Hormone may be vital in improving brain development in premature babies

Update: In January 2020, the New England Journal of Medicine published results from the completed PENUT (Preterm Epo Neuroprotection) Trial. The study found that erythropoietin (Epo) treatment administered to extremely preterm infants did not result in a lower risk of neurodevelopmental disabilities when tested at 2 years of age. Babies receiving Epo as part of the study required less transfusions in volume and number, resulting in a lower exposure to blood donors. Other research underway continues to study the use of Epo to treat term babies whose brains did not get enough oxygen at birth (asphyxia).

No soon-to-be parent ever wants to think they may meet their baby too soon, but this is unfortunately the reality for the parents of about 50,000 infants who are born premature in the U.S. each year. Premature babies often face a host of medical problems and also are at a higher risk for long-term neurodevelopmental disabilities. In fact, prematurity accounts for about 45 percent of kids with cerebral palsy, 35 percent of kids with vision impairment, and 25 percent of kids with mental or hearing impairment.

Seattle Children’s neonatologist Sandra Juul, MD, PhD, suspects a hormone called erythropoietin (Epo) holds the key to reducing the negative effects that premature birth can have on the brain, and she has launched a national, multi-center trial to test this theory.

In the randomized, placebo-controlled study, called the PENUT (Preterm Epo Neuroprotection) Trial, 940 extremely preterm infants (born between 24-28 weeks gestation) will be enrolled at 18 research centers and 29 hospitals across the nation. The University of Washington is the primary enrolling site in Washington, but eligible patients who are then transferred to Seattle Children’s Hospital will also be involved. The study is funded by the National Institute of Neurological Disorders and Stroke (NINDS).

“Between 40 to 50 percent of extremely preterm infants either die or have severe or moderate neurodevelopmental impairment,” said Juul. “With this research, we hope to have a significant impact on these outcomes and improve the quality of life for thousands of premature babies – so they are not left deaf or blind, with cerebral palsy or mentally impaired to the point that they fail in school.”

Why the focus on Epo?

Epo is a hormone that’s required for survival and is produced in the brain and kidneys. It has been used in a lower dose for many years to treat or prevent anemia in preemies because it stimulates the production of red blood cells, and can reduce the need for blood transfusions.

But Juul has found that Epo is also essential for the growing brain.

“There is a great deal of preclinical evidence that Epo improves brain development and protects the brain from injury. It does this by aiding in the development of neurons and also decreasing inflammation,” said Juul. “Recent clinical trials have proven that higher doses of Epo are safe, but now we want to know what impact it can have on a child’s future.”

Participants in the study will be enrolled immediately after delivery, before 24 hours of age, and will be given 1000 units/kilo of Epo every other day for six doses, a little more than double the dose usually given to treat anemia. Once the patient is 2 years of age, researchers will then test their mental and motor skills to see how the hormone affected brain development.

Juul said they are currently in the beginning of active enrollment, enrolling about 43 patients to date, and she said that parents have been very receptive to being involved.

“It’s a very difficult time for parents, but once they understand the risks their child faces, and that we have something that can potentially improve their child’s outcome, they are hopeful about the impact it may have,” she said.

Juul is a pioneer in neonatal neuroprotection research and has led the way in examining the potential benefit of Epo for the past 19 years. Her interest in the hormone first began when she learned that Epo receptors were present on mouse neurons and she started looking into what more this could mean.

Based on her years of previous research, she is optimistic about the improvement they will see in neurodevelopmental outcomes from this study.

“We want these children to be better – to be given a much greater chance at having a more normal life where they are able to reach their full potential,” she said.

To learn more about the study, please visit the PENUT Trial website.


If you are a member of the media and would like to arrange an interview with Dr. Juul, please contact Seattle Children’s PR team at 206-987-4500 or [email protected].