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. Women 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 4733 women who remained at risk of early birth more than seven days after an initial course of corticosteroids and 5700 babies between 23 and 34 weeks' gestation at trial enrolment 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.

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.    

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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 strategy: 

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 January 2015), 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 (a total of 4733 women and 5700 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, number needed to treat to benefit (NNTB) 17, 95% CI 11 to 32) and serious infant outcome (RR 0.84, 95% CI 0.75 to 0.94, seven trials, 5094 infants, NNTB 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. In women, for the two primary outcomes, there was no increase in infectious morbidity of chorioamnionitis or puerperal sepsis, and the likelihood of a caesarean birth was unchanged.