Efetividade das intervenções para prevenção de displasia broncopulmonar em recém-nascidos prematuros sob ventilação mecânica invasiva: overview de revisões sistemáticas / Effectiveness of interventions for the prevention of bronchopulmonary dysplasia in premature newborns under invasive mechanical ventilation: overview of systematic reviews

Contextualização: A displasia broncopulmonar é uma das principais causas de enfermidade respiratória crônica na infância, levando a hospitalizações frequentes e prolongadas e com altos índices de mortalidade, alterações do crescimento pôndero-estatural e desenvolvimento neuropsicomotor. Tamanho impacto justifica o grande investimento nas pesquisas para identificar suas causas e buscar alternativas para prevenção e tratamento. Objetivos: Avaliar a efetividade das intervenções para prevenção de displasia broncopulmonar em recém-nascidos prematuros com ventilação mecânica invasiva. Métodos: Trata-se de overview de revisões sistemáticas realizadas pela Colaboração Cochrane. Procedeu-se à busca na Cochrane Library (2022), utilizando os termos "neonatal prematurity" e "bronchopulmonary dysplasia". Foram incluídos todos os ensaios clínicos randomizados. O desfecho primário de análise foi a redução de morbimortalidade. Resultados: A estratégia de busca recuperou um total de 47 revisões sistemáticas. Oito foram incluídas, totalizando 94 ensaios clínicos randomizados e 10.511 participantes. Discussão: Os estudos demonstram efetividade de corticosteroides, mas é necessário cautela na dosagem e no momento correto para sua administração. O uso de surfactante sintético pode trazer benefícios respiratórios, mas requer novos estudos. Não se justifica o uso de pentoxifilina. Conclusão: A displasia broncopulmonar tornou-se um grande desafio para o neonatologista e as revisões sistemáticas Cochrane sugerem que a corticoterapia pode ser efetiva na prevenção dessa condição, embora novos estudos sejam recomendados para estabelecer dosagem ideal e melhor momento para a terapêutica.

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.

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.

Efficacy of noninvasive high-frequency oscillatory ventilation versus nasal intermittent positive pressure ventilation as post-extubation respiratory support in preterm infants: a Meta analysis / 中国当代儿科杂志

OBJECTIVES@#To systematically evaluate the efficacy and safety of noninvasive high-frequency oscillatory ventilation (NHFOV) versus nasal intermittent positive pressure ventilation (NIPPV) as post-extubation respiratory support in preterm infants.@*METHODS@#China National Knowledge Infrastructure, Wanfang Data, Chinese Journal Full-text Database, China Biology Medicine disc, PubMed, Web of Science, and the Cochrane Library were searched for articles on NHFOV and NIPPV as post-extubation respiratory support in preterm infants published up to August 31, 2022. RevMan 5.4 software and Stata 17.0 software were used for a Meta analysis to compare related indices between the NHFOV and NIPPV groups, including reintubation rate within 72 hours after extubation, partial pressure of carbon dioxide (PCO2) at 6-24 hours after switch to noninvasive assisted ventilation, and the incidence rates of bronchopulmonary dysplasia (BPD), air leak, nasal damage, periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP).@*RESULTS@#A total of 9 randomized controlled trials were included. The Meta analysis showed that compared with the NIPPV group, the NHFOV group had significantly lower reintubation rate within 72 hours after extubation (RR=0.67, 95%CI: 0.52-0.88, P=0.003) and PCO2 at 6-24 hours after switch to noninvasive assisted ventilation (MD=-4.12, 95%CI: -6.12 to -2.13, P<0.001). There was no significant difference between the two groups in the incidence rates of complications such as BPD, air leak, nasal damage, PVL, IVH, and ROP (P>0.05).@*CONCLUSIONS@#Compared with NIPPV, NHFOV can effectively remove CO2 and reduce the risk of reintubation, without increasing the incidence of complications such as BPD, air leak, nasal damage, PVL, and IVH, and therefore, it can be used as a sequential respiratory support mode for preterm infants after extubation.

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.

A multicenter prospective cohort study of late-onset sepsis and its poor prognosis in very low birth weight infants / 中华儿科杂志

Objective: To investigate the prevalence and poor prognosis of late-onset sepsis (LOS) in very low birth weight infant (VLBWI). Methods: This prospective, multicenter observational cohort study was conducted based on the data from Sina-Northern Neonatal Network (SNN). The general data, perinatal information and poor prognosis of 6 639 VLBWI, who were admitted to the 35 neonatal intensive care units from 2018 to 2021, were collected and analyzed. According to the occurrence of LOS during hospitalization, the VLBWI were assigned to the LOS group and non-LOS group. The LOS group was further divided into 3 subgroups according to the occurrence of neonatal necrotizing enterocolitis (NEC) and purulent meningitis. The Chi-square test or Fisher exact probability method, independent sample t test, Mann-Whitney U test and multivariate Logistic regression model were used to analyze the relationship between LOS and poor prognosis in VLBWI. Results: A total of 6 639 eligible VLBWI were enrolled, including 3 402 cases (51.2%) of males and 1 511 cases (22.8%) with LOS. The incidences of LOS in extremely low birth weight infants (ELBWI) and extremely preterm infants were 33.3% (392/1 176) and 34.2% (378/1 105), respectively. There were 157 cases (10.4%) who died in the LOS group and 48 cases (24.9%) in the subgroup of LOS complicated with NEC. Multivariate Logistic regression analysis showed that LOS complicated with NEC was associated with increased mortality and incidence of grade Ⅲ-Ⅳ intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL), moderate or severe bronchopulmonary dysplasia (BPD), and extrauterin growth retardation (EUGR) (ORadjust=5.27, 2.59, 3.04, 2.04; 95%CI 3.60-7.73, 1.49-4.50, 2.11-4.37, 1.50-2.79; all P<0.01); LOS complicated with purulent meningitis was also associated with increased mortality and incidence of grade Ⅲ-Ⅳ IVH or PVL, and moderate or severe BPD (ORadjust=2.22, 8.13, 3.69, 95%CI 1.30-3.37, 5.22-12.67, 2.49-5.48; all P<0.01); the infants without NEC or purulent meningitis in the LOS group was only associated with increased incidence of moderate or severe BPD (ORadjust=2.20, 95%CI 1.83-2.65, P<0.001). After ruling out contaminated bacteria, a total of 456 cases showed positive blood culture, including 265 cases (58.1%) of Gram-negative bacteria, 126 cases (27.6%) of Gram-positive bacteria, and 65 cases (14.3%) of fungi. The most common pathogenic bacteria was Klebsiella pneumoniae (n=147, 32.2%), followed by coagulase-negative Staphylococcus (n=72, 15.8%) and subsequently Escherichia coli (n=39, 8.6%). Conclusions: The incidence of LOS is high in VLBWI. Klebsiella pneumoniae is the most common pathogenic bacteria, followed by coagulase-negative Staphylococcus and Escherichia coli. LOS is associated with a poor prognosis for moderate to severe BPD. The prognosis of LOS complicated with NEC is poor with the highest mortality, and the risk of brain damage is significantly increased when LOS complicated with purulent meningitis.

Status of fungal sepsis among preterm infants in 25 neonatal intensive care units of tertiary hospitals in China / 中华儿科杂志

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.

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.

Tratamento da broncodisplasia pulmonar: uma revisão sistemática / Treatment of pulmonary broncodysplasia: a systematic review

Introdução: Displasia broncopulmonar (DBP) é uma grave complicação entre pré-termos, com incidência inversamente proporcional à idade gestacional. Resulta de processo inflamatório com desenvolvimento pulmonar anormal, gerando graves consequências. Apesar de serem limitadas e não afetarem substancialmente a evolução da doença, as opções terapêuticas para prevenção e tratamento da DBP são importantes, porém carecem de melhor elucidação. Objetivos: Abordar aspectos recentes da literatura quanto à prevenção e tratamento da DBP. Métodos: Revisão de literatura na base de dados MEDLINE, em 2021, incluindo ensaios clínicos controlados e randomizados, realizados em humanos e nos últimos 5 anos, excluindo estudos não diretamente relacionados ao tema. Resultados: A incidência de DBP foi menor naqueles casos leves expostos à budesonida inalatória, óleo de peixe intravenoso contendo emulsão lipídica (OP) e ácido docosahexaenoico (DHA). Houve aumento da sobrevida com uso de hidrocortisona em baixas doses, dexametasona com redução gradual da dose, por 42 dias, e dexametasona associada a corticosteroides pós-natais (este ainda com redução dos prejuízos no neurodesenvolvimento). Hidrocortisona, dexametasona, dipropianato de hidrofluoalcano-beclometasona inalado e OP reduziram o tempo ou a necessidade de ventilação e oxigenoterapia. A mortalidade foi menor nos estudos envolvendo hidrocortisona e elevada no que avaliou budesonida. As principais complicações foram sepse, retinopatia, hemorragia intraventricular e enterocolite necrosante, nos estudos abordando DHA, hidrocortisona, dexametasona e óxido nítrico inalado. Conclusão: Abordagens terapêuticas satisfatórias foram os glicocorticoides associado à terapia ventilatória e à abordagem precoce. Não houve benefícios com uso de ventilação com insuflações sustentadas, administração de dipropionato de hidrofluoralcano-beclometasona inalada e DHA.

Introduction: Bronchopulmonary dysplasia (BPD) is a complication among preterms, with an incidence inversely proportional to gestational age. It results from an inflammatory process that causes abnormal lung development, with severe consequences. Although therapeutic options are limited and do not substantially strike the course of the disease, they are important tools and need further elucidation. Purpose: Address the most recent aspects of the literature regarding the prevention and treatment of BPD. Methods: A literature review was carried out in the MEDLINE database, in 2021, in which only controlled and randomized clinical studies performed in humans in the last 5 years were included. Studies that were not directly related to the theme were excluded. Results: The incidence of BPD was lower in those cases exposed to inhaled budesonide, intravenous fish oil containing lipid emulsion (FO) and docosahexaenoic acid (DHA). There was improvement in survival with a lowdose use of hydrocortisone, dexamethasone with gradual dose reduction, and dexamethasone associated with postnatal corticosteroids (which generated reduction in neurodevelopmental impairments as well). Hydrocortisone, dexamethasone, inhaled hydrofluoalkane-beclomethasone dipropynate and FO reduced the time or need for ventilation and oxygen therapy. The main complications were sepsis, retinopathy, intraventricular hemorrhage and necrotizing enterocolitis in studies that addressed DHA, hydrocortisone, dexamethasone and inhaled nitric oxide. Conclusion: The therapeutic approaches that proved to be conclusive were the use of glucocorticoids associated with ventilatory therapy and an early approach. No benefits were found with the use of ventilation with sustained inflation, administration of inhaled hydrofluoralkane-beclomethasone dipropionate and DHA.

Avaliação do gasto metabólico, crescimento e composição coporal em recém-nascidos pré-termos com displasia broncopulmonar / Evaluation of metabolic expenditure, growth and body composition in preterm newborns with bronchopulmonary dysplasia

Os recém-nascidos pré-termos, principalmente os de extremo baixo peso, com os avanços tecnológicos estão sobrevivendo mais e garantir uma nutrição adequada é um dos grandes desafios da neonatologia. As morbidades encontradas, entre as quais a displasia broncopulmonar, contribuem de forma determinante no manejo hídrico e nutricional desta população. A displasia broncopulmonar (DBP) é uma das morbidades mais frequentes em recém-nascidos pré-termos, e com os avanços médicos, as técnicas menos agressivas de suporte ventilatório, o uso de corticosteroides antenatais e surfactante, a tendência é uma diminuição na sua incidência, o que não ocorreu na população de pré-termos extremos, devido à maior sobrevida desta população. A restrição do crescimento após o nascimento neste grupo de recém-nascidos com DBP decorre de diversos fatores: o maior gasto energético devido ao aumento do trabalho respiratório, a inflamação e o reparo tissular e a diminuição da ingesta alimentar, dificultando a oferta de um aporte nutricional adequado. A nutrição tem efeito direto sobre a maturação pulmonar e, portanto, a oferta insuficiente de nutrientes pode exacerbar os danos alveolares. O conhecimento do gasto energético de repouso pode auxiliar na programação da oferta de energia diária. Estudos com calorimetria indireta têm sido utilizados para verificar o gasto energético dos recém-nascidos. É importante, portanto, estudar o gasto metabólico e avaliar o seu impacto no crescimento pondero estatural e na composição corporal de recém-nascidos pré-termo com DBP, considerando as mudanças terapêuticas ocorridas. Os objetivos deste estudo foram: (i) avaliar o gasto metabólico, a composição corporal, e o crescimento pondero- estatural de recém-nascidos com e sem DBP na idade corrigida de termo; (ii) analisar a associação entre o gasto metabólico, a composição corporal e o crescimento (escores Z de peso, comprimento e perímetro cefálico) na idade corrigida de termo. Foram incluídos no estudo recém-nascidos com idade gestacional < 32 semanas, admitidos na Unidade de Terapia Intensiva Neonatal do Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira; foi considerada como exposição o desenvolvimento de DBP. A DBP foi definida pela necessidade de oxigênio às 36 semanas de idade corrigida. Foram excluídos do estudo recém-nascidos com malformações congênitas, síndromes vii genéticas, hidropisia fetal, infecções congênitas comprovadas e aqueles que estavam em suporte ventilatório no momento da avaliação do gasto energético. Para a avaliação do aporte nutricional foram registradas as quantidades de proteínas, lipídios, carboidratos e calorias efetivamente recebidas diariamente nas primeiras quatro semanas de vida e no momento de cada avaliação na idade corrigida de termo. Foram registradas informações gestacionais e perinatais. No momento de avaliação foi registrado o tipo de alimentação: leite materno exclusivo, leite materno complementado com fórmula, fórmula exclusiva ou fórmula especial. No caso dos recém-nascidos com DBP, foi registrada a terapia específica prescrita: diuréticos, corticoide, broncodilatadores. O gasto metabólico foi avaliado pela calorimetria indireta (Deltratac II Metabolic Monitor), realizada na idade corrigida de termo nos recém- nascidos com e sem DBP. Foi realizada avaliação antropométrica (peso, comprimento e perímetro cefálico) ao nascimento e na idade corrigida de termo. A composição corporal foi avaliada através da pletismografia por deslocamento de ar (PEA POD Infant Body Composition System) nos recém-nascidos com e sem DBP na idade corrigida de termo. Foram realizadas análises descritivas para estimar frequências, identificar padrões e analisar discrepâncias de dados. As variáveis contínuas foram expressas em média (DP), e asfrequências das variáveis categóricasforam expressas em porcentagens (%). O gasto energético de repouso, o volume do consumo de oxigênio, o volume do gás carbônico produzido, a porcentagem e o volume de massa livre de gordura, porcentagem e volume de massa gorda, as medidas antropométricas com osrespectivos escores Z na idade gestacional corrigida de termo foram comparados entre os recém-nascidos pré-termos com e sem DBP. Apesar de observamos maior gasto energético de repouso nos recém-nascidos com DBP na idade corrigida de termo, não se refletiu na composição corporal e no crescimento. Não observamos diferenças significativas na composição corporal e no crescimento entre os recém-nascidos com e sem DBP.

The technological advances in neonatology are resulting in a greater survival of preterm newborns, especially those with extremely low birth weight, and one of the great challenges of neonatology is to ensure an adequate nutrition for these newborns. Neonatal morbidities, including bronchopulmonary dysplasia, contribute decisively to the fluids and nutritional management of this population. Bronchopulmonary dysplasia (BPD) is one of the most frequent morbidities in preterm newborns, and with medical advances, less aggressive techniques of mechanical ventilation, the use of antenatal corticosteroids and surfactant, the tendency is for a decrease in its incidence; nevertheless, this did not occur in the extremely preterm population, due to the greater survival of this population. The growth restriction after birth in the BPD newborns group is due to several factors: the greater energy expenditure due to the increase in respiratory work, inflammation and tissue repair, and the decrease in food intake, making the offer of an adequate nutrition difficult. Nutrition has a direct effect on lung maturation and, therefore, insufficient nutrient supply can exacerbate alveolar damage. The knowledge of resting energy expenditure can improve the daily energy supply programming. Studies with indirect calorimetry have been used to verify the energy expenditure of newborns. Therefore, it is important to study the metabolic expenditure and assess its impact on growth and body composition of preterm newborns with BPD, considering the therapeutic changes that have occurred. The objectives of this study were: (i) to assess metabolic expenditure, body composition, and growth of newborns with and without BPD at term equivalent age; (ii) to analyze the association between metabolic expenditure, body composition and growth (weight, length and head circumference Z scores) at term equivalent age. Newborns with gestational age < 32 weeks, admitted to the Neonatal Intensive Care Unit of the National Institute of Women's, Children's and Adolescent´s Health Fernandes Figueira, were included in the study; the exposure considered was the development of BPD. BPD was defined by the need for oxygen at 36 weeks of corrected gestational age. The exclusion criteria were newborns with congenital malformations, genetic syndromes, hydrops fetalis, proven congenital infections, and those who were on ventilatory support at the time of the ix energy expenditure assessment. For the assessment of the nutritional intake, the daily quantities of proteins, lipids, carbohydrates, and calories effectively received in the first four weeks of life, and at the time of each assessment at term equivalent age were recorded. Gestational and perinatal information were recorded. The type of feeding was recorded at the assessment moments: exclusive breastfeeding, breast milk supplemented with formula, exclusive formula or special formula. In the case of newborns with BPD, the specific therapy prescribed was recorded: diuretics, corticosteroids, bronchodilators. Metabolic expenditure was assessed by indirect calorimetry (Deltratac II Metabolic Monitor), performed at term equivalent age in newborns with and without BPD. Anthropometric assessment (weight, length and head circumference) was performed at birth and at term equivalent age. Body composition was assessed using air displacement plethysmography (PEA POD Infant Body Composition System) in newborns with and without BPD at term equivalent age. Descriptive analyzes were performed to estimate frequencies, identify patterns and analyze data discrepancies. Continuous variables were expressed as mean (SD), and frequencies of categorical variables were expressed as percentages (%). Resting energy expenditure, volume of oxygen consumption, volume of carbon dioxide produced, percentage and volume of fat-free mass, percentage and volume of fat mass, anthropometric measurements with the respective Z-scores at term equivalent age were compared between preterm infants with and without BPD. Although we observed higher resting energy expenditure in newborns with BPD at term corrected age, this was not reflected in body composition and growth. We did not observe significant differences in body composition and growth between newborns with and without BPD.

Sex differences in clinical outcomes of extremely preterm infants/extremely low birth weight infants: a propensity score matching study / 中国当代儿科杂志

OBJECTIVES@#To study the effect of sex on the clinical outcome of extremely preterm infants (EPIs)/extremely low birth weight infants (ELBWIs) by propensity score matching.@*METHODS@#A retrospective analysis was performed for the medical data of 731 EPIs or ELBWIs who were admitted from January 1, 2011 to December 31, 2020. These infants were divided into two groups: male and female. A propensity score matching analysis was performed at a ratio of 1:1. The matching variables included gestational age, birth weight, percentage of withdrawal from active treatment, percentage of small-for-gestational-age infant, percentage of use of pulmonary surfactant, percentage of 1-minute Apgar score ≤3, percentage of mechanical ventilation, duration of mechanical ventilation, percentage of antenatal use of inadequate glucocorticoids, and percentage of hypertensive disorders in pregnancy. The two groups were compared in the incidence rate of main complications during hospitalization and the rate of survival at discharge.@*RESULTS@#Before matching, compared with the female group, the male group had significantly higher incidence rates of neonatal respiratory distress syndrome, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, and patent ductus arteriosus (P<0.05), while after matching, the male group only had a significantly higher incidence rate of BPD than the female group (P<0.05). There was no significant difference in the rate of survival at discharge between the two groups before and after matching (P>0.05).@*CONCLUSIONS@#Male EPIs/ELBWIs have a higher risk of BPD than female EPIs/ELBWIs, but male and female EPIs/ELBWIs tend to have similar outcomes.

Expert consensus on the follow-up management of bronchopulmonary dysplasia in preterm infants after discharge / 中国当代儿科杂志

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in preterm infants and seriously affects the quality of life of preterm infants. BPD is a life-threatening disease to preterm infants and may lead to serious sequelae including feeding difficulties, recurrent lower respiratory tract infection, airway hyperreactive diseases, growth retardation, and neurodevelopmental delay. In order to further standardize the follow-up management of preterm infants with BPD after discharge, based on related clinical evidence in China and overseas and practice experience, the Neonatal Evidence-Based Medicine Group, Committee of Neonatal Medicine, Cross-Strait Medical and Health Exchange Association, formulated this expert consensus from the aspects of the follow-up and management of respiratory diseases, growth and development, pulmonary hypertension, nerve dysplasia, metabolic bone disease, and vaccination of preterm infants with BPD after discharge.

Recent research on the mechanism of mesenchymal stem cells in the treatment of bronchopulmonary dysplasia / 中国当代儿科杂志

Bronchopulmonary dysplasia (BPD) is a chronic lung disease due to impaired pulmonary development and is one of the main causes of respiratory failure in preterm infants. Preterm infants with BPD have significantly higher complication and mortality rates than those without BPD. At present, comprehensive management is the main intervention method for BPD, including reasonable respiratory and circulatory support, appropriate enteral nutrition and parenteral nutrition, application of caffeine/glucocorticoids/surfactants, and out-of-hospital management after discharge. The continuous advances in stem cell medicine in recent years provide new ideas for the treatment of BPD. Various pre-clinical trials have confirmed that stem cell therapy can effectively prevent lung injury and promote lung growth and damage repair. This article performs a comprehensive analysis of the mechanism of mesenchymal stem cells in the treatment of BPD, so as to provide a basis for clinical applications.

Efficacy and safety of intratracheal administration of budesonide combined with pulmonary surfactant in preventing bronchopulmonary dysplasia: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of early intratracheal administration of budesonide combined with pulmonary surfactant (PS) in preventing bronchopulmonary dysplasia (BPD).@*METHODS@#A prospective randomized controlled trial was designed. A total of 122 infants with a high risk of BPD who were admitted to the neonatal intensive care unit of the Third Affiliated Hospital of Zhengzhou University from January to July 2021 were enrolled. The infants were randomly divided into a conventional treatment group with 62 infants (treated with PS alone at an initial dose of 200 mg/kg, followed by a dose of 100 mg/kg according to the condition of the infant) and an observation group with 60 infants (treated with PS at the same dose as the conventional treatment group, with the addition of budesonide 0.25 mg/kg for intratracheal instillation at each time of PS application). The two groups were compared in terms of the times of PS use, ventilator parameters at different time points, oxygen inhalation, incidence rate and severity of BPD, incidence rate of complications, and tidal breathing pulmonary function at the corrected gestational age of 40 weeks.@*RESULTS@#Compared with the conventional treatment group, the observation group had a significantly lower proportion of infants using PS for two or three times (P<0.05). Compared with the conventional treatment group, the observation group had a significantly lower fraction of inspired oxygen at 24 and 48 hours and 3, 7, and 21 days after administration, significantly shorter durations of invasive ventilation, noninvasive ventilation, ventilator application, and oxygen therapy, a significantly lower incidence rate of BPD, and a significantly lower severity of BPD (P<0.05). There was no significant difference in the incidence rate of glucocorticoid-related complications between the two groups (P>0.05).@*CONCLUSIONS@#Compared with PS use alone in preterm infants with a high risk of BPD, budesonide combined with PS can reduce repeated use of PS, lower ventilator parameters, shorten the duration of respiratory support, and reduce the incidence rate and severity of BPD, without increasing the incidence rate of glucocorticoid-related complications.

Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China.@*METHODS@#A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups.@*RESULTS@#Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05).@*CONCLUSIONS@#There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.

Función pulmonar: función pulmonar en pacientes con displasia broncopulmonar / Pulmonary function: pulmonary function in patients with bronchopulmonary dysplasia

La displasia broncopulmonar (DBP) es una complicación frecuente en los prematuros extremos. La detención de la alveolarización determina menor volumen pulmonar total, el cual se recupera al menos parcialmente en el trayecto de la vida. La vía aérea se ve afectada en su crecimiento en mayor proporción que los alvéolos, y en los pacientes con displasia severa va a existir hasta la etapa adulta una limitación al flujo aéreo debido a su menor calibre. En este artículo, se describirá el origen, hallazgos característicos y evolución de las alteraciones en la función pulmonar, especialmente, en los pacientes con la nueva DBP.

Bronchopulmonary dysplasia (BPD) is a frequent complication in extremely premature infants. The arrest of alveolarization determines a lower total lung volume, which recovers at least partially during life. The airway is affected in its growth to a greater extent than the alveoli, and in patients with severe dysplasia there will be airflow limitation until adulthood due to its smaller caliber. In this article, the origin, characteristic findings, and evolution of changes in lung function will be described, especially in patients with the new BPD.

Definición de displasia broncopulmonar propuesta por la Comisión Neo SOCHINEP / Definition of bronchopulmonary dysplasia proposed by the Neo SOCHINEP Commission

La displasia broncopulmonar (DBP) es la enfermedad crónica más frecuente del recién nacido prematuro. Los avances en su prevención y tratamiento han permitido una mayor sobrevida de prematuros más pequeños, pero su incidencia se ha mantenido estable en el tiempo, con una fisiopatología y presentación clínica que abarca un amplio espectro y que difiere de la DBP descrita originalmente hace más de 50 años. Aún existen controversias en su definición, la que se ha establecido en base al tratamiento, específicamente al requerimiento de soporte respiratorio. Las definiciones más utilizadas son el requerimiento de oxígeno por 28 días y a las 36 semanas de edad gestacional corregida (EGC). Recientemente se ha propuesto definirla en base al requerimiento de ventilación mecánica a las 36 semanas de EGC, lo que identificaría a los prematuros con DBP más grave y mayor probabilidad de complicaciones respiratorias y neurológicas en los 2 primeros años de vida. Nuestro objetivo en la comisión de Neo-SOCHINEP es el de recomendar la definición y clasificación que nos parece más adecuada para identificar a los prematuros portadores de DBP, considerando los aspectos fisiopatológicos, del compromiso de la función pulmonar y consecuencias prácticas de la definición en nuestro medio. También proponemos la definición del requerimiento de oxígeno en el prematuro cuando esta en neonatología, las condiciones e interpretación de la saturometría contínua cuando está pronto al alta y el seguimiento de la oxigenoterapia posterior al alta.

Bronchopulmonary dysplasia (BPD) is the most frequent chronic disease of the premature newborn. Advances in its prevention and treatment have allowed a greater survival of smaller preterm infants, but its incidence has remained stable over time, with a pathophysiology and clinical presentation that covers a wide spectrum and differs from the BPD originally described more than 50 years ago. There are still controversies in its definition, which has been established based on the treatment, specifically the requirement of respiratory support. The most used definitions are the oxygen requirement for 28 days and at 36 weeks of postmenstrual age (PMA). It has recently been proposed a definition based on the requirement of mechanical ventilation at 36 weeks of PMA, which would identify premature infants with more severe BPD and a greater probability of respiratory and neurological complications in the first 2 years of life. Our objective in the Neo-SOCHINEP commission is to recommend the definition and classification that we believe is most appropriate to identify premature infants with BPD, considering the pathophysiological aspects, the compromised lung function, and practical consequences of the definition in our medium. We also propose the definition of the oxygen requirement in premature infants when they are in neonatology, the conditions and interpretation of continuous saturation when they are soon discharged, and the follow-up of post-discharge oxygen therapy.