In the realm of neonatal medicine, the management and treatment of respiratory distress in late preterm infants stand as a critical challenge. Recent advances have sparked renewed interest in the application of surfactant replacement therapy beyond its traditional use in very preterm neonates. A groundbreaking study by Jeffreys and Dassios, published in Pediatric Research in 2025, dives deep into the nuances of surfactant therapy in late preterm respiratory disease, with an aim to delineate which infants are most likely to benefit from this intervention. Their work could reshape therapeutic strategies and improve outcomes for a vulnerable population.
Late preterm infants, born between 34 and 36 weeks’ gestation, occupy a unique clinical space. Although more mature than their extremely preterm counterparts, they remain at heightened risk for respiratory complications, including respiratory distress syndrome (RDS). Unlike earlier preterm infants who suffer from surfactant deficiency due to incomplete lung development, the clinical heterogeneity in late preterms hinges on complex interactions involving lung maturity, inflammation, and variable surfactant production. This complexity has made the determination of suitable candidates for surfactant replacement therapy an intricate medical puzzle.
The study rigorously evaluates the biophysical properties of pulmonary surfactant within this subgroup, highlighting how alterations in surfactant composition and function contribute to respiratory compromise. Pulmonary surfactant, a lipid-protein complex, reduces alveolar surface tension, preventing collapse during exhalation and facilitating gas exchange. In late preterm infants, partial surfactant deficiency or dysfunction may arise from incomplete synthesis or biophysical inactivation, for instance due to inflammatory cytokines or infection. Identifying molecular and clinical markers indicative of such dysfunction is pivotal for clinical decision-making.
Jeffreys and Dassios employed advanced biomarker profiling and imaging techniques to delineate surfactant status. Their methodology integrated quantitative measurements of surfactant lipids, surface tension dynamics, and real-time lung ultrasound scores. Notably, these diagnostic approaches transcend conventional radiographic evaluations, offering a more sensitive and mechanistic insight into lung physiology. The data underscore that not all late preterm infants with respiratory distress share the same pathophysiological substrate, warranting stratified treatment interventions.
One of the most striking revelations of the study is the identification of a subset of late preterm infants who exhibit significant surfactant dysfunction despite relatively mature gestational age. This subgroup, characterized by elevated markers of alveolar inflammation and dysregulated surfactant protein expression, responded favorably to exogenous surfactant administration. Clinical outcomes included reduced ventilator dependency, shorter hospital stays, and diminished incidence of chronic lung disease, heralding a paradigm shift in treatment protocols.
This differentiation of surfactant dysfunction versus pure structural immaturity or other etiologies of respiratory distress allows clinicians to refine therapeutic indications. The study emphasizes that indiscriminate surfactant therapy in all late preterms with respiratory distress is neither cost-effective nor clinically justified. Instead, a precision medicine approach, leveraging individualized assessment and biomarker-guided therapy, promises to optimize outcomes while minimizing risks.
Mechanistically, the study elaborates on how surfactant supplementation restores alveolar mechanics by re-establishing surface tension homeostasis and attenuating inflammatory cascades. The anti-inflammatory properties of certain surfactant proteins, particularly SP-A and SP-D, may also contribute to modulating immune responses in the neonatal lung. This dual role — mechanical stability and immunomodulation — positions surfactant as a critical therapeutic agent in the delicate interplay of lung development and injury.
In the broader context of neonatal care, these findings intersect with advances in non-invasive respiratory support and neonatal intensive care unit (NICU) protocols. The ability to accurately identify candidates for surfactant replacement could reduce reliance on invasive ventilation strategies, thereby mitigating ventilator-associated lung injury. Moreover, timely intervention prior to progression of respiratory failure may curtail long-term morbidities, including bronchopulmonary dysplasia, which carry lifelong health implications.
Jeffreys and Dassios also highlight implications for healthcare systems, particularly in resource allocation and policy-making. Surfactant preparations are costly and require specialized delivery methods. By targeting therapy to infants with proven surfactant deficiency or dysfunction, hospitals can reduce unnecessary interventions and associated healthcare burdens. Furthermore, enhanced diagnostic capabilities foster a more judicious use of surfactant, aligning with principles of value-based care.
Future directions suggested by the study include the development of bedside assays for surfactant function and expanded research into genetic and environmental factors influencing surfactant metabolism in late preterm neonates. There is also a call for large-scale randomized controlled trials to validate biomarker-guided treatment models and to explore novel surfactant formulations with enhanced anti-inflammatory properties.
In summary, the research by Jeffreys and Dassios marks a transformative step in neonatal respiratory medicine. By dissecting the pathophysiology of late preterm respiratory disease and pinpointing candidates for surfactant replacement therapy, it paves the way for personalized interventions that promise better survival and quality of life for these infants. The study exemplifies the fusion of precision diagnostics, molecular biology, and clinical therapeutics in addressing complex neonatal conditions.
As neonatal care evolves, such insights emphasize the importance of tailored treatment strategies grounded in mechanistic understanding. The hope remains that future neonatal outcomes will be defined less by the challenges of prematurity and more by the efficacy of targeted, science-driven care.
Subject of Research: Surfactant replacement therapy in late preterm infants with respiratory disease, and the identification of suitable candidates for this therapy.
Article Title: Surfactant replacement therapy in late preterm respiratory disease: Identifying suitable candidates.
Article References:
Jeffreys, E., Dassios, T. Surfactant replacement therapy in late preterm respiratory disease: Identifying suitable candidates. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04705-7
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