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1.
Zhonghua Er Ke Za Zhi ; 58(5): 381-386, 2020 May 02.
Artigo em Chinês | MEDLINE | ID: mdl-32392953

RESUMO

Objective: To compare the clinical diagnosis and outcomes of preterm infants with bronchopulmonary dysplasia (BPD) under two different diagnostic criteria. Methods: A retrospective study was performed in 157 preterm infants who were admitted to Neonatal Intensive Care Unit of the Children's Hospital, Zhejiang University School of Medicine from January 2015 to December 2018. Enrolled infants, with gestational age <32 weeks and survived >14 days, met the 2001 National Institute of Child Health and Human Development(NICHD) definition of moderate and severe BPD or died between 14 days of postnatal age and 36 weeks owing to persistent parenchymal lung disease and respiratory failure. The severities of BPD were revaluated according to the 2018 revised definition of BPD proposed by NICHD. Characteristics and outcomes of these infants were compared with the two different diagnostic criteria with t-test, nonparametric test or Chi-square test. Results: In the 157 enrolled infants (100 males), severities of BPD were classified as moderate in 62, severe in 84 and unclassifiable in 11 according to the 2001 NICHD criteria, while grade Ⅰ in 51, Ⅱ in 29, Ⅲ in 66 and ⅢA in 11 infants respectively according to the 2018 NICHD criteria. Duration of oxygen therapy, positive pressure ventilation and endotracheal intubation in grade Ⅱinfants of 2018 criteria were much longer than that in moderate infants of 2001 criteria (80 (65, 95) vs. 65 (59, 77) d, 52 (38, 58) vs.30 (19, 48) d, 10 (2, 17) vs.4 (0, 12) d, Z=-2.995, -3.750, -2.073, all P<0.05). Mortality of moderate and severe infants in 2001 criteria was 10.3% (15/146), while mortality of BPD in 2018 criteria was 16.6% (26/157). Mortality of grade Ⅲ and ⅢA BPD in 2018 criteria was much higher than mortality of severe BPD in 2001 criteria (33.8% (26/77) vs. 17.9%(15/84), χ(2)=5.357, P<0.05). Conclusion: Definition and classification of BPD based on 2001 NICHD criteria may cause missed or unclassified cases, resulting in the underestimation of the morbidity and mortality of infants with severe BPD.


Assuntos
Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/terapia , Displasia Broncopulmonar/mortalidade , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Pulmão , Masculino , Estudos Retrospectivos , Resultado do Tratamento
2.
J Perinatol ; 40(4): 607-615, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31925319

RESUMO

OBJECTIVES: To systematically review the diagnostic accuracy of brain natriuretic peptide (BNP) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) in bronchopulmonary dysplasia (BPD) and BPD-pulmonary hypertension (PH). STUDY DESIGN: PubMed, Embase, the Web of Science, and the Cochrane Library were searched in March 2019. We included studies that evaluated BNP or NT-proBNP in preterm neonates as a marker for predicting BPD, BPD or death, and BPD-PH. RESULTS: Nine studies evaluating NT-proBNP/BNP were included. The quality of evidence was low, using GRADE criteria. The diagnostic accuracy of NT-proBNP and BNP for diagnosing BPD-PH showed high sensitivity and specificity in infants with BPD. Lower sensitivities and specificities of NT-proBNP and BNP were reported for predicting BPD, BPD or death, compared with that for BPD-PH. CONCLUSIONS: Low quality evidence suggests that NT-proBNP and BNP have adequate diagnostic accuracy for diagnosing and monitoring BPD-PH and may be used to triage patients to receive an echocardiogram.


Assuntos
Displasia Broncopulmonar/diagnóstico , Hipertensão Pulmonar/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Biomarcadores/sangue , Displasia Broncopulmonar/sangue , Displasia Broncopulmonar/complicações , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/etiologia , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/sangue , Doenças do Prematuro/diagnóstico , Curva ROC , Padrões de Referência , Sensibilidade e Especificidade
3.
Am J Respir Crit Care Med ; 201(11): 1398-1406, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31995403

RESUMO

Rationale: Bronchopulmonary dysplasia (BPD) is a heterogenous condition with poorly characterized disease subgroups.Objectives: To define the frequency of three disease components: moderate-severe parenchymal disease, pulmonary hypertension (PH), or large airway disease, in a referral cohort of preterm infants with severe BPD. The association between each component and a primary composite outcome of death before hospital discharge, tracheostomy, or home pulmonary vasodilator therapy was assessed.Methods: This was a retrospective, single-center cohort study of infants born at <32 weeks' gestation with severe BPD who underwent both chest computed tomography with angiography (CTA) and echocardiography between 40 and 50 weeks postmenstrual age between 2011 and 2015. Moderate-severe parenchymal lung disease was defined as an Ochiai score ≥8 on CTA. PH was diagnosed by echocardiogram using standard criteria. Large airway disease was defined as tracheomalacia or bronchomalacia on bronchoscopy and/or tracheoscopy or CTA.Measurements and Main Results: Of 76 evaluated infants, 73 (96%) were classifiable into phenotypic subgroups: 57 with moderate-severe parenchymal disease, 48 with PH, and 44 with large airway disease. The presence of all three disease components was most common (n = 23). Individually, PH and large airway disease, but not moderate-severe parenchymal disease, were associated with increased risk for the primary study outcome. Having more disease components was associated with an incremental increase in the risk for the primary outcome (2 vs. 1: odds ratio, 4.9; 95% confidence interval, 1.4-17.2 and 3 vs. 1: odds ratio, 12.8; 95% confidence interval, 2.4-70.0).Conclusions: Infants with severe BPD are variable in their predominant pathophysiology. Disease phenotyping may enable better risk stratification and targeted therapeutic intervention.


Assuntos
Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/genética , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Fenótipo , Estudos Retrospectivos , Índice de Gravidade de Doença
4.
Pediatr Pulmonol ; 55(4): 899-908, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31995668

RESUMO

RATIONALE: Bronchopulmonary dysplasia (BPD) is associated with post-prematurity respiratory disease (PRD) in survivors of extreme preterm birth. Identifying early biomarkers that correlate with later development of BPD and PRD may provide insights for intervention. In a preterm baboon model, elevated gastrin-releasing peptide (GRP) is associated with BPD, and GRP inhibition mitigates BPD occurrence. OBJECTIVE: We performed a prospective cohort study to investigate whether urine GRP levels obtained in the first postnatal week were associated with BPD, PRD, and other urinary biomarkers of oxidative stress. METHODS: Extremely low gestational age infants (23-28 completed weeks) were enrolled in a US multicenter observational study, The Prematurity and Respiratory Outcomes Program (http://clinicaltrials.gov/ct2/show/NCT01435187). We used multivariable logistic regression to examine the association between urine GRP in the first postnatal week and multiple respiratory outcomes: BPD, defined as supplemental oxygen use at 36 + 0 weeks postmenstrual age, and post-PRD, defined by positive quarterly surveys for increased medical utilization over the first year (PRD score). RESULTS: A total of 109 of 257 (42%) infants had BPD, and 120 of 217 (55%) had PRD. On adjusted analysis, GRP level more than 80 was associated with BPD (adjusted odds ratio [aOR], 1.83; 95% confidence interval [CI], 1.03-3.25) and positive PRD score (aOR, 2.46; 95% CI, 1.35-4.48). Urine GRP levels correlated with duration of NICU ventilatory and oxygen support and with biomarkers of oxidative stress: allantoin and 8-hydroxydeoxyguanosine. CONCLUSIONS: Urine GRP in the first postnatal week was associated with concurrent urine biomarkers of oxidative stress and with later diagnoses of BPD and PRD.


Assuntos
Displasia Broncopulmonar/urina , Peptídeo Liberador de Gastrina/urina , Lactente Extremamente Prematuro , Doenças do Prematuro/urina , Doenças Respiratórias/urina , Biomarcadores/urina , Displasia Broncopulmonar/diagnóstico , Feminino , Humanos , Recém-Nascido , Doenças do Prematuro/diagnóstico , Modelos Logísticos , Masculino , Estudos Prospectivos , Transtornos Respiratórios , Doenças Respiratórias/diagnóstico
5.
Respir Res ; 20(1): 260, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752871

RESUMO

BACKGROUND: Extreme prematurity has been associated with exercise intolerance and reduced physical activity. We hypothesized that children with bronchopulmonary dysplasia (BPD) would be especially affected based on long-term lung function impairments. Therefore, the objective of this study was to compare exercise capacity and habitual physical activity between children born very and extremely preterm with and without BPD and term-born children. METHODS: Twenty-two school-aged children (aged 8 to 12 years) born with a gestational age < 32 weeks and a birthweight < 1500 g (9 with moderate or severe BPD (=BPD), 13 without BPD (=No-BPD)) and 15 healthy term-born children (=CONTROL) were included in the study. Physical activity was measured by accelerometry, lung function by spirometry and exercise capacity by an incremental cardiopulmonary exercise test. RESULTS: Peak oxygen uptake was reduced in the BPD-group (83 ± 11%predicted) compared to the No-BPD group (91 ± 8%predicted) and the CONTROL group (94 ± 9%predicted). In a general linear model, variance of peak oxygen uptake was significantly explained by BPD status and height but not by prematurity (p < 0.001). Compared to CONTROL, all children born preterm spent significantly more time in sedentary behaviour (BPD 478 ± 50 min, No-BPD 450 ± 52 min, CONTROL 398 ± 56 min, p < 0.05) and less time in moderate-to-vigorous-physical activity (BPD 13 ± 8 min, No-BPD 16 ± 8 min, CONTROL 33 ± 16 min, p < 0.001). Prematurity but not BPD contributed significantly to explained variance in a general linear model of sedentary behaviour and likewise moderate-to-vigorous-physical activity (p < 0.05 and p < 0.001 respectively). CONCLUSION: In our cohort, BPD but not prematurity was associated with a reduced exercise capacity at school-age. However, prematurity regardless of BPD was related to less engagement in physical activity and more time spent in sedentary behaviour. Thus, our findings suggest diverging effects of prematurity and BPD on exercise capacity and physical activity.


Assuntos
Displasia Broncopulmonar/fisiopatologia , Tolerância ao Exercício/fisiologia , Exercício Físico/fisiologia , Nascimento Prematuro/fisiopatologia , Comportamento Sedentário , Displasia Broncopulmonar/diagnóstico , Estudos de Casos e Controles , Criança , Estudos de Coortes , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Nascimento Prematuro/diagnóstico
6.
Pregnancy Hypertens ; 18: 82-87, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577982

RESUMO

OBJECTIVES: Angiogenic factors may be involved in lung development. To evaluate the relations between maternal and cord blood angiogenic factors (sFlt-1, placental growth factor [PlGF], soluble endogline [sEng], transforming growth factor ß [TGF-beta]) and their association with moderate and severe bronchopulmonary dysplasia (BPD) in very preterm growth-restricted infants. STUDY DESIGN: Prospective monocentric cohort study. Twenty-four mother-child dyads featuring antepartum preeclampsia, intra-uterine growth restriction (IUGR) and birth before 30 weeks' gestation were included. This ensured a 80% power to test whether sFlt-1 maternal levels would be twice as high in cases of BPD as in the absence of BPD. MAIN OUTCOME MEASURES: Four pro/anti-angiogenic factors from two pathways (sFlt-1, PlGF and sEng, TGF-beta) were measured in maternal serum before delivery (at the time of hospitalization or the day of birth) and in neonates' cord blood. Neonatal outcome was moderate to severe BPD, defined as oxygen requirement for at least 28 days and persistent need for oxygen or ventilatory support at 36 weeks' postmenstrual age. RESULTS: sFlt-1 levels were positively correlated in maternal serum and cord blood (rs = 0.83, p < .001) but levels of PlGF and TGF-beta and its receptor sEng were not. Among all the factors studied in cord and maternal blood, none was associated with BPD. CONCLUSIONS: In IUGR preterm babies born before 30 weeks' gestation from preeclamptic mothers, serum sFlt-1, PlGF and sEng, TGF-ß levels were not correlated with BPD. The increased BPD risk in preterm neonates born from preeclamptic mothers cannot be related to high sFlt-1 levels.


Assuntos
Indutores da Angiogênese/sangue , Displasia Broncopulmonar/diagnóstico , Retardo do Crescimento Fetal , Diagnóstico Pré-Natal , Adulto , Biomarcadores/sangue , Displasia Broncopulmonar/sangue , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue
7.
Pediatr Pulmonol ; 54(12): 1989-1996, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31486289

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) with airway hyperreactivity is a long-term pulmonary complication of prematurity. The endogenous nonadrenergic, noncholinergic signaling molecule, S-nitrosoglutathione (GSNO) and its catabolism by GSNO reductase (GSNOR) modulate airway reactivity. Tracheomalacia is a major, underinvestigated complication of BPD. We studied trachealis, left main bronchus (LB), and intrapulmonary bronchiolar (IPB) relaxant responses to GSNO in a murine hyperoxic BPD model. METHODS: Wild-type (WT) or GSNOR knockout (KO) newborn mice were raised in 60% (BPD) or 21% (control) oxygen during the first 3 weeks of life. After room air recovery, adult trachealis, LB, and IPB smooth muscle relaxant responses to GSNO (after methacholine preconstriction) were studied using wire myographs. Studies were repeated after GSNOR inhibitor (GSNORi) pretreatment and in KO mice. RESULTS: GSNO relaxed all airway preparations. GSNO relaxed WT BPD trachealis substantially more than WT controls (P < .05). Pharmacologic or genetic ablation of GSNOR abolished the exaggerated BPD tracheal relaxation to GSNO and also augmented BPD IPB relaxation to GSNO. LB ring contractility was not significantly different between groups or conditions. Additionally, GSNORi treatment induced relaxation of WT IPBs but not trachealis or LB. CONCLUSION: GSNO dramatically relaxed the trachealis in our BPD model, an effect paradoxically reversed by loss of GSNOR. Conversely, GSNOR inhibition augmented IBP relaxation. These data suggest that GSNOR inhibition could benefit both the BPD trachealis and distal airways, restoring relaxant responses to those of room air controls. Because therapeutic options are limited in this high-risk population, future studies of GSNOR inhibition are needed.


Assuntos
Broncodilatadores/uso terapêutico , Displasia Broncopulmonar/tratamento farmacológico , S-Nitrosoglutationa/uso terapêutico , Traqueomalácia/diagnóstico , Animais , Asma/tratamento farmacológico , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/diagnóstico , Modelos Animais de Doenças , Humanos , Hiperóxia , Recém-Nascido , Cloreto de Metacolina , Camundongos , Músculo Liso/metabolismo , Transdução de Sinais , Traqueia/metabolismo , Traqueomalácia/complicações , Traqueomalácia/tratamento farmacológico
8.
Pediatr Int ; 61(10): 945-950, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31487104

RESUMO

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in preterm infants who have been treated with supplemental oxygen and mechanical ventilation. Despite major advances in perinatal and neonatal medicine, limited progress has been made in reducing BPD rates. The use of mesenchymal stem cells (MSC) is a promising and innovative therapy for several diseases because they are easy to extract and they have low immunogenicity, anti-inflammatory properties, and regenerative ability. According to several pre-clinical studies that have used BPD animal models, one mechanism of action for MSC in BPD is mainly due to the paracrine effects of MSC-derived humoral factors, such as interleukin (IL)-6, IL-8, vascular endothelial growth factor, collagen, and elastin, rather than the multilineage and regenerative capacities of MSC. Cell-free preparations derived from MSC, including conditioned media and exosomes, remain a pre-clinical technology despite their great clinical potential. A first-in-human clinical trial of MSC treatment for BPD was performed as a phase I dose-escalation trial using umbilical cord blood-derived MSC. That trial demonstrated the short- and long-term safety and feasibility of MSC, given that significantly reduced inflammatory marker expression was observed in tracheal aspirates. As of recently, several clinical trials of MSC use for BPD are ongoing or are planned in some countries to investigate the efficacy of MSC in the prevention or treatment of BPD in premature infants. Many clinicians are currently awaiting the results from these trials so that MSC can be used clinically for human BPD.


Assuntos
Displasia Broncopulmonar/prevenção & controle , Transplante de Células-Tronco Mesenquimais/métodos , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/fisiopatologia , Displasia Broncopulmonar/terapia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Células-Tronco Mesenquimais/fisiologia , Resultado do Tratamento
9.
J Pediatr ; 215: 17-23, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31500862

RESUMO

OBJECTIVE: To describe the effect of systemic corticosteroids administered to treat evolving bronchopulmonary dysplasia on oxygen diffusion and ventilation efficiency. STUDY DESIGN: This was a retrospective cohort study of ventilated infants who received a 9-day course of dexamethasone in a tertiary neonatal unit. We calculated the transcutaneous oxygen saturation-to-fraction of inspired oxygen (FiO2) ratio (SFR), the ventilation perfusion ratio (VA/Q), and the ventilation efficiency index (VEI) before, during, and after the course of corticosteroids. The response to corticosteroids was calculated as the difference between the FiO2 percentage before starting steroids and the lowest FiO2 value during the course of steroid treatment. RESULTS: Seventy infants (38 males) with a median gestational age (GA) of 25.0 weeks (IQR, 24.3-26.0 weeks) and a median birth weight of 0.70 kg (IQR, 0.63-0.82 kg) were studied at a median postnatal age of 39 days (IQR, 29-48 days). The median SFR before treatment was 1.42 (IQR, 1.19-1.72), and the highest SFR was 2.35 (IQR, 1.87-2.83) after 9 days of treatment. The median VA/Q before treatment was 0.14 (IQR, 0.11-0.18) and was significantly higher at 72 hours after the start of treatment (0.22; IQR, 0.15-0.29; P < .001). The median VEI was 0.06 (IQR, 0.04-0.08) before treatment and was highest, 0.10 (IQR, 0.07-0.13) at 48 hours after starting treatment. The median rate of response to corticosteroids was 28% (IQR, 20%-37%). GA was significantly related to the response to corticosteroids (ρ = 0.283; P = .019). CONCLUSIONS: Oxygen diffusion continues to improve throughout the entire duration of a 9-day course of systemically administered corticosteroids in ventilated extremely preterm infants. More immature infants are less responsive to corticosteroids.


Assuntos
Displasia Broncopulmonar/terapia , Ritmo Circadiano/fisiologia , Dexametasona/administração & dosagem , Lactente Extremamente Prematuro , Cuidado Pós-Natal/métodos , Respiração Artificial/métodos , Volume de Ventilação Pulmonar/fisiologia , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/fisiopatologia , Feminino , Seguimentos , Idade Gestacional , Glucocorticoides/administração & dosagem , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Consumo de Oxigênio , Estudos Retrospectivos , Resultado do Tratamento
10.
Arch. bronconeumol. (Ed. impr.) ; 55(9): 465-471, sept. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-186156

RESUMO

Introduction: Endocan levels were found to be associated with severity and mortality of the respiratory system diseases. Objective: We aimed to figure out whether endocan was an important marker for the diagnosis, severity and follow-up of bronchopulmonary dysplasia (BPD). Materials and methods: Infants with moderate/severe BPD, and who required hydrocortisone treatment were included in the study group. Infants without BPD were allocated in the control group. Endocan levels were compared between the control group and the study group, and before and after the treatment in the study group. Results: A total of 148 infants, 74 infants in the control group and 74 infants in the BPD group, were included. The endocan level was higher in the BPD group than in the control group (P = .001). Endocan levels before treatment in the BPD group was found to be higher than endocan level after treatment (P = .021). Conclusion: Our study found that endocan levels increased in moderate/severe BPD. Serum endocan levels may be a safe and novel indicator for the follow-up of response to treatment and the prognosis of the severity of the disease


Introducción: Los niveles de endocan se han asociado con la mortalidad y la gravedad de enfermedades del aparato respiratorio. Objetivo: El objetivo fue averiguar si el endocan es un marcador útil para el diagnóstico, la gravedad y el seguimiento de la displasia broncopulmonar (DBP). Materiales y métodos: Se incluyeron en el estudio lactantes con DBP moderada/grave que requirieron tratamiento con hidrocortisona (grupo DBP). El grupo control lo constituyeron lactantes sin DBP. Los niveles de endocan se compararon entre el grupo control y el grupo de estudio y, en este último, tanto antes como después del tratamiento. Resultados: Se incluyeron un total de 148 lactantes; 74 en el grupo control y 74 en el grupo DBP. Los niveles de endocan fueron más elevados en el grupo DBP que en el grupo control (p = 0,001). Los niveles de endocan también resultaron superiores en el grupo DBP antes del tratamiento que después del mismo (p = 0,021). Conclusión: Nuestro estudio halló que los niveles de endocan se encuentran incrementados en la DBP moderada/grave. Los niveles séricos de endocan podrían utilizarse como un nuevo indicador seguro para el seguimiento de la respuesta al tratamiento y el pronóstico de gravedad de la enfermedad


Assuntos
Humanos , Lactente , Pulmão/patologia , Displasia Broncopulmonar/sangue , Recém-Nascido de muito Baixo Peso/sangue , Prognóstico , Proteoglicanas/análise , Pulmão/fisiopatologia , Biomarcadores/sangue , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/patologia , Índice de Gravidade de Doença , Hidrocortisona/uso terapêutico
11.
Eur. respir. j ; 54(3)Sept. 2019.
Artigo em Inglês | BIGG | ID: biblio-1026259

RESUMO

This document provides recommendations for monitoring and treatment of children in whom bronchopulmonary dysplasia (BPD) has been established and were discharged from the hospital, or who were older than 36 weeks of postmenstrual age. The guideline was based on pre-defined Population, Intervention, Comparison and Outcomes (PICO) questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. After considering the balance of desirable (benefits) and undesirable (burden, adverse effects) consequences of the intervention, the certainty of the evidence, and values, the Task Force made conditional recommendations for monitoring and treatment of BPD based on very low to low quality of evidence. We suggest monitoring with lung imaging using ionising radiation in a subgroup only, for example severe BPD or recurrent hospitalisations, and monitoring with lung function in all children. We suggest to give individual advice to parents regarding day care attendance. With regards to treatment, we suggest to use bronchodilators in a subgroup only, for example asthma-like symptoms, or reversibility in lung function, no treatment with inhaled or systemic corticosteroids, natural weaning of diuretics by the relative decrease in dose with increasing weight gain if diuretics are started in the neonatal period, and to treat with supplemental oxygen with a saturation target range of 90­95%. A multidisciplinary approach for children with established severe BPD after the neonatal period into adulthood is preferable. These recommendations should be considered until new and urgently needed evidence becomes available.


Assuntos
Humanos , Masculino , Feminino , Criança , Broncodilatadores/uso terapêutico , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/terapia , Administração dos Cuidados ao Paciente/métodos , Nascimento Prematuro/enfermagem
12.
Clin Drug Investig ; 39(11): 1093-1107, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31414269

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the need for oxygen therapy at 36 weeks postmenstrual age (PMA). Sildenafil has been shown to enhance the lung alveolarization and vascularization in newborn animal models after lung injury and has possible therapeutic potential for the prevention of BPD. OBJECTIVE: To perform a proof-of-concept, Phase II, pilot randomized, double-blind, clinical trial to study the efficacy of sildenafil in preventing BPD, in postnatal (< 24 h), extremely and very preterm infants. METHODS: This Phase II, pilot randomized, double-blind, clinical trial was conducted in the Neonatal Intensive Care Unit of Women's Wellness and Research Center, Doha, Qatar during 2012-2014. Infants of 240/7-296/7 weeks' gestation were eligible if they needed respiratory or oxygen support ≥ 25% at randomization, and if they were at a postnatal age of < 24 h at randomization. Forty preterm infants were randomly assigned to receive off-label oral sildenafil (0.5 mg/kg every 6 h) or a placebo solution, for one week. The primary endpoints were the incidence of BPD and death at 36 weeks PMA, and the side effects. Secondary outcomes included the incidence of BPD and the respiratory support at day 28 of life, duration of oxygen use, fraction of inspired oxygen use at 36 weeks and 28 days of life, duration of hospitalization, and the incidence of significant retinopathy of prematurity, severe intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and late sepsis. RESULTS: No significant differences were observed between the sildenafil and placebo study groups in mortality at 36 weeks PMA (10% vs 20%, p = 1), respiratory support at 36 weeks (30% vs 25%, p = 0.57), and side effects (0% vs 0%). For all other secondary outcomes, no significant differences were detected. CONCLUSIONS: While not associated with side effects, off-label oral sildenafil did not demonstrate benefits in the prevention of BPD or death in the extreme and very preterm infants. Future studies of dosing and efficacy that target different regimens of sildenafil are warranted before sildenafil is recommended for the prevention of BPD.


Assuntos
Displasia Broncopulmonar/prevenção & controle , Recém-Nascido Prematuro , Profilaxia Pré-Exposição/métodos , Estudo de Prova de Conceito , Citrato de Sildenafila/administração & dosagem , Vasodilatadores/administração & dosagem , Displasia Broncopulmonar/diagnóstico , Método Duplo-Cego , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Masculino , Projetos Piloto , Fatores de Risco
13.
J Perinat Med ; 47(6): 671-676, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31365347

RESUMO

Background Antioxidant enzymes may play a significant role in the development of bronchopulmonary dysplasia (BPD). The aim of the study was to assess the relationship between the level of extracellular superoxide dismutase (SOD3) in the serum at days 1 and 7 of life and the risk of developing BPD. Methods The study comprised 103 neonates born before 32 weeks' gestation with a birth weight of ≤1500 g. Results In the investigated group, the median serum SOD3 level at day 1 of life was 4.01 ng/mL [interquartile range (IQR) 2.59-5.09 ng/mL] and at day 7 of life 3.13 ng/mL (IQR 2.49-4.34 ng/mL). A statistically significant decrease in the serum SOD3 level was found in the first week of life, P < 0.0001. No correlation was found between the serum SOD3 level at day 1 of life and gestational age R = 0.07, P = 0.4543 and birth weight R = 0.10, P = 0.3083. No statistically significant correlation was found between the dynamics of change in the SOD3 level in serum at days 1 and 7 of life and the risk of BPD development for the definition of BPD at day 28 of life, P = 0.8764 nor at 36 weeks' postmenstrual age, P = 0.6598. Conclusion The study revealed a statistically significant decrease in the serum SOD3 level in the first week of life in very and extremely low birth weight infants born before 32 weeks of gestation. In the clinical setting, no relationship was observed between the level of SOD3 in serum and the risk of developing BPD.


Assuntos
Displasia Broncopulmonar , Recém-Nascido de Peso Extremamente Baixo ao Nascer/sangue , Recém-Nascido Prematuro/sangue , Superóxido Dismutase/sangue , Peso ao Nascer , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/epidemiologia , Correlação de Dados , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Polônia , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco
14.
Neoreviews ; 20(5): e272-e279, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31261079

RESUMO

Bronchopulmonary dysplasia (BPD) remains a common and challenging complication of prematurity, with limited effective strategies at the neonatologist's disposal. Throughout the years, our understanding of this complex syndrome has broadened. Instead of solely attributing this disease to the effects of prematurity and injuries to the lung from mechanical ventilation, it is now accepted to be a multifactorial disease. Recent research efforts have focused on investigating the gene-environment interactions that may influence an infant's susceptibility toward the development of BPD. So far, success has been limited but promising, offering hope that in the future, novel therapies will be available to ameliorate the risk for BPD.


Assuntos
Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/genética , Testes Genéticos/tendências , Estudos em Gêmeos como Assunto/tendências , Displasia Broncopulmonar/terapia , Testes Genéticos/métodos , Humanos , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Doenças do Prematuro/diagnóstico , Doenças do Prematuro/genética , MicroRNAs/genética , Respiração Artificial/métodos , Respiração Artificial/tendências , Estudos em Gêmeos como Assunto/métodos
15.
BMC Pediatr ; 19(1): 138, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039810

RESUMO

OBJECTIVE: To evaluate the association between hematological parameters at birth and the risk of moderate-severe bronchopulmonary dysplasia (BPD) in a cohort of extremely preterm infants. METHODS: This is a retrospective study of all extremely premature infants admitted to the neonatal intensive care unit, Shenzhen Maternity and Child Healthcare Hospital from January 2016 to May 2018. Extremely prematurity was defined as a delivery at a gestational age ≤ 28 weeks or a birth weight ≤ 1000 g. BPD was diagnosed if oxygen exposure exceeded 28 days and the severity was decided at 36 weeks PMA or discharge. Multivariable analysis was performed to assess the independence of the association between hematological parameters at birth and risk of moderate or severe BPD. RESULTS: A total of 115 extremely premature infants were analyzed in this study. The median platelet count, neutrophil and monocyte count at birth were significantly higher in infants with moderate-severe BPD compared to infants without BPD (228 vs 194*109/l, P = 0.004; 5.0 vs 2.95*109/l, P = 0.023; 0.88 vs 0.63*109/l, P = 0.026, respectively) whereas the mean platelet volume was significantly lower in infants with moderate-severe BPD than those without BPD (9.1 vs 9.4 fl, P = 0.002). After adjusting for covariates, the risk of moderate-severe BPD was independently associated with platelet count≥207*109/l (odds ratio 3.794, 95% confidence interval: 1.742-8.266, P = 0.001). CONCLUSION: Our findings suggest that hematologic parameters at birth are different in extremely preterm infants who will develop moderate-severe BPD. A higher platelet count at birth may increase the risk of moderate-severe BPD after extremely premature birth.


Assuntos
Displasia Broncopulmonar/sangue , Cuidados Críticos/métodos , Mortalidade Hospitalar/tendências , Lactente Extremamente Prematuro , Contagem de Plaquetas/métodos , Síndrome do Desconforto Respiratório do Recém-Nascido/sangue , Índice de Apgar , Peso ao Nascer , Análise Química do Sangue , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/epidemiologia , China , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Modelos Logísticos , Masculino , Análise Multivariada , Gravidez , Prognóstico , Síndrome do Desconforto Respiratório do Recém-Nascido/diagnóstico , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Análise de Sobrevida
16.
Respir Res ; 20(1): 102, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31126291

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a risk factor for respiratory disease in adulthood. Despite the differences in underlying pathology, patients with a history of BPD are often treated as asthmatics. We hypothesized that pulmonary outcomes and health-related quality of life (HRQoL) were different in adults born preterm with and without a history of BPD compared to asthmatics and healthy individuals. METHODS: We evaluated 96 young adults from the LUNAPRE cohort ( clinicaltrials.gov/ct2/show/NCT02923648 ), including 26 individuals born preterm with a history of BPD (BPD), 23 born preterm without BPD (preterm), 23 asthmatics and 24 healthy controls. Extensive lung function testing and HRQoL were assessed. RESULTS: The BPD group had more severe airway obstruction compared to the preterm-, (FEV1- 0.94 vs. 0.28 z-scores; p ≤ 0.001); asthmatic- (0.14 z-scores, p ≤ 0.01) and healthy groups (0.78 z-scores, p ≤ 0.001). Further, they had increased ventilation inhomogeneity compared to the preterm- (LCI 6.97 vs. 6.73, p ≤ 0.05), asthmatic- (6.75, p = 0.05) and healthy groups (6.50 p ≤ 0.001). Both preterm groups had lower DLCO compared to healthy controls (p ≤ 0.001 for both). HRQoL showed less physical but more psychological symptoms in the BPD group compared to asthmatics. CONCLUSIONS: Lung function impairment and HRQoL in adults with a history of BPD differed from that in asthmatics highlighting the need for objective assessment of lung health.


Assuntos
Asma/epidemiologia , Asma/fisiopatologia , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/fisiopatologia , Adolescente , Asma/diagnóstico , Displasia Broncopulmonar/diagnóstico , Estudos de Coortes , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Recém-Nascido , Masculino , Nascimento Prematuro/diagnóstico , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/fisiopatologia , Qualidade de Vida/psicologia , Testes de Função Respiratória/métodos , Adulto Jovem
17.
Rev Chil Pediatr ; 90(1): 36-43, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31095217

RESUMO

INTRODUCTION: Multiple factors influence the risk of morbidity and mortality of premature infants with intrauterine growth restriction (IUGR). The comparison of twins with different intrauterine growth allows evaluating the effect of the restriction, excluding maternal factors and prenatal mana gement. Our objective was to assess the effect of IUGR on acute and chronic morbidity, and mortality of extreme preterm twins. PATIENTS AND METHOD: Twins weighing less than 1500 grams and gesta tion equal to or less than 30 weeks, of the Neocosur Network. Separate analyses were performed on concordant twin pairs, and on mild and severe discordant twins, evaluating the effect of IUGR on morbidity and mortality. A multivariate analysis was performed in order to establish the impact of this effect. RESULTS: 459 twin pairs, 227 concordant twins, 110 of mild discordance, and 122 of severe discordance. Among the concordant ones, there was only a difference in oxygen uptake at 36 weeks. In those of mild discordance, the smaller twin presented a lower frequency of hyaline membrane disease and required fewer doses of surfactant, but had a higher risk of bronchopulmonary dysplasia (BPD) or death. In severe discordant twins, the smaller one presented higher mortality, sepsis, use and permanence in mechanical ventilation, despite the lower frequency of hyaline membrane disease. In multiple regression analysis, the combined risk of BPD or death was higher in the smaller twin and of severe discordance. CONCLUSION: In discordant twins, the acute respiratory pathology was more frequent in the larger one, although the risk of BPD or death was higher in the one with IUGR.


Assuntos
Displasia Broncopulmonar/etiologia , Doenças em Gêmeos/etiologia , Retardo do Crescimento Fetal/fisiopatologia , Sepse Neonatal/etiologia , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/mortalidade , Estudos de Casos e Controles , Doenças em Gêmeos/diagnóstico , Doenças em Gêmeos/mortalidade , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Modelos Logísticos , Masculino , Sepse Neonatal/diagnóstico , Sepse Neonatal/mortalidade , Gravidez , Prognóstico , Estudos Retrospectivos , Fatores de Risco
18.
Am J Respir Crit Care Med ; 200(6): 751-759, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-30995069

RESUMO

Rationale: Current diagnostic criteria for bronchopulmonary dysplasia rely heavily on the level and duration of oxygen therapy, do not reflect contemporary neonatal care, and do not adequately predict childhood morbidity.Objectives: To determine which of 18 prespecified, revised definitions of bronchopulmonary dysplasia that variably define disease severity according to the level of respiratory support and supplemental oxygen administered at 36 weeks' postmenstrual age best predicts death or serious respiratory morbidity through 18-26 months' corrected age.Methods: We assessed infants born at less than 32 weeks of gestation between 2011 and 2015 at 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.Measurements and Main Results: Of 2,677 infants, 683 (26%) died or developed serious respiratory morbidity. The diagnostic criteria that best predicted this outcome defined bronchopulmonary dysplasia according to treatment with the following support at 36 weeks' postmenstrual age, regardless of prior or current oxygen therapy: no bronchopulmonary dysplasia, no support (n = 773); grade 1, nasal cannula ≤2 L/min (n = 1,038); grade 2, nasal cannula >2 L/min or noninvasive positive airway pressure (n = 617); and grade 3, invasive mechanical ventilation (n = 249). These criteria correctly predicted death or serious respiratory morbidity in 81% of study infants. Rates of this outcome increased stepwise from 10% among infants without bronchopulmonary dysplasia to 77% among those with grade 3 disease. A similar gradient (33-79%) was observed for death or neurodevelopmental impairment.Conclusions: The definition of bronchopulmonary dysplasia that best predicted early childhood morbidity categorized disease severity according to the mode of respiratory support administered at 36 weeks' postmenstrual age, regardless of supplemental oxygen use.


Assuntos
Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/fisiopatologia , Medicina Baseada em Evidências/métodos , Doenças do Prematuro/diagnóstico , Doenças do Prematuro/fisiopatologia , Pediatria/métodos , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Masculino , Estados Unidos
19.
Pediatr Pulmonol ; 54(7): 1045-1051, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30950245

RESUMO

RATIONALE: Infants with severe bronchopulmonary dysplasia (sBPD) and airway obstruction may develop dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEPi ), which impairs patient/ventilator synchrony. OBJECTIVES: To determine if PEEPi is present in infants with sBPD during spontaneous breathing and if adjusting ventilator PEEP improves patient/ventilator synchrony and comfort. METHODS: Interventional study in infants with sBPD. PEEPi measured by esophageal pressure (Pes) and pneumotachometer, during pressure-supported breaths. PEEP i defined as the difference between Pes at start of the inspiratory effort minus Pes at onset of inspiratory flow. The set PEEP was adjusted to minimize PEEP i . "Best PEEP" was the setting with minimal wasted efforts (WE), an inspiratory effort seen on the Pes waveform without a corresponding ventilator breath. FiO 2 and SpO 2 measured pre- and post-PEEP adjustment. Sedation requirements evaluated 72 hours preprocedure and postprocedure. RESULTS: Twelve infants were assessed (gestational age, 24.9 ± 1.4 weeks; study age, 48.8 ± 1.5 weeks, postmenstrual age). Mean baseline ventilator PEEP was 16.4 cm H2 O (14-20 cm H 2 O). Eight infants required an increase, one, a reduction, and three, no change in the set PEEP. For the eight infants requiring an increase in set PEEP, there was an 18.9% reduction in WE and a reduction in FiO 2 (0.084 ± 0.058) requirements in the subsequent 24 hours. Conditional sedation was reduced in five infants postprocedure. No adverse events occurred during testing. CONCLUSION: PEEPi is measurable in infants with sBPD with concurrent esophageal manometry and flow-time tracings without the need for pharmacological paralysis. In those with PEEP i , increasing ventilator PEEP to offset PEEP i improves synchrony.


Assuntos
Displasia Broncopulmonar , Respiração por Pressão Positiva Intrínseca , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/terapia , Humanos , Recém-Nascido , Respiração por Pressão Positiva Intrínseca/diagnóstico , Respiração por Pressão Positiva Intrínseca/terapia , Ventiladores Mecânicos
20.
J Pediatr ; 209: 17-22.e2, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30961990

RESUMO

OBJECTIVE: To determine the impact of policy changes for pulse oximetry oxygen saturation (SpO2) alarm limits on neonatal mortality and morbidity among infants born very preterm. STUDY DESIGN: This was a retrospective cohort study of infants born very preterm in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants were classified based on treatment at a hospital with an SpO2 alarm policy change and study epoch (before vs after policy change). We used a generalized linear mixed model to determine the effect of hospital group and epoch on the primary outcomes of mortality and severe retinopathy of prematurity (ROP) and secondary outcomes of necrotizing enterocolitis, bronchopulmonary dysplasia, and any ROP. RESULTS: There were 3809 infants in 10 hospitals with an SpO2 alarm policy change and 3685 infants in 9 hospitals without a policy change. The nature of most policy changes was to narrow the SpO2 alarm settings. Mortality was lower in hospitals without a policy change (aOR 0.63; 95% CI 0.50-0.80) but did not differ between epochs in policy change hospitals. The odds of bronchopulmonary dysplasia were greater for hospitals with a policy change (aOR 1.65; 95% CI 1.36-2.00) but did not differ for hospitals without a policy change. Severe ROP and necrotizing enterocolitis did not differ between epochs for either group. The adjusted odds of any ROP were lower in recent years in both hospital groups. CONCLUSIONS: Changing SpO2 alarm policies was not associated with reduced mortality or increased severe ROP among infants born very preterm.


Assuntos
Displasia Broncopulmonar/diagnóstico , Enterocolite Necrosante/diagnóstico , Mortalidade Infantil/tendências , Lactente Extremamente Prematuro , Oximetria/métodos , Retinopatia da Prematuridade/diagnóstico , Displasia Broncopulmonar/epidemiologia , Estudos de Coortes , Enterocolite Necrosante/epidemiologia , Feminino , Política de Saúde , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Morbidade/tendências , Consumo de Oxigênio/fisiologia , Formulação de Políticas , Retinopatia da Prematuridade/epidemiologia , Estudos Retrospectivos , Inquéritos e Questionários
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