Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes

 

Abstract

Background

It has been unclear whether repeat dose(s) of prenatal corticosteroids are beneficial.

Objectives

To assess the effectiveness and safety of repeat dose(s) of prenatal corticosteroids.

Search methods

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2011), searched reference lists of retrieved studies and contacted authors for further data.

Selection criteria

Randomised controlled trials of women who had already received a single course of corticosteroids seven or more days previously and considered still at risk of preterm birth.

Data collection and analysis

We assessed trial quality and extracted data independently.

Main results

We included 10 trials (more than 4730 women and 5650 babies) with low to moderate risk of bias. Treatment of women who remain at risk of preterm birth seven or more days after an initial course of prenatal corticosteroids with repeat dose(s), compared with no repeat corticosteroid treatment, reduced the risk of their infants experiencing the primary outcomes respiratory distress syndrome (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.75 to 0.91, eight trials, 3206 infants, numbers needed to treat (NNT) 17, 95% CI 11 to 32) and serious infant outcome (RR 0.84, 95% CI 0.75 to 0.94, seven trials, 5094 infants, NNT 30, 95% CI 19 to 79).

Treatment with repeat dose(s) of corticosteroid was associated with a reduction in mean birthweight (mean difference (MD) -75.79 g, 95% CI -117.63 to -33.96, nine trials, 5626 infants). However, outcomes that adjusted birthweight for gestational age (birthweight Z scores, birthweight multiples of the median and small-for-gestational age) did not differ between treatment groups.

At early childhood follow-up no statistically significant differences were seen for infants exposed to repeat prenatal corticosteroids compared with unexposed infants for the primary outcomes (total deaths; survival free of any disability or major disability; disability; or serious outcome) or in the secondary outcome growth assessments.

Authors' conclusions

The short-term benefits for babies of less respiratory distress and fewer serious health problems in the first few weeks after birth support the use of repeat dose(s) of prenatal corticosteroids for women still at risk of preterm birth seven days or more after an initial course. These benefits were associated with a small reduction in size at birth. The current available evidence reassuringly shows no significant harm in early childhood, although no benefit.

Further research is needed on the long-term benefits and risks for the woman and baby. Individual patient data meta-analysis may clarify how to maximise benefit and minimise harm.    

 

Plain language summary

Repeat doses of prenatal corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease

This review shows that a repeat dose of prenatal corticosteroids given to women who remain at risk of an early birth after an initial course of prenatal corticosteroids helps the baby's lungs and reduces serious health problems in the first few weeks of life.

Infants born preterm (before 37 weeks' gestation) are at risk of difficulty breathing and lung disease because their lungs are not fully developed. Woman at risk of preterm birth include those with ruptured membranes, antepartum haemorrhage, preterm labour, cervical incompetence, pre-eclampsia or multiple pregnancy. Preterm babies who survive the early weeks of life are also at risk of long-term neurological disabilities such as epilepsy and cerebral palsy. A single course of corticosteroids, given to women who may give birth early, helps develop the baby's lungs. This benefit does not last beyond seven days. This review of 10 randomised controlled trials, involving more than 4730 women who remained at risk of early birth more than seven days after an initial course of corticosteroids and 5650 babies between 23 and 34 weeks' gestation showed that repeat dose(s) of prenatal corticosteroids reduced the risk of the baby having breathing difficulties and serious health problems in the first few weeks of life. Some of the trials showed that the baby may be smaller at birth but not if adjusted for gestational age nor by the time of hospital discharge. In four trials that followed up the babies to early childhood, no long-term benefits or harms were seen at 18 months to two years' corrected age. Further research is needed on the long-term benefits and risks for the woman and baby, which should include later child health, growth and development.

Repeat prenatal corticosteroid treatment could increase the risk of infection and suppress pituitary-adrenal function for the mother and her baby. For the women, there was no increase in infectious morbidity of chorioamnionitis or puerperal sepsis, and the likelihood of a caesarean birth was unchanged.

Betamethasone was the only corticosteroid evaluated. It is uncertain whether the effects seen for betamethasone would be the same for dexamethasone.

 

Resumen

Antecedentes

Dosis repetidas de corticosteroides prenatales en mujeres en riesgo de parto prematuro para mejorar los resultados de salud neonatales

Todavía no está claro si la/s dosis repetida/s de corticosteroides prenatales son beneficiosas.

Objetivos

Evaluar la eficacia y la seguridad de la/s dosis repetida/s de corticosteroides prenatales.

Estrategia de búsqueda

Se hicieron búsquedas en el Registro de Ensayos del Grupo Cochrane de Embarazo y Parto (Cochrane Pregnancy and Childbirth Group) (31 marzo 2011) y en listas de referencias de estudios recuperados y se contactó con los autores para obtener datos adicionales.

Criterios de selección

Ensayos controlados aleatorios en mujeres que habían recibido un ciclo único de corticosteroides siete o más días anteriormente y todavía se consideraron en riesgo de parto prematuro.

Obtención y análisis de los datos

Se evaluó la calidad de los ensayos y se extrajeron los datos.

Resultados principales

Se incluyeron diez ensayos (más de 4730 mujeres y 5650 recién nacidos) con riesgo de sesgo de bajo a moderado. El tratamiento de las mujeres que permanecen en riesgo de parto prematuro siete o más días después de un ciclo inicial con corticosteroides prenatales con dosis repetida/s, en comparación con ningún tratamiento repetido con corticosteroides, redujo el riesgo de que sus lactantes presentaran los resultados primarios síndrome de dificultad respiratoria (cociente de riesgos [CR] 0,83; intervalo de confianza [IC] del 95%: 0,75 a 0,91; ocho ensayos, 3206 lactantes, número necesario a tratar [NNT] 17; IC del 95%: 11 a 32) y resultado neonatal grave (CR 0,84; IC del 95%: 0,75 a 0,94; siete ensayos, 5094 lactantes, NNT 30; IC del 95%: 19 a 79).

El tratamiento con dosis repetida/s de corticosteroides se asoció con una reducción en la media del peso al nacer (diferencia de medias [DM] −75,79; IC del 95%: −117,63 a −33,96; nueve ensayos, 5626 lactantes). Sin embargo, los resultados que se ajustaron al peso al nacer para la edad gestacional (puntuaciones Z del peso al nacer, múltiplos de la mediana del peso al nacer y tamaño pequeño para la edad gestacional) no difirieron entre los grupos de tratamiento.

Al seguimiento en la niñez temprana no se observaron diferencias estadísticamente significativas en los lactantes expuestos a dosis repetidas de corticosteroides prenatales en comparación con los lactantes no expuestos en cuanto los resultados primarios (muertes totales; supervivencia sin cualquier discapacidad o discapacidad grave; discapacidad; o resultado grave) ni en el resultado secundario evaluaciones del crecimiento.

Conclusiones de los autores

Los efectos beneficiosos a corto plazo en los recién nacidos de menor dificultad respiratoria y menores problemas de salud graves en las primeras semanas después del nacimiento apoya el uso de dosis repetida/s de corticosteroides prenatales en las mujeres que todavía presentan riesgo de parto prematuro siete días o más después de un ciclo inicial. Estos efectos beneficiosos se asociaron con una reducción pequeña de la talla al nacer. De forma confiable las pruebas disponibles en la actualidad no muestran efectos perjudiciales significativos en la niñez temprana, aunque tampoco muestran efectos beneficiosos.

Se necesitan estudios de investigación adicionales sobre los efectos beneficiosos y los riesgos a largo plazo para la mujer y el recién nacido. El metanálisis de datos de pacientes individuales puede aclarar cómo se pueden maximizar los efectos beneficiosos y reducir los efectos perjudiciales.

Traducción

Traducción realizada por el Centro Cochrane Iberoamericano