Antenatal corticosteroid therapy: Historical and scientific basis to improve preterm birth management.

OBJECTIVE: The purpose of this review is to describe the historical and scientific basis of antenatal corticosteroids (ACS) therapy, to improve the management of preterm birth and decreasing rates of respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis and perinatal mortality in premature infants. STUDY DESIGN: We searched MEDLINE/PubMed electronic database, the Cochrane Library, using medical subheading search words such as "ACS", "corticosteroids", "betamethasone" or "dexamethasone", matching with "preterm birth". RESULTS: This practice was initiated by Liggins and Howie in 1972 and is supported by the initial comprehensive meta-analysis of Crowley, Chambers and Keirse, in 1990, the NIH Consensus Development Conference in 1994, the second Consensus Conference to evaluate repeated courses of corticosteroids in 2000 and the practice recommendations of obstetric societies worldwide. ACS therapy before anticipated preterm birth is one of the most important antenatal therapies and an important evidence-based practice for reducing mortality, and decreasing rates of complications in premature infants. CONCLUSIONS: Today, there is no controversy that women with preterm birth <34 weeks should be ACS treated. Actually, rescue courses are recommended; while multiple, serial, repeated or weekly courses, are not recommended. In any clinical conditions, as preterm premature rupture of membranes, multiple pregnancies, severe preeclampsia/HELLP syndrome and fetal growth restriction; ACS is recommended.

Estudio Descriptivo: Variación del Índice de Tiempo de Aceleración/Tiempo de Eyección Sistólico del Tronco de la Arteria Pulmonar por Efecto de Maduración Pulmonar con Corticoides en Fetos Prematuros. Clínica Humanitaria. Cuenca ­ Ecuador, 2016 / Descriptive Research: Variation of Acceleration Time/Ejection Time Index of the Trunk of the Pulmonary Arteries Due to the Lung Maturation Effect of Corticosteroids on Preterm Fetus. Clínica Humanitaria, 2016

INTRODUCCIÓN: El nacimiento prematuro representa un problema de salud pública importante a nivel mundial y en especial en países en vías de desarrollo. En el Ecuador, en el año 2014, la tasa de mortalidad infantil fue de 8.35 defunciones infantiles por cada 1 000 nacimientos y las principales causas de mortalidad infantil fueron la dificultad respiratoria del recién nacido y los trastornos con duración corta de la gestación. MÉTODOS: El presente es un estudio observacional, descriptivo y longitudinal, realizado con una muestra censal o por conveniencia de 36 mujeres que cursaron entre 24 y 34 semanas de gestación con feto único vivo, riesgo de parto pretérmino e indicación de maduración pulmonar con corticoides. Se recogió información de flujometría fetal para determinar el efecto del uso de corticoides para maduración pulmonar. Se realizaron pruebas de normalidad Shapiro-Wilk en los resultados obtenidos antes y después de la maduración pulmonar. Para el procesamiento de los datos se utilizaron los programas Microsoft Excel® y SPSS® v.20. RESULTADOS: La edad media de este grupo fue de 25.64 años, las media de semanas de gestación fue de 31.2. La patología más frecuente fue amenaza de parto pretérmino con un 72 %, seguida de ruptura prematura pretérmino de membranas con un 13.9 %. Existió una diferencia estadísticamente significativa entre los valores de los índices Tiempo de Acelereción / Tiempo de Eyección antes y después de la maduración pulmonar (0.272 ms y 0.310 ms, respectivamente; P < 0.0001). CONCLUSIONES: La comparación de las medias de los índices Tiempo de Acelereción / Tiempo de Eyección del tronco de la arteria pulmonar pre y post maduración pulmonar con corticoides evidenció una diferencia significativa importante. Los hallazgos sugieren que la maduración pulmonar con corticoides es eficaz para mejorar el flujo de arteria pulmonar en fetos prematuros.

BACKGROUND: Premature birth represents an important public health problem worldwide and especially in developing countries. In Ecuador (2014), the infant mortality rate reached 8.35 deaths per 1 000 births and their main causes were newborns respiratory distress and gestation period short-term disorders. METHODS: This is an observational longitudinal descriptive research; it was performed in a convenience sample that included 26 singlet on pregnant women between 24 and 34 weeks of gestation. They also were on risk of preterm delivery and had indication of lung maturation with corticosteroids. Information of the fetal pulmonary arteries flow was collected to determine the effect of corticosteroids in pulmonary maturation. RESULTS: Mean age was 25.64 years and had an average gestation of 31.2 weeks. Most common diseases were preterm labor threat (72 %) and premature rupture of membranes (13.9 %). There was a statistically significant difference between the values of Acceleration Time / Ejection Time indexes before and after lung maturation (0.272 ms vs. 0.310 ms respectively; P < 0.0001). CONCLUSIONS: Comparison of Acceleration Time / Ejection Time indexes from the trunk of the pulmonary arteries before and after lung maturation evidenced an important significant difference. The findings suggest that pulmonary maturation with corticosteroids is effective to improve the pulmonary arteries flow of preterm fetus.

[Related factors to lack of implementation of antenatal corticosteroids]. / Factores relacionados con la falta de aplicación de glucocorticoides antenatales.

BACKGROUND: Despite the known benefits of antenatal corticosteroids therapy its use in clinical practice is not generalized. OBJECTIVE: To identify factors related to antenatal corticosteroids non administration. METHODS: Cross-sectional and descriptive study that included patients admitted to Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", who had indication for antenatal corticosteroids therapy but did not receive it. Variables: antenatal corticosteroids therapy prescription, factors related to antenatal corticosteroids therapy non administration and lapsed time between diagnosis and birth. RESULTS: Antenatal corticosteroids therapy were not prescribed in 79 (94%) of 84 patients. Main related factors were imminent birth and severe maternal complication. The longer amount of time from diagnosis to birth was before hospitalization (91 vs. 9%, p <0.0005). CONCLUSION: The biggest and best opportunity for the administration of inducers of fetal lung maturity is during prenatal care, when cases with increased risk of preterm birth are detected.

Pregnancy outcomes and successful rate of nifedipine therapeutic protocol implementation in a hospital of San Juan.

PRIMARY OBJECTIVE: evaluation of Nifedipine protocol success defined as postponement of labor for 48 hours. SECONDARY OBJECTIVE: evaluation of the presence of risk factors in patients that develop preterm labor and delivery outcome. MATERIALS AND METHODS: Chart review retrospective study with patients admitted to the Hospital of the Metropolitan Area of San Juan in the period of January 1,2009 to December 31, 2010 with diagnosis of preterm labor. A total of 382 patient's records were evaluated for inclusion and exclusion criteria. 48 met all the requirements to be included in the study. RESULTS: There were 68.8% patients who successfully completed the 48 hours postponement of labor required to administer corticosteroid therapy for fetal lung maturation. Risk factors for preterm labor commonly observed in the study group were urinary tract infection (60.4%), previous preterm labor (43.8%), multiple gestations (12.5%), and preterm premature rupture of membranes (10.4%). DISCUSSION: The use of Nifedipine therapy in patients with preterm labor between 24-34 weeks of gestational age can be effective in the postponement of labor for 48 hours so that the patient can receive corticosteroid fetal lung maturation therapy. The most common risk factor observed in this group of patients with preterm labor was urinary tract infection.

Effects of sildenafil on the fetal growth of guinea pigs and their ability to survive induced intrapartum asphyxia.

OBJECTIVE: Our goal was to determine whether sildenafil increased fetal weight and favored fetal tolerance to induced asphyxia at birth in guinea pigs. STUDY DESIGN: Twenty guinea pigs were randomly allocated to placebo (n = 10) or sildenafil 50 microg/kg (n = 5) or 500 microg/kg (n = 5), starting from day 35 of gestation to delivery. Fetuses were delivered by cesarean section. Fetal asphyxia was induced by clamping the umbilical cord at birth for 5 minutes. RESULTS: Sildenafil protected the pups against induced asphyxia at birth in a dose-dependent manner (eg, partial pressure (tension) of carbon dioxide levels were 75.9 +/- 19.3, 66.9 +/- 18.8, and 54.8 +/- 13.0 in the control and low- and high-dose sildenafil groups, respectively). The high-dose sildenafil group of piglets gained 1.5 times more body weight. CONCLUSION: In guinea pigs, low doses of sildenafil administered from day 35 to the end of gestation favored fetal tolerability to induced intrapartum asphyxia. High doses of sildenafil increased fetal weight.

[Fetal lung maturity delayed on diabetic pregnancies]. / Retraso en la madurez pulmonar fetal en embarazadas complicadas con diabetes gestacional.

OBJECTIVE: To determine the fetal lung maturity in a group of pregnant patients complicated by gestational diabetes or impaired glucose tolerance, metabolic controlled patients, as well as to identify the modifications of the phospholipids lung profile by effect of antenatal steroids. PATIENTS AND METHODS: 231 pregnant patients were included in an observational, longitudinal, clinical and descriptive study from January 1st 2000 to April 30th 2003. All those included presented gestational diabetes or impaired glucose tolerance according to the criteria of Carpenter. The metabolic control was demonstrated by means of glycosylated hemoglobin figures minor to 6.5%, and glucose monitoring (<95 mg/dL before meals and < 120 mg/dL two hours after each meal). The amniocentesis was performed just before the use of antenatal steroids and 48 hours after. The phospholipids lung profile was performed applying the Hallman and Kulovich method. RESULTS: By means of the Student's t-test non significant results were obtained for the general characteristics of both groups, except for the evolution of the phospholipids lung profile in the post-treatment group with antenatal steroids. As for the evolution of the fractions in the profile of the weekly phospholipids, an ANOVA test was applied with a p < 0.001 coefficient of statistical significance for the phosphatidylglycerol fraction. CONCLUSIONS: Delay of fetal lung maturity was shown in all the fractions of the phospholipids lung profile. In the group of patients with pregnancies of 36 weeks or more there was shown no correspondence among gestational age and the state of fetal lung maturity (60.75%), in comparison to that reported in existing literature. There were not reported cases of respiratory distress syndrome in the newborns.

[Prenatal corticoid therapy in hypertensive syndromes of pregnancies and its effects in maternal blood pressure]. / Corticoterapia pré-natal nas síndromes hipertensivas da gestação e seus efeitos na pressão arterial materna.

PURPOSE: To evaluate the behaviour of blood pressure among hypertensive pregnants during glucocorticoid therapy (LIGGINS scheme) in order to accelerate the maturity of fetal lung. METHODS: In a retrospective study, 27 pregnant with a story of hypertensive disorder, between 24 and 34 weeks, during glucocorticoid cycle were avaluated. For this matter, statistical analisis were performed using the means of systolic (SBP) and diastolic blood pressure during the therapy days, on the day before and on the day after. The results were statistically analyzed with F statistic test ( significant if p<005) RESULTS: There was no statistical variance in blood pressure levels, neither in SBP nor in DBP. There was no difficulty in clinical controls and no change in antihypertensive drugs related to glucocorticoid therapy. CONCLUSIONS: Our results show observe the safety of glucocorticoid therapy among pregnant women with hypertensive disorders related to the possible raising of the blood pressure levels.

[The induction of fetal lung maturity in pre-eclampsia]. / Inducción de madurez pulmonar fetal en preeclampsia.

The consensus of the world literature shows that the prematurity is the first cause of perinatal morbidity and mortality. In this period several are the complications to short and long term that they can be presented, but seems be that it is the respiratory distress syndrome (RDS) the principal cause of this problems. This syndrome is frequent in the neonate of mothers with severe preeclampsia of early appearance in which exists the need of interruption the pregnancy. There are some articles, that show that preeclampsia by itself or the steroids given antenatally to the mother may accelerated the fetal lung maturity. The objective of the present study was analyze the behavior of the phospholipids responsible for the fetal lung maturity in amniotic fluid, with the administration of steroids to mothers with preeclampsia, and its correlation with the presentation of the RDS in the RDS in the newborn. 31 patients were included in the study, all of them with severe preeclampsia without complications, between 28 and 33 weeks of pregnancy. Twenty one patients received 12 mg of betametasone i.m. in 2 doses one each day (Group 1) and 10 patients who did not receive the steroid (Group 2). All the births were by cesarean section, amniocentesis was done during this procedure. The relation L/E > or = were observed in 81% of the patients of group 1. In the group 2 the relation L/E < or = 2 were observed in 80% of the cases. The RDS was present in 47% of the neonates in Group 1 and in 100% of the group that did not receive betametasone (p 0.004). The perinatal mortality (20%) was present only in the that did not receive betametasone. The findings of the present paper shows that the administration of betametasone in patients with severe preeclampsia accelerated the fetal lung maturity more the disease in consequence the frequency and severity of the RDS were less.

The effects of prenatal intraamniotic surfactant or dexamethasone administration on lung development are comparable to changes induced by tracheal ligation in an animal model of congenital diaphragmatic hernia: studies of lung glycogen content, elastic fiber density, and collagen content.

BACKGROUND/PURPOSE: A new noninvasive therapeutic strategy, which consisted of prenatal intraamniotic administration of porcine surfactant or dexamethasone, was previously used to prevent the functional and structural immaturity of lungs associated with congenital diaphragmatic hernia (CDH), and its effects on lung development were comparable with the changes induced by tracheal ligation (TL). The purpose of this study is to verify if this novel therapeutic modality has any effect in the elevated concentration of lung glycogen and altered contents of lung elastic fiber and collagen promoted by CDH. METHODS: A pilot study was performed to investigate in the rabbit model if the infused drugs in the amniotic cavity were aspirated by the CDH and non-CDH fetuses, and if there was correspondence between lung immaturity and high glycogen concentration in lung tissue. Experimental groups consisted of 50 pregnant rabbits that underwent surgery on gestational day 24 or 25 to create left-sided diaphragmatic hernias in 56 fetuses, which were divided in groups according to the procedures: CDH (n = 12), CDH plus TL (n = 16), CDH plus intraamniotic administration of Curosurf (40 mg, n = 12), and CDH plus intraamniotic administration of dexamethasone (n = 16). On gestational day 30, the fetuses were delivered by cesarean section, and 28 normal unoperated fetuses served as controls. The lungs were weighed and submitted to biochemical determination of glycogen, morphometric evaluation of elastic fibers, and colorimetric analysis of collagen. RESULTS: In all CDH and non-CDH fetuses of the pilot study, the amniotic content was massively aspirated into the lungs and trachea. There was an increase in lung glycogen content of fetuses at 24 days' gestation in comparison with 20-day gestational age fetuses, followed by a decrease in the near full-term fetuses. In the fetuses of the experimental groups, CDH decreased the lung weight to body weight ratios of lungs ipsilateral to the hernia. These changes were reversed by TL but not by intraamniotic administration of surfactant or dexamethasone. Lung glycogen concentrations in the lungs of CDH fetuses were significantly higher than those in the control group. These changes were reversed by intraamniotic administration of surfactant but not by dexamethasone administration or TL. In the lungs ipsilateral to the hernia, surfactant administration promoted a significant decrease in glycogen content to levels lower than control lungs. CDH promoted a decrease in the linear density of elastic fibers in both lungs, ipsilateral and contralateral to the hernia. This alteration was partially corrected by TL and surfactant administration, although dexamethasone administration had no effect. The concentrations of collagen in both lungs were increased significantly by CDH, and these alterations could not be reversed by TL. In the lungs ipsilateral to the hernia, intraamniotic administration of surfactant or dexamethasone promoted a significant decrease in the lung concentration of collagen but not to control levels. CONCLUSIONS: The positive effects of intraamniotic surfactant or dexamethasone administration on lung maturity of fetuses with CDH were observed. This therapy may be a substitute for TL.

Extensión del uso prenatal de corticoides para la inducción de la madurez pulmonar fetal / Extension of the prenatal use of corticoids for the fetal lung maturation

Al no hallar datos de nuestro país acerca de la extensión del uso prenatal de corticoides para la inducción de la madurez pulmonar fetal, nos propusimos efectuar una encuesta con un diseño de observación descriptiva, aprovechando las actividades docentes de nuestro grupo, tomando nota además, del nivel de capacitación de los profesionales consultados. Se interrogó acerca del uso rutinario o no de corticoides solos o asociados con TRH en 4 situaciones clínicas: amenaza de parto prematuro y rotura prematura de membranas antes de las 30 semanas de gestación y entre las 30 y 34 semanas. También se dieron 3 opciones para justificar el uso no rutinario. Fueron obtenidas 101 respuestas. En la amenaza de parto prematuro el uso rutinario alcanzó casi el 85 por ciento, mientras que en la rotura prematura de membranas varió entre el 58 por ciento y el 63 por ciento según la edad gestacional. Tanto en la amenaza de parto prematuro como en la rotura prematura de membranas la frecuencia de asociación corticoides-TRH fue significativamente mayor en el grupo menor de 30 semanas con respecto al grupo entre 30 y 34 semanas, siendo el principal argumento para no usarlo sistemáticamente la carencia de efecto beneficioso (AU)

El uso de inductores de la maduración pulmonar en pacientes con trabajo de parto prematuro / The use of inducers of pulmonary maturity in patients with premature birth labor

La prematuridad constituye en la actualidad un serio problema de salud pública (10,2 por ciento ). Fue responsable de un número elevado de muertes neonatales hasta 1972, cuando Liggings y Howie observaron que administrando esteroides a la madre disminuyó la incidencia de distrés respiratorio. Se quiere demostrar la eficacia de los inductores de la madurez pulmonar en pacientes con trabajo de parto prematuro entre 32 y 34 semanas. Se tomaron 100 historias de pacientes con la característica mencionada excluyéndose la que tenian patología de base asociada, de las cuales 42 recibieron tratamiento (Dexametasona, Aminofilina e Hidrocortisona) y 58 control sin tratamiento. Se inicia la observación con número de gesta y parto prematuro, donde la mayoría tenia entre I y II gestas (57 por ciento ), los recién nacidos en general presentaron Apgar al minuto mayor o igual a 6 (33 por ciento ) y a los cinco no hubo con menor de seis. El parto eutócico con episiotomía amplia es la mejor vía de terminación del embarazo. El apgar al minuto no varía cuando recibe tratamiento (15 por ciento ) o no (18 por ciento ). Cuando se comparó la Dexametasona con el grupo control fue de 16,17 por ciento (x2 = 1.10), en la Hidrocortisona y la Aminofilina la diferencia fue de 1,1 por ciento (x2 = 1.05) y 8,9 por ciento (x2 = 0,43) respectivamente. No fue significativa la diferencia (p > 7.8). Un 25 por ciento de neonatos pretérmino con peso menor o igual a 2.5 kg no presentaron SDR a pesar de no haber recibido tratamiento, encontrándose una diferencia del 6 por ciento con respecto a los que lo recibieron, con dilatación menor o igual a 5 cm; esto es indicativo de que no es suficiente tiempo para que los inductores tengan efecto. En la ruptura prematura los inductores no producen una disminución significativa del SDR por tanto no hay necesidad de indicarlos. Las complicaciones más frecuentes de los recién nacidos fueron: riesgo de infección (14 por ciento ), ictericia (7 por ciento ), síndrome de membrana hialina (6 por ciento ), mal formación congénita (2 por ciento ) y se presentaron 2 muertes perinatales. No se reportaron complicaciones maternas. Se concluye que no se recibe ningún beneficio con la administración de inductores de la madurez pulmonar a madres en trabajo de parto prematuro espóntáneo donde el nacimiento sea antes de las 24 horas. Se recomienda usar con ciertas condiciones

Effects of a protein-free, synthetic surfactant on survival and pulmonary function in preterm lambs.

We have created a totally synthetic, protein-free surfactant (Exosurf) composed of dipalmitoylphosphatidylcholine, hexadecanol, and tyloxapol. We studied the effects of endotracheal instillation of Exosurf on survival and pulmonary function of preterm lambs delivered at 131 to 133 days gestation (term 148 days). Exosurf treatment was compared with instillation of surface-active material prepared from lung lavages of adult sheep and with no instillation. Lambs were delivered by cesarean section, paralyzed, and mechanically ventilated. The Exosurf group survived longer (80% alive at 11 hours) than did the no instillation group (30% alive at 11 hours) (P less than 0.05). There were no statistically significant differences between the Exosurf and sheep surfactant groups. We conclude that Exosurf, a synthetic surfactant, produces significant improvement in survival and pulmonary function in preterm lambs.