Guía fármacoterapeutica de amenaza de parto pretérmino / Pharmacotherapeutic guide of the risk of premature birth / Guia farmacoterapêutico do risco de parto prematuro

El parto pretérmino representa un reto terapéutico ya que su tratamiento oportuno disminuye la morbilidad y mortalidad \r\nneonatal. Afecta de 5 a 11% de todos los partos en el mundo, entre 9 y 10% en países de bajos ingresos y de 6 a 11,9% en países \r\ncon altos ingresos. Es el responsable de 70% de las muertes neonatales y 37% de las muertes en infantes así como el causante de \r\n25 a 50% de los casos de falla en el desarrollo neurológico en niños. Por lo anterior, es importante realizar un adecuado tamizaje \r\ny tratamiento de las pacientes que se encuentran en riesgo de parto pretérmino. Para ello, se realizó una guía fármacoterapeutica \r\nbasada en la mejor evidencia para su manejo.

preterm labor represents a therapeutic challenge because \r\nopportune treatment decreases neonatal morbidity and \r\nmortality. It affects 5-11% of all worldwide births. Of these \r\nbirths 9-10% occurred in low-income countries and 6-11.9% in \r\nhigh-income countries. Preterm labor is responsible for 70% \r\nof neonatal deaths and 37% of infant deaths; it causes 25-50% \r\nof the cases of neurological development failure in children. \r\nBecause of this, it is important to perform adequate screening \r\nand treatment of patients at risk for preterm delivery. A pharma\r\n-\r\nceutical guide based on the best evidence for its management \r\nwas performed.

O parto prematuro representa um desafio terapêutico, uma vez \r\nque seu tratamento oportuno diminui a morbidez e mortali\r\n-\r\ndade neonatal. Afeta de 5 a 11% de todos os partos no mundo, \r\nsendo que, entre 9 e 10% ocorrem em países de baixa renda, \r\ne de 6 a 11,9%, em países de alta renda. É responsável por 70% \r\ndas mortes neonatais e 37% das mortes em recém-nascidos, \r\nassim como é o causador de 25 a 50% dos casos de falha no \r\ndesenvolvimento neurológico em crianças. Por este motivo, \r\né importante realizar uma triagem e tratamento adequados \r\ndas pacientes que se encontram em risco de parto prematuro. \r\nPortanto, foi elaborado um guia farmacoterapêutico com base \r\nna melhor evidência para seu manuseio.

Factores asociados a estancia hospitalaria prolongada en neonatos / Factors associated with prolonged hospital stay in infants

Objetivo: Evaluar los factores que están presentes al ingreso del recién nacido a una unidad de cuidados intensivos neonatales y que están asociados a una estancia prolongada. Pacientes y Método: Estudio de casos y controles no pareado, con 555 neonatos, 111 con estancia superior a 7 días y 444 con estancia entre 1 y 7 días, hospitalizados entre los años 2005 y 2010. Se evaluaron factores maternos (edad, gravidez, seguridad social, educación, control prenatal, estado civil, antecedente de preeclampsia, ruptura prolongada de membranas, corioamnionitis, infecciones) y neonatales (edad al ingreso, edad gestacional, peso al nacer, sexo, vía de nacimiento, vía de ingreso, Apgar y tipo de reanimación) previos a la hospitalización que estuvieron asociados con estancias prolongadas. Los análisis se hicieron con STATA® 11.0, empleando la regresión logística en el análisis multivariado. Resultados: Factores maternos como control prenatal con menos de 5 visitas (ORa: 2,7; IC 95 por ciento: 1,3-5,5), carencia de seguridad social en salud (ORa: 1,9; IC 95 por ciento: 1,4-29), gravidez de 3 o más gestaciones (ORa: 1,7; IC 95 por ciento: 1,1-2,7) y neonatales como peso al nacer menor a 2.000 g (ORa: 4,2; IC 95 por ciento: 1,9-9,5), necesidad de reanimación cardiorespiratoria (ORa: 4,2; IC 95 por ciento: 2-9,1), edad gestacional menor a 36 semanas (ORa: 3,9; IC 95 por ciento: 2-7,7) e ingreso a la unidad neonatal por urgencia o remisión desde otro centro hospitalario (ORa: 2,8; IC 95 por ciento: 1,7-4,6), se hallaron asociados a estancia mayor a 7 días. Conclusiones: Las complicaciones intrahospitalarias que condicionan una estancia prolongada fueron seguridad social en salud, escolaridad materna y control prenatal, y deben ser consideradas en la evaluación de los indicadores de calidad de atención hospitalaria.

Objective: To evaluate factors present on newborn admission to a neonatal intensive care and associated with a prolonged hospital stay. Patients and Method: Non-matched case-control study, with 555 infants, 111 with more than 7 days of hospital stay and 444 who stayed hospitalized between 1 and 7 days, between 2005 and 2010. Pre hospitalization maternal factors (age, pregnancy, health insurance, education, prenatal care, marital status, history of preeclampsia, prolonged rupture of membranes, chorioamnionitis infection) and neonatal ones (age at admission, gestational age, birth weight, gender, delivery practice, route of admission, Apgar and type of resuscitation) that were associated with prolonged hospital stay were analyzed. Analyses were conducted using STATA 11.0 and logistic regression in the multivariate analysis. Results: Maternal factors such as prenatal care with less than 5 doctor visits (AOR 2.7, 95 percent CI 1.3-5.5), lack of social health insurance (AOR 1.9, 95 percent CI 1.4-29), pregnant three or more times (AOR 1.7, 95 percent CI 1.1-2.7), neonatal birth weight under 2,000 g (AOR 4.2, 95 percent CI 1.9-9.5), need for cardiopulmonary resuscitation (AOR 4.2, 95 percent CI 2-9.1), gestational age less than 36 weeks (AOR 3.9, 95 percent CI 2-7.7) and admission to the neonatal unit through emergency room or referral from another hospital (AOR 2.8, 95 percent CI 1.7-4.6) were associated with hospital stays longer than 7 days. Conclusions: In-hospital complications that affect a prolonged stay at the health center were social health insurance, maternal education and prenatal care, and these should be considered in the evaluation of the hospital care quality indicators.

Escala predictiva diagnóstica de infección urinaria en neonatos febriles sin foco aparente / A diagnostic predictive scale for urinary tract infection in febrile infants without an apparent focus

Introduction: Urinary tract infection (UTI) is the most frequent bacterial infection in infants with nonspecific clinical manifestations. Objective: To validate a predictive scale for UTI in febrile infants without apparent source and hospitalized in a neonatal unit. Patients and Method: A nested case-control study was conducted on 158 infants with febrile UTI, culture-confirmed, and on 346 febrile infants without apparent focus in whom UTI was ruled out, and also, hospitalized in a neonatal unit. The analysis was performed using Stata® 11. Associations were determined using odds ratio (OR) with 95 percent confidence interval. To find the predictive scale, multivariate analysis was performed using logistic regression and establishing major and minor criteria according to regression coefficient. Yield was calculated by sensitivity, specificity and area under ROC curve. The new predictive scale was validated by 108 new febrile neonates. Results: The major criteria to predict UTI were abnormal urinalysis and Gram positive cells without centrifugation, and among the minor criteria, male, age at time of fever, previous neonatal hospitalization, abnormal temperature (38.5°C or more, persistent fever, hypothermia) and 1.7 mg/dL C reactive protein or higher, resulting positive with the presence of one mayor or three minor criteria. It showed good performance with 100% sensitivity (CI 95 percent:98.3-100 percent), 92.3 percent specificity (CI 95 percent: 85.8-98.9 percent) and 0.962 area under ROC (95 percent CI: 0.932-0.991) when validated on 108 new febrile neonates without focus. Conclusions: The new predictive scale allows predicting UTI with good yield in infants with fever without an identified source.

Introducción: La infección de tracto urinario (ITU) es la infección bacteriana más frecuente en neonatos, con manifestaciones clínicas inespecíficas. Objetivo: Validar una Escala Predictiva de ITU en neonatos febriles sin foco aparente, hospitalizados en una unidad neonatal. Pacientes y Método: Estudio caso control anidado en una cohorte, realizado en 158 neonatos febriles con ITU, confirmada por cultivo y 346 neonatos febriles sin foco aparente, en quienes se descartó ITU, hospitalizados en una unidad neonatal. El análisis se realizó con Stata® 11. Las asociaciones se determinaron mediante odds ratio (OR), con su intervalo de confianza de 95 por ciento. Para hallar la Escala Predictiva, se realizó análisis multivariado mediante regresión logística, estableciendo criterios mayores y menores de acuerdo al coeficiente de regresión, mientras el rendimiento se determinó con sensibilidad, especificidad y área bajo ROC. La nueva Escala Predictiva se validó con 108 neonatos febriles nuevos. Resultados: Los criterios mayores para la predicción diagnóstica de ITU fueron uroanálisis alterado y Gram de orina sin centrifugar positivo, y los criterios menores, sexo masculino, edad al momento de la fiebre mayor a 7 días, hospitalización neonatal previa, alteración de la temperatura (38,5°C o más, fiebre persistente, hipotermia) y proteína C reactiva 1,7 mg/dL o mayor, siendo positiva con un criterio mayor o tres menores. Esta mostró buen rendimiento con sensibilidad 100 por ciento (IC 95 por ciento: 98,3-100 por ciento), especificidad 92,3 por ciento (IC 95 por ciento: 85,8-98,9 por ciento) y área bajo ROC 0,962 (IC 95 por ciento: 0,932-0,991) cuando se validó en 108 nuevos neonatos febriles sin foco. Conclusiones: La nueva Escala Predictiva permite con buen rendimiento predecir una ITU en neonatos con fiebre sin foco aparente.

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.

Sepsis neonatal por streptococcus grupo B y bacterias gram negativas: prevalencia y riesgo de meningitis / Sepsis neonatal group B streptococcus and gram negative bacteria: prevalence and risk of meningitis

Introducción: La sepsis y meningitis son importante causa de morbi-mortalidad neonatal. Objetivo: Identificar la prevalencia y riesgo de meningitis en neonatos con sepsis por Streptococcus del grupo B (SGB) y bacterias Gram negativas (BGN), además de comparar factores de riesgo, características clínicas y de laboratorio. Pacientes y Método: Estudio de corte transversal con 30 neonatos con SGB y 41 con BGN. Los datos fueron analizados en Stata® 11.0, empleando medidas de tendencia central y dispersión de acuerdo a su distribución para comparar diferencias. Las variables categóricas fueron comparadas con prueba de χ2 o Exacta de Fisher y las asociaciones mediante razones de prevalencia (RP) y odds ratio (OR) con su intervalo de confianza de 95 por ciento. Se empleó un nivel de probabilidad < 0,05 como criterio de significancia. Resultados: La prevalencia de meningitis entre neonatos con sepsis fue 16,9 por ciento (IC 95 por ciento: 7,5-26,3 por ciento). El 33,3 por ciento (10/30) de sepsis por SGB se asoció a meningitis, mientras 4,9 por ciento (2/40) a sepsis por BGN, hallándose una asociación entre sepsis y meningitis en neonatos con SGB (OR: 9,5; IC 95 por ciento: 1,7-94,3). El 80 por ciento (IC 95 por ciento: 44,4-97,5 por ciento) de casos de meningitis asociada a sepsis por SGB ocurrió en neonatos mayores de 72 h de vida. Conclusión: La meningitis fue más frecuente en neonatos con sepsis por SGB, principalmente en casos de sepsis tardía. La asociación entre sepsis por BGN y meningitis fue menos frecuente en sepsis temprana, y no se halló en sepsis tardía.

Introduction: Sepsis and meningitis are major causes of neonatal morbidity and mortality. Objective: To identify the prevalence and risk of meningitis in neonates with sepsis due to group B Streptococcus (GBS) and gram-negative bacteria (GNB), and to compare risk factors, clinical and laboratory characteristics. Patients and Method: Cross-sectional study of 30 infants with infections due to GBS and 41 due to BGN. Data were analyzed by Stata® 11.0, using measures of central tendency and dispersion, according to their distribution, to compare differences. Categorical variables were compared using χ2 test or Fisher's Exact Test and associations using prevalence ratios (PR) and odds ratio (OR) with 95 percent confidence interval. A level of probability of < 0.05 was used as a significance criterion. Results: The prevalence of meningitis among infants with sepsis was 16.9 percent (95 percent CI: 7.5-26.3 percent. 33.3 percent(10/30) of sepsis due to GBS was associated with meningitis, while 4.9 percent (2/40) was associated with GNB, finding a clear connection between sepsis and meningitis in neonates with GBS (OR: 9.5; CI 95 percent:1.7-94.3). 80 percent (CI 95 percent: 44,4-97,5 percent) of cases of meningitis associated with GBS sepsis occurred in infants older than 72 hours. Conclusion: Meningitis was more common in infants with GBS sepsis, mainly in cases of late-onset sepsis. The association between GNB sepsis and meningitis was less frequent in early sepsis, and was not found in late sepsis.

Acute hepatotoxicity of Crotalus durissus terrificus (South American rattlesnake) venom in rats

Venom of the South American rattlesnake, Crotalus durissus terrificus (Cdt), presents myotoxic and neurotoxic outcomes, but reports on its effects on the liver are scarce. This study examined the hepatotoxicity resulting from Cdt venom administration (100, 200 and 300 miug/kg) in male Wistar rats. Animais were studies at 3, 9 and 12 hours after venom injection. The hepatotoxicity was assessed through serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma glutamyl transferase (GGT), bilirrubin and also by histopathological evaluation. All the different concentrations of Cdt venom resulted in increased levels of hepatic enzymes, when compared with the control group, except for the 100 miug/kg dose, which presented normal levels at 9 and 12 hours after venom administration. Bilirrubin levels remained unchanged by Cdt venom. Histological analysis revealed endothelial damage, inflammatory cell infiltration, as well as sinusoidal and portal congestion. Based on these observations, we may conclude that Cdt venom causes dose- and time-dependent hepatic damage in rats, characterized by elevated hepatic enzyme levels and histological alterations

Neutralization of the edema-forming, defibrinating and coagulant effects of Bothrops asper venom by extracts of plants used by healers in Colombia

We determined the neutralizing activity of 12 ethanolic extracts of plants against the edema-forming, defibrinating and coagulant effects of Bothrops asper venom in Swiss Webster mice. The material used consisted of the leaves and branches of Bixa orellana (Bixaceae), Ficus nymphaeifolia (Moraceae), Struthanthus orbicularis (Loranthaceae) and Gonzalagunia panamensis (Rubiaceae); the stem barks of Brownea rosademonte (Caesalpiniaceae) and Tabebuia rosea (Bignoniaceae); the whole plant of Pleopeltis percussa (Polypodiaceae) and Trichomanes elegans (Hymenophyllaceae); rhizomes of Renealmia alpinia (Zingiberaceae), Heliconia curtispatha (Heliconiaceae) and Dracontium croatii (Araceae), and the ripe fruit of Citrus limon (Rutaceae). After preincubation of varying amounts of each extract with either 1.0 æg venom for the edema-forming effect or 2.0 æg venom for the defibrinating effect, the mixture was injected subcutaneously (sc) into the right foot pad or intravenously into the tail, respectively, to groups of four mice (18-20 g). All extracts (6.2-200 æg/mouse) partially neutralized the edema-forming activity of venom in a dose-dependent manner (58-76 percent inhibition), with B. orellana, S. orbicularis, G. panamensis, B. rosademonte, and D. croatii showing the highest effect. Ten extracts (3.9-2000 æg/mouse) also showed 100 percent neutralizing ability against the defibrinating effect of venom, and nine prolonged the coagulation time induced by the venom. When the extracts were administered either before or after venom injection, the neutralization of the edema-forming effect was lower than 40 percent for all extracts, and none of them neutralized the defibrinating effect of venom. When they were administered in situ (sc at the same site 5 min after venom injection), the neutralization of edema increased for six extracts, reaching levels up to 64 percent for C. limon.