Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-, middle- and high-income countries: a multicentre, international, prospective cohort study

Background: congenital anomalies are the 5th leading cause of under-5 mortality, globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care. Limited literature exists on these conditions in low- and middle-income countries (LMICs). We compared the outcomes of the seven commonest gastrointestinal congenital anomalies in low-, middle- and high-income countries (LICs, MICs, and HICs), globally, and identified factors associated with mortality. Methods: the Global PaedSurg Research Collaboration, consisting of healthcare professionals who provide surgical care for neonates and children with congenital anomalies, performed a multicentre, international prospective cohort study of consecutive patients, under 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s Disease. Recruitment was for a minimum of 1-month between October 2018 and April 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using REDCap. Follow-up was to 30 days post-primary intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We used chi-squared to compare mortality between country income strata, and penalised regression to identify factors associated with mortality (Risk Ratio [RR], 95% Confidence Interval [CI], p value). Findings: we included 3849 patients with 3975 study conditions (560 oesophageal atresia, 448 congenital diaphragmatic hernia, 681 intestinal atresia, 453 gastroschisis, 325 exomphalos, 991 anorectal malformation, and 517 Hirschsprung’s Disease) from 264 hospitals (89 HICs, 166 MICs, 9 LICs) in 74 countries. Mortality amongst all patients was 39·8% (37/93) in LICs, 20·4% (583/2860) in MICs, and 5·6% (50/896) in HICs (p<0·001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (90·0% [9/10] LICs, 31·9% [97/304] MICs, 1·4% [2/139] HICs, p<0·001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included: country income status (LIC [RR 2·78, CI 1·88-4·11, p<0·001], MIC [RR 2·11, CI 1·59-2·79, p<0·001] vs HIC), sepsis at presentation (RR 1·20, CI 1·04-1·40, p=0·016), higher American Society of Anesthesiologists score (ASA) at primary intervention (ASA 4-5 [RR 1·82, CI 1·40-2·35, p<0·001], ASA 3 [RR 1·58, CI 1·30-1·92, p<0·001] vs ASA 1-2), surgical safety checklist not used (RR 1·39, CI 1·02-1·90, p=0·035), and ventilation or parenteral nutrition unavailable when needed (RR 1·96, CI 1·41-2·71, p<0·001, or RR 1·35, CI 1·05-1·74, p=0·018, respectively). Administration of parenteral nutrition (RR 0·61, CI 0·47-0·79, p<0·001), and use of a peripherally inserted central catheter (RR 0·65, CI 0·5-0·86, p=0·002), or percutaneous central line (RR 0·69, CI 0·48-1·00, p=0·049) were associated with lower mortality. Interpretation: unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-, middle- and high-income countries. Improving access to quality neonatal surgical care in LMICs is vital to achieve Sustainable Development Goal 3·2 to ‘end preventable deaths in neonates and children under five by 2030’. Funding: Wellcome Trust (Funder Reference: 203905/Z/16/Z).