Infants born with an extremely low birth rate have the potential to develop neurodevelopmental disabilities, such as cerebral palsy (CP), mental disabilities, and learning and attention deficits during school age. As of today, successful neuroprotective interventions have yet to be developed, but a group of scientists have found that two drugs, erythropoietin and darbepoetin, have a strong potential to have neuroprotective effects in infants.
Erythropoietin and darbepoetin are in a class of drugs called erythropoiesis stimulating agents (ESAs), which have been used clinically over 20 years to help stimulate red cell production. Erythropoietin stimulates red blood cell production in adults who have anemia attributable to end-stage renal disease or cancer. Darbepoetin is a biologically modified long-acting ESA that allows dosing every 1 to 4 weeks due to the increased half-life of the drug. Darbepoetin is also used for adults with anemia attributable to end-stage renal disease or cancer. In addition, darbepoetin was shown to have a similar half-life in infants. Premature infants also lack the ability to make new red blood cells so they often need frequent blood transfusions to replace blood taken for lab tests. However, use of erythropoiesis stimulating agents are shown to decrease the number of blood transfusions in premature infants.
In this research study, scientists performed a randomized, masked, and multicenter study comparing erythropoietin, darbepoetin, and placebo given through 35 weeks post conceptual age, with transfusions administered according to protocol. The surviving infants were evaluated at 3.5 and 4 years of age, and the primary outcome was the infant’s composite cognitive score. Assessments of full-scale IQ, general language, and overall measure of executive function, on the basis of tests evaluating inhibitory control and spatial working memory, were conducted.
Rather gathering data, scientists would that the infants randomized to receive the ESAs had better cognitive outcomes compared with placebo recipients at 3.5 and 4 years of age. Specifically, they scored about 12 points higher on average on IQ tests than the untreated infants, but about 10 points lower than the normal weight infants. Furthermore, on tests measuring memory and impulsive behavior, the treated infants had similar results as the infants born at normal weight.
This study mostly examined white and hispanic infants, so larger studies that include more diverse patient populations are needed to determine whether ESAs can help a broader range of infants. Thus, it is still too soon to recommend the medicines for treating developmental delays. However, treatment for medical problems and developmental delays due to prematurity has not kept pace, so this particular finding was significant.
I am glad to see that there are steps being taken to study the developmental delays in premature infants. Possibly in the future, parents can be relieved that their premature infants will be able to avoid potential developmental issues. However, in the future, I hope that there will be more research focusing on other developmental issues associated with premature birth. Do you believe that this finding will have a large impact in the future? What other areas of study related to premature birth do you think researchers should focus on in the future?
Ohls, R. K., Cannon, D. C., Phillips, J., et al. Preschool Assessment of Preterm Infants Treated With Darbepoetin and Erythropoietin. Pediatrics. 2016