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Research on lung surfactant has exerted a great impact on newborn respiratory care and significantly improved survival and outcome of preterm infants with respiratory distress syndrome (RDS) due to surfactant deficiency because of lung immaturity. Current clinical, animal-derived, surfactants are among the most widely tested compounds in neonatology However, limited availability, high production costs, and ethical concerns about using animal-derived products constitute important limitations in their universal application. Synthetic lung surfactant offers a promising alternative to animal-derived surfactant by providing improved consistency, quality and purity, availability and scalability, ease of production and lower costs, acceptance, and safety for the treatment of neonatal RDS and other lung conditions. Third-generation synthetic surfactants built around surfactant protein B (SP-B) and C (SP-C) peptide mimics stand at the forefront of innovation in neonatal pulmonary medicine, while nasal continuous positive airway pressure (nCPAP) has become the standard non-invasive respiratory support for preterm infants. nCPAP can prevent the risk of chronic lung disease (bronchopulmonary dysplasia) and reduce lung injury by avoiding intubation and mechanical ventilation, is a relatively simple technique and can be initiated safely and effectively in the delivery room. Combining nCPAP with noninvasive, preferably aerosol, delivery of synthetic lung surfactant promises to improve respiratory outcomes for preterm infants, especially in low-and-middle income countries.
Research on lung surfactant has exerted a great impact on newborn respiratory care and significantly improved survival and outcome of preterm infants with respiratory distress syndrome (RDS) due to surfactant deficiency because of lung immaturity. Current clinical, animal-derived, surfactants are among the most widely tested compounds in neonatology However, limited availability, high production costs, and ethical concerns about using animal-derived products constitute important limitations in their universal application. Synthetic lung surfactant offers a promising alternative to animal-derived surfactant by providing improved consistency, quality and purity, availability and scalability, ease of production and lower costs, acceptance, and safety for the treatment of neonatal RDS and other lung conditions. Third-generation synthetic surfactants built around surfactant protein B (SP-B) and C (SP-C) peptide mimics stand at the forefront of innovation in neonatal pulmonary medicine, while nasal continuous positive airway pressure (nCPAP) has become the standard non-invasive respiratory support for preterm infants. nCPAP can prevent the risk of chronic lung disease (bronchopulmonary dysplasia) and reduce lung injury by avoiding intubation and mechanical ventilation, is a relatively simple technique and can be initiated safely and effectively in the delivery room. Combining nCPAP with noninvasive, preferably aerosol, delivery of synthetic lung surfactant promises to improve respiratory outcomes for preterm infants, especially in low-and-middle income countries.
<b><i>Background:</i></b> Bronchopulmonary dysplasia (BPD) is the most common long-term complication of extreme preterm birth. It is associated with lifelong multisystemic consequences. Advances in neonatal care have not reduced the incidence of BPD and no new breakthrough therapy has been successfully translated into the clinic in recent decades. <b><i>Summary:</i></b> Current evidence demonstrates benefit of new modalities of first-line noninvasive positive pressure ventilation, selected strategies of postnatal corticosteroid administration, alternative surfactant delivery methods, and caffeine. Promising emerging therapies that are being translated from bench to bedside include mesenchymal stromal cells (MSCs), insulin-like growth factor 1/binding protein-3 (IGF-1/IGFBP-3), and interleukin 1 receptor (IL-1R) antagonist (anakinra). Strong preclinical data support efficacy of MSCs in attenuating neonatal lung injury. Early-phase clinical trials have already demonstrated safety and feasibility in preterm infants. Phase II studies that aimed at demonstrating efficacy are currently underway. Both IGF-1/IGFBP-3 and IL-1R antagonist present with biological plausibility and animal data of efficacy. Phase I/II clinical trials are currently recruiting patients. <b><i>Key Messages:</i></b> Early noninvasive respiratory support, late systemic dexamethasone, less invasive surfactant administration, and caffeine are proven strategies in reducing the risk of BPD. Potentially disruptive therapies – MSCs, IGF-1/IGFBP-3, and anakinra – are being advanced to clinical trials and their efficacy in remains to be demonstrated. Continued research efforts are needed in the growing population of extremely preterm infants at risk of developing BPD.
Purpose To compare five pulmonary surfactant (PS) administration strategies for neonates with respiratory distress syndrome (RDS), including intubation-surfactant-extubation (InSurE), thin catheter administration, laryngeal mask airway (LMA), surfactant nebulization (SN), and usual care, with a particular emphasis on the comparison of the LMA and SN with other strategies. Methods We conducted a systematic search of MEDLINE, EMBASE, PUBMED, and Cochrane CENTRAL databases up to November 2023. Two authors independently conducted data extraction, and assessed bias using the Cochrane Risk of Bias Tool. Frequency-based random-effects network meta-analyses were executed. Results A total of 36 trials and 4035 infants were included in the analysis. LMA (OR: 0.20, 95%CI: 0.09 to 0.42) and Less Invasive Surfactant Administration (LISA) (OR: 0.17, 95%CI: 0.09 to 0.32) significantly reduced intubation rates compared to usual care. SN had a higher intubation rate compared to LISA (OR: 3.36, 95%CI: 1.46 to 7.71) and LMA (OR: 2.92, 95%CI: 1.10 to 7.71). LMA had a higher incidence of BPD compared to LISA (OR: 2.59, 95%CI: 1.21 to 5.54). SN ranked second to LISA in preventing BPD and death, but its efficacy decreased after excluding high-risk studies. SN and LMA had the lowest incidence of adverse events during administration.SN had the highest likelihood of secondary administration. Most results were rated as low or very low quality, with findings related to SN significantly impacted by high-risk trials. Conclusions The thin catheter strategy minimized intubation risk and showed a better composite effect in reducing both mortality and BPD incidence. SN and LMA each showed safety and some clinical benefits in the subpopulations where they were studied, but their efficacy needs further validation through high-quality studies. Registration This study was registered in PROSPERO (CRD42023463756).
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