Searching molecular biomarkers correlating with BSID-III at 24 months in infants with neonatal hypoxic-ischemic encephalopathy

Autores de IIS La Fe

• Mari Merce Cascant Vilaplana

  Autor

• Jose David Piñeiro Ramos

  Autor

• Álvaro José Solaz García

  Autor

• Inmaculada Lara Cantón

  Autor

• Laura Isabel Izquierdo Izquierdo

  Autor

• Roberto Llorens Salvador

  Autor

• María Del Pilar Marín Muela

  Autor

• Ester Torres Martínez

  Autor

• Nuria Boronat González

  Autor

• Julia Kuligowski

  Autor

• Máximo Vento Torres

  Autor

Participantes ajenos a IIS La Fe

• Molitor, C
• Mohareb, F
• Quintás, G
• HYPOTOP Study Grp

Grupos

• Perinatología

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:center dot The early prediction of outcomes of neonatal hypoxic-ischemic encephalopathy (NE) is of key importance in reducing neonatal mortality and morbidity.center dot Alterations of the metabolome and miRNAs had been observed in NE.center dot 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.center dot Specific miRNAs and metabolites that allow prediction of middle-term neurodevelopmental outcomes of newborns with NE undergoing hypothermia treatment were identified.

Keywords

• Metabolomics; MicroRNAs; Neurodevelopmental outcomes; Brain injury; Newborn