Whole-Blood Gene Expression and Hypoxic-Ischemic Encephalopathy at Birth.
Whole-blood gene expression distinguished mild from moderate-severe hypoxic-ischemic encephalopathy at birth
Whole-Blood Gene Expression and Hypoxic-Ischemic Encephalopathy at Birth.
IMPORTANCE: Mild hypoxic-ischemic encephalopathy (hypoxic-ischemic encephalopathy) spans a broad spectrum of neurological dysfunction, making early identification challenging and leading to undertreatment or overtreatment.
To investigate whether whole-blood gene expression at birth is associated with hypoxic-ischemic encephalopathy severity (mild, moderate, or severe), to characterize pathways underlying differential expression, and to evaluate temporal changes over the first 72 hours compared with matched healthy controls.
DESIGN, SETTING, AND PARTICIPANTS: This case-control study combines data from the Cooling in Mild Encephalopathy (Cooling in Mild Encephalopathy) pilot randomized clinical trial from October 31, 2019, to April 28, 2023, recruiting infants with mild hypoxic-ischemic encephalopathy and data from 2 prospective observational studies (January 1, 2017, to June 1, 2019, and September 30, 2019, to September 30, 2025) enrolling infants with moderate or severe hypoxic-ischemic encephalopathy and healthy control infants.
genes differed with mild hypoxic-ischemic encephalopathy, distinct from moderate-severe and controls
The median birth weight was 3.3 kg (IQR, 3.0-3.6 kg) for infants with moderate or severe hypoxic-ischemic encephalopathy, 3.3 kg (IQR, 3.1-3.5 kg) for infants with mild hypoxic-ischemic encephalopathy, and 3.4 kg (IQR, 3.0-3.6 kg) for controls.
The median gestational age was 40.0 weeks (IQR, 39.0-40.6 weeks) for infants with mild hypoxic-ischemic encephalopathy, 39.3 weeks (IQR, 39.0-41.0 weeks) for infants with moderate hypoxic-ischemic encephalopathy, and 39.4 weeks (IQR, 39.0-40.4 weeks) for infants with severe hypoxic-ischemic encephalopathy.
In this case-control study of infants with hypoxic-ischemic encephalopathy, whole-blood gene expression at birth was associated with hypoxic-ischemic encephalopathy severity, distinguishing infants with mild hypoxic-ischemic encephalopathy from both controls and those with moderate or severe encephalopathy, supporting its role in risk stratification during the period when neuroprotective interventions remain possible and clinical diagnosis may still be challenging.