Mortality in Outpatients with Bronchopulmonary Dysplasia.

OBJECTIVES: To study the demographic and clinical characteristics of preterm infants with bronchopulmonary dysplasia (BPD) to identify the factors most strongly predictive of outpatient mortality, with the goal of identifying those individuals at greatest risk. STUDY DESIGN: Demographic and clinical characteristics were retrospectively reviewed for 862 subjects recruited from an outpatient BPD clinic. Characteristics of the deceased and living participants were compared using nonparametric analysis. Regression analysis was performed to identify factors associated with mortality. RESULTS: Of the 862 subjects, 13 (1.5%) died during follow-up, for an overall mortality rate of approximately 15.1 deaths per 1000 subjects. Two patients died in the postneonatal period (annual mortality incidence, 369.9 per 100 000), 9 died between age 1 and 4 years (annual mortality incidence, 310.2 per 100 000), and 2 died between age of 5 and 14 years (annual mortality incidence, 71.4 per 100 000). After adjusting for gestational age and BPD severity, mortality was found to be associated with the amount of supplemental oxygen required at discharge from the neonatal intensive care unit (adjusted hazard ratio [aHR], 4.10; P = .001), presence of a gastrostomy tube (aHR, 8.13; P = .012), and presence of a cerebrospinal fluid (CSF) shunt (aHR, 4.31; P = .021). CONCLUSIONS: The incidence of mortality among preterm infants with BPD is substantially higher than that seen in the general population. The need for greater amounts of home supplemental oxygen and the presence of a gastrostomy tube or CSF shunt were associated with an increased risk of postdischarge mortality. Future studies should focus on clarifying risk factors for the development of severe disease to allow for early identification and treatment of those at highest risk.

Loop Diuretics in Severe Bronchopulmonary Dysplasia: Cumulative Use and Associations with Mortality and Age at Discharge.

OBJECTIVES: To measure between-center variation in loop diuretic use in infants developing severe bronchopulmonary dysplasia (BPD) in US children's hospitals, and to compare mortality and age at discharge between infants from low-use centers and infants from high-use centers. STUDY DESIGN: We performed a retrospective cohort study of preterm infants at <32 weeks of gestational age with severe BPD. The primary outcome was cumulative loop diuretic use, defined as the proportion of days with exposure between admission and discharge. Infant characteristics associated with loop diuretic use at P < .10 were included in multivariable models to adjust for center differences in case mix. Hospitals were ranked from lowest to highest in adjusted use and dichotomized into low-use centers and high-use centers. We then compared mortality and postmenstrual age at discharge between the groups through multivariable analyses. RESULTS: We identified 3252 subjects from 43 centers. Significant variation between centers remained despite adjustment for infant characteristics, with use present in an adjusted mean range of 7.3% to 49.4% of days (P < .0001). Mortality did not differ significantly between the 2 groups (aOR, 0.98; 95% CI, 0.62-1.53; P = .92), nor did postmenstrual age at discharge (marginal mean, 47.3 weeks [95% CI, 46.8-47.9 weeks] in the low-use group vs 47.4 weeks [95% CI, 46.9-47.9 weeks] in the high-use group; P = .96). CONCLUSIONS: A marked variation in loop diuretic use for infants developing severe BPD exists among US children's hospitals, without an observed difference in mortality or age at discharge. More research is needed to provide evidence-based guidance for this common exposure.

Trends in Perinatal Practices and Neonatal Outcomes of Very Low Birth Weight Infants during a 16-year Period at NEOCOSUR Centers.

OBJECTIVE: To describe trends in mortality, major morbidity, and perinatal care practices of very low birth weight infants born at NEOCOSUR Neonatal Network centers from January 1, 2001, through December 31, 2016. STUDY DESIGN: A retrospective analysis of prospectively collected data from all inborn infants with a birthweight of 500-1500 g and 23-35 weeks of gestation. RESULTS: We examined data for 13 987 very low birth weight infants with a mean birth weight of 1081 ± 281 g and a gestational age of 28.8 ± 2.9 weeks. Overall mortality was 26.8% without significant changes throughout the study period. Decreases in early onset sepsis from 6.3% to 2.8% (P <.001), late onset sepsis from 21.1% to 19.5% (P = .002), retinopathy of prematurity from 21.3% to 13.8% (P <.001), and hydrocephalus from 3.8% to 2.4% (P <.001), were observed. The incidence for bronchopulmonary dysplasia decreased from 17.3% to 16% (P = .043), incidence of severe intraventricular hemorrhage was 10.4%, necrotizing enterocolitis 11.1%, and periventricular leukomalacia 3.8%, and did not change over the study period. Administration of antenatal corticosteroids increased from 70.2% to 82.3% and cesarean delivery from 65.9% to 75.4% (P <.001). The use of conventional mechanical ventilation decreased from 67.7% to 63.9% (P <.001) and continuous positive airway pressure use increased from 41.3% to 64.3% (P <.001). Survival without major morbidity increased from 37.4% to 44.5% over the study period (P <.001). CONCLUSIONS: Progress in perinatal and neonatal care at network centers was associated with an improvement in survival without major morbidity of very low birth weight infants during a 16-year period. However, overall mortality remained unchanged.

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

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.

Association of Center-Specific Patient Volumes and Early Respiratory Management Practices with Death and Bronchopulmonary Dysplasia in Preterm Infants.

OBJECTIVES: To describe variability in admission volumes and approach to early respiratory support between neonatal intensive care units in the Australian and New Zealand Neonatal Network and to evaluate whether these center-specific factors are associated with death and bronchopulmonary dysplasia. STUDY DESIGN: This retrospective cohort study included 19 099 neonates born between 25 and 32 weeks' gestation and admitted to 1 of 25 NICUs from 2007 to 2013. Center-specific factors evaluated were annual admission volume and rate of using continuous positive airway pressure (CPAP) rather than intubation as the first mode of respiratory support. Logistic regression was used to examine any association of these center-specific factors with death, BPD, and death or survival with BPD (death/BPD). Analysis was performed separately for 2 gestation groups (25-28 weeks and 29-32 weeks inclusive). RESULTS: Admission volumes and rates of early CPAP use varied widely across centers. Higher admission volumes were associated with lower odds of death or survival with BPD in the 25-28 week group (aOR 0.93, 99% CI 0.88-0.99 per increase of 10 babies per center annually). Centers with higher early CPAP use did not have lower odds of death or BPD than centers that intubated more frequently. CONCLUSIONS: Higher admission volumes are associated with more favorable outcomes for the more preterm infants in the Australian and New Zealand Neonatal Network. Further investigation is required to explore why the individual benefits of early CPAP do not translate to better outcomes for centers that use this approach most frequently.

Bronchopulmonary Dysplasia in Very Preterm Infants with Symptomatic Congenital Cytomegalovirus Infection: A Propensity Score-Matched Analysis.

OBJECTIVE: To assess whether symptomatic congenital cytomegalovirus infection (cCMV) is associated with bronchopulmonary dysplasia (BPD) and mortality in very preterm infants (gestational age ≤32 weeks). STUDY DESIGN: We performed a retrospective study using the Kids' Inpatient Database for 2003, 2006, 2009, and 2012. Diagnoses of BPD and symptomatic cCMV were determined using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Among patients with in-hospital birth at ≤32 weeks of gestation, cases of symptomatic cCMV were matched with infants without cCMV using propensity score matching at 1:2 ratio. Outcomes of BPD and in-hospital mortality were assessed using conditional logistic regression. RESULTS: Of 204 818 in-hospital births with gestational age ≤32 weeks, we identified 208 cases of symptomatic cCMV, 177 of which underwent matching. Symptomatic cCMV was associated with higher odds of BPD (OR, 2.34; 95% CI, 1.41-3.87), but was not significantly associated with in-hospital all-cause mortality (OR, 1.18, 95% CI, 0.64-2.17). CONCLUSIONS: Symptomatic cCMV was associated with BPD but not with in-hospital mortality among very preterm infants. Further study is needed to determine the risk of BPD among infants with cCMV to allow for evaluation of possible preventive measures.

The Impact of Time Interval between Extubation and Reintubation on Death or Bronchopulmonary Dysplasia in Extremely Preterm Infants.

OBJECTIVE: To explore the relation between time to reintubation and death or bronchopulmonary dysplasia (BPD) in extremely preterm infants. STUDY DESIGN: This was a subanalysis from an ongoing multicenter observational study. Infants with birth weight ≤1250 g, requiring mechanical ventilation, and undergoing their first elective extubation were prospectively followed throughout hospitalization. Time to reintubation was defined as the time interval between first elective extubation and reintubation. Univariate and multivariate logistic regression analyses were performed to evaluate associations between time to reintubation, using different observation windows after extubation (24-hour intervals), and death/BPD (primary outcome) or BPD among survivors (secondary outcome). aORs were computed with and without the confounding effects of cumulative mechanical ventilation duration. RESULTS: Of 216 infants included for analysis, 103 (48%) were reintubated at least once after their first elective extubation. Reintubation was associated with lower gestational age/weight and greater morbidities compared with infants never reintubated. After adjusting for confounders, reintubation within observation windows ranging between 24 hours and 3 weeks postextubation was associated with increased odds of death/BPD (but not BPD among survivors), independent of the cumulative mechanical ventilation duration. Reintubation within 48 hours from extubation conferred higher risk-adjusted odds of death/BPD vs other observation windows. CONCLUSIONS: Although reintubation after elective extubation was independently associated with increased likelihood of death/BPD in extremely preterm infants, the greatest risk was attributable to reintubation within the first 48 hours postextubation. Prediction models capable of identifying the highest-risk infants may further improve outcomes.

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.

Covariation of Neonatal Intensive Care Unit-Level Patent Ductus Arteriosus Management and In-Neonatal Intensive Care Unit Outcomes Following Preterm Birth.

OBJECTIVE: To test the hypothesis that neonatal intensive care unit (NICU)-specific changes in patent ductus arteriosus (PDA) management are associated with changes in local outcomes in preterm infants. STUDY DESIGN: This retrospective repeated-measures study of aggregated data included infants born 400-1499 g admitted within 2 days of delivery to NICUs participating in the California Perinatal Quality Care Collaborative. The period 2008-2015 was divided into four 2-year epochs. For each epoch and NICU, we calculated proportions of infants receiving cyclooxygenase inhibitor (COXI) or PDA ligation and determined NICU-specific changes in these therapies between consecutive epochs. Generalized estimating equations were used to examine adjusted relationships between NICU-specific changes in PDA management and contemporaneous changes in local outcomes. RESULTS: We included 642 observations of interepoch change at 119 hospitals summarizing 32 094 infants. NICU-specific changes in COXI use and ligation showed significant dose-response associations with contemporaneous changes in adjusted local outcomes. Each percentage point decrease in NICU-specific proportion treated with either COXI or ligation was associated with a 0.21 percentage point contemporaneous increase in adjusted local in-hospital mortality (95% CI 0.06, 0.33; P = .005) among infants born 400-749 g. In contrast, decreasing NICU-specific ligation rate among infants 1000-1499 g was associated with decreasing adjusted local bronchopulmonary dysplasia (P = .009) and death or bronchopulmonary dysplasia (P = .01). CONCLUSIONS: NICU-specific outcomes of preterm birth co-vary with local PDA management. Treatment for PDA closure may benefit some infants born 400-749 g. Decreasing NICU-specific rates of COXI use or ligation were not associated with increases in local adjusted rates of examined adverse outcomes in larger preterm infants.

Antibiotic Exposure and Risk for Death or Bronchopulmonary Dysplasia in Very Low Birth Weight Infants.

We assessed the association between antibiotic exposure in the first 2 weeks of life and development of bronchopulmonary dysplasia in a cohort of very low birth weight infants. After controlling for the severity of illness, each additional day of antibiotic therapy was associated with both an increased risk for and severity of bronchopulmonary dysplasia.

Early Cumulative Supplemental Oxygen Predicts Bronchopulmonary Dysplasia in High Risk Extremely Low Gestational Age Newborns.

OBJECTIVE: To assess the prognostic accuracy of early cumulative supplemental oxygen (CSO) exposure for prediction of bronchopulmonary dysplasia (BPD) or death, and to evaluate the independent association of CSO with BPD or death. STUDY DESIGN: We performed a secondary analysis of the Trial of Late Surfactant, which enrolled 511 infants born at ≤28 weeks gestational age who were mechanically ventilated at 7-14 days of life. Our primary outcome was BPD or death at 36 weeks postmenstrual age, as determined by a physiological oxygen/flow challenge. Average daily supplemental oxygen (fraction of inspired oxygen - 0.21) was calculated. CSO was calculated as the sum of the average daily supplemental oxygen over time periods of interest up to 28 days of age. Area under the receiver operating curve (AUROC) values were generated to evaluate the accuracy of CSO for prediction of BPD or death. The independent relationship between CSO and BPD or death was assessed in multivariate modeling, while adjusting for mean airway pressure. RESULTS: In the study infants, mean gestational age at birth was 25.2 ± 1.2 weeks and mean birth weight was 700 ± 165 g. The AUROC value for CSO at 14 days was significantly better than that at earlier time points for outcome prediction (OR, 0.70; 95% CI, 0.65-0.74); it did not increase with the addition of later data. In multivariate modeling, a CSO increase of 1 at 14 days increased the odds of BPD or death (OR, 1.7; 95% CI, 1.3-2.2; P < .0001), which corresponds to a 7% higher daily supplemental oxygen value. CONCLUSION: In high-risk extremely low gestational age newborns, the predictive accuracy of CSO plateaus at 14 days. CSO is independently associated with BPD or death. This index may identify infants who could benefit from early intervention to prevent BPD.

Prediction of Late Death or Disability at Age 5 Years Using a Count of 3 Neonatal Morbidities in Very Low Birth Weight Infants.

OBJECTIVE: To evaluate bronchopulmonary dysplasia (BPD), serious brain injury, and severe retinopathy of prematurity (ROP) as predictors of poor long-term outcome in very low birth weight infants. STUDY DESIGN: We examined the associations between counts of the 3 morbidities and long-term outcomes in 1514 of 1791 (85%) infants with birth weights of 500-1250 g who were enrolled in the Caffeine for Apnea of Prematurity trial from October 1999, to October 2004, had complete morbidity data, and were alive at 36 weeks postmenstrual age (PMA). BPD was defined as use of supplemental oxygen at 36 weeks PMA. Serious brain injury on cranial ultrasound included grade 3 and 4 hemorrhage, cystic periventricular leucomalacia, porencephalic cysts, or ventriculomegaly of any cause. Poor long-term outcome was death after 36 weeks PMA or survival to 5 years with 1 or more of the following disabilities: motor impairment, cognitive impairment, behavior problems, poor general health, deafness, and blindness. RESULTS: BPD, serious brain injury, and severe ROP occurred in 43%, 13%, and 6% of the infants, respectively. Each of the 3 morbidities was similarly and independently correlated with poor 5-year outcome. Rates of death or disability (95% CI) in children with none, any 1, any 2, and all 3 morbidities were 11.2% (9.0%-13.7%), 22.9% (19.6%-26.5%), 43.9% (35.5%-52.6%), and 61.5% (40.6%-79.8%), respectively. CONCLUSIONS: In very low birth weight infants who survive to 36 weeks PMA, a count of BPD, serious brain injury, and severe ROP predicts the risk of a late death or survival with disability at 5 years.

Effects of therapeutic approach on the neonatal evolution of very low birth weight infants with patent ductus arteriosus / Efeitos da abordagem terapêutica da persistência de canal arterial sobre a evolução neonatal de recém-nascidos de extremo baixo peso

OBJECTIVE: To analyze the effects of treatment approach on the outcomes of newborns (birth weight [BW] < 1,000 g) with patent ductus arteriosus (PDA), from the Brazilian Neonatal Research Network (BNRN) on: death, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH III/IV), retinopathy of prematurity requiring surgical (ROPsur), necrotizing enterocolitis requiring surgery (NECsur), and death/BPD. METHODS: This was a multicentric cohort study, retrospective data collection, including newborns (BW < 1000 g) with gestational age (GA) < 33 weeks and echocardiographic diagnosis of PDA, from 16 neonatal units of the BNRN from January 1, 2010 to Dec 31, 2011. Newborns who died or were transferred until the third day of life, and those with presence of congenital malformation or infection were excluded. Groups: G1 - conservative approach (without treatment), G2 - pharmacologic (indomethacin or ibuprofen), G3 - surgical ligation (independent of previous treatment). Factors analyzed: antenatal corticosteroid, cesarean section, BW, GA, 5 min. Apgar score < 4, male gender, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE II), respiratory distress syndrome (RDS), late sepsis (LS), mechanical ventilation (MV), surfactant (< 2 h of life), and time of MV. Outcomes: death, O2 dependence at 36 weeks (BPD36wks), IVH III/IV, ROPsur, NECsur, and death/BPD36wks. Statistics: Student's t-test, chi-squared test, or Fisher's exact test; Odds ratio (95% CI); logistic binary regression and backward stepwise multiple regression. Software: MedCalc (Medical Calculator) software, version 12.1.4.0. p-values < 0.05 were considered statistically significant. RESULTS: 1,097 newborns were selected and 494 newborns were included: G1 - 187 (37.8%), G2 - 205 (41.5%), and G3 - 102 (20.6%). The highest mortality was observed in G1 (51.3%) and the lowest in G3 (14.7%). The highest frequencies of BPD36wks (70.6%) ...

OBJETIVO: Analisar os efeitos da terapêutica adotada para o canal arterial (CA) em recém-nascidos (RN) < 1.000gadmitidos em unidades neonatais (UN) da Rede Brasileira de Pesquisas Neonatais (RBPN), sobre os desfechos: óbito, displasia broncopulmonar (DBP), hemorragia intraventricular grave (HIVIII/IV), retinopatia da prematuridade cirúrgica (ROPcir), enterocolite necrosante cirúrgica (ECNcir) e o desfecho combinado óbito e DBP. MÉTODOS: Estudo multicêntrico, de coorte, coleta de dados retrospectiva, incluindo RN de 16 UN da RBPN de 01/01/2010 a 31/12/2011, PN < 1.000 g, idade gestacional (IG) < 33 semanas e diagnóstico ecocardiográfico de PCA. Excluídos: óbitos ou transferências até o terceiro dia de vida, infecções congênitas ou malformações. Grupos:G1 - conservadora (sem intervenção medicamentosa ou cirúrgica), G2 - farmacológica (indometacina ou ibuprofeno) e G3 - cirúrgico (com ou sem tratamento farmacológico anterior). Analisou-se: uso de esteroide antenatal, parto cesárea, PN, IG, Apgar5' < 4, sexo masculino, SNAPPE II, síndrome do dDesconforto respiratório (SDR), sepse tardia, ventilação mecânica (VM), surfactante < 2 horas de vida, tempo de VM e os desfechos: óbito, dependência de oxigênio com 36 semanas (DBP36s), HIV III/IV, ROPcir, ECNcir e óbito/DBP36s. Estatística: Teste t-Student, Qui-Quadrado ou teste Exato de Fisher. Testes de Regressão Binária Logística e Regressão Múltipla Stepwise Backward. MedCalc (Medical Calculator) software, versão 12.1.4.0.p < 0,05. RESULTADOS: Foram selecionados 1.097 RN e 494 foram incluídos: G1-187 (37,8%), G2-205 (41,5%) e G3-102 (20,6%). Verificou-se: maior mortalidade (51,3%) no G1 e menor no G3(14,7%); maior frequência DBP36s (70,6%) e ROPcir (23,5%) ...

An update on the impact of postnatal systemic corticosteroids on mortality and cerebral palsy in preterm infants: effect modification by risk of bronchopulmonary dysplasia.

Infants at higher risk of bronchopulmonary dysplasia had increased rates of survival free of cerebral palsy after postnatal corticosteroid treatment in a previous metaregression of data from 14 randomized controlled trials. The relationship persists and is stronger in an updated analysis with data from 20 randomized controlled trials.

Educating neonatal nurses in Brazil: a before-and-after study with interrupted time series analysis.

BACKGROUND: Preterm birth contributes significantly to infant mortality and morbidity, including blindness from retinopathy of prematurity (ROP). Access to intensive neonatal care is expanding in many countries, but care is not always optimal, one factor being that nursing is often by inadequately trained nurse assistants. OBJECTIVE: The aim of this study was to evaluate whether an educational package for nurses improves a range of outcomes including survival rates and severe ROP in 5 neonatal units in Rio de Janeiro, Brazil. METHODS: The study design included an uncontrolled before-and-after study in 5 units, with interrupted time series analysis. Participatory approaches were used to develop a self-administered educational package for control of pain, oxygenation, infection, nutrition, and temperature and to improve supportive care ('POINTS of Care'). Educational materials and DVD clips were developed and training skills of nurse tutors were enhanced. There were two 1-year periods of data collection before and after a 3-month period of self-administration of the education package. RESULTS: Overall, 74% of 401 nurses and nurse assistants were trained. A total of 679 and 563 infants were included in the pre- and post-training periods, respectively. Despite improvement in knowledge and nursing practices, such as the delivery and monitoring of oxygen, there was no change in survival (pre-training 80%, post-training 78.2%), severe ROP (1.6 vs. 2.8%), sepsis (11.3 vs. 12.3 cases per 1,000 infant days) or other outcomes. Outcomes worsened over the pre-intervention period but the change to an improvement after the intervention was not statistically significant. During the study period many trained staff left the units, but few were replaced. CONCLUSIONS: Future studies need to focus on barriers to implementation, team building, leadership and governance, as well as the acquisition of knowledge and skills.

Effects of therapeutic approach on the neonatal evolution of very low birth weight infants with patent ductus arteriosus.

OBJECTIVE: To analyze the effects of treatment approach on the outcomes of newborns (birth weight [BW] < 1,000 g) with patent ductus arteriosus (PDA), from the Brazilian Neonatal Research Network (BNRN) on: death, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH III/IV), retinopathy of prematurity requiring surgical (ROPsur), necrotizing enterocolitis requiring surgery (NECsur), and death/BPD. METHODS: This was a multicentric, cohort study, retrospective data collection, including newborns (BW < 1000 g) with gestational age (GA) < 33 weeks and echocardiographic diagnosis of PDA, from 16 neonatal units of the BNRN from January 1, 2010 to Dec 31, 2011. Newborns who died or were transferred until the third day of life, and those with presence of congenital malformation or infection were excluded. Groups: G1 - conservative approach (without treatment), G2 - pharmacologic (indomethacin or ibuprofen), G3 - surgical ligation (independent of previous treatment). Factors analyzed: antenatal corticosteroid, cesarean section, BW, GA, 5 min. Apgar score < 4, male gender, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE II), respiratory distress syndrome (RDS), late sepsis (LS), mechanical ventilation (MV), surfactant (< 2 h of life), and time of MV. OUTCOMES: death, O2 dependence at 36 weeks (BPD36wks), IVH III/IV, ROPsur, NECsur, and death/BPD36wks. STATISTICS: Student's t-test, chi-squared test, or Fisher's exact test; Odds ratio (95% CI); logistic binary regression and backward stepwise multiple regression. Software: MedCalc (Medical Calculator) software, version 12.1.4.0. p-values < 0.05 were considered statistically significant. RESULTS: 1,097 newborns were selected and 494 newborns were included: G1 - 187 (37.8%), G2 - 205 (41.5%), and G3 - 102 (20.6%). The highest mortality was observed in G1 (51.3%) and the lowest in G3 (14.7%). The highest frequencies of BPD36wks (70.6%) and ROPsur were observed in G3 (23.5%). The lowest occurrence of death/BPD36wks occurred in G2 (58.0%). Pharmacological (OR 0.29; 95% CI: 0.14-0.62) and conservative (OR 0.34; 95% CI: 0.14-0.79) treatments were protective for the outcome death/BPD36wks. CONCLUSION: The conservative approach of PDA was associated to high mortality, the surgical approach to the occurrence of BPD36wks and ROPsur, and the pharmacological treatment was protective for the outcome death/BPD36wks.

A hyperoxic lung injury model in premature rabbits: the influence of different gestational ages and oxygen concentrations.

BACKGROUND: Many animal models have been developed to study bronchopulmonary dysplasia (BPD). The preterm rabbit is a low-cost, easy-to-handle model, but it has a high mortality rate in response to the high oxygen concentrations used to induce lung injury. The aim of this study was to compare the mortality rates of two models of hyperoxia-induced lung injury in preterm rabbits. METHODS: Pregnant New Zealand white rabbits were subjected to caesarean section on gestational day 28 or 29 (full term  = 31 days). The premature rabbits in the 28-day gestation group were exposed to room air or FiO2 ≥95%, and the rabbits in the 29-day gestation group were exposed to room air or FiO2  = 80% for 11 days. The mean linear intercept (Lm), internal surface area (ISA), number of alveoli, septal thickness and proportion of elastic and collagen fibers were quantified. RESULTS: The survival rates in the 29-day groups were improved compared with the 28-day groups. Hyperoxia impaired the normal development of the lung, as demonstrated by an increase in the Lm, the septal thickness and the proportion of elastic fibers. Hyperoxia also decreased the ISA, the number of alveoli and the proportion of collagen fibers in the 28-day oxygen-exposed group compared with the control 28-day group. A reduced number of alveoli was found in the 29-day oxygen exposed animals compared with the control 29-day group. CONCLUSIONS: The 29-day preterm rabbits had a reduced mortality rate compared with the 28-day preterm rabbits and maintained a reduction in the alveoli number, which is comparable to BPD in humans.

Eficacia de tres tipos de surfactante exógeno en prematuros con enfermedad de membrana hialina / Effectiveness of three types of exogenous surfactant in preterm infants with hyaline membrane disease

Introducción: La enfermedad de membrana hialina es causa importante de mortalidad neonatal. El objetivo de esta investigación fue evaluar la eficacia de tres tipos de surfactante exógeno en prematuros. Pacientes y Método: Estudio de cohorte retrospectiva, en 93 neonatos prematuros, > 24 semanas y > 500 g de peso al nacer, 31 para cada surfactante. La exposición fue la administración de 1ª dosis bovactant (Alveofact®) 50 mg/kg, beractant (Survanta®) 100 mg/kg inicial, y poractant alfa (Curosurf®) 200 mg/kg. Las variables en estudio incluyeron tiempo de ventilación mecánica, tiempo de oxigenoterapia, estancia hospitalaria, necesidad de segunda dosis de surfactante, eventos adversos por la administración del surfactante y complicaciones por prematuridad. Además, se evaluó mortalidad, displasia broncopulmonar (DBP) y mortalidad o DBP. Análisis estadístico mediante Stata® 11.0, empleando X² o Prueba Exacta de Fisher para variables cualitativas y Pruebas ANOVA o Kruskal-Wallis para cuantitativas y riesgo relativo para las asociaciones, todas con su intervalo de confianza de 95%. Resultados: No hubo diferencias para sexo, peso y edad gestacional al nacer entre los 3 grupos. No se hallaron diferencias estadísticamente significativas para tiempo de ventilación mecánica, tiempo de oxigenoterapia, administración de una segunda dosis de surfactante, estancia hospitalaria y complicaciones entre los 3 grupos. Los eventos adversos por administración de surfactante se presentaron para beractant y poractant alfa. Ocurrieron 30 (32,3 por ciento) muertes, 8 (25,8 por ciento) para bovactant, 10 (32,3 por ciento) beractant y 12 (38,7 por ciento) poractant alfa (p > 0,05). La mortalidad y/o DBP ocurrió en 10 (32,2 por ciento) neonatos con bovactant, 10 (32,2 por ciento) con beractant y 14 (45,2 por ciento) con poractant alfa (p > 0,05). Conclusiones: Los resultados primarios y secundarios entre los tres surfactantes evaluados fueron muy similares...

Introduction: Hyaline membrane disease is an important cause of neonatal mortality. The objective of this research is to evaluate the efficacy of three different exogenous surfactants in premature infants. Patients and Method: A retrospective cohort analysis in 93 preterm infants > 24 weeks and birth weight > 500 g was performed, 31 infants for each surfactant. Exposure consisted of the 1st dose of bovactant (Alveofact®) 50 mg/kg, beractant (Survanta®) 100 mg/kg initially, and poractant alfa (Curosurf®) 200 mg/kg. The variables included duration of mechanical ventilation, duration of oxygen therapy, hospital stay, need for second dose of surfactant, adverse events surfactant administration and prematurity complications. Mortality and bronchopulmonary dysplasia (BPD) were evaluated. Statistical analysis was performed using Stata® 11.0, X² or Fisher exact test for qualitative variables and ALNOVA or Kruskal-Wallis tests for quantitative and association relative risk, all with 95 percent confidence level. Results: There were no gender, weight and gestational age differences at birth among the three groups. No statistically significant differences were found regarding duration of mechanical ventilation, duration of oxygen therapy, administration of a second dose of surfactant, hospital stay and complications among the three groups. Adverse events related to surfactant administration occurred for beractant and poractant alpha. There were 30 (32.3 percent) deaths, 8 (25.8 percent) associated to bovactant, 10 (32.3%) to beractant and 12 (38.7 percent) to poractant alpha (p > 0.05). Mortality and/or BDP occurred in 10 (32.2 percent) infants who received bovactant, 10 (32.2 percent) beractant and 14 (45.2 percent) with poractant alpha (p > 0.05). Conclusions: The primary and secondary outcomes among the three surfactants tested were similar, taking into account the limitations of the work.

[The clinical course and one year forcast for a cohort of premature infants who were discharged with home oxygen in Bogota, Colombia]. / Curso clínico y pronóstico a un año de una cohorte de prematuros dados de alta con oxígeno domiciliario en Bogotá, Colombia.

OBJECTIVE: Documenting the clinical course and forecast for a concurrent cohort of discharged preterm infants who received home oxygen in Bogota, Colombia. METHODS: This was a prospective study of a concurrent cohort of 194 newborn infants having 34 weeks gestational age (GA) or less at birth who were born in 12 institutions and followed up for one year of corrected age to assess mortality, morbidity, growth and development. RESULTS: Oxygen dependency was mild in 49 infants (25.3 %) and moderate-severe in 145 of them (74.7 %). There were 3 deaths; vital status was known in 169 infants at 40 weeks GA (87.1 %) and 103 (53%) at 1 year. Breast feeding at term was successful in 147 (75.8 %) infants. Growth indices at one year were appropriate (8,991 g weight, 73 cm height and 46.2 cm head circumference) 74.1 % of the cohort were still receiving home oxygen at 40 weeks and and 22.7 % at 3 months and oxygen was discontinued on average on postnatal day 109. 56.8 % of the cohort were readmitted to hospital at least once, 47% of them because of respiratory conditions. Only 71 % had ophthalmological screening and retinopathy of prematurity (ROP) was detected in 38 % of cases (4 severe cases: 3 laser surgery and 1 blind infant). Neuro-psychomotor and sensorial screening tests were only performed on 19 % of the infanys. CONCLUSION: More than 60 % of newborn infants discharged with home oxygen lacked structured follow-up. Oxygen-dependancy in infants is complex; our data suggested that there is plenty of room for improvement in Bogotá in that respect.

Curso clínico y pronóstico a un año de una cohorte de prematuros dados de alta con oxígeno domiciliario en Bogotá, Colombia / The clinical course and one year forcast for a cohort of premature infants who were discharged with home oxygen in Bogota, Colombia

Objetivo Documentar el curso clínico y pronóstico de una cohorte de niños prematuros dados de alta con oxígeno domiciliario en Bogotá, Colombia. Método Cohorte prospectiva de 194 prematuros de 34 o menos semanas de edad gestacional (EG) al nacer, egresados de 12 unidades neonatales con oxígeno suplementario, seguidos hasta la edad corregida de 12 meses para determinar supervivencia, crecimiento, desarrollo y morbilidad. Resultados 49 niños (25,3 %) tenían una oxigenodependencia leve y 145 (74,7 %) moderada-severa. Se presentaron 3 muertes (1,5 %), el estado vital a 40 semanas de EG fue conocido en 169 pacientes (87,1 %) y en 103 (53 %) a 12 meses. La lactancia materna fue exitosa en 147 (75,8 %) niños a 40 semanas. La antropometría al año fue: peso 8 991 g, talla 73 cm y perimetro craneano 46,2 cm. A las 40 semanas y a 3 meses 74,1 % y 22,7 % de la cohorte aún utilizaba oxígeno el cual fue descontinuado en promedio a los109 días postnatales. El 56,8 % de los niños tuvo al menos un reingreso y 47 % por patologías respiratorias. Sólo se tamizó para retinopatía al 71 % y en ellos la incidencia de retinopatía de la prematurez (ROP) fue 38 % con 3 cirugías y 1 niño ciego. Un tamizado neuropsicomotor y sensorial se realizó solamente en 19 % encontrando algún tipo de alteración neuropsicomotriz en 30 %, refractiva en 40 % y auditiva en 5 %. Conclusión Más del 60 % de los niños oxígeno-dependientes fueron dados de alta sin plan de seguimiento estructurado. El problema de los niños oxigenodependientes es complejo y nuestros datos sugieren un gran espacio para mejorar el seguimiento.

Objective Documenting the clinical course and forecast for a concurrent cohort of discharged preterm infants who received home oxygen in Bogota,Colombia. Methods This was a prospective study of a concurrent cohort of 194 newborn infants having 34 weeks gestational age (GA) or less at birth who were born in 12 institutions and followed up for one year of corrected age to assess mortality, morbidity, growth and development. Results Oxygen dependency was mild in 49 infants (25.3 %) and moderate-severe in 145 of them (74.7 %). There were 3 deaths; vital status was known in 169 infants at 40 weeks GA (87.1 %) and 103 (53%) at 1 year. Breast feeding at term was successful in 147 (75.8 %) infants. Growth indices at one year were appropriate (8,991 g weight, 73 cm height and 46.2 cm head circumference) 74.1 % of the cohort were still receiving home oxygen at 40 weeks and and 22.7 % at 3 months and oxygen was discontinued on average on postnatal day 109. 56.8 % of the cohort were readmitted to hospital at least once, 47% of them because of respiratory conditions. Only 71 % had ophthalmological screening and retinopathy of prematurity (ROP) was detected in 38 % of cases (4 severe cases: 3 laser surgery and 1 blind infant). Neuro-psychomotor and sensorial screening tests were only performed on 19 % of the infanys. Conclusion More than 60 % of newborn infants discharged with home oxygen lacked structured follow-up. Oxygen-dependancy in infants is complex; our data suggested that there is plenty of room for improvement in Bogotá in that respect.