Palestine, West Bank Palestinian Medical Complex ( PMC), Ramallah In Arabic script National/Local (ethical) - 6 193 Palestine, West Bank Rafidia Surgery Hospital, Nablus In Arabic script National/Local (ethical) - 7 194 Palestine, West Bank Red Crescent Society, Hebron In Arabic script National/Local (ethical) - 195 Papua New Guinea Mount Hagen General Hospital Director Clinical Excellence Local (Hospital) - 8 196 Papua New Guinea Port Moresby General Hospital Director Medical Services and Ethical Committee Local (Ethical) - 9 197 Peru Cayetano Heredia Hospital Institutional Committee of Ethics and Investigation Local (Ethical) - 10 198 Peru Guillermo Almenara National Hospital, Lima Ethical Committee Local (Ethical) 174-2018 11 199 Peru Hospital Dos de Mayo Ethics committee in biomedical research Local (Ethical) 085-2018-CEIB-HNDM 12 200 Peru Hospital Nacional Alberto Sabogal Sologuren Institutional committee on ethics in research Local (Ethical) 549-OAIyD-HNASS-ESSALUD- For peer review only 2018 13 79-UCP-DC-GQ-HNASS- 14 ESSALUD-2018 15 201 Peru Hospital Nacional Docente Madre Niño San Committee of Institutional Ethics and Research Local (Ethical) 12200-18 Bartolomé 16 202 Peru Hospital Nacional Edgardo Rebagliati Martins Ethics Committee Local (Ethical) 943-OCIYD-GHNERM-GRPR- http://bmjopen.bmj.com/ 17 ESSALUD-2018 18 19 203 Peru Hospital Regional Del Cusco Research committee and training unit Local (Hospital) 8868-18. 204 Peru Instituto Nacional de Salud Del Niño Institutional Committee of Ethics and Investigation Local (Ethical) PI-64/18 20 205 Peru Instituto Nacional de Salud de Nino de San Institutional Committee of Ethics and Investigation Local (Ethical) PI-2018-246 21 Borja 22 206 Peru Instituto Nacional Materno Perinatal Health Minister Local (Hospital) 699-2018-DEN/INMP 23 207 Peru Pediatric Emergencies Hospital Head of the Teaching and Research Support Office Local (Hospital) 065-2018-OADI-HEP/MINSA 208 Philippines Philippines Children’s Medical Center Institutional Review Board – Ethics Committee Local (Ethical) PCMC IRB-EC 2018-040 24 209 Romania Children Clinical Hospital of Brasov, Ethical Committee Local (Ethical) - 25 Brasov/University of Brasov on September 23, 2021 by guest. Protected copyright. 26 210 Romania Marie Curie Hospital in Bucharest Ethical Committee Local (Ethical) - 27 211 Serbia Clinical Centre for Paediatric Surgery and Ethics Committee of the Faculty of Medicine University Local (Ethical) 12-3182-2/11 Orthopaedics, Clinical Center Niš of Niš President 28 212 Serbia University Children’s Hospital Ethics Committee Local (Ethical) 14/390 29 213 South Africa Frere Hospital Clinical Governance Committee and Frere and Cecilia Local (Ethical) FCMHREC/013/2019 30 Makiwane Hospitals Research Ethics Committee 214 South Africa Greys Hospital, Pietermaritzburg Subcommittee of Biomedical Research Ethics Local (Ethical) BCA221/13 31 Committee 32 215 South Africa Grootte Schurr Hospital Human Research Ethics Committee and Medical Local (Ethical) 572/2018 and RCC158 33 Services Manager 34 216 South Africa Red Cross War Memorial Human Research Ethics Committee and Medical Local (Ethical) 572/2018 and RCC158 Services Manager 35 217 South Africa Tygerberg Children’s Hospital Human Research Ethics Committee and Medical Local (Ethical) N18/09/101 36 Services Manager 37 218 Sri Lanka Lady Ridgeway Hospital for Children Ethical Committee Local (Ethical) - 38 219 Sudan Khartoum University Hospital Head of Department of Paediatric Surgery Local (Departmental) - 220 Syria Aleppo University Hospital Dean of Faculty of Medicine Local (Dean) - 39 221 Syria AlShahbaa Hospital, Aleppo city Head of Alshahbaa Private Hospital Local (Hospital) - 40 41 42 7 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 222 Syria Tishreen University Hospital In Arabic Local (Ethical) - 4 223 Thailand Bangkok Ramathibodi Hospital Institutional Review Board Local (Ethical) 07-61-17 5 224 Thailand Chiangmai Jiraporn Khorana Ethics Committee Local (Ethical) SUR-2561-05619 225 Thailand Hatyai Hospital Research Ethics Committee Local (Ethical) 80/2561 6 226 Thailand Khon Kaen University Ethics Committee for Human Research Local (Ethical) HE611526 7 227 Thailand National Institute of Child Health (QSNICH) Research Ethics Review Committee Local (Ethical) 61-065 8 228 Thailand Siriraj Hospital Institutional Review Board Local (Ethical) 687/2561(EC2) 9 229 Thailand Sisaket Hospital Research Ethics Committee Local (Ethical) 071/2561. 10 230 Tunisia CHU Hedi Chaker Hospital President of the Ethical Committee Local (Ethical) - 231 Tunisia Fattouma Bourguiba Hospital President of the Ethical Committee Local (Ethical) - 11 232 Turkey Adana State Training Hospital Head Physician Local (Hospital) 60247264-799-41 12 233 Turkey Amerikan Hospital,For Istanbul peerEthics Committeereview Chairman onlyLocal (Ethical) 2018.235.irbi.028. 13 234 Turkey Bezmialem University School of Medicine Hospital President Local (Hospital) 54022451-050.05.04 14 235 Turkey Biruni University Hospital University Ethics Committee Local (Ethical) - 236 Turkey Gazi University School of Medicine University Dean Local (Dean) 24074710-604.01.01-47 15 237 Turkey Karadeniz technical University Head Physician Local (Hospital) E.10031 16 238 Turkey Koç University Ethics Committee Chairman Local (Ethical) 2018.235.irbi.028 17 239 Turkey Muğla Education and Research Hospital Chief of Staff Local http://bmjopen.bmj.com/ (Hospital) 2018.235.IRB1.028 18 240 Uzbekistan Republican Perinatal Center In local script Local (Ethical) 000174 241 Uzbekistan Republican Specialized Scientific Practical In local script Local (Ethical) - 19 Medical Center of Pediatrics, Tashkent 20 242 Zambia University Teaching Hospital, Lusaka ERES Converge I Institutional Review Board Local (Ethical) 2018-Sept-001 21 TOTAL MICs: 217 22 High-Income Countries (HICs) 243 Australia Children’s Hospital at Westmead, Sydney Research Governance Officer and Human Research Local (Ethical) LNR/18/SCHN/347 23 Ethics Committee 24 244 Australia Gold Coast University Hospital Human Research Ethics Committee Local (Ethical) HREC/18/QGC/47042 25 245 Australia Monash Children’s Hospital, Victoria Human Research Ethics Committees Local on September 23, 2021 by guest. Protected copyright. (Ethical) HREC/43418/MonH-2018- 26 67965(v1) 246 Australia The Royal Children’s Hospital, Melbourne Murdoch Children’s Research Institute and Research Local (Ethical) QA/50138/RCHM-2018 27 Ethics and Governance Officer 28 247 Austria Medical University of Graz Ethics Committee Local (Ethical) 31-157 ex. 18/19 29 248 Austria Medical University of Vienna, Spitalgasse Ethics Committee Local (Ethical) 2006/2018 30 249 Belgium Queen Fabiola University Children's Hospital Ethics Committee Local (Ethical) B406201837832 250 Brunei Darussalam RIPAS Hospital, Bandar Seri Begawan Medical and Health Research and Ethics Committee Local (Ethical) MHREC/MOH/2018/7 31 251 Canada Ste-Justine Children’s Hospital Scientific Research Committee and Research Ethics Local (Ethical) 2019-2158 32 Board for Ethical Review 33 252 Chile San Juan de Dios Hospital Ethics Committee for Scientific Investigation Local (Ethical) 47/2018 34 253 Czech Republic Fakultni Nemocnice BRNO Ethics Committee Local (Ethical) 13-130219/EK 254 Czech Republic University Hospital Hradec Kralove Ethics Committee Local (Ethical) 201812 s17p 35 255 Czech Republic University Hospital Motol Ethics Committee Local (Ethical) - 36 256 England Alder Hey Children’s Hospital Governance and Quality Assurance Team Local (Hospital) 5714 37 257 England Birmingham Children’s Hospital Clinical Audit Registration and Management System Local (Hospital) CARMS-30164 38 258 England Bristol Royal Hospital for Children Audit Governor Local (Hospital) - 259 England Evelina Children's Hospital, Guy's & St.Thomas' Audit Team Local (Hospital) 8956 39 NHS Trust 40 41 42 8 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 260 England John Radcliffe Hospital, Oxford Clinical Effectiveness Committee Local (Hospital) 5150 4 261 England King’s College Hospital Governance Manager Local (Hospital) CH011 5 262 England Leeds General Infirmary Clinical Director and Deputy Caldicott Guardian Local (Hospital) Globalpaedsurg 263 England Leicester and Kettering Hospitals Clinical Audit Facilitator Local (Hospital) 9482e 6 264 England Nottingham Hospital Audit Department Local (Hospital) 18-350C 7 265 England Southampton General Hospital Audit Department Local (Hospital) SEV/0049 8 266 England St Georges Hospital Audit Department Local (Hospital) AUD1000163 9 267 France CHU Amiens Ethical Review Board National (Ethical) 18.105 10 268 France CHU Amiens-Picardie, Amiens Ethical Review Board National (Ethical) 18.105 269 France CHU Angers Ethical Review Board National (Ethical) 18.105 11 270 France CHU APHM-Marseille Ethical Review Board National (Ethical) 18.105 12 271 France CHU APHP-BicêtreFor peerEthical reviewReview Board onlyNational (Ethical) 18.105 13 272 France CHU APHP-Necker Ethical Review Board National (Ethical) 18.105 14 273 France CHU APHP-Robert Debré Ethical Review Board National (Ethical) 18.105 274 France CHU Bordeaux Ethical Review Board National (Ethical) 18.105 15 275 France CHU Limoges Ethical Review Board National (Ethical) 18.105 16 276 France CHU Poitiers Ethical Review Board National (Ethical) 18.105 17 277 France CHU Rennes Ethical Review Board Nationalhttp://bmjopen.bmj.com/ (Ethical) 18.105 18 278 France CHU Rouen Ethical Review Board National (Ethical) 18.105 279 France CHU StEtienne Ethical Review Board National (Ethical) 18.105 19 280 France CHU Toulouse Ethical Review Board National (Ethical) 18.105 20 281 Germany Frankfurt University Hospital Ethics Committee Local (Ethical) 346/18 21 282 Germany Hospital St. Barbara Elisabeth Halle Ethics Committee Local (Ethical) - 22 283 Germany Krankenhaus Barmherzige Brüder Regensburg Ethics Committee Local (Ethical) 19-1263-101 284 Germany Kinderchirurgie Vivantes Neukölln, Berlin Coordinator of Clinical Research and Academic Local (Hospital) - 23 Teaching 24 285 Germany Medical Faculty Otto-von-Guericke University Executive Director of Ethics Committee Local (Ethical) 151/18 25 Magdeburg on September 23, 2021 by guest. Protected copyright. 26 286 Germany Universitat zu Lubeck Ethics Committee Local (Ethical) 18-249 287 Italy San Matteo Hospital Secretary to the Head of Science Technology Local (Hospital) 20180097159 27 288 Hungary Albert Szent-Györgyi Clinical Centre, Szeged Human Investigation Review Board Local (Ethical) 4413 28 289 Lithuania Children‘s Hospital, Affiliate of Vilnius University Chairman Local (Hospital) 18VSR-1735 29 Hospital SK 158200-18/9-1061-562 30 290 Lithuania Lithuanian University of Health Sciences Chairman of Kaunas RBTEK Local (Hospital) - 291 New Zealand Christchurch Hospital Quality Co-ordinator Childs Health and Audit Group Local (Hospital) BE-2-82 31 292 New Zealand Starship Children's Hospital, NZ Southern health and Disability Ethics Committee Local (Ethical) 18/STH/143 32 293 New Zealand Waikato Hospital Director of Quality and Patient Safety Local (Hospital) RD018104 33 294 New Zealand Wellington Hospital Operations Manager Child Health Service Local (Hospital) - 34 295 Poland Department of Children’s Developmental Bioethical Commission Local (Ethical) KNW/0022/KB/204/I/18 Defects Surgery and Traumatology 35 296 Poland Medical University of Gdańsk Bioethical Committee for Research Local (Ethical) NKBBN/456/2018 36 297 Poland Medical University of Silesia, Katowice Bioethical Commission Local (Ethical) KNW/0022/KB/172/18 37 298 Poland Warsaw Children’s Memorial Health Institute Bioethical Commission and Ethical Committee Local (Ethical) 20/KBE/2018 38 Assembly 299 Poland Wladyslaw Buskowski Children’s Hospital Bioethical Commission Local (Ethical) 44/2018 39 300 Poland Wroclaw University Bioethical Commission Local (Ethical) 133/XV R/2017 40 41 42 9 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 301 Qatar Sidra Medecine, Doha Institutional Review Board Local (Ethical) 1808029580 4 302 Saudi Arabia King Fahd Armed Forces Hospital Director of the Research Center, Research and Ethics Local (Ethical) REC 261 5 Committee 303 Saudi Arabia King Saud University College of Medicine Institutional Review Board Local (Ethical) E-18-3427 6 304 Scotland Glasgow Children’s Hospital, NHS Greater Caldicott Guardian Local (Hospital) - 7 Glasgow and Clyde 8 305 Scotland Royal Hospital for Sick Children Associate Medical Director Local (Hospital) - 9 306 Singapore KK Women’s and Children’s Hospital, Little Head of Department Local (Departmental) - India 10 307 South Korea Cheonnam National University Hospital, Dong- Chonnam National University Hospital Biomedical Local (Ethical) - 11 gu, Gwangju Research Ethics Review Committee Chairperson 12 308 South Korea Samsung Medical Centre Institutional Review Board Local (Ethical) 2018-09-110 309 South Korea Seoul National UniversityFor Children’s peer Hospital Institutional review Review Board onlyLocal (Ethical) H-1810-050-977 13 310 South Korea Seoul St. Marys Hospital Institutional Review Board Local (Ethical) KC18OCGI0669 14 311 Spain Barcelona Sant Joan de Déu Hospital Secretary of CEIM Sant Joan de Déu Local (Hospital) - 15 312 Spain Complejo Hospitalario Universitario de a Head of Paediatric Surgery Unit Local (Departmental) - 16 Coruña (CHUAC) 17 313 Spain Hospital Clinico Universitario de Valladolid Director Manager and CEIM of Valladoid Health Area Local http://bmjopen.bmj.com/ (Hospital) - 314 Spain Maternal Hospital Infantil de Badajoz Secretary of the Ethical Investigation Committee of Local (Ethical) - 18 Badajoz Clinic 19 315 Spain Zaragoza Hospital Universitario Miguel Favourable Report Project of Biomedical Research a Local (Hospital) - 20 Secretary of the CEIC Aragón (CEICA) 21 316 Sweden Lund Skåne University Hospital Pediatric Care Consultation group for quality registers Local (Hospital) - Hospital 22 317 Sweden Queen Silvia Children’s Hospital Area Manager of QSCH and Head of operations or unit Local (Hospital) - 23 manager 24 318 Sweden Sachs Children’s Hospital Patient Area Director Local (Hospital) - 25 319 Sweden Uppsala University Children’s Hospital Section Chief, Paediatric Surgery Clinician Local on September 23, 2021 by guest. Protected copyright. (Departmental) - 320 Switzerland Inselspital/University Hospital, Bern Kantonale Ethics Committee Local (Ethical) - 26 321 UAE Danat Al Emarat Hospital Head of Surgery Local (Departmental) - 27 322 Uruguay University De La Republica Facultad de Service Chief for the Neonatal Department Local (Departmental) - 28 Medicina 29 323 Uruguay Centro Hospitalario Pereira Rossell Audit Team Local (Hospital) - 324 USA Ann and Robert H. Lurie Children’s Hospital of Institutional Review Board Local (Ethical) IRB 2019-2334 30 Chicago 31 325 USA Beaumont’s Children’s Hospital in Royal Oak Institutional Review Board Local (Ethical) IRB 2018-402 32 326 USA Children’s Hospital of Wisconsin Institutional Review Board Local (Ethical) 1352795-2 33 327 USA Dartmouth-Hitchcock Medical Center Committee for the Protection of Human Subjects Local (Ethical) STUDY00031666 328 USA Le Bonheur Children’s Hospital Memphis UTHSC Institutional Review Board Local (Ethical) 18-06176-XP 34 329 USA Nationwide Children’s Hospital Institutional Review Board Office Local (Ethical) IRB18-01005 35 330 USA New York Presbyterian Morgan Stanley Institutional Review Board Local (Ethical) IRB-AAAS0645 36 Children’s Hospital 37 331 USA Oregon Health and Science University Institutional Review Board Local (Ethical) STUDY00018665 332 USA Phoenix Children’s Hospital Institutional Review Board Local (Ethical) PCH IRB #18-100 38 333 USA University of Miami Institutional Review Board Local (Ethical) 20181054 39 334 USA University of Michigan Co-chairs of Institutional Review Board MED Local (Ethical) HUM 00151299 40 335 USA University of Texas Medical Branch Institutional Review Board Vice Chairman Local (Ethical) IRB18-0318 41 42 10 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from
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1 2 3 336 USA UT Southwestern Medical Center Children’s Institutional Review Board Local (Ethical) STU 072018-058 4 Hospital 5 337 USA Yale New Haven Hospital Institutional Review Board Local (Ethical) 2000024339 TOTAL HICs: 95 6 OVERALL TOTAL: 337 7 8 9 10 11 12 For peer review only 13 14 15 16 17 http://bmjopen.bmj.com/ 18 19 20 21 22 23 24 25 on September 23, 2021 by guest. Protected copyright. 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 11 43 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Page 35 of 36 BMJ Open
1 2 3 Management and Outcomes of Gastrointestinal Congenital Anomalies in Low-, BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Middle- and High-Income Countries: Protocol for a Multi-Centre, International, 5 6 Prospective Cohort Study 7 8 9 STROBE checklist detailing where each item is addressed in the protocol 10
11 Section where this is 12 Item covered in the 13 No Recommendation manuscript 14 Title and abstract 1 (a) Indicate the study’s design with a commonly used term in the title or the abstract Title, abstract 15 (b) Provide in the abstract an informative and balanced summary of what was done Abstract and what was found 16 Introduction 17 18 Background/rationale 2 ExplainFor the scientific peer background andreview rationale for the investigation only being reported Introduction Objectives 3 State specific objectives, including any prespecified hypotheses Objective 19 Methods 20 Study design 4 Present key elements of study design early in the paper Abstract, Methods - 21 Study Design 22 Setting 5 Describe the setting, locations, and relevant dates, including periods of recruitment, Methods 23 exposure, follow-up, and data collection 24 Participants 6 (a) Give the eligibility criteria, and the sources and methods of selection of participants. Methods – inclusion/ Describe methods of follow-up exclusion criteria, 25 outcome measures 26 (b) For matched studies, give matching criteria and number of exposed and unexposed Not Applicable 27 Variables 7 Clearly define all outcomes, exposures, predictors, potential confounders, and effect Methods – Outcomes, modifiers. Give diagnostic criteria, if applicable Data Collection, Data 28 Analysis, Appendix 29 Data sources/ 8* For each variable of interest, give sources of data and details of methods of Table 1, Methods – 30 measurement assessment (measurement). Describe comparability of assessment methods if there is sample selection, 31 more than one group Appendix 1 and 2 Bias 9 Describe any efforts to address potential sources of bias Data quality, data 32 validation 33 Study size 10 Explain how the study size was arrived at Sample size calculation 34 Quantitative 11 Explain how quantitative variables were handled in the analyses. If applicable, describe Not applicable 35 variables which groupings were chosen and why Statistical methods 12 (a) Describe all statistical methods, including those used to control for confounding Data Analysis 36 (b) Describe any methods used to examine subgroups and interactions Data Analysis
37 (c) Explain how missing data were addressed Data Analysis http://bmjopen.bmj.com/ 38 (d) If applicable, explain how loss to follow-up was addressed Data Analysis 39 (e) Describe any sensitivity analyses Data Analysis Results 40 41 Participants 13* (a) Report numbers of individuals at each stage of study—eg numbers potentially Estimated Study eligible, examined for eligibility, confirmed eligible, included in the study, completing Population 42 follow-up, and analysed 43 (b) Give reasons for non-participation at each stage Not applicable 44 (c) Consider use of a flow diagram Not applicable Descriptive data 14* (a) Give characteristics of study participants (eg demographic, clinical, social) and Not applicable
45 on September 23, 2021 by guest. Protected copyright. information on exposures and potential confounders 46 (b) Indicate number of participants with missing data for each variable of interest Not applicable 47 (c) Summarise follow-up time (eg, average and total amount) Not applicable 48 Outcome data 15* Report numbers of outcome events or summary measures over time Not applicable 49 Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and Not applicable 50 their precision (eg, 95% confidence interval). Make clear which confounders were 51 adjusted for and why they were included 52 (b) Report category boundaries when continuous variables were categorized Not applicable (c) If relevant, consider translating estimates of relative risk into absolute risk for a Not applicable 53 meaningful time period 54 Other analyses 17 Report other analyses done—eg analyses of subgroups and interactions, and Data Analysis 55 sensitivity analyses Discussion 56 57 Key results 18 Summarise key results with reference to study objectives Not applicable 58 Limitations 19 Discuss limitations of the study, taking into account sources of potential bias or Strengths and imprecision. Discuss both direction and magnitude of any potential bias Limitations 59 Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations, Not applicable 60 multiplicity of analyses, results from similar studies, and other relevant evidence
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3 Generalisability 21 Discuss the generalisability (external validity) of the study results Not applicable BMJ Open: first published as 10.1136/bmjopen-2019-030452 on 3 September 2019. Downloaded from 4 Other information
5 Funding 22 Give the source of funding and the role of the funders for the present study and, if Additional Information 6 applicable, for the original study on which the present article is based 7 8 9 10 11 12 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44
45 on September 23, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
2 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml