Historical perspective on surfactant therapy: Transforming hyaline membrane disease to respiratory distress syndrome.

Lung surfactant is the first drug so far designed for the special needs of the newborn. In 1929, Von Neergard described lung hysteresis and proposed the role of surface forces. In 1955-1956, Pattle and Clements found direct evidence of lung surfactant. In 1959, Avery discovered that the airway's lining material was not surface-active in hyaline membrane disease (HMD). Patrick Bouvier Kennedy's death, among half-million other HMD-victims in 1963, stimulated surfactant research. The first large surfactant treatment trial failed in 1967, but by 1973, prediction of respiratory distress syndrome using surfactant biomarkers and promising data on experimental surfactant treatment were reported. After experimental studies on surfactant treatment provided insight in lung surfactant biology and pharmacodynamics, the first trials of surfactant treatment conducted in the 1980s showed a striking amelioration of severe HMD and its related deaths. In the 1990s, the first synthetic and natural surfactants were accepted for treatment of infants. Meta-analyses and further discoveries confirmed and extended these results. Surfactant development continues as a success-story of neonatal research.

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.

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

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.

Mildred T. Stahlman: a centenarian who pioneered modern scientific neonatal intensive care.

Neonatology pioneer Mildred (Millie) T. Stahlman celebrated her 100th birthday on July 31, 2022. Her distinguished career at Vanderbilt University Medical Center in Nashville, TN, is reviewed to commemorate this milestone. Stahlman was arguably the first to establish a modern neonatal intensive care unit in 1961, successfully utilizing negative pressure ventilation and umbilical arterial and venous catheters to monitor blood gasses and pH levels. She received early invaluable training in newborn physiology at the Karolinska Institute in Stockholm, Sweden, under John Lind and Petter Karlberg, and at Vanderbilt under Elliot V. Newman. Stahlman also consulted with luminaries Geoffrey Dawes, Donald Barron, and L. Stanley James. As director of the Vanderbilt NICU, she trained 80 fellows from more than 20 countries. The latter 20 years of her career were highlighted by collaborations with Jeff Whitsett. She was the recipient of the AAP Virginia Apgar Award, the APS John Howland Medal, and served as a member of the Institute of Medicine.

Natural Versus Synthetic Surfactant Therapy in Respiratory Distress Syndrome of Prematurity.

OBJECTIVES: To compare the clinical efficacy and the cost of treatment between the newborns who received either a natural or a protein-free synthetic surfactant for respiratory distress syndrome (RDS) of prematurity. METHODS: This is a retrospective analytical study incorporating comparisons of clinical parameters and cost in newborns having RDS of prematurity who received either Survanta (bovine lung extract), a natural surfactant or Surfact (protein-free colfosceril palmitate), a synthetic surfactant. RESULTS: There were 100 newborns who received either of the natural (n = 52) or synthetic (n = 48) surfactant with mean (SD) gestational age and mean (SD) birth weight of 31.5 (2.6) wk, 1425 (461) g and 32.2 (2.2) wk, 1519 (413) g, respectively. Majority of the newborns (> 90%) received endotracheal surfactant within the first 24 h of life and had similar baseline characteristics in either group. No differences were noted in ventilator settings on admission and 24 h after surfactant/admission. Oxygen requirement, extubation age, complications, hospital stay, and mortality were similar across groups, except that the necrotizing enterocolitis was noted only in natural surfactant group. There was a significant pharmacy cost savings in synthetic surfactant group. CONCLUSION: Synthetic surfactant was comparable to natural surfactant with regard to outcomes, like ventilator settings, hospital stay, and mortality. Pharmacy cost was less in synthetic surfactant group.

Implementation of less-invasive surfactant administration in a Canadian neonatal intensive care unit.

BACKGROUND: Less-invasive surfactant administration (LISA) is a recent technique used extensively in Europe but rarely used in North America. The aim of this study was to describe our experience following LISA implementation using poractant in a Canadian neonatal intensive care (NICU). METHODS: A retrospective analysis was conducted from June 2017 to April 2021 of LISA procedures in preterm infants. Data were collected on patient characteristics, outcomes following LISA, laryngoscopy, and adverse events. The primary outcome was the rate of successful LISA procedures. SETTING: Level IIIa academic NICU. RESULTS: LISA was successful in 93 of 101 infants (92%). Median gestational age was 30.9 weeks (interquartile range [IQR]: 29.4-33.0). All infants received atropine and fentanyl premedication. Eight LISA procedures were unsuccessful: five because of thoracic rigidity and three because of inability to expose the vocal cords. In the 93 successful procedures, a second dose of surfactant was needed for 15 of 93 infants (16.1%), either by repeated LISA (7/15; 7.5%) or by endotracheal intubation (8/15; 8.6%). In 63.4% of successful procedures, one laryngoscopy attempt was made. The median duration of laryngoscopy attempts was 60 s (IQR: 52-110). Two types of catheters were used: the multi-access catheter (MAC) or the Angiocath in 67% and 33% of procedures, respectively. One infant had bradycardia and 30.6% had profound desaturation of <75%. CONCLUSION: LISA with poractant alfa was implemented in a Canadian NICU with a high degree of procedural success. Fentanyl may lead to more adverse events with a risk of interrupting LISA and may not be the ideal agent for this procedure. These results may encourage wider dissemination of LISA in North America.

Incidence, Predictors and Outcomes of Noninvasive Ventilation Failure in Very Preterm Infants.

Non-invasive ventilation (NIV) is now considered the first-line treatment for respiratory distress syndrome in preterm infants. We aimed to evaluate the rates of non-invasive ventilation failure rate in very preterm infants, as well as to identify its predictors and associated outcomes. We designed a single-center retrospective cohort study including infants ≤32 weeks gestational age and ≤1500 g. The NIV failure was defined as the need for intubation at <72 h of life. After applying inclusion and exclusion criteria, 154 patients were included in the study, with a mean GA of 29.7 ± two weeks. The NIV failure rate was 16.2% (n = 25) and it was associated with lower bronchopulmonary dysplasia (BPD)-free survival (OR 0.08; 95% CI 0.02−0.32) and higher incidence of intraventricular hemorrhage > II (OR 6.22; 95% CI 1.36−28.3). These infants were significantly smaller in GA and weight. Higher FiO2 during resuscitation (OR 1.14; 95% CI 1.06−1.22) and after surfactant administration (OR 1.17; 95% CI 1.05−1.31) represented independent risk factors for NIV failure. In conclusion, NIV failure is frequent and it could be predicted by a higher oxygen requirement during resuscitation and a modest response to surfactant therapy. Importantly, this NIV failure is associated with worse clinical outcomes.

Using lactate dehydrogenase to predict the severity of respiratory distress in term newborn infants with no perinatal asphyxia.

BACKGROUND: We aimed to establish whether knowledge of lactate dehydrogenase (LDH) levels on day 1, as well as the change in these levels in the first three days, could be of clinical benefit in the diagnosis and/or prediction of severity of respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN). METHODS: A retrospective study was conducted on 275 term infants (35 with RDS and 240 with TTN) admitted to the neonatal intensive care unit from January 2014 to June 2019. LDH levels were measured on admission and after three days. RESULTS: Both RDS and TTN groups had elevated LDH levels during admission. LDH levels were significantly higher in the RDS group than in the TTN group on both days. LDH levels in both groups significantly correlated with both the duration of respiratory support required, as well as the number of hospital days. We used these outcomes as a measure of severity of these conditions. CONCLUSIONS: In patients with respiratory distress, it may not be clinically useful to use LDH levels on day 1 to differentiate between RDS and TTN, despite the statistically significant differences, because of the overlapping values. However, LDH levels on day 1 and day 3 may predict the degree and duration of the required respiratory support for both RDS and TTN groups.

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.

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.

European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2019 Update.

As management of respiratory distress syndrome (RDS) advances, clinicians must continually revise their current practice. We report the fourth update of "European Guidelines for the Management of RDS" by a European panel of experienced neonatologists and an expert perinatal obstetrician based on available literature up to the end of 2018. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, need for appropriate maternal transfer to a perinatal centre and timely use of antenatal steroids. Delivery room management has become more evidence-based, and protocols for lung protection including initiation of CPAP and titration of oxygen should be implemented immediately after birth. Surfactant replacement therapy is a crucial part of management of RDS, and newer protocols for its use recommend early administration and avoidance of mechanical ventilation. Methods of maintaining babies on non-invasive respiratory support have been further developed and may cause less distress and reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation using caffeine and, if necessary, postnatal steroids are also important considerations. Protocols for optimising general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome.

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.

Rapid diagnosis of respiratory distress syndrome by oral aspirate in premature newborns.

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 25microbubbles/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.

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.

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.

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.