Use of budesonide associated with a pulmonary surfactant to prevent bronchopulmonary dysplasia in premature newborns - A systematic review

Abstract Objective: Among the mechanisms proposed for the development of bronchopulmonary dysplasia is the increase in the pulmonary inflammatory process and oxidative stress. Thus, the control of this process may result in improvements in bronchopulmonary dysplasia-related outcomes. This study aims to analyze the current scientific evidence regarding the use of budesonide, a potent anti-inflammatory drug, associated with a pulmonary surfactant to prevent bronchopulmonary dysplasia. Methods: A systematic review of the literature was performed on the Embase and MEDLINE platforms, and studies that compared budesonide with pulmonary surfactant versus pulmonary surfactant for treating respiratory distress syndrome were included. The primary outcome was a reduction in bronchopulmonary dysplasia or death. Results: Four randomized clinical trials and two observational studies were included in this systematic review. Three of the randomized clinical trials found a reduction in bronchopulmonary dysplasia or death in the use of budesonide with the surfactant, all the other studies (1 clinical trial and 2 observational studies) found no statistical differences between the groups for the primary outcomes. The three main studies showed a reduction in the primary outcome; however, all studies showed great heterogeneity regarding the type of surfactant (poractant or beractant) and the method of administration. Conclusion: Robust clinical studies, in a heterogeneous population, using porcine surfactant associated with budesonide, with administration by a minimally invasive technique are necessary for there to be a recommendation based on scientific evidence for its widespread use.

Fisiología respiratoria: fisiología del surfactante pulmonar / Physiology of pulmonary surfactant

El proceso de respiración y el intercambio gaseoso requiere la interacción de variadas fuerzas en los distintos tejidos y órganos involucrados. La tensión superficial a nivel alveolar provocaría colapso de dichas estructuras de no ser por las características del surfactante que lo recubre. Revisaremos en este articulo la fisiología involucrada en su estructura física, producción y efectos pulmonares.

The process of breathing and gas exchange requires the interaction of various forces in the different tissues and organs involved. The surface tension at the alveolus would cause collapse of these structures without of the surfactant that covers it. We will review in this article the physiology involved in its physical structure, production, and pulmonary effects.

Expectant Versus Interventionist Care in the Management of Severe Preeclampsia Remote from Term: A Systematic Review / Cuidado expectante versus cuidado intervencionista no tratamento da pré-eclâmpsia grave a distância: uma revisão sistemática

Abstract Objective To compare the effects of expectant versus interventionist care in the management of pregnant women with severe preeclampsia remote from term. Data sources An electronic search was conducted in the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), Cochrane Central Register of Controlled Trials (CENTRAL), Latin American and Caribbean Health Sciences Literature (LILACS, for its Spanish acronym), World Health Organization's International Clinical Trials Registry Platform (WHO-ICTRP), and Open- Grey databases. The International Federation of Gynecology and Obstetrics (FIGO, for its French acronym), Royal College of Obstetricians and Gynaecologists (RCOG), American College of Obstetricians and Gynecologists (ACOG), and Colombian Journal of Obstetrics and Gynecology (CJOG) websites were searched for conference proceedings, without language restrictions, up to March 25, 2020. Selection of studies Randomized clinical trials (RCTs), and non-randomized controlled studies (NRSs) were included. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to evaluate the quality of the evidence. Data collection Studies were independently assessed for inclusion criteria, data extraction, and risk of bias. Disagreements were resolved by consensus. Data synthesis Four RCTs and six NRS were included. Low-quality evidence from the RCTs showed that expectant care may result in a lower incidence of appearance, pulse, grimace, activity, and respiration (Apgar) scores<7 at 5 minutes (risk ratio [RR]: 0.48; 95% confidence interval [95%CI]: 0.23%to 0.99) and a higher average birth weight (mean difference [MD]: 254.7 g; 95%CI: 98.5 g to 410.9 g). Very low quality evidence from the NRSs suggested that expectant care might decrease the rates of neonatal death (RR: 0.42; 95%CI 0.22 to 0.80), hyalinemembrane disease (RR: 0.59; 95%CI: 0.40 to 0.87), and admission to neonatal care (RR: 0.73; 95%CI: 0.54 to 0.99). Nomaternal or fetal differences were found for other perinatal outcomes. Conclusion Compared with interventionist management, expectant care may improve neonatal outcomes without increasing maternal morbidity and mortality.

Resumo Objetivo Comparar os efeitos dos cuidados expectantes versus intervencionistas no manejo de gestantes com pré-eclâmpsia grave distante do termo. Fontes de dados Foi realizada uma busca eletrônica no Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), Cochrane Central Register of Controlled Trials (CENTRAL), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS, para o espanhol) acrônimo), Plataforma Internacional de Registro de Ensaios Clínicos da Organização Mundial da Saúde (OMS-ICTRP) e bancos de dados OpenGrey. Foram pesquisados os sites da Federação Internacional de Ginecologia e Obstetrícia (FIGO, por sua sigla em francês), do Royal College of Obstetricians e Ginecologistas (RCOG), do American College of Obstetricians e Ginecologistas (ACOG) e do Colombian Journal of Obstetrics and Gynecology (CJOG) procedimentos da conferência, sem restrições de idioma, até 25 de março de 2020. Seleção de estudos Ensaios clínicos randomizados (RCTs) e estudos controlados não randomizados (NRSs) foram incluídos. A abordagem de Classificação de Recomendações, Avaliação, Desenvolvimento e Avaliação (GRADE) foi usada para avaliar a qualidade da evidência. Coleta de dados Os estudos foram avaliados de forma independente quanto aos critérios de inclusão, extração de dados e risco de viés. As discordâncias foram resolvidas por consenso. Síntese de dados Quatro RCTs e seis NRS foram incluídos. Evidências de baixa qualidade dos ECRs mostraram que o cuidado expectante pode resultar em uma incidência menor de pontuações de aparência, pulso, careta, atividade e respiração (Apgar) <7 em 5 minutos (razão de risco [RR]: 0,48; intervalo de confiança de 95% [IC 95%]: 0,23% a 0,99) e um peso médio ao nascer superior (diferença média [MD]: 254,7 g; IC 95%: 98,5 ga 410,9 g). Evidências de qualidade muito baixa dos NRSs sugeriram que os cuidados expectantes podem diminuir as taxas de morte neonatal (RR: 0,42; IC de 95% 0,22 a 0,80), doença da membrana hialina (RR: 0,59; IC de 95%: 0,40 a 0,87) e admissão à assistência neonatal (RR: 0,73; IC 95%: 0,54 a 0,99). Nenhuma diferença materna ou fetal foi encontrada para outros resultados perinatais. Conclusão Em comparação com o manejo intervencionista, o cuidado expectante pode melhorar os resultados neonatais sem aumentar a morbidade e mortalidade materna.

Hallazgos de autopsias en la infección por COVID-19 / Autopsy findings in COVID-19 Infection

RESUMEN Fundamento: la neumonía por COVID-19 es una enfermedad recién conocida que se ha extendido de manera rápida por todo el mundo. Los fundamentos patogénicos y los cambios histopatológicos que provoca el COVID-19 no se comprenden en su totalidad, lo cual atenta contra la identificación clínica adecuada de los pacientes y la implementación de estrategias terapéuticos eficaces. Objetivo: describir los hallazgos histopatológicos hallados en autopsia de casos confirmados de COVID-19. Métodos: la evidencia se recopiló mediante una búsqueda en PubMed de publicaciones en idioma inglés, utilizando las palabras claves: coronavirus, COVID-19, autopsy y síndrome de dificultad respiratoria aguda en varias combinaciones en el año 2020. Solo se hallaron cinco artículos con información sobre los resultados de las autopsias de casos confirmados con COVID-19. Resultados: desde el inicio de la pandemia en diciembre de 2019 se han publicado siete informes de autopsias de casos confirmados con COVID-19, recogidos en cuatro artículos. Todas las autopsias han coincidido en el principal hallazgo: daño alveolar difuso con formación de membrana hialina, lo cual se correlaciona con las manifestaciones clínicas del síndrome de dificultad respiratoria aguda. Conclusiones: el COVID-19 produce principalmente daño alveolar, el cual consiste en edema pulmonar con formación de membrana hialina que se expresa clínicamente como un síndrome de dificultad respiratoria aguda.

ABSTRACT Background: COVID-19 pneumonia is a recently recognized disease that has spread rapidly throughout the world. The pathogenic foundations and histopathological changes caused by COVID-19 are not fully understood, which undermines the proper clinical identification of patients and the implementation of effective therapeutic strategies. Objective: to describe the histopathological findings found at autopsy of confirmed cases of COVID-19. Methods: evidence was collected by searching PubMed for English language publications, using the keywords: coronavirus, COVID-19, autopsy and acute respiratory distress syndrome in various combinations in 2020. Only five articles were found with information on the autopsy results of confirmed cases with COVID-19. Results: since the start of the pandemic in December 2019, seven autopsy reports of confirmed cases with COVID-19 have been published, collected in 4 articles. All autopsies have agreed on the main finding: diffuse alveolar damage with hyaline membrane formation, which correlates with the clinical manifestations of acute respiratory distress syndrome. Conclusions: COVID-19 mainly produces alveolar damage, which consists of pulmonary edema with hyaline membrane formation, which is clinically expressed as an acute respiratory distress syndrome.

Uso convencional de surfactante en recién nacidos con enfermedad de membrana hialina / Conventional use of surfactant in newborns with hyaline membrane disease

La enfermedad de membrana hialina se debe a la deficiencia de surfactante en los pulmones de los recién nacidos especialmente los menores de 37 semanas de gestación. El manejo materno con corticoides prenatales en este grupo, disminuye la morbimortalidad asociada a esta patología neonatal. Se analiza desde el punto de la evidencia actualmente existente la administración de surfactante a estos prematuros y se revisa el tipo de surfactante a administrar, cuando es el mejor momento para administrarlo, la dosis y la forma de administrarlo.

Hyaline membrane disease is due to surfactant deficiency in the lungs of newborns, especially those younger than 37 weeks gestation. Maternal management with prenatal corticosteroids in this group reduces the morbidity and mortality associated with this neonatal pathology. The administration of surfactant to these preterm infants is analyzed from the point of the currently existing evidence and the type of surfactant to be administered is reviewed, when is the best time to administer it, the dose and the form of administration.

A clinical study of respiratory distress in neonates

Background: Respiratory distress is a medical emergency responsible for most of the admissions in NICUs during neonatal period. It is a major contributor to neonatal morbidity and mortality and results from a variety of respiratory and non-respiratory etiology. It occurs in 0.96 to 12% of live births and responsible for about 20% of neonatal mortality. Aim of study to find out the proportion of patients with different etiology of respiratory distress in neonates.Methods: The present study is a prospective, descriptive study which was carried out at neonatal units attached to SMS Medical College, Jaipur. All the neonates with respiratory distress admitted in NICU admitted from April 2012 to March 2013were selected for the present study. Detailed history including antenatal history, natal history, postnatal history with thorough clinical examinations and investigations done in each case and were recorded in the performa.Results: A total of 500 neonates were admitted and among them 375 were inborn (delivered in our hospitals) and 125 out-born (referred to our hospitals from outside). In inborn group hyaline membrane disease (HMD) was the most common cause (32%) of respiratory distress and in out-born congenital pneumonia/septicaemia (34.4%). There was male preponderance in both inborn and out-born groups with male: female ratio 1.45:1 and 1.6:1 respectively.Conclusions: Majority of cases in both inborn and out-born groups were preterm (56.8% and 54.4% respectively) which emphasises the need for care of mother during antenatal period for prevention of premature delivery.

Rapid diagnosis of respiratory distress syndrome by oral aspirate in premature newborns / Diagnóstico rápido da síndrome do desconforto respiratório por aspirado bucal em recém-nascidos prematuros

Abstract Objective: The stable microbubble test on gastric aspirate and on amniotic fluid has been used for the diagnosis of respiratory distress syndrome in the newborn. However, no study has performed this test on oral aspirates from premature infants. The objective of this study was to evaluate the performance of the stable microbubble test on oral aspirates from preterm newborns to predict respiratory distress syndrome. Method: This study included infants with gestational age <34 weeks. Oral fluids were obtained immediately after birth and gastric fluids were collected within the first 30 minutes of life. The samples were frozen and tested within 72 hours. Results: The sample was composed of paired aspirates from 64 newborns, who were divided into two groups: respiratory distress syndrome group (n = 21) and control group (n = 43). The median (interquartile range) of the stable microbubble count in the oral samples of infants with respiratory distress syndrome was significantly lower than that of infants who did not develop respiratory symptoms: respiratory distress syndrome group = 12 (8 -22) stable microbubbles/mm2; control group = 100 (48 -230) microbubbles/mm2 (p < 0.001). The correlation between microbubble count in gastric and oral aspirates was 0.90 (95% confidence interval = 0.85 -0.95; p < 0.001). Considering a cut-off point of 25 microbubbles/mm2, the sensitivity and the specificity of the stable microbubble test were 81.4% and 85.7%, respectively. Conclusion: The study suggests that the stable microbubble test performed on oral aspirate is a reliable alternative to that performed on gastric fluid for the prediction of respiratory distress syndrome in the newborn.

Resumo Objetivo: O teste das microbolhas estáveis no aspirado gástrico e no líquido amniótico foi usado no diagnóstico da síndrome do desconforto respiratório do recém-nascido. Contudo, nenhum estudo fez esse teste nos aspirados bucais de neonatos prematuros. O objetivo deste estudo foi avaliar o desempenho do teste das microbolhas estáveis em aspirados bucais de recém-nascidos prematuros para prever síndrome do desconforto respiratório. Método: Este estudo incluiu neonatos com idade gestacional < 34 semanas. Os fluidos orais foram obtidos imediatamente após o nascimento e os fluidos gástricos foram coletados nos primeiros 30 minutos de vida. As amostras foram congeladas e testadas em 72 horas. Resultados: A amostra foi composta de aspirados pareados de 64 recém-nascidos, divididos em dois grupos: grupo de síndrome do desconforto respiratório (n = 21) e grupo de controle (n = 43). A mediana (intervalo interquartil) da contagem das microbolhas estáveis nas amostras de fluido oral dos neonatos com síndrome do desconforto respiratório foi significativamente menor que a dos neonatos que não desenvolveram sintomas respiratórios: grupo de síndrome do desconforto respiratório = 12 (8-22) microbolhas estáveis/mm2; grupo de controle = 100 (48-230) microbolhas/mm2 (p < 0,001). A correlação entre a contagem das microbolhas nos aspirados gástricos e bucais foi 0,90 (intervalo de confiança de 95% = 0,85-0,95; p < 0,001). Considerando um ponto de corte de 25 microbolhas/mm2, a sensibilidade e a especificidade do teste das microbolhas estáveis foram 81,4% e 85,7%, respectivamente. Conclusão: O estudo sugere que o teste das microbolhas estáveis feito no aspirado bucal é uma opção confiável ao fluido gástrico para a predição da síndrome do desconforto respiratório do recém-nascido.

Betametasona fosfato para la prevención de Síndrome de Dificultad Respiratoria (SDR) del recién nacido de pretérmino / Betamethasone phosphate for the prevention of Respiratory Distress Syndrome (RDS) in the preterm newborn

RESUMEN Introducción: El estándar para inducción de madurez pulmonar en fetos con riesgo de nacer prematuramente es la administración de 12 mg de betametasona acetato/fosfato por dos veces espaciada cada 24 horas. El uso establecido en algunos hospitales públicos en Chile es con dos dosis de 12 mg betametasona fosfato aunque no existen estudios publicados sólo con betametasona fosfato sobre la incidencia de Síndrome de Distress Respiratorio (SDR). Objetivo: Evaluar efecto de betametasona en su forma fosfato como tratamiento antenatal para inducción de madurez fetal pulmonar en la incidencia SDR debido a membrana hialina en prematuros menores de 34 semanas de edad gestacional. Comparar el efecto de betametasona fosfato con el efecto publicado de betametasona acetato/fosfato. Material y método: Análisis de incidencia de SDR en prematuros nacidos en Hospital Padre Hurtado entre 24+0 y 34+0 semanas que recibieron betametasona fosfato para madurez pulmonar y aquellos que no la recibieron. Resultados: De 1.265 neonatos estudiados, 722 completaron dos dosis (57,5%); 436 sólo una dosis (34,5%) y 107 (8,5%) no recibieron corticoides antenatales. La incidencia de SDR debido a membrana hialina en el grupo con dos dosis fue 8,7%, una dosis 25,3% y 32,7% en los no tratados (p<0,001). Para SDR severo las incidencias fueron 6,7%, 12,6% y 16,8% respectivamente (p<0,001). Conclusiones: Inducción de madurez fetal pulmonar con betametasona fosfato en dos dosis de 12 mg IM separadas por 24 horas otorga una reducción significativa de incidencia de SDR semejante a la publicada con betametasona acetato/fosfato en iguales dosis.

ABSTRACT The standard for induction of lung maturity in fetuses at risk of being born prematurely is the administration of 12 mg of betamethasone acetate/phosphate two doses separated by 24 hours. The established use in some public hospitals in Chile is with two doses of 12 mg betamethasone phosphate although there are no studies published with betamethasone phosphate alone on the incidence of respiratory distress syndrome (RDS). Objective: To evaluate the effect of betamethasone in its phosphate form as antenatal treatment for the induction of fetal lung maturity in the incidence of RDS due to hyaline membrane in preterm infants less than 34 weeks of gestational age. To compare the effect of betamethasone phosphate with the published effect of betamethasone acetate/phosphate. Material and method: Analysis of the incidence of RDS in preterm infants born at Hospital Padre Hurtado between 24 + 0 and 34 + 0 weeks who received betamethasone phosphate for lung maturity and those who did not receive it. Results: Of 1,265 infants studied, 722 completed two doses (57.5%); 436 only one dose (34.5%) and 107 (8.5%) did not receive antenatal corticosteroids. The incidence of RDS due to hyaline membrane in the group with two doses was 8.7%, one dose 25.3% and 32.7% in the untreated ones (p <0.001). For severe RDS, incidences were 6.7%, 12.6% and 16.8% respectively (p <0.001). Conclusions: Induction of fetal lung maturity with betamethasone phosphate in two doses of 12 mg IM separated by 24 hours gives a significant reduction in the incidence of RDS similar to that published with betamethasone acetate/phosphate in equal doses.

Analysis on mortality among moderate to late preterm infants born in Lempira province, the Republic of Honduras, from January 2015 to June 2017 / 国際保健医療

Objective  Preterm birth is the major cause for neonatal deaths in low and middle income countries. The aim of this report is to evaluate the proportions of deaths of moderate to late preterm infants born at 32 to 36 weeks of gestations as well as the neonates with low birth weights weighing from 1500g to 2499g among the total neonatal deaths and analyze their causes of deaths in Lempira province, the Republic of Honduras. Study design  A secondary analysis based on the data sets from the regional office of Ministry of Health.Methods  We obtained data sets on infant mortality from January 2015 to June 2017 compiled by a regional office of Ministry of Health in Lempira province. We then calculated proportions of each cause of death in the groups of newborn infants stratified by gestational weeks and birth weights.Results  During the study period, a total of 253 neonatal deaths were recorded, comprising 66.9% of the total infant deaths (n=378). The number of the newborn infants who died during early neonatal period was 201 (79.4%). The number of preterm newborn infants who died during neonatal period was 146 (57.7%) and 70 (27.6%) were born at moderate to late preterm periods. 103 (40.7%) were born with their birth-weights below 2500g, and the number of those weighing from 1500g to 2499g were 61 (24.1%). The leading cause of deaths of moderate to late preterm infants was hyaline membrane disease (n=25/48: 52.1%), as was the case with low birth weight infants weighing from 1500g to 2499g. Conclusion  It was shown that approximately one fourths of neonatal deaths occurred in moderate to late preterm infants in Lempira province during the study period. Approximately half of these preterm infants died of hyaline membrane disease, who could have been saved with simple and low-cost equipment such as bubble continuous positive airway pressure.

Restricción de crecimiento aumenta el riesgo de displasia broncopulmonar, muerte y sepsis en gemelos de 30 o menos semanas de gestación / Growth restriction increases the risk of bronchopulmonary dysplasia, death, and sepsis in twins of 30 weeks or less of gestation

INTRODUCCIÓN: Múltiples factores influyen en el riesgo de morbimortalidad del prematuro con restricción del crecimiento intrauterino (RCIU). La comparación de gemelos con crecimiento intrauterino discordante permite evaluar su efecto, excluyendo factores maternos y manejo prenatal. Nuestro objetivo fue evaluar el efecto de la RCIU sobre la morbilidad aguda, crónica y mortalidad, en parejas de recién nacidos gemelares prematuros extremos. PACIENTES Y MÉTODO: Gemelos menores de 1500 g y 30 semanas de gestación, de la Red Neocosur. Se realizaron análisis separados de pares de gemelos concordantes, discordantes leves y severos, evaluando el efecto de la RCIU sobre morbi-mortalidad. Se realizó análisis multivariado para establecer magnitud del efecto. RESULTADOS: 459 pares de gemelos, 227 concordantes, 110 discordantes leves y 122 severos. Entre los concordantes solo hubo diferencia en uso de oxígeno a las 36 semanas. En discordantes leves, el menor tuvo menos enfermedad de membrana hialina y requirió menos dosis de surfactante, pero tuvo un mayor riesgo de Displasia broncopulmonar (DBP) o muerte. En discordantes severos, el menor presentó mayor mortalidad, sepsis, utilización y permanencia en ventilación mecánica, pese a menor frecuencia de enfermedad de membrana hialina. En regresión múltiple, el riesgo combinado de DBP o muerte fue mayor en gemelo menor y discordante severo. CONCLUSIÓN: En gemelos discordantes, la patología respiratoria aguda fue más frecuente en el gemelo mayor, aunque el riesgo de DBP o muerte fue mayor en el gemelo con RCIU.

INTRODUCTION: Multiple factors influence the risk of morbidity and mortality of premature infants with intrauterine growth restriction (IUGR). The comparison of twins with different intrauterine growth allows evaluating the effect of the restriction, excluding maternal factors and prenatal mana gement. Our objective was to assess the effect of IUGR on acute and chronic morbidity, and mortality of extreme preterm twins. PATIENTS AND METHOD: Twins weighing less than 1500 grams and gesta tion equal to or less than 30 weeks, of the Neocosur Network. Separate analyses were performed on concordant twin pairs, and on mild and severe discordant twins, evaluating the effect of IUGR on morbidity and mortality. A multivariate analysis was performed in order to establish the impact of this effect. RESULTS: 459 twin pairs, 227 concordant twins, 110 of mild discordance, and 122 of severe discordance. Among the concordant ones, there was only a difference in oxygen uptake at 36 weeks. In those of mild discordance, the smaller twin presented a lower frequency of hyaline membrane disease and required fewer doses of surfactant, but had a higher risk of bronchopulmonary dysplasia (BPD) or death. In severe discordant twins, the smaller one presented higher mortality, sepsis, use and permanence in mechanical ventilation, despite the lower frequency of hyaline membrane disease. In multiple regression analysis, the combined risk of BPD or death was higher in the smaller twin and of severe discordance. CONCLUSION: In discordant twins, the acute respiratory pathology was more frequent in the larger one, although the risk of BPD or death was higher in the one with IUGR.

A study of spectrum of pulmonary pathology and expression of thyroid transcription factor-1 during neonatal period

Context: Neonatal period is the single most hazardous period of life. The major causes of neonatal death are prematurity and respiratory distress syndrome. We report a series of neonatal autopsies in our Neonatal Intensive Care Unit with special emphasis on pulmonary pathology. The spectrum of pathological changes in the lungs and thyroid transcription factor-1 (TTF-1) expression was studied in detail with reference to its spatial distribution. Aims: This study aims to analyze the causes of neonatal death with special attention to pulmonary pathology along with associated histopathological changes in lungs. We also evaluated the expression of TTF-1 at different levels of the airway. Materials and Methods: After taking consent and anthropometric measurements, autopsy was performed. Weights of all organs were taken, and histological sections were examined under hematoxylin and eosin stain. TTF-1 immunostaining was done on lung sections. Localization of TTF-1 was evaluated at the intrapulmonary level of terminal bronchioles (TBs), distal bronchioles, and alveoli. Results: We performed a series of 25 autopsies in neonates. In our series, most of the neonates were preterm (64%), had low birth weight (44%), and died within the first 7 days of life (80%). Majority (60%) of the neonates died due to pulmonary causes, followed by septicemia (24%), congenital anomalies (12%), and birth injury (4%). Among the respiratory causes, hyaline membrane disease (HMD) was diagnosed in maximum number of cases (32%), followed by pneumonia (12%) and pulmonary hemorrhage (12%). The TTF-1 expression in TBs, distal airways, and alveoli was significantly reduced or absent in cases of HMD compared to the control group. Conclusions: In this study, we observed that HMD is the most common cause of perinatal death among respiratory disorders, and in this disease, the expression of TTF-1 is significantly reduced in TBs, distal airways, and alveoli compared to the control group.

Investigation of the value of stable micro bubble test for early diagnosis of hyaline membrane disease in premature infants / 天津医药

Objective To explore the value of stable micro bubble test (SMT) for early diagnosis of hyaline membrane disease (HMD), and to provide early intervention for clinical diagnosis method of hyaline membrane disease in premature infants. Methods A total of 288 premature infants admitted to neonatal intensive care unit (NICU) of Ankang City Central Hospital from January 1st, 2013 to January 1st, 2016 were involved into the study. The primary gastric juice 1-2 mL was extracted for SMT test within 30 minutes after the birth. The number of the stable micro bubble with diameter<15μm was counted by low magnification. The clinical symptoms and X-ray results within 6 h after the birth were used as the gold standard of diagnosis of HMD. The premature infants were divided into the case group and control group. The general information was compared between two groups. The optimal critical stable micro bubble value was determined by the ROC curve. The number of micro bubbles <5/mm2, <10/mm2, <15/mm2 and <20/mm2 were used as the threshold, and the sensitivity, specificity, positive and negative predictive values were calculated for HMD diagnosis. Results Among the 288 cases of premature infants, 91 cases (31.6%) were diagnosed as HMD, 197 cases (68.4%) were diagnosed as non HMD. There were lower gestational age, lower birth weight and more proportion of male babies in the case group compared with those of control group (P<0.05). There were no significant differences in prenatal usage of hormones, premature rupture of membranes, the proportion of cesarean section and 5-min Apgar scores between two groups. The number of micro bubbles of 15/mm2 was the optimal threshold for diagnosis of HMD, and AUC was 0.80 (0.73-0.84). When the number of micro bubbles of 5/mm2 was used for the diagnosis, 38 cases were in line with the diagnosed as HMD. When the number of micro bubbles of 10-15/mm2 was used for the diagnosis, 16 cases were in line with diagnosed as HMD. The number of micro bubbles of<15/mm2 was used as boundary value of HMD. The sensitivity, specificity, positive predictive value, negative predictive value and Youden index for SMT prediction and early diagnosis of HMD were 89.0%, 91.4%, 82.7%, 94.7%and 80.4%, which can be used as predictive indicators of HMD. Conclusion SMT test is simple, rapid, economic, high sensitivity and good specificity, which can effectively predict and early diagnose HMD, and have high clinical value.

Investigation of the value of stable micro bubble test for early diagnosis of hyaline membrane disease in premature infants / 天津医药

Objective To explore the value of stable micro bubble test (SMT) for early diagnosis of hyaline membrane disease (HMD), and to provide early intervention for clinical diagnosis method of hyaline membrane disease in premature infants. Methods A total of 288 premature infants admitted to neonatal intensive care unit (NICU) of Ankang City Central Hospital from January 1st, 2013 to January 1st, 2016 were involved into the study. The primary gastric juice 1-2 mL was extracted for SMT test within 30 minutes after the birth. The number of the stable micro bubble with diameter<15μm was counted by low magnification. The clinical symptoms and X-ray results within 6 h after the birth were used as the gold standard of diagnosis of HMD. The premature infants were divided into the case group and control group. The general information was compared between two groups. The optimal critical stable micro bubble value was determined by the ROC curve. The number of micro bubbles <5/mm2, <10/mm2, <15/mm2 and <20/mm2 were used as the threshold, and the sensitivity, specificity, positive and negative predictive values were calculated for HMD diagnosis. Results Among the 288 cases of premature infants, 91 cases (31.6%) were diagnosed as HMD, 197 cases (68.4%) were diagnosed as non HMD. There were lower gestational age, lower birth weight and more proportion of male babies in the case group compared with those of control group (P<0.05). There were no significant differences in prenatal usage of hormones, premature rupture of membranes, the proportion of cesarean section and 5-min Apgar scores between two groups. The number of micro bubbles of 15/mm2 was the optimal threshold for diagnosis of HMD, and AUC was 0.80 (0.73-0.84). When the number of micro bubbles of 5/mm2 was used for the diagnosis, 38 cases were in line with the diagnosed as HMD. When the number of micro bubbles of 10-15/mm2 was used for the diagnosis, 16 cases were in line with diagnosed as HMD. The number of micro bubbles of<15/mm2 was used as boundary value of HMD. The sensitivity, specificity, positive predictive value, negative predictive value and Youden index for SMT prediction and early diagnosis of HMD were 89.0%, 91.4%, 82.7%, 94.7%and 80.4%, which can be used as predictive indicators of HMD. Conclusion SMT test is simple, rapid, economic, high sensitivity and good specificity, which can effectively predict and early diagnose HMD, and have high clinical value.

Efectividad del tratamiento con Alveofact® y Curosurf® en prematuros de 32 semanas o menos con enfermedad de membrana hialina en Buga, Valle del Cauca, entre los años 2006 y 2013 / Effectiveness of treatment with Alveofact® and Curosurf® in preterm infants born at 32 weeks or less with hyaline membrane disease in Buga, Valle del Cauca between 2006 and 2013

RESUMEN Introducción: la enfermedad de membrana hialina, es una patología que afecta a prematuros, principalmente los menores de 30 semanas. Existen en el momento actual varios tipos de surfactantes para el tratamiento de esta entidad, los cuales han mostrado eficacia similar, pero algunos resultan ser más costo-efectivos que otros. Objetivo: evaluar la efectividad de Alveofact® versus Curosurf®, en neonatos prematuros ≤ 32 semanas, con enfermedad de membrana hialina, efectos colaterales de la administración, complicaciones neonatales y comparar los costos de su administración. Materiales y método: estudio de cohorte retrospectiva, en 136 neonatos prematuros, ≥ 24 semanas y ≥ 500g de peso al nacer; 64 de ellos fueron tratados con Alveofact® y 72 con Curosurf®. La exposición consistió en la administración de una dosis de Alveofact® (bovactant) 100mg/Kg y Curosurf® (poractant alfa) 200mg/Kg inicialmente, y como segunda dosis se suministró 100mg/Kg para cada uno. Posteriormente, se evaluó tiempo de ventilación mecánica, de oxigenoterapia, estancia, necesidad de segunda dosis, efectos colaterales por la administración y complicaciones; adicionalmente, mortalidad y displasia broncopulmonar. El análisis estadístico se realizó con Stata® 11.0, empleando Chi2 o Prueba exacta de Fisher, prueba t-test no pareado o Wilcoxon rank-sum. Resultados: no se hallaron diferencias significativas para tiempo de ventilación mecánica, oxigenoterapia, segunda dosis, estancia y complicaciones entre Alveofact® y Curosurf®. Adicionalmente, la displasia broncopulmonar se presentó en el 22,8% y la mortalidad en el 30,1%, sin diferencia significativa entre los dos surfactantes. Conclusiones: los resultados de esta investigación muestran que ambos surfactantes son igual de efectivos, pero el Curosurf® resulta más costoso. MÉD.UIS. 2016;29(3):13-25.

ABSTRACT Introduction: hyaline membrane disease, is a condition that affects preterm infants, especially those under 30 weeks. There are at present various types of surfactants for the treatment of this entity, which have shown similar efficacy, but some turn out to be more cost-effective than others. Objective: to evaluate the effectiveness of Alveofact® versus Curosurf® in preterm infants ≤32 weeks with hyaline membrane disease, side effects of administration, neonatal complications and to compare the costs of administration of the two surfactants. Materials and method: retrospective cohort study in 136 preterm infants ≥ 24 weeks and ≥ 500 g birth weight; 64 of them were treated with Alveofact ® and 72 with Curosurf ®. The exposure was the administration of a first dose of Alveofact ® (bovactant) 100mg/Kg and Curosurf ® (poractant alpha) 200mg/Kg and 100mg/Kg second dose for each group. Duration of mechanical ventilation, oxygen therapy, stay, need for second dose, side effects and complications administration were evaluated; additionally, mortality and bronchopulmonary dysplasia. Statistical analysis was performed with Stata ® 11.0 using Chi2 or Fisher exact test, t-test or unpaired Wilcoxon rank-sum. Results: no significant differences in duration of mechanical ventilation, oxygen therapy, second dose, stay and complications between Alveofact ® and Curosurf ® were found. The bronchopulmonary dysplasia occurred in 22.8% and 30.1% mortality, with no significant difference between the two surfactants. Conclusions: the results of this research show that both surfactants are equally effective, but Curosurf ® is more expensive. MÉD.UIS.2016;29(3):13-25.

"Clinical Observation of neonatal hyaline membrane disease about the treatment injected into the ""PS""by tracheal catheter" / 中国基层医药

Objective To investigate the therapeutic effect of injectingPSby Scalp needle-induced tra-cheal catheter on treatment of neonatal hyaline membrane disease.Methods 26 cases were chosen as control group who were treated in our hospital NICU department during January,2013 to December,2013;the other 31 cases as improved group during January,2014 to January,2015.After administration therapy of drug,the injection time,chest X-ray and blood gas analysis were researched as observation indexes respectively.Results The amelioration of chest X-ray:29 cases in the improved group and 19 cases in the control group after 48 hours treatment,χ2 =4.457, P=0.035;The amelioration of blood gas analysis:pH:(7.38 ±0.08) in improved group and (7.26 ±0.04) in the control group,t=4.981,P=0.030;PaCO2 (mmHg):(39 ±6) in the improved group and (50 ±10) in the control group,t=5.897,P=0.019;PaO2(mmHg):(77 ±6) in the improved group and (67 ±10) in the control group,t=8.026,P=0.006.Conclusion The therapeutic effect of improved group is obviously better than the control group.

A doença da membrana hialina em prematuros de baixo peso / Hyaline membrane disease in low birth weight preterm infants

Introdução: O objetivo do estudo foi determinar a prevalência da Doença da Membrana Hialina (DMH) em prematuros de baixo peso e suas principais complicações. Métodos: Foi realizado um estudo descritivo do tipo série de casos. A população em estudo foram 34 prematuros com peso inferior a 1500 gramas e/ou idade gestacional inferior a 32 semanas nascidos no período de julho de 2010 a julho de 2011 no Hospital Universitário de Canoas/RS. Resultados: Pré-eclâmpsia e trabalho de parto prematuro foram as causas mais frequentes de parto pré-termo. DMH ocorreu em todos os recém-nascidos com peso inferior a 1000 gramas. Em prematuros com peso ao nascer entre 1001 e 1250 gramas e 1251 e 1499 gramas, a prevalência da DMH foi de 71,4% e 44,4%, respectivamente. A complicação da DMH mais frequente foi a persistência do canal arterial. Conclusões: A prevalência da DMH encontrada foi de 100% nos prematuros com peso até 1000 gramas e de 71,4% nos RNs com peso entre 1001g e 1250g. Nos prematuros com peso de 1251g a 1499g, a prevalência foi de 44,4% (AU)

Introduction: The aim of the study was to determine the prevalence of hyaline membrane disease (HMD) in preterm, low birth weight infants and its major complications. Methods: A descriptive study of the case series was conducted. The study population were 34 preterm infants weighing less than 1500 grams and/or gestational age less than 32 weeks born from July 2010 to July 2011 at the University Hospital of Canoas, RS. Results: Pre-eclampsia and preterm labor were the most frequent causes of preterm birth. HMD occurred in all newborns weighing less than 1000 grams. In premature infants with birth weights between 1001 and 1250 grams and 1251 grams and 1499, the prevalence of DMH was 71.4% and 44.4%, respectively. The most frequent complication of DMH was the persistent ductus arteriosus. Conclusions: The prevalence of DMH was 100% in preterm infants weighing up to 1000 grams and 71.4% in newborns weighing between 1001g to 1250g. In premature infants weighing 1251g to 1499g, the prevalence was 44.4% (AU)

Conceitos atuais sobre avaliação da maturidade pulmonar fetal / Current concepts on the assessment of fetal lung maturity

A Síndrome do Desconforto Respiratório (SDR), também conhecida como Doença da Membrana Hialina, é uma das principais causas de morbidade e mortalidade neonatal. O principal fator associado à SDR é a produção insuficiente de surfactante pulmonar, o que geralmente está associada à prematuridade. Alguns protocolos internacionais recomendam que a confirmação da maturidade pulmonar fetal seja realizada em partos eletivos antes de 39 semanas de gestação. Diversos são os métodos capazes de avaliar a maturidade pulmonar fetal, como a Relação Lecitina/Esfingomielina,a Pesquisa de Corpos Lamelares, a Relação Surfactante/Albumina, o percentual deFosfatidilglicerol, o Índice de Estabilidade da Espuma e o Shake Test ou Teste de Clements. Este estudo visa apresentar os principais métodos disponíveis e as recomendações atuais sobre quando realizar a avaliação da maturidade pulmonar fetal.(AU)

The Respiratory Distress Syndrome (RDS), also known as hyaline membrane disease, is a major cause of neonatal morbidity and mortality. The main factor associated with RDS is the insufficient production of pulmonary surfactant, which is usually associated with prematurity. Some international guidelines recommend that the confirmation of fetal lung maturity is performed in elective deliveries before 39 weeks of gestation. There are several methods to assess fetal lung maturity, such as the Lecithin/Sphingomyelin ratio, the Lamellar Body Count, the Surfactant/Albumin ratio, the percentage of phosphatidylglycerol, the Foam Stability Index and the Shake Test or Clements test. This study aims to present the main available methods and current recommendations on when to conduct the evaluation of fetal lung maturity.(AU)

Eficacia de tres tipos de surfactante exógeno en prematuros con enfermedad de membrana hialina / Effectiveness of three types of exogenous surfactant in preterm infants with hyaline membrane disease

Introducción: La enfermedad de membrana hialina es causa importante de mortalidad neonatal. El objetivo de esta investigación fue evaluar la eficacia de tres tipos de surfactante exógeno en prematuros. Pacientes y Método: Estudio de cohorte retrospectiva, en 93 neonatos prematuros, > 24 semanas y > 500 g de peso al nacer, 31 para cada surfactante. La exposición fue la administración de 1ª dosis bovactant (Alveofact®) 50 mg/kg, beractant (Survanta®) 100 mg/kg inicial, y poractant alfa (Curosurf®) 200 mg/kg. Las variables en estudio incluyeron tiempo de ventilación mecánica, tiempo de oxigenoterapia, estancia hospitalaria, necesidad de segunda dosis de surfactante, eventos adversos por la administración del surfactante y complicaciones por prematuridad. Además, se evaluó mortalidad, displasia broncopulmonar (DBP) y mortalidad o DBP. Análisis estadístico mediante Stata® 11.0, empleando X² o Prueba Exacta de Fisher para variables cualitativas y Pruebas ANOVA o Kruskal-Wallis para cuantitativas y riesgo relativo para las asociaciones, todas con su intervalo de confianza de 95%. Resultados: No hubo diferencias para sexo, peso y edad gestacional al nacer entre los 3 grupos. No se hallaron diferencias estadísticamente significativas para tiempo de ventilación mecánica, tiempo de oxigenoterapia, administración de una segunda dosis de surfactante, estancia hospitalaria y complicaciones entre los 3 grupos. Los eventos adversos por administración de surfactante se presentaron para beractant y poractant alfa. Ocurrieron 30 (32,3 por ciento) muertes, 8 (25,8 por ciento) para bovactant, 10 (32,3 por ciento) beractant y 12 (38,7 por ciento) poractant alfa (p > 0,05). La mortalidad y/o DBP ocurrió en 10 (32,2 por ciento) neonatos con bovactant, 10 (32,2 por ciento) con beractant y 14 (45,2 por ciento) con poractant alfa (p > 0,05). Conclusiones: Los resultados primarios y secundarios entre los tres surfactantes evaluados fueron muy similares...

Introduction: Hyaline membrane disease is an important cause of neonatal mortality. The objective of this research is to evaluate the efficacy of three different exogenous surfactants in premature infants. Patients and Method: A retrospective cohort analysis in 93 preterm infants > 24 weeks and birth weight > 500 g was performed, 31 infants for each surfactant. Exposure consisted of the 1st dose of bovactant (Alveofact®) 50 mg/kg, beractant (Survanta®) 100 mg/kg initially, and poractant alfa (Curosurf®) 200 mg/kg. The variables included duration of mechanical ventilation, duration of oxygen therapy, hospital stay, need for second dose of surfactant, adverse events surfactant administration and prematurity complications. Mortality and bronchopulmonary dysplasia (BPD) were evaluated. Statistical analysis was performed using Stata® 11.0, X² or Fisher exact test for qualitative variables and ALNOVA or Kruskal-Wallis tests for quantitative and association relative risk, all with 95 percent confidence level. Results: There were no gender, weight and gestational age differences at birth among the three groups. No statistically significant differences were found regarding duration of mechanical ventilation, duration of oxygen therapy, administration of a second dose of surfactant, hospital stay and complications among the three groups. Adverse events related to surfactant administration occurred for beractant and poractant alpha. There were 30 (32.3 percent) deaths, 8 (25.8 percent) associated to bovactant, 10 (32.3%) to beractant and 12 (38.7 percent) to poractant alpha (p > 0.05). Mortality and/or BDP occurred in 10 (32.2 percent) infants who received bovactant, 10 (32.2 percent) beractant and 14 (45.2 percent) with poractant alpha (p > 0.05). Conclusions: The primary and secondary outcomes among the three surfactants tested were similar, taking into account the limitations of the work.

Pulmonary surfactants and their role in pathophysiology of lung disorders.

Surfactant is an agent that decreases the surface tension between two media. The surface tension between gaseous-aqueous interphase in the lungs is decreased by the presence of a thin layer of fluid known as pulmonary surfactant. The pulmonary surfactant is produced by the alveolar type-II (AT-II) cells of the lungs. It is essential for efficient exchange of gases and for maintaining the structural integrity of alveoli. Surfactant is a secretory product, composed of lipids and proteins. Phosphatidylcholine and phosphatidylglycerol are the major lipid constituents and SP-A, SP-B, SP-C, SP-D are four types of surfactant associated proteins. The lipid and protein components are synthesized separately and are packaged into the lamellar bodies in the AT-II cells. Lamellar bodies are the main organelle for the synthesis and metabolism of surfactants. The synthesis, secretion and recycling of the surfactant lipids and proteins is regulated by complex genetic and metabolic mechanisms. The lipid-protein interaction is very important for the structural organization of surfactant monolayer and its functioning. Alterations in surfactant homeostasis or biophysical properties can result in surfactant insufficiency which may be responsible for diseases like respiratory distress syndrome, lung proteinosis, interstitial lung diseases and chronic lung diseases. The biochemical, physiological, developmental and clinical aspects of pulmonary surfactant are presented in this article to understand the pathophysiological mechanisms of these diseases.

Morbilidad en el recién nacido menor de 1 500 g / Morbidity in newborns weighing less than 1500 g

Introducción: el parto pretérmino de un recién nacido con peso menor de 1 500 g, constituye uno de los problemas más importantes para la salud materno-infantil, ya que en este grupo de pacientes se concentra la mayor parte de la morbilidad y mortalidad perinatal. Objetivo: identificar eventos perinatales en partos pretérmino con recién nacidos menores de 1 500 g. Métodos: se realizó un estudio descriptivo de 80 gestantes con edad gestacional entre 28,0 y 36,6 sem que presentaron partos pretérmino con recién nacidos menores de 1 500 g pertenecientes al Hospital Ginecobstétrico "Ramón González Coro", desde enero de 2008 a diciembre de 2010. El análisis descriptivo de los datos se realizó mediante distribuciones de frecuencias absolutas y relativas. Se utilizó la prueba Chi Cuadrado (X²) con un 95 % de confiabilidad. Resultados: el 75 % presentó factores de riesgo. Predominaron los trastornos hipertensivos del embarazo, el asma bronquial y la anemia con un 48,8 %, 7,5 % y 6,3 % respectivamente. El 45 % de los partos fue secundario a una rotura prematura de membranas pretérmino. El bajo peso al nacer predominó en el 56,3 % del total. El 29,8 % presentó restricción del crecimiento fetal y el 28,6 % enfermedad de membrana hialina. Conclusiones: las tres cuartas partes presentaron factores de riesgo. Predominó la hipertensión arterial y la preeclampsia como factores de riesgo principales. La causa más frecuente de parto pretérmino fue la rotura prematura de membranas. La restricción del crecimiento intrauterino y la enfermedad de membrana hialina fueron las complicaciones más frecuentes.

Introduction: preterm delivery of an infant weighing less than 1 500 g is one of the most important health problems for a mother and her child, as perinatal morbidity and mortality are concentrated in this patient population. Objective: to identify perinatal events in preterm birth infants weighing less than 1 500 g. Methods: a descriptive study was carried out to identify perinatal events in 80 pregnant women with gestational age between 28.6-36.6 weeks. These patients had preterm birth infants weighing less than 1 500 grams. They were all attended at Ramón González Coro OB/GYN Hospital, from January 2008 to December 2010. This descriptive data analysis used distributions of absolute and relative frequencies. The chi-square test (X²) was used, showing 95 % confidence. Results: 75 % had risk factors. Pregnancy hypertensive disorders (48.8 %), asthma (7.5 %), and anemia (6.3 %) were predominant. 45 % of births occurred after premature rupture of membranes. Low birth weight prevailed in 56.3 % of the total. 29.8 % had fetal growth restriction and 28.6% had hyaline membrane disease. Conclusions: risk factors were present in three quarters of the patients. Hypertension and pre-eclampsia predominated as major risk factors. The most common cause of preterm birth was premature rupture of membranes. Intrauterine growth restriction and hyaline membrane disease were the most frequent complications.