Johns Hopkins researchers have discovered that increased blood levels of a protein specific to central nervous system cells that are vital to the brain's structure can help physicians identify newborns with brain injuries due to lack of oxygen.
Measurements of the protein can also track how well a body-cooling therapy designed to prevent permanent brain damage is working. A detailed report of the Hopkins team's finding is published in the current American Journal of Obstetrics and Gynecology.
The yearlong study looked at 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) and compared them with those in babies born at the same point in the pregnancy without brain injury."
HIE may cause death in the newborn period or result in developmental delay, mental retardation or cerebral palsy. In the United States, the incidence of HIE is 1 to 8 cases per 1000 births.
"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," says Ernest M. Graham, M.D., associate professor of gynecology and obstetrics and a maternal-fetal medicine expert at Johns Hopkins. "Now we know this biomarker can serve as a valid predictor of disease, injury evolution and outcome in newborns," he adds.
As part of the study, researchers 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.
"Obstetricians and neonatologists face the challenging task of quickly identifying HIE in newborns, because current markers for identification have been imprecise," says Graham. "GFAP tests may fill that need."
Infants in the study who had abnormal brain MRI scans and were treated with whole-body cooling had the highest levels of GFAP. The treatment lowers body temperature to 92.3 degrees Fahrenheit, beginning within six hours of birth and continuing for three days.
"Even though cooling therapy decreases the risk of death and neurological damage in newborns, it is far from perfect therapy, and its effectiveness varies from baby to baby," says co-investigator Allen Everett, M.D., a pediatric cardiologist at the Johns Hopkins Children's Center. "We don't really know for sure if during the 72 hours of cooling the brain is actually recovering. Biomarkers like GFAP can remove that uncertainty by telling physicians how the brain is responding, allowing them to tailor treatments accordingly."
Half of the babies with brain injury in this study had increased levels of GFAP after completion of the 72 hour cooling period, Graham noted. "The increase after cooling could result from continued brain injury or could be evidence of rewarming injury. We have no surrogate markers of therapeutic success. It is possible that brain proteins such as GFAP will fill this gap."
According to Graham, mild cooling immediately after HIE preserves cerebral energy metabolism, reduces cytotoxic edema and improves histological and functional outcome.
"Although preliminary, the researchers' findings may pave the way for a larger study of blood samples and at longer and deeper cooling to see how well this biomarker can help gauge the effectiveness of treatment. Future studies are necessary to learn how increased GFAP levels are associated with neurological disability, as assessed by long-term follow-up and degree of injury on brain MRI," Graham says.