Lipid Profiles from Dried Blood Spots Reveal Lipidomic Signatures of Newborns Undergoing Mild Therapeutic Hypothermia after Hypoxic-Ischemic Encephalopathy.

Rebekah Nixon,Ping K Yip,Paul Clarke,Vennila Ponnusamy,Albert Koulman,Benjamin Jenkins,Adina T Michael-Titus,Divyen K Shah,Ting Hin Richard Ip

doi:10.3390/nu13124301

Abstract

Hypoxic-ischemic encephalopathy (HIE) is associated with perinatal brain injury, which may lead to disability or death. As the brain is a lipid-rich organ, various lipid species can be significantly impacted by HIE and these correlate with specific changes to the lipidomic profile in the circulation. Objective: To investigate the peripheral blood lipidomic signature in dried blood spots (DBS) from newborns with HIE. Using univariate analysis, multivariate analysis and sPLS-DA modelling, we show that newborns with moderate–severe HIE (n = 46) who underwent therapeutic hypothermia (TH) displayed a robust peripheral blood lipidomic signature comprising 29 lipid species in four lipid classes; namely phosphatidylcholine (PC), lysophosphatidylcholine (LPC), triglyceride (TG) and sphingomyelin (SM) when compared with newborns with mild HIE (n = 18). In sPLS-DA modelling, the three most discriminant lipid species were TG 50:3, TG 54:5, and PC 36:5. We report a reduction in plasma TG and SM and an increase in plasma PC and LPC species during the course of TH in newborns with moderate–severe HIE, compared to a single specimen from newborns with mild HIE. These findings may guide the research in nutrition-based intervention strategies after HIE in synergy with TH to enhance neuroprotection.

Highlights

Lipid extraction was successful from dried blood spots (DBS) for the samples from 64 (82%) newborns; a total of 78 samples (21—mild Hypoxic-ischemic encephalopathy (HIE) group, 57—moderate–severe HIE group) were processed
We demonstrate that in newborns with moderate–severe HIE treated with therapeutic hypothermia (TH), there is an overall reduction in TG and SM classes and an increase in the PC and LPC classes of lipids in comparison to the mild HIE group, in the peripheral circulation, detected using DBS
We demonstrated that several lipid species differentiate between newborns with mild HIE and those with moderate–severe HIE undergoing TH

Summary

Introduction

Hypoxic-ischemic encephalopathy (HIE) remains an important global cause of death and disability in newborns [1]. Mild therapeutic hypothermia (TH) is shown to be effective in reducing death and disability, with a numbers needed to treat value of seven [2], and is considered a standard of care [3,4]. The brain contains the largest quantities and the widest diversity of lipid classes and species (Supplementary Table S1) of all the organs in the body [5]. Their functions include lipid–protein and lipid–lipid interactions, lipid trafficking, signal transduction, 4.0/)

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