Metabolic response to extended continuous positive airway pressure in premature infants.

BACKGROUND

Extending the duration of continuous positive airway pressure (CPAP) in preterm infants with respiratory distress may improve lung function.

OBJECTIVE

Assess the impact of extended CPAP (eCPAP) on the metabolomic profile and relationship to lung function.

DESIGN/

METHODS

Infants ≤32 weeks' gestational age were randomized to bubble eCPAP with room air or discontinued CPAP (dCPAP). Functional residual capacity (FRC) was measured at randomization and at 2 weeks. Blood samples obtained during treatment were subjected to UHPLC:MS/MS (Metabolon Inc.) and metabolomic data were analyzed by ANCOVA.

RESULTS

eCPAP infants had greater increases in both FRC (2.1-fold, p = 0.005) and weight (1.13-fold, p = 0.03). Of 1230 total metabolites detected, levels of 87 were higher at p < 0.05 and 75 were lower in eCPAP infants. A new plateau level for key metabolites occurred at 5 ± 2 days after discontinuing CPAP. Sub pathway enrichment (p < 0.05) occurred for bilirubin degradation products (7.7-fold) and acylcarnitines (3.5-fold), all higher in dCPAP. Blood levels of some metabolites were correlated with FRC and weight gain.

CONCLUSION

Discontinuation of CPAP altered the blood metabolome and impaired gain in FRC and weight. Extending CPAP may reduce the work of breathing, improve mitochondrial utilization of fatty acids, and provide more energy for lung and body growth.

IMPACT: Discontinuing CPAP in premature infants recovering from respiratory distress altered levels of 14% of detected blood metabolites within 1 week and reduced gain in lung function and body weight at 2 weeks. Biochemical sub pathway enrichment occurred for acylcarnitines with higher circulating levels of 22 fatty acid metabolites in infants coming off CPAP. Extending CPAP beyond the current guidelines for discontinuation may reduce the work of breathing, improve mitochondrial utilization of fatty acids, and provide more energy for lung development and body growth.