Published online September 28, 2009
PEDIATRICS Vol. 124 No. 4 October 2009, pp. e681-e687 (doi:10.1542/peds.2008-2701)
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ARTICLE

Higher Cumulative Doses of Erythropoietin and Developmental Outcomes in Preterm Infants

Mark S. Brown, MD, MSPHa, Delphine Eichorst, MDb, Brenda LaLa-Black, OTRc and Robin Gonzalez, MA, CCC-SLPc

a Department of Pediatrics, Eastern Maine Medical Center, Bangor, Maine; and Departments of
b Pediatrics
c Rehabilitation Services, Presbyterian/St Luke's Medical Center, Denver, Colorado

OBJECTIVE: We hypothesized that higher cumulative doses of recombinant erythropoietin (rEPO) for extremely preterm infants during the first 6 postnatal weeks would improve developmental outcomes, as evidenced in evaluations with the Bayley Scales of Infant Development-II Revised.

METHODS: This was a retrospective cohort study with a data set for a group (N = 366) of infants of <1500 g and ≤30 weeks of gestation that was created initially to examine the association between rEPO treatment and retinopathy of prematurity. Infants who underwent developmental follow-up evaluations at corrected age of >12 months were included. The associations between rEPO doses and higher Bayley Scales of Infant Development Psychomotor Developmental Index and Mental Developmental Index (MDI) scores were estimated in multivariate linear regression analyses.

RESULTS: Eighty-two infants underwent developmental evaluations after 12 months. The median age of evaluation was 25 months. The median 6-week cumulative rEPO dose was 3750 U/kg. In multivariate analyses, Psychomotor Developmental Index (PDI) scores were associated with transfusions, female gender, birth weight, and 5-minute Apgar scores (R2 = 0.39). MDI scores were associated with 6-week rEPO dose, female gender, prenatal steroid treatment for ≥48 hours, and breast milk feedings (R2 = 0.40).

CONCLUSIONS: These findings identify a dose-response relationship between rEPO treatment and improved MDI scores. They are consistent with findings of adult studies and animal brain injury models and await confirmation.

Key Words: premature infant • developmental delay • recombinant erythropoietin

Abbreviations: rEPO—recombinant erythropoietin • PDI—Psychomotor Developmental Index • MDI—Mental Developmental Index

Accepted May 29, 2009.


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