WHO ACTION‑I Trial: Advancing Evidence‑Based Care for Preterm Newborns in Low‑Resource Settings

Preterm birth remains one of the leading causes of neonatal mortality globally, particularly in low- and middle-income countries where access to advanced neonatal care is limited. Complications of preterm birth account for an estimated 35 percent of deaths in the first 28 days of life, underscoring the urgent need for proven, scalable interventions that improve survival and long-term outcomes for newborns.

Antenatal corticosteroids (ACS) have long been recognized as a cornerstone of care for women at risk of early preterm birth in high-income settings. These medications accelerate fetal lung maturation and reduce the risk of respiratory distress, intraventricular hemorrhage, and neonatal death. However, evidence supporting their safe and effective use in low-resource settings had been limited and, in some cases, conflicting. The World Health Organization ACTION-I Trial was designed to address this critical evidence gap.

The WHO ACTION-I Trial was a large, multi-country, multi-centre, double-blind, placebo-controlled randomized clinical trial conducted across hospitals in Bangladesh, India, Kenya, Nigeria, and Pakistan. It enrolled women between 26 weeks 0 days and 33 weeks 6 days of gestation who were at high risk of imminent preterm birth within 48 hours. Participants were randomized to receive either intramuscular dexamethasone or a matching placebo.

A key strength of ACTION-I was its emphasis on implementation within real-world hospital settings that met minimum standards of maternal and neonatal care. These included accurate gestational age assessment using ultrasound, trained obstetric clinicians to identify eligible women, and facility-based neonatal services capable of caring for preterm infants. This approach ensured that the trial evaluated not only the effectiveness of ACS but also the conditions under which they can be safely delivered.

The results of the ACTION-I Trial demonstrated a significant reduction in neonatal mortality among babies whose mothers received dexamethasone, with approximately a 16 percent decrease compared with placebo. The trial also showed a reduction in the combined outcome of stillbirth or neonatal death, reinforcing the life-saving potential of antenatal corticosteroids when used appropriately. Importantly, there was no increase in maternal bacterial infections, addressing a major safety concern associated with steroid use in pregnancy.

Beyond clinical outcomes, ACTION-I provided compelling evidence of cost-effectiveness. Economic analyses showed that antenatal dexamethasone averted substantial numbers of neonatal deaths and disability-adjusted life years across all participating countries and was cost-saving compared with no intervention. These findings are particularly relevant for health systems operating under significant resource constraints.

For the Center for African Newborn Health & Nutrition(CANHENT), the ACTION-I Trial aligns closely with core priorities in evidence-based practice, health systems strengthening, and policy-relevant research. The trial reinforces the importance of delivering proven interventions within adequately prepared health facilities rather than scaling them indiscriminately. It also highlights the role of high-quality research in shaping global and national guidelines for maternal and newborn care.

ACTION-I has directly informed World Health Organization recommendations on the use of antenatal corticosteroids, providing clarity on when, where, and how these medications should be administered in low-resource settings. For countries with a high burden of preterm birth, including Nigeria, the findings offer a strong foundation for integrating ACS into national newborn health strategies while prioritizing investments in facility readiness and workforce capacity.

In conclusion, the WHO ACTION-I Trial represents a major advance in global newborn health research. It confirms that antenatal corticosteroids can safely reduce neonatal mortality in low-resource hospital settings when delivered as part of a minimum package of quality care. For CANHENT and its partners, the trial offers both robust evidence and a practical framework for translating research into action to reduce preventable newborn deaths worldwide.