A recent study published in JAMA Network Open investigated the long-term effects of the intubate-recruit-surfactant-extubate (IN-REC-SUR-E) technique in extremely preterm neonates. The multicenter randomized clinical trial followed infants who received IN-REC-SUR-E, a lung recruitment maneuver using high-frequency oscillatory ventilation (HFOV) before surfactant administration, and compared them to those treated with the standard intubate-surfactant-extubate (IN-SUR-E) technique. The primary aim was to determine if IN-REC-SUR-E offered improved neurodevelopmental, growth, and respiratory outcomes at 2 years corrected postnatal age (cPNA).
The study, conducted across 35 tertiary neonatal intensive care units (NICUs) in Italy, enrolled spontaneously breathing extremely preterm neonates (24 0/7 to 27 6/7 weeks’ gestation) who met failure criteria for continuous positive airway pressure within the first 24 hours of life. A total of 137 infants were followed up at cPNA 2 years, with 64 in the IN-SUR-E group and 73 in the IN-REC-SUR-E group.
Key Findings
The primary outcome, the occurrence of death after discharge or major disability at cPNA 2 years, showed no significant difference between the two groups. Specifically, 20.3% of children in the IN-SUR-E group experienced this outcome compared to 13.7% in the IN-REC-SUR-E group (P=.36). Secondary outcomes, including neurodevelopmental issues such as cerebral palsy and cognitive impairment, also showed no significant differences.
Anthropometric measurements, including weight, length, and head circumference, were similar between the groups. Furthermore, the incidence of recurrent respiratory infections and hospitalizations due to respiratory causes did not differ significantly.
Implications for Clinical Practice
According to the researchers, these findings suggest that the IN-REC-SUR-E technique is a safe method for the measured outcomes. The study's lead author, Francesca Gallini from the Neonatology Unit, Ospedale Isola Tiberina, Gemelli Isola, Rome, Italy, noted that the results could aid clinicians in decision-making for the best strategy to administer surfactant, considering long-term outcomes.
Multivariable Analysis
A multivariable log-binomial regression analysis revealed that birth weight was associated with lower odds of death or major disability (OR, 0.74; 95% CI, 0.56-0.96; P=.03), while intraventricular hemorrhage greater than grade 2 was associated with higher odds (OR, 3.42; 95% CI, 1.13-10.66; P=.04). The treatment type (IN-REC-SUR-E vs. IN-SUR-E) did not significantly affect the primary outcome.
Study Limitations
The authors acknowledged several limitations, including the lack of a priori estimate of composite death or major disability in the original RCT design. The overlapping SARS-CoV-2 pandemic also influenced hospitalization rates, and the reliance on retrospective anamnestic data collected via questionnaires submitted to parents during follow-up appointments. Additionally, the study lacked nutritional data on breastmilk versus formula milk administration and objective assessments of lung volumes.
Future Directions
Despite these limitations, the researchers emphasize the need for further multicenter studies to confirm their results and to prospectively evaluate neurodevelopmental outcomes, growth, and respiratory health in patients treated with IN-REC-SUR-E compared to IN-SUR-E. The study team plans to include lung function tests for planned follow-up of the whole multicenter population of the IN-REC-SUR-E vs IN-SUR-E RCT that will enroll children aged 5 years and older.
