Association between newborn screening analytes and hypoxic ischemic encephalopathy

Lindsay A Wilson,Sandra Juul,Mark Walker,Julian Little,Steven Hawken,Thierry Lacaze-Masmonteil,Kumanan Wilson,Malia S Q Murphy,Deshayne B Fell,Coralie A Wong,Beth K Potter,Pranesh Chakraborty

doi:10.1038/s41598-019-51919-x

Abstract

Hypoxic ischemic encephalopathy (HIE) is a major cause of neonatal mortality and morbidity. Our study sought to examine whether patterns of newborn screening analytes differed between infants with and without neonatal HIE in order to identify opportunities for potential use of these analytes for diagnosis in routine clinical practice. We linked a population-based newborn screening registry with health databases to identify cases of HIE among term infants (≥37 weeks’ gestation) in Ontario from 2010–2015. Correlations between HIE and screening analytes were examined using multivariable logistic regression models containing clinical factors and individual screening analytes (acyl-carnitines, amino acids, fetal-to-adult hemoglobin ratio, endocrine markers, and enzymes). Among 731,841 term infants, 3,010 were diagnosed with HIE during the neonatal period. Multivariable models indicated that clinical variables alone or in combination with hemoglobin values were not associated with HIE diagnosis. Although the model was improved after adding acyl-carnitines and amino acids, the ability of the model to identify infants with HIE was moderate. Our findings indicate that analytes associated with catabolic stress were altered in infants with HIE; however, future research is required to determine whether amino acid and acyl-carnitine profiles could hold clinical utility in the early diagnosis or clinical management of HIE. In particular, further research should examine whether cord blood analyses can be used to identify HIE within a clinically useful timeframe or to guide treatment and predict long-term health outcomes.

Highlights

Metabolic profiling of infants diagnosed with Hypoxic Ischemic Encephalopathy (HIE) has identified a number of putative biomarkers that predict injury severity and long-term outcomes, revealing several markers consistent with perturbations in energy metabolism associated with the condition[14]
Our study has demonstrated a moderate association between patterns of metabolites identified through routinely collected newborn screening samples and a diagnosis of HIE
The elevated amino acid and acyl-carnitine levels observed in our cohort of infants with HIE are consistent with the known pathophysiology of systemic hypoxic trauma

Summary

Introduction

Metabolic profiling of infants diagnosed with HIE has identified a number of putative biomarkers that predict injury severity and long-term outcomes, revealing several markers consistent with perturbations in energy metabolism associated with the condition[14]. These include altered Krebs cycle and amino acid metabolites, these have not been validated nor demonstrated as feasible for translation into clinical practice[14]. In order to inform this potential opportunity for the development of a novel approach to identifying HIE in a clinical setting, the primary objective of our study was to assess whether there were any associations between the metabolic profiles generated through a provincial newborn screening program in Ontario, Canada and a diagnosis of HIE in a large, population-based cohort of infants

Objectives

Methods

Results

Conclusion