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.

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.

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.

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.

Clinical characteristics and risk factors of 341 very preterm/very low birth weight infants with bronchopulmonary dysplasia / 中国医师杂志

Objective:To investigate clinical characteristics and potential risk factors of very preterm/very low birth weight infants with bronchopulmonary dysplasia (BPD).Methods:A retrospective epidemiological study was performed in 341 neonates with birth weights<1 500 g or gestational age between 23 + 0 to 31 + 6 weeks, who were born in Foshan Women and Children Hospital and were admitted to neonatal intensive care units (NICU) within 24 hours of birth. These neonates were divided into non-BPD group and BPD group. Clinical characteristics and potential risk factors were comparatively analyzed between groups. Risk factors for BPD were identified by binary logistic regression analysis. Results:Among the total of 341 enrolled neonates, including 255 neonates without BPD and 86 neonates with BPD, the total incidence of BPD was 25.2%. The incidences of BPD in the infants with gestational age of <30 weeks, 30-32 weeks, and >32 weeks, as well as birth weight <1 000 g, 1 000-1 499 g, and ≥1 500 g were 43.8%(63/144), 15.1%(22/146), 2.0%(1/51), 80.0%(36/45), 20.2%(41/203), 9.7%(9/93), respectively. The gestational age, birth weight, the proportion of cesarean section, and extubation rate within 7 days were lower in BPD group than those in non-BPD group [(28.5±2.4)weeks vs (30.7±1.8)weeks, (1 087.9±312.8)g vs (1 418.4±247.9)g, 54.6%(47/86) vs 75.7%(193/255), 57.1%(44/77) vs 90.0%(108/120), all P<0.05]. Compared to the non-BPD group, the proportion of Apgar score of ≤7 points 5 minutes after birth [16.3%(14/86) vs 2.4%(6/255)], postnatal endotracheal intubation rate [62.8%(54/86) vs 27.4%(70/255)], volume of red blood cell transfusion ≥3 times [31.4%(27/86) vs 6.3%(16/255)], pulmonary surfactant (PS) utilization [82.6%(71/86) vs 44.7%(114/255)], rate of conventional mechanical ventilation [89.5%(77/86) vs 47.0%(120/255)], combined with hemodynamically significant patent ductus arteriosus (HsPDA) [34.9%(30/86) vs 8.2%(21/255)], diagnosed with neonatal respiratory distress syndrome (NRDS) [94.2%(81/86) vs 5.9%(15/255)], combined with clinically diagnosed sepsis [17.4%(15/86) vs 7.0%(18/255)], combined with ≥3 stage retinopathy of prematurity (ROP) [20.9%(18/86) vs 2.7%(7/255)] and mortality [10.5%(9/86) vs 0.8%(2/255)], length of conventional mechanical ventilation, duration of oxygen consumption, and length of hospital stays were higher in the BPD group (all P<0.05). The results of multivariate logistic regression analysis showed that small gestational age ( OR=1.285, 95% CI: 1.010-1.633), Apgar score ≤7 points within 5 min of birth ( OR=5.712, 95% CI: 1.411-23.115), mechanical ventilation duration ( OR=1.113, 95% CI: 1.043-1.188) and oxygen duration ( OR=1.139, 95% CI: 1.092-1.188) were high risk factors for the development of BPD, while heavier birth weight ( OR=0.996, 95% CI: 0.994-0.998) was protective factor for BPD. Conclusions:The smaller the gestational age and the lower the birth weight, the higher the incidence of BPD, Apgar score≤7 points within 5 min of birth, long conventional mechanical ventilation time, and long duration of oxygen consumption are the risk factors for BPD. Prevention of premature delivery, reduction of asphyxia at birth, reduction of endotracheal intubation and invasive ventilation duration, and reduction of oxygen use time are effective measures to reduce the occurrence of BPD.

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.

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.

Establishment and validation of a nomograph model for prediction of bronchopulmonary dysplasia in very low birth weight infants born earlier than 32 weeks / 中华围产医学杂志

Objective:To investigate the risk factors of bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) infants with gestational age ≤32 weeks within 28 days after birth and to establish and validate the nomogram model for BPD prediction.Methods:We retrospectively chose VLBW infants with gestational age ≤32 weeks who survived to postmenstrual age (PMA) 36 weeks and were admitted to the neonatal intensive care unit of Peking University Third Hospital from January 2016 to April 2020 as the training cohort. BPD was diagnosed in accordance with the 2018 criteria. The clinical data of these infants were collected, and the risk factors of BPD were analyzed by Chi-square test, Mann-Whitney U test, and multivariate logistic regression, and a nomogram model was established. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to assess the predictive performance. Decision curve analysis (DCA) was constructed for differentiation evaluation, and the calibration chart and Hosmer-Lemeshow goodness of fit test were used for the calibration evaluation. Bootstrap was used for internal validation. VLBW infants with gestational age ≤32 weeks survived to PMA 36 weeks and admitted to Hebei Chengde Maternal and Child Health Hospital from October 2017 to February 2022 were included as the validation cohort. ROC curve and calibration plot were conducted in the validation cohort for external validation. Results:Of the 467 premature infants included in the training cohort, 104 were in the BPD group; of the 101 patients in the external validation cohort, 16 were in the BPD group. Multivariate logistic regression analysis showed that low birth weight ( OR=0.03, 95% CI: 0.01-0.13), nosocomial pneumonia ( OR=2.40, 95% CI: 1.41-4.09), late-onset sepsis ( OR=2.18, 95% CI: 1.18-4.02), and prolonged duration of endotracheal intubation ( OR=1.61, 95% CI: 1.26-2.04) were risk factors for BPD in these groups of infants (all P<0.05). According to the multivariate logistic regression analysis results, a nomogram model for predicting BPD risk was established. The AUC of the training cohort was 0.827 (95% CI: 0.783-0.872), and the ideal cut-off value for predicted probability was 0.206, with a sensitivity of 0.788 (95% CI: 0.697-0.862) and specificity of 0.744 (95% CI: 0.696-0.788). The AUC of the validation cohort was 0.951 (95% CI:0.904-0.999). Taking the prediction probability of 0.206 as the high-risk threshold, the sensitivity and specificity corresponding to this value were 0.812 (95% CI: 0.537-0.950) and 0.882 (95% CI: 0.790-0.939). The Hosmer-Lemeshow goodness-of-fit test in the training and validation cohort showed a good fit ( P>0.05). DCA results showed a high net benefit of clinical intervention in very preterm infants when the threshold probability was 5%~80% for the training cohort. Conclusion:Low birth weight, nosocomial pneumonia, late-onset sepsis, and prolonged tracheal intubation duration are risk factors for BPD. The established nomogram model has a certain value in predicting the risk of BPD in VLBW less than 32 weeks.

Association between ureaplasma urealyticum colonization in respiratory tract and bronchopulmonary dysplasia in extremely preterm or extremely low birth weight infants / 中华围产医学杂志

Objective:To investigate the association between ureaplasma urealyticum (UU) colonization in the respiratory tract and bronchopulmonary dysplasia (BPD) in extremely preterm or extremely low birth weight infants.Methods:This was a retrospective study involving preterm infants with gestational age <28 weeks or birth weight <1 000 g who was hospitalized in the Neonatal Intensive Care Unit (NICU) of Chengdu Women's and Children's Central Hospital from June 2019 to March 2022. Respiratory tract secretion was collected for UU DNA detection within 24 h after admission. All the participants were divided into the UU-positive or negative groups based on the detection results. Clinical characteristics of the two groups were analyzed using Mann-Whitney U, t-, or Chi-square tests (Fisher exact test). Results:A total of 82 infants were enrolled, including 31 cases (37.8%) in the UU-positive group and 51 patients (62.2%) in the negative group. Among the 30 cases treated with azithromycin in the positive group, 27 (90.0%, 27/30) turned negative after two courses of treatment. The rates of premature rupture of membranes [51.6% (16/31) vs 17.6% (9/51), χ2=10.50] and prenatal antibiotic exposure [71.0% (22/31) vs 47.1% (24/51), χ2=4.47] in the UU-positive group were both higher than those in the UU-negative group (both P<0.05). Multivariate logistic regression analysis showed that premature rupture of membranes ( OR=5.893, 95% CI: 2.016-17.228) and gestational age ( OR=0.663, 95% CI: 0.441-0.999) were independent risk factors for UU colonization (both P<0.05). UU-positive group had a longer duration of oxygen use [ M ( P25- P75), 1 756 h (1 385-2 088 h) vs 1 357 h (1 128-1 656 h), Z=2.98], a longer length of hospital stay [81 d (70-105 d) vs 68 d (59-84 d), Z=3.05], and higher hospitalization costs [(201 574±70 326) yuan vs (161 288±53 412) yuan, t=－2.74] compared to the UU negative group (all P<0.05). The incidence of BPD [74.2% (23/31) vs 47.1% (24/51), χ2=5.80] and retinopathy of prematurity [93.4% (29/31) vs 74.5% (38/51), χ2=4.68] in the UU positive group was higher than those in the UU-negative group (both P<0.05). No significant correlation was found between UU colonization and the severity of BPD ( P>0.05). Conclusion:UU colonization may increase the incidence of BPD, but there was no clear correlation with the severity of BPD.

A case of survived extremely preterm infant with severe bronchopulmonary dysplasia after comprehensive therapy / 中华围产医学杂志

This article reported the comprehensive management of an extremely preterm infant with severe bronchopulmonary dysplasia. The patient born at 26 +6 gestational weeks was transferred to Children's Hospital of Fudan University due to invasive mechanical ventilation dependence at 61 d after birth and was diagnosed with severe bronchopulmonary dysplasia. A comprehensive treatment plan was adopted, including appropriate fluid restriction, improving nutrition, glucocorticoid administration, using antibiotics against Ureaplasma urealyticum infection to reduce pulmonary parenchymal lesions and alleviating pulmonary hypertension. The preterm infant was successfully extubated to non-invasive ventilation and subsequently weaned to a high-flow nasal cannula. Then, the patient was discharged at 372 d after birth (correct gestational age nine months and six days). At the 3-month follow-up after discharge, the patient remained on high-flow oxygen, but with lower flow and concentration of oxygen. Moreover, the growth, development and lung images were significantly improved. Follow-up to correct gestational age one year and 11 months, the child was not on oxygen any more, but on rehabilitation due to language and motor development retardation.

Current status and trends of bronchopulmonary dysplasia in preterm infants: a Chinese bibliometric study / 中国新生儿科杂志

Objective:To study the current status and existing problems of bronchopulmonary dysplasia (BPD) in preterm infants in Chinese literature using bibliometric methods.Methods:Using "preterm infants", "BPD" and "chronic lung disease of prematurity"(Chinese version)as keywords, Wanfang database was searched up to August 27th, 2022. Literature published in high-influencing journals were selected for bibliometrical and social network analysis.Results:A total of 2 172 articles published in 311 journals were included. The number of articles increased rapidly year by year, involving studies on the risk factors and respiratory management of BPD. Dynamic researches focused on the following topics:1,selection of multiple non-invasive ventilation modes combined with minimally invasive surfactant administration; 2,the application of caffeine and glucocorticoids and 3, follow-up after discharge.Conclusions:In the past 40 years, research on BPD in preterm infants in China has mainly focused on risk factors and prevention. However, research on pathogenesis and other aspects needs to be strengthened.

Risk factors and prognosis of pulmonary hypertension associated with bronchopulmonary dysplasia in extremely preterm infants / 中国新生儿科杂志

Objective:To study the risk factors and prognosis of pulmonary hypertension(PH) associated with bronchopulmonary dysplasia (BPD) in extremely preterm infants(EPIs).Methods:From January 2020 to December 2021, EPIs [gestational age (GA) <32 w] with BPD admitted to NICU of our hospital were retrospectively assigned into two groups: BPD with late-onset PH(PH group) and BPD without late-onset PH(non-PH group). Their general condition, treatment and prognosis were compared and the risk factors of late-onset PH were analyzed.Results:A total of 229 EPIs with BPD were enrolled, including 24(10.5%) in the PH group and 205(89.5%) in the non-PH group. The PH group had significantly smaller GA [(27.9±2.3) w vs. (28.7±1.8) w], longer mechanical ventilation [42.0(16.0, 84.0) d vs. 9.0(2.0, 23.0) d], longer hospital stay [100.5(86.3, 142.0) d vs. 77.0(56.5, 96.5)d],higher incidence of early-onset PH(54.2% vs. 9.3%) and higher mortality rate(33.3% vs. 9.8%) than the non-PH group ( P<0.05). Multivariate logistic regression analysis showed prolonged mechanical ventilation ( OR=1.046, 95% CI 1.011~1.064), early-onset PH ( OR=5.414, 95% CI 1.796~16.323) were independent risk factors for BPD with late-onset PH. 8(33.3%) patients in the PH group died, including 2 with grade Ⅱ BPD and 6 grade Ⅲ BPD. Conclusions:Prolonged mechanical ventilation and early-onset PH are independent risk factors for late-onset PH in BPD infants. BPD infants with late-onset PH have longer hospital stay, higher mortality and worse prognosis.

Effects of patent ductus arteriosus on bronchopulmonary dysplasia in very low birth weight preterm infants / 中国新生儿科杂志

Objective:To study the effects of patent ductus arteriosus (PDA) on bronchopulmonary dysplasia (BPD) in very low birth weight preterm infants (VLBWIs).Methods:From January 2018 to December 2020,VLBWIs hospitalized in NICU of our hospital were retrospectively analyzed.They were assigned into BPD group and non-BPD group according to whether BPD occurred. Clinical data including the severity of BPD , the diameter and duration of PDA and ibuprofen usage were analyzed. The predictive values of PDA diameter and duration for BPD were calculated using area under curve (AUC) of receiver operating characteristic curve (ROC) analysis.Results:A total of 173 VLBWIs were enrolled, including 42 in the BPD group and 131 in the non-BPD group. The incidence of hemodynamically significant PDA (hsPDA) in the BPD group was significantly higher than the non-BPD group (45.2% vs. 22.1%, P=0.001).hsPDA ( OR=2.806, 95% CI 1.307-5.745, P=0.005), PDA diameter ≥1.5 mm ( OR=7.003, 95% CI 1.323-48.884, P<0.001) and PDA duration >1 w ( OR=7.754, 95% CI 1.203-49.989, P=0.031) were all risk factors for BPD.As for the severity of BPD, hsPDA, PDA diameter ≥1.5 mm, PDA duration >1 w and FiO 2max >30% within 72 h after birth were risk factors for grade Ⅱ~Ⅲ BPD. The incidence of ibuprofen usage was significantly higher in grade Ⅱ~Ⅲ BPD group. If the diameter of PDA was 1.25 mm, the AUC was 0.806 (95% CI 0.706-0.906, P<0.001), sensitivity 82.6% and specificity 68.7% for grade Ⅱ~Ⅲ BPD. If the PDA duration was 10.5 d, the AUC was 0.821 (95% CI 0.718-0.925, P<0.001), sensitivity 65.2% and specificity 91.3%. Conclusions:hsPDA, larger PDA diameter and longer PDA duration are risk factors for the occurrence and severity of BPD in VLBWIs.

Risk factors and clinical outcomes of early-onset pulmonary hypertension in preterm infants with gestational age≤ 32 weeks / 中国新生儿科杂志

Objective:To study the risk factors and clinical outcomes of early pulmonary hypertension in preterm infants with gestational age(GA)≤32 w.Methods:From October 2017 to May 2021,preterm infants with GA≤ 32 w admitted to NICU of our hospital were retrospectively studied. According to their echocardiography 2 w after birth, the infants were assigned into early-onset pulmonary hypertension (ePH) group and non-PH group. SPSS 21.0 statistical software was used to analyze the general status, complications and clinical outcomes of the two groups. Multiple logistic regression was used to analyze the risk factors of early-onset PH.Results:A total of 183 cases were enrolled, including 24 in the ePH group and 159 in the non-PH group. The incidences of birth asphyxia, hemodynamically significant patent ductus arteriosus (hsPDA), FiO 2≥30% within 6 h after birth, late-onset PH, severe bronchopulmonary dysplasia(BPD) and intracranial hemorrhage(ICH) in the ePH group were significantly higher than the non-PH group( P<0.05). hsPDA was the independent risk factor for early-onset PH ( OR=11.781, 95% CI 4.192-33.108). Conclusions:Preterm infants with GA≤32 w and early-onset PH are at increased risks of ICH, late-onset PH and severe BPD, hsPDA is the independent risk factor for early-onset PH.

The role of miR-15b and vascular endothelial growth factor in the pathogenesis of novel bronchopulmonary dysplasia in neonatal rats / 中国新生儿科杂志

Objective:To study the role of miRNA-15b and vascular endothelial growth factor (VEGF) in the pathogenesis of novel bronchopulmonary dysplasia (nBPD) in rats.Methods:A total of 100 newborn SD rats were randomly assigned into BPD group and control group with 50 rats in each group. The BPD group was placed in oxygen chamber with 60% oxygen concentration and the control group received atmospheric air. The morphological changes of lung tissues were observed on 1 d, 7 d, 14 d and 21 d and the radial alveolar counts (RAC) and alveolar septal thickness (AST) were measured. The expression of miR-15b was measured using real-time quantitative PCR and the expression of VEGF in lung tissue was examined using ELISA method.Results:With prolonged oxygen exposure, the lung tissue of the BPD group showed a decrease in the number of alveoli, a gradual loss of the normal structure of alveoli and a significant widening of the alveolar septum. On 7 d, 14 d and 21 d, RAC values [(6.19±0.29) vs. (6.86±0.92), (5.35±0.67) vs.(9.75±0.34), (3.96±0.45) vs. (10.04±0.52)] were significantly lower in the BPD group than the control group ( P<0.05). On 7 d, 14 d and 21 d,the levels of AST in BPD group were significantly higher than the control group [(6.87±0.41) μm vs. (6.43±0.31) μm, (8.94±0.25) μm vs. (5.36±0.26) μm, (9.61±0.30) μm vs. (4.55±0.32) μm] ( P<0.05). On 7 d, 14 d and 21 d,the miR-15b expression in BPD group were significantly higher than the control group [(1.12±0.11) vs. (0.84±0.09), (1.33±0.09) vs. (0.73±0.07), (1.66±0.15) vs. (0.45±0.10)] ( P<0.05).On 7 d, 14 d and 21 d, VEGF in BPD group were significantly lower than the control group [(10.89±1.67) pg/ml vs. (23.86±4.38) pg/ml, (8.75±1.28) pg/ml vs. (53.94±3.49) pg/ml, (4.66±1.12) pg/ml vs. (70.37±3.10) pg/ml] ( P<0.05). Conclusions:MiR-15b and VEGF may play a role in the development of nBPD.

The effects of quality improvement program on the incidence of bronchopulmonary dysplasia in very preterm infants / 中国新生儿科杂志

Objective:To evaluate the effects of quality improvement (QI) program on the incidence of bronchopulmonary dysplasia (BPD) in very preterm infants (VPIs) [gestational age (GA)<32 weeks].Methods:From July to December 2017,VPIs admitted to the Department of Neonatology of Yancheng Maternity and Child Health Care Hospital were retrospectively enrolled and were assigned into pre-quality improvement program group (Pre-QI group).From July to December 2018, VPIs were assigned into post-quality improvement program group (Post-QI group). QI program included delayed umbilical cord clamping (DCC), early postnatal nasal continuous positive airway pressure ventilation (nCPAP) and minimally invasive pulmonary surfactant therapy (MIST). The clinical data and prognostic indicators of the two groups of VPIs and their mothers were compared. Independent sample t-test or continuity-adjusted Chi-square test (or Fisher's exact test) and Logistic regression were used for statistical analysis. Results:A total of 204 VPIs were enrolled, including 96 cases in Pre-QI group and 108 cases in Post-QI group. 1 min Apgar score and hematocrit on admission to the neonatal intensive care unit (NICU) in the Post-QI group were significantly higher than the Pre-QI group( P<0.05). The incidence of delivery room resuscitation, endotracheal intubation at birth and endotracheal intubation in NICU in the Post-QI group were significantly lower than the Pre-QI group( P<0.05). The application of pulmonary surfactant and mechanical ventilation, the incidence of neonatal respiratory distress syndrome and BPD in the Post-QI group were lower than the Pre-QI group ( P<0.05). After adjusting for confounding factors, Logistic regression analysis showed that DCC ( aOR=0.261,95% CI 0.091~0.718, P=0.023), nCPAP ( aOR=0.284,95% CI 0.123~0.667, P=0.015), MIST ( aOR=0.276,95% CI 0.114~0.627, P=0.011) were protective factors of BPD, and MV ( aOR=2.023,95% CI 1.048~3.918, P=0.036) was risk factor of BPD. Conclusions:The QI program consisting of DCC, early nCPAP and MIST for VPIs can reduce the incidence of BPD.

Predictive value of serum thrombospondin-1 and transforming growth factor-β1 levels in preterm infants with bronchopulmonary dysplasia / 中国小儿急救医学

Objective:To study the early predictive values of serum thrombospondin-1(TSP-1)and transforming growth factor-β1(TGF-β1) for bronchopulmonary dysplasia(BPD)in preterm infants.Methods:From September 2020 to April 2022, preterm infants with gestational age<32 weeks and ≥28 weeks as well as birth weight<1 500 g admitted to neonatal intensive care unit within 2 hours after birth were enrolled in the study.The dynamic changes of serum TSP-1 and TGF-β1 levels in preterm infants were observed on 1st, 7th, 14th, and 28th day after birth.Preterm infants were divided into BPD group and non-BPD group according to the diagnostic criteria of BPD.Receiver operating characteristic(ROC) curve and area under curve(AUC)was used to analyze the predictive value of serum TSP-1 and TGF-β1 for preterm infants with BPD.Results:According to the diagnostic criteria of BPD, 38 cases were in the BPD group and 52 cases in the non-BPD group.There was no significant difference in gestational age, birth weight and gender between the two groups( P>0.05). The levels of TSP-1 and TGF-β1 in the serum of BPD group were gradually increased, which were significantly higher than those of non-BPD group on the 1st, 7th, 14th, and 28th day( P<0.001). ROC results showed that AUC of TSP-1, TGF-β1 and their combination for predicting BPD were 0.889(95% CI 0.819~0.959), 0.826(95% CI 0.743~0.910), and 0.923(95% CI 0.870~0.976), respectively.The sensitivity were 86.80%, 86.70%, 89.50%, and the specificity were 86.50%, 73.10%, 80.80%, respectively.Cutoff values of TSP-1 and TGF-β1 for predicting BPD were 44.50 μg/L and 6.13 μg/L, respectively. Conclusion:Combined detection of serum TSP-1 and TGF-β1 on the first day after birth has an early predictive value for BPD in preterm infants.