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.

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%) ...

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.

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.

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.

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.

Use of corticosteroids and the outcome of infants with bronchopulmonary dysplasia

Ventilator-dependent premature infants are often treated with dexamethasone. Several trials showed that steroids while improve pulmonary compliance and facilitate extubation, some treated infants may have adverse effects, such as alterations of growth curves. We conducted this retrospective study to evaluate the effects of steroids on mechanical ventilation, oxygen therapy, hospital length stay and mortality, in ventilator-dependent infants with bronchopulmonary dysplasia (BPD) (defined as the need of oxygen supplementation at 28 days of life). Twenty-six newborns with BPD were evaluated during 9 3/4 42 days postpartum (mean = 31 days) and were divided into two groups: Group I - 14 newborns that did not receive dexamethasone, and Group II - 12 newborns that received dexamethasone at 14 3/421 days of life. Dexamethasone was given at a dose of 0.25 mg per kilogram of body weight twice daily intravenously for 3 days, after which the dose was tapered. RESULTS: There were no statistically significant differences in the mean length of mechanical ventilation (Group I - 37 days, Group II - 35 days); oxygen supplementation (Group I - 16 days, Group II - 29 days); hospital stay (Group I - 72 days, Group II - 113 days); mortality (Group I - 35.7 percent, Group II - 41.6 percent). At birth, Group II was lighter (BW: Group I - 1154 grams +/- 302, Group II - 791 grams +/- 165; p<0.05) and smaller (height: Group I - 37.22 cm +/- 3.3, Group II - 33.5 +/- 2.4; <0.05) than Group I. At 40 weeks, there were no statistically significant differences between groups in relation to anthropometric measurements. CONCLUSIONS: The use of corticosteroids in bronchopulmonary dysplasic infants may influence the somatic growth during its use. However, after its suspension, a recovery seems to occur, suggesting that its influence could be transitory.