Surfactant Administration Methods in Preterm Infants With RDS: A Swedish Cohort Study

A Prospective Observational Study of Surfactant AdministrationMethods for Preterm Infants With Respiratory Distress SyndromeWith Long-term Follow-up in the Swedish Neonatal Quality Register

The goal of this observational study is to evaluate different methods of surfactant administration in preterm infants with respiratory distress syndrome (RDS). Preterm infants often have immature lungs and a deficiency of surfactant, a substance that helps keep the lungs open and supports oxygen exchange.Surfactant can be delivered to the lungs using different techniques, including INSURE (brief intubation), LISA (via a thin catheter), SALSA (via a laryngeal mask airway), and traditional administration via endotracheal intubation followed by mechanical ventilation. The main question this study aims to answer is:Which method of surfactant administration is associated with better clinical outcomes in preterm infants with RDS?The study will prospectively collect clinical data on infants receiving surfactant as part of standard care, with long-term follow-up using data from the Swedish Neonatal Quality Register. The results are intended to be used to inform the design of a future randomized multicenter study.

Study Overview

• Status: Not yet recruiting
• Conditions: Respiratory Distress Syndrome in Premature Infant; Respiratory Distress Syndrome of Newborn; Respiratory Distress Syndrome (& [Hyaline Membrane Disease]); Respiratory Distress Syndrome (RDS); Respiratory Distress Syndrome (Neonatal)

Detailed Description

Background Complications of preterm birth are the leading cause of child mortality worldwide, with respiratory distress syndrome (RDS) as a major contributor. RDS is primarily caused by surfactant deficiency due to immature lungs. Early surfactant therapy, in combination with antenatal corticosteroids and non-invasive respiratory support such as continuous positive airway pressure (CPAP), is central to treatment. However, mechanical ventilation is associated with an increased risk of lung injury and bronchopulmonary dysplasia (BPD), prompting the development of less invasive surfactant administration techniques.

Surfactant Administration Methods Three main methods are currently used in spontaneously breathing preterm infants. The INSURE method involves transient intubation for surfactant delivery followed by extubation. Less Invasive Surfactant Administration (LISA) uses a thin catheter inserted below the vocal cords under laryngoscopy, allowing continued spontaneous breathing. LISA is recommended as first-line treatment in European guidelines due to improved outcomes compared to INSURE. However, both methods require laryngoscopy and are technically demanding, with potential adverse events.

Surfactant Administration via Laryngeal or Supraglottic Airways (SALSA) is a newer, less invasive technique that delivers surfactant via a supraglottic airway without laryngoscopy or passage through the vocal cords. Preliminary studies suggest comparable effectiveness to INSURE and CPAP, with potential safety advantages. Historically, SALSA has been limited to larger infants due to lack of appropriately sized devices, but newly available CE-marked devices now enable its use in extremely preterm infants.

Rationale Despite widespread use of INSURE, LISA, and SALSA, there are no direct comparisons between LISA and SALSA, and real-world data on their implementation, safety, and outcomes are limited. In Sweden, these methods are used variably across neonatal units, and their relative use and outcomes have not been systematically evaluated. The availability of smaller supraglottic airway devices now allows evaluation of SALSA in the most vulnerable population, including extremely preterm infants.

Aim The primary aim is to prospectively evaluate and compare the feasibility, safety, clinical performance, and procedural characteristics of surfactant administration methods (SALSA, LISA, INSURE) in spontaneously breathing preterm infants in a real-world clinical setting.

Secondary aims include comparison with infants receiving surfactant via intubation followed by mechanical ventilation, evaluation of short- and long-term clinical outcomes, and generation of data to inform the design of a future randomized multicentre trial.

Study Design This is a prospective, multicentre, observational study conducted in neonatal intensive care units (NICUs) in Region Västra Götaland (VGR), Sweden. No interventions are introduced, and all treatment decisions are made according to local clinical guidelines.

Study Population Eligible participants are preterm infants (37 weeks' gestation) receiving their first surfactant treatment within 48 hours of birth due to suspected or confirmed RDS. Infants are included regardless of administration method.

Data Collection and Follow-up Data are collected from routine clinical documentation, structured procedure forms, clinician surveys, and the Swedish Neonatal Quality Register (SNQ). Variables include perinatal factors, procedural details, respiratory outcomes, and morbidity. Infants are followed until discharge and, where applicable, at 2 and 5.5 years of age using SNQ data.

Outcomes The primary outcome is treatment failure, defined as the need for mechanical ventilation or repeat surfactant administration within 72 hours. Secondary outcomes include changes in oxygenation, need for respiratory support, adverse events, procedural characteristics, and short- and long-term morbidity and mortality. Clinician-reported feasibility and ease of use are also assessed.

Statistical Considerations All eligible infants will be included over a three-year period, with an expected sample size of approximately 300 infants. Analyses will include descriptive statistics, unadjusted comparisons, and multivariable regression models, with propensity score matching to address confounding.

Ethics Ethical approval has been granted by the Swedish Ethical Review Authority. Written informed consent is obtained from caregivers for participation and for permission to collect and analyse observational data. Participation is voluntary and does not affect the infant's clinical care.

Significance This study will provide real-world evidence on the use, safety, and outcomes of different surfactant administration methods, including the implementation of SALSA in extremely preterm infants. The results will inform clinical practice and provide essential data for the design of a future large-scale randomized multicentre trial.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Anders Elfvin, Professor; Phone Number: +46313438073; Email: anders.elfvin@vgregion.se
• Study Contact Backup: Name: Mårten Larsson, M.D; Phone Number: +46704240972; Email: marten.larsson@vgregion.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Newborn infants admitted to neonatal units in Västra Götaland Region, Sweden.

Description

Inclusion Criteria:

• Patient has received surfactant by any administration method
• Gestational age below 37 weeks'
• First surfactant treatment given before 48 hours of age
• Confirmed or suspected diagnosis of respiratory distress syndrome (RDS)

Exclusion Criteria:

• Not fulfilling above inclusion criteria

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
SALSA; Surfactant Administration via Laryngeal or Supraglottic Airway
LISA; Less Invasive Surfactant Administration using a thin catheter applied below the vocal cords guided by laryngoscopy
INSURE; Intubation-Surfactant-Extubation. Followed by positive pressure ventilation or brief period (<1 hour) of mechanical ventilation
Group/Cohort Description: Intubation-Surfactant-Extubation. Followed by positive pressure ventilatio; Continued on mechanical ventilation >1 hour

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mechanical ventilation or repeat surfactant within 72 hours after first surfactant treatment delivered by LISA, SALSA or INSURE method	Categorical variable (Yes/No). Decision to initiate mechanical ventilation via intubation will be made at the discretion of the treating physician, guided by the local NICU criteria for mechanical ventilation. Data is extracted from medical records.	Within 72 hours after first surfactant treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bradycardia <100 bpm (any duration)	Categorical variable (Yes/No). Measured by pulse oximetry and noted by team performing procedure.	During the procedure, an average of 5-10 minutes
Oesophageal/upper airway injury	Categorical (Yes/No). Observations of infant during and post-procedure. Details provided if present.	During and within an hour from procedure.
Bradycardia <60 bpm (any duration)	Categorical variable (Yes/No). Measured by pulse oximetry and noted by team performing procedure.	During the procedure, an average of 5-10 minutes
Desaturation to SpO₂ <80% lasting ≥30 seconds (single episode)	Categorical variable (Yes/No). Measured by pulse oximetry and noted by team performing procedure.	During the procedure, an average of 5-10 minutes
Duration of bradycardia <100 and <60 bpm	Continous variable. Measured by pulse oximetry.	During the procedure, an average of 5-10 minutes
Duration of desaturation <80%, <60% and <40%	Continuous variable (seconds). Measured by pulse oximetry.	During the procedure, an average of 5-10 minutes
Surfactant-like content in gastric aspirate	Continous variable, ml.	Directly after first surfactant administration
Proportion of administered surfactant recovered in gastric aspirate	Continuous variable (%). Fraction (calculated from residual aspirated surfactant and total dose (mL). Observed by clinical team during procedure and noted in CRF.	Directly after first surfactant administration
Surfactant reflux	Categorical variable (Yes/No). Clinical reflux of surfactant during procedure.	Directly after first surfactant administration
Δ-FiO₂: Hourly change in FiO₂ from pre-procedure to 12 hours post-procedure	Continuous variable.	Within 15 minutes before the procedure to 12 hours after first surfactant administration
Δ-SpO2/FiO2-ratio: Change in SpO₂/FiO₂ ratio from pre-procedure to 4 hours post-procedure	Continuous variable.	Within 15 minutes before the procedure to 4 hours after first surfactant administration
Early failure: Mechanical ventilation within 1 hour of first surfactant administration	Categorical variable (Yes/no).	Within 1 hour after first surfactant administration
Mechanical ventilation within 72 hours of first surfactant administration	Categorical variable (Yes/No). Decision to initiate mechanical ventilation via intubation will be made at the discretion of the treating physician, guided by the local NICU criteria for mechanical ventilation. Data is extracted from medical records.	Within 72 hours after first surfactant administration
Repeat surfactant within 72 hours of first surfactant administration	Categorical variable (Yes/No). Decision to repeat surfactant will be made at the discretion of the treating physician, guided by the local NICU guideline. Data is extracted from medical records. When	Within 72 hours after first surfactant administration
Documented reason for mechanical ventilation	Categorical (Nominal).	Within 72 hours after first surfactant administration
Documented reason for repeat surfactant	Categorical (nominal).	Within 72 hours after first surfactant administration
FiO2 requirement at time of intubation	Numerical variable.	Within 72 hours after first surfactant administration
Mechanical ventilation at any time during admission and duration	Categorical variable (Yes/No). Decision to initiate mechanical ventilation via intubation will be made at the discretion of the treating physician, guided by the local NICU criteria for mechanical ventilation.	Before discharge (about 2-20 weeks)
Total cumulative days of CPAP/NIPPV	Numerical variable (days). Data is collected from medical record.	Before discharge (about 2-20 weeks)
Total cumulative days of mechanical ventilation (any mode)	Numerical variable (days).	Before discharge (about 2-20 weeks)
Total cumulative days of nasal high flow cannula	Numerical variable (days). Data is collected from medical record.	Before discharge (about 2-20 weeks)
Total cumulative days of any respiratory support (MV, CPAP/NIPPV, HNFC, or oxygen cannula)	Numerical variable (days). Data is collected from medical record.	Before discharge (about 2-20 weeks)
FiO2 requirement before repeat surfactant	Numerical variable.	Within 72 hours after first surfactant administration
Time to repeat surfactant	Numerical variable.	Before discharge (about 2-20 weeks)
Time to mechanical ventilation	Numerical variable.	Before discharge (about 2-20 weeks)
Total cumulative days of mechanical ventilation, conventional	Numerical variable.	Before discharge (about 2-20 weeks)
Total cumulative days of supplemental O2	Numerical variable.	Before discharge (about 2-20 weeks)
Systemic (oral or intravenous) steroid treatment due to lung disease	Age, date and duration.	Before discharge (about 2-20 weeks)
Death	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
Time to death	Numerical variable.	Before discharge (about 2-20 weeks)
Cause of death	Categorical (Nominal).	Before discharge (about 2-20 weeks)
Intraventricular heamorrhage (IVH)	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
Highest grade of IVH, any side	Categorical (ordinal)	Before discharge (about 2-20 weeks)
Post-haemorrhagic ventricular dilatation (PHVD)	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
Cystic periventricular leukomalacia (cPVL)	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
Bronchopulmonary dysplasia (BPD)	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
Severe BPD	Categorical (Yes/No).	Before discharge (about 2-20 weeks)
Pneumothorax	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
Thoracic drain	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
Early Onset Sepsis, culture verified	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
Early Onset Sepsis, clinical diagnosis	Categorical (Yes/No).	Before discharge (about 2-20 weeks)
Late Onset Sepsis, culture verified	Categorical (Yes/No).	Before discharge (about 2-20 weeks)
Late Onset Sepsis, clinical diagnosis	Categorical (Yes/No).	Before discharge (about 2-20 weeks)
Necrotizing Enterocolitis (NEC)	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
NEC with perforation	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
NEC with surgical treatment	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
Spontaneous intestinal perforation	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
Persistent ductus arteriosus (PDA), medical treatment	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
PDA requiring, surgical treatment	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
Examined for retinopathy of prematurity (ROP)	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
Maximim ROP any side, grade	Categorical (ordinal).	Before discharge (about 2-20 weeks)
ROP ≥ grade 3	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
ROP treatment	Categorical (Yes/No)	Before discharge (about 2-20 weeks)
Major neonatal morbidity	Categorical (Yes/No). BPD, IVH ≥3, cPVL, ROP ≥ 3, or NEC with perforation.	Before discharge (about 2-20 weeks)
Weight at discharge	Numerical variable. Grams.	Before discharge (about 2-20 weeks)
Δ-weight at discharge	Numerical variable. Grams.	Before discharge (about 2-20 weeks)
Supplemental oxygen at discharge from hospital	Categorical variable (Yes/No).	Before discharge (about 2-20 weeks)
Duration of admission (in-patient care)	Numerical variable. Days.	Before discharge (about 2-20 weeks)
Asthma or obstructive respiratory symptoms during the past 12 months	Categorical (nominal).	Follow-up at 2 years of age
Treatment for above obstructive symptoms during the past 12 months	Categorical (nominal).	Follow-up at 2 years of age
Speech and language development	Categorical (ordinal)	Follow-up at 2 years of age
Visual impairment	Categorical (Yes/No)	Follow-up at 2 years of age
Visual impairment, left; right	Categorical (ordinal).	Follow-up at 2 years of age
Hearing impairment	Categorical (Yes/no)	Follow-up at 2 years of age
Hearing impairment, left; right	Categorical (ordinal)	Follow-up at 2 years of age
Bayley score (all scores for all categories)	Numerical variable.	Follow-up at 2 years of age
Assessed as normal development at follow-up	Categorical (Yes/No).	Follow-up at 2 years of age
Assessed as not normal in following area	Catetorical (nominal). Motor deficiency; Cognition, communication; Visual; Hearing	Follow-up at 2 years of age
Seizure disorder	Categorical (ordinal)	Follow-up at 2 years of age
Hydrocephalus	Categorical (categorical)	Follow-up at 2 years of age
Cerebral paresis	Categorical (Yes/No).	Follow-up at 2 years of age
Gross motor function scale	Categorical (ordinal).	Follow-up at 2 years of age
Any new diagnoses after discharge	ICD- 10-codes.	Follow-up at 2 years of age
Asthma or obstructive respiratory symptoms during the past 12 months	Categorical (nominal).	Follow-up at 5,5 years of age
Treatment for above during the past 12 months	Categorical (ordinal)	Follow-up at 5,5 years of age
Visual impairment	Categorical (Yes/No).	Follow-up at 5,5 years of age
Visual impairment, left	Categorical (ordinal).	Follow-up at 5,5 years of age
Visual impairment, right	Categorical (ordinal).	Follow-up at 5,5 years of age
Hearing impairment	Categorical (Yes/No)	Follow-up at 5,5 years of age
Hearing impairment, left	Categorical (ordinal)	Follow-up at 5,5 years of age
Hearing impairment, right	Categorical (ordinal)	Follow-up at 5,5 years of age
Speech and language development	Categorical (ordinal)	Follow-up at 5,5 years of age
Seizure disorder	Categorical (ordinal)	Follow-up at 5,5 years of age
Hydrocephalus	Categorical (ordinal)	Follow-up at 5,5 years of age
Cerebral paresis	Categorical (Yes/No).	Follow-up at 5,5 years of age
Gross motor function scale	Categorical (ordinal).	Follow-up at 5,5 years of age
Manual abilities classification system	Numerical variable.	Follow-up at 5,5 years of age
WIPPSI, (all scores for all categories)	Numerical variable.	Follow-up at 5,5 years of age
Strengths and difficulties questionnaire (SDQ) scores	Numerical variable.	Follow-up at 5,5 years of age
Any new diagnoses after discharge	ICD-10 codes	Follow-up at 5,5 years of age
Assessed as normal development at follow-up	Categorical (Yes/No)	Follow-up at 5,5 years of age
Assessed as not normal in following area	Categorical (nominal)	Follow-up at 5,5 years of age

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain score	Continous variable. Using neonatal pain scale. Centre specific and scale may vary.	Before, during and up to 1h after procedure

Collaborators and Investigators

• Sponsor: Vastra Gotaland Region
• Collaborators: Göteborg University
• Investigators: Principal Investigator: Anders Elfvin, Professor, Department of Neonatology, Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Region Västra Götaland, Sweden

Publications and helpful links

General Publications

• Abdel-Latif ME, Davis PG, Wheeler KI, De Paoli AG, Dargaville PA. Surfactant therapy via thin catheter in preterm infants with or at risk of respiratory distress syndrome. Cochrane Database Syst Rev. 2021 May 10;5(5):CD011672. doi: 10.1002/14651858.CD011672.pub2.
• Abdel-Latif ME, Walker E, Osborn DA. Laryngeal mask airway surfactant administration for prevention of morbidity and mortality in preterm infants with or at risk of respiratory distress syndrome. Cochrane Database Syst Rev. 2024 Jan 25;1(1):CD008309. doi: 10.1002/14651858.CD008309.pub3.
• Sweet DG, Carnielli VP, Greisen G, Hallman M, Klebermass-Schrehof K, Lavizzari A, Ozek E, Te Pas A, Roehr CC, Saugstad OD, Simeoni U, Vento M, Visser GHA, Speer CP. European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2025. Neonatology. 2026 Mar 9:1-26. doi: 10.1159/000551062. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Estimated): April 27, 2026
• Primary Completion (Estimated): April 27, 2029
• Study Completion (Estimated): August 27, 2029

Study Registration Dates

• First Submitted: April 17, 2026
• First Submitted That Met QC Criteria: April 17, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: INSURE; Premature infants; Intubation; RDS; Preterm infants; Respiratory Distress Syndrome; Laryngeal Mask Airway; LISA; Supraglottic Airway; SALSA; Surfactant therapy; Less Invasive Surfactant Therapy; Surfactant via Laryngeal or Supraglottic Airway
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Respiratory Distress Syndrome, Newborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Premature Birth; Respiratory Distress Syndrome; Pulmonary Atelectasis; Hyaline Membrane Disease
• Other Study ID Numbers: DNR 2026-00189-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data may be made available upon reasonable request to the principal investigator. Data will be shared in a de-identified form to the greatest extent possible, following review and approval to ensure compliance with informed consent provisions, ethics committee approval, and applicable legal and data protection requirements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No