Sixteen RCTs (n=1,136) were included in the review. Methodological quality of the trials was considered to be fair to good. Nine RCTs used moderately early treatment and seven used delayed treatment
There were no statistically significant differences between treatment and placebo groups in mortality rates for either moderately early or delayed treatment trials. There was a statistically significantly lower risk of the combined outcome of 36-week postmenstrual age mortality and BPD in treatment groups in the moderately early trials (RR 0.70, 95% CI 0.57 to 0.86) and a trend towards a significant effect in trials of delayed treatment (RR 0.91, 95% CI 0.84 to 1.00); the authors stated that the risk of BPD as a single outcome was also reduced.
Subgroup analysis showed that these effects were most pronounced in trials that uses cumulative doses of at least 4mg/kg (BPD alone RR 0.53, 95% CI 0.28 to 0.98 and combined outcome RR 0.57 95% CI 0.39 to 0.84). However, metaregression did not show a significant relationship between the cumulative dose of dexamethasone and risk of mortality or bronchopulmonary dysplasia.
A statistically significant inverse relationship with dose was found for the risk of the combined outcome of mortality or cerebral palsy in the moderately early trials with a decrease of 6.2% for each incremental mg/kg cumulative dexamethasone dose; this was not the case for the delayed treatment trials. This pattern of results was also found for the outcome of an MDI score 2 standard deviations below the mean with a decrease of 6.6% for each incremental mg/kg cumulative dexamethasone dose. There was no relationship between dose and short-term respiratory benefits.