Early prediction of bronchopulmonary dysplasia by urinary metabolomics: a case-control study

Bronchopulmonary dysplasia (BPD), the most frequent complication of extreme preterm birth, lacks not only of a comprehensive definition but also of effective treatments and predictive tools. Metabolomics is a valuable tool to unravel the underlying pathogenetic pathways of diseases and identify possible early markers. The objective of this study was to find metabolic signatures of subsequent BPD development, defined and stratified as per Jobe and Bancalari 2001 NHICD Consensus.

In this observational case-control study, we initially enrolled 161 very preterm unmatched infants, collected their urine samples during the first 24 hours of life and performed metabolomics evaluations on these samples. Patients were then followed until 36 weeks postmenstrual age. To reduce the influence of gestational age and other confounders on metabolome, we applied a nested case-control matching procedure that allowed the selection of 25 BPD cases and 25 non-BPD controls.

Multivariate and univariate data analysis led to the recognition of 17 metabolites related to BPD development in the first day of life, of which three were identified: L-Glutamic acid (p value=0.038), o-Hydroxyphenylacetic acid (p=0.039), L-Homoserine (p value=0.020). Some of these metabolites are known to play a role in the protection against oxidative stress and/or inflammatory response, two of the most known factors involved in BPD pathogenesis. In particular, L-Glutamic acid and its ionic form glutamate were increased in infants developing BPD suggesting a role as promising marker of the disease.

Our findings pave the way to better characterise early origin of BPD from a metabolic point of view towards a better biological framework of the disease and, eventually, its prediction and possible new treatments.