The impact of smoking on COVID-19-related mortality: a Brazilian national cohort study.

INTRODUCTION: Current evidence suggests the potential heightened vulnerability of smokers to severe coronavirus disease (COVID-19) outcomes. AIMS: This study aimed to analyze the clinical outcomes and mortality related to tobacco use in a cohort of hospitalized Brazilian COVID-19 patients. METHODS: This retrospective cohort study analyzed adults hospitalized for COVID-19 in Brazil using the SIVEP-Gripe database (official data reported by public and private healthcare facilities for monitoring severe acute respiratory syndrome cases in Brazil). The inclusion criteria were patients over 18 years of age with a positive RT-qPCR test for SARS-CoV-2. The analysis focused on in-hospital mortality, considering smoking as an exposure variable, and included covariates such as age, gender, and comorbidities. Smoking history was collected from the self-reported field in the database. Statistical analyses included descriptive statistics, crude Odds Ratios, and multivariable binary logistic regression. RESULTS: This study included 2,124,285 COVID-19 patients, among whom 44,774 (2.1 %) were smokers. The average age of the smokers was higher than that of the never-smokers (65.3 years vs. 59.7 years). The clinical outcomes revealed that smokers had higher rates of intensive care unit admission (51.6 % vs. 37.2 % for never-smokers), invasive ventilatory support (31.5 % vs. 20.2 % for never-smokers), and higher mortality (42.7 % vs. 31.8 % for never smokers). In the multivariable analysis, smokers demonstrated a heightened risk of death (aOR 1.23; 95 % CI 1.19-1.25). CONCLUSIONS: This large populational-based cohort study confirms the current evidence and underscore the critical importance of recognizing smoking as a substantial risk factor for adverse outcomes in COVID-19 patients.

Outcomes of SARS-CoV-2 and seasonal viruses among 2 million adults hospitalized for severe acute respiratory infection during the COVID-19 pandemic in Brazil.

BACKGROUND: The outbreak of the COVID-19 pandemic has had a profound impact on the circulation of seasonal respiratory viruses. This study aimed to compare the outcomes of SARS-CoV-2 and seasonal viruses in adults hospitalized with severe acute respiratory infection (SARI) during the COVID-19 pandemic. METHODS: This population-based cohort study included patients aged > 18 years hospitalized for SARI in Brazil between February 2020 and February 2023. The primary outcome was in-hospital mortality. A competing risk analysis was used to account for competing events. RESULTS: In total, 2,159,171 patients were included in the study. SARS-CoV-2 was the predominant virus (98.7%). The cumulative incidence of in-hospital mortality was 33.1%, 31.5%, 21.0%, 18.7%, and 18.6%, for patients positive for SARS-CoV-2, adenovirus, RSV, influenza, and other viruses, respectively. SARS-CoV-2 accounted for 99.3% of the deaths. Older age, male sex, comorbidities, hospitalization in the northern region, and oxygen saturation <95% were the common risk factors for death among all viruses. CONCLUSIONS: In this large cohort study, individuals infected with SARS-CoV-2 or adenovirus had the highest risk of mortality. Irrespective of the virus type, older age, male sex, comorbidities, hospitalization in vulnerable regions, and low oxygen saturation were associated with an increased risk of fatality.

The association between schizophrenia and increased COVID-19 mortality in a cohort of over 2 million people in Brazil.

OBJECTIVE: To describe the clinical outcomes and risk factors of death related to mental disorders in a cohort of Brazilian hospitalized patients with COVID-19. METHODS: This retrospective cohort study utilized the Brazilian database SIVEP-Gripe to analyze patients aged ≥18 years who had been hospitalized with COVID-19 between 2020 and 2022. The exposure of interest were mental disorders (anxiety, depression, schizophrenia, and bipolar disorder), identified through self-reported fields. The primary outcome was in-hospital mortality. Covariates included demographic and clinical features. Descriptive statistics, t-tests, chi-square tests, and binary logistic regression were used to analyze the data. RESULTS: A cohort of 2,124,285 patients was included in the analysis, with 23,246 individuals (1.1%) having self-reported mental disorders. Among these mental disorders, depression was the most prevalent (52.3%). The mortality rate of the patients with mental disorders was 30.8%. Analysis of risk factors for mortality revealed that age, gender, region, dyspnea, low oxygen saturation, and comorbidities were associated with an increased risk of death. Patients with schizophrenia had a higher mortality risk (aOR:1.68;95%CI:1.54-1.81). CONCLUSIONS: Patients diagnosed with schizophrenia have a greater likelihood of COVID-19- related death than those without mental health conditions. These findings underscore the significant effect of serious mental disorders on COVID-19 mortality.

Outcomes of SARS-CoV-2 and Seasonal Viruses Among Children Hospitalized in Brazil.

BACKGROUND AND OBJECTIVES: Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts with other respiratory viruses is crucial for developing effective public health strategies in the postpandemic era. This study aimed to compare the outcomes of SARS-CoV-2 and seasonal viruses in children and adolescents hospitalized with severe acute respiratory infection (SARI). METHODS: This population-based, retrospective cohort study included children and adolescents hospitalized with SARI from February 2020 to February 2023 in Brazil. The main exposure of interest was viral etiology. The primary outcome was in-hospital mortality. Competing risk analysis was used to account for time dependency and competing events. RESULTS: A total of 235 829 patients had available results of the viral tests, with SARS-CoV-2 predominance. According to the competing-risk survival analysis, the estimated probability of a fatal outcome at 30 days of hospitalization according to the viral strain was 6.5%, 3.4%, 2.9%, 2.3%, 2.1%, and 1.8%, for SARS-CoV-2, coinfection, adenovirus, influenza, other viruses, and respiratory syncytial virus, respectively. Individuals with a positive test for SARS-CoV-2 had hazard of death 3 times higher than subjects with a negative test (hazard ratio, 3.3; 95% confidence interval, 3.1-3.5). After adjustment by the competing-risk multivariable analysis, admission in Northeast and North regions, oxygen saturation <95%, and the presence of comorbidities were risk factors for death in all viral strains. CONCLUSIONS: SARS-CoV-2 infection had the highest hazard of in-hospital mortality in this pediatric cohort hospitalized with SARI. Regardless of viral etiology, the presence of underlying medical conditions was a risk factor for death.

Association of Prior COVID-19 Vaccination With SARS-CoV-2 Infection and Death in Children and Young Persons During the Omicron Variant Period in Brazil.

This case-control study evaluates nationwide information surveillance systems in Brazil to estimate vaccine effectiveness against outcomes of COVID-19 in children and young persons.

Effectiveness of BNT162b2 and CoronaVac vaccines against omicron in children aged 5 to 11 years.

BACKGROUND: This study aimed to estimate vaccine effectiveness (VE) against omicron variant infection and severe corona virus disease 2019 (COVID-19) in children aged 5-11 years hospitalized with acute respiratory syndrome. METHODS: A test-negative, case-control analysis was conducted from February 2022 to June 2022. We enrolled 6950 eligible children, including 1102 cases and 5848 controls. VE was calculated after immunization with one and two doses of BNT162b2 or CoronaVac. The outcomes were hospitalization with acute respiratory symptoms and detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19. The adjusted odds ratio for the association of prior vaccination and outcomes was used to estimate VE. RESULTS: For fully vaccinated children, the overall estimated VE against hospitalization with SARS-CoV-2 infection was 42% [95% confidence interval (CI) 26 to 54]. VE peaked at 29-42 days (67%, 95% CI 40% to 82%) and then declined to 19% (95% CI, - 20% to 45%) at 57-120 days after the second dose. The BNT162b2 vaccine had a similar VE against hospitalization with SARS-CoV-2 infection (45%, 95% CI, 20 to 61) compared to the CoronaVac vaccine (40%, 95% CI, 17% to 56%). Among cases, 56 (5%) children died; 53 (94.6%) were not fully vaccinated. For cases, the two-dose schedule effectiveness against ICU admission, need for invasive ventilation, severe illness, and death were 10% (95% CI, - 54%-45%), 22% (95% CI - 70%-68%), 12% (95% CI, - 62%-52%), and 16% (95% CI, - 77%-75%), respectively. CONCLUSIONS: For hospitalized children aged 5-11 years during the omicron-predominant period in Brazil, two doses of both vaccines had moderate effectiveness against hospitalization with acute respiratory symptoms and SARS-CoV-2 infection and offered limited protection against endpoints of COVID-19 severity.

Outcomes and risk factors for death among hospitalized children and adolescents with kidney diseases and COVID-19: an analysis of a nationwide database.

BACKGROUND: Patients with kidney diseases (KD) appear to be at particularly high risk for severe COVID-19. This study aimed to characterize the clinical outcomes and risk factors for COVID-19-related death in a large cohort of hospitalized pediatric patients with KD. METHODS: We performed an analysis of all pediatric patients with KD and COVID-19 registered in SIVEP-Gripe, a Brazilian nationwide surveillance database, between February 16, 2020, and May 29, 2021. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk by using cumulative incidence function. RESULTS: Among 21,591 hospitalized patients with COVID-19, 290 cases (1.3%) had KD. Of these, 59 (20.8%) had a fatal outcome compared with 7.5% of the non-KD cohort (P < 0.001). Pediatric patients with KD had an increased hazard of death compared with the non-KD cohort (Hazard ratio [HR] = 2.85, 95% CI 2.21-3.68, P < 0.0001). After adjustment, the factors associated with the death among KD patients were living in Northeast (HR 2.16, 95% CI 1.13-4.31) or North regions (HR 3.50, 95% CI 1.57-7.80), oxygen saturation < 95% at presentation (HR 2.31, 95% CI 1.30-4.10), and presence of two or more associated comorbidities (HR 2.10, 95% CI 1.08-4.04). CONCLUSIONS: Children and adolescents with KD had a higher risk of death compared with the non-KD cohort. The higher risk was associated with low oxygen saturation at admission, living in socioeconomically disadvantaged regions, and presence of other pre-existing comorbidities. A higher resolution version of the Graphical abstract is available as Supplementary information.

Clinical Impact and Risk Factors of Mortality in Hospitalized Children and Adolescents With Hematologic Diseases and COVID-19: An Observational Retrospective Cohort Study.

This study aimed to evaluate the risk factors for COVID-19-related death in a large cohort of hospitalized children with hematological disorders. We performed an analysis of all pediatric patients with COVID-19 registered in a Brazilian nationwide surveillance database between February 2020 and May 2021. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk by using the cumulative incidence function. Among 21,591 hospitalized pediatric patients with COVID-19, 596 cases (2.8%) had hematological diseases. Sixty-one children (27.4%) with malignant hematological diseases had a fatal outcome as compared with 4.2% and 7.4% of nonmalignant hematological and nonhematological cohorts, respectively ( P <0.0001). Children with hematological diseases had a significant increased hazard of death compared with those without these conditions (hazard ratio [HR],=2.40, 95% confidence interval, 1.98 - 2.91). In multivariable analysis, the factors associated with death were the presence of malignant hematological disease (HR, 2.22, 95% CI 1.47 - 3.36), age >10 years (HR 2.19, 95% CI 1.46 - 3.19), male (HR 1.52, 95% CI 1.02 - 2.27), oxygen saturation <95% (HR 2.02, 95% CI 1.38 - 2.96), and abdominal pain at admission (HR 2.75, 95% CI 1.76 - 4.27). Children with malignant hematological diseases had a higher risk of death compared with those without these disorders.

Maternal risk factors for congenital anomalies of the kidney and urinary tract: A case-control study.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are significant causes of pediatric morbidity and mortality. The spectrum of CAKUT can be part of a syndrome, but most of these abnormalities occur as isolated and sporadic forms. The etiology of human CAKUT is unknown in the majority of cases. This case-control study aimed to investigate the association between maternal characteristics and the occurrence of CAKUT and specific CAKUT phenotypes. METHODS: In this case-control study, 29,653 newborns were evaluated consecutively in a tertiary neonatal unit using the Latin American Collaborative Study of Congenital Malformations (ECLAMC) registry. Newborns without congenital anomalies were matched to CAKUT cases by sex, date, and place of birth at a ratio of 3:1. For analysis purposes, the cases were stratified into four subgroups: upper tract abnormalities (UTA), including ureteropelvic junction obstruction, vesicoureteral reflux, primary megaureter and others (n = 239), lower urinary tract obstruction (LUTO) (n = 79), cystic diseases (n = 59) and agenesis/hypodysplasia (n = 28). Multivariable logistic regression analyses were used to calculate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for associations between the maternal risk factors and the presence of CAKUT. RESULTS: The prevalence of non-syndromic CAKUT in our sample was 13 per 1000 live births. Data records allowed the analysis of 405 cases and 1208 controls. After adjustment by the binary regression logistic, three covariates remained associated as risk factors for the entire spectrum of CAKUT: consanguinity (Odds ratio [OR], 7.1, 95%CI, 2.4-20.4), family history of CAKUT (OR, 6.4, 95%CI, 1.9-21.3), and maternal chronic hypertension (OR, 14.69, 95%CI, 3.2-67.5) (Figure). These risk factors persisted consistently across the various CAKUT phenotypes with minor variations. Consanguinity was the only factor consistently associated with almost all CAKUT phenotypes. Maternal hypertension was associated with all phenotypes except for the agenesis/hypodysplasia group. The prevalence of CAKUT cases was 15 times higher in hypertensive mothers (3%) compared to normotensive mothers (0.2%). CONCLUSION: Our study suggests that an increased risk of CAKUT is associated with consanguinity, a positive family history of CAKUT, and maternal hypertension. However, the prevalence of these risk factors in our cohort was rare and most cases presented as sporadic forms.

The association between pre-existing asthma and reduced risk of death among children and adolescents hospitalized with COVID-19 in Brazil.

OBJECTIVE: There have been conflicting reports on the relationship between asthma and COVID-19 severity. This study aimed to compare the risk of death among children with asthma and healthy peers hospitalized due to COVID-19. METHODS: We carried out an analysis of all pediatric patients 2-19 years of age with asthma and COVID-19 registered in Influenza Epidemiological Surveillance Information System-Gripe, a Brazilian nationwide surveillance database, between February 2020 and March 2022. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk using the cumulative incidence function. RESULTS: Among 30,405 hospitalized children with COVID-19, 21,340 (70.2%) had no comorbidities, 6444 (21.2%) had comorbidities other than asthma, 2165 (7.1%) had asthma, and 465 (1.5%) had asthma with other comorbidities. The estimated probability of a fatal outcome for each group was 4.1%, 14.9%, 2.1%, and 10.7%, respectively. After adjustment, children with asthma had a 60% reduction in the hazard of death than healthy peers (hazard ratio [HR] = 0.39, 95% confidence interval [CI], 0.29-0.53, p < 0.0001). Among children with asthma and no other comorbidities, two covariates were independently associated with in-hospital mortality, age ≥12 years, HR = 4.0, 95% CI, 2.5-6.4), and low oxygen saturation at admission (HR = 2.3, 95% CI, 1.4-3.2). CONCLUSION: Children with asthma and no comorbidities had a lower risk of death compared with healthy peers after controlling for clinical and demographic confounding factors.

Vaccine Effectiveness against SARS-CoV-2 Variants in Adolescents from 15 to 90 Days after Second Dose: A Population-Based Test-Negative Case-Control Study.

OBJECTIVE: The objective of this study was to estimate the vaccine effectiveness (VE) against hospitalization and severe illness in adolescents due to infection with SARS-CoV-2 variants (gamma, delta, and omicron). STUDY DESIGN: A test-negative, case-control analysis was conducted in Brazil from July 2021 to March 2022. We enrolled 8458 eligible individuals (12-19 years of age) hospitalized with an acute respiratory syndrome, including 3075 cases with laboratory-proven COVID-19 and 4753 controls with negative tests for COVID-19. The primary exposure of interest was vaccination status. The primary outcome was SARS-CoV-2 infection during gamma/delta vs omicron-predominant periods. The aOR for the association of prior vaccination and outcomes was used to estimate VE. RESULTS: In the pre-omicron period, VE against COVID-19 hospitalization was 88% (95% CI, 83%-92%) and has dropped to 59% (95% CI, 49%-66%) during the omicron period. For hospitalized cases of COVID-19, considering the entire period of the analysis, 2-dose schedule was moderately effective against intensive care unit admission (46%, [95% CI, 27-60]), need of mechanical ventilation (49%, [95% CI, 32-70]), severe COVID-19 (42%, [95% CI, 17-60]), and death (46%, [95% CI, 8-67]). There was a substantial reduction of about 40% in the VE against all end points, except for death, during the omicron-predominant period. Among cases, 240 (6.6%) adolescents died; of fatal cases, 224 (93.3%) were not fully vaccinated. CONCLUSION: Among adolescents, the VE against all end points was substantially reduced during the omicron-predominant period. Our findings suggest that the 2-dose regimen may be insufficient for SARS-CoV-2 variants and support the need for updated vaccines to provide better protection against severe COVID-19.

Global scientific production in the pre-Covid-19 Era: An analysis of 53 countries for 22 years.

Based on an extensive analysis of public databases, we provide an overview of the global scientific output and describe the dynamics of the profound changes in the scientific enterprise during the last decades. The analysis included the scientific production of 53 countries over the 1996-2018 period. During this period, the production of articles per year has tripled. There was a strong correlation between the growth of the global gross domestic product and the increase in the number of articles (R2 = 0.973, P<0.001). Six countries showed a robust increment of their scientific production and are currently among the top 20 in the ranking of world scientific production (China, India, South Korea, Brazil, Turkey, and Iran). The mean annual growth rate was about 12.7% for these six countries. The share of the global scientific production of these countries increased from 7% in 1996 to 27.8% in 2018. Conversely, the participation of the 10 most traditional countries has dropped from 73% to 45% during the same period. In conclusion, we believe that our findings may contribute to further studies aiming to evaluate the impact and changes of the scientific endeavor over the next years in light of the forthcoming new world framework.

Outcomes and risk factors of death among hospitalized children and adolescents with obesity and COVID-19 in Brazil: An analysis of a nationwide database.

BACKGROUND: Obesity is a well-recognized risk factor for critical illness and death among adult patients with SARS-CoV-2 infection. OBJECTIVE: This study aimed to characterize the clinical outcomes and risk factors of death related to obesity in a cohort of hospitalized paediatric patients with COVID-19. METHODS: We performed an analysis of all paediatric patients with obesity and COVID-19 registered in SIVEP-Gripe, a Brazilian nationwide surveillance database, between February 2020 and May 2021. The primary outcome was time to death, which was evaluated by using cumulative incidence function. RESULTS: Among 21 591 hospitalized paediatric patients with COVID-19, 477 cases (2.2%) had obesity. Of them, 71 (14.9%) had a fatal outcome as compared with 7.5% for patients without obesity (hazard ratio [HR] = 2.0, 95% confidence interval [CI] 1.59-2.53, p < 0.001). After adjustment, the factors associated with death among patients with obesity were female gender (HR = 2.8, 95% CI 1.70-4.61), oxygen saturation < 95% (HR = 2.58, 95% CI 1.38-4.79), presence of one (HR = 1.91, 95% CI 1.11-3.26), and two or more comorbidities (HR = 4.0, 95% CI 2.21-7.56). CONCLUSIONS: Children and adolescents with obesity had higher risk of death compared with those without obesity. The higher risk of death was associated with female gender, low oxygen saturation at admission, and presence of other comorbidities.

Risk factors for COVID-19-related mortality in hospitalized children and adolescents with diabetes mellitus: An observational retrospective cohort study.

BACKGROUND: Diabetes has been recognized as a major comorbidity for COVID-19 severity in adults. This study aimed to characterize the clinical outcomes and risk factors for COVID-19-related death in a large cohort of hospitalized pediatric patients with diabetes. METHODS: We performed an analysis of all pediatric patients with diabetes and COVID-19 registered in SIVEP-Gripe, a Brazilian nationwide surveillance database, between February 2020 and May 2021. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk by using cumulative incidence function. RESULTS: Among 21,591 hospitalized pediatric patients with COVID-19, 379 (1.8%) had diabetes. Overall, children and adolescents with diabetes had a higher prevalence of ICU admission (46.6% vs. 26%), invasive ventilation (16.9% vs. 10.3%), and death (15% vs. 7.6%) (all P < 0.0001). Children with diabetes had twice the hazard of death compared with pediatric patients without diabetes (Hazard ratio [HR] = 2.0, 95% CI, 1.58-2.66). Among children with diabetes, four covariates were independently associated with the primary outcome, living in the poorest regions of the country (Northeast, HR, 2.17, 95% CI 1.18-4.01, and North, (HR 4.0, 95% CI 1.79-8.94), oxygen saturation < 95% at admission (HR 2.97, 95% CI 1.64-5.36), presence of kidney disorders (HR 3.39, 95% CI 1.42-8.09), and presence of obesity (HR 3.77, 95% CI 1.83-7.76). CONCLUSION: Children and adolescents with diabetes had a higher risk of death compared with patients without diabetes. The higher risk of death was associated with clinical and socioeconomic factors.

Comparison of the First and Second Waves of the Coronavirus Disease 2019 Pandemic in Children and Adolescents in a Middle-Income Country: Clinical Impact Associated with Severe Acute Respiratory Syndrome Coronavirus 2 Gamma Lineage.

OBJECTIVE: To evaluate the severity and clinical outcomes of the SARS-CoV-2 gamma variant in children and adolescents hospitalized with COVID-19 in Brazil. STUDY DESIGN: In this observational retrospective cohort study, we performed an analysis of all 21 591 hospitalized patients aged <20 years with confirmed SARS-CoV-2 infection registered in a national database in Brazil. The cohort was divided into 2 groups according to the predominance of SARS-CoV-2 lineages (WAVE1, n = 11 574; WAVE2, n = 10 017). The characteristics of interest were age, sex, geographic region, ethnicity, clinical presentation, and comorbidities. The primary outcome was time to death, which was evaluated by competing-risks analysis, using cumulative incidence functions. A predictive Fine and Gray competing-risks model was developed based on the WAVE1 cohort with temporal validation in the WAVE2 cohort. RESULTS: Compared with children and adolescents admitted during the first wave, those admitted during the second wave had significantly more hypoxemia (52.5% vs 41.1%; P < .0001) and intensive care unit admissions (28.3% vs 24.9%; P < .0001) and needed more noninvasive ventilatory support (37.3% vs 31.6%; P < .0001). In-hospital deaths and death rates were 896 (7.7%) in the first wave and 765 (7.6%) in the second wave (P = .07). The prediction model of death included age, ethnicity, region, respiratory symptoms, and comorbidities. In the validation set (WAVE2), the C statistic was 0.750 (95% CI, 0.741-0.758; P < .0001). CONCLUSIONS: This large national study found a more severe spectrum of risk for pediatric patients with COVID-19 caused by the gamma variant. However, there was no difference regarding the probability of death between the waves.

Modified score function for monotone likelihood in the semiparametric mixture cure model.

The cure fraction models are intended to analyze lifetime data from populations where some individuals are immune to the event under study, and allow a joint estimation of the distribution related to the cured and susceptible subjects, as opposed to the usual approach ignoring the cure rate. In situations involving small sample sizes with many censored times, the detection of nonfinite coefficients may arise via maximum likelihood. This phenomenon is commonly known as monotone likelihood (ML), occurring in the Cox and logistic regression models when many categorical and unbalanced covariates are present. An existing solution to prevent the issue is based on the Firth correction, originally developed to reduce the estimation bias. The method ensures finite estimates by penalizing the likelihood function. In the context of mixture cure models, the ML issue is rarely discussed in the literature; therefore, this topic can be seen as the first contribution of our paper. The second major contribution, not well addressed elsewhere, is the study of the ML issue in cure mixture modeling under the flexibility of a semiparametric framework to handle the baseline hazard. We derive the modified score function based on the Firth approach and explore finite sample size properties of the estimators via a Monte Carlo scheme. The simulation results indicate that the performance of coefficients related to the binary covariates are strongly affected to the imbalance degree. A real illustration, in the melanoma dataset, is discussed using a relatively novel data set collected in a Brazilian university hospital.

Postnatal urinary tract dilatation classification: improvement of the accuracy in predicting kidney injury.

BACKGROUND: The grading of urinary tract dilatation (UTD) on postnatal sonography is a fundamental step to establish rational management for infants with antenatal hydronephrosis (ANH). The aim of this study was to compare the prediction accuracy of UTD grading systems for relevant clinical outcomes. In addition, we propose a refinement of the UTD classification by adding quantitative measurements and evaluate its impact on accuracy. METHODS: Between 1989 and 2019, 447 infants diagnosed with isolated AHN were prospectively followed. The events of interest were surgical interventions and kidney injury. Comparison of performance of the grading systems and the impact on the accuracy of a modified UTD classification (including the size of the kidney parenchyma) was assessed by the area under the receiver-operating characteristic curve (AUC). RESULTS: Of 447 infants, 131 (29%) underwent surgical intervention and 26 (5.8%) had developed kidney injury. The median follow-up time was 9 years (IQ range, 7-12 years). The performance for detecting the need for surgical intervention was excellent for all grading systems (AUC > 0.90). However, for predicting kidney injury, the modified UTD classification exhibited significant improvement in accuracy (AUC = 0.913, 95%CI, 0.883-0.937) as compared with UTD classification (AUC = 0.887, 95%CI, 0.854-0.915) (P = 0.027). CONCLUSIONS: Our study confirms that the hydronephrosis grading systems provide excellent accuracy in discriminating patients who need surgical intervention among infants with AHN. Our findings suggest that the inclusion of kidney parenchymal thickness to UTD classification might increase the accuracy for predicting infants who may develop kidney injury. A higher resolution version of the Graphical abstract is available as Supplementary information.