Jose L. Tapia

The effect of early dexamethasone administration on bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome

OBJECTIVES This study was carried to evaluate the effect of early administration of dexamethasone on the incidence of bronchopulmonary dysplasia (BPD) and/or death in surfactant-treated preterm infants with respiratory distress syndrome (RDS). STUDY DESIGN In a multicenter, double-blind, placebo-controlled trial, 109 preterm infants with RDS and birth weights between 700 and 1600 gm, who were treated with mechanical ventilation and surfactant, were randomly assigned before 36 hours of life to receive dexamethasone (n = 55) or placebo (n = 54) for 12 days. RESULTS There were no differences in the incidence of BPD and/or death between groups. However, fewer patients in the dexamethasone group were oxygen-dependent at 36 weeks after conception (8% vs 33%, p < 0.05). The dexamethasone group had a lower incidence of necrotizing enterocolitis (0% vs 9%, p < 0.05). The incidence of arterial hypertension, hyperglycemia, and sepsis was not affected by the treatment. Basal and poststimulation serum cortisol levels did not differ between groups. CONCLUSION The administration of dexamethasone early in the course of RDS does not decrease the incidence of BPD and/or death in preterm infants. However, dexamethasone may reduce oxygen dependency at 36 weeks after conception.

Randomized Trial of Early Bubble Continuous Positive Airway Pressure for Very Low Birth Weight Infants

OBJECTIVE To determine whether very low birth weight infants (VLBWIs), initially supported with continuous positive airway pressure (CPAP) and then selectively treated with the INSURE (intubation, surfactant, and extubation to CPAP; CPAP/INSURE) protocol, need less mechanical ventilation than those supported with supplemental oxygen, surfactant, and mechanical ventilation if required (Oxygen/mechanical ventilation [MV]). STUDY DESIGN In a multicenter randomized controlled trial, spontaneously breathing VLBWIs weighing 800-1500 g were allocated to receive either therapy. In the CPAP/INSURE group, if respiratory distress syndrome (RDS) did not occur, CPAP was discontinued after 3-6 hours. If RDS developed and the fraction of inspired oxygen (FiO(2)) was >0.35, the INSURE protocol was indicated. Failure criteria included FiO(2) >0.60, severe apnea or respiratory acidosis, and receipt of more than 2 doses of surfactant. In the Oxygen/MV group, in the presence of RDS, supplemental oxygen without CPAP was given, and if FiO(2) was >0.35, surfactant and mechanical ventilation were provided. RESULTS A total of 256 patients were randomized to either the CPAP/INSURE group (n = 131) or the Oxygen/MV group (n = 125). The need for mechanical ventilation was lower in the CPAP/INSURE group (29.8% vs 50.4%; P = .001), as was the use of surfactant (27.5% vs 46.4%; P = .002). There were no differences in death, pneumothorax, bronchopulmonary dysplasia, and other complications of prematurity between the 2 groups. CONCLUSION CPAP and early selective INSURE reduced the need for mechanical ventilation and surfactant in VLBWIs without increasing morbidity and death. These results may be particularly relevant for resource-limited regions.

Bronchopulmonary dysplasia: incidence, risk factors and resource utilization in a population of South-American very low birth weight infants

OBJECTIVE To determine the incidence of bronchopulmonary dysplasia, its risk factors and resource utilization in a large South American population of very low birth weight infants. METHODS Prospectively collected data in infants weighing 500 to 1,500 g born at 16 NEOCOSUR Network centers from 10/2000 through 12/2003. Multivariate relative risk and 95% confidence intervals were estimated by Poisson regression with robust error variance to find factors that affected the risk of bronchopulmonary dysplasia. RESULTS 1,825 very low birth weight infants survivors were analyzed. Mean birth weight and gestational age were 1085+/-279 g and 29+/-3 weeks respectively. Bronchopulmonary dysplasia incidence averaged 24.4% and survival without bronchopulmonary dysplasia augmented with increasing gestational age. A higher birth weight and gestational age and a female gender all decreased the risk for bronchopulmonary dysplasia. Factors that independently increased that risk were surfactant requirement, mechanical ventilation, airleak, patent ductus arteriosus, late onset sepsis and necrotizing enterocolitis. Bronchopulmonary dysplasia infants had more days of hospitalization (91+/-27 vs. 51+/-19), of mechanical ventilation (19+/-20 vs. 4+/-7) and oxygen therapy (72+/-30 vs. 8+/-14) in comparison with non BPD infants. CONCLUSIONS Bronchopulmonary dysplasia incidence was 24.4% in a large South American population and is related to greater resource utilization. Risk factors for bronchopulmonary dysplasia in this study were: surfactant requirement, mechanical ventilation, airleak, patent ductus arteriosus, late onset sepsis and necrotizing enterocolitis. These studies may provide useful information in the design of effective preventive perinatal strategies.

Effects of a dairy product fortified with multiple micronutrients and omega-3 fatty acids on birth weight and gestation duration in pregnant Chilean women

OBJECTIVE To test the hypothesis that maternal food fortification with omega-3 fatty acids and multiple micronutrients increases birth weight and gestation duration, as primary outcomes. DESIGN Non-blinded, randomised controlled study. SETTING Pregnant women received powdered milk during their health check-ups at 19 antenatal clinics and delivered at two maternity hospitals in Santiago, Chile. SUBJECT Pregnant women were assigned to receive regular powdered milk (n = 477) or a milk product fortified with multiple micronutrients and omega-3 fatty acids (n = 495). RESULTS Intention-to-treat analysis showed that mean birth weight was higher in the intervention group than in controls (65.4 g difference, 95% confidence interval (CI) 5-126 g; P = 0.03) and the incidence of very preterm birth (0.80 just for mean birth weight and birth length in the on-treatment analysis; birth length in that analysis had a difference of 0.57 cm (95% CI 0.19-0.96 cm; P = 0.003). CONCLUSIONS The new intervention resulted in increased mean birth weight. Associations with gestation duration and most secondary outcomes need a larger sample size for confirmation.

An intervention analysis of air quality data at Santiago, Chile

Abstract Air quality data at Santiago, Chile (PM10, PM2.5 and ozone) from 1989 to 1998 are analyzed with the goal of estimating trends in and impacts of public policies on air quality levels. Those policies, in effect since the late 1980s, have been essentially aimed at PM10 pollution abatement. The analyses show that fall and winter air quality has been improving consistently, specially the PM2.5 levels. The estimated trends for the monthly averages of PM10 concentrations range from −1.5 to −3.3% per annum, whereas the trends for monthly averages of PM2.5 concentrations range from −5 to −7% per annum. The monthly averages of ground ozone daily maxima do not have a significant trend for two of the downtown monitor sites; at the other three monitoring sites (including the one with the highest impacts) there is a clear downward trend between −5 and −3% per annum. The seasonal averages of a declimatized ozone production rate show a downward trend from 1988 through 1995, and no additional improvements have occurred thereafter. These mixed results for ground ozone levels are ascribed to a shift in the magnitude and spatial distribution of emissions in the city, and so there is a need for additional ozone abatement policies and further research on air pollution abatement options.

Displasia broncopulmonar: incidência, fatores de risco e utilização de recursos em uma população sul-americana de recém-nascidos de muito baixo peso

OBJETIVO: Determinar a incidencia de displasia broncopulmonar, os fatores de risco e a utilizacao de recursos em uma ampla populacao sul-americana de recem-nascidos de muito baixo peso ao nascer METODOS: Dados prospectivamente registrados de criancas com peso ao nascer entre 500 a 1.500 g, nascidas em 16 centros neonatais pertencendo a rede NEOCOSUR entre 10/2000 a 12/2003. A analise multivariada de Poisson com variância robusta foi utilizada para determinar os fatores de risco relativo e intervalo de confianca de 95% que afetam o risco de apresentacao de displasia broncopulmonar RESULTADOS: Foram analisados 1.825 recem-nascidos de muito baixo peso ao nascer. As medias de peso ao nascer e a idade gestacional foram de 1.085±279g e 29±3 semanas, respectivamente. A incidencia de displasia broncopulmonar foi de 24,4%, e a sobrevida sem displasia broncopulmonar aumentou quanto maior foi a idade gestacional. Maior peso ao nascer, maior idade gestacional e sexo feminino estiveram associados a um menor risco de displasia broncopulmonar. Aumentaram o risco de displasia broncopulmonar: ventilacao mecânica, necessidade de surfactante, escape aereo, persistencia do canal arterial, sepse tardia e enterocolite necrotizante. As criancas com displasia broncopulmonar requerem um maior tempo hospitalizacao (91±27 versus 51±19), de ventilacao mecânica (19±20 versus 4±7) e de oxigenioterapia (72±30 versus 8±14). CONCLUSOES: A incidencia de displasia broncopulmonar foi de 24,4% em uma ampla populacao sul-americana e se relaciona com uma maior utilizacao de recursos. Os fatores de risco associados a displasia broncopulmonar encontrados nesse estudo foram: ventilacao mecânica, necessidade de surfactante, escape aereo, persistencia do canal arterial, sepse tardia e enterocolite necrotizante. As informacoes contidas neste estudo podem ser uteis para o delineamento de estrategias perinatais de prevencao da morbidade.

A New Score for Predicting Neonatal Very Low Birth Weight Mortality Risk in the NEOCOSUR South American Network

OBJECTIVE:To develop and validate a model for very low birth weight (VLBW) neonatal mortality prediction, based on commonly available data at birth, in 16 neonatal intensive care units (NICUs) from five South American countries.STUDY DESIGN:Prospectively collected biodemographic data from the Neonatal del Cono Sur (NEOCOSUR) Network between October 2000 and May 2003 in infants with birth weight 500 to 1500 g were employed. A testing sample and crossvalidation techniques were used to validate a statistical model for risk of in-hospital mortality. The new risk score was compared with two existing scores by using area under the receiver operating characteristic curve (AUC).RESULTS:The new NEOCOSUR score was highly predictive for in-hospital mortality (AUC=0.85) and performed better than the Clinical Risk Index for Babies (CRIB) and the NICHD risk models when used in the NEOCOSUR Network. The new score is also well calibrated — it had good predictive capability for in-hospital mortality at all levels of risk (HL test=11.9, p=0.85). The new score also performed well when used to predict in hospital neurological and respiratory complications.CONCLUSIONS:A new and relatively simple VLBW mortality risk score had a good prediction performance in a South American network population. This is an important tool for comparison purposes among NICUs. This score may prove to be a better model for application in developing countries.

Stroke Patterns in Neonatal Group B Streptococcal Meningitis

Neonatal group B streptococcus meningitis causes neurologic morbidity and mortality. Cerebrovascular involvement is a common, poorly studied, and potentially modifiable pathologic process. We hypothesized that imaging patterns of focal brain infarction are recognizable in neonatal group B streptococcal meningitis. A consecutive case series included term neonates with the following: (1) bacterial meningitis, (2) acute group B streptococcal infection (positive cerebrospinal fluid/blood culture), (3) brain magnetic resonance imaging within 14 days, and (4) acute intraparenchymal focal infarctions (restricted diffusion). Lesions within known arterial territories were classified as arterial ischemic stroke. Clinical presentations, investigations, and neurologic outcomes were recorded. Eight newborns (50% female) with focal infarction were identified. Five presented early (<1 week), and all manifested clinical shock and elevated acute-phase reactants. Less than 50% had prenatal group B streptococcal screening, while 2 of 3 screened were negative. Two distinct patterns of focal infarction were identified: (1) deep perforator arterial stroke to basal ganglia, thalamus, and periventricular white matter (7/8, 88%), and (2) superficial injury with patchy, focal infarctions of the cortical surface (6/8, 75%). Outcomes (mean 23.8 months) were poor, with severe disability or death in 6/8 (75%). Recognizable stroke patterns contribute to severe neurologic outcomes and represent a potentially modifiable pathophysiologic process in neonatal group B streptococcal meningitis.

Impacto del síndrome de dificultad respiratoria en recién nacidos de muy bajo peso de nacimiento: estudio multicéntrico sudamericano

OBJECTIVE To analyze the incidence, risk factors, major morbidity, mortality and resource employment in very low birth weight infants (< 1500 g) with respiratory distress syndrome (RDS). METHODS Descriptive study using prospectively obtained on-line information from a data base of 20 units belonging to the South American Neocosur Network. A total of 5991 VLBW infants were registered during years 2002-2007. RESULTS The mean gestacional age was 29.1 weeks (95% CI 29.06-29.21) and the mean of birth weight was 1100.5 g (95% CI 1093.79-1107.37). The global incidence of RDS was 74% (95% CI 73-75). Antenatal steroids were administered to 73% of this population. The main risk factor was lower gestational age (p< 0.001); where as prenatal steroids (OR: 0.59; 95% CI 0.49-0.72), female gender (OR: 0.77; 95% CI 0.67-0.89) and premature rupture of membranes (OR: 0.81; 95% CI 0.68-0.96) were protective factors. Antenatal steroids was also associated with a decrease in mortality in those infants that presented with RDS (OR: 0.40; 95% CI 0.34-0.47). Use of resources was higher in the group with RDS, with a greater use of surfactant (74.3% vs. 7.3%, p< 0.001), mechanical ventilation (82.1% vs. 23.8%, p< 0.001), and more days of oxygen (median of 8 vs. 1 day, p< 0.001) and hospitalization (median of 61 vs. 45 days, p< 0.001). RDS was associated to an increase risk in the incidence of ROP, PDA, late onset sepsis, severe IVH and oxygen requirement at 36 weeks of corrected gestational age. CONCLUSIONS RDS had a high incidence in very low birth weight infants, despite the frequent use of antenatal steroids. VLBW Infants with RDS had a higher mortality and an increase risk of relevant morbidity. RDS also increased use of resources.

A risk prediction model for severe intraventricular hemorrhage in very low birth weight infants and the effect of prophylactic indomethacin.

Objective:Develop a risk prediction model for severe intraventricular hemorrhage (IVH) in very low birth weight infants (VLBWI).Study Design:Prospectively collected data of infants with birth weight 500 to 1249 g born between 2001 and 2010 in centers from the Neocosur Network were used. Forward stepwise logistic regression model was employed. The model was tested in the 2011 cohort and then applied to the population of VLBWI that received prophylactic indomethacin to analyze its effect in the risk of severe IVH.Result:Data from 6538 VLBWI were analyzed. The area under ROC curve for the model was 0.79 and 0.76 when tested in the 2011 cohort. The prophylactic indomethacin group had lower incidence of severe IVH, especially in the highest-risk groups.Conclusion:A model for early severe IVH prediction was developed and tested in our population. Prophylactic indomethacin was associated with a lower risk-adjusted incidence of severe IVH.