Perinatal asphyxia, also known as hypoxic-ischemic encephalopathy (HIE), affects roughly 2-3 per 1,000 live births in the United States. The injury is caused by poor blood and oxygen flow to the brain around the time of birth. HIE can cause severe long-term effects, such as neurodevelopmental delays, cerebral palsy, heart problems, and even death.
For decades, neonatologists have relied on a scientifically proven form of therapy for HIE. Using a cooling blanket over the baby, therapeutic hypothermia helps lower the overall body temperature, reducing inflammation and promoting proper brain healing after injury. However, not much is known on how preterm infants respond to the therapy, as previous studies validating the therapy's effectiveness were only completed in term and near-term infants.
A new multisite clinical trial, led by researchers at the UNC School of Medicine and the University of Utah Health Sciences Center and funded by the NICHD Neonatal Research Network, found that the first line treatment for HIE does not improve health outcomes-and may harm- infants born at 33-, 34-, and 35-weeks' gestation. Their findings were published in JAMA Pediatrics.
"Before this study, it was not known if preterm infants with HIE benefitted from therapeutic hypothermia," said Matthew Laughon, MD, MPH, professor of neonatal-perinatal medicine and co-author on the study. "We found that this form of therapy, more likely than not, harms preterm infants. This is not something that should be done routinely for pre-term babies."
The NICHD Neonatal Research Network conducted a randomized clinical trial across 19 Neonatal Research Network centers around the United States, including the University of North Carolina-Chapel Hill, to determine whether therapeutic hypothermia was effective at reducing severe disability and/or death in preterm infants.
Over the course of seven years, 168 preterm infants with HIE were recruited and studied in the clinical trial. Researchers divided participants into two groups to see if hypothermia or normothermia (normal body temperature) saw better health outcomes. Within six hours of birth, 83 preterm infants were given hypothermia treatment, as part of the treatment group, and 69 preterm infants were kept at normal body temperature, as part of the control group.
The results were clear. Out of the 83 participants who received therapeutic hypothermia, 29 (35%) of them were diagnosed with severe disability or death. Whereas, in group who received normothermia, 20 of the 69 (29%) participants were diagnosed with severe disability or death.
More research is needed to understand why exactly preterm babies do not respond well to therapeutic hypothermia. However, Laughon says this study serves as a great jumping off point, to at least prevent further death and disability in this patient population.
"The main message of the study is that we should always study therapies in different populations or new environments before being routinely adopted by the field," said Laughon, who is also a member of the UNC Children's Research Institute. "Preterm infants are fragile and require specialized care. We must adjust our therapies to continue treating them as such."
Despite one therapy being deemed ineffective in preterm infants, more work is being done in the field to help improve health outcomes for those living with HIE through adjuvant therapies, like drugs or medications.
"Premature infants should not receive the hypothermia, but there may be medicines in the future that can help them," said Laughon. "There is hope for those babies who come out with HIE."
