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

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 middle-income 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 low-income 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 low-income, 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

Insecticide resistance spectrum and prevalence of L1014F <em>kdr</em> type mutation in <em>Anopheles gambiae s.l.</em> in Abia State, Nigeria

Anopheles gambiae s.l. is the primary vector of malaria, a debilitating disease responsible for substantial mortality and morbidity in Sub-saharan Africa. This study evaluated the insecticide resistance status and the frequency of L1014F kdr mutation in An. gambiae [Diptera: Culicidae, Giles 1902] within Abia State, Nigeria. Immature stages of An. gambiae (s.l.) were collected from Umudike, Agalaba, and Ebem communities and reared to adulthood. Batches of 25 sugar-fed female mosquitoes, aged 3–5 days, were exposed to four types of WHO insecticide-impregnated papers, i.e., 4% DDT, 0.75% Permethrin, 0.1% Bendiocarb, and 5% Malathion, for one hour and the mortalities were recorded after a recovery period of 24 h. Mosquito species were identified using morphological and molecular methods, and kdr mutation L1014F was genotyped. Anopheles gambiae (s.l.) was highly resistant to permethrin (Umudike-18.8% mortality, Agalaba-17.5%, Ebem- 49.0%) but showed no resistance to DDT (0.0%) in the three locations. Conversely, all the locations recorded complete susceptibility to malathion (100%). Although complete susceptibility to bendiocarb was reported from Umudike (100%) and Ebem-Ohafia (100%), resistance was reported from Agalaba (87.5%). PCR analyses showed that An. gambiae (s.l.) were predominantly An. gambiae s.s. in Umudike (90.0%), Agalaba (67.5%) and Ebem (67.5%), whereas the rest were An. coluzzii. Very high frequencies of the L1014F kdr mutation was observed in all locations [Umudike (1.00), Agalaba (0.98), and Ebem-ohafia (0.95)]. The worrisome resistance to bendiocarb in Agalaba suggests the existence of metabolic resistance that needs to be clarified. The high occurrence of L1014F resistance mutation in populations calls for urgent implementation of integrated vector control strategies in Abia State