Dexamethasone lowers risk of neonatal death and stillbirth among preterm pregnancies;NEJM

Antenatal glucocorticoids have long been promoted as the key intervention for reducing preterm infant mortality and morbidity. However, the generalizability of this evidence to low-resource settings was called into question in 2015, when a large population-based trial conducted in six low-resource countries showed that efforts to scale up the use of antenatal glucocorticoids could lead to harm. In that trial, scaling up of glucocorticoids did not reduce mortality among infants who were below the fifth percentile for birth weight (a proxy for preterm birth) and unexpectedly was associated with an increase in the incidence of neonatal death, stillbirth, and suspected maternal infection in the population overall.

Taking a cue from such findings, World Health Organization (WHO) recommended that antenatal glucocorticoids should be used only under certain conditions, including the accurate assessment of gestational age, imminent preterm birth, the absence of maternal infection, and adequate care for childbirth and preterm newborns.

With this background, the research team conducted a multicountry, randomized trial involving pregnant women between 26 weeks 0 days and 33 weeks 6 days of gestation who were at risk for preterm birth. The participants were assigned to intramuscular dexamethasone or identical placebo.

The primary outcomes were neonatal death alone, stillbirth or neonatal death, and possible maternal bacterial infection; neonatal death alone and stillbirth or neonatal death were evaluated with superiority analyses, and possible maternal bacterial infection was evaluated with a noninferiority analysis with the use of a prespecified margin of 1.25 on the relative scale.

Data analysis revealed the following facts.

· A total of 2852 women (and their 3070 fetuses) from 29 secondary- and tertiary-level hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan underwent randomization.

· The trial was stopped for benefit at the second interim analysis. Neonatal death occurred in 278 of 1417 infants (19.6%) in the dexamethasone group and in 331 of 1406 infants (23.5%) in the placebo group (relative risk, 0.84; 95% confidence interval [CI], 0.72 to 0.97; P=0.03).

· Stillbirth or neonatal death occurred in 393 of 1532 fetuses and infants (25.7%) and in 444 of 1519 fetuses and infants (29.2%), respectively (relative risk, 0.88; 95% CI, 0.78 to 0.99; P=0.04); the incidence of possible maternal bacterial infection was 4.8% and 6.3%, respectively (relative risk, 0.76; 95% CI, 0.56 to 1.03).

· There was no significant between-group difference in the incidence of adverse events.

"The results of our trial provide reassurance regarding the beneficial effects of 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. Although smaller trials conducted in low- and middle-income countries have suggested benefits, most of them were not placebo-controlled trials."wrote the team.

For the full article follow the link: https://www.nejm.org/media/doi/full/10.1056/NEJMoa2022398

Primary source:NEJM