Temporal-spatial analysis of hospitalizations for bronchiolitis in Brazil: prediction of epidemic regions and periods for immunization against the Respiratory Syncytial Virus / Análise temporal-espacial de hospitalizações por bronquiolite no Brasil: previsão das regiões e períodos epidêmicos para imunização contra o vírus sincicial respiratório

Abstract Objective: Due to the high cost and short term of passive immunization against the respiratory syncytial virus, the main virus causing acute viral bronchiolitis, predicting epidemic regions and epidemic months is extremely important. The objective of this study is to identify both the month when the seasonal peak begins and Brazilian regions and states with the highest incidence of monthly hospitalizations due acute viral bronchiolitis. Methods: Based on data obtained from DATASUS, monthly hospitalization rates due acute viral bronchiolitis were calculated for every 10,000 live births to children under 12 months of age in all Brazilian states and the Federal District between 2000 and 2019. Seasonal autoregressive integrated moving average models were estimated to forecast monthly hospitalization rates in 2020. Results: A higher incidence of hospitalizations was found for male children, especially under six months of age. As for Brazilian regions, between 2000 and 2019, the South region registered the highest incidence of hospitalizations, followed by the Southeast, Midwest, North and Northeast regions, in this order. Considering the seasonal peak, the period between March and July 2020 comprised the highest expected hospitalization rates. Conclusions: Palivizumab is suggested to be started between February/March and June/July for most Brazilian states, with the exception of Rio Grande do Sul, which, in addition to presenting the highest rates of hospitalizations for acute viral bronchiolitis per 10,000 live births, has the longest seasonal peak between May and September.

RESUMO Objetivo: Em razão do alto custo e do curto prazo da imunização passiva contra o vírus sincicial respiratório, principal vírus causador de bronquiolite viral aguda, a previsão das regiões e meses epidêmicos é extremamente importante. Objetiva-se identificar o mês de início do pico sazonal e as regiões e Estados brasileiros de maior incidência de hospitalizações mensais por bronquiolite viral aguda. Métodos: Com dados obtidos no Departamento de Informática do Sistema Único de Saúde do Brasil, foram calculadas as taxas mensais de hospitalizações por bronquiolite viral aguda a cada 10 mil nascidos vivos de crianças com idade inferior a 12 meses, em todos os Estados brasileiros e no Distrito Federal, no período entre 2000 e 2019. Modelos sazonais autorregressivos integrados e de médias móveis foram estimados para a previsão das taxas mensais de hospitalizações em 2020. Resultados: Verificou-se maior incidência de hospitalizações em crianças do sexo masculino, principalmente naquelas com idade inferior a seis meses. Em relação às regiões brasileiras, entre 2000 e 2019, a Região Sul apresentou a maior incidência de hospitalizações, seguida pelas Regiões Sudeste, Centro-Oeste, Norte e Nordeste, respectivamente. Quanto ao pico sazonal, o período entre março e julho de 2020 compreende as maiores taxas de hospitalizações previstas. Conclusões: Sugere-se o início da administração do Palivizumab entre fevereiro/março e junho/julho para a maioria dos Estados brasileiros, com exceção do Rio Grande do Sul, que, além de apresentar as maiores taxas de hospitalizações por bronquiolite viral aguda a cada 10.000 nascidos vivos, possui o pico sazonal de maior duração entre maio e setembro.

Evaluation of respiratory complications in a cohort of preterm infants who did not receive palivizumab monoclonal antibodies / Evaluación de complicaciones respiratorias en cohorte de prematuros no contemplados con el anticuerpo monoclonal palivizumab / Avaliação das intercorrências respiratórias em coorte de prematuros não contemplados com o anticorpo monoclonal palivizumabe

ABSTRACT Objectives: to analyze the occurrence of respiratory complications over the first year of life in preterm infants who did not receive palivizumab monoclonal antibodies. Methods: analytical retrospective cohort study with preterm infants born between 2012 and 2016 in Uberlândia, state of Minas Gerais, Brazil. Data collection occurred from January to November 2018, by consulting hospital and primary healthcare medical records. Data were processed with the Poisson regression model, with p<0.05. Results: of a total of 5,213 preterm births, 504 (9.7%) met the inclusion criteria. The preterm infants in this subset were assisted 2,899 times in primary care, which resulted in 1,098 (37.5%) medical diagnoses, of which 803 (78.5%) involved the respiratory tract. Preterm babies fed on formula milk at hospital discharge had more diagnoses of respiratory diseases. Maternal age (p=0.039), respiratory diagnosis at hospital discharge (p=0.028), and number of sporadic appointments (p<0.001) showed a significant association with bronchiolitis; number of sporadic appointments showed a significant association with occurrence of respiratory diseases; and breastfeeding had a protective effect against the development of bronchiolitis. Conclusions: preterm infants who did not receive palivizumab showed a high percentage of respiratory diseases, and breastfeeding helped protect them against bronchiolitis. It is recommended that these preterm babies be monitored in primary health care.

RESUMEN Objetivos: investigar complicaciones respiratorias en el primer año de vida de prematuros no contemplados con anticuerpo monoclonal palivizumab. Métodos: estudio de cohorte retrospectivo, analítico, con prematuros nacidos entre 2012 y 2016 en Uberlândia, MG. Datos recolectados de enero a noviembre de 2018 en historias clínicas hospitalarias y de atención básica. Se utilizó modelo de regresión de Poisson, considerándose p<0,05. Resultados: de 5.513 nacimientos prematuros, 504 (9,7%) atendieron criterios; estos prematuros recibieron 2.899 consultas en atención básica; 1.098 (37,5%) con diagnóstico médico; 803 (78,5%) del tracto respiratorio. Prematuros con fórmula láctea al alta hospitalaria recibieron más diagnósticos de enfermedades respiratorias. Edad materna (p=0,039), diagnóstico respiratorio al alta (p=0,028), cantidad de consultas eventuales (p<0,001) mostraron asociación significativa con bronquiolitis. Conclusiones: prematuros sin palivizumab mostraron elevado porcentaje de enfermedades respiratorias; se observó efecto protector de la lactancia materna. Se recomienda el seguimiento de dichos prematuros en atención primaria.

RESUMO Objetivos: investigar intercorrências respiratórias no primeiro ano de vida de prematuros não contemplados com anticorpo monoclonal palivizumabe. Métodos: estudo de coorte retrospectivo, analítico, com prematuros nascidos entre 2012 e 2016, em Uberlândia, MG. Coleta realizada de janeiro a novembro de 2018, em prontuários hospitalar e da atenção básica. Utilizou-se modelo de regressão de Poisson; considerou-se p<0.05. Resultados: de 5.213 nascimentos prematuros, 504 (9,7%) atenderam os critérios; esses prematuros tiveram 2.899 atendimentos na atenção básica; 1.098 (37,5%) com diagnóstico médico, 803 (78,5%) do trato respiratório. Prematuros com fórmula láctea na alta hospitalar tiveram mais diagnósticos de doenças respiratórias. Idade materna (p=0,039), diagnóstico respiratório na alta (p=0,028), número de consultas eventuais (p<0,001) apresentaram associação significativa com bronquiolite. Consultas eventuais foram significantes para doenças respiratórias; o aleitamento materno mostrou-se protetor para bronquiolite. Conclusões: prematuros sem palivizumabe apresentaram elevado percentual de doenças respiratórias; observou-se efeito protetor do aleitamento materno. Recomenda-se vigilância desses prematuros na atenção primária.

Risk factors for recurrent wheezing in preterm infants who received prophylaxis with palivizumab / Fatores de risco para sibilância recorrente em crianças pré-termo que receberam profilaxia com palivizumabe

ABSTRACT Objective: To determine the prevalence of recurrent wheezing (RW) in preterm infants who received prophylaxis against severe infection with respiratory syncytial virus (RSV) and to identify genetic susceptibility (atopy or asthma) and risk factors for RW. Methods: This was a cross-sectional study involving preterm infants who received prophylaxis with palivizumab at a referral center in Brazil during the first two years of age. A structured questionnaire was administered in a face-to-face interview with parents or legal guardians. Results: The study included 410 preterm infants (median age = 9 months [0-24 months]). In the sample as a whole, 111 children (27.1%; [95% CI, 22.9-31.5]) had RW. The univariate analysis between the groups with and without RW showed no differences regarding the following variables: sex, ethnicity, maternal level of education, gestational age, birth weight, breastfeeding, number of children in the household, day care center attendance, pets in the household, and smoking caregiver. The prevalence of RW was twice as high among children with bronchopulmonary dysplasia (adjusted OR = 2.08; 95% CI, 1.11-3.89; p = 0.022) and almost five times as high among those with a personal/family history of atopy (adjusted OR = 4.96; 95% CI, 2.62-9.39; p < 0.001) as among those without these conditions. Conclusions: Preterm infants who received prophylaxis with palivizumab but have a personal/family history of atopy or bronchopulmonary dysplasia are more likely to have RW than do those without these conditions.

RESUMO Objetivo: Determinar a prevalência de sibilância recorrente (SR) em crianças pré-termo que receberam profilaxia contra infecção grave pelo vírus sincicial respiratório (VSR) e identificar susceptibilidade genética (atopia ou asma) e fatores de risco para SR. Métodos: Estudo transversal envolvendo crianças pré-termo que receberam profilaxia com palivizumabe em um centro de referência no Brasil durante os primeiros dois anos de vida. Um questionário estruturado foi aplicado em entrevista presencial com os pais ou responsáveis. Resultados: O estudo incluiu 410 crianças pré-termo (mediana de idade = 9 meses [0-24 meses]). Na amostra total, 111 crianças (27,1%; IC95%: 22,9-31,5) apresentavam SR. A análise univariada entre os grupos com e sem SR não mostrou diferenças em relação às seguintes variáveis: sexo, etnia, escolaridade materna, idade gestacional, peso ao nascer, aleitamento materno, número de crianças no domicílio, frequência em creche, presença de animais de estimação no domicílio e cuidador tabagista. A prevalência de SR foi duas vezes maior entre crianças com displasia broncopulmonar (OR ajustada = 2,08; IC95%: 1,11-3,89; p = 0,022) e quase cinco vezes maior entre aquelas com história pessoal/familiar de atopia (OR ajustada = 4,96; IC95%: 2,62-9,39; p < 0,001) do que entre aquelas sem essas condições. Conclusões: Crianças pré-termo que receberam profilaxia com palivizumabe, mas apresentam história pessoal/familiar de atopia ou displasia broncopulmonar, têm maior probabilidade de apresentar SR do que aquelas sem essas condições.

Caracterización de prematuros ingresados por bronquiolitis en el Hospital Nacional de Niños / Characterization of premature patients admitted for bronchiolitis at the National Children's Hospital

Resumen Antecedentes: La bronquiolitis es la infección del tracto respiratorio inferior más frecuente en lactantes. El virus respiratorio sincicial es el principal agente y responde hasta por un 85 % de los casos. Los principales factores de riesgo asociados son: sexo masculino; lactantes menores; prematuros; patologías médicas de fondo como: cardiopatía congénita, displasia broncopulmonar, síndrome de Down y enfermedades neuromusculares; así como otros factores ambientales y sociales. El objetivo de este estudio fue caracterizar los prematuros, el tratamiento utilizado, el perfil de la inmunofluorescencia viral, las complicaciones, el uso de palivizumab y los costos de hospitalización en pacientes hospitalizados por bronquiolitis durante enero de 2011 y diciembre de 2011. Pacientes y métodos: Estudio observacional, descriptivo, basado en la revisión retrospectiva de expedientes clínicos de una serie de pacientes hospitalizados en el Hospital Nacional de Niños de la Caja Costarricense de Seguro Social. Se incluyeron todos los pacientes menores de 2 años egresados con el diagnóstico de bronquiolitis durante 2011, con el antecedente de prematuridad (menor de 37 semanas de edad gestacional). Resultados: Se incluyó un total de 141 pacientes; un 63 % (n=89) de sexo masculino, promedio de edad 5,7 meses (rango 0-24). Un 43 % (n=61) de los pacientes manifestó bronquiolitis antes de los 3 meses de edad. Con respecto a la edad gestacional, se obtuvo que el 35,46 % de los pacientes eran de 32 a 35 semanas, de 35 a 37 semanas un 31,2 %, de 30 a 32 semanas un 19,86 % y el resto menores de las 29 semanas. En 93 niños (66 %) se anotó el antecedente de tabaquismo en el entorno del hogar; de forma específica, en 17 % de estos pacientes se presentó el antecedente de tabaquismo pasivo, al reportarse que el padre o el abuelo eran los fumadores activos. El antecedente heredofamiliar de asma fue positivo en el 41,8 %. Con respecto al tratamiento recibido durante su hospitalización, el 100 % ameritó oxígeno suplementario y un 61 % recibió nebulizaciones con salbutamol; los esteroides sistémicos se utilizaron en el 33 % de los pacientes y solo en un 29 % se utilizó la terapia antibiótica. Un 28 % de la población estudiada presentó complicaciones, de los cuales 28 (19,86 %) prematuros ameritaron soporte ventilatorio. El hallazgo de atelectasia en la radiografía de tórax se evidenció en el 7,8 % de los pacientes. Únicamente un 4,25 % de los pacientes tuvo una sobreinfección bacteriana. Debido a la dificultad de los accesos venosos de este grupo de niños, 14 (9,93 %) ameritaron la colocación de catéter venoso central. El rango de estancia hospitalaria fue de 1 a 31 días, con un promedio de 7; la hospitalización en la Unidad de Cuidados Intensivos alcanzó un rango de 5 a 18 días, con un promedio de 10, y el promedio de la necesidad de ventilación mecánica asistida fue de 8,2 días, y de cánula de alto flujo de 2,8 días. Únicamente un 6,38 % (n=9) tenía el antecedente de haber recibido profilaxis con palivizumab: la mayoría había recibido más de dos dosis y ninguno de los pacientes había completado el esquema de las 5 dosis. Durante 2011, el Hospital reportó que el costo promedio diario fue de ¢ 766 476. Con un total de 1001 días de hospitalización acumulada, se estimó un costo directo de ¢ 767 242 142, equivalente a $ 1 522 306 (dólares estadounidenses). Conclusión: El perfil de los prematuros en este estudio es muy similar a lo reportado internacionalmente, por ser un grupo de prematuros con prevalencia más elevada de complicaciones que la población pediátrica general. Dado el costo que implica el internamiento de estos pacientes, es necesario evaluar la aplicación de intervenciones como el palivizumab para prevenir la hospitalización y disminuir otros costos al sistema de salud solidario.

Abstract Background: Bronchiolitis is the most common lower respiratory tract infection in infants. Respiratory Syncytial Virus is the main agent and responds in up to 85% of cases. The main associated risk factors are: male sex, young infants, premature infants, underlying medical conditions such as: congenital heart disease, bronchopulmonary dysplasia, Down syndrome and neuromuscular diseases; as well as other environmental and social factors. The objective of this study was to characterize preterm infants, the treatment used, the viral immunofluorescence profile, complications, the use of palivizumab, and hospitalization costs in patients hospitalized for bronchiolitis during January 2011 and December 2011. Methods: An observational, descriptive study, based on a retrospective review of clinical records of a series of hospitalized patients at the National Children's Hospital (HNN) of the Costa Rican Social Security Fund. All patients under 2 years of age who were discharged with a diagnosis of bronchiolitis during 2011, with a history of prematurity (less than 37 weeks gestational age) were included. Results: A total of 141 patients were included, 63% (n = 89) were male, with an average age of 5.7 months (range 0-24). 43% (n = 61) of patients with Bronchiolitis manifested before 3 months of age. With regard to gestational age, it was found that 35.46% of the patients were between 32 and 35 weeks, 31.2% from 35 to 37 weeks, 19.86% from 30 to 32 weeks and the rest were under 29 weeks. In 93 children (66%) a history of smoking was noted in the home environment; specifically, 17% of these patients had a history of passive smoking as the father or grandfather was reported as active smokers. In relation to the hereditary family history of asthma, it was positive in 41.8%. Regarding the treatment received during their hospitalization, 100% required supplemental oxygen and 61% received nebulizations with salbutamol; systemic steroids were used in 33% of patients and antibiotic therapy was used in only 29%. 28% of the population studied presented complications, of which 28 (19.86%) premature babies required ventilatory support. The finding of atelectasis on the chest X-ray occurred in 7.8% of the patients. Only 4.25% of the patients had a bacterial superinfection. Due to the difficulty of the venous access in this group of children, 14 (9.93%) of them required the placement of a central venous catheter. The range of hospital stay was from 1 to 31 days with an average of 7 days, hospitalization in the Intensive Care Unit reached a range of 5 to 18 days with an average of 10 days and the average need for assisted mechanical ventilation It was 8.2 days and the high-flow cannula was 2.8 days. Only 6.38% (n = 9) had a history of having received prophylaxis with Palivizumab, the majority had received more than two doses, and none of the patients had completed the 5-dose schedule. During that year 2011, the hospital reported that the average daily cost was ¢ 766 476; With a total of 1001 cumulative hospitalization days, a total direct cost of ¢ 767 242 142 was estimated, equivalent to $ 1 522 306 (US dollars). Conclusion: The profile of the characteristics of premature infants in this study is very similar to that reported internationally, as it is a group of premature infants with a higher prevalence of complications than the general pediatric population. Given the cost involved in the hospitalization of these patients, it is necessary to evaluate the application of interventions such as palivizumab to prevent hospitalization and reduce other costs to the solidarity health system.

Costo-efectividad incremental del Palivizumab en prematuros en la Seguridad Social de Costa Rica / Incremental cost- effectiveness of palivizumab in premature at Costa Rican Social Security / Custo-efetividade incremental do palivizumabe em prematuros da Previdência Social da Costa Rica / Coût-efficacité incrémental du Palivizumab chez les prématurés de la Sécurité Sociale du Costa Rica

Resumen Objetivo Estimar la eficiencia mediante el análisis costo-efectividad incremental de la terapia con Palivizumab contra la práctica clínica habitual en el período 2010-2017. Materiales y Métodos Se realizó una evaluación económica completa del tipo costo-efectividad y el horizonte temporal fue de un año (sin tasa de descuento). El estudio considero la perspectiva de la Seguridad Social, se incluyeron siete hospitales y las variables de efectividad se seleccionaron a partir de la información disponible en la literatura científica. Los costos se expresaron en dólares americanos para cada año. Se hizo el análisis árbol de decisiones con los datos agrupados y el análisis costo-efectividad medio e incremental de sensibilidad al considerar la edad gestacional como variable clasificadora. Se consideraron los principios éticos pertinentes. Resultados Se encontraron datos de 200 prematuros con Palivizumab y 206 sin la administración del tratamiento. El análisis del árbol de decisiones mostró un costo efectividad incremental de US$1,799.00. El costo-efectividad medio fue más alto en prematuros con Palivizumab y el costo-efectividad incremental en el sub grupo de 32 a 35 semanas resultó el de más costo-efectivo. Al intervalo de confianza del 90 y 95%, el rango del valor promedio del costo total del tratamiento es amplio por lo que el costo es sensible al cambio. Conclusiones El Palivizumab es mayor en costo-efectivo en prematuros de 32 a 35 semanas de edad gestacional.

Abstract Objective To estimate the efficiency by incremental cost effectiveness analysis of palivizumab therapy against the usual clinical practice in 2010-2017 period. Materials and methods A complete economic evaluation of the cost effectiveness type was carried out and the time horizon was one year, without discount rate, the study was carried out from the perspective of Social Security, seven hospitals were included and the effectiveness variables were selected from the available information in the literature scientifically, the costs were expressed in US dollars for each year. The decision tree analysis was carried out with the grouped data and the average and incremental cost effectiveness and sensitivity analysis when considering gestational age as a classification variable. Relevant ethical principles were considered. Results Data of 200 premature infants were found with palivizumab and 206 without the administration of this treatment. The decision tree analysis showed an incremental cost effectiveness of US $ 1,799. The average cost effectiveness was higher in premature infants with palivizumab and the incremental cost effectiveness in the subgroup 32-35 weeks was the most effective cost. At the 90 and 95% confidence interval, the range of the average value of the total treatment cost is wide, so the cost is sensitive to change. Conclusions Palivizumab is more effective cost in premature of 32-35 weeks of gestational age.

Resumo Objetivo Estimar a eficiência através da análise de custo-efetividade incremental da terapia com Palivizumab em relação à prática clínica habitual no período 2010-2017. Materiais e Métodos Foi realizada uma avaliação econômica completa do tipo custo-efetividade e o horizonte temporal foi de um ano (sem taxa de desconto). O estudo considerou a perspectiva da Previdência Social, sete hospitais e as variáveis de efetividade foram incluídas foram selecionados a partir das informações disponíveis na literatura científica. Os custos foram expressos em dólares americanos para cada ano. A análise da árvore de decisão foi feita com os dados agrupados e a análise de custo-efetividade média e incremental da sensibilidade a considere a idade gestacional como uma variável classificatória. Princípios éticos relevantes foram considerados. Resultados Foram encontrados dados de 200 bebês prematuros com Palivizumab e 206 sem administração do tratamento. A análise da árvore de decisão mostrou um custo incremental de $1.799,00. O custo-benefício médio foi maior em prematuros com Palivizumab, e o custo-efetividade incremental no subgrupo de 32 a 35 semanas foi o mais econômico. No intervalo de confiança de 90 e 95%, a faixa do valor médio do custo total do tratamento é ampla, tornando o custo sensível à mudança. Conclusões O palivizumabe é mais econômico em prematuros de 32 a 35 semanas de idade gestacional.

Résumé Objectif Estimer l'efficience, au moyen de l'analyse coût-efficacité incrémental, du traitement par Palivizumab par rapport à la pratique clinique habituelle au cours de la période 2010-2017. Méthodologie Une évaluation économique complète de type coût-efficacité a été réalisée sur un horizon temporel d'un an (sans taux d'actualisation). L'étude a été réalisée dans le contexte de la Sécurité Sociale. Sept hôpitaux ont été inclus et les variables d'efficacité ont été sélectionnées sur la base des informations disponibles dans la littérature scientifique. Les coûts ont été exprimés en dollars américains par an. L'analyse de l'arbre de décisions a été réalisée avec les données groupées, ainsi que l'analyse du rapport coût-efficacité moyen et incrémental de sensibilité en considérant l'âge gestationnel comme variable de classification. Les principes éthiques pertinents ont été appliqués. Résultats Des données concernant 200 nourrissons prématurés traités avec Palivizumab et 206 sans ce traitement ont été réunies. L'analyse de l'arbre de décisions a montré un coût-efficacité incrémental de 1 799 $ US. Le rapport coût-efficacité moyen a été plus élevé chez les nourrissons prématurés avec Palivizumab et le coût-efficacité incrémental dans le sous-groupe de 32 à 35 semaines a été le plus rentable. Avec un intervalle de confiance de 90 et 95%, la fourchette de la valeur moyenne du coût total du traitement est large, de sorte que le coût est sensible au changement. Conclusions Le Palivizumab est plus rentable chez les bébés prématurés de 32 à 35 semaines d'âge gestationnel.

Doenças respiratórias em crianças prematuras em Uberlândia-MG / Respiratory diseases in premature children in Uberlândia-MG

A bronquiolite, causada pelo vírus sincicial respiratório (VSR), é a doença mais frequente do trato respiratório inferior em prematuros e a primeira causa de hospitalização de recémnascidos (RN) no mundo. Sem uma vacina contra o VSR para uso populacional, o Palivizumabe (PVZ), um anticorpo monoclonal, tem sido indicado para profilaxia da doença grave por VSR. Beneficiam-se com PVZ crianças menores de um ano de idade, nascidas prematuras com Idade Gestacional (IG) menor ou igual a 28 semanas e crianças com até dois anos de idade com doença pulmonar crônica ou doença cardíaca congênita com repercussão hemodinâmica demonstrada. Este estudo de coorte retrospectivo, analítico, objetivou analisar o adoecimento de crianças prematuras, por complicações respiratórias, nascidas entre 2012 e 2016 em Uberlândia, MG e que não foram contempladas com PVZ. Extraíram-se dados dos prontuários de 504 crianças, tanto no Hospital de Clínicas da Universidade Federal quanto nas Unidades de Saúde do município. A média de idade materna foi de 26,1 anos, 281(55,9%) tinham ensino médio e 274 (55,1%) eram de cor não branca. Tiveram gestações anteriores, 306 (60,7%) mães que realizaram, na gestação atual, média de 7,8 consultas de pré-natal. Maior prevalência (371;73,6%) para parto cesáreo, 255 (50,7%) crianças do sexo masculino; IG média de 34,2 semanas e 385 (76,4%) com baixo peso ao nascer. Identificaram-se 270 (54%) RN com internação em Unidade de Terapia Intensiva (UTI); 284 (58,7%) bebês com, pelo menos, um diagnóstico respiratório na internação e 267 (53,3%) receberam alta hospitalar após sete ou mais dias. Na alta, 186 (36,6%) RN estavam em aleitamento materno exclusivo. Ao longo do primeiro ano de vida, identificaram-se 2.899 atendimentos de rotina e eventuais; média de 5,75 consultas para cada criança. Em 1.437 atendimentos foram diagnosticadas doenças com maior frequência para doenças do trato respiratório 803(55,8%), seguidas das doenças do aparelho digestivo 141(9,8%), doenças nutricionais e metabólicas 73(5%) e doenças do ouvido 72 (5%), respectivamente. Dos 561 episódios de doenças do trato respiratório superior (DTRS), as Infecções das Vias Aéreas Superiores (IVAS) e a nasofaringite aguda (resfriado comum) corresponderam a 477 (85%) episódios. Em relação aos 242 episódios de doenças respiratórias do trato respiratório inferior (DRTI) 105 (29,5%) crianças foram acometidas com 147 (60,7%) episódios de bronquiolite, média de 0,43 episódios. Em 44 (3,33%) atendimentos, houve necessidade de hospitalização, sendo três (0,14%) em UTI. Verificou-se correlação entre o número de consultas eventuais (NCE) e o número de episódios de doenças respiratórias. Crianças com somente fórmula láctea na alta hospitalar tiveram um número médio maior de episódios de doenças respiratórias no primeiro ano de vida. A idade da mãe, o diagnóstico respiratório na alta hospitalar e o NCE apresentaram associação significativa com adoecimento por bronquiolite. As DTRS foram mais frequentes nessa coorte, com média de 2,16 episódios de doença respiratória por criança no primeiro ano de vida. O NCE foi significante para doenças respiratórias e o aleitamento materno mostrou-se como fator protetor para este desfecho. Da análise do adoecimento das crianças prematuras, a ocorrência de bronquiolite revela a importância de atender estas crianças em tempo oportuno para evitar desfechos desfavoráveis como hospitalização. Evidencia-se também a importância de rastrear crianças com diagnóstico respiratório em uso de fórmula na alta hospitalar para orientar medidas preventivas de doenças respiratórias

Bronchiolitis, caused by the respiratory syncytial virus (RSV), is the most common disease of the lower respiratory tract in premature infants and the leading cause of hospitalization of newborns (NB) in the world. Without a RSV vaccine for population use, Palivizumab (PVZ), a monoclonal antibody, has been indicated for the prophylaxis of severe RSV disease. Children under one year of age, premature babies with gestational age (GA) less than or equal to 28 weeks and children up to two years of age with chronic lung disease or congenital heart disease with demonstrated hemodynamic repercussion benefit from PVZ. This retrospective, analytical cohort study aimed to analyze the illness of premature children, due to respiratory complications, born between 2012 and 2016 in Uberlândia, MG and who were not treated with PVZ. Data was extracted from the medical records of 504 children, both at the Clinical Hospital of the Federal University and in the Health Units of the municipality. The mean maternal age was 26.1 years, 281 (55.9%) had high school and 274 (55.1%) were non-white. There were previous pregnancies, 306 (60.7%) mothers who had, in the current pregnancy, an average of 7.8 prenatal consultations. Higher prevalence (371; 73.6%) for cesarean delivery, 255 (50.7%) male children; Mean IG of 34.2 weeks and 385 (76.4%) with low birth weight. 270 (54%) NB with admission to the Intensive Care Unit (ICU) were identified; 284 (58.7%) babies with at least one respiratory diagnosis on admission and 267 (53.3%) were discharged after seven or more days. At discharge, 186 (36.6%) NBs were exclusively breastfed. During the first year of life, 2,899 routine and occasional visits were identified; average of 5.75 consultations for each child. In 1,437 visits, diseases were diagnosed more frequently for diseases of the respiratory tract 803 (55.8%), followed by diseases of the digestive system 141 (9.8%), nutritional and metabolic diseases 73 (5%) and diseases of the ear 72 (5%), respectively. Of the 561 episodes of upper respiratory tract disease (URTD), Upper Airway Infections (UAI) and acute nasopharyngitis (common cold) corresponded to 477 (85%) episodes. Regarding the 242 episodes of respiratory diseases of the lower respiratory tract (LRTD) 105 (29.5%) children were affected with 147 (60.7%) episodes of bronchiolitis, average of 0.43 episodes. In 44 (3.33%) visits, there was a need for hospitalization, three (0.14%) in the ICU. There was a correlation between the number of occasional visits (NOV) and the number of episodes of respiratory diseases. Children with milk formula only at hospital discharge had a higher average number of episodes of respiratory diseases in the first year of life. The mother's age, the respiratory diagnosis at hospital discharge and the NOV showed a significant association with illness from bronchiolitis. URTD were more frequent in this cohort, with an average of 2.16 episodes of respiratory disease per child in the first year of life. NOV was significant for respiratory diseases and breastfeeding was shown to be a protective factor for this outcome. From the analysis of the illness of premature children, the occurrence of bronchiolitis reveals the importance of attending these children in a timely manner to avoid unfavorable outcomes such as hospitalization. It also highlights the importance of screening children with respiratory diagnosis using formula at hospital discharge to guide preventive measures against respiratory diseases

Uso de palivizumab en recién nacidos prematuros / Use of palivizumab in premature newborns

El Palivizumab es una terapia biológica perteneciente a la familia de los anticuerpos monoclonales IgG, indicado para la prevención de enfermedad respiratoria inferior grave causada por el Virus Sincitial Respiratorio (VSR) en neonatos prematuros con factores de riesgo. Los recién nacidos pretérminos (RNPT) se consideran los más susceptibles a dichas enfermedades en comparación con los recién nacidos a términos (RNT) sanos, lo que se traduce en mayores ingresos a Unidades De Cuidados intensivos Neonatales (UCIN), mayores costos hospitalarios y mayor morbi-mortalidad. La profilaxis con Palivizumab según la última actualización de la Academia Americana de Pediatría (AAP) se puede administrar a los recién nacidos ≥ 29 semanas y 0 días de gestación que son menores de 12 meses en el inicio de la temporada del VSR o sean dados de alta durante ella. Para los recién nacidos durante la estación del VSR, se necesitarán al menos 5 dosis. Dada la controversia que existe actualmente en el uso de Palivizumab, por sus altos costos y discrepancias en las indicaciones relacionadas con la edad gestacional decidimos hacer una revisión bibliográfica del uso de Palivizumab en RNPT...(AU)

Clinical Features of Respiratory Syncytial Virus Infection in Neonates: A Single Center Study

PURPOSE: The aim of this study was to investigate the clinical characteristics of Respiratory syncytial virus (RSV) infection during the neonatal period to provide information that is useful in clinical practice and suggest extension of the palivizumab administration. METHODS: Neonates admitted to the National Health Insurance Service Ilsan Hospital neonatal intensive care unit due to respiratory symptoms and for whom multiplex reverse transcription-polymerase chain reaction and multiplex real time-polymerase chain reaction tests were performed between October 2011 and May 2016 were included in this study. Medical records were retrospectively reviewed, and data was collected for 156 neonates. RESULTS: Among the 156 neonates, RSV was detected in 114 (73.1%), non-RSV in 25 (16%), and no virus in 17 (10.9%). The majority were full term infants (92.4%) and peak incidence of RSV infection was in January. Post-natal care center infection was more common in the RSV group (46.6%) than that in the other virus groups (24%, P=0.0243). Clinical symptoms were severe in the RSV group in contrast to that in the non-RSV or others groups. The RSV group frequently needed oxygen therapy (P=0.0001) and the duration of hospital stays were longer (P=0.0001). CONCLUSION: RSV is a significant cause of respiratory infection in neonates and the severity is higher in contrast to that with other viral causes of infection. Infants in post-natal care centers have a high-risk of developing RSV infections; therefore, palivizumab administration may be considered in this group to prevent hospitalization and reduce the duration of hospital stay.

Avaliação do programa de uso da imunoglobulina palivizumabe no Estado de São Paulo, Brasil / Assessment of the program for use of the monoclonal antibody palivizumab in São Paulo State, Brazil / Evaluación del programa de uso de la inmunoglobulina palivizumab en el Estado de São Paulo, Brasil

O objetivo deste estudo foi avaliar o programa de uso da imunoglobulina palivizumabe no Estado de São Paulo, Brasil. Adotou-se o referencial de avaliação proposto por Donabedian, e os dados foram discutidos com base nas recomendações da Portaria que regulamenta o uso da palivizumabe em rede nacional e no Manual de Normas e Procedimentos para Vacinação. Foram incluídos os 16 locais de aplicação do estado, bem como 693 crianças/mães inscritas no programa em 2014 (85,1% da população elegível). Para avaliação da estrutura e processo foram criados escores que permitiram classificar os locais de aplicação em adequado, parcialmente adequado e inadequado, quando havia até 10%, de 11-20% e superior a 20% de desconformidades, respectivamente. Para a avaliação de resultado, buscou-se associação entre falha na tomada da palivizumabe e a necessidade de hospitalização por doença/sintomatologia respiratória, baseando-se em odds ratio pontual e intervalar, com intervalo de 95% de confiança e valor de p crítico < 0,05. Dos 11 postos de aplicação que tiveram estrutura classificada como adequada, apenas dois apresentaram processo adequado, quatro apresentaram processo inadequado e cinco parcialmente adequados. O risco de hospitalização em UTI por doença/sintomatologia respiratória aumentou em média 30% a cada falha (p = 0,003; OR = 1,30; IC95%: 1,09-1,55). Conclui-se que ter estrutura do programa de uso da imunoglobulina no Estado de São Paulo favorável não resultou, necessariamente, em processo adequado. Em geral, a situação da estrutura foi melhor do que a de processo. Mostrou-se relevante a aplicação de todas as doses da imunoglobulina para a prevenção de internação por doença/sintomatologia respiratória.

This study aimed to assess the program for use of the monoclonal antibody palivizumab in São Paulo State, Brazil. The evaluation adopted the frame of reference proposed by Donabedian, and the data were discussed on the basis of the guidelines from the Ruling on the use of palivizumab in the national network and in the Manual on Standards and Procedures for Vaccination. Sixteen application services in the state were included, with 693 children/mothers enrolled in the program in 2014 (85.1% of the eligible population). For the structure and process evaluation, scores were created that allowed classifying the application services as adequate, partially adequate, and inadequate (non-compliance rates were ≤ 10%, 11-20%, and > 20%, respectively). Results were evaluated according to the association between failure to administer palivizumab and need for hospitalization due to respiratory disease/symptoms, based on the point and interval odds ratios, with 95% confidence interval and critical p-value < 0.05. Of the 11 application services whose structure was classified as adequate, only two showed adequate process, four showed inadequate process, and five partially adequate process. Risk of ICU admission due to respiratory disease/symptoms increased on average by 30% for each failure (p = 0.003; OR = 1.30; 95%CI: 1.09-1.55). In conclusion, having a favorable structure for the program for use of palivizumab in São Paulo State did not necessarily result in an adequate process. In general, the situation with the structure was better than the process. All doses of the monoclonal antibody need to be administered in order to prevent hospitalization from respiratory disease/symptoms.

El objetivo de este estudio fue evaluar el programa de uso de la inmunoglobulina palivizumab en el Estado de São Paulo, Brasil. Se adoptó el sistema referencial de evaluación propuesto por Donabedian, donde los datos se discutieron en base a las recomendaciones del decreto que regula el uso del palivizumab en la red nacional y en el Manual de Normas y Procedimientos para la Vacunación. Se incluyeron 16 espacios de aplicación en el estado, así como a 693 niños/madres inscritas en el programa en 2014 (85,1% de la población elegible). Para la evaluación de la estructura y proceso se crearon marcadores que permitieron clasificar los lugares de aplicación como: adecuado, parcialmente adecuado e inadecuado, cuando había hasta un 10%, de 11-20% y superior al 20% de discordancias, respectivamente. Para la evaluación del resultado, se buscó la asociación entre el fallo en la toma del palivizumab y la necesidad de hospitalización por enfermedad/sintomatología respiratoria, basándose en la razón de probabilidades puntual y con intervalos, con un intervalo del 95% de confianza y valor de p crítico < 0,05. De los 11 puestos de aplicación que contaron con una estructura clasificada como adecuada, solamente dos presentaron un proceso adecuado, cuatro presentaron proceso inadecuado y cinco parcialmente adecuados. El riesgo de hospitalización en la UTI por enfermedad/sintomatología respiratoria aumentó de media un 30% con cada fallo (p = 0,003; OR = 1,30; IC95%: 1,09-1,55). Se concluye que contar con una estructura del programa de uso de la inmunoglobulina en el Estado de São Paulo no resultó favorable, necesariamente, en un proceso adecuado. En general, la situación de la estructura fue mejor que la del proceso. Se mostró relevante la aplicación de todas las dosis de inmunoglobulina para la prevención del internamiento por enfermedad/sintomatología respiratoria.

One-year observational study of palivizumab prophylaxis on infants at risk for respiratory syncytial virus infection in Latin America / Estudo observacional de um ano da profilaxia com palivizumabe em neonatos com risco para infecção por vírus sincicial respiratório na América Latina

Abstract Objective: This study aims to describe real world palivizumab use and effectiveness in high-risk Latin American infants and young children. Method: Prospective, multicenter observational study with infants at risk for severe RSV infection who received palivizumab according to routine clinical practice. Subjects were followed for one year with monthly visits after the first dose of palivizumab. An infant was considered adherent if receiving all the expected injections or five or fewer injections within appropriate inter-dose intervals. Annual incidence rates and risk factors of lower respiratory tract infection (LRTI) hospitalization were determined through Poisson regression models (α = 0.05). Results: The study enrolled 458 children from seven countries in Latin America, from February 2011 to September 2012. The majority (98%) were born <36 weeks gestation. Overall, patients received 83.7% of their expected injections and 86.7% completed one year of follow-up. Of the 61 LRTI hospitalizations, 12 episodes were due to RSV infection. The RSV-associated hospitalization rate was 2.9 per 100 patient-years. Bronchopulmonary dysplasia was identified as an independent risk factor for LRTI hospitalization. A total of 1165 adverse events were recorded during one year of follow-up. One hundred and two patients (22.3%) had a total of 135 serious adverse events, but no events were considered to be related to palivizumab. Conclusions: The rate of RSV hospitalization in high-risk infants in Latin America was low and aligned with those observed in randomized control trials and observational studies. Palivizumab prophylaxis appeared effective and had a good safety profile in this population.

Resumo Objetivo: Descrever o uso e a eficácia do palivizumabe no mundo real em neonatos e jovens crianças de alto risco latino-americanas. Método: Estudo observacional prospectivo multicêntrico com neonatos em risco devido a infecção grave por VSR que receberam palivizumabe de acordo com a prática clínica de rotina. Os indivíduos foram acompanhados por um ano, com visitas mensais após a primeira dose de palivizumabe. Um neonato foi considerado adepto se recebeu todas as injeções esperadas ou ≤ 5 injeções nos intervalos entre doses adequados. As taxas de incidência anuais e os fatores de risco de internação por infecção do trato respiratório inferior (ITRI) foram determinados por meio dos modelos de regressão de Poisson (α = 0,05). Resultados: O estudo inscreveu 458 crianças de sete países da América Latina, de fevereiro de 2011 a setembro de 2012. A maioria (98%) nasceu com < 36 semanas. Em geral, os pacientes receberam 83,7% de suas injeções esperadas e 86,7% completaram um ano de acompanhamento. Das 61 internações por ITRI, 12 episódios foram devidos a infecção por VSR. A taxa de internação associada ao VSR foi de 2,9 em cada 100 pacientes-ano. A displasia broncopulmonar foi identificada como um fator de risco independente da internação por ITRI. Foram registrados 1.165 eventos adversos durante um ano de acompanhamento; 122 (22,3%) apresentaram 135 eventos adversos graves, porém nenhum deles foi considerado relacionado ao palivizumabe. Conclusões: A taxa de internação por VSR em neonatos de alto risco na América Latina foi baixa e em linha com as observadas em ensaios clínicos controlados randomizados e estudos observacionais. A profilaxia com palivizumabe pareceu eficaz e com bom perfil de segurança nessa população.

Uso de palivizumab en el control de un brote de VRS en una unidad de cuidado intensivo neonatal / Use of palivizumab in the control of an outbreak of respiratory syncytial virus in a neonatal intensive care unit

El virus respiratorio sincicial (VRS) es una causa importante de morbilidad en pediatría, especialmente en los menores de 2 años. Los grupo de mayor riesgo de presentar una infección grave son los recién nacidos prematuros (RNPrT) menores de 35 semanas de edad gestacional, los pacientes portadores de enfermedad pulmonar crónica y los pacientes portadores de cardiopatías congénitas congestivas. La presencia de un brote de VRS en la unidad de cuidados intensivo neonatal (UCIN) se asocia a resultados desfavorables, incluyendo la muerte. Palivizumab es un anticuerpo monoclonal que se usa para la prevención de la infección por VRS en pacientes de riesgo durante la época epidémica estacional y cuyo uso no está formalmente indicado para el control de brotes. Se describe un brote de VRS en época epidémica en una UCIN y les medidas tomadas para su control. El uso de palivizumab asociado al uso óptimo de medidas de aislamiento para el control de infecciones virales respiratorias pareciera ser altamente efectivo en el control de un brote de VRS en la UCIN.

Respiratory syncytial virus (RSV) infection is the leading cause of morbidity in infants. High risk group presents serious infections, particularly preterm birth. An RSV outbreak occurred in the neonatal intensive care and we described the control measurements taken, including the use of palivizumab

Impact of the use of immunoglobulin palivizumab in the State of São Paulo: a cohort study / Impacto do uso da imunoglobulina palivizumabe no Estado de São Paulo: estudo de coorte / Impacto del uso de la inmunoglobulina palivizumab en el Estado (provincia) de São Paulo: estudio de cohorte

ABSTRACT Introduction: the use of palivizumab as prophylaxis of the respiratory syncytial virus is not a consensus. In Brazil, it is a public health program, but other countries do not consider it cost-effective. Objective: to identify the rate of hospitalization in Intensive Care Unit for respiratory illness or symptoms among children who received the immunoglobulin palivizumab, the proportion of children who failed to take any of the recommended doses and the impact of that failure on hospitalization. Method: cohort study conducted with 693 children enrolled in the palivizumab program in 2014 (85.1% of the population), with monthly assessment from April to September through a telephone call to the mothers or caregiver. The probability of hospitalization in the Intensive Care Unit related to failure in taking the palivizumab, was analyzed through multiple logistic regression, with p<0,05. Results: the hospitalization rate was 18.2%; 2.3% of the children did not receive all the recommended immunoglobulin doses; the probability of hospitalization for respiratory illness or symptoms increased by an average of 29% at each missed dose (p=0.007; OR=1.29, CI=1.07-1.56). Conclusion: the increase in the chance of hospitalization related to missed immunoglobulin doses indicates the need to implement health education actions and active search for absent children by the health services.

RESUMO Introdução: o uso da palivizumabe como profilaxia do vírus sincicial respiratório não é consenso. No Brasil, constitui programa de saúde pública, mas outros países não a consideram custo-efetiva. Objetivo: identificar a taxa de hospitalização em Unidade de Terapia Intensiva por doença ou sintomatologia respiratória entre crianças que receberam imunoglobulina palivizumabe, a proporção de crianças que falharam na tomada de alguma das doses indicadas e o impacto dessa falha na hospitalização. Método: estudo de coorte, incluídas 693 crianças inscritas no programa em 2014 (85,1% da população), com seguimento mensal de abril a setembro, por ligação telefônica às mães/responsáveis. A chance de hospitalização, em Unidade de Terapia Intensiva, em função da falha, foi avaliada por regressão logística múltipla, adotando-se p crítico <0,05. Resultados: a taxa de hospitalização foi de 18,2%; não receberam todas as doses da imunoglobulina 2,3% das crianças; a chance de hospitalização por doença ou sintomatologia respiratória aumentou, em média, 29% a cada falha na tomada de alguma dose (p=0,007; OR=1,29, IC=1,07-1,56). Conclusão: o aumento da chance de hospitalização na vigência de falha na tomada de alguma dose da imunoglobulina indica a necessidade de implementação de ações de educação em saúde e busca ativa de crianças faltosas pelos serviços de saúde.

RESUMEN Introducción: el uso de la palivizumab como profilaxis del virus sincitial respiratorio no es consenso a nivel mundial. En el Brasil, está incluido en el programa de salud pública, pero en otros países no se lo considera costo-efectivo. Objetivo: identificar el porcentaje de hospitalización en Unidades de Terapia Intensiva por enfermedad o sintomatología respiratoria entre niños que recibieron inmunoglobulina palivizumab, determinar la proporción de niños que no tomaron alguna de las dosis indicadas y el impacto de dicha falla en la hospitalización. Método: estudio de cohorte, realizado entre 693 niños inscriptos en el programa en 2014 (85,1% de la población), con seguimiento mensual de abril a septiembre, a través de pláticas telefónicas con las madres/responsables. La probabilidad de hospitalización en una Unidad de Terapia Intensiva, en función de la falla, se evaluó por regresión logística múltiple, adoptando el p crítico <0,05. Resultados: la tasa de hospitalización fue del 18,2%; el 2,3% de los niños no recibió todas las dosis de la inmunoglobulina; la probabilidad de hospitalización por enfermedad o sintomatología respiratoria aumentó en un promedio del 29% a cada falla en la toma de alguna dosis (p = 0,007; OR = 1,29, IC = 1,07-1,56). Conclusión: el aumento de la probabilidad de hospitalización cuando hay falla en la ingestión de alguna dosis de la inmunoglobulina indica la necesidad de implantar acciones educativas en salud y que los servicios de salud se ocupen eficazmente de buscar a los niños faltantes.

Factores de riesgo para infección por Virus Sincicial Respiratorio en Venezuela: Reunión de expertos. Octubre 2013 / Risk factors for Infecction by Respiratory Sincitial Virus in Venezuela: Experts meeting. October 2013

El Virus Sincicial Respiratorio (VSR) es uno de los agentes causales más frecuentes de Infecciones respiratorias en niños menores de 2 años. La forma clínica más frecuente es la bronquiolitis. Dentro de esta población vulnerable son más susceptibles los lactantes que nacieron antes de las 32 semanas de gestación y aquellos portadores de displasia broncopulmonar en tratamiento o cardiopatía congénita cianógena, con insuficiencia cardiaca o hipertensión pulmonar; considerándose también susceptibles los lactantes con anomalías pulmonares, enfermedades neuromusculares, fibrosis quística o inmunosupresión severa. El VSR produce cambios inflamatorios crónicos que implican secuelas a corto, mediano y largo plazo. La prevención ha demostrado ser la mejor medida para reducir las complicaciones y costos de la enfermedad y, en este sentido, la profilaxis con Palivizumab es efectiva en los lactantes de riesgo para infección severa por VSR. El siguiente artículo tiene como finalidad establecer los criterios para la profilaxis con Palivizumab.

Respiratory syncytial virus (RSV) is one of the most common causative agents of respiratory infections in children under 2 years of age. The most common clinical form is bronchiolitis. Within this vulnerable population, infants born before 32 weeks gestation and those with bronchopulmonary dysplasia or with cyanotic congenital heart disease, heart failure or pulmonary hypertension are more susceptible; infants with lung anomalies, neuromuscular diseases, cystic fibrosis or severe immunosuppression are also at risk. RSV causes chronic inflammatory changes that lead to short, medium and long term sequelae. Prevention has proven to be the best measure to reduce complications and costs and palivizumab prophylaxis has been effective in infants at risk. The following article aims to review the risk factors involved in infection by respiratory syncytial virus and establish the criteria for prophylaxis with palivizumab.

Respiratory syncytial virus seasonality in Brazil: implications for the immunisation policy for at-risk populations

Respiratory syncytial virus (RSV) infection is the leading cause of hospitalisation for respiratory diseases among children under 5 years old. The aim of this study was to analyse RSV seasonality in the five distinct regions of Brazil using time series analysis (wavelet and Fourier series) of the following indicators: monthly positivity of the immunofluorescence reaction for RSV identified by virologic surveillance system, and rate of hospitalisations per bronchiolitis and pneumonia due to RSV in children under 5 years old (codes CID-10 J12.1, J20.5, J21.0 and J21.9). A total of 12,501 samples with 11.6% positivity for RSV (95% confidence interval 11 - 12.2), varying between 7.1 and 21.4% in the five Brazilian regions, was analysed. A strong trend for annual cycles with a stable stationary pattern in the five regions was identified through wavelet analysis of the indicators. The timing of RSV activity by Fourier analysis was similar between the two indicators analysed and showed regional differences. This study reinforces the importance of adjusting the immunisation period for high risk population with the monoclonal antibody palivizumab taking into account regional differences in seasonality of RSV.

Actualización en displasia broncopulmonar / Bronchopulmonary displasia update

Bronchopulmonary dysplasia is one of the most common pediatric chronic lung diseases. In the recent decades the advances made in perinatal care and the increase survival of extreme preterm have shown an overall change in the characteristics of this disease giving rise to the concept of new dysplasia. In the development of the disease is essential the exposure of the immature lung to various factors such as nutritional deficiency, pre and post-natal infections, persistent ductus arteriosus, and genetic susceptibility. This article reviews the most important characteristics of this disease, treatment and follow-up.

La displasia broncopulmonar (DBP) es una de las enfermedades pulmonares crónicas frecuentes en pediatría. Los avances experimentados en las últimas décadas en cuidados perinatales y la sobrevida de prematuros cada vez más extremos han demostrado un cambio global en las características de esta enfermedad dando lugar al concepto de nueva displasia, en cuyo desarrollo son fundamentales la exposición del pulmón inmaduro a diversos factores como deficiencia nutricional, infecciones pre y post-natales, ductus arterioso persistente, y susceptibilidad genética. El presente articulo revisa las características más relevantes de esta patología, su enfrentamiento global, manejo y seguimiento ambulatorio.

Prevenção de Infecções pelo Vírus Sincicial Respiratório (VSR): uso do palivizumabe / Respiratory Syncytial Vírus (RSV) infection prevention: palivizumab use

Introdução: o vírus sincicial respiratório (VSR) pode causar quadros graves de bronquiolites e pneumonias, principalmente em grupos de risco como prematuros, cardiopatas e portadores de pneumopatias. O palivizumabe (PVZ) trouxe grande avanço na prevenção dessa doença e, devido ao alto custo, a Secretaria de Estado da Saúde de Minas Gerais (SES-MG) disponibiliza o produto aos grupos de alto risco. Objetivo: orientar os pediatras quanto à prevenção da infecção pelo VSR com orientações práticas sobre a prescrição do PVZ em MG. Métodos: são apresentados os critérios de inclusão para o uso dessa medicação em MG segundo portaria do Ministério da Saúde de 2013, como também os procedimentos adequados para a prescrição e fornecimento segundo normas da SES-MG. Resultados e conclusões: o conhecimento sobre o uso do PVZ para a prevenção do VSR e dos fluxos adequados para a prescrição e aplicação dessa medicação é fundamental para a prevenção da bronquiolite, portanto, deve ser amplamente divulgado entre os pediatras. Dessa forma, poderá ocorrer a redução dos casos graves, diminuindo a prevalência de sequelas e óbitos por essa doença.(AU)

Introduction: Respiratory Syncytial Vírus (RSV) can cause severe cases of bronchiolitis and pneumonia especially in risk groups such as premature neonates, cardiac patients and children with lung disease. Palivizumab (PVZ) has been successfully used in the prevention of this disease and due to the high cost, the Health's Secretary of Minas Gerais (SESMG) provides the product to high-risk groups. Objective: guide pediatricians regarding the prevention of RSV infection with practical guidelines for the prescription of PVZ in MG. Methods: Here are the inclusion criteria for the application of this medication in MG following the guidelines of the Ministry of Health in 2013, as well as the proper procedures for the prescription and supply according to standards of SES-MG. Results and Conclusions: Knowledge about the use of PVZ for the prevention of RSV and about the guidelines for prescription and application of this medication are key to the prevention of bronchiolitis, therefore should be widely disseminated to pediatricians. Thus may occur the reduction of severe cases decreasing the prevalence of sequelae and deaths from this disease.(AU)

Retrospective Multicenter Study of Respiratory Syncytial Virus Prophylaxis in Korean Children with Congenital Heart Diseases

BACKGROUND AND OBJECTIVES: We conducted a review of current data on respiratory syncytial virus (RSV) prophylaxis with palivizumab, in Korean children with congenital heart diseases (CHD). In 2009, the Korean guideline for RSV prophylaxis had established up to five shots monthly per RSV season, only for children <1 year of age with hemodynamic significance CHD (HS-CHD). SUBJECTS AND METHODS: During the RSV seasons in 2009-2015, we performed a retrospective review of data for 466 infants with CHD, examined at six centers in Korea. RESULTS: Infants received an average of 3.7±1.9 (range, 1-10) injections during the RSV season. Fifty-seven HS-CHD patients (12.2%) were hospitalized with breakthrough RSV bronchiolitis, with a recurrence in three patients, one year after the initial check-up. Among patients with simple CHD, only five (1.1%) patients received one additional dose postoperatively, as per the limitations set by the Korean guideline. Among the 30 deaths (6.4%), five (1.1%) were attributed to RSV infection; three to simple CHD, one to Tetralogy of Fallot, and one to hypertrophic cardiomyopathy (HCM). Of the three HCM patients that exceeded guidelines for RSV prophylaxis, two (66.6%) were hospitalized, and one died of RSV infection (33.3%). CONCLUSION: In accordance to the Korean guideline, minimal injections of palivizumab were administered to patients having HS-CHD

Respiratory Syncytial Virus Related Readmission in Preterm Infants Less than 34 weeks' Gestation Following Discharge from a Neonatal Intensive Care Unit in Korea

This study was done to evaluate respiratory syncytial virus (RSV) related readmission (RRR) and risk factors of RRR in preterm infants 1 yr after discharge from the NICU, were enrolled. The average GA and birth weight of the infants was 30(+5) +/- 2(+5) weeks and 1,502 +/- 474 g, respectively. The RRR rate of enrolled infants was 8.4% (96/1,140), and RSV accounted for 58.2% of respiratory readmissions of infants who had laboratory tests confirming etiological viruses. Living with elder siblings (odd ratio [OR], 2.68; 95% confidence interval [CI], 1.68-4.28; P < 0.001), and bronchopulmonary dysplasia (BPD) (OR, 2.95; 95% CI, 1.44-6.04; P = 0.003, BPD vs. none) increased the risk of RRR. Palivizumab prophylaxis (OR, 0.06; 95% CI, 0.03-0.13; P < 0.001) decreased the risk of RRR. The risk of RRR of infants of 32-33 weeks' gestation was lower than that of infants < 26 weeks' gestation (OR, 0.11; 95% CI, 0.02-0.53; P = 0.006). This was a nationwide study that evaluated the rate and associated risk factors of RRR in Korean preterm infants. Preterm infants with BPD or living with siblings should be supervised, and administration of palivizumab to prevent RRR should be considered.

Evaluation of Timeliness of Palivizumab Immunoprophylaxis Based on the Epidemic Period of Respiratory Syncytial Virus: 22 Year Experience in a Single Center

PURPOSE: This study aimed to analyze the epidemic period of RSV infection and evaluate the appropriate time of palivizumab immunoprophylaxis. METHODS: From January 1991 to July 2012, nasopharyngeal (NP) aspirates were obtained from patients who visited Seoul National University Children's Hospital for respiratory symptoms. NP samples were used to detect respiratory viruses. Among them, we analyzed the positive number and detection rate of RSV infection in two-week interval. The beginning of RSV season was defined when RSV positive number was more than 4 and RSV detection rate was over 10%. From January 2007 to March 2014, we analyzed the starting time of palivizumab immunoprophylaxis for the infants at high risk. RESULTS: The RSV detection rate was 2,013/21,698 (9.69%) over 22 years. The median RSV season was from 2nd-3rd week of October to 1st- 2nd week of February. The earliest starting week was the 3rd week of July in year 2001, and the latest end week was the 3rd week of May in year 1990. Palivizumab immunoprophylaxis was initiated most frequently at the 3rd week of October (18.7%). However, the percentage of starting palivizumab on the 1st week of September has increased from 3.8% in the year 2007 to 14.1% in 2013. CONCLUSIONS: The year to year variability of RSV season exists. The starting time of palivizumab immunoprophylaxis should be adjusted based on the season of RSV epidemic.

Effect of Prophylactic Palivizumab on Admission Due to Respiratory Syncytial Virus Infection in Former Very Low Birth Weight Infants with Bronchopulmonary Dysplasia

The aim of this study was to observe the effects of prophylactic palivizumab on hospitalization secondary to respiratory syncytial virus (RSV) infection (RSVhospitalization) in former very low birth weight infants (VLBWI) with bronchopulmonary dysplasia (BPD). This study also sought to identify the risk factors of RSVhospitalizationin this particular infant population. A prospective observational study was conducted between September 2007 and April 2008 in seven Korean hospitals. Children with a history of very low birth weight, a diagnosis of BPD and who were <2 yr old at the onset of the RSV season were included in this study. Palivizumab injections were administered monthly for a maximum of five months during the RSV season. RSVhospitalization rates were reviewed, and RSVhospitalization rates between subgroups were categorized by gestational age, birth weight, and duration of ventilator care. A total of 90 subjects completed the follow-up interviews. The mean gestational age at birth was 26.1+/-1.7 weeks, and the mean birth weight was 889.4+/-222.2 g. The incidence of RSVhospitalization in the study population was 8.9% (8/90), and the mean hospital stay was 11.0+/-5.5 days, including one death. There were no statistically significant differences in the patients' demographic characteristics or risk factors for RSV hospitalization. When subgroup analyses were conducted, there were still no statistically significant differences. The administration of palivizumab prophylaxis during the entire RSV season is important in VLBWI with BPD, regardless of their gestational age and birth weight, or previous ventilator dependency.