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

Rol de anticuerpos anti-Toxoplasma gondii en la activación de la respuesta inmune en mujeres embarazadas.

Objectives: the study aimed to evaluate in vitro the role of anti T. gondiiin activating immune responses in pregnant women. Methods: the study was performed with peripheral blood mononuclear cells (PBMC) of pregnant women with chronic toxoplasmosis (n = 15) were stimulated in the presence and absence of autologous plasma (PA) (anti T. gondii antibody). Results: the data show that in PBMC stimulated in the absence of autologous plasma there is increased cell proliferation (P < 0.05) than cells in the presence of autologous plasma. Levels of IFN- ã produced in both conditions (PA and SBF) were similar. Comparing the production of IFN- ã vs IL - 10 shows increased production of Th1 cytokines. Conclusions: in general, our results suggest that the antibodies present in autologous plasma modulate the immune response in pregnant women with chronic toxoplasmosis, such that the immune system does not exacerbate or inhibit this specific response. The presence of antibodies to T. gondii not affecting IFN- ã production in pregnant women with chronic toxoplasmosis, but if cell proliferation.Objetivos: el estudio tuvo como objetivo evaluar in vitro el rol de anticuerpos anti T. gondii en la activacion de la respuesta inmune en mujeres embarazadas. Metodos: el estudio se realizo con celulas mononucleares de sangre periferica (PBMC) de mujeres embarazadas con toxoplasmosis cronica (n=15) que fueron estimuladas en presencia y ausencia de plasma autologo (PA) (anticuerpos anti T. gondii). Resultados: los datos muestran que en PBMC estimuladas en ausencia de plasma autologo existe mayor proliferacion celular (P<0.05) que celulas en presencia de plasma autologo. Niveles de IFN-�Á producidos en ambas condiciones (PA y SBF) fueron similares. Comparando la produccion de IFN-�Á vs IL-10 muestra mayor produccion de citoquinas Th1. Conclusiones: en general nuestros resultados sugieren que los anticuerpos presentes en el plasma autologo modulan la respuesta inmune en mujeres embarazadas con toxoplasmosis cronica, de tal modo que el sistema inmune no exacerbe o inhiba esta respuesta especifica. La presencia de anticuerpos anti T. gondii no influyen en produccion de IFN-�Á en mujeres embarazadas con toxoplasmosis cronica, pero si en la proliferacion celular