Abstract: For this update, 12 trials (1557 women and 1661 infants) were included. Dexamethasone was associated with a reduced risk of intraventricular haemorrhage (IVH) compared with betamethasone (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.21 to 0.92; four trials, 549 infants). No statistically significant differences were seen for other primary outcomes: respiratory distress syndrome (RDS) (RR 1.06, 95% CI 0.88 to 1.27; five trials, 753 infants) and perinatal death (neonatal death RR 1.41, 95% CI 0.54 to 3.67; four trials, 596 infants). Similarly, very few differences were seen for secondary outcomes such as rate of admission to the neonatal intensive care unit (NICU) although in one trial, those infants exposed to dexamethasone, compared with betamethasone, had a significantly shorter length of NICU admission (mean difference (MD) -0.91 days, 95% CI -1.77 to -0.05; 70 infants). Results for biophysical parameters were inconsistent, but mostly no clinically important differences were seen. Compared with intramuscular dexamethasone, oral dexamethasone significantly increased the incidence of neonatal sepsis (RR 8.48, 95% CI 1.11 to 64.93) in one trial of 183 infants. No statistically significant differences were seen for other outcomes reported. Apart from a reduced maternal postpartum length of stay for women who received betamethasone at 12-hourly intervals compared to 24-hourly intervals in one trial (MD -0.73 days, 95% CI -1.28 to -0.18; 215 women), no differences in maternal or neonatal outcomes were seen between the different betamethasone dosing intervals assessed. Similarly, no significant differences in outcomes were seen when betamethasone acetate and phosphate was compared with betamethasone phosphate in one trial. It remains unclear whether one corticosteroid (or one particular regimen) has advantages over another. Dexamethasone may have some benefits compared with betamethasone such as less IVH, and a shorter length of stay in the NICU. The intramuscular route may have advantages over the oral route for dexamethasone, as identified in one small trial. Apart from the suggestion that 12-hour dosing may be as effective as 24-hour dosing of betamethasone based on one small trial, few other conclusions about optimal antenatal corticosteroid regimens were able to be made. No long-term results were available except for a small subgroup of 18 month old children in one trial. Trials comparing the commonly used corticosteroids are most urgently needed, as are trials of dosages and other variations in treatment regimens.

Plain-language summary: Most trials have compared the two most commonly used corticosteroids before early birth, dexamethasone and betamethasone. In this review of 12 trials (involving 1557 women and 1661 infants) of moderate quality, 10 trials compared dexamethasone and betamethasone; one trial compared two different ways of giving dexamethasone and one trial compared two different ways of giving betamethasone. We found that dexamethasone and betamethasone showed similar results, although there was less bleeding of the brain and a shorter length of neonatal intensive care unit hospital stay for dexamethasone compared with betamethasone. On the basis of one trial, giving dexamethasone by injection (intramuscularly) may be better than giving the drug to the mother by mouth (orally). Usually the drug is given in two doses 24 hours apart and one trial showed that this interval could perhaps be reduced to 12 hours if required. We need more studies to establish which is the best drug and what is the best way to give it, and babies in these trials need to be followed up over a long period to monitor any effects on child and adult development.