Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries

Study Overview
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Brief Summary
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This study is a multi-centre, international, prospective cohort study of congenital anomalies to compare outcomes between LMICs and high-income countries (HICs) globally.

Detailed Description
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Background: Congenital anomalies have risen to become the 5th leading cause of death in children under 5-years of age globally, yet limited literature exists, particularly from low- and middle-income countries (LMICs) where most of these deaths occur. Aim: To undertake a multi-centre prospective cohort study of congenital anomalies to compare outcomes between LMICs and high-income countries (HICs) globally. Methods: The Global PaedSurg Research Collaboration will be established consisting of children's surgical care providers from around the world to participate in the study; collaborators will be co-authors of resulting presentations and publication(s). Data will be collected on patients presenting primarily with seven congenital anomalies (oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation and Hirschsprung's disease) for a minimum of one month between Oct 2018 - April 2019. Anonymous data will be collected on patient demographics, clinical status, interventions and outcome. Data will be captured using the secure, online data collection tool REDCap. The primary outcome will be all-cause in-hospital mortality and the secondary outcomes will be occurrence of post-operative complications. Chi-squared analysis will be used to compare mortality between LMICs and HICs. Multilevel, multivariate logistic regression analysis will be undertaken to identify patient level and hospital level factors affecting outcomes with adjustment for confounding factors. P<0.05 will be deemed significant. Study approval will be sought from all participating centres. Funding has been granted by the Wellcome Trust. Outcomes: The study aims to be the first large-scale, geographically comprehensive, multi-centre prospective cohort study of a selection of common congenital anomalies to define current management and outcomes globally. Results will be used to aid advocacy and global health prioritisation and inform future interventional studies aimed at improving outcomes.

Official Title
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Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries: A Multi-Centre, International, Prospective Cohort Study

Conditions
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Oesophageal Atresia, Congenital Diaphragmatic Hernia, Intestinal Atresia, Gastroschisis, Exomphalos, Anorectal Malformation, Hirschsprung Disease

Intervention / Treatment
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* Other: Comparisons will be made between LMICs and HICs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any neonate, infant or child under the age of 16-years, presenting for the first time, with one of the study conditions can be included in the study. Children who have NOT previously received any surgery for their condition. Children who have received basic resuscitative and supportive care for their condition at a different healthcare facility and then been transferred to the study centre. Patients presenting primarily with one of the study conditions who receive palliative care or no care must be included within the study to reflect true outcomes. Exclusion Criteria: Any neonate, infant or child with one of the study conditions who has previously received surgery (including a stoma) for their condition If they have recently received surgery for their condition, were discharged and then represented with a complication of the surgery during the study period they should NOT be included in the study.

Ages Eligible for Study
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Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Oesophageal atresia (OA) +/- tracheo-oesophageal fistula (TOF)<br> | Other: Comparisons will be made between LMICs and HICs<br>* Countries will be defined as low, middle or high-income using the World Bank classification.<br>|
| Congenital diaphragmatic hernia (CDH)<br> | Other: Comparisons will be made between LMICs and HICs<br>* Countries will be defined as low, middle or high-income using the World Bank classification.<br>|
| Intestinal atresia (IA)<br> | Other: Comparisons will be made between LMICs and HICs<br>* Countries will be defined as low, middle or high-income using the World Bank classification.<br>|
| Gastroschisis<br> | Other: Comparisons will be made between LMICs and HICs<br>* Countries will be defined as low, middle or high-income using the World Bank classification.<br>|
| Exomphalos<br> | Other: Comparisons will be made between LMICs and HICs<br>* Countries will be defined as low, middle or high-income using the World Bank classification.<br>|
| Anorectal malformation (ARM)<br> | Other: Comparisons will be made between LMICs and HICs<br>* Countries will be defined as low, middle or high-income using the World Bank classification.<br>|
| Hirschsprung's disease<br> | Other: Comparisons will be made between LMICs and HICs<br>* Countries will be defined as low, middle or high-income using the World Bank classification.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause, in-hospital mortality | This will include all patients in the study, both those who did not receive an intervention and those that did. For patient's hospitalised for over 30-days following primary intervention, a 30-day post-primary intervention mortality rate will be utilised. For patients who do not receive a primary intervention (conservative generic ward care only) but remain alive and hospitalised at 30-days following primary admission will have this time point used for recording their mortality status for the primary outcome. | Mortality whilst in hospital during primary admission, up to a maximum of 30-days following primary intervention or 30-days following presentation for those who do not receive an intervention and are still in hospital. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surgical site-infection | This is defined by the Centre for Disease Control as including one or more of the following within 30-days of surgery: 1) purulent drainage 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; 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) there is an abscess within the wound (clinically or radiologically detected). | Occurring within 30-days of primary intervention | 
| Wound dehiscence | All layers of the wound open post-operatively | Occurring within 30-days of primary intervention | 
| Need for re-intervention | Need for a second unplanned intervention within 30-days of the primary intervention. | Occurring within 30-days of primary intervention | 
| Condition specific complications | OA: pneumonia, mediastinitis, pneumothorax, chylothorax, haemothorax, anastomotic leak, anastomotic stricture, recurrent TOF, other. CDH: air leak, chylothorax, recurrence, adhesional obstruction. IA: anastomotic leak/ stenosis, short-gut, missed additional atresia, adhesive bowel obstruction. Gastroschisis: ischaemic bowel, abdominal compartment syndrome, necrotising enterocolitis. Exomphalos: ruptured sac. ARM: electrolyte disturbance, high stoma output (over 20mls/kg/day), stoma prolapse/ retraction/ herniation, peri-stoma skin breakdown (or perianal if primary reconstruction was undertaken without a covering stoma), anal stenosis. Hirschsprung's disease: enterocolitis, electrolyte disturbance, high stoma output (over 20mls/kg/day), stoma prolapse/ retraction/ herniation, peri-stoma skin breakdown (or perianal if primary pull-through was undertaken without covering stoma), anal stenosis, post-operative obstruction, anastomotic leak. | Occurring within 30-days of primary intervention | 
| Condition specific outcome variables | Oesophageal atresia: time to first oral feed (in days) and time to full oral feeds (in days) | Occurring within 30-days of primary intervention | 
| Length of hospital stay | In days, including the first and last day. Time from admission to death in patients who do not survive. | Maximum 30-days post-intervention or following presentation for those who do not receive an intervention | 
| 30-day post primary intervention mortality |  | Death within 30-days of primary intervention or 30-days of presentation in those who do not receive an intervention | 
| Ventilation requirement | Need for any ventilation (excluding during anaesthetic for interventions) and duration of ventilation in days | Occurring within 30-days of primary intervention or admission for those not receiving an intervention | 
| Time to first enteral feed | In days, including the day of the primary intervention and the day when enteral feeds were started. | Occurring within 30-days of primary intervention or admission for those not receiving an intervention | 
| Time to full enteral feeds | In days, including the day of the primary intervention and the day when full enteral feeds were achieved. | Occurring within 30-days of primary intervention or admission for those not receiving an intervention | 
| Parenteral nutrition requirement | Need for any parenteral nutrition and total duration of parenteral nutrition in days for those who receive it. | Occurring within 30-days of primary intervention or admission for those not receiving an intervention |