Growth phenotypes of very low birth weight infants for prediction of neonatal outcomes from a Brazilian cohort: comparison with INTERGROWTH

Abstract Objective: To assess the predictive value of selected growth phenotypes for neonatal morbidity and mortality in preterm infants < 30 weeks and to compare them with INTERGROWTH-21st (IG21). Methods: Retrospective analysis of data from the Brazilian Neonatal Research Network (BNRN) database for very low birth weight (VLBW) at 20 public tertiary-care university hospitals. Outcome: the composite neonatal morbidity and mortality (CNMM) consisted of in-hospital death, oxygen use at 36 weeks, intraventricular hemorrhage grade 3 or 4, and Bell stage 2 or 3 necrotizing enterocolitis. Selected growth phenotypes: small-for-gestational-age (SGA) defined as being < 3rd (SGA3) or 10th (SGA10) percentiles of BW, and large-for-gestational-age (LGA) as being > 97th percentile of BW. Stunting as being < 3rd percentile of the length and wasting as being < 3rd percentile of BMI. Single and multiple log-binomial regression models were fitted to estimate the relative risks of CNMM, comparing them to IG21. Results: 4,072 infants were included. The adjusted relative risks of CNMM associated with selected growth phenotypes were (BNRN/IG21): 1.45 (0.92-2.31)/1.60 (1.27-2.02) for SGA; 0.90 (0.55-1.47)/1.05 (0.55-1.99) for LGA; 1.65 (1.08-2.51)/1.58 (1.28-1.96) for stunting; and 1.48 (1.02-2.17) for wasting. Agreement between the two references was variable. The growth phenotypes had good specificity (>95%) and positive predictive value (70-90%), with poor sensitivity and low negative predictive value. Conclusion: The BNRN phenotypes at birth differed markedly from the IG21 standard and showed poor accuracy in predicting adverse neonatal outcomes.

Sanitary measures to contain COVID-19 spread decreased pediatric hospitalizations due to other respiratory infections in São Paulo, Brazil

Abstract Objective After the Covid-19 pandemics hit Brazil and sanitary measures were adopted to contain its dissemination, pediatric hospital admissions were apparently fewer than usual. The authors aimed to describe the time trends of public hospital admissions of children and adolescents due to respiratory infections (RIs) in São Paulo State, Brazil, before and after the adoption of sanitary measures to contain the dissemination of Covid-19. Methods Ecological, time-series study on the monthly average number of admissions per day of children and adolescents (< 16 years) admitted to public hospitals of São Paulo due to acute RIs between January 2008 and March 2021. Data from 2008 to 2019 were used to adjust the statistical model, while data from 2020 and 2021 were compared to the values predicted by the model. Results In 2020 and 2021, the number of hospital admissions was significantly lower than predicted by the time series. However, lethality was three times higher in these years, compared to the previous, and six times higher in patients with Covid-19, compared to those without the disease. Hospitalization costs in 2020 and 2021 were lower than in previous years. Conclusions These findings suggest that the sanitary measures adopted to contain the dissemination of Covid-19 also effectively reduce the transmission of other respiratory viruses. Policymakers and administrators can use this knowledge as a guide to planning preventative interventions that could decrease the number and severity of RIs and related hospital admissions in children and adolescents, decreasing the burden on the public health system.

Vitamin A deficiency and association between serum retinol and IGF-1 concentrations in Brazilian children with Down syndrome

Abstract Objective: To determine the prevalence of vitamin A deficiency (VAD) and serum concentrations of retinol, correlating them with IGF-1 concentrations in preschoolers with DS. Methods: Cross-sectional study was conducted on 47 children with DS aged 24 to 72 months, in Ribeirão Preto, Brazil. VAD was determined by the relative dose-response (RDR) test. Retinol serum concentration ≤ 0.70 μmol/L and IGF-1 serum concentration below the 3rd percentile for sex and age were considered to represent deficiency. C-reactive protein (CRP) was determined at the beginning of the study. Weight, height, and information about fever and/or diarrhea were obtained at the beginning of the study. Results: VAD prevalence was 25.5% (12/47), and 74.5% (35/47) of the children had deficient retinol before the intervention. CRP was not associated with VAD. Mean IGF-1 were 103.5 ng/mL (SD = 913) for the group with VAD and 116.3 ng/mL (SD = 54.9) for the group with no VAD (p-value = 0.85); 8.5% (4/47) of the children showed deficient IGF-1, but without VAD. No association was observed between VAD and IGF-1 deficiency. A moderate positive correlation was observed between pre-intervention retinol and IGF-1 (ρ = 0.37; p-value = 0.01). Conclusion: a high prevalence of VAD and deficient retinol was observed and there was a positive correlation between serum retinol and IGF-1.

Impact of children with complex chronic conditions on costs in a tertiary referral hospital

ABSTRACT OBJECTIVES To investigate the impact of complex chronic conditions on the use of healthcare resources and hospitalization costs in a pediatric ward of a public tertiary referral university hospital in Brazil. METHODS This is a longitudinal study with retrospective data collection. Overall, three one-year periods, separated by five-year intervals (2006, 2011, and 2016), were evaluated. Hospital costs were calculated in three systematic samples of 100 patients each, consisting of patients with and without complex chronic conditions in proportion to their participation in the studied year. RESULTS Over the studied period, the hospital received 2,372 admissions from 2,172 patients. The proportion of hospitalized patients with complex chronic conditions increased from 13.3% in 2006 to 16.9% in 2016 as a result of a greater proportion of neurologically impaired children, which rose from 6.6% to 11.6% of the total number of patients in the same period. Patients' complexity also progressively increased, which greatly impacted the use of healthcare resources and costs, increasing by 11.6% from 2006 (R$1,300,879.20) to 2011 (R$1,452,359.71) and 9.4% from 2011 to 2016 (R$1,589,457.95). CONCLUSIONS Hospitalizations of pediatric patients with complex chronic conditions increased from 2006 to 2016 in a Brazilian tertiary referral university hospital, associated with an important impact on hospital costs. Policies to reduce these costs in Brazil are greatly needed.

Retratamento com surfactante em prematuros de muito baixo peso: preditores de risco e sua influência nos resultados neonatais / Retreatment with surfactant in very low birth weight preterm infants: risk predictors and their influence on neonatal outcomes

ABSTRACT Objective: To assess clinical predictors and outcomes associated to the need for surfactant retreatment in preterm infants. Methods: Retrospective cohort study, including very low birth weight preterm infants from January 2006 to December 2015 who underwent surfactant replacement therapy. Beractant was used (100 mg/kg), repeated every six hours if FiO2 ≥0.40. The subjects were classified into two groups: single surfactant dose; and more than one dose (retreatment). We evaluated maternal and neonatal predictors for the need of retreatment and neonatal outcomes associated to retreatment. Results: A total of 605 patients (44.5%) received surfactant; 410 (67.8%) one dose, and 195 (32.2%) more than one dose: 163 (83.5%) two doses and 32 (16.4%) three doses. We could not find clinical predictors for surfactant retreatment. Retreatment was associated to a greater chance of BPD in infants >1000 g (RR 1.78; 95%CI 1.30‒2.45) and ≤1000 g (RR 1.33; 95%CI 1.04‒1.70), in infants with gestational age<28 weeks (RR 1.56; 95%CI 1.12‒2.18) and ≥28 weeks (RR 1.50; 95%CI 1.17‒1.92), in neonates with early sepsis (RR 1.48; 95%CI 1.20‒1.81), and in infants not exposed to antenatal corticosteroids (RR 1.62; 95%CI 1.20‒2.17) Conclusions: We could not find predictor factors associated to surfactant retreatment. The need for two or more doses of surfactant was significantly related to bronchopulmonary dysplasia.

RESUMO Objetivo: Avaliar preditores clínicos e resultados associados à necessidade de retratamento com surfactante. Métodos: Coorte retrospectiva com prematuros de muito baixo peso, no período de janeiro de 2006 a dezembro de 2015, em uso de terapia de reposição de surfactante. O surfactante utilizado foi beractante (100 mg/kg), repetido a cada seis horas se FiO2≥0.40. Foram analisados dois grupos: dose única de surfactante e mais de uma dose (retratamento). Foram avaliados preditores maternos e neonatais para retratamento e resultados neonatais. Resultados: 605 pacientes (44,5%) receberam surfactante; 410 (67,8%) uma dose e 195 (32,2%) mais de uma dose: 163 (83,5%) duas doses e 32 (16.4%) três doses. Não foram encontrados fatores associados ao retratamento com surfactante. A displasia broncopulmonar (DBP) foi associada ao retratamento (p<0.01). A presença de retratamento aumentou a chance de ocorrência de DBP em neonatos >1000 g (RR 1,78; IC95% 1,30‒2,45) e ≤1000 g (RR 1,33; IC95% 1,04‒1,70), em recém-nascidos com idade gestacional <28 semanas (RR 1,56; IC95% 1,12‒218) e ≥28 semanas (RR 1,50; IC95% 1,17‒1,92), naqueles com sepse precoce (RR 1,48; IC95% 1,20‒1,81), e nos que não foram expostos ao corticoide antenatal (RR 1,62; IC95% 1,20‒2,17). Conclusões: Não encontramos fatores preditores associados à necessidade de retratamento. A necessidade de duas ou mais doses de surfactante está associada à displasia broncopulmonar.

Comorbidities and the risk of death among individuals infected by COVID-19 in Espírito Santo, Brazil

Abstract INTRODUCTION: We investigated the association of self-reported comorbidities with fatality risk among individuals infected with Coronavirus disease 2019 (COVID-19) in Espírito Santo State, Brazil. METHODS: We included 212,620 individuals, ≥30 years old. The data were obtained from the COVID-19 panel. Kaplan-Meier curves and Cox regression model were used. RESULTS: COVID-19-positive individuals presenting with chronic conditions were at a higher risk of fatality than individuals without these comorbidities. Age had a significant effect on these relationships. CONCLUSIONS: Comorbidities were associated with an increased risk of fatality. Middle-aged people (30-59 years) with comorbidities should also be considered as a vulnerable group.

Feasibility of very short-term forecast models for COVID-19 hospital-based surveillance

Abstract INTRODUCTION: We evaluated the performance of Bayesian vector autoregressive (BVAR) and Holt's models to forecast the weekly COVID-19 reported cases in six units of a large hospital. METHODS: Cases reported from epidemiologic weeks (EW) 12-37 were selected as the training period, and from EW 38-41 as the test period. RESULTS: The models performed well in forecasting cases within one or two weeks following the end of the time-series, but forecasts for a more distant period were inaccurate. CONCLUSIONS: Both models offered reasonable performance in very short-term forecasts for confirmed cases of COVID-19.

Long-term forecasts of the COVID-19 epidemic: a dangerous idea

Abstract INTRODUCTION: Mathematical models have been used to obtain long-term forecasts of the COVID-19 epidemic. METHODS: The daily COVID-19 case count in two Brazilian states was used to show the potential limitations of long-term forecasting through the application of a mathematical model to the data. RESULTS: The predicted number of cases at the end of the epidemic and at the moment that the peak occurs, is highly dependent on the length of the time series used in the predictive model. CONCLUSIONS: Predictions obtained during the course of the COVID-19 pandemic need to be viewed with caution.

Short-term forecasting of daily COVID-19 cases in Brazil by using the Holts model

Abstract: INTRODUCTION: We evaluated the performance of the Holt's model to forecast the daily COVID-19 reported cases in Brazil and three Brazilian states. METHODS: We chose the date of the first COVID-19 case to April 25, 2020, as the training period, and April 26 to May 3, 2020, as the test period. RESULTS: The Holt's model performed well in forecasting the cases in Brazil and in São Paulo and Minas Gerais states, but the forecasts were underestimated in Rio de Janeiro state. Conclusions: The Holt's model can be an adequate short-term forecasting method if their assumptions are adequately verified and validated by experts.

Placental measurements and their association with birth weight in a Brazilian cohort / Medidas placentárias e sua associação com o peso ao nascer em uma coorte brasileira

ABSTRACT: Introduction: Epidemiological studies have shown associations between placental measurements and perinatal and later life outcomes. Objectives: To report placental measurements and evaluate their association with birth weight in a Brazilian birth cohort. Methods: Retrospective cohort study with 958 mothers, placentas, and newborns delivered at the Ribeirão Preto Medical School Hospital, Universidade de São Paulo, Brazil, in 2010 and 2011. The information was collected from interviews, medical records, and pathology reports. The placental measurements were: weight, largest and smallest diameters, eccentricity, thickness, shape, area, and birth weight/placental weight and placental weight/birth weight ratios. We analyzed the associations between birth weight and placental measurements using multiple linear regression. Results: Placental weight alone accounted for 48% of birth weight variability (p < 0.001), whereas placental measurements combined (placental weight, largest and smallest diameters, and thickness) were responsible for 50% (p < 0.001). When adjusted for maternal and neonatal characteristics, placental measurements explained 74% of birth weight variability (p < 0.001). Conclusion: Placental measurements are powerful independent predictors of birth weight. Placental weight is the most predictive of them, followed by the smallest diameter.

RESUMO: Introdução: Estudos epidemiológicos demonstraram associações entre medidas placentárias, resultados perinatais e futuros. Objetivos: Descrever medidas placentárias e avaliar suas associações com peso ao nascer numa coorte de nascimentos brasileira. Metodologia: Estudo de coorte retrospectiva de 958 mães, placentas e recém-nascidos no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, Brasil, em 2010 e 2011. As informações foram coletadas por entrevistas, prontuários médicos e laudos de patologia. As medidas placentárias foram: peso, diâmetros maior e menor, excentricidade, espessura, forma, área, relações peso ao nascer/ peso da placenta e peso da placenta/ peso ao nascer. As associações entre peso ao nascer e medidas placentárias foram examinadas por meio de regressão linear múltipla. Resultados: O peso da placenta foi responsável por 48% da variabilidade do peso ao nascer (p < 0,001), enquanto o conjunto de medidas placentárias (peso, diâmetros maior e menor e espessura) foi responsável por 50% (p < 0,001). Quando ajustadas pelas características maternas e neonatais, as medidas placentárias explicaram 74% da variabilidade do peso ao nascer (p < 0,001). Conclusão: medidas placentárias são preditores independentes do peso ao nascer. O peso placentário é o mais forte preditor dentre elas, seguido pelo diâmetro menor.

Modelagem Bayesiana do risco de infecção tuberculosa para estudos com perdas de seguimento / Modelaje Bayesiano del riesgo de infección tuberculosa para estudios con pérdidas de seguimiento / Bayesian model for the risk of tuberculosis infection for studies with individuals lost to follow-up

OBJETIVO: Desenvolver um modelo estatístico baseado em métodos Bayesianos para estimar o risco de infecção tuberculosa em estudos com perdas de seguimento, comparando-o com um modelo clássico determinístico. MÉTODOS: O modelo estocástico proposto é baseado em um algoritmo de amostradores de Gibbs, utilizando as informações de perdas de seguimento ao final de um estudo longitudinal. Para simular o número desconhecido de indivíduos reatores ao final do estudo e perdas de seguimento, mas não reatores no tempo inicial, uma variável latente foi introduzida no novo modelo. Apresenta-se um exercício de aplicação de ambos os modelos para comparação das estimativas geradas. RESULTADOS: As estimativas pontuais fornecidas por ambos os modelos são próximas, mas o modelo Bayesiano apresentou a vantagem de trazer os intervalos de credibilidade como medidas da variabilidade amostral dos parâmetros estimados. CONCLUSÕES: O modelo Bayesiano pode ser útil em estudos longitudinais com baixa adesão ao seguimento.

OBJECTIVE: To develop a statistical model based on Bayesian methods to estimate the risk of tuberculosis infection in studies including individuals lost to follow-up, and to compare it with a classic deterministic model. METHODS: The proposed stochastic model is based on a Gibbs sampling algorithm that uses information of lost to follow-up at the end of a longitudinal study. For simulating the unknown number of reactors at the end of the study and lost to follow-up, but not reactors at time 0, a latent variable was introduced in the new model. An exercise of application of both models in the comparison of the estimates of interest was presented. RESULTS: The point estimates obtained from both models are near identical; however, the Bayesian model allowed the estimation of credible intervals as measures of precision of the estimated parameters. CONCLUSIONS: The Bayesian model can be valuable in longitudinal studies with low adherence to follow-up.

OBJETIVO: Desarrollar un modelo estadístico en basado en métodos Bayesianos para estimar el riesgo de infección tuberculosa en estudios con pérdidas de seguimiento, comparándolo con un modelo clásico deterministico. MÉTODOS: El modelo estocástico propuesto se basa en un algoritmo de muestreadotes de Gibbs, utilizando las informaciones de pérdidas de seguimiento al final de un estudio longitudinal. Para simular el número desconocido de individuos reactores al final del estudio y pérdidas de seguimiento, pero no reactores en el tiempo inicial, una variable latente fue introducida en el nuevo modelo. Se presenta un ejercicio de aplicación de ambos modelos para comparación de las estimaciones generadas. RESULTADOS: Las estimaciones puntuales suministradas por ambos modelos son próximas, pero el modelo Bayesiano presentó la ventaja de traer los intervalos de credibilidad como medidas de variabilidad muestral de los parámetros estimados. CONCLUSIONES: El modelo Bayesiano puede ser útil en estudios longitudinales con baja adhesión al seguimiento.