Swiss medical centres vary significantly when it comes to outcomes of neonates with a very low gestational age.

AIM: This study quantified the impact of perinatal predictors and medical centre on the outcome of very low-gestational-age neonates (VLGANs) born at <32 completed weeks in Switzerland. METHODS: Using prospectively collected data from a 10-year cohort of VLGANs, we developed logistic regression models for three different time points: delivery, NICU admission and seven days of age. The data predicted survival to discharge without severe neonatal morbidity, such as major brain injury, moderate or severe bronchopulmonary dysplasia, retinopathy of prematurity (≥stage three) or necrotising enterocolitis (≥stage three). RESULTS: From 2002 to 2011, 6892 VLGANs were identified: 5854 (85%) of the live-born infants survived and 84% of the survivors did not have severe neonatal complications. Predictors for adverse outcome at delivery and on NICU admission were low gestational age, low birthweight, male sex, multiple birth, birth defects and lack of antenatal corticosteroids. Proven sepsis was an additional risk factor on day seven of life. The medical centre remained a statistically significant factor at all three time points after adjusting for perinatal predictors. CONCLUSION: After adjusting for perinatal factors, the survival of Swiss VLGANs without severe neonatal morbidity was strongly influenced by the medical centre that treated them.

Stress oxydant chez l'enfant prématuré : causes, biomarqueurs et possibilités thérapeutiques [Oxidative stress after preterm birth: Origins, biomarkers, and possible therapeutic approaches].

The survival of preterm babies has increased over the last few decades. However, disorders associated with preterm birth, known as oxygen radical diseases of neonatology, such as retinopathy, bronchopulmonary dysplasia, periventricular leukomalacia, and necrotizing enterocolitis are severe complications related to oxidative stress, which can be defined by an imbalance between oxidative reactive species production and antioxidant defenses. Oxidative stress causes lipid, protein, and DNA damage. Preterm infants have decreased antioxidant defenses in response to oxidative challenges, because the physiologic increase of antioxidant capacity occurs at the end of gestation in preparation for the transition to extrauterine life. Therefore, preterm infants are more sensitive to neonatal oxidative stress, notably when supplemental oxygen is being delivered. Furthermore, despite recent advances in the management of neonatal respiratory distress syndrome, controversies persist concerning the oxygenation saturation targets that should be used in caring for preterm babies. Identification of adequate biomarkers of oxidative stress in preterm infants such as 8-iso-prostaglandin F2α, and adduction of malondialdehyde to hemoglobin is important to promote specific therapeutic approaches. At present, no therapeutic strategy has been validated as prevention or treatment against oxidative stress. Breastfeeding should be considered as the main measure to improve the antioxidant status of preterm infants. In the last few years, melatonin has emerged as a protective molecule against oxidative stress, with antioxidant and free-radical scavenger roles, in experimental and preliminary human studies, giving hope that it can be used in preterm infants in the near future.

The role of cathepsin K in lung development and newborn chronic lung injury.

Chronic lung diseases, specifically bronchopulmonary dysplasia (BPD), are still causing mortality and morbidity amongst newborn infants. High protease activity has been suggested to have a deleterious role in oxygen-induced lung injuries. Cathepsin K (CatK) is a potent protease found in fetal lungs, degrading collagen and elastin. We hypothesized that CatK may be an important modulator of chronic lung injury in newborn infants and neonatal mice. First we measured CatK protein levels in repeated tracheal aspirate fluid samples from 13 intubated preterm infants during the first two weeks of life. The amount of CatK at 9-13 days was low in infants developing chronic lung disease. Consequently, we studied CatK mRNA expression in oxygen-exposed wild-type (WT) rats at postnatal day (PN) 14 and found decreased pulmonary mRNA expression of CatK in whole lung samples. Thereafter we demonstrated that CatK deficiency modifies lung development by accelerating the thinning of alveolar walls in newborn mice. In hyperoxia-exposed newborn mice CatK deficiency resulted in increased number of pulmonary foam cells, macrophages and amount of reduced glutathione in lung homogenates indicating intensified pulmonary oxidative stress and worse pulmonary outcome due to CatK deficiency. Conversely, transgenic overexpression of CatK caused slight enlargement of distal airspaces with increased alveolar chord length in room air in neonatal mice. While hyperoxic exposure inhibited alveolarization and resulted in enlarged airspaces in wild-type mice, these changes were significantly milder in CatK overexpressing mice at PN7. Finally, we showed that the expression of macrophage scavenger receptor 2 (MSR2) mRNA was down-regulated in oxygen-exposed CatK-deficient mice analyzed by microarray analysis. Our results demonstrate that CatK seems to participate in normal lung development and its expression is altered during pulmonary injury. In the presence of pulmonary risk factors, like high oxygen exposure, low amount of CatK may contribute to aggravated lung injury while sustained or slightly elevated amount of CatK may even protect the newborn lungs from excessive injury. Besides collagen degrading and antifibrotic function of CatK in the lungs, it is obvious that CatK may affect macrophage activity and modify oxidative stress response. In conclusion, pulmonary proteases, specifically CatK, have distinct roles in lung homeostasis and injury development, and although suggested, broad range inhibition of proteases may not be beneficial in newborn lung injury.

Effect of postnatal malnutrition on hyperoxia-induced newborn lung development

Several factors are associated with bronchopulmonary dysplasia. Among them, hyperoxia and lung immaturity are considered to be fundamental; however, the effect of malnutrition is unknown. Our objective was to evaluate the effects of 7 days of postnatal malnutrition and hyperoxia on lung weight, volume, water content, and pulmonary morphometry of premature rabbits. After c-section, 28-day-old New Zealand white rabbits were randomized into four groups: control diet and room air (CA, N = 17), control diet and ≥95% O2 (CH, N = 17), malnutrition and room air (MA, N = 18), and malnutrition and ≥95% O2 (MH, N = 18). Malnutrition was defined as a 30% reduction of all the nutrients provided in the control diet. Treatments were maintained for 7 days, after which histological and morphometric analyses were conducted. Lung slices were stained with hematoxylin-eosin, modified orcein-resorcin or picrosirius. The results of morphometric analysis indicated that postnatal malnutrition decreased lung weight (CA: 0.83 ± 0.19; CH: 0.96 ± 0.28; MA: 0.65 ± 0.17; MH: 0.79 ± 0.22 g) and water content, as well as the number of alveoli (CA: 12.43 ± 3.07; CH: 8.85 ± 1.46; MA: 7.33 ± 0.88; MH: 6.36 ± 1.53 x 10-3/mm) and elastic and collagen fibers. Hyperoxia reduced the number of alveoli and increased septal thickening and the mean linear intercept. The reduction of alveolar number, collagen and elastic fibers was intensified when malnutrition and hyperoxia were associated. These data suggest that dietary restriction enhances the magnitude of hyperoxia-induced alveolar growth arrest and lung parenchymal remodeling. It is interesting to consider the important influence of postnatal nutrition upon lung development and bronchopulmonary dysplasia.

Ventilación mecanica y uso de oxígeno en prematuros tratados con citrato de cafeina o aminofilina

Las consecuencias de la inmadurez orgánica junto con las dificultades en la adaptación a la vida extrauterina, traen consigo difíciles retos y altos costos, referidos en lo económico y en las vidas humanas dentro de las unidades de recién nacidos: cientos de neonatos fallecen por las complicaciones asociadas a la prematuridad. Las complicaciones respiratorias, ocupan el primer lugar de todos estos problemas y es un enorme reto el hallar estrategias que logren rápidamente la independencia y autonomía de la mecánica respiratoria del prematuro, lo que incluye el menor tiempo posible del uso de oxígeno, pues se sabe de las consecuencias negativas e irreversibles de la ventilación mecánica sobre la arquitectura pulmonar y el estado hemodinámico, así como la toxicidad del oxígeno sobre los pulmones mismos y la retina (displasia broncopulmonar y retinopatía).

Efectos de la ventilación mecánica con heliox en niños y adolescentes con patología bronquial obstructiva

Evaluar si el Heliox reduce la resistencia en la vía aérea en niños y adolescentes con patología bronquial obstructiva que requieren ventilación mecánica. Materiales y Métodos: Estudio prospectivo observacional descriptivo en niños y adolescentes con patología bronquial obstructiva y ventilación mecánica con Fi02 ≤ 0,5. Medición de variables: resistencia, presión pico, presión media de la vía aérea, presión meseta, volumen corriente, autoPEEP, distensibilidad, PetCO2, ventilación de espacio muerto antes de inicio de heliox y a los 30 minutos, 2, 4, 6, 12, 18 y 24 horas y diariamente hasta suspenderlo por extubación o FiO2 > 0,5. Resultados: Resultados parciales, incluyó 9 pacientes encontrando descenso significativo de resistencia espiratoria a los 30 minutos (51,2 vs 32,3; p=0,0008 ), 2 horas ( 51,2 vs 33,4; p=0,0019) y 4 horas (51,2 vs 30,7; p=0,0012) así como de la resistencia inspiratoria a la hora 2 (48,6 vs 36,2; p = 0,013) y hora 4 (48,6 vs 30 ; p=0,004). Se observó tendencia al descenso de la PetCO2 que no fue significativa (52,3 vs 34,3: p=0,06). No se evidenció cambios en las variables; autoPEEP, presión pico, presión media de la vía aérea, distensibilidad, ventilación de espacio muerto, presión meseta y volumen corriente antes y después del inicio del Heliox. Conclusión: La ventilación mecánica con Heliox en niños con patología bronquial obstructiva parece ser que reduce de manera significativa la resistencia de la vía aérea, con tendencia al descenso de la PetC02. Se necesitan estudios prospectivos al menos observacionales analíticos que corroboren estos hallazgos.

Uso del Sildenafil en hipertensión pulmonar del recién nacido. Revisión sistemática de la literatura

Antecedentes El desarrollo de la hipertensión pulmonar en el recién nacido es una condición grave que supone un peligro para su vida. Se ha propuesto el uso del sildenafil como tratamiento para esta enfermedad, sin embargo no ha sido evaluada su eficacia a través de una revisión sistemática. Objetivos Determinar el efecto del sildenafil en el manejo de recién nacidos con diagnóstico de hipertensión pulmonar a través de la realización de una revisión sistemática de la literatura. Metodología Se planteó la realización de una revisión sistemática de la literatura. La búsqueda fue realizada a través de las bases de datos: Pubmed, Embase, LiLaCS y Cochrane library. Se incluyeron ensayos clínicos controlados y estudios de cohortes publicados en los idiomas inglés y español. Las variables cualitativas fueron estimadas como riesgos relativos o odds ratios con sus IC95%, las variables cualitativas como diferencias de promedios con sus IC95%. Resultados Se incluyeron 4 estudios en la revisión sistemática. Dos estudios compararon el sildenafil contra el placebo. El uso del sildenafil se relacionó con una menor mortalidad y mejoría en los parámetros ventilatorios. Conclusión: Es aconsejable el uso del sildenafil en el manejo de la hipertensión pulmonar en niños.

Morbilidad y mortalidad en prematuros menores de 1500 gramos en un hospital regional del 2011 a 2013

Introducción: El presente estudio pretende determinar la mortalidad y caracterizar morbilidad de este grupo de recién nacidos, para establecer planes de mejoramiento. Materiales y método: Estudio descriptivo retrospectivo de corte transversal. Se revisaron 158 historias clínicas de los recién nacidos prematuros menores de 1500 gramos hospitalizados en la unidad de cuidados intensivos neonatales del Hospital Universitario Departamental de Nariño durante el periodo 2011 al 2013. La información fue analizada estadísticamente. Resultados: Se encontró que de 5447 nacidos vivos el 2,9 % fueron menores de 1500 gramos. 52,5 % eran de género masculino, 63,9% nacieron por cesárea. El 23,4 % no recibió esteroides antenatales. La tasa de mortalidad para el periodo de estudio en este grupo de pacientes fue de 7.3 por mil nacidos vivos. El 100% de los recién nacidos de menos de 750 gr fallecieron. Mientras que no se registro ninguna sobrevida de menos de 24 semanas. Conclusiones: Podría establecerse este como límite de viabilidad el peso al nacer < 750 gr y menos de 24 semanas de gestación, en donde la muerte es prácticamente la regla, siempre teniendo en cuenta evaluar cuidadosamente cada caso particular. La morbilidad de los prematuros de muy bajo peso al nacer esta en los rangos reportados en la literatura.

Avaliação da suplementação com vitamina E, na forma natural ou sintética, em mulheres no pós-parto imediato e sua concentração no colostro

The Vitamin E consists of eight chemically homologous forms, designated alpha, beta, gamma and delta tocopherols and tocotrienols. Biologically, the alpha-tocopherol (α-TOH) is the most important. Commercially, are found two types of α-TOH a natural (RRR-alpha-tocopherol) and another synthetic (all-rac-alpha-tocopherol). Both forms are absorbed in the intestine, the liver is a preference in favor of forms 2R, due to transfer protein α-TOH. It has higher affinity to these stereoisomers. Newborns are considered high risk for vitamin E deficiency, mainly premature, these have breast milk as a food source for maintenance of serum α-TOH. Clinical signs such as thrombocytosis, hemolytic anemia, retrolental fibroplasia, intraventricular hemorrhage, bronchopulmonary dysplasia and spinocerebellar degeneration can be found in case of a low intake of α-TOH. Thus, maternal supplementation on postpartum with α-TOH can be an efficient way to increase levels of vitamin E in breast milk and thus the consequently increase the supply of micronutrient for the newborn. However, most studies with vitamin E supplementation have been conducted in animals and little is known about the effect of maternal supplementation in humans, as well as on its efficiency to increase levels of α-TOH in human milk, depending on the shape natural or synthetic. The study included 109 women, divided into three groups: control without supplementation (GC) (n=36), supplemented with natural capsule (GNAT) (n=40) and the synthetic capsule (GSINT) (n=33). Blood samples were collected for determination of maternal nutritional status, and colostrums at initial contact and after 24 hours post-supplementation. Analyses were performed by High Performance Liquid Chromatography. Values of α-TOH in serum below 499.6mg/dL were considered deficient. We used the Kruskal-Wallis test and Tukey test to confirm the increase of alpha-tocopherol in milk and efficiency of administered capsules. Daily consumption of α-TOH was based on daily intake of 500 mL of colostrum by the newborn and compared with the nutritional requirement for children from 0 to 6 months of age, 4 mg / day. The mothers had mean concentration of serum α-TOH in 1016 ± 52, 1236 ± 51 and 1083 ± 61 mg / dL, in CG, GNAT and GSINT respectively. There were no women with deficiiency. The GC did not change the concentrations of α-TOH in colostrum. While women supplemented with natural and synthetic forms increased concentrations of α-TOH colostrum in 57.6% and 39%, respectively. By comparing supplemented groups, it was observed a significant difference (p=0.04), the natural capsule more efficient than the synthetic, approximately 49.6%. Individually, 21.1% of the women provided below 4mg/day of α-TOH, after supplementation for this index declined4.1%. Thus, maternal supplementation postpartum raised the levels of alpha-tocopherol in colostrum, and increased efficiency was observed with the natural form

Crescimento de prematuros de extremo baixo peso nos primeiros dois anos de vida

OBJETIVO: Analisar o padrão de crescimento de prematuros de extremo baixo peso (EBP) até 24 meses de idade corrigida, a influência da displasia broncopulmonar (DBP) e os fatores de risco para falha de crescimento. MÉTODOS: Coorte de prematuros <1.000g de gestação única, nascidos e acompanhados em um centro terciário. O crescimento foi avaliado por meio de escores-z para peso, comprimento e perímetro cefálico ao nascimento, com 40 semanas, aos 3, 6, 12, 18 e 24 meses de idade corrigida. Dentre 81 sobreviventes, 70 foram estudados e estratificados em dois grupos: DBP (n=41) e sem DBP (n=29). Foi realizada análise bivariada com teste t ou Mann-Whitney, qui-quadrado ou Exato de Fisher, e análise multivariada com regressão logística. RESULTADOS: em ambos os grupos, o escore-z de peso diminuiu significantemente entre o nascimento e 40 semanas. Houve um pico de incremento nos escores-z de peso, comprimento e perímetro cefálico entre 40 semanas e três meses. No grupo sem DBP, os escores-z atingiram a faixa normal a partir dos seis meses e assim permaneceram até 24 meses de idade corrigida. Crianças com DBP tiveram menores escores-z de peso e perímetro cefálico no primeiro ano, mas equipararam-se às sem DBP no segundo ano de vida. A regressão logística mostrou que catch-down no escore-z de peso com 40 semanas foi fator de risco para falha de crescimento. CONCLUSÕES: Prematuros EBP apresentam catch-up precoce do crescimento nos primeiros dois anos. Crianças com DBP têm pior crescimento ponderal. A restrição do crescimento pós-natal prediz a falha de crescimento nos primeiros anos.

Growth and developmental outcomes of the extremely preterm infant

Objetive: To provide information for pediatricians and neonatologists to create realistic outcome expectations and thus help plan their actions. Sources of data: Searches were made of the Cochrane Library, MEDLINE, and Lilacs databases. Summary of the findings: The assessment of growth and development over the first 2-3 years must adjust chronological age with respect of the degree of prematurity. There is special concern regarding the prognoses of small for gestational age preterm infants, and for those with bronchopulmonary dysplasia. Attention must be directed towards improving the nutrition of extremely low birth weight infants during their first years of life; these infants have high prevalence levels of failure to catch-up on growth, diseases and rehospitalizations during their first 2 years. They are frequently underweight and shorter than expected during early childhood, but delayed catch-up growth may occur between 8 and 14 years. Extremely low birth weight infants are at increased risk of neurological abnormalities and developmental delays during their first years of life. Educational, psychological, and behavioral problems are frequent during school years. Teenage and adult outcomes show that although some performance differences persist, social integration is not impaired. Conclusions: The growth and neurodevelopment of all ELBW infants must be carefully monitored after discharge, to ensure that children and their families receive adequate support and intervention to optimize prognoses. Copyright © 2005 by Sociedade Brasileira de Pediatria.

Preeclampsia: Early and late neonatal outcomes

Newborn infants exposed to preeclampsia (PE) present increased short-term morbidity, mainly respiratory diseases such as respiratory distress syndrome and bronchopulmonary dysplasia. Gastrointestinal problems are also frequent, although a higher risk of necrotizing enterocolitis has not been confirmed. These problems could be related not just to PE itself but also to prematurity or intrauterine growth restriction, which frequently occur in this maternal disease. Other findings, however, seem to be due to the direct effect of the maternal disease; these findings include an increased frequency of neutropenia and thrombocytopenia and a lower incidence of cerebral disorders, such as periventricularintraventricular hemorrhage and cerebral palsy. The evaluation of long-term outcome shows increasing evidence that PE has important implications for the future health of the mother and her child, suggesting that PE is not a simple gestational disorder but a clinical syndrome with an unclear etiology, a genetic component, and a complex pathophysiology. This syndrome involves important maternal and fetal vascular alterations that can persist and cause diseases in later life. The divergence in results on outcomes for children exposed to PE could, in part, be due to methodological differences in the studies, most of which are retrospective case-control studies. Better evidence on prognosis is obtained from cohort studies. Even in the cohort studies, differences in patient characteristics and severity of maternal disease, as well as sample size, follow-up time, and main outcome measures certainly contribute to the variability in results reported in the literature. © 2012 by the American Academy of Pediatrics. All rights reserved.

Marcadores de estresse oxidativo e de inflamação em vias aéreas e prognóstico respiratório de prematuros de mães hipertensas e normotensas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Níveis plasmáticos de vitamina A em recém-nascidos de pré-termo de muito baixo peso e relação com a Displasia Broncopulmonar

Pós-graduação em Pediatria - FMB

Vitamina E no plasma de recém-nascidos de pré-termo de muito baixo peso no primeiro mês de vida. Relação com a vitamina E recebida

Pós-graduação em Pediatria - FMB