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.

Construction of early risk prediction models for bronchopulmonary dysplasia in preterm infants / 中国当代儿科杂志

OBJECTIVES@#To construct risk prediction models for bronchopulmonary dysplasia (BPD) in preterm infants on postnatal days 3, 7, and 14.@*METHODS@#A retrospective analysis was performed on the medical data of 414 preterm infants, with a gestational age of <32 weeks and a birth weight (BW) of <1 500 g, who were admitted to the neonatal intensive care unit from July 2019 to April 2021. According to the diagnostic criteria for BPD revised in 2018, they were divided into a BPD group with 98 infants and a non-BPD group with 316 infants. The two groups were compared in terms of general status, laboratory examination results, treatment, and complications. The logistic regression model was used to identify the variables associated with BPD. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of models.@*RESULTS@#The logistic regression analysis showed that BW, asphyxia, grade III-IV respiratory distress syndrome (RDS), acute chorioamnionitis, interstitial pneumonia, fraction of inspired oxygen (FiO@*CONCLUSIONS@#BW, asphyxia, grade III-IV RDS, acute chorioamnionitis, interstitial pneumonia, FiO

A review on the effect of Claudin-18 on bronchopulmonary dysplasia in preterm infants / 中国当代儿科杂志

Bronchopulmonary dysplasia (BPD) has the main manifestations of pulmonary edema in the early stage and characteristic alveolar obstruction and microvascular dysplasia in the late stage, which may be caused by structural and functional destruction of the lung epithelial barrier. The Claudin family is the main component of tight junction and plays an important role in regulating the permeability of paracellular ions and solutes. Claudin-18 is the only known tight junction protein solely expressed in the lung. The lack of Claudin-18 can lead to barrier dysfunction and impaired alveolar development, and the knockout of Claudin-18 can cause characteristic histopathological changes of BPD. This article elaborates on the important role of Claudin-18 in the development and progression of BPD from the aspects of lung epithelial permeability, alveolar development, and progenitor cell homeostasis, so as to provide new ideas for the pathogenesis and clinical treatment of BPD.

Association of early nutrition deficiency with the risk of bronchopulmonary dysplasia: a Meta analysis / 中国当代儿科杂志

OBJECTIVE@#To systematically evaluate the association of early nutrition intake with the risk of bronchopulmonary dysplasia (BPD).@*METHODS@#PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and Weipu Periodical Database were searched for the observational studies on the association between early nutrition intake and BPD. RevMan 5.3 software was used to perform a Meta analysis of eligible studies.@*RESULTS@#Eight observational studies were included, with 548 infants with BPD and 522 infants without BPD. The Meta analysis showed that the BPD group had a significantly lower caloric intake than the non-BPD group within the first week after birth and in the first 2 weeks after birth (@*CONCLUSIONS@#Early nutrition deficiency may be associated with the development of BPD, and more attention should be paid to enteral feeding of infants at a high risk of BPD to achieve total enteral feeding as soon as possible.

Restricción de crecimiento aumenta el riesgo de displasia broncopulmonar, muerte y sepsis en gemelos de 30 o menos semanas de gestación / Growth restriction increases the risk of bronchopulmonary dysplasia, death, and sepsis in twins of 30 weeks or less of gestation

INTRODUCCIÓN: Múltiples factores influyen en el riesgo de morbimortalidad del prematuro con restricción del crecimiento intrauterino (RCIU). La comparación de gemelos con crecimiento intrauterino discordante permite evaluar su efecto, excluyendo factores maternos y manejo prenatal. Nuestro objetivo fue evaluar el efecto de la RCIU sobre la morbilidad aguda, crónica y mortalidad, en parejas de recién nacidos gemelares prematuros extremos. PACIENTES Y MÉTODO: Gemelos menores de 1500 g y 30 semanas de gestación, de la Red Neocosur. Se realizaron análisis separados de pares de gemelos concordantes, discordantes leves y severos, evaluando el efecto de la RCIU sobre morbi-mortalidad. Se realizó análisis multivariado para establecer magnitud del efecto. RESULTADOS: 459 pares de gemelos, 227 concordantes, 110 discordantes leves y 122 severos. Entre los concordantes solo hubo diferencia en uso de oxígeno a las 36 semanas. En discordantes leves, el menor tuvo menos enfermedad de membrana hialina y requirió menos dosis de surfactante, pero tuvo un mayor riesgo de Displasia broncopulmonar (DBP) o muerte. En discordantes severos, el menor presentó mayor mortalidad, sepsis, utilización y permanencia en ventilación mecánica, pese a menor frecuencia de enfermedad de membrana hialina. En regresión múltiple, el riesgo combinado de DBP o muerte fue mayor en gemelo menor y discordante severo. CONCLUSIÓN: En gemelos discordantes, la patología respiratoria aguda fue más frecuente en el gemelo mayor, aunque el riesgo de DBP o muerte fue mayor en el gemelo con RCIU.

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.

Inflammatory and oxidative stress airway markers in premature newborns of hypertensive mothers

Although oxidative stress and inflammation are important mechanisms in the pathophysiology of preeclampsia and preterm diseases, their contribution to the respiratory prognosis of premature infants of hypertensive mothers is not known. Our objective was to determine the levels of oxidative stress and inflammation markers in the airways of premature infants born to hypertensive and normotensive mothers, in the first 72 h of life, and to investigate whether they are predictors of bronchopulmonary dysplasia (BPD)/death. This was a prospective study with premature infants less than 34 weeks’ gestation on respiratory support who were stratified into 2 groups: 32 premature infants of hypertensive mothers and 41 of normotensive women, with a mean gestational age of 29 weeks. Exclusion criteria were as follows: diabetes mellitus, chorioamnionitis, malformation, congenital infection, and death within 24 h after birth. The outcome of interest was BPD/death. Malondialdehyde (MDA), nitric oxide (NO), and interleukin 8 (IL-8) were measured in airway aspirates from the first and third days of life and did not differ between the groups. Univariate and multivariate statistical analyses were performed. The concentrations of MDA, NO, and IL-8 were not predictors of BPD/death. Premature infants who developed BPD/death had higher levels of IL-8 in the first days of life. The gestational age, mechanical ventilation, and a small size for gestational age were risk factors for BPD/death. In conclusion, the biomarkers evaluated were not increased in premature infants of hypertensive mothers and were not predictors of BPD/death.

La nueva displasia broncopulmonar desde el punto de vista de neumólogo pediatra / New bronchopulmonary dysplasia, from a pediatric pulmonologist´s perspective

Bronchopulmonary dysplasia (BPD) is the most prevalent chronic lung disease of prematurity. The so-called new BPD has replaced the classic BPD described by Northway, as a result of maternal use of corticosteroids, early surfactant and less aggressive mechanical ventilation and the survival of younger premature, born during the canalicular stage and that completed their alveolization outside the uterus. The new BPD is a less severe disease, but lung function is impaired in the long-term. An update of the new BPD, focused on the management after discharge from neonatology, from a pediatric pulmonologist perspective is presented.

La Displasia Broncopulmonar (DBP) es la enfermedad pulmonar crónica más prevalente del prematuro. La denominada nueva DBP ha reemplazado a la DBP clásica descripta por Northway, como consecuencia del uso de corticoides maternos, surfactante precoz, ventilación mecánica menos agresiva y la sobrevivencia de prematuros más pequeños, que nacen en etapa canalicular de su desarrollo pulmonar y completan su alveolización fuera del útero. La nueva DBP es una patología menos severa, pero con compromiso funcional respiratorio a largo plazo. A continuación se describe una actualización de la nueva DBP, enfocada en el manejo realizado luego del alta de neonatología, desde el punto de vista del Neumólogo Pediatra.

Risk Factors for Late-onset Hyponatremia and Its Influence on Neonatal Outcomes in Preterm Infants

Late-onset hyponatremia (LOH), hyponatremia occurring after two weeks of age with the achievement of full feeding, is the result of a negative sodium balance caused by inadequate salt intake or excessive salt loss due to immature renal or intestinal function in preterm infants. The aims of our study were to identify the risk factors for LOH and its influence on neonatal outcomes. This was a retrospective cohort analysis of 161 preterm infants born before 34 weeks of gestation between June 2009 and December 2010 at Seoul National University Hospital. LOH was defined as a sodium level < or = 132 mEq/L or 133-135 mEq/L with oral sodium supplementation. LOH occurred in 49 (30.4%) of the studied infants. A lower gestational age, a shorter duration of parenteral nutrition, the presence of respiratory distress syndrome, the use of furosemide, and feeding with breast milk were significant risk factors for LOH. In terms of neonatal outcomes, the infants with LOH had longer hospital stays and higher risks of bronchopulmonary dysplasia and retinopathy of prematurity requiring surgery. LOH lasting at least 7 days significantly increased moderate to severe bronchopulmonary dysplasia, periventricular leukomalacia, and extra-uterine growth retardation. LOH is commonly observed in preterm infants; it may be a risk factor for bronchopulmonary dysplasia and retinopathy of prematurity or a marker of illness severity.

Lesao pulmonar induzida pela ventilacao em recem-nascidos prematuros / Ventilator-induced lung injury in preterm infants

A necessidade de intubação e do uso de ventilação mecânica na prematuridade está relacionada à chamada lesão pulmonar induzida pela ventilação e à consequente displasia broncopulmonar. Busca-se a melhor compreensão dos mecanismos de lesão envolvendo resposta inflamatória mediada pelas citocinas para o desenvolvimento de novas estratégias protetoras. Pesquisou-se na base de dados PubMed, incluindo artigos relevantes, os unitermos "ventilator induced lung injury preterm", "continuous positive airway pressure", "preterm" e "bronchopulmonary dysplasia". Dados e informações significativas foram compilados em tópicos, com o objetivo de formar uma visão crítica e plena acerca da lesão induzida pela ventilação e de suas consequências ao prematuro. Foi revisado o papel das citocinas pró-inflamatórias como mediadores da lesão, especialmente interleucinas 6 e 8, e fator de necrose tumoral alfa. Foram apresentadas evidências em estudos com animais e também em humanos, mostrando que breves períodos de ventilação mecânica são suficientes para a liberação dessas interleucinas inflamatórias. Também foram revisadas outras formas de ventilação mecânica e de ventilação não invasiva, como alternativas protetoras aos modos convencionais. Concluiu-se que o uso de ventilação não invasiva, a intubação com administração precoce de surfactante e a extubação rápida para CPAP nasal, além de estratégias que regulam o volume corrente evitando o volutrauma (como a ventilação com volume garantido), são medidas protetoras da lesão pulmonar induzida pela ventilação mecânica no prematuro.

In preterm infants, the need for intubation and mechanical ventilation is associated with ventilator-induced lung injuries and subsequent bronchopulmonary dysplasia. The aim of the present review was to improve the understanding of the mechanisms of injury that involve cytokine-mediated inflammation to contribute to the development of new preventive strategies. Relevant articles were retrieved from the PubMed database using the search terms "ventilator-induced lung injury preterm", "continuous positive airway pressure", "preterm", and "bronchopulmonary dysplasia". The resulting data and other relevant information were divided into several topics to ensure a thorough, critical view of ventilation-induced lung injury and its consequences in preterm infants. The role of pro-inflammatory cytokines (particularly interleukins 6 and 8 and tumor necrosis factor alpha) as mediators of lung injury was assessed. Evidence from studies conducted with animals and human newborns is described. This evidence shows that brief periods of mechanical ventilation is sufficient to induce the release of pro-inflammatory cytokines. Other forms of mechanical and non-invasive ventilation were also analyzed as protective alternatives to conventional mechanical ventilation. It was concluded that non-invasive ventilation, intubation followed by early surfactant administration and quick extubation for nasal continuous positive airway pressure, and strategies that regulate tidal volume and avoid volutrauma (such as volume guarantee ventilation) protect against ventilator-induced lung injury in preterm infants.

High Incidence of Rickets in Extremely Low Birth Weight Infants with Severe Parenteral Nutrition-Associated Cholestasis and Bronchopulmonary Dysplasia

Risk factors for rickets of prematurity have not been re-examined since introduction of high mineral formula, particularly in ELBW infants. We analyzed the incidence and the risk factors of rickets in extremely low birth weight (ELBW) infants. As a retrospective case-control study from 2004 to 2008, risk factors were analyzed in 24 patients with rickets versus 31 patients without. The frequency of rickets in ELBW infants was 24/55 (44%). Infants with rickets were diagnosed at 48.2 +/- 16.1 days of age, and improved by 85.3 +/- 25.3 days. By radiologic evaluation, 29% were grade 1 rickets, 58% grade 2 and 13% grade 3. In univariate analysis, infants with rickets had significantly higher incidence of patent ductus arteriosus, parenteral nutrition associated cholestasis (PNAC), severe PNAC and moderate/severe bronchopulmonary dysplasia (BPD). In multiple regression analysis, after adjustment for gestation and birth weight, rickets significantly correlated with severe PNAC and with moderate/severe BPD. Serum peak alkaline phosphatase levels were significantly elevated in rickets (P < 0.001). In ELBW infants, the incidence of rickets of prematurity remains high and the incidence of severe PNAC and moderate/severe BPD was significantly increased 18 and 3 times, respectively.

Influência de fatores maternos e neonatais no desenvolvimento da displasia broncopulmonar / Influence of maternal and neonatal factors on bronchopulmonary dysplasia development

OBJETIVO: Analisar as características epidemiológicas da displasia broncopulmonar (DBP) e suas relações com condições maternas e neonatais em uma unidade neonatal. MÉTODOS: Estudo transversal, descritivo e analítico, sendo os dados coletados através da análise de prontuários envolvendo recém-nascidos (RNs) pré-termo com peso ao nascimento inferior a 1.500 g e idade gestacional abaixo de 37 semanas internados em uma unidade neonatal. RESULTADOS: Foram estudados 323 recém-nascidos com média do peso ao nascimento de 1.161 g (± 231 g), idade gestacional entre 24 e 36,5 semanas com incidência da DBP de 17,6 por cento. Entre os RNs que desenvolveram DBP, a média de dias de uso de assistência ventilatória mecânica invasiva (AVMI), ventilação não invasiva (VNI) e oxigênio foi, respectivamente, 17,6 dias, 16,2 dias e 46,1 dias, sendo significativamente maior naqueles RNs que desenvolveram a DBP (p < 0,001). A ocorrência da DBP foi significativamente maior nos RNs com diagnóstico de persistência do canal arterial (PCA). CONCLUSÃO: A incidência da DBP neste estudo foi semelhante à encontrada na literatura mundial. Não houve associação entre a presença de infecção materna e o uso de corticoide antenatal com a DBP. Os RNs que fizeram uso de surfactante tiveram maior incidência da DBP porque tinham menor PN e menor IG. A ocorrência da PCA e DBP simultaneamente está associada ao maior tempo de uso de AVMI, VNI e oxigênio.

OBJECTIVE: To review epidemiological features of bronchopulmonary dysplasia (BPD) and its relationship with maternal and neonatal conditions in a neonatal unit. METHODS: Cross-sectional, descriptive and analytical study involving preterm newborns (NBs) with a birth weight lower than 1,500 g and gestational age under 37 weeks. Data was collected through a review of medical records of these newborns admitted to a neonatal unit. RESULTS: The study included 323 newborns with a mean birth weight of 1,161 g (± 231 g), gestational age between 24 and 36.5 weeks, with a BPD incidence of 17.6 percent. Among the NBs developing BPD, the mean of days using invasive mechanical ventilation (IMV), non-invasive ventilation (NIMV), and supplemental oxygen was 17.6, 16.2, and 46.1 days, respectively, with a time significantly longer for those NBs developing BPD (p < 0.001). BPD occurred significantly more often in NBs with a patent ductus arteriosus (PDA). CONCLUSION: BPD incidence in this study was similar to that found in the literature. No BPD association with maternal infection and antenatal corticosteroid use was found. NBs receiving exogenous surfactant had a higher BPD incidence because they had lower BW and GA. Concomitant occurrence of PDA and BPD is associated with staying longer on IMV, NIMV and supplemental oxygen.

Initial respiratory management in preterm infants and bronchopulmonary dysplasia

BACKGROUND: Ventilator injury has been implicated in the pathogenesis of bronchopulmonary dysplasia. Avoiding invasive ventilation could reduce lung injury, and early respiratory management may affect pulmonary outcomes. OBJECTIVE: To analyze the effect of initial respiratory support on survival without bronchopulmonary dysplasia at a gestational age of 36 weeks. DESIGN/METHODS: A prospective 3-year observational study. Preterm infants of <32 weeks gestational age were classified into 4 groups according to the support needed during the first 2 hours of life: room air, nasal continuous positive airway pressure, intubation/surfactant/extubation and prolonged mechanical ventilation (defined as needing mechanical ventilation for more than 2 hours). RESULTS: Of the 329 eligible patients, a total of 49 percent did not need intubation, and 68.4 percent did not require prolonged mechanical ventilation. At a gestational age of 26 weeks, there was a significant correlation between survival without bronchopulmonary dysplasia and initial respiratory support. Preterm infants requiring mechanical ventilation showed a higher risk of death and bronchopulmonary dysplasia. After controlling for gestational age, antenatal corticosteroid use, maternal preeclampsia and chorioamnionitis, the survival rate without bronchopulmonary dysplasia remained significantly lower in the mechanically ventilated group. CONCLUSIONS: In our population, the need for more than 2 hours of mechanical ventilation predicted the development of bronchopulmonary dysplasia in preterm infants with a gestational age >26 weeks (sensitivity =89.5 percent and specificity = 67 percent). The need for prolonged mechanical ventilation could be an early marker for the development of bronchopulmonary dysplasia. This finding could help identify a target population with a high risk of chronic lung disease. Future research is needed to determine other strategies to prevent bronchopulmonary dysplasia in this high-risk group of patients.

Ruptura prematura das membranas amnióticas no pré-termo: fatores associados à displasia broncopulmonar / Preterm premature rupture of the fetal membranes: factors associated with bronchopulmonary dysplasia

OBJETIVO: identificar os fatores obstétricos e neonatais associados ao desfecho de displasia broncopulmonar em pacientes com amniorrexe prematura no pré-termo. MÉTODOS: foram analisados 213 prontuários do Instituto Fernandes Figueira, entre 1998 e 2002, cujas pacientes evoluíram com quadro de amniorrexe prematura <34 semanas de gestação. Foram excluídas gestações múltiplas. As variáveis de natureza clínico-obstétricas e neonatais foram cotejadas com o desfecho de displasia broncopulmonar. Os dados foram submetidos à análise bivariada, sendo os valores que exibiam significância estatística (p<0,05) submetidos à regressão logística. RESULTADOS: a prevalência de displasia broncopulmonar foi de 6.10 por cento. A análise univariada dos fatores associados ao desfecho de displasia broncopulmonar exibiu os seguintes resultados: tempo de ventilação mecânica neonatal >10 dias (OR: 54,00 [11,55-278,25] p=0,000); idade gestacional <30 semanas (OR: 6,33 [1,26-43,06] p=0,017) peso <1.000 g (OR: 4,82 [1,34-17,53] p=0,010); peso <1.500 g (OR: 14,09 [1,82-300,50] p=0,003; persistência do canal arterial (OR: 12,33 [3,07-50,10], p=0,000); doença da membrana hialina (OR: 8,46 [2,21-35,00] p=0,000); pneumonia congênita (OR: 7,48 [2,03-27,93] p=0,000); uso de surfactante neonatal (OR: 19,66 [4,54-97,76] p=0,000) e infecção neonatal (OR: 7,67 [0,99-163,79] p=0,049). No modelo multivariado final, somente as variáveis "ventilação mecânica">10 dias (p=0,001) e "uso de surfactante" (p=0,040) permaneceram independentemente associadas ao desfecho. CONCLUSÕES: observou-se que os fatores associados à displasia broncopulmonar são de natureza neonatal, sendo que a ventilação mecânica duradoura e o uso de surfactante neonatal influenciaram no desenvolvimento dessa doença.

PURPOSE: to analyze obstetric and neonatal factors associated with bronchopulmonary dysplasia outcome in patients with preterm premature amniorrhexis. METHODS: we analyzed 213 medical records of patients of Fernandes Figueira Institute who suffered premature amniorrhexis (<34 weeks of gestation) in the period from 1998 to 2002. Multiple gestations were excluded. Clinical-obstetric and neonatal variables were considered in relation to the bronchopulmonary dysplasia outcome. Data were subjected to bivariate analysis, and the values showing statistical significance (p<0.05) were subjected to logistic regression analysis. RESULTS: the prevalence of bronchopulmonary dysplasia was 6.10 percent. Univariate analysis of the factors associated with the pulmonary dysplasia outcome were: neonatal mechanical ventilation for more than ten days(OR: 54.00 [11.55-278.25] p=0.000); birth gestational age of less than 30 weeks (OR: 6.33 [1.26- 43.06] p=0.017); birth weight <1,000 g (OR: 4.82 [1.34-17.53] p=0.010); birth weight <1.500 g (OR: 14.09 [1.82-300.50] p=0.003; patent ductus arteriosus (OR: 12.33 [3.07-50.10], p=0.000); hyaline membrane disease (OR: 8.46 [2.21-35.00] p=0.000); congenital pneumonia (OR: 7.48 [2.03-27.93] p=0.000); use of neonatal surfactant (OR: 19.66 [4.54-97.76] p=0.000), and neonatal infection (OR: 7.67 [0.99-163.79] p=0.049). In the final multivariate model, only the variables "neonatal mechanical ventilation">10 days (p=0.001) and "use of a surfactant" (p=0.040) remained independently associated with bronchopulmonary dysplasia. CONCLUSIONS: the factors associated with bronchopulmonary dysplasia are related to neonatal features, asprolonged mechanical ventilation and the use of a surfactant influencethe development of thedisease.

Fluid and electrolyte balance during the first week of life and risk of bronchopulmonary dysplasia in the preterm neonate

BACKGROUND: Early fluid and electrolyte imbalances may be associated with an increased risk of bronchopulmonary dysplasia. OBJECTIVE: We sought to establish an association between fluid and electrolyte balance in the first week of life and the risk of bronchopulmonary dysplasia. METHODS: Clinical charts of 205 neonates <32 weeks gestational age and/or <1,250 g birth weight (admitted to our NICU between 1997 and 2008) were analyzed. Clinical features, fluid and electrolyte balance were analyzed for the first 7 days of life using multivariate models of generalized estimation equations. A p value <0.05 was considered significant in all of the hypothesis tests. RESULTS: The prevalence of bronchopulmonary dysplasia was 22 percent. Lower gestational age and birth weight, male gender, less frequent use of antenatal steroids, respiratory distress syndrome, use of surfactant, patent ductus arteriosus, duration of invasive ventilation and NICU stay were significantly associated with bronchopulmonary dysplasia. The variation in serum values of potassium, phosphorus and creatinine during the first week of life also revealed an association with bronchopulmonary dysplasia. Higher mean plasma calcium values were associated with spontaneous closure of the patent ductus arteriosus. The use of indomethacin to induce patent ductus arteriosus closure was significantly higher in bronchopulmonary dysplasia patients. CONCLUSIONS: Differences in renal function and tubular handling of potassium and phosphorus are present during the first week of life among preterm neonates who will develop bronchopulmonary dysplasia. The higher rate of patent ductus arteriosus and indomethacin use may influence these differences. Serum levels of calcium also appear to play a role in spontaneous ductus arteriosus closure.

Bronchopulmonary dysplasia in very low birth weight infants.

Objective. To determine the risk factors for development of bronchopulmonary dysplasia (BPD) by evaluating mild and moderate/severe BPD in extramural neonates with a birth weight <1501 g. Methods. A case-control study was conducted between January 1, 2004- December 31, 2006. Patients with BPD and without BPD were compared. Bronchopulmonary dysplasia was diagnosed and classified according to the Bancalari criteria. One-hundred and six (106) extramural premature infants with a birth weight <1501 g and admitted to the Neonatal Unit in the first three days of life and survived for more than 28 postnatal days were included. Patients with multiple congenital anomalies and complex cardiac pathologies were excluded. The maternal and neonatal risk factors, clinical features, mechanical ventilation treatment were compared. The principal risk factors for BPD development were analyzed and followed by logistic regression test. Results. The diagnosis was mild BPD in 27 of the 106 patients and moderate/severe BPD in 29. The incidence of BPD was 52.8%. Fifty of 106 patients had no BPD. Analysis of risk factors revealed that gestational age ≤28 weeks (p=0.019), birth weight ≤1000 g (p=0.007), hypothermia (p=0.003), acidosis (p=0.003) and hypotension (p=0.005) at admission, respiratory distress syndrome (RDS) ( p<0.001), mechanical ventilation therapy (p<0.001), surfactant therapy (p=0.005), higher amount of mean fluid therapy on 7th days (p=0.008), nosocomial infection (p<0.001), higher amount of mean packed red cell transfusions (p<0.001) and more than two packed red cell transfusions (p=0.033) were risk factors associated with the development of BPD. Multivariant logistic regression analysis showed acidosis at admission (OR 5.12, 95%CI 1.17–22.27, p=0.029), surfactant treatment (OR 7.53, 95%CI 2.14–26.45, p=0.002), nosocomial infections (OR 4.66, 95%CI 1.27–17.12, p=0.02) and PDA (OR 9.60, 95%CI 2.23–41.22, p=0.002) were risk factors increasing the severity of BPD. Conclusion. The most important risk factors for BPD development in our study were RDS and nosocomial infections while the presence of acidosis at admission, surfactant administration, nosocomial infections and the presence of PDA were the most important risk factors regarding BPD severity. Presence of acidosis at admission as a risk factor emphasized the importance of suitable transport conditions for premature infants.

Actualización en presentación y patogénesis de la displasia broncopulmonar / Update on presentation and pathogenesis of brochopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) remains as the most frequent chronic lung disease seen among babies with very low birth weight, contributing to their morbidity and mortality. An increase in the survival of very immature babies due to improvement in pre and post natal care, has resulted in an increase in the number of newborns with BDP, although there have been no changes in the actual incidence of the disease. Objective: Lo describe the evolution of DBP in recent decades, the current definition, and to describe and analyze the risk factors involved in the pathogenesis of this disease. Until a few years ago, the terms BPD and chronic lung disease were used as synonyms. After the workshop sponsored by the National Institute of Health in the United States in 2001, it was recommended that the term BPD be used to describe the pulmonary sequelae of immature babies. Classic severe BPD, as described by Northway et al over forty years ago, has evolved into milder forms of chronic pulmonary damage, the so-called "new BPD", characterized by impairment of alveolarizacion and vascularization of the immature lung in response to multiple injuries. BPD is a multifactorial disease where major risk factors are related to pulmonary immaturity, hyperoxia, baro/volutrauma, as well as inflamation and infection. Genetic susceptibility has recently been shown to be another important risk factor. Conclusion: Bronchopulmonary Dysplasia continues to be the most frequent sequelae affecting low birth weight infants. In the past four decades, the disease has been better defined, and new pathogenetic risk factors have been established.

La Displasia Broncopulmonar (DBP) continúa siendo la enfermedad pulmonar crónica más frecuente que afecta al recién nacido de muy bajo peso, contribuyendo a su morbilidad y mortalidad. El aumento en la sobrevida de los recién nacidos muy inmaduros, debido a la mejoría en el cuidado pre y post natal, ha aumentado el número de recién nacidos con displasia, sin cambios en su incidencia. El objetivo de esta revisión es representar los cambios en la presentación clínica de la DBP en las últimas décadas y describir la definición recientemente instituida, junto con analizar y actualizar los factores de riesgos involucrados en la patogénesis de esta enfermedad. Hasta hace algunos años el término DBP o Enfermedad Pulmonar Crónica se usaban como sinónimos; sin embargo luego del taller patrocinado por Instituto Nacional de Salud de Estados Unidos en el año 2001, se recomendó utilizar el término de DBP para describir las secuelas pulmonares del recién nacido muy inmaduro. La DBP clásica severa descrita por Northway y cols hace más de 40 años, ha evolucionado a formas más leves de daño pulmonar crónico, la denominada "Nueva DBP", caracterizada por un deterioro y/o detención de la alveolarización y vascularización del pulmón inmaduro en respuesta a múltiples injurias. La DBP es una enfermedad multifactorial siendo los principales factores de riesgo la inmadurez pulmonar, la hiperoxia, el baro-volutrauma, y la inflamación-infección. Recientemente se ha demostrado que la susceptibilidad genética puede ser otro factor de riesgo. La ventilación mecánica continúa siendo un importante factor de riesgo, por lo cual debe ser utilizada con precaución y sólo cuando esté claramente indicada. La persistencia del ductus arterioso se ha asociado también a DBP, por lo cual el cierre farmacológico precoz podría disminuir la incidencia de esta complicación. Conclusión: La DBP continúa siendo la secuela pulmonar crónica más frecuente que afecta al RN de muy bajo peso...

Displasia broncopulmonar: perfil dos recém-nascidos pré-termo no Hospital Universitário Norte do Paraná nos anos de 2000 a 2005 / Bronchopulmonary dysplasia: profile of the preterm newborns born in the North of Paraná University Hospital in the years 2000-2005

Objetivo: Conhecer as características pré, peri e pós-natais e verificar a evolução dos recém-nascidos pré-termos (RNPT) com diagnóstico de displasia broncopulmonar (DBP) nascidos entre 2000 e 2005 no Hospital Universitário Norte do Paraná (HUNPR). Materiais e métodos: Realizado um estudo descritivo. Resultados: Verificou-se que a idade gestacional média foi de 27,3 ± 3 semanas e dois dias e o peso médio ao nascer foi 985,4 ± 310,9 gramas 20 RN (55,6%) foram do sexo masculino e 16 (44,4%) do feminino. Dos RNPT, 24 (66,7%) utilizaram surfactante, o tempo médio de uso de ventilação mecânica foi de 28,6 ± 18,9 dias, com 12,4 ± 9,1 dias em CPAP e a FiO2máx% média foi de 88,8 ± 18,2%. O tempo médio de internação foi de 99,4 ± 53,5 dias 3,4 ± 3,3 tiveram em média outras reinternações nos primeiros anos de vida, sendo 82,6% devido a problemas respiratórios. A idade média das mães foi de 26 ± 7 anos 34 (94,4%) realizaram pré-natal, 22 (61,1%) partos foram cesáreas e 14 (38,9%) normais 16 (44,4%) utilizaram corticoide antenatal. Durante o período de internação na Unidade de Terapia Intensiva neonatal (UTI) 18 (50,0%) dos RN realizaram fisioterapia e 11 (30,6%) realizam fisioterapia atualmente. Conclusão: Observou-se que os RNPT com DBP nascidos no HUNPR foram os de menores idades gestacionais e baixo peso de nascimento e que necessitaram de tempo prolongado em ventilação mecânica. Tais fatores, associados ao tempo de internação neonatal prolongado, implicam em reinternações frequentes, verificando-se a necessidade de acompanhamento clínico multiprofissional nos primeiros anos de vida.

Decreased Expression of Transforming Growth Factor-beta1 in Bronchoalveolar Lavage Cells of Preterm Infants with Maternal Chorioamnionitis

Maternal chorioamnionitis has been associated with abnormal lung development. We examined the effect of maternal chorioamnionitis on the expression of transforming growth factor-beta1 (TGF-beta1) in the lungs of preterm infants. A total of 63 preterm (< or =34 weeks) infants who were intubated in the delivery room were prospectively enrolled. Their placentas were examined for the presence of chorioamnionitis. Bronchoalveolar lavage (BAL) fluid and cells were obtained shortly after birth. TGF-beta1 was measured in BAL fluid and TGF-beta1 mRNA expression was determined by reverse transcription polymerase chain reaction (RT-PCR) in BAL cells. TGF-beta1 mRNA expression in BAL cells showed a positive correlation with gestational age (r=0.414, p=0.002). TGF-beta1 mRNA expression was significantly decreased in the presence of maternal chorioamnionitis (0.70+/-0.12 vs. 0.81+/-0.15, p=0.007). Adjustment for gestational age, birth weight, and delivery mode did not nullify the significance. TGF-beta1 mRNA expression was marginally significantly decreased in preterm infants who developed bronchopulmonary dysplasia (BPD) later (0.75+/-0.11 vs. 0.82+/-0.15, p=0.055). However, adjustment for gestational age, patent ductus arteriosus (PDA), and maternal chorioamnionitis nullified the significance. These results might be an indirect evidence that maternal chorioamnionitis may inhibit normal lung development of fetus.

Avaliação tomográfica pulmonar tardia em prematuros com displasia broncopulmonar e persistência de canal arterial / Late pulmonary tomography assessment in premature infants with bronchopulmonary dysplasia submitted to patent ductus arteriosus managemnent

OBJETIVO: Avaliação tomográfica do parênquima pulmonar de crianças nascidas prematuras de muito baixo peso, com persistência do canal arterial submetidas a tratamento clínico ou cirúrgico e que apresentaram displasia broncopulmonar. MÉTODOS: Entre dezembro de 2006 e janeiro de 2007, 14 crianças foram submetidas à tomografia computadorizada de alta resolução (TCAR), que nasceram prematuras, peso inferior a 1500 gramas, com displasia broncopulmonar (DBP) e persistência do canal arterial (PCA), os quais necessitaram tratamento para oclusão do canal, sendo divididos em dois grupos: A - clínico (n = 6) e B - cirúrgico (n = 8). Nove pacientes eram do sexo masculino e cinco, do feminino, com idade média de 36,5±4,3 meses. As TCAR foram analisadas por dois observadores independentes e as lesões quantificadas em cada paciente. Para análises estatísticas, foi utilizado o teste de Mann-Whitney e considerados significantes valores de p<0,05. RESULTADOS: No grupo A, o achado mais freqüente foi vidro fosco multifocal. No grupo B, as lesões tipo vidro fosco multifocal, atelectasia e áreas de redução da atenuação e dos vasos foram preponderantes (62,5 por cento). Houve diferença estatisticamente significante entre os grupos, com maiores médias nos tempos de intubação, utilização de oxigênio e de internação no grupo B. Porém, quanto ao número de lesões encontradas na TCAR, não houve diferença estatisticamente significante (p=0,0787). CONCLUSÃO: A TCAR empregada tardiamente demonstrou não haver diferença significativa entre o tratamento clínico ou cirúrgico visando ocluir o canal arterial nas lesões do parênquima pulmonar dos recém-nascidos prematuros com PCA que desenvolveram displasia broncopulmonar.

OBJECTIVE: To assess through high-resolution computed tomography the pulmonary parenchyma of children prematurely born with both very low birth weight and patent ductus arteriosus submitted to medical or surgical treatment that developed bronchopulmonary dysplasia. METHODS: Between December 2006 and January 2007, 14 children prematurely born with a weight less than 1500g with bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA) were submitted to high-resolution computed tomography (HRCT). All of them underwent surgical closure of the canal divided into two groups: A - medical (n=6) and B - surgical (n=8). The pool of patients comprised 9 baby boys and 5 girls who were 36.5±4.3 month-old. The HRCT were analyzed by two independent observers and quantified in each patient. The statistical analyses were assessed using the Mann-Whitney test, and p<0.05 was considered statistically significant. RESULTS: Three patients presented normal tomographies, being two of A group and one of B. In A, the most frequent finding was multifocal ground-glass opacity. In B, multifocal ground-glass opacity, atelectasis, and low attenuation areas with relatively decreased number and caliber of vessels were prevalent (62.5 percent). There was a statistically significant difference between both groups, with B having higher averages in the intubation times, use of oxygen, and admission. However, as to the number of injuries found on HRCT there was no statistically significant difference (p=0.0787). CONCLUSION: The lately use of HRCT have shown no significant difference between both medical and surgical treatment aiming at to occlude the PDA in pulmonary parenchyma injuries of premature with PDA that developed bronchopulmonary dysplasia.

Tempo de ventilação mecânica e desenvolvimento de displasia broncopulmonar / Duration of mechanical ventilation and development of bronchopulmonary dysplasia

OBJETIVO: Verificar a associação entre o tempo de uso da ventilação mecânica e o desenvolvimento de displasia broncopulmonar em recém-nascidos com peso de nascimento < 1500 g. MÉTODOS: Pesquisa retrospectiva em recém-nascidos com peso de nascimento < 1500 g que utilizaram ventilação mecânica. Foram excluídos as malformações congênitas maiores, transferências e óbitos antes do 28° dia de vida. Foram analisados três grupos de acordo com o tempo de uso da ventilação mecânica: 1 a 7 dias, 8 a 14 dias e > 15 dias. Foi calculada a razão de chance para o desenvolvimento de displasia broncopulmonar em cada período de utilização da ventilação mecânica. RESULTADOS: Dos 216 prontuários avaliados, 121 preencheram os critérios de inclusão. As médias do peso de nascimento e idade gestacional foram de 1199,8 g e 31,8 semanas. No período de 1 a 7 dias de uso da ventilação mecânica, 15,5 por cento dos recém-nascidos evoluíram com displasia broncopulmonar; no período de 8 a 14 dias, 60 por cento; e no período > 15 dias, 88,2 por cento; com razão de chance de 0,16, 11,25 e 16,36, respectivamente. CONCLUSÃO: A possibilidade de um recém-nascido com peso de nascimento < 1500 g desenvolver displasia broncopulmonar foi 11 vezes maior naqueles que permaneceram em ventilação mecânica por até 14 dias e esta chance aumentou ainda mais nos que foram ventilados por mais de 15 dias, devendo a equipe que presta atendimento ao paciente de alto risco estar empenhada na extubação dos recém-nascidos ainda na primeira semana de vida.

OBJECTIVE: Verify the association between duration of mechanical ventilation and development of bronchopulmonary dysplasia in neonates weighting at birth less than 1500g. METHODS: Retrospective study conducted with neonates weighting less than 1500g at birth submitted to mechanical ventilation. Neonates presenting major birth defects, transferred to other services or died before the 28th day of life were excluded from the study. Three groups were analyzed according to duration of mechanical ventilation: 1 to 7 days, 8 to 14 days and more than 15 days. The chance ratio of developing bronchopulmonary dysplasia was calculated for each group. RESULTS: From the 216 clinical histories assessed, 121 met the criteria for inclusion in the study. Mean birth weight and gestational age were 1199.8 g and 31.8 weeks. Of all neonates submitted to mechanical ventilation from 1 to 7 days, 15.5 percent developed bronchopulmonary dysplasia; from 8 to 14 days 60 percent and from more than 15 days, 88.2 percent; chance ratios were equal to 0.16; 11.25 and 16.36, respectively. CONCLUSION: The chance of a neonate weighting less than 1500 g developing bronchopulmonary dysplasia was 11 times higher in those submitted to mechanical ventilation for up to 14 days. This chance was even higher in those ventilated for more than 15 days. That is why the nursing staff assisting high risk patients should consider the possibility of extubating neonates during their first week of life.