What is it about?
Perinatal asphyxia (PA), or a lack of oxygen during birth, is a major cause of infant death and long-term disability, especially in developing nations (Low-Income and Lower-Middle-Income Countries, or LILMICs). In these areas, the standard life-saving treatment, therapeutic hypothermia (body cooling), is often unavailable or less effective. This study reviewed 12 randomized controlled trials (RCTs) involving over 1,000 newborns with PA in LILMICs to see if protective medications could be an effective alternative. The research found that using these pharmacologic agents showed great potential for improving outcomes. Key Findings: • Improved Survival: The medications collectively improved the survival rate of affected newborns. • Better Short-Term Health: Babies who received the drugs had better short-term results, including being more successful at feeding by mouth (successful oral feeding), less need for anticonvulsants, and having normal results on their brain imaging scans (neuroimaging features), when they were discharged from the hospital. • Most Effective Drugs: Magnesium Sulphate was the most consistently effective drug for improving these immediate short-term outcomes. Melatonin showed the greatest benefit in terms of overall survival. • Some studies also found that children continued to show better development up to 19 months after treatment. The conclusion is that these neuroprotective drugs show promise for improving both survival and brain function in newborns with PA in LILMICs. More large-scale studies are needed to confirm these results and establish these drugs as reliable treatments where cooling therapy is not a viable option.
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Why is it important?
This work matters because it tackles a critical gap in newborn care in low-resource settings. Perinatal asphyxia is a leading cause of newborn death and disability worldwide, especially in low- and lower-middle-income countries (LILMIC) where advanced treatments like cooling therapy are hard to implement. Furthermore, current evidence does not confirm the effectiveness of therapeutic hypothermia in low- and lower-middle income countries. By testing medicines that are cheaper, easier to deliver, and more widely available than cooling equipment, the research points to practical options that could save lives where resources are limited. The findings show that certain drugs can improve survival and early recovery, and may even support longer-term development. This systematic review and meta-analysis pulls together data from multiple trials, strengthening the case for pharmacologic treatments as viable alternatives. If confirmed by larger, high-quality studies, these medicines could become standard care in places where current therapies are not feasible, reducing global health inequalities. It is important because it offers hope for safer, more practical ways to protect newborns’ brains and improve survival in the very settings where the burden of perinatal asphyxia is greatest.
Perspectives
This systematic review and meta-analysis on pharmacologic neuroprotective agents is critical, not just for informing global health policy, but also for providing a solid evidence base directly relevant to further investigations of similar pharmacological agents in low- and middle-income countries. 1. Validating the Search for Alternatives: The study confirms that the conventional standard of care, therapeutic hypothermia, faces significant limitations and has unproven efficacy in Low-Income and Lower-Middle-Income Countries (LILMICs). Given that Sub-Saharan Africa (SSA)—including Nigeria—accounts for nearly half (46%) of global perinatal asphyxia (PA)-related deaths, the finding that drug alternatives show potential is hugely encouraging and validates the necessity of exploring feasible options. 2. Guiding Future Research: The review highlights that the included studies are geographically imbalanced, with a severe paucity of Randomised Controlled Trials (RCTs) from SSA; only one study was from Africa (Egypt). This emphasizes a critical research gap that new studies on other potential medicines may fill, which aligns perfectly with the study’s call to explore novel, effective agents that target oxidative stress—a key mechanism in PA brain injury. The review's structure, methodology, and focus on practical outcomes (survival, oral feeding, seizure control) provides a robust methodological framework for new trials in a low-resource setting like Nigeria. 3. Providing Evidence for Clinical Actionability: The strong evidence supporting the use of specific, available drugs is immediately actionable: The review gives High certainty evidence that Magnesium Sulphate improves both successful oral feeding at discharge and normal neurological outcomes at one month. This positions Magnesium Sulphate as a high-priority, accessible option for improving early recovery. Also, Melatonin and Erythropoietin showed promise for improving survival and long-term neurodevelopment (up to 19 months for erythropoietin), respectively, warranting further investigation in larger, SSA-based trials. In conclusion, this systematic review is a blueprint for equitable care, confirming that pharmacologic agents are not merely theoretical alternatives but promising, scalable treatment options. For newer trials on other potential drugs like antioxidants, it provides the essential evidence base and methodological impetus to pursue such studies in Nigeria, directly addressing the regional imbalance and the urgent need for local, effective solutions to combat PA.
Victor Ayeni
Babcock University
Read the Original
This page is a summary of: Pharmacologic neuroprotective agents for the treatment of perinatal asphyxia in low-income and lower-middle-income countries: A systematic review and meta-analysis of randomised controlled trials, PLOS One, December 2025, PLOS,
DOI: 10.1371/journal.pone.0337798.
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