Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes
8 April 2016
When compared with placebo or no treatment, repeat doses of corticosteroids in women still at risk of preterm birth 7 days or more after the initial dose were associated with:
- Reduction in the risk of respiratory distress syndrome and fewer serious health problems in the first few weeks of life
- Reduction in mean birth weight prior to adjustment for gestational age.
- There was no increase in infectious morbidity of chorioamnionitis or puerperal sepsis in the mothers.
- No long term benefits or harms were seen in early childhood for the infants.
Evidence included in this review
10 randomized controlled trials with a total of 4733 women and 5700 babies between 24-34 weeks were included in this review. All trials were conducted in high income countries (US, Canada, Australia and New Zealand, Finland, India and 20 countries collaborated in one study). Betamethasone was the corticosteroid used and regimens and time of administrations varied.
The trials were of moderate to excellent quality of evidence. All 10 reviewed trials were of moderate to high methodological quality with moderate to low risk of bias. Placebo was used in all the trials and data was available for all recruited women and babies with little or no loss to follow up. 4 of the trials followed the infants till 18-24 months of age.
Until new information is available, the use of a 12 mg. of betamethasone intramuscularly 24 hours apart seven or more days after initial course of corticosteroids is supported by results of this review in women at risk of preterm birth to reduce the risk of neonatal respiratory distress syndrome and serious neonatal outcomes. There was a reduction in some measures of grow at birth but early childhood follow up showed no substantive differences in survival, neurosensory disabilities, childhood behavior or general health between the exposed and unexposed premature infants.
Further research to assess the long term significance of the effects of anthropometric differences observed at birth is required. Appropriate trials are needed to determine if similar effects will be seen if dexamethasone (which is cheaper and more easily available in middle to low income countries) is used.
Citation: Crowther CA, McKinlay CJD, Middleton P, Harding JE. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes. Cochrane Database of Systematic Reviews 2015, Issue 7. Art. No.: CD003935.DOI: 10.1002/14651858.CD003935.pub4.
It has been unclear whether repeat dose(s) of prenatal corticosteroids are beneficial.
To assess the effectiveness and safety of repeat dose(s) of prenatal corticosteroids.
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.
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.
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.
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.
This RHL summary should be cited as: WHO Reproductive Health Library: Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes: RHL summary (last revised 8 April 2016). The WHO Reproductive Health Library; Geneva: World Health Organization.