Metabolic analysis of infants with bronchopulmonary dysplasia under early nutrition therapy: An observational cohort study

Abstract

To assess the amino acid and fatty acid metabolite patterns between infants with and without bronchopulmonary dysplasia in different nutritional stages after birth and identify metabolic indicators of bronchopulmonary dysplasia. This was an observational cohort of preterm infants born at a gestational age ≤32 + 6 weeks and with a body weight ≤2000 g. Amino acid and carnitine profiles were measured in dried blood spots (DBSs) during the early nutrition transitional phase using tandem mass spectrometry. Bronchopulmonary dysplasia was defined as oxygen dependence at 36 weeks of postmenstrual age or 28 days after birth. Metabolomic analysis was employed to define metabolites with significant differences, map significant metabolites into pathways, and identify metabolic indicators of bronchopulmonary dysplasia. We evaluated 45 neonates with and 40 without bronchopulmonary dysplasia. Four amino acids and three carnitines showed differences between the groups. Three carnitines (C0, C2, and C6:1) were high in the bronchopulmonary dysplasia group mostly; conversely, all four amino acids (threonine, arginine, methionine, and glutamine (Gln)) were low in the bronchopulmonary dysplasia group. Pathway analysis of these metabolites revealed two pathways with significant changes (p < 0.05). ROC analysis showed Gln/C6:1 at total parenteral nutrition phase had both 80% sensitivity and specificity for predicting the development of bronchopulmonary dysplasia, with an area under the curve of 0.81 (95% confidence interval 0.71–0.89). Amino acid and fatty acid metabolite profiles changed in infants with bronchopulmonary dysplasia after birth during the nutrition transitional period, suggesting that metabolic dysregulation may participate in the development of bronchopulmonary dysplasia. Our findings demonstrate that metabolic indicators are promising for forecasting the occurrence of bronchopulmonary dysplasia among preterm neonates.