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

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 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 of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Synergistic Influence of <i>Arbuscular mycorrhizal</i> Fungi Inoculation with Nanoparticle Foliar Application Enhances Chili (<i>Capsicum annuum</i> L.) Antioxidant Enzymes, Anatomical Characteristics, and Productivity under Cold-Stress Conditions

In this study, we aimed to evaluate the effects of Arbuscular mycorrhiza fungus (AMF) inoculation, foliar application of zinc oxide and selenium nanoparticles (ZnO-NPs and Se-NPs), and their combined interactions on the growth and productivity of chili pepper under cold-stress conditions. Two field experiments were successfully conducted during the winter seasons of 2021 and 2022 in an experimental field at the Faculty of Agriculture, Cairo University, Giza, Egypt. The results showed that, under cold stress, the combination of AMF inoculation and ZnO-NPs + Se-NPs as a foliar spray increased the average fruit weight by 92.4% and 98.7%, and the number of fruits by 34.6% and 54.8 compared to control treatment in the 2021 and 2022 seasons, respectively. Additionally, the combination of AMF and a mixture of nanoparticles (ZnO-NPs + Se-NPs) significantly increased the total marketable yield by 95.8% and 94.7% compared to the control, which recorded values of 2.4 and 1.9 kg m−2 in the 2021 and 2022 seasons, respectively. Furthermore, the combination of AMF and a mixture of nanoparticles (ZnO-NPs + Se-NPs) showed the highest total content of ascorbic acid and capsaicin in chili fruits compared to the other treatments. The combination of AMF and a mixture of nanoparticles (ZnO-NPs + Se-NPs) stimulated the accumulation of peroxidase (POD) and nitrogen glutamate dehydrogenase (GDH) while decreasing hydrogen peroxide (H2O2) and lipid peroxidation (MDA) contents. SDS analysis revealed that the application of ZnO-NPs, Se-NPs, AMF + ZnO-NPs, and AMF + ZnO-NPs + Se-NPs induced the emergence of new protein bands and reconstitution of those damaged by cold stress. Regarding histological structure, the combination of AMF inoculation and ZnO-NPs + Se-NPs as a foliar spray showed an enhancement in the thickness of grana thylakoids and increased the number of chloroplasts. Intriguingly, the findings showed that AMF and a mixture of nanoparticles (ZnO-NPs + Se-NPs) could offer guidance for increasing plant development and productivity under cold-stress conditions