Acylcarnitine profile in neonatal hypoxic-ischemic encephalopathy: The value of butyrylcarnitine as a prognostic marker

Abstract

Optimal prognostic markers evaluating early neuroprotective interventions in neonatal hypoxic-ischemic encephalopathy (HIE) are lacking. This study was designed to assess the prognostic value of acylcarnitines in neonatal HIE.An observational cohort study was conducted over 10 years in 67 HIE. Variables analyzed included sex, blood cord pH, Apgar score, hypothermia treatment (yes/no), neuron-specific enolase (NSE) levels, and clinical outcome (neurological examination, brain magnetic resonance imaging [MRI], and electroencephalogram) before discharge and at 6 months. Acylcarnitine profiles were analyzed by tandem-mass spectrometry on dried-blood spots collected on day 3 for newborn screening. A cohort of healthy newborns was used as control group.HIE patients had significantly increased C4, C5, C5:1, C6, C6-OH, C8 levels (all P < .01) and decreased long-chain acylcarnitine levels (P < .03). Hypothermia treatment was associated with a decrease in C4 levels (p = 0.005) and an increase in most long-chain acylcarnitine levels (P < .01). A significant association was found between C4 levels and NSE on day 1 of hypothermia treatment (P = .002) and abnormal brain magnetic resonance imaging (MRI) at discharge (P = .037). In the hypothermia group, C4 levels decreased in patients with favorable outcomes but remained high in those who progressed unfavorably.C4 appears to be a good prognostic marker in HIE, as blood levels correlated with NSE levels and abnormal MRI findings. Furthermore, hypothermia did not lead to decreased levels in patients with adverse outcomes.

Figure 1

Flow diagram of patients evaluated on the study period. IMD: inherited metabolic diseases.

Figure 2

Positive correlation between Butyrylcarnitine and NSE determinations in patients under hypothermia treatment. The figure refers to Butyrylcarnitine samples taken at third day of life and NSE samples determined on 27 patients on the first day of therapeutic hypothermia. We found a significant positive correlation (Pearson Correlation = 0.57; P = .002) between Butyrylcarnitine and NSE, which means that at a higher level of NSE, a higher increase in Butyrylcarnitine levels, which would highlight this metabolite as a marker of neuronal insult, since NSE is considered one of the best prognostic biomarkers for HIE. The red circle marks the patients with good outcome.