Can antenatal dexamethasone prevent mortality and morbidity among late preterm newborns?

India: The largest efficacy trial of antenatal corticosteroids found no substantive changes in the risk estimates for neonatal death, perinatal death, or respiratory distress syndrome, of women receiving antenatal corticosteroids at 34 weeks gestation or greater in a low-resource country setting. The article was published in the Lancet journal eClinicalMedicine. 

Globally, 11% of live births babies are born preterm(32 to <37 weeks gestation). Compared to babies born at term, preterm babies have higher rates of respiratory, infectious, and neurological morbidities; elevated risks of adverse health outcomes persisting into childhood and later life. Babies born in the late preterm period (34 to <37 weeks) experience a significantly higher rate of morbidity and mortality than those born at term. (WHO) recommended antenatal corticosteroids (ACS) used for pregnant women at risk of preterm birth from 24 to 34 weeks gestation, but is a lack of evidence of the benefit of ACS beyond 34 weeks. The WHO guideline panel acknowledged that further efficacy trials in low-resource countries on ACS use in both early and late preterm populations were a high research priority. There is currently insufficient evidence on the safety and efficacy of antenatal corticosteroids in preventing mortality and severe morbidity amongst late preterm newborns in low-resource countries.

The results of the WHO ACTION-I(Antenatal CorticosTeroids for Improving Outcomes in preterm Newborn) trial on the efficacy of dexamethasone in the early preterm period have been reported previously. In this article, the authors describe the findings of the WHO ACTION-II trial, which aimed to assess the safety and efficacy of dexamethasone when given to women at risk of late preterm birth, in hospitals in low-resource countries.

Researchers recruited 782 women, at risk of imminent preterm birth between 34 weeks 0 days and 36 weeks 0 days of gestation and randomized them (1:1) to a course of 6 mg intramuscular dexamethasone or identical placebo in four hospitals. Primary outcomes were neonatal death, any baby death (stillbirth or neonatal death), severe neonatal respiratory distress, and possible maternal bacterial infection. Secondary outcomes include maternal and newborn mortality and morbidities, and process of care outcomes.

Key findings of the study,

• Neonatal death occurred in 2.7% and 2.8% of liveborn babies in the dexamethasone group and the placebo group, respectively (RR 0.95)

• Any baby death occurred in 3.8% of infants in the dexamethasone group and 4.4%of infants in the placebo group (RR 0.87).

• Severe neonatal respiratory distress was infrequent in both groups (0.8% vs 0.5%; RR 1.56).

• The possible maternal bacterial infection did not differ between groups (2.3% vs. 3.8%, RR 0.60)

• Fewer neonates in the dexamethasone group required resuscitation at birth (RR 0.38).

• Other secondary outcomes were similar in the two arms.

The trial had to be stopped due to lower than expected prevalence of primary outcomes and slow recruitment.

The authors conclude that antenatal dexamethasone did not result in a reduction in neonatal death, stillbirth or neonatal death, or severe neonatal respiratory distress. A reduction in neonatal resuscitation at birth for newborns was identified and there was no evidence of the difference between groups for neonatal hypoglycemia. The overall trend of effects suggests that the potential benefit of dexamethasone in late preterm cannot be excluded, and further trials are required.

Reference:

WHO ACTION Trials Collaborators Open Access Published:February 11, 2022DOI:https://doi.org/10.1016/j.eclinm.2022.101285