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OBJECTIVE: In this study, we evaluated the safety of early discharge (ED) of newborns born to coronavirus disease 2019 (COVID-19)-positive mothers. STUDY DESIGN: All ED newborns from the postpartum wards of the Fondazione Policlinico Gemelli between January 1, 2022, and February 28, 2022, were retrospectively analyzed. Newborns from mothers with COVID-19 and those from uninfected mothers were considered. The primary outcome was to evaluate whether the rate of the composite outcome, which was the percentage of rehospitalization/access in emergency room (RH/ER) within the first week from discharge, differed between neonates born to mother with COVID-19 (COVID-19 group) and those born to uninfected mothers (no COVID-19 group). The secondary outcomes were to assess the quality of feeding and number of outpatient visits in the follow-up clinic between the two cohorts of patients. RESULTS: One hundred and thirty-four newborns in the no COVID-19 group and 26 in the COVID-19 group were analyzed. The rate of RH/ER in the no COVID-19 group was of 6 over 134 newborns (0.045, 95% confidence image [CI]: 0.017-0.095), while in COVID-19 group, it was of 2 over 26 newborns (0.077), which does not differ from the expected rate (1.17 over 26 newborns, 0.045, 95% CI: 0.017-0.095). CONCLUSION: ED for newborns from mothers with COVID-19 could be an actionable safe strategy. KEY POINTS: · We evaluated the feasibility of early discharge (ED) of mothers with COVID-19 and their newborns.. · Rate of rehospitalization between newborns from uninfected mothers and infected ones was comparable.. · ED could be an actionable practice for newborns from mothers with COVID-19..
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Doenças do Prematuro/genética , Leucina-tRNA Ligase/genética , Falência Hepática Aguda/genética , Anormalidades Múltiplas/genética , Asfixia Neonatal/genética , Colestase/etiologia , Evolução Fatal , Retardo do Crescimento Fetal/etiologia , Humanos , Lactente , Recém-Nascido Prematuro , Doenças do Prematuro/fisiopatologia , Recém-Nascido Pequeno para a Idade Gestacional , Intestinos/anormalidades , Falência Hepática Aguda/fisiopatologia , Masculino , SíndromeRESUMO
OBJECTIVES: To evaluate the changes in end-expiratory lung volume during an oxygenation-guided stepwise recruitment procedure in elective high-frequency ventilation. We hypothesized that high continuous distending pressure impedes pulmonary blood flow as evidenced by reduced lung volume measurements using respiratory inductive plethysmography. Changes in oxygenation, ventilation, and peripheral perfusion were evaluated as secondary outcomes. DESIGN: A prospective, single center, observational, nonrandomized study. SETTING: The study was conducted in a neonatal ICU in Italy. PATIENTS: High-frequency ventilated preterm infants with respiratory distress syndrome. INTERVENTIONS: During the recruitment procedure, end-expiratory lung volume measured by respiratory inductive plethysmography, oxygen saturation, perfusion index, regional cerebral and perirenal tissue oxygenation, heart rate, transcutaneous PCO2, and tidal volume were simultaneously recorded at each airway pressure step. MEASUREMENTS AND MAIN RESULTS: In 12 preterm newborns (gestational age, 27.4 ± 0.2 wk; birth weight, 979 ± 198 g), high-frequency ventilation was initiated at a continuous distending pressure of 10 cm H2O and incrementally increased by 1-2 cm H2O every 2-5 minutes until FIO2 was less than or equal to 0.25. End-expiratory lung volume progressively increased during the initial recruitment, but decreased at the maximum airway pressure in nine patients, indicative of a reduction in pulmonary perfusion. At the end of recruitment, tidal volume was significantly higher (p = 0.002) and oxygenation was significantly improved (p = 0.002); however, mean perfusion index, postductal saturation, and mean renal tissue oxygenation values were significantly reduced (p < 0.05) compared with baseline. Mean cerebral tissue oxygenation and mean transcutaneous PCO2 values were reduced but failed to reach significance. CONCLUSIONS: High distending lung pressures increased oxygenation but decreased peripheral perfusion with no adverse cerebral side effects. Coupled with the reduction in respiratory inductive plethysmography-derived lung volume, high continuous distending pressure had adverse cardiopulmonary effects. Incorporation of lung volume and hemodynamic and oxygenation variables may guide optimum lung volume determination during high-frequency ventilation recruitment procedure while preventing adverse effects on the pulmonary circulation.
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Ventilação de Alta Frequência/métodos , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Síndrome do Desconforto Respiratório do Recém-Nascido/fisiopatologia , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Gasometria , Feminino , Hemodinâmica , Humanos , Recém-Nascido , Itália , Medidas de Volume Pulmonar , Masculino , Estudos Prospectivos , Volume de Ventilação PulmonarRESUMO
OBJECTIVE: To evaluate whether acute histologic chorioamnionitis (HCA) diagnosed in the placenta may be associated with an increased occurrence of bronchopulmonary dysplasia (BPD) or death among extremely low gestational age neonates (ELGAN). METHODS: This Italian single-center case-control retrospective study involved ELGAN admitted to the neonatal intensive care unit between January 2019 and June 2022. Infants born from pregnant women with acute and severe HCA, identified as stage ≥2 and grade 2 HCA, (HCA-infants) were compared with infants of pregnant women without chorioamnionitis or with stage 1, grade 1 chorioamnionitis (no-HCA-infants). RESULTS: Among 101 eligible ELGAN, 63 infants had complete clinical and histologic data relevant to the study: thirty infants were included in the HCA-infants group and 33 in the no-HCA-infants group. Neonatal and maternal demographic and clinical characteristics were similar between the two groups. Infants born from mothers with acute and severe HCA had significantly higher occurrence of composite BPD or death (18 [60%] vs. 9 [27%]; P = 0.012), as well as higher incidence of severe forms of BPD (6 [30%] vs. 2 [6%]; P = 0.045). In multiple logistic regression analysis, after adjustment for confounding covariates, HCA was an independent risk factor for BPD or death (OR, 4.49; 95% CI: 1.47-13.71). CONCLUSIONS: This is the first study showing that in utero exposure to acute and severe HCA is an independent risk factor for the occurrence of composite BPD or death among ELGAN.
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Displasia Broncopulmonar , Corioamnionite , Humanos , Feminino , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/mortalidade , Corioamnionite/epidemiologia , Estudos Retrospectivos , Gravidez , Recém-Nascido , Estudos de Casos e Controles , Adulto , Itália/epidemiologia , Lactente Extremamente Prematuro , Masculino , Unidades de Terapia Intensiva Neonatal , Fatores de Risco , Idade Gestacional , Mortalidade InfantilRESUMO
BACKGROUND: Diaphragm dysfunction is associated with poor outcomes in critically ill patients. Ventilator-induced diaphragmatic dysfunction (VIDD), including diaphragm atrophy (DA), is poorly studied in newborns. We aimed to assess VIDD and its associations in newborns. METHODS: Single-center prospective study. Diaphragm thickness was measured at end-inspiration (TDI) and end-expiration (TDE) on the right midaxillary line. DA was defined as decrease in TDE ≥ 10%. Daily measurements were recorded in preterm newborns on invasive mechanical ventilation (IMV) for ≥2 days. Clinical characteristics of patients and extubation failure were recorded. Univariate analysis, logistic regression, and mixed models were performed to describe VIDD and associated factors. RESULTS: We studied 17 patients (median gestational age 270/7 weeks) and 22 IMV cycles (median duration 9 days). Median TDE decreased from 0.118 cm (interquartile range [IQR] 0.094-0.165) on the first IMV day to 0.104 cm (IQR 0.083-0.120) on the last IMV day (p = .092). DA occurred in 11 IMV cycles (50%) from 10 infants early during IMV (median: second IMV day). Mean airway pressure (MAP) and lung ultrasound score (LUS) on the first IMV day were significantly higher in patients who developed DA. DA was more frequent in patients with extubation failure than in those with extubation success within 7 days (83.3 vs. 33.3%, p = .038). CONCLUSIONS: DA, significantly associated with extubation failure, occurred in 58.8% of the study infants on IMV. Higher MAP and LUS at IMV start were associated with DA. Our results suggest a potential role of diaphragm ultrasound to assess DA and predict extubation failure in clinical practice.
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Respiração Artificial , Desmame do Respirador , Lactente , Humanos , Recém-Nascido , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , Desmame do Respirador/métodos , Estudos Prospectivos , Diafragma/diagnóstico por imagem , Extubação/efeitos adversos , Extubação/métodos , Recém-Nascido Prematuro , Atrofia/patologiaRESUMO
Background: There are no guidelines regarding enteral feeding (EF) of infants with hypoxic-ischemic encephalopathy (HIE) during and shortly after therapeutic hypothermia; consequently, clinical practice is, to date, still variable. The objective of this study is to assess whether a minimal EF strategy during therapeutic hypothermia may be associated with a shorter time to full EF of infants with HIE and to identify the clinical variables that independently affect the time to full EF. Methods: A retrospective study, covering the period from 1 January 2015 to 30 June 2022 was performed at the Neonatal Intensive Care Unit of the Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, which compared infants with HIE who received minimal EF during therapeutic hypothermia with those who did not. Results: Seventy-eight infants received minimal EF during therapeutic hypothermia, while 75 did not. Infants who were fed reached full EF significantly faster than those who were not. Moreover, they received parenteral nutrition and maintained central venous lines for a shorter time. A multivariate analysis, taking into account the variable of clinical severity, confirmed that minimal EF is an independent beneficial factor for reaching full EF in a shorter time and mechanical ventilation and seizures are independent factors for a longer time to full EF. Conclusions: Minimal EF during therapeutic hypothermia is associated with a shorter time to full EF in stable infants with HIE. Further prospective studies are needed to better define the enteral nutrition strategy for infants during therapeutic hypothermia, regardless of the severity of clinical conditions.
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BACKGROUND: Candida mannan (Mn) detection in bronchoalveolar lavage fluid (BALF) was shown to be useful for earlier identification and preemptive therapy targeting in preterm infants at high risk of invasive Candida infection. We investigated whether early detection of Candida Mn in BALF is associated with the presence of some neutrophilic products, as markers of prenatal infection/inflammation. METHODS: BALF specimens were collected during the first 48 h of life from mechanically ventilated preterm newborns. Samples were analyzed by high-performance liquid chromatography-electrospray ionization-mass spectrometry. The relative amounts of α-defensins 1-4 and S100A proteins were measured by extracted ion current peak area. Absolute and differential white cell counts in BALF were obtained. Mn antigen concentrations were determined by the Platelia Candida antigen kit. RESULTS: Twenty-five studied neonates were divided into two groups: Mn-positive group and Mn-negative group. Levels of α-defensins 1-4 and S100A12 were significantly higher in the Mn-positive group than in the Mn-negative group. Moreover, positive significant correlations between the absolute number of neutrophils and the levels of α-defensins 1-4 and S100A8 were observed. CONCLUSION: The detection of Mn antigen in BALF of preterm infants is consistent with evidence of an innate immune response in their lungs as demonstrated by higher levels of α-defensins and S100A proteins.
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Líquido da Lavagem Broncoalveolar/microbiologia , Candida/isolamento & purificação , Recém-Nascido Prematuro , Proteínas S100/metabolismo , alfa-Defensinas/metabolismo , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Recém-Nascido , Masculino , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
INTRODUCTION: The immediate effects of exogenous surfactant on lung volume and hemodynamics in preterm infants have been poorly studied. MATERIALS AND METHODS: Lung volume, SpO2, perfusion index, regional SO2, transcutaneous partial pressure of CO2 were simultaneously monitored and recorded ten minutes after surfactant tracheal instillation in elective HFOV ventilated preterm infants with RDS. OUTCOMES: Despite a reduction in gas exchange during the first 5 minutes post surfactant instillation, most likely dependent on airway obstruction, lung volume increases rapidly in HFOV preterm infants with RDS. After 5 minutes from administration of surfactant, lung volume, gas exchange and PI reach stable values and CDP can be safely reduced.
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Ventilação de Alta Frequência , Surfactantes Pulmonares/uso terapêutico , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Medidas de Volume Pulmonar , Troca Gasosa PulmonarRESUMO
MAS is a common cause of neonatal respiratory distress in term and post-term neonates. Meconium staining of the amniotic fluid occurs in about 10-13% of normal pregnancies, and about 4% of these infants develop respiratory distress. In the past, MAS was diagnosed mainly on the basis of history, clinical symptoms, and chest radiography. Several authors have addressed the ultrasonographic assessment of the most common respiratory patterns in neonates. In particular, MAS is characterised by a heterogeneous alveolointerstitial syndrome, subpleural abnormalities with multiple lung consolidations, characterised by a hepatisation aspect. We present six cases of infants with a clinical history of meconium-stained fluid who presented with respiratory distress at birth. Lung ultrasound allowed the diagnosis of MAS in all the studied cases, despite the mild clinical picture. All children had the same ultrasound pattern with diffuse and coalescing B-lines, pleural line anomalies, air bronchograms, and subpleural consolidations with irregular shapes. These patterns were distributed in different areas of the lungs. These signs are specific enough to distinguish between MAS and other causes of neonatal respiratory distress, allowing the clinician to optimise therapeutic management.
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Intrahepatic cholestasis of pregnancy (ICP) complicates among 0.2-2% of pregnancies and has been associated with adverse perinatal outcomes, including sudden stillbirth, meconium strained fluid, preterm birth, perinatal asphyxia, and transient tachypnea of the newborn. The diagnosis of "bile acids pneumonia" was previously proposed and a causative role of bile acids (BA) was supposed with a possible mechanism of action including surfactant dysfunction, inflammation, and chemical pneumonia. In the last few years, the role of lung ultrasound (LUS) in the diagnosis and management of neonatal respiratory distress syndrome has grown, and LUS scores have been introduced in the literature, as an effective predictor of the need for surfactant treatment among neonates with respiratory distress syndrome. We present four cases of infants born from pregnancies complicated by ICP, who developed respiratory distress syndrome early after birth. Lung ultrasound showed the same pattern for all infants, corresponding to a homogeneous alveolar-interstitial syndrome characterized by a diffuse coalescing B-line pattern (white lung). All infants evaluated require non-invasive respiratory support and in three cases surfactant administration, despite the near-term gestational age, with rapid improvement of respiratory disease and a good clinical outcome.
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Extremely preterm infants frequently require some form of respiratory assistance to facilitate the cardiopulmonary transition that occurs in the first hours of life. Current resuscitation guidelines identify as a primary determinant of overall newborn survival the establishment, immediately after birth, of adequate lung inflation and ventilation to ensure an adequate functional residual capacity. Any respiratory support provided, however, is an important contributing factor to the development of bronchopulmonary dysplasia. The risks correlated to invasive ventilatory techniques increase inversely with gestational age. Preterm infants are born at an early stage of lung development and are more susceptible to lung injury deriving from mechanical ventilation. Any approach aiming to reduce the global burden of preterm lung disease must implement lung-protective ventilation strategies that begin from the newborn's first breaths in the delivery room. Neonatologists today must be able to manage both invasive and noninvasive forms of respiratory assistance to treat a spectrum of lung diseases ranging from acute to chronic conditions. We searched PubMed for articles on preterm infant respiratory assistance. Our narrative review provides an evidence-based overview on the respiratory management of preterm infants, especially in the acute phase of neonatal respiratory distress syndrome, starting from the delivery room and continuing in the neonatal intensive care unit, including a section regarding exogenous surfactant therapy.
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BACKGROUND: Artificial intelligence (AI) is a promising field in the neonatal field. We focused on lung ultrasound (LU), a useful tool for the neonatologist. Our aim was to train a neural network to create a model able to interpret LU. METHODS: Our multicentric, prospective study included newborns with gestational age (GA) ≥ 33 + 0 weeks with early tachypnea/dyspnea/oxygen requirements. For each baby, three LU were performed: within 3 h of life (T0), at 4-6 h of life (T1), and in the absence of respiratory support (T2). Each scan was processed to extract the region of interest used to train a neural network to classify it according to the LU score (LUS). We assessed sensitivity, specificity, positive and negative predictive value of the AI model's scores in predicting the need for respiratory assistance with nasal continuous positive airway pressure and for surfactant, compared to an already studied and established LUS. RESULTS: We enrolled 62 newborns (GA = 36 ± 2 weeks). In the prediction of the need for CPAP, we found a cutoff of 6 (at T0) and 5 (at T1) for both the neonatal lung ultrasound score (nLUS) and AI score (AUROC 0.88 for T0 AI model, 0.80 for T1 AI model). For the outcome "need for surfactant therapy", results in terms of area under receiver operator characteristic (AUROC) are 0.84 for T0 AI model and 0.89 for T1 AI model. In the prediction of surfactant therapy, we found a cutoff of 9 for both scores at T0, at T1 the nLUS cutoff was 6, while the AI's one was 5. Classification accuracy was good both at the image and class levels. CONCLUSIONS: This is, to our knowledge, the first attempt to use an AI model to interpret early neonatal LUS and can be extremely useful for neonatologists in the clinical setting.
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Doenças do Recém-Nascido , Pneumonia , Surfactantes Pulmonares , Síndrome do Desconforto Respiratório do Recém-Nascido , Recém-Nascido , Humanos , Lactente , Estudos Prospectivos , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Inteligência Artificial , Pulmão/diagnóstico por imagem , Surfactantes Pulmonares/uso terapêutico , Ultrassonografia , Pneumonia/tratamento farmacológico , TensoativosRESUMO
BACKGROUND: Tactile stimulation manoeuvres stimulate spontaneous breathing in preterm newborns. The aim of this study is to evaluate the effect of early respiratory physiotherapy on the need for mechanical ventilation during the first week of life in preterm infants with respiratory failure. METHODS: This is a monocentric, randomised controlled trial. Preterm infants (gestational age ≤ 30 weeks) not intubated in the delivery room and requiring non-invasive respiratory support at birth were eligible for the study. The intervention group received early respiratory physiotherapy, while the control group received only a daily physiotherapy program (i.e., modifying the infant's posture in accordance with the patient's needs). RESULTS: between October 2019 and March 2021, 133 preterm infants were studied, 68 infants in the study group and 65 in routine care. The study group showed a reduction in the need for mechanical ventilation (not statistically significant) and a statistically significant reduction in hemodynamically significant patent ductus arteriosus with respect to the control group (19/68 (28%) vs. 35/65 (54%), respectively, p = 0.03). CONCLUSIONS: early respiratory physiotherapy in preterm infants requiring non-invasive respiratory support at birth is safe and has proven to be protective against haemodynamically significant PDA.
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OBJECTIVE: To propose an early lung ultrasound (LUS) score for the prediction of the need for respiratory assistance in newborns of gestational age (GA) ≥ 33 weeks presenting respiratory distress. STUDY DESIGN AND SETTING: Multicenter, prospective observational study in third-level neonatal intensive care units. PATIENT SELECTION: Infants with GA ≥ 33 + 0 weeks with respiratory distress within 3 h of life. METHODS: Three LUS for each patient were collected: within 3 h of life (T0), at 4-6 h of life (T1), and at the resolution of symptoms (T2). The primary aim was to assess the validity of the early LUS score in predicting the need for continuous positive airway pressure (CPAP). We also evaluated the validity of the score in predicting the need for surfactant, the scores' trend in our population, and any correlation with the duration of ventilation and oxygen therapy. RESULTS: Sixty-two patients were enrolled in the study. The mean GA was 36 weeks. The receiver operating characteristic analysis for the LUS T0 and T1 yielded area under the curves of 0.91 and 0.82 in predicting the need for CPAP, respectively. LUS score cut off of 6 (sensitivity 84.8%, specificity 86.2%) and 5 (sensitivity 66.7%, specificity 100%) were calculated at T0 and T1, respectively. We found significant correlations between LUS score and respiratory assistance, surfactant administration, and SpO2 /FiO2 ratio. CONCLUSION: An early LUS score is a good noninvasive predictor of the need for respiratory assistance with CPAP and surfactant administration in newborns with GA ≥ 33 weeks.
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Ventilação não Invasiva , Surfactantes Pulmonares , Síndrome do Desconforto Respiratório do Recém-Nascido , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Pulmão/diagnóstico por imagem , Surfactantes Pulmonares/uso terapêutico , Síndrome do Desconforto Respiratório do Recém-Nascido/diagnóstico por imagem , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Tensoativos , UltrassonografiaRESUMO
Respiratory distress (RD) is one of the most common causes of admission to the neonatal intensive care unit. Correct diagnosis and timely intervention are crucial. Lung ultrasonography (LU) is a useful diagnostic tool for the neonatologist in the diagnosis of RD; the neonatal lung ultrasonography score (nLUS) can be used in the diagnostic process, but some authors hypothesise that it is also useful for the management of some neonatal RD. The aim of this study is to analyse the changes in nLUS score before (T0) and after (T1) the start of respiratory support with nasal CPAP in neonates over 32 weeks of age with RD. Thirty-three newborns were enrolled in this retrospective study. LU was performed before and after the start of CPAP. The median nLUS scores at T0 and T1 were 9 (IQR 7−12) and 7 (IQR 4−10), respectively, and showed a significant difference (p < 0.001). The magnitude of reduction in nLUS score, expressed as a percentage, was inversely related to the need for subsequent administration of exogenous surfactant. The study suggests the usefulness of the nLUS score in assessing the response to CPAP in neonates over 32 weeks gestational age.
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The newborn's microbiota composition at birth seems to be influenced by maternal microbiota. Maternal vaginal microbiota can be a determining factor of spontaneous Preterm Birth (SPPTB), the leading cause of perinatal mortality. The aim of the study is to investigate the likelihood of a causal relationship between the maternal vaginal microbiota composition and neonatal lung and intestinal microbiota profile at birth, in cases of SPPTB. The association between the lung and/or meconium microbiota with the subsequent development of bronchopulmonary dysplasia (BPD) was also investigated. Maternal vaginal swabs, newborns' bronchoalveolar lavage fluid (BALF) (1st, 3rd, 7th day of life) and first meconium samples were collected from 20 women and 23 preterm newborns with gestational age ≤ 30 weeks (12 = SPPTB; 11 = Medically Indicated Preterm Birth-MIPTB). All the samples were analyzed for culture examination and for microbiota profiling using metagenomic analysis based on the Next Generation Sequencing (NGS) technique of the bacterial 16S rRNA gene amplicons. No significant differences in alpha e beta diversity were found between the neonatal BALF samples of SPPTB group and the MIPTB group. The vaginal microbiota of mothers with SPPTB showed a significant difference in alpha diversity with a decrease in Lactobacillus and an increase in Proteobacteria abundance. No association was found between BALF and meconium microbiota with the development of BPD. Vaginal colonization by Ureaplasma bacteria was associated with increased risk of both SPPTB and newborns' BPD occurrence. In conclusion, an increase in α-diversity values and a consequent fall in Lactobacillus in vaginal environment could be associated to a higher risk of SPPTB. We could identify neither a specific neonatal lung or meconium microbiota profiles in preterm infants born by SPPTB nor a microbiota at birth suggestive of subsequent BPD development. Although a strict match has not been revealed between microbiota of SPPTB mother-infant couples, a relationship cannot be excluded. To figure out the reciprocal influence of the maternal-neonatal microbiota and its potential role in the pathogenesis of SPPTB and BPD further research is needed.
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For the newborns needing respiratory support at 36 weeks postmenstrual age, regardless of the type of ventilation used, it is critical to take into account the mechanics properties of both airways and lungs affected by severe bronchopulmonary dysplasia (sBPD). Ventilator strategies, settings, and weaning must change dramatically after sBPD is established, but to date there is almost no high-quality evidence base supporting a specific approach to guide the optimal ventilator management and weaning in patients with sBPD. Weaning from invasive mechanical ventilation, management of the immediately postextubation period, and weaning from noninvasive ventilation in patients with sBPD are the topics covered in this chapter.
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Displasia Broncopulmonar , Ventilação não Invasiva , Displasia Broncopulmonar/terapia , Humanos , Recém-Nascido , Respiração Artificial , Desmame do Respirador , Ventiladores MecânicosRESUMO
The study investigates the role of the oxidative and proteolytic inactivation of alpha-1 antitrypsin (AAT) in the pathogenesis of bronchopulmonary dysplasia (BPD) in premature infants. Bronchoalveolar lavage fluid (BALF) samples were collected on the 3rd day of life from mechanically ventilated neonates with gestational age ≤ 30 weeks and analyzed without previous treatment (top-down proteomics) by reverse-phase high-performance liquid chromatography-electrospray ionization mass spectrometry. AAT fragments were identified by high-resolution LTQ Orbitrap XL experiments and the relative abundances determined by considering the extracted ion current (XIC) peak area. Forty preterm neonates were studied: 20 (50%) did not develop BPD (no-BPD group), 17 (42.5%) developed mild or moderate new-BPD (mild + moderate BPD group), and 3 (7.5%) developed severe new-BPD (severe BPD group). Eighteen fragments of AAT and a fragment of AAT oxidized at a methionine residue were identified: significantly higher values of AAT fragments 25-57, 375-418, 397-418, 144-171, and 397-418 with oxidized methionine were found in the severe BPD group. The significantly higher levels of several AAT fragments and of the fragment 397-418, oxidized in BALF of preterm infants developing BPD, underlie the central role of an imbalance between proteases and protease inhibitors in exacerbating lung injury and inducing most severe forms of BPD. The study has some limitations, and between them, the small sample size implies the need for further confirmation by larger studies.