Outcomes of extremely low birth weight infants given early high-dose erythropoietin

Abstract

Objective To evaluate long-term outcomes of 60 extremely low birth weight (ELBW) infants treated with or without three injections of high-dose erythropoietin (Epo). Study Design A retrospective analysis of anthropometric and neurodevelopmental outcome data comparing 30 ELBW infants enrolled in a phase I/II study examining the pharmacokinetics of high-dose Epo (500, 1000 and 2500 U/kg × 3 doses) administered to 30 concurrent controls. Result Birth characteristics and growth from 4 to 36 months were similar for untreated and Epo-treated patients. Multiple linear regression analysis of neurodevelopmental follow-up scores from 17/25 Epo-treated and 18/26 control infants identified that Epo correlated with improvement of cognitive (R = 0.22, P = 0.044) and motor (R = 0.15, P = 0.026) scores. No negative long-term effects of Epo treatment were evident. Conclusion Retrospective analysis of the only available long-term follow-up data from ELBW infants given high-dose Epo treatment suggests that Epo treatment is safe and correlates with modest improvement of neurodevelopmental outcomes.

Recombinant human erythropoietin improves neurological outcomes in very preterm infants

“…This high‐dose rhEPO in rodents was equivalent to that in preterm infants given at a high dose of 1,000 to 2,500U/kg 20. Based on those results from neonatal rodent brain injury models, clinical studies showed that high‐dose rhEPO (2,500–3,000U/kg) administered after birth was well tolerated in preterm and term infants14, 20, 33, 37, 42 and conferred neuroprotection 16, 36. In a previous study using low‐dose rhEPO to prevent anemia in preterm infants, it was observed that preterm infants with rhEPO treatment also had significant neurodevelopmental improvement 38.…”

“…Hearing status was determined from parental reports and supplemented with auditory brainstem response measurements. Deafness was defined as a hearing disability that required amplification 33. Blindness was defined as a corrected visual acuity of <20/200 33.…”

“…Deafness was defined as a hearing disability that required amplification 33. Blindness was defined as a corrected visual acuity of <20/200 33. Moderate or severe disabilities were defined as survival with at least 1 of the following complications: cerebral palsy, MDI < 70, deafness, or blindness.…”

Cognitive Outcomes of Preterm Infants Randomized to Darbepoetin, Erythropoietin, or Placebo

“…Recent clinical studies also suggest a potential for neonatal neuroprotection. 7,8,21,22 European investigators reported improved developmental outcomes at age 8 to 12 years in former Epo-treated preterm infants, especially those who had significant brain injury during initial hospitalization. 11 Brown and colleagues reported improved cognitive…”

A Review of Regulatory Guidance for Conducting Hepatic Impairment Studies: A Case Study in Oncology

“…Considering the importance of the effects of liver function impairment on PK during drug development, the FDA published a guidance document in May 2003 on the design, conduct, analysis, and reporting of hepatic impairment studies and their impact on dosing and labeling [19] . Soon after, the EMEA provided guidelines in August 2005 for PK evaluation of medicinal products in patients with impaired hepatic function [5] .…”