Targeted urine metabolomics for enhanced diagnosis of hypoxic-ischemic encephalopathy in newborns: A pilot study.

Abstract

While therapeutic hypothermia (cooling treatment) is successful in preventing hypoxic ischemic encephalopathy (HIE), current diagnosis is limited to clinical features and serum lactate. Many newborns at risk of HIE are not identified within the therapeutic window and consequently miss the opportunity for cooling treatment. We hypothesized that metabolomic analysis could more accurately identify infants at risk of HIE compared to other commonly used techniques, such as serum lactate. Newborns admitted for therapeutic hypothermia for HIE, were recruited (n = 11) and compared to four healthy infants. A targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform was used to measure metabolites in urine samples. We identified 15 metabolites that differentiated infants with HIE from healthy controls. The metabolomic signature was subsequently utilized to blindly and accurately re-identify the same infants 3 days later, after clinical recovery, with 100% accuracy, as their metabolic profiles resembled those of non-hypoxic healthy infants. The diagnostic performance of LC-MS/MS was superior to that of lactate alone. Urine metabolomic profiling has the potential to more accurately identify neonates at risk of long-term neurologic injury than lactate alone.

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