Plasma Biomarkers of Evolving Encephalopathy and Brain Injury in Neonates with Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: The objective of the study was to evaluate the relationship between a panel of candidate plasma biomarkers and (1) death or severe brain injury on magnetic resonance imaging (MRI) and (2) dysfunctional cerebral pressure autoregulation as a measure of evolving encephalopathy. STUDY DESIGN: Neonates with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) at 2 level IV neonatal intensive care units were enrolled into this observational study. Patients were treated with therapeutic hypothermia (TH) and monitored with continuous blood pressure monitoring and near-infrared spectroscopy. Cerebral pressure autoregulation was measured by the hemoglobin volume phase (HVP) index; a higher HVP index indicates poorer autoregulation. Serial blood samples were collected during TH and assayed for Tau, glial fibrillary acidic protein, and neurogranin. MRIs were assessed using National Institutes of Child Health and Human Development scores. The relationships between the candidate biomarkers and (1) death or severe brain injury on MRI (defined as a National Institutes of Child Health and Human Development score of ≥ 2B) and (2) autoregulation were evaluated using bivariate and adjusted logistic regression models. RESULTS: Sixty-two patients were included. Elevated Tau levels on days 2-3 of TH were associated with death or severe injury on MRI (aOR: 1.06, 95% CI: 1.03-1.09; aOR: 1.04, 95% CI: 1.01-1.06, respectively). Higher Tau was also associated with poorer autoregulation (higher HVP index) on the same day (P = .022). CONCLUSIONS: Elevated plasma levels of Tau are associated with death or severe brain injury by MRI and dysfunctional cerebral autoregulation in neonates with HIE. Larger-scale validation of Tau as a biomarker of brain injury in neonates with HIE is warranted.

Perinatal Inflammatory Biomarkers and Respiratory Disease in Preterm Infants.

OBJECTIVE: To measure plasma levels of vascular endothelial growth factor (VEGF) and several cytokines (Interleukin [IL]-6 IL-8, IL-10) during the first week of life to examine the relationship between protein expression and likelihood of developing respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD). STUDY DESIGN: Levels of IL-6, IL-8, IL-10, and VEGF were measured from plasma obtained from preterm patients during the first week of life. Newborns were recruited from a single center between April 2009 and April 2019. Criteria for the study included being inborn, birth weight of less than 1500 grams, and a gestational age of less than 32 weeks at birth. RESULTS: The development of RDS in preterm newborns was associated with lower levels of VEGF during the first week of life. Higher plasma levels of IL-6 and IL-8 plasma were associated with an increased likelihood and increased severity of BPD at 36 weeks postmenstrual age. In contrast, plasma levels of VEGF, IL-6, IL-8, and IL-10 obtained during the first week of life were not associated with respiratory symptoms and acute care use in young children with BPD in the outpatient setting. CONCLUSIONS: During the first week of life, lower plasma levels of VEGF was associated with the diagnosis of RDS in preterm infants. Preterm infants with higher levels of IL-6 and IL-8 during the first week of life were also more likely to be diagnosed with BPD. These biomarkers may help to predict respiratory morbidities in preterm newborns during their initial hospitalization.