519 - Therapeutic Efficacy of Intratracheal Budesonide Delivered with Surfactant in Preterm Infants: A Meta-analysis with Subgroup Evaluation of Extremely Preterm and Extremely Low Birth Weight Neonates

Publication Number: 3500.519

Bhumika Bheemavarapu, Akron Children's Hospital, Akron, OH, United States; Anjani Mahesh Kumar Cherukuri, Guntur Medical College, Guntur, Andhra Pradesh, India

Background: Bronchopulmonary dysplasia (BPD) continues to be a leading cause of morbidity and mortality in preterm infants, especially among those who are extremely preterm or have extremely low birth weight (ELBW). Intratracheal co-administration of budesonide with surfactant has been proposed to reduce pulmonary inflammation and improve respiratory outcomes, yet existing evidence from randomized and observational studies remains heterogeneous.

Objective: To assess the efficacy and safety of intratracheal budesonide combined with surfactant versus surfactant alone in reducing BPD and mortality in preterm infants, including subgroup analyses for ELBW and extremely preterm populations.

Design/Methods: A systematic search of PubMed, Embase, and the Cochrane Library was conducted to identify randomized controlled trials and observational studies evaluating intratracheal budesonide-surfactant therapy compared to surfactant alone. Data were pooled using a random-effects model in RevMan Version 5.4. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. Subgroup analyses were performed for ELBW ( < 1000 g) and extremely preterm ( < 28 weeks of gestation) infants.

Results: Thirteen studies comprising 2,961 infants were included for BPD analysis. Co-administration of budesonide with surfactant significantly reduced BPD incidence (RR = 0.85; 95% CI 0.74-0.97; p = 0.02; I² = 63%). In the ELBW and extremely preterm subgroup (n = 1,518), no significant reduction was observed (RR = 0.97; 95% CI 0.91-1.04; p = 0.41; I² = 0%). For mortality, pooled data from eight studies (n = 2,473) showed no statistically significant difference (RR = 0.82; 95% CI 0.59-1.15; p = 0.25; I² = 46%). The composite outcome of BPD or death, analyzed from eight studies (n = 2,851), was also not significantly different between groups (RR = 1.02; 95% CI 0.96-1.07; p = 0.56; I² = 0%).

Conclusion(s): Intratracheal budesonide and surfactant combination therapy significantly reduces the incidence of BPD in preterm infants without increasing mortality. However, the benefit appears attenuated among extremely preterm and ELBW subgroups. These findings support the potential role of this therapy as an early anti-inflammatory intervention in preterm neonates, though further large-scale studies are warranted to confirm long-term safety and neurodevelopmental outcomes.

Figure 1. Effect of Intratracheal Budesonide-Surfactant on Bronchopulmonary Dysplasia
(a) Incidence of bronchopulmonary dysplasia (BPD) in preterm infants treated with budesonide + surfactant versus surfactant alone.(b) Subgroup analysis restricted to extremely preterm and extremely low-birth-weight infants.


Figure 2. Mortality and Composite Outcomes Following Budesonide-Surfactant Therapy
(a) Risk of death before 36 weeks postmenstrual age.
(b) Composite outcome of bronchopulmonary dysplasia or death.