Less invasive surfactant administration versus intubation-surfactant-extubation in the treatment of neonatal respiratory distress syndrome: a systematic review and meta-analyses

Abstract Objectives To compare LISA with INSURE technique for surfactant administration in preterm with gestational age (GA) < 36 weeks with RDS in respect to the incidence of pneumothorax, bronchopulmonary dysplasia (BPD), need for mechanical ventilation (MV), regional cerebral oxygen saturation (rSO2), peri‑intraventricular hemorrhage (PIVH) and mortality. Methods A systematic search in PubMed, Embase, Lilacs, CINAHL, SciELO databases, Brazilian Registry of Randomized Clinical Trials (ReBEC), Clinicaltrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) was performed. RCTs evaluating the effects of the LISA technique versus INSURE in preterm infants with gestational age < 36 weeks and that had as outcomes evaluation of the rates of pneumothorax, BPD, need for MV, rSO2, PIVH, and mortality were included in the meta-analysis. Random effects and hazard ratio models were used to combine all study results. Inter-study heterogeneity was assessed using Cochrane Q statistics and Higgin's I2 statistics. Results Sixteen RCTs published between 2012 and 2020 met the inclusion criteria, a total of 1,944 preterms. Eleven studies showed a shorter duration of MV and CPAP in the LISA group than in INSURE group. Two studies evaluated rSO2 and suggested that LISA and INSURE transiently affect brain autoregulation during surfactant administration. INSURE group had a higher risk for MV in the first 72 h of life, pneumothorax, PIVH and mortality in comparison to the LISA group. Conclusion This systematic review and meta-analyses provided evidence for the benefits of the LISA technique in the treatment of RDS, decreasing CPAP time, need for MV, BPD, pneumothorax, PIVH, and mortality when compared to INSURE.

Improvement effects of azithromycin on bronchopulmonary dysplasia in neonatal rats and its mechanism / 中国药房

OBJECTIVE To investigate the improvement effects of azithromycin on bronchopulmonary dysplasia （BPD） in neonatal rats based on hypoxia-inducible factor-1α（HIF-1α）/HIF-2α/vascular endothelial growth factor （VEGF） pathway. METHODS Sixty newborn SD rats were randomly divided into negative control group （NC）， BPD group， azithromycin group and budesonide group （positive control）， with 15 rats in each group. Rats in NC group were given normal breathing air， while rats in other three groups were exposed to high-concentration oxygen for 14 days to establish BPD rat models. After successful modeling， rats in azithromycin group were intraperitoneally injected with azithromycin 200 mg/kg， and rats in budesonide group were atomized with budesonide 1.5 mg/kg once a day for 14 consecutive days， while rats in BPD group and NC group were not treated. Pathological changes of lung tissue， radial alveolar count and mean alveolar intercept of rats were observed in each group. The white blood cell count in bronchoalveolar lavage fluid （BALF） and the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， superoxide dismutase （SOD）， catalase （CAT） and malondialdehyde （MDA） were detected； mRNA and protein expressions of VEGF， HIF-1α， HIF-2α were also detected. RESULTS Compared with NC group， the lung tissue in BPD group was obviously damaged； the white blood cell count， average alveolar intercept and the levels of TNF-α， IL-6， IL-1β and MDA were significantly increased； the radial alveolar count， SOD and CAT levels， the relative expressions of VEGF， HIF-1α， HIF-2α mRNA and protein were significantly decreased （P＜0.05）. Compared with BPD group， the changes of the above indexes in azithromycin group and budesonide group were significantly reversed （P＜0.05）. CONCLUSIONS Azithromycin can obviously improve the symptoms of BPD in rats， reduce inflammation and oxidative stress， and exert lung protection， the mechanism of which may be realized by activating HIF-1α/HIF-2α/VEGF pathway.

Management of lung diseases under ultrasound monitoring: potential to make bronchopulmonary dysplasia in preterm infants as an avoidable disease / 中国当代儿科杂志

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants. Despite significant progress in the understanding of its etiology, mechanisms, prevention, and treatment, the prognosis remains poor. BPD not only has a high mortality rate but also causes persistent respiratory, neurological, and cardiovascular impairments in survivors. The author's team has successfully prevented the occurrence of BPD by managing neonatal lung diseases under lung ultrasound monitoring for nearly 7 years, opening up a new approach in BPD prevention. This article provides a brief overview of the approach, aiming to facilitate further research and provide more scientifically sound management strategies to prevent or minimize the occurrence of BPD.

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.

The clinical value of lung ultrasound in premature infants with bronchopulmonary dysplasia

SUMMARY OBJECTIVE: This study aimed to explore the risk factors of bronchopulmonary dysplasia in premature infants and the clinical application value of lung ultrasound in the diagnosis of bronchopulmonary dysplasia. METHODS: A total of 80 premature infants with a gestational age of <32 weeks or a birth weight of <1,500 g who were treated in our hospital from January to August 2021 were randomly divided into a bronchopulmonary dysplasia group (n=12) and a non-bronchopulmonary dysplasia group (n=62). The clinical data, lung ultrasound, and X-ray image characteristics of the two groups were compared. RESULTS: Among the 74 preterm infants, 12 preterm infants were diagnosed with bronchopulmonary dysplasia, and 62 preterm infants were determined not to have bronchopulmonary dysplasia. There were significant differences in sex, severe asphyxia, invasive mechanical ventilation, premature membrane ruptures, and intrauterine infection between the two groups (p<0.05). Lung ultrasound showed abnormal pleural lines and alveolar-interstitial syndrome in all 12 patients with bronchopulmonary dysplasia and vesicle inflatable signs in 3 patients. Before clinical diagnosis, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of lung ultrasound in the diagnosis of bronchopulmonary dysplasia were 98.65, 100, 98.39, 92.31, and 100%, respectively. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of X-rays in the diagnosis of bronchopulmonary dysplasia were 85.14, 75.00, 87.10, 52.94, and 94.74%, respectively. CONCLUSION: The diagnostic efficiency of lung ultrasound for premature bronchopulmonary dysplasia is better than that of X-rays. The application of lung ultrasound can screen patients with bronchopulmonary dysplasia early for timely intervention.

Tamaño del léxico en niños(as) muy prematuros y prematuros extremos de 24 meses: un estudio transversal / Vocabulary size in very preterm and extremely preterm infants: a cross-sectional study

Las investigaciones muestran que un número importante de niños nacidos prematuros (antes de las 37 semanas de gestación) presentan dificultades en su desarrollo, entre ellas el desarrollo lingüístico. Las investigaciones previas indican que algunas complicaciones biomédicas, como la hemorragia intraventricular (los grados III y IV), la leucomalacia periventricular y la displasia broncopulmonar, incrementan la probabilidad de presentar alteraciones en el desarrollo de la cognición y/o del lenguaje, por lo que se hace necesario realizar investigaciones que proporcionen más información y con ello poder anticiparse a posibles consecuencias en los aprendizajes futuros de estos niños nacidos bajo la condición de prematuridad. Es así, que los objetivos de este estudio fueron medir el tamaño del léxico temprano en niños muy prematuros y prematuros extremos (con y sin complicaciones biomédicas) a los 24 meses de edad corregida, así como también determinar la asociación entre número de complicaciones biomédicas presentes y el tamaño del léxico. Para ello, se trabajó con 108 niños divididos en tres grupos: 39 niños prematuros de alto riesgo (con complicaciones biomédicas), 36 niños prematuros de bajo riesgo (sin complicaciones biomédicas asociadas a alteraciones del lenguaje y /o cognición) y 33 niños nacidos de término. Todos fueron evaluados con el Inventario II de Desarrollo de Habilidades Comunicativas MacArthur-Bates. Los resultados muestran que los niños nacidos de término tienen significativamente mayor tamaño del léxico que los prematuros, no existiendo diferencias en los resultados entre prematuros de bajo riesgo y los prematuros de alto riesgo. Por otra parte, el tamaño del léxico no presenta correlación con las complicaciones biomédicas.

Research shows that a significant number of children born preterm (before 37 weeks of gestation) have developmental difficulties, among them disturbances in language development. Studies indicate that some biomedical complications such as intraventricular hemorrhage (grades III and IV), periventricular leukomalacia, and bronchopulmonary dysplasia increase the probability of cognitive and/or language development disorders. Therefore, there is a need to conduct more studies that provide information that allows anticipating possible consequences in the learning process of children born prematurely. The aims of this study were to measure the early vocabulary size in very preterm and extremely preterm children (with and without biomedical complications) at 24 months of corrected age and to determine the association between the number of biomedical complications and vocabulary size. To that effect, we worked with 108 children divided into three groups: 39 high-risk preterm children (with biomedical complications), 36 low-risk preterm children (without biomedical complications associated with language and/or cognitive disturbances), and 33 full-term children. All children were evaluated using the MacArthur-Bates Communicative Development Inventory II. The results show that the vocabulary size of full-term children is significantly larger than that of preterm children and that no differences exist between the group of high-risk versus low-risk preterm children. On the other hand, vocabulary size does not correlate withbiomedical complications.

Impact of the Koala Project on clinical outcomes of preterm infants in two maternity hospitals / Impacto do Projeto Coala nos resultados clínicos de pacientes prematuros em duas maternidades

ABSTRACT Objective: To describe the impact of the Koala project (Actively Controlling Target Oxygen) on clinical outcomes in patients born with less than 36 weeks of gestation, in two maternity hospitals, comparing before and after the strategy implementation. Methods: This is an intervention study with 100 preterm infants with gestational age ≤36 weeks, who used oxygen in two maternity hospitals between January 2020 and August 2021. One of the hospitals was a private institution and the other was philanthropic. The goal for the target oxygen saturation with this project was 91-95%. Comparisons between the two stages (before and after the implementation of the project) were made evaluating the outcomes of retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, and deaths. The continuous variables were described using mean, median, standard deviation and interquartile interval. The significance level adopted was 5% and the software used was R Core Team 2021 (version 4.1.0). Results: After oxygen control use according to the Koala protocol, there was a significant reduction in the cases of retinopathy of prematurity (p<0.001) and bronchopulmonary dysplasia (p<0.001). There were no deaths in the second stage, and there was a non-significant increase in the absolute number of necrotizing enterocolitis cases. Conclusions: The Koala project seems to be an effective and feasible strategy to reduce adverse situations in the management of premature children, but research with a greater sample is needed.

RESUMO Objetivo: Descrever o impacto do projeto Coala (Controle Ativo de Oxigênio Alvo) nos desfechos clínicos em pacientes nascidos com menos de 36 semanas de gestação, em duas maternidades, comparando antes e depois da implementação da estratégia. Métodos: Trata-se de um estudo de intervenção com cem prematuros vivos, com idade gestacional ≤36 semanas, que utilizaram oxigênio em duas maternidades entre janeiro de 2020 e agosto de 2021. A meta para a saturação de oxigênio alvo com este projeto foi de 91-95%. Comparações entre as duas etapas (antes e depois da implantação do projeto) foram feitas avaliando os desfechos de retinopatia da prematuridade, displasia broncopulmonar, enterocolite necrosante e óbitos. As variáveis contínuas foram descritas por meio de média, mediana, desvio padrão e intervalo interquartil. O nível de significância adotado foi de 5% e o software empregado foi o R Core Team 2021 (versão 4.1.0). Resultados: Observou-se que, após o uso de controle de oxigênio segundo o protocolo Coala, houve redução significativa nos casos de retinopatia da prematuridade (p<0,001) e displasia broncopulmonar (p<0,001). Não houve óbitos na segunda etapa e houve aumento não significativo no número absoluto de casos de enterocolite necrosante. Conclusões: O projeto Coala parece ser uma estratégia eficaz e viável para reduzir situações adversas no manejo de crianças prematuras, mas pesquisas com amostras maiores são necessárias.

Caracterización de la displasia broncopulmonar según dos definiciones en prematuros chilenos / Characterization of bronchopulmonary dysplasia in relation with two definitions in chilean preterm infants

Existen controversias en la definición de la displasia broncopulmonar, siendo las más utilizadas el requerimiento de O2 durante 28 días o a las 36 semanas de edad gestacional corregida (EGC). Nuestro objetivo fue determinar la incidencia y características clínicas de los prematuros nacidos antes de las 32 semanas (RNP≤ 32s) con requerimiento de O2 a los 28 días de vida (DBP28d) y a las 36 semanas de EGC (DBP36s) en una unidad neonatal de Santiago, Chile, entre los años 2012 y 2019. Es un estudio descriptivo, retrospectivo con componente analítico. La población estudiada incluyó 535 RNP≤ 32s, vivos a las 36 semanas o dados de alta después de las 34 semanas de EGC. De los 242 prematuros DBP28d, 203 (83,88%) fueron DBP36s; 16 de los 242 (6%) requirió O2 durante menos de 28 días consecutivos, de los cuales 7, aún lo requerían a las 36 semanas. Los predictores de DBP36s fueron: sexo masculino (OR 2,42, IC del 95%: 1,24-4,69), peso al nacer (OR 1, IC del 95%: 0,99-1), edad gestacional (OR 0,75, IC del 95%: 0,57-0,97), APGAR a los 5 min, (OR 0,01, IC del 95%: 0,003-0,05), el requerimiento de presión positiva continua o cánula nasal de alto flujo (OR 1,1, IC del 95%: 1,04-1,17) y días de ventilación mecánica invasiva (OR 1,1,95% IC: 1-1,2). Conclusiones: No encontramos una diferencia significativa en la incidencia de DBP entre las definiciones de DBP28d y DBP36s; y la mayoría de los RNP< 32s con diagnóstico de DBP36s se pudieron identificar a los 28 días de vida.

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in premature newborns. It is commonly defined as a need for supplemental O2 for 28 days or at 36 weeks postmenstrual age (PMA) (BPD36w). Our objective was to determine the incidence and clinical characteristics of premature neonates born at less than 32 weeks (PNB< 32w) with O2 requirement at 28 days of life (DBP28d) and DBP36w in a neonatal unit of Santiago, Chile, between 2012 and 2019. This is a descriptive, retrospective study with an analytical component. The study population included 535 PNB< 32w, alive at 36 weeks or discharged after 34 PMA. Of the 242 premature BPD28d, 203 (83,88%) were BPD36w; 16 (6%) required O2 for less than 28 consecutive days, of which 7 still required it at 36 weeks. The predictors of BPD36w were: male (OR 2.42, 95% CI: 1.24-4.69), birth weight (OR 1, 95% CI: 0.99-1), gestational age (OR 0.75, 95% CI: 0.57-0.97), APGAR at 5 min, (OR 0.01, 95% CI: 0.003-0.05), continuous positive pressure or high-flow nasal cannula requirement (OR 1.1, 95% CI: 1.04-1.17) and days of invasive mechanical ventilation (OR 1.1, 95% CI: 1-1.2). Conclusions: We did not find a significant difference in the incidence of BPD between the definitions of BPD28d and BPD36s; and the majority of PNB < 32w diagnosed with BPD36w can be identified at 28 days of life.

Tempo de transição alimentar e método de alimentação na alta hospitalar de prematuros com displasia broncopulmonar / Feeding transition time and feeding method at hospital discharge of preterm infants with bronchopulmonary dysplasia

RESUMO Objetivo Comparar o tempo de transição alimentar e a forma de alimentação por via oral na alta hospitalar, entre recém-nascidos prematuros com diagnóstico de displasia broncopulmonar e prematuros sem o diagnóstico. Métodos Estudo transversal, retrospectivo com base na coleta de dados nos prontuários. Foram coletados dados de 78 recém-nascidos, em uma maternidade de referência. A amostra foi estratificada em dois grupos, de acordo com a presença do diagnóstico de displasia broncopulmonar, sendo um grupo de prematuros com displasia broncopulmonar e outro sem. Foram analisados o tempo de transição alimentar e o método de alimentação na alta hospitalar de ambos os grupos. Resultados Houve diferença significativa no tempo de transição alimentar e no método de alimentação na alta hospitalar entre os grupos. Os recém-nascidos pré-termo com displasia broncopulmonar apresentaram média de 18,03 (± 5,5) dias de transição e saíram em uso de mamadeira. Conclusão O grupo com displasia broncopulmonar necessitou de maior tempo de transição alimentar e teve menor frequência de aleitamento materno exclusivo, em relação ao grupo sem o diagnóstico.

ABSTRACT Purpose To compare the time of food transition and the form of oral feeding at hospital discharge, between premature newborns diagnosed with bronchopulmonary dysplasia and premature newborns without the diagnosis. Methods Cross-sectional, retrospective study based on data collection from medical records. Data were collected from 78 newborns, in a reference maternity hospital, in which the sample was stratified into two groups according to the presence or absence of the diagnosis of bronchopulmonary dysplasia. The time of food transition and the feeding method at hospital discharge were analyzed for both groups. Results There was a significant difference in the time of food transition and in the feeding method at hospital discharge between the groups. Preterm newborns with bronchopulmonary dysplasia had an average of 18.03 (± 5.5) transition days and left using a bottle. Conclusion The group with bronchopulmonary dysplasia required a longer time of food transition and fewer ( of its ) infants had exclusive breastfeeding compared to the group without the diagnosis.

Displasia broncopulmonar y severa restricción del crecimiento intrauterino en neonato de 850 gramos al nacer

Introducción: La displasia broncopulmonar es una enfermedad pulmonar crónica de inicio en edad neonatal. La restricción del crecimiento intrauterino se define como fracaso del feto para alcanzar su potencial de crecimiento genéticamente determinado. Objetivo: Describir el manejo interdisciplinario de la displasia broncopulmonar y revisar la literatura sobre el tema. Caso clínico: Se presenta el caso de un neonato hijo de madre adolescente producto de su primera gestación, la cual llevó un adecuado control prenatal. Presentó restricción del crecimiento intrauterino grado IV caracterizada por alteraciones en el ultrasonido Doppler en relación con insuficiencia placentaria severa y oligohidramnios, motivo por el cual se interrumpe el embarazo por parto distócico por cesárea a las 34+1 semanas, con bolsa rota al nacer, líquido amniótico claro y muy escaso. Nace en buenas condiciones clínicas con 850 gramos de peso. En los primeros días de vida, comenzó con manifestaciones clínicas de sepsis; se diagnosticó enterocolitis necrotizante luego presentó un súbito deterioro clínico debido a la aparición de hemorragia pulmonar. Con 695 gramos de peso, se inició tratamiento con ventilación mecánica invasiva, la cual se prolongó por un período de 30 días. Después del destete de la ventilación mecánica, el niño mantuvo una dependencia del oxígeno durante 71 días más; como manifestación de la displasia broncopulmonar. Se realizaron interconsultas con especialistas en Cardiología, Hematología, Imagenología, Nutrición, Inmunología y Genética; y, en colectivo, se decidió, la terapéutica desarrollada. El neonato evolucionó satisfactoriamente. Conclusiones: Se mostró el manejo interdisciplinario de la displasia broncopulmonar. Se consultó la bibliografía actualizada.

Introduction: Bronchopulmonary dysplasia is a chronic lung disease of neonatal age onset. Intrauterine growth restriction is defined as failure of the fetus to reach its genetically determined growth potential. Objective: To describe the interdisciplinary management of bronchopulmonary dysplasia and review the literature on the subject. Case report: The case of a newborn son of an adolescent mother, product of her first pregnancy, which had an adequate prenatal control, is presented. She presented grade IV intrauterine growth restriction characterized by alterations in the Doppler ultrasound in relation to severe placental insufficiency and oligohydramnios, which is why the pregnancy was terminated due to dystocic delivery by cesarean section at 34+1 weeks, with a ruptured bag at birth, liquid clear and very scanty amniotic. He was born in good clinical condition with a weight of 850 grams. In the first days of life, he began with clinical manifestations of sepsis; necrotizing enterocolitis was diagnosed, then he presented a sudden clinical deterioration due to the appearance of pulmonary hemorrhage. Weighing 695 grams, treatment with invasive mechanical ventilation was started, which lasted for a period of 30 days. After weaning from mechanical ventilation, the child remained oxygen dependent for a further 71 days; as a manifestation of bronchopulmonary dysplasia. Interconsultations were made with specialists in Cardiology, Hematology, Imaging, Nutrition, Immunology and Genetics; and, collectively, it was decided, the therapy developed. The neonate evolved satisfactorily. Conclusions: The interdisciplinary management of bronchopulmonary dysplasia was shown. The updated literature was consulted.

Traqueostomía en prematuros con displasia broncopulmonar grave / Tracheostomy in premature infants with severe bronchopulmonary dysplasia

Los recién nacidos con displasia broncopulmonar dependientes de ventilación mecánica a las 36 semanas, corresponden en general a prematuros menores de 27 semanas con morbilidad grave: enterocolitis, infecciones, retinopatía, retraso en el crecimiento y secuelas del neurodesarrollo. Si la extubación no es posible entre las 40 y 50 semanas, se indica una traqueostomía, normalmente acompañada de una gastrostomía. La decisión depende del apoyo ventilatorio, de la morbilidad asociada (neurológica, hipertensión pulmonar, lesiones de la vía aérea) y del grado de desnutrición. La traqueostomía optimiza el manejo ventilatorio, disminuye la necesidad de sedación, facilita la movilidad, la neurorrehabilitación y el alta al hogar en ventilación domiciliaria. La edad óptima de ejecución no está estandarizada, pero hay evidencia que muestra beneficios en el neurodesarrollo si se realiza antes de los 120 días de vida. La mayoría de los prematuros traqueostomizados son manejados en domicilio y a los 5 años ya se encuentran decanulados.

Newborns with bronchopulmonary dysplasia (BPD) dependent on mechanical ventilation at 36 weeks, generally correspond to newborns younger than 27 weeks with severe morbidity: enterocolitis, infections, retinopathy, growth retardation and neurodevelopmental sequelae. If extubation is not possible at 40-50 weeks post menstrual age, a tracheostomy is indicated, usually accompanied by a gastrostomy. The decision depends on ventilatory support, associated morbidity (neurological, pulmonary hypertension, airway lesions) and the degree of malnutrition. Tracheostomy optimizes ventilatory management, reduces the need for sedation, facilitates mobility, neurorehabilitation, and discharge on home ventilation. The optimal age for tracheostomy is not standardized, but there is evidence showing neurodevelopmental benefits if it is performed before 120 days. Most tracheostomized newborns are managed at home and at 5 years of age they are already decannulated.

METTL3 promotes hyperoxia-induced pyroptosis in neonatal bronchopulmonary dysplasia by inhibiting ATG8-mediated autophagy

Abstract Objectives N6-Methyladenosine (m6A) modification plays a vital role in lung disorders. However, the potential of m6A in neonatal Bronchopulmonary Dysplasia (BPD) has not been reported. This study aimed to investigate the roles of METTL3 in BPD. Methods BPD models were established by hyperoxia in vivo and in vitro. Histological analysis was determined using HE staining. Gene expression was determined using Western blotting, qRT-PCR, and immunofluorescence. The release of IL-1β and IL-18 was detected using ELISA. The m6A sites of ATG8 were predicted by SCRAPM and verified by MeRIP assay. The location of GSDMD and ATG8 was determined by FISH assay. The interaction between ATG8 and GSDMD was detected using Coimmunoprecipitation (Co-IP). Cell pyroptosis was determined using flow cytometry and TUNEL assays. Results METTL3 was overexpressed in BPD, which was accompanied by an increase in m6A levels. Interestingly, METTL3 suppressed hyperoxia-mediated damage and pyroptosis in BEAS-2B cells and promoted cell autophagy. METTL3-mediated m6A modification of ATG8 suppressed its expression and disrupted the interaction between ATG8 and GSDMD. However, autophagy inhibition induced pyroptosis in BEAS-2B cells. In vivo assays showed that METTL3-mediated autophagy inhibition induced a decrease in the radial alveolar count and an increase in the mean linear intercept and promoted cell pyroptosis. Conclusion In conclusion, METTL3-mediated cell pyroptosis promotes BPD by regulating the m6A modification of ATG8. This may provide new insight into the development of BPD.

Right ventricular myocardial performance index (Tei) in premature infants

SUMMARY OBJECTIVE: The objective of this study was to evaluate the right ventricular myocardial performance index) based on echocardiography in very low birth weight premature neonates, close to hospital discharge. METHODS: This was a prospective cross-sectional study that included premature neonates with birth weight <1,500 g and gestational age <37 weeks at the Intermediate Neonatal Unit of Bonsucesso Federal Hospital from July 2005 to July 2006. The infants underwent two-dimensional color Doppler echocardiography, being the right ventricular myocardial performance index evaluated close to hospital discharge. We compared the neonatal and echocardiographic variables in neonates with and without bronchopulmonary dysplasia. RESULTS: A total of 81 exams were analyzed. The mean birth (standard deviation) weight and gestational age were 1,140 (235) g and 30 (2.2) weeks, respectively. The incidence of bronchopulmonary dysplasia was 32%. The mean right ventricle myocardial performance index (standard deviation) of the sample was 0.13 (0.06). We found a significant difference in aortic diameter [non-bronchopulmonary dysplasia 0.79 (0.07) vs. bronchopulmonary dysplasia 0.87 (0.11) cm, p=0.003], left ventricle in diastole [non-bronchopulmonary dysplasia 1.4 (0.19) vs. bronchopulmonary dysplasia 1.59 (0.21) cm, p=0.0006], ventricular septal thickness [non-bronchopulmonary dysplasia 0.23 (0.03) vs. bronchopulmonary dysplasia 0.26 (0.05) cm, p=0.032], and "a" measurement [(= sum of the isovolumetric contraction time, ejection time, and isovolumetric relaxation time) when calculating the myocardial performance index (p=0.01)]. CONCLUSION: Higher "a" interval in neonates with bronchopulmonary dysplasia suggests right ventricle diastolic dysfunction. We conclude that the right ventricle myocardial performance index is an important indicator both of ventricular function and for serial follow-up testing of very low birth weight premature neonates, especially those with bronchopulmonary dysplasia.

Association between early parenteral nutrition and the development of bronchopulmonary dysplasia in preterm infants / 中国当代儿科杂志

OBJECTIVES@#To study the relationship between early parenteral nutrient intake and the development of bronchopulmonary dysplasia (BPD) in preterm infants with gestational age less than 32 weeks who could not receive enteral nutrition within one week after birth.@*METHODS@#A retrospective study was conducted on preterm infants born between October 2017 and August 2022 with gestational age less than 32 weeks who were admitted to the Neonatal Intensive Care Unit in Children's Hospital of Soochow University within 24 hours after birth and relied solely on parenteral nutrition within the first week of life. The study population included 79 infants with BPD and 73 infants without BPD. Clinical data during hospitalization were compared between the two groups.@*RESULTS@#The proportions of infants with weight loss of more than 10% after birth, extrauterine growth retardation, and parenteral nutrition-associated cholestasis in the BPD group were higher than in the non-BPD group (P<0.05). The time to regain birth weight, time to achieve full enteral feeding, and corrected gestational age at discharge were longer in the BPD group than in the non-BPD group. The Z-scores of physical growth at corrected gestational age of 36 weeks were lower in the BPD group than in the non-BPD group (P<0.05). The BPD group had a higher fluid intake and a lower calories intake in the first week than the non-BPD group (P<0.05). The starting dose and total amount of amino acids, glucose, and lipids in the first week were lower in the BPD group than in the non-BPD group (P<0.05). The BPD group had a higher glucose-to-lipid ratio on the third day and higher energy-to-nitrogen and glucose-to-lipid ratios on the seventh day after birth than the non-BPD group (P<0.05).@*CONCLUSIONS@#Preterm infants with BPD had lower intake of amino acids and lipids and a lower proportion of calories provided by amino acids and lipids in the first week of life, which suggests an association between early parenteral nutrition intake and the development of BPD.

Changes and significance of type 2 innate lymphoid cells and their related factors in bronchopulmonary dysplasia / 中国当代儿科杂志

OBJECTIVES@#To investigate the changes and significance of type 2 innate lymphoid cells (ILC2), interleukin-33 (IL-33), interleukin-25 (IL-25), thymic stromal lymphopoietin (TSLP), interleukin-5 (IL-5), and interleukin-13 (IL-13) in peripheral blood of preterm infants with bronchopulmonary dysplasia (BPD).@*METHODS@#A total of 76 preterm infants with a gestational age of <32 weeks and a length of hospital stay of ≥14 days who were admitted to the Department of Pediatrics of the Affiliated Hospital of Jiangsu University from September 2020 to December 2021 were enrolled. According to the diagnostic criteria for BPD, they were divided into a BPD group with 30 infants and a non-BPD group with 46 infants. The two groups were compared in terms of the percentage of ILC2 and the levels of IL-33, IL-25, TSLP, IL-5, and IL-13 in peripheral blood on days 1, 7, and 14 after birth.@*RESULTS@#The BPD group had significantly lower birth weight and gestational age than the non-BPD group (P<0.05). On days 7 and 14 after birth, the BPD group had significantly higher levels of ILC2, IL-33, TSLP, and IL-5 than the non-BPD group (P<0.05), and these indices had an area under the curve of >0.7 in predicting the devolpment of BPD (P<0.05). Multivariate logistic regression analysis showed that after adjusting for gestational age and birth weight, peripheral blood IL-33, TSLP and IL-5 on days 7 and 14 after birth were closely related to the devolpment of BPD (P<0.05).@*CONCLUSIONS@#Early innate immune activation and upregulated expression of related factors may be observed in preterm infants with BPD. ILC2, IL-33, TSLP, and IL-5 may be used as biological indicators for early diagnosis of BPD.

Influence of bronchopulmonary dysplasia on cerebral blood flow in preterm infants: a prospective study based on arterial spin labeling / 中国当代儿科杂志

OBJECTIVES@#To investigate local cerebral blood perfusion in preterm infants with bronchopulmonary dysplasia (BPD) based on cerebral blood flow (CBF) values of arterial spin labeling (ASL).@*METHODS@#A prospective study was conducted on 90 preterm infants with a gestational age of <32 weeks and a birth weight of <1 500 g who were born in the Department of Obstetrics and admitted to the Department of Neonatology in the Third Affiliated Hospital of Zhengzhou University from August 2021 to June 2022. All of the infants underwent cranial MRI and ASL at the corrected gestational age of 35-40 weeks. According to the presence or absence of BPD, they were divided into a BPD group with 45 infants and a non-BPD group with 45 infants. The two groups were compared in terms of the CBF values of the same regions of interest (frontal lobe, temporal lobe, parietal lobe, occipital lobe, thalamus, and basal ganglia) on ASL image.@*RESULTS@#Compared with the non-BPD group, the BPD group had a significantly lower 1-minute Apgar score, a significantly longer duration of assisted ventilation, and a significantly higher incidence rate of fetal distress (P<0.05). After control for the confounding factors such as corrected age and age at the time of cranial MRI by multiple linear regression analysis, compared with the non-BPD group, the BPD group still had higher CBF values of the frontal lobe, temporal lobe, parietal lobe, occipital lobe, basal ganglia, and thalamus at both sides (P<0.05).@*CONCLUSIONS@#BPD can increase cerebral blood perfusion in preterm infants, which might be associated with hypoxia and a long duration of assisted ventilation in the early stage.

Progress on the role of circRNAs in lung development / 国际儿科学杂志

Many circular RNAs(circRNAs)have been discovered and identified as noncoding RNA in various organisms in a specie-, tissue-, disease-and developmental stage-specific manner, and have been demonstrated to play essential roles in myriad life processes, such as embryo and tissue development, aging, insulin secretion, vascular disease and cancer.The normal development of lung morphology, structure and function is the physiological basis of breath.Accumulating evidences have been demonstrated that circRNAs might be involved in lung development and play important roles in lung development and related diseases like bronchopulmonary dysplasia(BPD).This review will summarize the biological functions of circRNAs and focus particularly on the potential implications of circRNAs in lung development and BPD.

Progress of blood biomarkers in early prediction of bronchopulmonary dysplasia / 国际儿科学杂志

Bronchopulmonary dysplasia(BPD)is one of the most serious lung disease in the small gestational preterm infants, which may affect their development in infancy and adult quality of life.Blood samples of premature infants are easy to be collected and detected, and their biological markers are helpful for early prediction of BPD, which is of great significance for reducing the incidence of severe BPD and improving the poor prognosis of infants.In recent years, a variety of biological markers have been found in cord blood and serum of premature infants, including matrix metalloproteinase 9, tissue inhibitor of metalloproteinases 1, soluble Klotho protein, vascular endothelial growth factor, interleukin and N-terminal pro-brain natriuretic peptides, etc., some of which have been applied in clinic.It has broad application prospect for screening high-risk premature infants with BPD and effectively predicting the occurrence and severity of early BPD.

Progress of T lymphocytes in the pathogenesis of bronchopulmonary dysplasia in premature infants / 国际儿科学杂志

Bronchopulmonary dysplasia(BPD)is a severe complication in premature infants, and the pathogenesis remains complex, potentially involving pulmonary inflammatory injury and faulty reparative response.T-cell immaturity in preterm neonates and the upregulation of related harmful regulatory genes, as well as the imbalance of T-cell homeostasis, have been reported to contribute significantly to the development of inflammatory diseases.Growing evidence suggests that alterations in the levels and functions of T cell subsets may participate in the development of BPD, serving as a new avenue for BPD prevention and treatment.Herein, we summarize recent advancements in understanding the role of T lymphocytes in the pathogenesis of BPD.

Advances in neutrophil extracellular traps in bronchopulmonary dysplasia / 国际儿科学杂志

Due to the development of neonatal intensive care, the survival rate of very preterm infants and very low birth weight infants has been significantly improved, and the incidence of bronchopulmonary dysplasia (BPD) has been obviously increasing year by year.The pathogenesis of BPD has not been clear, it is considered that inflammation is an important link in the occurrence and development of BPD at present.Neutrophils can use their neutrophil extracellular traps (NETs) to capture and kill pathogens and reduce inflammation, but excessive formation of NETs is easy to induce inflammatory imbalance, so as to damage normal cells or tissues and participate in the pathophysiological process of BPD.This paper reviews the structure, formation, function and regulatory role of NETs in BPD, and the targeted treatment strategies and potential research directions of NETs in BPD.