Antenatal dexamethasone reduces risk of neonatal death, stillbirth

Antenatal use of dexamethasone significantly reduces the risk of neonatal death and stillbirth among women at risk of early preterm birth in low-resource countries, according to the WHO ACTION-I* study.

“The results of our trial provide reassurance regarding the beneficial effects of [antenatal] glucocorticoids with respect to reducing neonatal mortality in low-resource settings, and they expand the scarce body of evidence from low- and middle-income countries,” according to the researchers.

Researchers gathered data from 29 secondary- and tertiary-level hospitals in Bangladesh, India, Kenya, Nigeria, and Pakistan and included 2,852 women (from 26 weeks 0 days to 33 weeks 6 days of gestation) who were at risk for early preterm birth. Participants were randomized to receive either intramuscular injection of dexamethasone 6 mg (n=1,429) or placebo (n=1,423) every 12 hours for up to a maximum of four doses or until hospital discharge or birth. [N Engl J Med 2020;383:2514-2525]

Among liveborn infants, the rate of neonatal death alone within the completed 28 days of life was significantly lower in the dexamethasone arm compared with the placebo arm (19.6 percent vs 23.5 percent; relative risk [RR], 0.84, 95 percent confidence interval [CI], 0.72–0.97; p=0.03).

Subjects in the dexamethasone arm also had a significantly lower incidence of stillbirth or neonatal death than those in the placebo arm (25.7 percent vs 29.2 percent; RR, 0.88, 95 percent CI, 0.78–0.99; p=0.04).

Significantly fewer women on dexamethasone had a composite of possible maternal bacterial infection than those on placebo (4.8 percent vs 6.3 percent; RR, 0.76, 95 percent CI, 0.56–1.03; p=0.002 for noninferiority).

In the per-protocol population, a lower rate of possible maternal bacterial infection was also observed among women in the dexamethasone arm than the placebo arm (4.5 percent vs 6.4 percent; RR, 0.70).

Serious adverse events occurred at a comparable rate of 1.1 percent among women in both treatment groups, whereas none was reported among the neonates.

“The use of antenatal dexamethasone that was targeted to women at risk for imminent preterm birth in hospitals with minimum resources for maternal and preterm newborn care resulted in significantly lower risks of neonatal death [alone] and stillbirth or neonatal death, … without any evidence of harm to women or newborns,” the researchers concluded.

“Our findings are generally consistent with the results of a meta-analysis of 22 trials that were mostly conducted in high-resource settings,” the researchers added.

“The observed benefits with respect to neonatal mortality appeared to increase with tocolysis and with the duration of foetal exposure to dexamethasone; the role of tocolytic agents in safely delaying early preterm birth in women who are eligible for the use of antenatal glucocorticoids also merits further investigation,” they suggested.

*WHO ACTION-I: World Health Organization Antenatal CorTicosteroids for Improving Outcomes in preterm Newborns