Prematurity continues to be the foremost cause of neonatal mortality and morbidity across the globe, with pulmonary complications representing a significant portion of these adverse outcomes. Among these pulmonary complications, surfactant deficiency stands out as a critical factor directly contributing to respiratory distress syndrome (RDS) in preterm infants. Researchers have long sought innovative approaches to enhance surfactant production and function in immature lungs, aiming to improve survival rates and quality of life for these vulnerable neonates. A groundbreaking study by Moskowitzova et al., recently published in Pediatric Research, sheds new light on a promising method to address this challenge using combined transamniotic delivery of surfactant protein mRNAs.
The pulmonary surfactant system is essential for reducing surface tension within alveoli, preventing lung collapse, and enabling efficient gas exchange. Surfactant proteins B (SPB) and C (SPC) play crucial roles in the biophysical and biochemical integrity of this system, facilitating surfactant spreading and stability in the air-liquid interface of the alveolar space. Deficiency in these proteins, particularly in infants born prematurely, leads to insufficient surfactant activity, contributing to increased lung compliance and respiratory compromise. Traditional surfactant replacement therapies, while beneficial, often fall short of addressing the underlying protein deficits in a timely and efficient manner, prompting the search for alternative delivery strategies.
The novel approach investigated by Moskowitzova and colleagues centers on the transamniotic administration of messenger RNA (mRNA) encoding SPB and SPC directly into the amniotic fluid. This method exploits the naturally occurring fetal breathing movements, whereby the mRNA is inhaled into the fetal lungs, allowing for endogenous protein synthesis in situ. Such an approach aims to overcome the limitations of exogenous surfactant replacement by stimulating the fetus’s own surfactant production machinery before birth, potentially mitigating or even preventing the onset of severe RDS postnatally.
To explore this concept, the research team employed a rodent model representative of preterm human lung development. The model allowed for controlled investigation of isolated versus combined delivery of SPB and SPC mRNAs transamniotically. Their hypothesis was that combined delivery would synergistically enhance surfactant production more effectively than either protein mRNA alone, given the interdependent functions and cooperative effects these proteins exert within the surfactant complex.
Detailed analyses revealed that fetuses receiving combined SPB and SPC mRNA demonstrated significantly higher surfactant production compared to those treated with either mRNA in isolation or controls. Importantly, the transamniotic route proved to be a feasible and minimally invasive method for prenatal intervention, with the mRNA effectively reaching lung tissue and initiating protein expression. The study’s findings were supported by both biochemical assays and physiological measures indicating improvement in surfactant functionality and lung mechanics.
This research carries profound implications for the future of neonatal care and prenatal therapy. By moving surfactant augmentation into the prenatal period via mRNA delivery, clinicians could theoretically reduce the incidence and severity of neonatal respiratory complications. The technique leverages advancements in mRNA technology, which has garnered remarkable attention in recent years due to its success in vaccine development and other medical applications, demonstrating its versatility beyond infectious disease contexts.
Moreover, the study propels the concept of precision medicine into the realm of perinatal care. Tailoring mRNA interventions to preterm infants’ developmental stage and specific deficits in surfactant proteins could optimize treatment efficacy and minimize side effects. The natural biological process of transamniotic exposure aligns well with fetal physiology, reducing the need for invasive postnatal interventions that carry risks such as barotrauma and infection.
Despite its promise, several challenges remain to be addressed before clinical translation. The long-term safety of prenatal mRNA delivery must be thoroughly investigated, particularly concerning potential immune responses or off-target effects. Additionally, optimal dosing, timing, and delivery mechanisms require refinement to maximize therapeutic windows and ensure reproducibility in human subjects.
The developmental intricacies of surfactant protein synthesis and regulation also warrant deeper exploration. While SPB and SPC are essential, the roles of other surfactant components, such as SP-A and SP-D, and their interaction networks remain integral to crafting comprehensive surfactant enhancement strategies. Future research may explore multiplexed or sequential delivery approaches, expanding upon the foundational work demonstrated here.
Furthermore, the ethical and practical considerations of administering experimental therapies prenatally necessitate rigorous clinical trial design and stakeholder engagement. Maternal and fetal health must be safeguarded with transparent risk-benefit assessments, ensuring that innovations in neonatal medicine align with parental values and societal standards of care.
The broader implications of this work underscore the transformative potential of mRNA therapeutics beyond neonatal medicine. By demonstrating targeted prenatal intervention capabilities, this study opens avenues for treating a variety of congenital and developmental disorders before birth, heralding a paradigm shift in how clinicians might approach early-life disease prevention and management.
In summary, the combined transamniotic administration of SPB and SPC mRNA represents a sophisticated and forward-thinking strategy to augment fetal lung surfactant production. Moskowitzova et al.’s research offers compelling evidence that such an intervention can boost surfactant synthesis and improve pulmonary outcomes in a preterm rodent model, potentially revolutionizing neonatal intensive care. This pioneering work lays the groundwork for a new era where mRNA-based prenatal therapies could mitigate some of the most enduring challenges associated with prematurity.
The urgent need to reduce neonatal mortality and morbidity from respiratory distress underscores the timeliness and relevance of these findings. As scientific understanding of fetal lung development deepens and mRNA delivery methods evolve, the prospect of safer, more effective treatments for surfactant deficiency moves closer to reality. The clinical landscape could soon witness a shift from reactive postnatal therapy to proactive prenatal intervention, dramatically enhancing survival and long-term health trajectories for premature infants worldwide.
Ultimately, the study serves as a testament to the power of interdisciplinary innovation, integrating molecular biology, fetal physiology, and therapeutic technology. It sparks important discussions within the scientific and medical communities about harnessing the full potential of mRNA modalities and unlocking new frontiers in maternal-fetal medicine. The future of neonatal care, illuminated by such transformative research, promises hope where there was once profound vulnerability.
Subject of Research: Pulmonary surfactant deficiency in premature infants and prenatal therapeutic enhancement using mRNA technology.
Article Title: Combined transamniotic delivery of surfactant proteins B and C mRNA enhances preterm fetal surfactant production in a rodent model.
Article References:
Moskowitzova, K., Scire, E.M., Dang, T.T. et al. Combined transamniotic delivery of surfactant proteins B and C mRNA enhances preterm fetal surfactant production in a rodent model. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04493-0
Image Credits: AI Generated
DOI: https://doi.org/10.1038/s41390-025-04493-0
Tags: biophysical properties of pulmonary surfactantdual mRNA delivery for surfactant productionenhancing surfactant function in immature lungsimproving survival rates in preterm newbornsinnovative therapies for neonatal respiratory issuesneonatal mortality and morbidity factorspulmonary complications in neonatal carerespiratory distress syndrome treatmentsurfactant deficiency in preterm infantssurfactant protein B and C rolessurfactant replacement therapy limitationstransamniotic delivery of mRNAs
