Early Prediction of Hypoxic-Ischemic Brain Injury by a New Panel of Biomarkers in a Population of Term Newborns.

Simona Negro,Giuseppe Buonocore,Floris Groenendaal,Elisa Belvisi,Frank Van Bel,Fabrizio Proietti,Manon J N L Benders,Maria Luisa Tataranno,Serafina Perrone,Caterina Coviello,Linda S De Vries,Mariangela Longini

doi:10.1155/2018/7608108

Abstract

This research paper is aimed at evaluating the predictive role of a default panel of oxidative stress (OS) biomarkers for the early identification of infants at high risk of HIE and their validation through the correlation with MRI findings. A multicenter prospective observational study was performed between March 2012 and April 2015 in two European tertiary NICUs. Eighty-four term infants at risk for HIE (pH < 7, BE < −13 mmol/L, and 5′ Apgar < 5) were enrolled. Three were excluded for chromosomal abnormalities and one due to lack of blood samples. The final population was divided according to the severity of perinatal hypoxia into 2 groups: mild/moderate HIE and severe HIE. Advanced oxidation protein products (AOPP), non-protein-bound iron (NPBI), and F2-isoprostanes (F2-IsoPs) were measured in blood samples at P1 (4–6 hours), P2 (24–72 hours), and P3 (5 days), in both groups. MRIs were scored for the severity of brain injury, using a modified Barkovich score. The mean GA was 39.8 weeks (SD 1.4) and the mean birth weight 3538 grams (SD 660); 37 were females and 43 males. Significantly lower 5′ Apgar score, pH, and BE and higher Thompson score were found in group II compared to group I at birth. Group II showed significantly higher AOPP and NPBI levels than group I (mean (SD) AOPP: 15.7 (15.5) versus 34.1 (39.2), p = 0.033; NPBI 1.1 (2.5) versus 3.9 (4.4), p = 0.013) soon after birth (P1). No differences were observed in OS biomarker levels between the two groups at P2 and P3. A regression model, including adjustment for hypothermia treatment, gender, and time after birth, showed that AOPP levels and male gender were both risk factors for higher brain damage scores (AOPP: OR 3.6, 95% CI (1.1–12.2) and gender: OR 5.6, 95% CI (1.2–25.7), resp.). Newborns with severe asphyxia showed higher OS than those with mild asphyxia at birth. AOPP are significantly associated with the severity of brain injury assessed by MRI, especially in males.

Highlights

Birth asphyxia is largely recognized as the most frequent cause of acute interruption of oxygen to the fetus and the most common cause of brain damage [1]
The inclusion criteria were the presence of perinatal asphyxia defined as at least three of the following criteria: (1) late decelerations on fetal monitoring or meconium staining; (2) delayed onset of respiration, resuscitation, or ventilation of at least 10 min; (3) Apgar scores < 5 at 5 minutes; (4) arterial cord blood pH < 7.1 with a base deficit > 16 mmol/L or serum lactate > 10 mmol/L; (5) multiorgan failure, followed by symptoms of encephalopathy, such as altered alertness, abnormal tone, feeding difficulties, or seizures demonstrated by a Thompson score ≥ 7 and/or
The mild group was not considered for hypothermia, while the severe group was considered eligible for hypothermia

Summary

Introduction

Birth asphyxia is largely recognized as the most frequent cause of acute interruption of oxygen to the fetus and the most common cause of brain damage [1]. MRI is the gold standard for the early evaluation of brain injury after HIE, including traditional neuroimaging methods and advanced imaging techniques (DWI, 1H-MRS, and ASL) [8,9,10,11]. In this context, the use of specific biomarkers that will increase within the first hours of life in hypoxic-ischemic neonates may help in the early diagnosis of HIE and promptly identify neonates who may qualify for neuroprotection.

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Conclusion