In a groundbreaking study published in Pediatric Research, a multinational team of scientists has uncovered critical insights into how pulmonary comorbidities affect the efficacy of surfactant therapy in late preterm infants. This multicenter cohort study challenges prevailing assumptions about neonatal respiratory care and paves the way for significantly more tailored and effective treatments. Late preterm infants, typically born between 34 and 37 weeks of gestation, represent a vulnerable population often requiring respiratory support, yet detailed understanding of how preexisting lung conditions influence therapeutic outcomes has been scant.
Pulmonary surfactant, a complex mixture of lipids and proteins, is fundamental to reducing surface tension in the alveoli and maintaining pulmonary stability. Surfactant replacement therapy has revolutionized neonatal care for infants born prematurely with respiratory distress syndrome (RDS). However, variations in treatment efficacy have been observed in infants exhibiting additional pulmonary comorbidities such as bronchopulmonary dysplasia (BPD), persistent pulmonary hypertension of the newborn (PPHN), and congenital pulmonary malformations. This study meticulously stratifies these comorbidities to assess their precise impact on surfactant responsiveness in late preterm babies.
Utilizing data collected from multiple neonatal intensive care units (NICUs) across Europe, the researchers conducted an extensive cohort study involving hundreds of late preterm infants receiving surfactant therapy. Sophisticated statistical models were employed to isolate the effects of specific pulmonary comorbidities from confounding variables, such as gestational age variations, birth weight, and antenatal steroid exposure. The results elucidate that certain comorbidities markedly diminish the effectiveness of standard surfactant formulations, suggesting the need for modified therapeutic strategies.
One of the pivotal discoveries in this study is the differential response related to the presence of inflammatory lung diseases. Infants with underlying pulmonary inflammation showed a significantly blunted improvement in oxygenation indices following surfactant administration compared to their counterparts without inflammation. This finding underscores the crucial interplay between inflammatory processes and surfactant function, providing a potential mechanistic explanation involving surfactant protein degradation and impaired biophysical activity within inflamed alveoli.
Furthermore, the study highlights that late preterm infants with pulmonary hypertension experience altered pulmonary vascular reactivity that interferes with the distribution and efficacy of surfactant delivered via conventional routes. These infants demonstrated protracted ventilatory support requirements and a higher incidence of supplemental oxygen dependency beyond the neonatal period. This observation compels the neonatal community to reconsider current administration protocols, possibly incorporating adjunctive pharmacological agents aimed at modulating vascular tone to optimize surfactant distribution.
Strikingly, the presence of congenital pulmonary malformations such as congenital pulmonary airway malformation (CPAM) or bronchogenic cysts created complex scenarios where surfactant therapy alone failed to reverse respiratory dysfunction effectively. The anatomical aberrations disrupted normal alveolar architecture and surfactant compartmentalization, indicating that surgical correction may be necessary before surfactant therapy can yield optimal results. This revelation calls for a more integrated approach that combines imaging diagnostics, surgical evaluation, and respiratory support strategies in late preterm infants.
The implications of these findings extend beyond immediate treatment protocols. They signify that neonatal intensive care providers must adopt a more nuanced, individualized approach to surfactant replacement therapy, recognizing the heterogeneity within the late preterm population. Precision medicine approaches, integrating patient-specific pulmonary pathology profiles, may enhance survival rates and long-term respiratory outcomes in this fragile demographic. Tailoring surfactant type, dose, and administration technique based on comorbidity profiles may become standard practice in the near future.
Moreover, the study delves into the biochemical alterations in surfactant composition and function associated with different pulmonary comorbidities. Advanced analytical techniques, including mass spectrometry and immunoassays, revealed that surfactant extracted from infants with complicated pulmonary disease exhibits altered lipid-protein ratios and dysfunctional surfactant proteins critical for stability and spreadability. Such molecular insights provide tangible targets for designing next-generation synthetic surfactants or adjunct treatments that replenish deficient components or protect surfactant from inflammatory degradation.
In addition to the biochemical dimension, the research team used high-resolution imaging and lung function measurements to correlate structural abnormalities with functional responses to surfactant therapy. This comprehensive phenotyping approach allowed for the identification of phenotypic biomarkers predictive of poor therapeutic outcomes, enabling early risk stratification and intervention customization. The integration of imaging biomarkers with biochemical data marks a transformative leap in neonatal respiratory research, pointing toward multimodal diagnostics as a cornerstone of future surfactant therapy optimization.
Equally noteworthy is the study’s impact on understanding surfactant pharmacokinetics and biodistribution in the context of pulmonary comorbidities. The researchers used radiolabeled surfactant preparations to track lung deposition in various pathological conditions, revealing that abnormal alveolar-capillary barriers and altered pulmonary fluid dynamics profoundly affect surfactant dispersion and clearance. These insights could inform modified delivery methods, including aerosolized surfactant or surfactant combined with therapeutic nanoparticles, to overcome delivery barriers in diseased lungs.
While surfactant therapy had historically been one-size-fits-all, this study elucidates the importance of precision dosing regimens. Infants with specific comorbidities required adjusted dosing intervals or amounts to achieve adequate alveolar surfactant pools. Over- or under-dosing in these contexts risks exacerbating lung injury or insufficient treatment, respectively. The findings advocate for dynamic dosing algorithms that incorporate real-time markers of lung function and surfactant activity, supported by point-of-care diagnostics.
The study also sheds light on long-term respiratory morbidity related to initial surfactant response variations. Infants with suboptimal therapeutic responses exhibited higher incidences of chronic lung disease and impaired pulmonary function well into infancy and early childhood. These correlations emphasize that early pulmonary comorbidities and surfactant therapy outcomes can have profound lifelong consequences, underscoring the urgency of refining neonatal interventions.
Importantly, the researchers call for further clinical trials that incorporate stratification by pulmonary comorbidity profiles. Such trials are essential to validate tailored surfactant formulations or novel adjunct therapies. The study’s multicenter nature ensures wide applicability of results across diverse healthcare settings but also reveals regional variations in comorbidity prevalence and management practices, highlighting the need for global standardized guidelines informed by these new insights.
In conclusion, this landmark study transforms our understanding of surfactant therapy in late preterm infants by illuminating the significant role of pulmonary comorbidities in shaping treatment outcomes. It bridges molecular biology, pharmacology, and clinical care, offering a comprehensive roadmap for the development of precision respiratory medicine in neonatology. As surfactant replacement continues to be a cornerstone of neonatal intensive care, adapting therapies to address complex pulmonary pathologies holds unprecedented potential to improve survival and quality of life for the most vulnerable newborns.
The research represents a clarion call to clinicians, scientists, and industry to innovate surfactant therapies beyond traditional paradigms and embrace a future of personalized neonatal respiratory care. Neonatologists are now better equipped with the knowledge needed to optimize treatments, mitigate long-term complications, and ultimately enhance the trajectory of infants born at the margins of term. This study not only raises essential scientific questions but also ignites hope for tangible clinical breakthroughs in the care of late preterm infants worldwide.
Subject of Research: Pulmonary comorbidities and their impact on surfactant therapy responsiveness in late preterm infants
Article Title: Pulmonary comorbidities and response to surfactant in late preterm infants: a multicenter cohort study
Article References:
Sadowska-Krawczenko, I., Hożejowski, R., Mazela, J. et al. Pulmonary comorbidities and response to surfactant in late preterm infants: a multicenter cohort study. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04634-5
Image Credits: AI Generated
DOI: 01 December 2025
