ESAs Administered Early Boost Preemies' Cognitive Scores

ESAs Administered Early Boost Preemies' Cognitive Scores

May 12, 2014

Prematurely born infants who received erythropoiesis-stimulating agents (ESAs) in the first 60 hours of life registered significantly higher cognitive scores at 18 to 22 months and higher scores on tests of object permanence (OP), according to a prospective, randomized study.

The research, led by Robin K. Ohls, MD, from the Department of Pediatrics, University of New Mexico, Albuquerque, builds on the researcher's more than 2 decades of work with ESAs and was published online May 12 in Pediatrics.

For more than 20 years, ESAs have been the clinical workhorse used to stimulate red cell production, from preemies to adults with anemia, and to decrease the number and volume of transfusions. Animal studies showed neuroprotection in the developing brain, providing tantalizing hints of the potential for similar results in preemies.

Roughly 500,000 babies, or 1 in 8, are born preterm, or before 37 weeks of pregnancy, according to the Centers for Disease Control and Prevention. Although such neurodevelopmental disabilities as cerebral palsy and learning and attention deficits are common among children who were extremely low weight at birth, there are no successful neuroprotective interventions, Dr. Ohls and colleagues write.

The researchers sought to determine whether premature infants who received ESAs would require fewer transfusions and whether darbepoetin (Darbe), a biologically modified long-acting ESA, would be effective in improving developmental outcomes.

They enrolled 102 infants older than 48 hours who weighed 500 to 1250 g at birth at 4 high-elevation centers in New Mexico, Utah, and Colorado. Ultimately, 29 infants received 400 U/kg erythropoietin (Epo) subcutaneously 3 times per week; 27 received 10 μg/kg Darbe, given subcutaneously once with additional 2 sham doses per week; and 24 infants received 3 placebo doses weekly. The infants were evaluated at age 18 to 22 months.

"Infants randomized to ESAs had significantly higher composite cognitive scores, and scored higher on the test for OP, with a trend towards higher language scores," Dr. Ohls and colleagues write. "Scores were similar between Epo and Darbe groups for all tests, with the exception of OP, for which scores in the Darbe group were higher than those in the Epo group (P = .01). None of the infants in the Darbe group had a cognitive score <85."

Dr. Ohls tells Medscape Medical News that 100 is normal in the scale they are using; preemies in the treatment groups were registering cognitive outcome scores of 96.2 to 97.9, which is very close to term and almost a 10-point difference from the placebo group, which had scores of 88.7.

"It's probably one of the largest differences, based on a single treatment, of any intervention we've done," she said.

With funding from the National Institutes of Health, the researchers are using complex testing and magnetic resonance imaging to look at whether ESA-related gains translate to longer-term benefits for children aged 4 and 6 years, when developmental and behavioral differences can become more pronounced. "We're still kind of trying to ferret that out," she told Medscape Medical News.

"Darbe and Epo administration to preterm infants resulted in higher cognitive, and OP scores at 18 to 22 months' corrected age," the authors conclude.

"As such, Epo and Darbe may serve as a beneficial therapy for preterm infants not only in the acute hospitalization in which the risk for anemia exists, but also as possible neuroprotective agents to improve neurodevelopmental outcomes."

Financial support for the study was provided by the Thrasher Research Fund, the University of New Mexico, and the University of Colorado. The authors have disclosed no relevant financial relationships.

Pediatrics. Published online May 12, 2014.