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Prevención del Parto Prematuro

1.- Recomendación / Juicio del Panel y Evidencia

1. En embarazadas menores de 16 semanas de edad gestacional con aumento de riesgo de parto prematuro por indicación médica, el Ministerio de Salud RECOMIENDA USAR aspirina (100-150 mg) por sobre no utilizarla.
Comentarios del Panel de Expertos:
La definición de aumento del riesgo de parto prematuro que se utilice para aplicar esta recomendación debe considerar los siguientes antecedentes de las 11-14 SEMANAS si están disponibles:
►Clínicas, tales como pre eclampsia o restricción de crecimiento intrauterino en embarazo previo, enfermedades renales, trombofilias, índice masa corporal elevado, aumento de la presión arterial, etc.
►Biofísicas, tales como el aumento de resistencia de arterias uterinas y presión arterial media.
►Bioquímicas, tales como factor de crecimiento placentario o Proteína plasmática asociada al embarazo.

El Panel de Expertos analizó y debatió cada uno de las preguntas de la “Tabla de la evidencia a la decisión”, considerando tanto la evidencia de investigación, experiencia clínica, conocimiento de gestión o experiencia de los pacientes. Una vez consensuada la postura del panel respecto a las preguntas, emitieron un juicio seleccionando la opción de respuesta que mejor representaba la opinión del conjunto (destacada con color). Finalmente cuando el panel emitió su juicio sobre todas las preguntas, se emitió la recomendación.

A continuación se presenta la “Tabla de la evidencia a la decisión” con el resumen de los juicios, la evidencia de investigación evaluada, consideraciones adicionales y comentarios planteados por el panel.

 1.- ¿El problema es una prioridad?
No Probablemente no Probablemente sí Varía No lo sé

El problema ha sido definido como prioritario en el marco de las Garantías Explícitas en Salud (GES), régimen integral de salud que prioriza un grupo de patologías o problemas de salud, garantizando el acceso a tratamiento oportuno y de calidad.

 2.- ¿Qué tan significativos son los efectos deseables anticipados?
Trivial Pequeño Moderado Grande Varía No lo sé

Grandes: El panel de expertos consideró que los efectos deseables de usar bevacizumab son grandes, en función de la evidencia de investigación, experiencia clínica, conocimiento de gestión o experiencia de los pacientes.

Evidencia de investigación

Tabla de Resumen de Resultados (Summary of Findings)

Aspirina precoz en mujeres con alto riesgo de parto prematuro

Pacientes

Mujeres embarazadas con alto riesgo de parto prematuro

Intervención

Aspirina

Comparación

Placebo

Desenlaces

Efecto relativo

(IC 95%)

Efecto absoluto estimado*

Certeza de la evidencia

(GRADE)

Mensajes clave en términos sencillos

SIN

aspirina

CON

aspirina

Diferencia

(IC 95%)

Hipertensión gestacional

RR 0,54

(0,41 a 0,70)

(12 ensayos/ 838
pacientes) [12]

287
por 1000

155

por 1000

Diferencia: 132 pacientes menos por 1000

(169 menos 86 a menos)

⊕⊕⊕⊕3

Alta

La aspirina disminuye la incidencia de hipertensión gestacional.

Eclampsia

RR 0,94

(0,59 a 1,48)

(9 ensayos/ 22584
pacientes) [12]

3
por 1000

3
por 1000

Diferencia: 0 pacientes por 1000

(1 menos a 2 más)

⊕⊕◯◯1,2,3

Baja

La aspirina podría tener poco o nulo efecto en la incidencia de eclampsia

Mortalidad materna

RR 2,57

(0,39 a 17,06)

(3 ensayos/ 12709
pacientes) [12]

0
por 1000

0
por 1000

Diferencia: 0 pacientes por 1000

(0 a 3 más)

⊕⊕⊕◯1,3

Moderada

El uso de aspirina probablemente no impacta en la mortalidad materna

Parto prematuro
(< 37 semanas)

RR 0,89

(0,81 a 0,97)

(10 ensayos/ 3252
pacientes) [12]

381
por 1000

339
por 1000

Diferencia: 42 pacientes menos por 1000

(72 menos a11 menos)

⊕⊕⊕⊕3

Alta

La aspirina disminuye la incidencia de parto prematuro

Mortalidad neonatal y fetal

RR 0,69

(0,53 a 0,90)

(17 ensayos/ 4443
pacientes) [12]

58
por 1000

40
por 1000

Diferencia: 18 pacientes menos por 1000

(27 menos a 6 menos)

⊕⊕⊕⊕3

Alta

La aspirina disminuye la mortalidad neonatal y fetal

IC 95%: Intervalo de confianza del 95%.
RR: Riesgo relativo.
GRADE: grados de evidencia del GRADE Working Group (ver más adelante).
*Los riesgos SIN aspirina están basados en los riesgos del grupo control en los estudios. El riesgo CON aspirina (y su intervalo de confianza) está calculado a partir del efecto relativo (y su intervalo de confianza).
1 Se disminuyó un nivel de certeza de evidencia por indirecta, ya que el estimador de efecto proviene de la población de cualquier mujer embarazada y no exclusivamente de mujeres de alto riesgo, escenarios que el panel de expertos considera diferentes.
2 Se disminuyó un nivel de certeza de evidencia por imprecisión ya que a cada extremo del intervalo de confianza pudiese conllevar una decisión diferente.
3 Se decidió no disminuir certeza de evidencia por riesgo de sesgo, pese a que algunos ensayos presentaban secuencia de aleatorización no clara, ya que la mayoría de los ensayos grandes presentaban menor sesgo.
Fecha de elaboración de la tabla: 8 de Mayo de 2018

Referencia

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103. Jamaica 1998. Unpublished

Búsqueda y Síntesis de Evidencia

 3.- ¿Qué tan significativos son los efectos indeseables anticipados?
Grande Moderado Pequeño Trivial Varía No lo sé

Pequeños: El panel de expertos consideró que los efectos indeseables de usar aspirina de dosis baja son pequeños, en función de la evidencia de investigación, experiencia clínica, conocimiento de gestión o experiencia de los pacientes.

Evidencia de investigación

Tabla de Resumen de Resultados (Summary of Findings)

Aspirina precoz en mujeres con alto riesgo de parto prematuro

Pacientes

Mujeres embarazadas con alto riesgo de parto prematuro

Intervención

Aspirina

Comparación

Placebo

Desenlaces

Efecto relativo

(IC 95%)

Efecto absoluto estimado*

Certeza de la evidencia

(GRADE)

Mensajes clave en términos sencillos

SIN

aspirina

CON

aspirina

Diferencia

(IC 95%)

Hipertensión gestacional

RR 0,54

(0,41 a 0,70)

(12 ensayos/ 838
pacientes) [12]

287
por 1000

155

por 1000

Diferencia: 132 pacientes menos por 1000

(169 menos 86 a menos)

⊕⊕⊕⊕3

Alta

La aspirina disminuye la incidencia de hipertensión gestacional.

Eclampsia

RR 0,94

(0,59 a 1,48)

(9 ensayos/ 22584
pacientes) [12]

3
por 1000

3
por 1000

Diferencia: 0 pacientes por 1000

(1 menos a 2 más)

⊕⊕◯◯1,2,3

Baja

La aspirina podría tener poco o nulo efecto en la incidencia de eclampsia

Mortalidad materna

RR 2,57

(0,39 a 17,06)

(3 ensayos/ 12709
pacientes) [12]

0
por 1000

0
por 1000

Diferencia: 0 pacientes por 1000

(0 a 3 más)

⊕⊕⊕◯1,3

Moderada

El uso de aspirina probablemente no impacta en la mortalidad materna

Parto prematuro
(< 37 semanas)

RR 0,89

(0,81 a 0,97)

(10 ensayos/ 3252
pacientes) [12]

381
por 1000

339
por 1000

Diferencia: 42 pacientes menos por 1000

(72 menos a11 menos)

⊕⊕⊕⊕3

Alta

La aspirina disminuye la incidencia de parto prematuro

Mortalidad neonatal y fetal

RR 0,69

(0,53 a 0,90)

(17 ensayos/ 4443
pacientes) [12]

58
por 1000

40
por 1000

Diferencia: 18 pacientes menos por 1000

(27 menos a 6 menos)

⊕⊕⊕⊕3

Alta

La aspirina disminuye la mortalidad neonatal y fetal

IC 95%: Intervalo de confianza del 95%.
RR: Riesgo relativo.
GRADE: grados de evidencia del GRADE Working Group (ver más adelante).
*Los riesgos SIN aspirina están basados en los riesgos del grupo control en los estudios. El riesgo CON aspirina (y su intervalo de confianza) está calculado a partir del efecto relativo (y su intervalo de confianza).
1 Se disminuyó un nivel de certeza de evidencia por indirecta, ya que el estimador de efecto proviene de la población de cualquier mujer embarazada y no exclusivamente de mujeres de alto riesgo, escenarios que el panel de expertos considera diferentes.
2 Se disminuyó un nivel de certeza de evidencia por imprecisión ya que a cada extremo del intervalo de confianza pudiese conllevar una decisión diferente.
3 Se decidió no disminuir certeza de evidencia por riesgo de sesgo, pese a que algunos ensayos presentaban secuencia de aleatorización no clara, ya que la mayoría de los ensayos grandes presentaban menor sesgo.
Fecha de elaboración de la tabla: 8 de Mayo de 2018

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83. Fan CF, Song M.. A small dose of aspirin for prevention of preeclampsia. Chinese Journal of Birth Health and Heredity.. 2005;13:68–69
84. Mesdaghinia, Elaheh, Talari, Hamidreza, Abedzadeh-Kalahroudi, Masomeh. Effect of aspirin for prevention of preeclampsia in women with abnormal ultrasonic findings in uterine artery. Feyz Journals of Kashan University of Medical Sciences. 2011;15(2):98-104
85. Dekker, GA. Prediction and prevention of pregnancy-induced hypertensive disorders: a clinical and pathophysiologic study. [MD thesis]. Rotterdam, The Netherlands: University Medical School. 1989;:91-102
86. Shenoy S, Chandrika D, Pisharody R. RCT of low dose aspirin to prevent the progression of pregnancy induced hypertension grade A to B. Journal of Clinical Epidemiology. 1999;52(Suppl 1):28S
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Búsqueda y Síntesis de Evidencia

 4.- ¿Cuál es la certeza general de la evidencia sobre efectos?
Muy baja Baja Moderada Alta Ningún estido incluído

Moderada: Existe confianza respecto del efecto de usar aspirina de dosis baja.

Evidencia de investigación

Desenlaces (Outcomes)

Importancia

Certeza de la evidencia
(GRADE)

Parto prematuro

CRITICAL

⨁⨁⨁◯
MODERATEa

Mortalidad perinatal

CRITICAL

⨁⨁⨁◯
MODERATEa

Pre-eclampsia

CRITICAL

⨁⨁⨁⨁
HIGHa

a. El funnel plot de revisiones que han analizado un conjunto mayor de ensayos (inicio AAS antes de las 16 semanas por cualquier causa) es asimetrico

 5.- ¿Hay incertidumbre importante o variabilidad sobre qué tanto valora la gente los desenlaces principales?
Incertidumbre o variabilidad importantes Posiblemente hay incertidumbre o variabilidad importantes Probablemente no hay incertidumbre ni variabilidad importantes No hay variabilidad o incertidumbre importante

No hay variabilidad o incertidumbre importante: El panel de expertos consideró que no existe variabilidad o incertidumbre importante respecto a lo que la mayoría de los pacientes podrían llegar a elegir, en función de la evidencia de investigación, experiencia clínica, conocimiento de gestión o experiencia de los pacientes.

Evidencia de investigación

No se encontraron estudios que abordaran valores y preferencias de los pacientes respecto de esta pregunta.
• Estudio canadiense (n=220) y australiano (n=345) basado en pacientes con discapacidad visual debido con edema macular diabético, agregaron un tercer grupo con ranibizumab+láser. Ambos observaron que a los 12 meses los grupos con ranibizumab presentaban mayor mejoría en la escala VFQ-25 que el grupos láser (p<0,05) (2,3). Respecto a la percepción del paciente respecto a su vista postratamiento, al mes 12 el 46% del grupo de ranibizumab y el 50% del grupo láser+ranibizumab indicaron que valoraban su visión como excelente o buena, mejorando en relación al 21% y 23% de la medición inicial. Por otro lado, el 24% del grupo con monoterapia de láser indicaron estas categorías a los 12 meses, siendo levemente mejor al resultado inicial de un 22% (3).

Búsqueda y Síntesis de Evidencia

 6.- El balance entre efectos deseables e indeseables favorece la intervención o la comparación?
Favorece la comparación Probablemente favorece la comparación No favorece la intervención ni la comparación Probablemente favorece la intervención Favorece la intervención Varía No lo sé

Favorece la intervención: Considerando que la intervención es “usar aspirina de dosis baja” y la comparación es “no usar”, el panel de experto opinó que el balance entre efectos deseables e indeseables claramente favorece usar aspirina de dosis baja.

 7.- ¿Qué tan grandes son los recursos necesarios (costos)?
Costos extensos Costos moderados Costos y ahorros despreciables Ahorros moderados Ahorros extensos Varía No lo sé

Costos y ahorros despreciables: El panel de expertos consideró que para implementar la intervención usar aspirina de dosis baja no implica ni recursos ni ahorros significativos, en función de los antecedentes recolectados, experiencia clínica, conocimiento de gestión o experiencia de los pacientes.

Evidencia de investigación

Aspirina 100mg
Valor comprimido mercado público $4,8 (x30): $144
Valor comprimido privado (IMS Health) $67 (x30): $2.100

Búsqueda y Síntesis de Evidencia

 8.- ¿La costo-efectividad de la intervención beneficia la intervención o la comparación?
Favorece la comparación Probablemente favorece la comparación No favorece la intervención ni la comparación Probablemente favorece la intervención Favorece la intervención Varía Ningún estudio incluido

Favorece la intervención: Considerando que la intervención es “usar aspirina de dosis baja” y la comparación es “no usar”, el panel de experto opinó que claramente la alternativa más costo-efectiva es usar aspirina de dosis baja.

Evidencia de investigación

No se encontraron estudios de costo efectividad

Búsqueda y Síntesis de Evidencia

 9.- ¿Cuál sería el impacto en equidad en salud?
Reducido Probablemente reducido Probablemente ningún impacto Probablemente aumentado Aumentado Varía No lo sé

Aumentada: El panel de expertos consideró que la equidad en salud aumentaría, dado que se identificó grupos o contextos desaventajados que podrían mejorar su situación si se recomendase la intervención usar aspirina de dosis baja.

 10.- ¿La intervención es aceptable para las partes interesadas?
No Probablemente no Probablemente sí Varía No lo sé

Sí: El panel de expertos consideró que usar aspirina de dosis baja SÍ es aceptable para las partes interesadas (profesionales de la salud, gestores de centros de salud, directivos servicios de salud, pacientes, cuidadores, seguros de salud, otros).

 11.- ¿Es factible implementar la intervención?
No Probablemente no Probablemente sí Varía No lo sé

Sí: El panel de expertos consideró que usar aspirina de dosis baja SÍ es factible implementar, contemplando la capacidad de la red asistencial, los recursos humanos disponibles a nivel país, recursos financieros, preferencias de los pacientes, etc.