Frecuencia cardiaca y movimientos fetales posterior a la administracion de betametasona para maduración pulmonar fetal (Fetal heart rate and movements after betamethasone administrationfor fetal lung maturity)Yolima Ruiz-Lopez1, Keibis Jiménez-Castillejo1, Eduardo-Reyna Villasmil1, Duly Torres-Cepeda1, Joel Santos-Bolivar1, Jhoan Aragon-Charris1, Jorly Mejia-Montilla1, Nadia Reyna-Villasmil2.1 Servicio de Obstetricia y Ginecología, Maternidad “Dr. Nerio Belloso”, Hospital “Dr. Urquinaona”, Maracaibo - Venezuela.2 Centro de Investigaciones Endocrino-Metabólicas “Dr. Félix Gómez”, Maracaibo – Venezuela. [ARTICULO ORIGINAL]Recibido: 31 de Diciembre de 2012. Aceptado: 03 de Abril de 2013.ResumenEl objetivo de la investigación fue demostrar las modificaciones de la frecuencia cardiaca y los movimientos fetales producidas por la administración de betametasona para maduración pulmonar fetal. Se realizó una investigación de tipo explicativa, prospectiva y longitudinal con un diseño cuasi-experimental y una muestra no probabilística de 106 gestantes entre 24 y 34 semanas, con diagnóstico de amenaza de parto pretérmino tratadas con betametasona (12 mg intramuscular cada 24 horas por dos dosis) que acudieron al Hospital Central “Dr. Urquinaona”. Se evaluaron los movimientos fetales y frecuencia cardiaca materna y fetal. No se encontraron diferencias significativas en la frecuencia cardiaca materna comparado con los valores iniciales (p = ns). Se observó que el valor inicial de la frecuencia cardiaca fetal fue de 135,1±9,7 latidos por minuto para aumentar luego a 137,2±8,9 latidos por minuto (p = ns) para presentar un nuevo aumento hasta (142,9±9,9 latidos por minuto) que fue significativo comparado con los valores iniciales (p < 0,05). Se observó una disminución significativa de movimientos fetales medidos en 30 minutos después de la primera inyección (23,1±6,0 movimientos comparado con 14,8±7,0 movimientos), para aumentar después de la segunda inyección pero aun presentando valores significativamente más bajos comparado con los valores iniciales (20,0 ±6,7 movimientos; p < 0,05). Se concluye que la administración de betametasona para maduración pulmonar fetal produce incremento significativo en la frecuencia cardiaca y reducción marcada de los movimientos fetales.Palabras claveBetametasona, Maduración pulmonar, Movimientos fetales.AbstractThe objective of research was to demonstrate fetal heart rate and movements modifications by the use of betamethasone for fetal lung maturity. An explicative, prospective and longitudinal research was done with a quasi-experimental design and a non-probabilistic sample of 106 pregnant patients between 24 and 34 weeks treated with betamethasone (12 mg IM BID) that assisted to Hospital Central “Dr. Urquinaona.” Fetal movements, maternal and fetal heart rates were evaluated. There were not differences in materna heart rate compared with initial values (p = ns). There was observed that fetal heart rate initial values were 135.1±9.7 beats per minute and increases to 137.2±8.9 beats per minute (p = ns) and showed a new increase to 142.9±9.9 beats per minute that was significant compared with initial values (p < 0.05). There was observed a significant decrease in fetal movement measured in 30 minutes after first injection (23,1±6,0 movements compared with 14,8±7,0 movements), to increase after second injection but still were significant lower compared with initial values (20,0±6,7 movewments; p < 0.05). It is concluded that the use of betamethasone for induction of fetal lung maturity produced significant reduction in fetal movements and an increase of fetal heart rate.KeywordsBetamethasone, Lung maturity, Fetal movements.IntroducciónLa eficacia de la administración de corticosteroides prenatales para la inducción de la maduración pulmonar fetal ha sido ampliamente demostrada (1). Los esteroides más estudiados son la betametasona y la dexametasona, los cuales son ampliamente utilizados para este propósito debido a su alta capacidad para atravesar la placenta y su larga vida media (2). Estos dos compuestos son casi idénticos desde el punto de vista estructural, y solo difieren entre ellos en la posición alfa y beta del grupo metilo en la posición 16 (3).Varios estudios han sugerido que la administración de corticosteroides prenatales afecta la frecuencia cardiaca fetal (4). Sin embargo, efectos opuestos se han observado en respuesta a la betametasona cuando se compara con otros corticosteroides. Se ha encontrado que la betametasona induce modificaciones transitorias de la frecuencia cardiaca (5,6), número de desaceleraciones (5,7) y amplitud máxima de las aceleraciones (5). En algunos casos ocurre supresión marcada de la frecuencia cardiaca lo cual puede mal interpretarse como sufrimiento fetal (8). Esto produce un parto iatrogénico de un feto prematuro. Jellyman y col. (6) reportaron que algunos corticosteroides aumentan la variación de la frecuencia cardiaca.Debido a que la monitorización pre-parto de la frecuencia cardiaca fetal es una herramienta importante para la determinación del bienestar fetal, los efectos farmacológicos de los corticosteroides sobre los parámetros de la frecuencia cardiaca son importantes en la práctica clínica, por lo que el objetivo de la investigación fue demostrar las modificaciones de la frecuencia cardiaca y los movimientos fetales producidas por la administración de betametasona para maduración pulmonar fetal.MetodologíaLa investigación de este estudio fue explicativa, prospectiva y longitudinal con un diseño cuasi-experimental y una muestra no probabilística intencional de 106 pacientes que acudieron a la consulta prenatal de alto riesgo del Hospital Central “Dr. Urquinaona". El Comité de Ética del hospital aprobó la investigación y se obtuvo el consentimiento informado de todas las pacientes.Se incluyeron embarazadas entre 18 y 40 años de edad, con embarazos de 24 a 34 semanas de gestación un índice de masa corporal menor de 30 Kg/m2 y embarazos de alto riesgo que ameritaron la administración de betametasona para la inducción de la maduración pulmonar fetal. Se excluyeron las embarazadas con polihidramnios, hemorragia del tercer trimestre, sospecha de restricción del crecimiento intrauterino del feto (circunferencia cefálica, circunferencia abdominal y longitud del fémur menor del percentil 10 de referencia) (9), síndrome de HELLP, amenaza de parto pretérmino, alteraciones de la frecuencia cardiaca fetal, gestaciones múltiples, presencia de infección intrauterina o materna activa, enfermedad hipertensiva crónica o gestacional, enfermedad cardiaca, hepática, renal o sistémica crónica, diabetes mellitus pre o gestacional y hábito tabáquico. También se excluyeron a las pacientes que recibieron cualquier otro medicamento diferente a la vitaminoterapia y aquellas que se negaron a participar en la investigación. A todas las gestantes seleccionadas por los investigadores se les explicó el estudio y luego de su consentimiento, se les realizó la historia clínica integral, tomando en cuenta la anamnesis (fecha de la última regla, paridad, edad gestacional), examen físico (peso, talla, índice de masa corporal, frecuencia cardiaca, presión arterial y otros hallazgos) y el perfil biofísico. Una vez seleccionadas las pacientes se le administró inyecciones intramusculares de betametasona (12 mg) por dos días consecutivos. El índice de masa corporal (IMC) se calculó por el peso dividido por la talla al cuadrado (kg/m2).61Las mediciones de la frecuencia cardiaca y los movimientos fetales se realizaron en todas las pacientes entre las 12 m y las 6 pm tomando en cuenta el ritmo circadiano de la actividad biofísica del feto. Las mediciones de frecuencia cardiaca materna y fetal se realizaron en tres ocasiones: La primera, antes de la administración de la primera dosis de betametasona; la segunda, 24 horas después de la segunda y última inyección; y la tercera ocasión, siete días luego de la administración de la última dosis de betametasona para la maduración pulmonar fetal. Todas las pacientes fueron colocadas en posición supina, ligeramente lateralizada a la izquierda para evitar la hipotensión supina. La frecuencia cardiaca fue evaluada y analizada utilizando medios electrónicos (Sonicaid® BD4000xs). El sistema suministra información computarizada sobre la frecuencia cardiaca basal, aceleraciones y desaceleraciones y características de los episodios. Cada periodo de observación fue de 60 minutos. Posteriormente se realizó una evaluación ecográfica de 30 minutos usando un Ecógrafo General Electric® Logiq Pro 3 utilizando un transductor abdominal convexo. Fueron evaluados los movimientos del tronco, los miembros y respiratorios.Figura 2. Relación entre la frecuencia cardíaca fetal con respecto a las dosis de Betametasona.Los datos se expresaron como valores absolutos y relativos, y otros como media aritmética±desviación estándar y son presentados en tablas. Se utilizará la prueba de ANOVA con post-test de Dunnet tomando como control los valores iniciales. Se consideró p < 0,05 como nivel de confiabilidad estadística.ResultadosSe incluyeron 106 pacientes que fueron sometidas a inyecciones de betametasona para inducir la maduración pulmonar fetal. La edad promedio de las pacientes fue de 22,6±5,1 años y la edad gestacional al momento del tratamiento fue de 31,8±3,0 semanas. El IMC de las pacientes fue de 26,7±5,2 Kg/m2.Figura 1. Relación entre la frecuencia cardíaca materna con respecto a las dosis de Betametasona.En la tabla 1 se muestran los valores iniciales y las modificaciones de la frecuencia cardiaca materna, frecuencia cardiaca fetal y movimientos fetales. Con relación a la frecuencia cardiaca materna, se observó que el valor inicial fue de 87,5±8,3 latidos por minuto, luego de la inyección de la primera dosis de betametasona los valores fueron de 83,7±9,8 latidos por minuto y luego de la segunda inyección los valores promedio fueron de 85,4±10,6 latidos por minuto. No se encontraron diferencias significativas comparado con los valores iniciales (figura 1; p = ns). Al analizar la frecuencia cardiaca fetal (figura 2), se observó que el valor inicial fue de 135,1±9,7 latidos por minuto para aumentar luego a 137,2±8,9 latidos por minuto (p = ns) para presentar un nuevo aumento hasta 142,9±9,9 latidos por minuto que fue significativo comparado con los valores iniciales (p < 0,05). Con respecto a los valores de movimientos fetales medidos en 30 minutos (figura 3), el valor inicial fue de 23,1±6,0 movimientos para presentar una disminución significativa y alcanzar 14,8±7,0 movimientos después de la primera inyección, para presenta un ligero aumento después de la segunda inyección (20,0±6,7 movimientos) pero aun presentando valores significativamente más bajos comparado con los valores iniciales (p < 0,05).Al relacionar la frecuencia cardiaca materna con los movimientos fetales, se observó que en ninguno de los tres periodos existía una relación significativa entre estos dos parámetros (inicial r=0,091, luego de la primera inyección r=-0,110 y luego de la segunda inyección r=-0,275; p=ns).62Con respecto a las variaciones de la frecuencia cardiaca materna, frecuencia cardiaca fetal y movimientos fetales por índice de masa corporal de las embarazadas (tabla 2) y por semanas de gestación (tabla 3). No se observaron diferencias estadísticamente significativas en los valores promedio de las tres determinaciones en cada uno de los periodo de medición en las pacientes con índice de masa corporal <25 kg/m2, entre 25-29 kg/m2 y aquellas con >30 kg/m2 (p=ns). Tampoco se encontraron diferencias entre las pacientes con embarazos <30 semanas, aquellos entre 30 y 32 semanas y con las pacientes de >33 semanas (p=ns). Figura 3. Relación entre los movimientos detales con respecto a las dosis de Betametasona.DiscusiónEl principal hallazgo de la presente investigación es que la inyección de betametasona para la inducción de la maduración pulmonar fetal es que produce aumento en la frecuencia cardiaca fetal y una disminución transitoria de los movimientos fetales, elementos utilizados para la evaluación del bienestar fetal. 63Tabla 1. Modificaciones en la frecuencia cardiaca materna, Frecuencia cardiaca fetal y movimientos fetales.n=106PrimeraMedición(Antes de la primera dosis)SegundaMedición(24 horas después de la segunda dosis)TerceraMedición(7 días despuésde la segunda dosis)Frecuencia cardiaca materna,latidos por minuto87,5 +/- 8,384,7 +/- 9,885,4 +/- 10,6Frecuencia cardiaca fetal,latidos por min135,1 +/- 12,7137,2 +/- 18,9142,9 +/- 19,9*Movimientos fetalesen 30 minutos23,1 +/- 6,014,8 +/- 7,0*20,0 +/- 9,7* * p < 0,05 comparado con los valores iniciales.Los resultados de esta investigación son apoyados por las observaciones de de Heus y col. (7) quienes reportaron una disminución de los movimientos fetales, al igual que los movimientos respiratorios y la variabilidad de la frecuencia cardiaca fetal en respuesta a la betametasona. En contraste, Jellyman y col. (6) observaron un incremento de la variabilidad a corto plazo 2 días después de la inyección de corticosteroides. En esta investigación, no se encontró los efectos supresores de los corticosteroides sobre la frecuencia cardiaca fetal en las pacientes tratadas con betametasona, como se ha descrito para otros corticosteroides. De Heus y col. (7) propusieron que las diferencias entre sus hallazgos y los resultados de Jellyman y col. (6) no pueden ser explicadas por la administración de diferentes periodos de medición (periodos cortos o largos), respectivamente. En la presente investigación se observó el aumento de la frecuencia cardiaca, lo cual es contrario a lo descrito previamente.Las discrepancias entre los resultados de los tres estudios es particularmente sorprendente, debido a que investigaciones previas (6,7) y esta investigación es que en todos se utilizó análisis electrónico de la frecuencia cardiaca fetal y las tres poblaciones tenían edades gestacionales similares. Sin embargo, la población de un estudio fue única, ya que 21 de los 28 fetos fueron obtenidos por cesárea debido a sufrimiento fetal agudo (6). Estas características podrían sugerir que esos fetos estaban posiblemente enfrentando condiciones hipoxémicas al momento de la evaluación, lo cual puede posiblemente haber alterado las respuestas del sistema nervioso central a los esteroides.Los movimientos corporales y de los miembros (al igual que los movimientos respiratorios) presentaron una respuesta temporal diferente en relación a la exposición a la corticosteroides para lo descrito para la frecuencia cardiaca fetal (6,7). En efecto, este parámetro fue marcadamente afectado por el uso de la betametasona. Aunque se ha descrito que la respuesta a otros corticosteroides es menos pronunciada en comparación a la betametasona, la reducción de los movimientos en más de 50% después de la primera inyección y mayor del 15% después de la segunda inyección permitió establecer diferencias estadísticamente significativas al compararlo con los valores iniciales. Después de la primera inyección de betametasona, 5 fetos (10,8%) presentaron menos de 5 movimientos en 30 minutos. Cuando se analizó la relación de este hecho con la presencia de disminución de la frecuencia cardiaca fetal, se observó que ninguno de los 5 fetos presentó frecuencias cardiacas que podrían ser consideradas patológicas (< 120 latidos x min). Este hallazgo sobre los efectos supresores de la betametasona sobre los movimientos fetales puede ser debido a una susceptibilidad individual de algunos fetos a los efectos farmacológicos de los corticosteroides. Sin embargo, el tamaño muestral es muy pequeño para comprobar esa hipótesis. Se debe ser cuidadoso en este aspecto, ya que la observación 64Tabla 2. Modificaciones de la frecuencia cardiaca materna, frecuencia cardiaca fetal y movimientos fetales por indice de masa corporal.Índice de Masa Corporaln=106<25 kg/m2(n = 29)25 - 29 Kg/m2(n = 45)> 30 Kg/m2(n = 32)Frecuencia cardiaca materna,latidos por minuto.Primera mediciónSegunda mediciónTercera medición88,0±6,384,4±11,183,1±10,986,8±7,386,0±11,084,6± 9,184,5±7,984,9±10,583,5±12,2Frecuencia cardiaca fetal,latidos por min.Primera mediciónSegunda mediciónTercera medición137,0±15,7139,0±17,9145,5±21,5135,7±12,4133,7±17,3147,9±21,1132,6±12,1134,4±20,1140,3±20,1Movimientos fetalesen 30 minutos.Primera mediciónSegunda mediciónTercera medición24,2±5,616,4± 8,220,7±9,225,2±5,919,9±7,220,6±10,822,0±6,014,1±6,320,9±8,5de valores bajos de movimientos fetales, como parte del perfil biofísico fetal, puede llevar a una interrupción iatrogénica del embarazo.Solo se puede especular sobre los mecanismos por los cuales los corticosteroides causan modificaciones en la frecuencia cardiaca y en los movimientos fetales. Debido a que las actividades físicas y la frecuencia cardiaca están sujetas a un ritmo circadiano (10), es posible que la supresión del eje hipófisis - suprarrenal por la administración de esteroides exógenos afecte la variación diurna. La reactividad máxima de la frecuencia cardiaca y los movimientos fetales durante las últimas 10 semanas de gestación son generalmente observadas en las horas finales de la noche (4), cuando las concentraciones de corticosteroides tienden a ser más bajas. En un modelo de ovejas, los movimientos respiratorios fetales muestran una relación inversa con las concentraciones de ACTH fetal (11). Echeverria y col. (12) han propuesto que la baja actividad fetal en las horas de la mañana y la alta actividad fetal en las horas de la tarde se correlacionan inversamente con las concentraciones de cortisol. Debido a que los corticosteroides maternas atraviesan la placenta, se puede pensar en la existencia de una retroalimentación endocrina trans-placentaria de la actividad de la hipófisis - suprarrenal (12). Es posible, por lo tanto, que la modificación observada en la frecuencia cardiaca fetal y en los movimientos fetales posterior a la administración de corticosteroides refleje una exageración de los mecanismos endocrinos normales los cuales afectan los patrones de actividad fetal in utero.Tabla 3. Modificaciones de la frecuencia cardiaca materna, frecuencia cardiaca fetal y movimientos fetales por semana de gestación.Semanas de Gestaciónn=106< 30 semanas(n = 16)30 - 32 semanas(n = 49)> 33 semanas(n = 41)Frecuencia cardiaca materna,latidos por minuto.Primera mediciónSegunda mediciónTercera medición86,5 +/- 7,986,0 +/- 9,682,7 +/- 13,386,2 +/- 7,784,0 +/- 12,184,4 +/- 8,386,9 +/- 6,585,2 +/- 6,783,8 +/- 10,6Frecuencia cardiaca fetal,latidos por min.Primera mediciónSegunda mediciónTercera medición133,9 +/- 11,9139,9 +/- 18,4144,4 +/- 21,3136,4 +/- 14,3132,1 +/- 19,0147,3 +/- 22,1136,4 +/- 14,3132,1 +/- 19,0147,3 +/- 22,1Movimientos fetalesen 30 minutos.Primera mediciónSegunda mediciónTercera medición23,1 +/- 6,114,8 +/- 7,919,9 +/- 9,924,7 +/- 6,315,4 +/- 7,921,2 +/- 9,623,8 +/- 5,315,5 +/- 7,320,5 +/- 9,3Un mecanismo alternativo puede ser el efecto supresor directo de los corticosteroides sobre la actividad neural fetal. La betametasona rápidamente atraviesa la placenta (13) y los receptores de glucocorticoides se presentan en gran cantidad en el tejido cortical cerebral y los núcleos subcorticales, incluyendo las porciones medias del cerebro (3). La capacidad de los glucocorticoides sintéticos de suprimir la actividad neural también ha sido documentada. Es posible, que un efecto supresor cerebral sobre el sistema activador reticular y / o los centros funcionales del cerebro, afecte los estados conductuales del feto y por lo tanto afectar la frecuencia cardiaca fetal y los movimientos fetales. Aunque los estados conductuales fetales no están completamente organizados antes de las 36 semanas, los variables estados individuales pueden ser afectados por intervenciones farmacológicas (14).Las contracciones uterinas inducidas por los corticosteroides pueden ser también un mecanismo potencial para los cambios observados, al menos con relación a los movimientos fetales. Se ha demostrado un aumento en la actividad uterina posterior luego de la administración de betametasona intramuscular (15), y estas inyecciones son frecuentemente utilizadas en modelos animales con ovejas para iniciar el parto (16). La reducción o cese de los movimientos en respuesta a las contracciones parece solo ocurrir en la fase activa del parto y no durante la fase latente de este (17). Ninguna de las pacientes en la presente investigación estaba en fase activa del parto.Es probable que otros fármacos administrados a las pacientes con embarazos pre-términos induzcan las modificaciones en los movimientos fetales. Existen reportes que las pacientes tratadas con clorhidrato de isoxuprina u otros betamiméticos como tocolíticos junto con betametasona o dexametasona, generalmente no afectan las características de la frecuencia cardiaca fetal (18), ya que solamente producen elevación de la frecuencia cardiaca materna comparado con los valores iniciales (19). Más aún, los movimientos fetales tienden a aumentar, más que a disminuir, en respuesta a los betamiméticos (5).65También se debe considerar que los efectos producidos por la betametasona en esta investigación sobre la frecuencia cardiaca fetal y los movimientos fetales puede ser un verdadero sufrimiento fetal. Esta es una posibilidad poco probable, considerando la naturaleza transitoria de los efectos. Más aún, de Heus y col. (7) suministraron evidencia de valores normales de oxígeno fetal posterior a la administración de betametasona, demostrado por la ausencia de cambios en los movimientos oculares fetales. En un modelo animal, la hipoxia moderada o severa está generalmente asociada con disminución de los movimientos oculares fetales (1). La posibilidad que aparezca una verdadera hipoxia, por lo tanto, es poco probable pero no puede ser completamente excluida sin la realización de otras investigaciones.Desde el punto de vista práctico, sin embargo, los obstetras podrían enfrentarse ocasionalmente a fetos que muestran modificaciones de la frecuencia cardiaca y disminución de los movimientos corporales y respiratorios posterior a la administración de corticosteroides. Debido a que los corticosteroides suprimen componentes de dos de las más importantes herramientas para la determinación del bienestar fetal (el análisis de la frecuencia cardiaca fetal y el perfil biofísico), el diagnóstico diferencial entre efectos fisiopatológicos y farmacológicos puede ser extremadamente difícil. La forma óptima para la determinación del bienestar fetal bajo estas circunstancias aún debe ser determinada. 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Avan Biomed.Avan Biomed. 2013; 2(2): 60-7.Avances en BiomedicinaPublicación Oficial del Instituto de Inmunología ClínicaMérida-VenezuelaVolumen 2(2), May-Ago 2013, p 60-7Copyright: © ULA 2013Depósito Legal: PPI201102ME3935ISSN: 2244-7881Frecuencia cardíaca, movimientos fetales y betametasona. Ruiz-Lopez Y y col.Ruiz-Lopez Y y col. Frecuencia cardíaca, movimientos fetales y betametasonaiVBORw0KGgoAAAANSUhEUgAAAFkAAACCCAYAAAAt8mRDAAAAAXNSR0IArs4c6QAAAAlwSFlzAAAO
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