Two-stage learning-based prediction of bronchopulmonary dysplasia in very low birth weight infants: a nationwide cohort study

IntroductionThe aim of this study is to develop an enhanced machine learning-based prediction models for bronchopulmonary dysplasia (BPD) and its severity through a two-stage approach integrated with the duration of respiratory support (RSd) using prenatal and early postnatal variables from a nationwide very low birth weight (VLBW) infant cohort.MethodsWe included 16,384 VLBW infants admitted to the neonatal intensive care unit (NICU) of the Korean Neonatal Network (KNN), a nationwide VLBW infant registry (2013–2020). Overall, 45 prenatal and early perinatal clinical variables were selected. A multilayer perceptron (MLP)-based network analysis, which was recently introduced to predict diseases in preterm infants, was used for modeling and a stepwise approach. Additionally, we applied a complementary MLP network and established new BPD prediction models (PMbpd). The performances of the models were compared using the area under the receiver operating characteristic curve (AUROC) values. The Shapley method was used to determine the contribution of each variable.ResultsWe included 11,177 VLBW infants (3,724 without BPD (BPD 0), 3,383 with mild BPD (BPD 1), 1,375 with moderate BPD (BPD 2), and 2,695 with severe BPD (BPD 3) cases). Compared to conventional machine learning (ML) models, our PMbpd and two-stage PMbpd with RSd (TS-PMbpd) model outperformed both binary (0 vs. 1,2,3; 0,1 vs. 2,3; 0,1,2 vs. 3) and each severity (0 vs. 1 vs. 2 vs. 3) prediction (AUROC = 0.895 and 0.897, 0.824 and 0.825, 0.828 and 0.823, 0.783, and 0.786, respectively). GA, birth weight, and patent ductus arteriosus (PDA) treatment were significant variables for the occurrence of BPD. Birth weight, low blood pressure, and intraventricular hemorrhage were significant for BPD ≥2, birth weight, low blood pressure, and PDA ligation for BPD ≥3. GA, birth weight, and pulmonary hypertension were the principal variables that predicted BPD severity in VLBW infants.ConclusionsWe developed a new two-stage ML model reflecting crucial BPD indicators (RSd) and found significant clinical variables for the early prediction of BPD and its severity with high predictive accuracy. Our model can be used as an adjunctive predictive model in the practical NICU field

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