Related Experiment Video
Updated: Jun 23, 2025
Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants
Published on: March 14, 2013
Searching molecular biomarkers correlating with BSID-III at 24 months in infants with neonatal hypoxic-ischemic
Mari Merce Cascant-Vilaplana1, Jose David Piñeiro-Ramos1, Álvaro Soláz-García1,2
1Neonatal Research Group, Health Research Institute La Fe, Valencia, Spain.
Insights
Early prediction of neonatal hypoxic-ischemic encephalopathy (NE) outcomes is crucial. Researchers identified specific metabolites and miRNAs that can help predict neurodevelopmental outcomes in NE infants undergoing therapeutic hypothermia.
Area of Science:
- Neonatal Medicine
- Biochemistry
- Genetics
Background:
- Neonatal hypoxic-ischemic encephalopathy (NE) poses significant risks for mortality and morbidity.
- Early prediction of NE outcomes is vital for timely intervention and improved patient care.
- Alterations in miRNA expression and metabolic profiles are observed in NE patients.
Purpose of the Study:
- To analyze miRNA expression and metabolic patterns in NE neonates.
- To assess the predictive performance of these biomarkers for neurodevelopmental outcomes.
- To identify specific metabolites and miRNAs for predicting outcomes in NE infants.
Main Methods:
- Plasma samples from NE patients and healthy controls were collected before, during, and after therapeutic hypothermia.
- miRNA sequencing and quantification of metabolites (hypoxia-related, energy, steroid, tryptophan metabolism) were performed.
- Neurodevelopmental outcomes were assessed at 24 months using the Bayley Scales of Infant Development (BSID-III).
Main Results:
- Distinct miRNA and metabolic profiles differentiated NE infants from controls and correlated with neurodevelopmental outcomes.
- Specific metabolites (e.g., 4-androstene-3,17-dione, testosterone, betaine, xanthine, lactate) and 68 miRNAs showed predictive value (AUCs ≥ 0.6).
- Xanthine, betaine, and several miRNAs significantly correlated with BSID-III sub-scales.
Conclusions:
- Identified metabolites and miRNAs show potential for predicting middle-term neurodevelopmental outcomes in NE.
- These biomarkers can aid in supporting clinical decisions for NE management.
- The study provides novel insights into the molecular mechanisms underlying NE outcomes.
Abstract:
An early prediction of outcomes of neonatal hypoxic-ischemic encephalopathy (NE) is of key importance in reducing neonatal mortality and morbidity. The objectives were (i) to analyze the characteristics of miRNA expression and metabolic patterns of neonates with NE and (ii) to assess their predictive performance for neurodevelopmental outcomes. Plasma samples from moderate/severe NE patients (N = 92) of the HYPOTOP study were collected before, during, and after therapeutic hypothermia (TH) and compared to a control group (healthy term infants). The expression of miRNAs and concentrations of metabolites (hypoxia-related and energy, steroid, and tryptophan metabolisms) were analyzed. Neurodevelopmental outcomes were evaluated at 24 months postnatal age using Bayley Scales of Infant Development, ed. III, BSID-III. Differences in miRNA and metabolic profiles were found between NE vs. control infants, abnormal (i.e., mildly and moderately abnormal and severe) vs. normal, and severe vs. non-severe (i.e., normal and mildly and moderately abnormal) BSID-III. 4-Androstene-3,17-dione, testosterone, betaine, xanthine, and lactate were suitable for BSID-III outcome prediction (receiver operating characteristic areas under the curve (AUCs) ≥ 0.6), as well as 68 miRNAs (AUCs of 0.5-0.9). Significant partial correlations of xanthine and betaine levels and the expression of several miRNAs with BSID-III sub-scales were found. Conclusion: We have identified metabolites/miRNAs that might be useful to support the prediction of middle-term neurodevelopmental outcomes of NE. What is known and what is new: • The early prediction of outcomes of neonatal hypoxic-ischemic encephalopathy (NE) is of key importance in reducing neonatal mortality and morbidity. • Alterations of the metabolome and miRNAs had been observed in NE. • We performed miRNA sequencing and quantified selected metabolites (i.e., lactate, pyruvate, ketone bodies, Krebs cycle intermediates, tryptophan pathway, hypoxia-related metabolites, and steroids) by GC- and LC-MS. • Specific miRNAs and metabolites that allow prediction of middle-term neurodevelopmental outcomes of newborns with NE undergoing hypothermia treatment were identified.
