Antenatal dexamethasone reduces mortality in preterm infants in low-resource countries.

Abstract

Oladapo, OT, et al. (2020). ‘Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries’ The New England Journal of Medicine. PMID: 33095526. Antenatal corticosteroids (ANC) improve survival and decrease morbidity in premature infants.1, 2 However, their use has been controversial in low-resource countries (LRC) due to the ACT study, which questioned the safety and efficacy of ANC.3. The ACT study had limitations; it did not collect or process the data on the use of co-interventions affecting outcomes, thus confounding the results. They used birthweight percentiles instead of gestational age to define the target subgroup, thus misclassifying some term infants as preterm. To answer the question better, Oladapo et al., the WHO ACTION collaborators, designed a multi-country randomised control blinded study. This study found a significant reduction in neonatal death and stillbirth and death with the use of antenatal dexamethasone without increasing maternal morbidity or mortality. The researchers adhered to stricter inclusion and exclusion criteria. They obtained accurate gestational age ultrasound dating, enrolled women who were at risk of preterm birth within 48 h and delivered in hospitals equipped with essential standard resources to support preterm newborns. The discrepant results of the WHO ACTION and ACT trials highlight an important learning point for high-resource countries (HRC). The WHO ACTION trial assessed ANC efficacy in highly selected populations managed in settings equipped with standard resources, whilst the ACT trial evaluated the consequence of massive implementation of ANC in uncontrolled situations. Indiscriminate administration of interventions such as ANC might be harmful; thus, patients in LRC must be carefully assessed for eligibility before receiving interventions with known benefits in HRC. Previous studies show benefit for premature newborns exposed to ANC in LRC,4, 5 but these studies are not placebo-controlled. Strengths of this study include the size, randomisation, blinding and multinational. The study was designed to identify and recruit patients and foetuses who would potentially receive the most benefit from ANC. Reporting data with and without the use of multiple imputations and using the false-discovery-rate approach amplified the significance of findings. Additionally, because the primary outcome in this study was neonatal death, not respiratory distress syndrome or other morbidities, the crucial impact of ANC on reducing preterm mortality in LRC is apparent. One weakness is the clinical management of the mother-baby dyad varied depending on local resources and guidelines. This may alter outcomes depending on the training and protocols of a particular centre. Data were analysed with and without stratifying for study site. Despite this, there was still benefit to preterm newborns exposed to antenatal dexamethasone demonstrating its favourable impact on mortality and morbidity, which is important as it will be used in many LRC. Prematurity is the leading cause of death in children under age 5 worldwide.6 Low-cost, high-impact preventive interventions are needed to help reduce this burden. This study reaffirms that dexamethasone is safe, efficacious and cost-saving for LRC to reduce their hospital-based stillbirth or neonatal mortality in premature infants. Dexamethasone has the potential to make a major impact on the survival of premature newborns in LRC when used with the appropriate clinical protocolised approach. None. https://ebneo.org/category/reviews/.