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

Ratlarda Oluşturulan Kostik Özofagus Yaralanma Sonrası Striktür Oluşumuna Contractubex’İn (Extractum Cepae Ve Ekleri) Koruyucu Etkisi

Kaza ile kostik madde alımı çocularda ciddi özofageal striktürün en sık nedenidir. Bu çalışmanın amacı Contractubex’in koroziv özofageal yanık sonrası oluşan striktür oluşumunu engellemedeki etkinliği belirlemektir. Yirmidört sıçan 4 gruba bölündü. 1ml %10 sodyum NaOH solüsyonu izole edilmiş özofageal segmente verilip 3 dakika beklenerek standart özofagus hasar modeli oluşturuldu. Grup K’da yanık modeli oluşturulmadı ve tedavi verilmedi. Grup Y’de (özofageal yanık) yanık modeli oluşturuldu. Grup T1 ve Grup T2’de yanık modeli oluşturularak sırasıyla 100/mg/gün ve 200 mg/gün Contractubex® 4 hafta boyunca özofagus girişinden gavaj ile verildi. Tedavi etkinliği 4 hafta sonra Sİ, histopatolojik hasar skorlaması, dokuda HP tespiti ve sıçanların deney önce ve sonrası ağırlık ölçümüyle değerlendirildi. Ortalama Sİ değerleri Grup Y ile karşılaştırıldığında Grup T1 ve T2’de daha düşüktü (sırasıyla p = 0,0082, 0,0046). HP değerleri Grup Y ile karşılaştırıldığında Grup T1 ve T2’nin değerlerine göre yüksek olduğu görüldü ve istatistiksel olarak anlamlı bulundu (sırasıyla p = 0,0077, 0,0016). Histopatolojik hasar skorlaması değerlendirildiğinde Grup K kadar anlamlı olmasa da tedavi gruplarının kollajen depozisyonu, mukozal ve submukozal hasar Grup Y’ye göre düşüktü (sırasıyla p = 0,0059, 0,0002). Sonuçlar Grup T1 ve T2 arasında benzer olduğu için tedavinin dozdan bağımsız olduğu düşünüldü. Grup K kadar olmasa da yanık grubuna göre tedavi gruplarının kilo alımının arttığı gözlendi. Deneysel olarak ratlarda korozif özofageal yanıklarının tedavisinde ilk kez kullanılan Contractubex® antioksidan, antienflamatuar, yara iyileştirici, fibroblast oluşumunu inhibe edici etkileri ile 66 tedavi gruplarında yanık grubuna göre hidroksiprolin düzeylerini düşürerek, histopatalojik hasarlanmayı azaltarak ve belirgin stenozu önleyerek darlığı azaltıcı etki göstermiştir.Unconsciously caustic ingestion is one of the most common problems causing serious esophageal strictures in children. The aim of this study was to determine the efficiency of Contractubex® in preventing stricture formation after corrosive esophageal burns (CEB). Twenty-four rats were divided into 4 groups. CEB was created by instillation of 1 ml of 10% NaOH solution into the isolated esophageal segment for 3 min. Group K (control) was uninjured and untreated. Group Y (esophageal burn) was CEB created but untreated. Group T1 and T2 were CEB created and received 100mg/kg/day and 200mg/kg/day contractubex treatment for 4 weeks orally via gavage. Efficiency of the treatment was assessed after the 4th week by evaluating stenosis index (SI) and histopathologic damage score, determining tissue hydroxyproline content (HP) and measuring the weight of the rats before and after the experiment. Mean SI was statistically lower in the groups T1 and T2 when compared with Group Y (p = 0,0082, 0,0046, respectively). When HP levels compared with Group Y treatment groups T1 and T2 was statistically significant( p = 0,0077, 0,0016 respectively). In terms of histopathological damage score, although it was not as significant as Group K, in treatment groups, collagen deposition, mucosal and submucosal damage were lower than Group Y (p= 0,0059, 0,0002 respectively). The results were similar between Group T1 and Group T2 (p>0,05); the treatment was independent of dosage. Although not as much as Group K, it was observed that the weight gain of the treatment groups increased compared to the Group Y. Contractubex®, which was used for the first time for the treatment of experimental CEB in rats, with its antifibrotic, antioxidant, anti-inflammatory and wound healing effects; was efficient in reducing stricture formation by decreasing HP levels and histopathologic damage, preventing stenosis and weight gain in higher dosages in the treatment group