Mecanismos de lesión cerebral en niños prematuros / Mechanisms of brain injury of the premature baby

Los nacimientos prematuros son uno de los principales indicadores de salud de un país. Están asociados a una alta mortalidad e importante morbilidad en niños con parálisis cerebral y otros trastornos del neurodesarrollo, incluyendo problemas cognitivos y del aprendizaje. Los principales tipos de lesión encefálica en los recién nacidos prematuros son: a) las lesiones de la sustancia blanca, generalmente asociadas a alteraciones neuronales y axonales en la corteza cerebral y otras zonas de sustancia gris; b) hemorragias intracraneanas que incluyen las de la matriz germinal, intraventriculares e intraparenquimatosas y c) del cerebelo. Las lesiones de sustancia blanca incluyen la leucomalacia periventricular quística, no quística (con focos de necrosis microscópicos) y lesiones difusas de sustancia blanca, no necróticas. Estas lesiones tienen múltiples factores etiológicos. Las características anatómicas y fisiológicas de las estructuras vasculares periventriculares predisponen a la sustancia blanca a ser muy vulnerable a las situaciones de isquemia cerebral y, en interacción con factores infecciosos/inflamatorios, activan a las microglías generando estrés oxidativo (por liberación de radicales libres del oxígeno y del nitrógeno), liberación de citoquinas proinflamatorias, liberación de glutamato, fallo energético y alteración de la integridad vascular. Todo lo anteriormente mencionado genera una particular vulnerabilidad de los pre-oligodendrocitos que termina alterando la mielinización. La hipoxia-isquemia también puede producir necrosis neuronal selectiva en diferentes regiones encefálicas. La matriz germinal es un área altamente vascularizada en la región subependimaria periventricular con una estructura capilar muy frágil que la predispone a las hemorragias.

Preterm birth is one of the main country health indicators. It is associated with high mortality and significant morbidity in preterm newborns with cerebral palsy and potential long-term neurodevelopmental disabilities like cognitive and learning problems. The main lesions could be: a) white matter injuries, generally associated with cortical and other regions of grey matter neuronal-axonal disturbances; b) intracranial hemorrhage that includes germinal matrix, intraventricular and parenchymal, c) cerebellum injuries. The white matter lesions include cystic and non-cystic (with microscopic focal necrosis) periventricular leukomalacia and non-necrotic diffuse white matter injury. Multiple etiologic factors are associated with these injuries. Anatomical and physiological characteristics of periventricular vascular structures predispose white matter to cerebral ischemia and, interacting with infection/inflammation factors, activate microglia, generating oxidative stress (mediated by free oxygen and nitrogen radicals), pro-inflammatory cytokine and glutamate toxicity, energetic failure and vascular integrity disturbances. All these factors lead to a particular vulnerability of pre-oligodendrocytes that will affect myelination. Hypoxia-ischemia also may produce selective neuronal necrosis in different cerebral regions. Germinal matrix is a highly vascularized zone beneath ependymal or periventricular region that constitutes a capillary bed with a particular structural fragility that predispose it to hemorrhage.

Corioamnionitis histológica y morbimortalidad neonatal: aproximación al síndrome de respuesta inflamatoria fetal / Chorioamnionitis neonatal morbidity: approach to fetal inflammatory response syndrome

Antecedentes: El síndrome de respuesta inflamatoria fetal (SRIF) es una entidad relacionada con la presencia de inflamación intrauterina y suele asociarse a infección intraamniótica. Su consecuencia más grave es la lesión cerebral y posterior desarrollo de parálisis cerebral. Objetivo: Evaluar la relación entre el síndrome de respuesta inflamatoria fetal y el desarrollo de complicaciones neonatales. Método: Estudio descriptivo y retrospectivo, realizado en el Hospital Universitario La Paz de Madrid, buscando una aproximación al SRIF desde la corioamnionitis histológica/funiculitis. El grupo de estudio constituido por 35 gestaciones simples pretérmino recogidas durante el primer semestre de 2008 y en las que la anatomía patológica de la placenta y anexos ovulares demostró la presencia de una corioamnionitis histológica y/o funiculitis. Resultados: Siete casos (20 por ciento) presentaban clínica sospechosa de infección intraamniótica, si bien en 28 gestantes (80 por ciento) existían factores de riesgo asociados al síndrome de respuesta inflamatoria fetal. Mortalidad perinatal en el grupo estudiado fue de 11,4 por ciento (4 casos). Sólo en 2 pacientes (5,7 por ciento) se pudo relacionar la muerte con el SRIF. En 28 recién nacidos (80 por ciento) se encontró algún tipo de patología, siendo la misma inherente a dicho síndrome en 17 casos (48,6 por ciento), destacando sepsis neonatal (40 por ciento), leucomalacia periventricular (14,3 por ciento) y displasia broncopulmonar (5,7 por ciento). Conclusión: Se comprueba el alto riesgo neonatal del SRIF. El conocimiento de esta condición, abre una serie de controversias diagnósticas y terapéuticas que obliga a una reevaluación de los protocolos actuales de manejo de la amenaza de parto pretérmino y la rotura prematura de membranas de pretérmino.

Background: The fetal inflammatory response syndrome (FIRS) is an entity related to intrauterine inflammation which is commonly associated with intraamniotic infection. The most serious consequence is the neurologic damage and the subsequent development of cerebral palsy. Aims: To evaluate the relationship between the fetal inflammatory response syndrome and the development of neonatal complications. Method: Descriptive and retrospective study realized in "La Paz" University Hospital of Madrid, looking for an approximation to the FIRS from histologic chorioamnionitis/funisitis. Group of study constituted by 35 single preterm gestations collected during the first semester of 2008 and in which the pathologic anatomy study of the placenta and annexes showed the presence of histological corioamnionitis and / or funisitis. Results: Suspicious clinic was found in 7 cases (20 percent) but in 28 cases (80 percent) risk factors associated to FIRS were present. Perinatal mortality found was 11.4 percent (4 cases). Only in 2 cases (5.7 percent) the cause was relationated with FIRS. Pathology associated was found in 28 newborn (80 percent), being 17 cases (48.6 percent) pathology associated with the fetal inflammatory response syndrome, enhancing neonatal sepsis (40 percent), periventricular leukomalacia (14.3 percent), and bronchopulmonar dysplasia (5.7 percent). Conclusion: It is verified that FIRS enteals a high neonatal risk. The knowledge of this entity opens some diagnostic and therapeutic controversies. Current management protocols of preterm labor and preterm premature rupture of membranes should be revised.

Sepse neonatal como fator de risco para leucomalácia periventricular em pré-termos de muito baixo peso / Periventricular leukomalacia in very low birth weight preterm neonates with high risk for neonatal sepsis

OBJETIVO: Verificar a associação de leucomalácia periventricular (LPV) e sepse neonatal em recém-nascidos de muito baixo peso (RNMBP). MÉTODOS: Foram incluídos RNMBP com suspeita clínica de infecção nascidos na instituição de 01/08/2005 a 31/07/2007. Foram excluídos óbitos antes dos 14 dias, malformações do sistema nervoso central e infecções congênitas. Foi realizado ultra-som cerebral no terceiro dia e semanalmente até a sexta semana de vida ou alta. LPV foi diagnosticada por hiperecogenicidade difusa periventricular persistente por mais de 7 dias, ou por cistos periventriculares. RNMBP foram divididos em grupos com e sem LPV. Sepse foi definida por manifestação clínica com cultura positiva. Os testes t, Mann-Whitney, qui-quadrado e regressão logística foram usados. RESULTADOS: Foram incluídos 88 RNMBP, sendo que 62 (70,5 por cento) sobreviveram e 51 (57,8 por cento) tiveram LPV. Os grupos foram semelhantes no peso de nascimento, idade gestacional, escore de Apgar, tipo de parto, SNAPPE-II, presenças de enterocolite necrosante, persistência de canal arterial e óbitos. Sepse e ventilação mecânica foram mais freqüentes no grupo com LPV (23,5 e 2,7 por cento, p = 0,005; 86 e 59 por cento, p = 0,004, respectivamente). Na regressão logística, ambos foram fatores de risco independentes para LPV (p = 0,027 e 0,015, respectivamente). CONCLUSÃO: Corioamnionite é fator de risco definido para LPV. Demonstramos que sepse neonatal também é fator de risco importante. Acreditamos que a resposta inflamatória sistêmica seja o principal fator envolvido na etiopatogenia da LPV em RNMBP.

OBJECTIVE: To investigate the association between periventricular leukomalacia (PVL) and neonatal sepsis in very low birth weight infants (VLBWI). METHODS: We studied VLBWI with a clinical suspicion of infection who had been born at our institution between the 1st of August, 2005 and the 31st of July, 2007. Children were excluded if they died before reaching 14 days, had malformations of the central nervous system or congenital infections. Ultrasound brain scans were carried out on the third day and weekly up until the sixth week of life or discharge. Periventricular leukomalacia was diagnosed by persistent diffuse periventricular hyperechogenecity for more than 7 days, or by periventricular cysts. The VLBWI were separated into two groups on the basis of the presence or absence of PVL. Sepsis was defined as clinical manifestation plus a positive culture. The Mann-Whitney, chi-square and t tests were applied followed by logistic regression. RESULTS: A total of 88 VLBWI were studied. Of these, 62 (70.5 percent) survived and 51 (57.8 percent) had PVL. Both groups were similar in terms of birth weight, gestational age, Apgar score, type of delivery, SNAPPE-II score, presence of necrotizing enterocolitis, persistent ductus arteriosus and deaths. Sepsis and mechanical ventilation were more common in the group with PVL (23.5 and 2.7 percent, p = 0.005; 86 and 59 percent, p = 0.004, respectively). Both of these were identified as, independent risk factors for PVL by logistic regression (p = 0.027 and 0.015, respectively). CONCLUSIONS: Chorioamnionitis has been defined as a risk factor for PVL. We have demonstrated that neonatal sepsis is also an important risk factor. We believe that the systemic inflammatory response is the principal factor involved in the etiopathogenesis of PVL among VLBWI.

Daño neurológico de orígen intrauterino: tan lejos, tan cerca / Neurological damage of intrauterine origin: so far, so near

Se examina la relación entre infección intrauterina, parto prematuro, morbilidad neonatal y alteraciones neurológicas a distancia. La evidencia indica la asociación entre la exposición antenal a infecciones y las complicaciones a corto y largo plazo