Elevated Protein Biomarker Predict Brain Injury in Newborns

Increased blood levels of a protein specific to central nervous system cells help physicians identify newborns with brain injuries due to lack of oxygen.

Measurements of the protein that are vital to the brain’s structure can also track how well a body-cooling therapy designed to prevent permanent brain damage is working.

Scientists at the Johns Hopkins Children's Center (Baltimore, MD, USA) studied the levels of glial fibrillary acidic protein (GFAP) in 23 newborns born between 36 and 41 weeks’ gestation who were diagnosed with clinical oxygen deficiency to the brain (hypoxic-ischemic encephalopathy, or HIE). They compared these levels with those from babies born at the same point in the pregnancy without brain injury.

The investigators developed an electrochemiluminescent sandwich immunoassay for GFAP using the Mesoscale platform (MesoScale Discovery; Gaithersburg, MD, USA). This method uses a trio of mouse monoclonal antibodies for capture and a rabbit polyclonal for detection. The lower limit of quantitation was 0.04 ng/mL; values below this were reported as zero.

As part of the study, the scientists obtained the GFAP protein from cord blood at the time of birth, from neonatal blood drawn upon admission to the neonatal intensive care unit (NICU) and from daily blood specimens over a seven-day period. GFAP levels were significantly higher in babies with brain injury due to a lack of oxygen during the first week of life. Infants in the study, who had abnormal brain MRI scans and treated with whole-body cooling, had the highest levels of GFAP. The treatment lowers body temperature to 33.5 °C, beginning within six hours of birth and continuing for three days. Half of the babies with brain injury in this study had increased levels of GFAP after completion of the 72-hour cooling period.

Ernest M. Graham, MD, a maternal-fetal medicine expert at Johns Hopkins, noted that GFAP, a circulating brain-specific protein, is already measured in adult patients after stroke, cardiac arrest, or traumatic brain injury in an effort to provide a prognosis for survival or brain damage. He added, “Now we know this biomarker can serve as a valid predictor of disease, injury evolution, and outcome in newborns." The authors concluded that GFAP could be used to more specifically and sensitively diagnose brain injury at birth. This could facilitate triage of infants into HIE treatment protocols with hypothermia plus adjuvant treatments, serve as an intermediate outcome to benchmark evolving HIE therapies, and give prognostic information to the parents of these at risk children.

The study was published September 2011, in the American Journal of Obstetrics and Gynecology .

Related Links:
Johns Hopkins Children's Center
MesoScale Discovery