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Am J Perinatol 2021; 38(07): 734-740
DOI: 10.1055/s-0039-3400981
Original Article

Utilization of Erythropoietin within the United States Neonatal Intensive Care Units from 2008 to 2017

Kaashif A. Ahmad 
1   Pediatrix Medical Group of Texas–San Antonio, San Antonio, Texas
2   Department of Pediatrics, Baylor College of Medicine, San Antonio, Texas
3   Center for Research, Education, Quality and Safety, MEDNAX, Sunrise, Florida
,
Monica M. Bennett
4   Center for Clinical Effectiveness, Baylor Scott & White Health, Dallas, Texas
,
Sandra E. Juul
5   Department of Pediatrics, University of Washington, Seattle, Washington
,
Robin K. Ohls
6   Department of Pediatrics, University of Utah, Salt Lake City, Utah
,
Reese H. Clark
3   Center for Research, Education, Quality and Safety, MEDNAX, Sunrise, Florida
,
Veeral N. Tolia
3   Center for Research, Education, Quality and Safety, MEDNAX, Sunrise, Florida
7   Pediatrix Medical Group of Texas, Dallas, Texas
8   Department of Pediatrics, Baylor University Medical Center, Dallas, Texas
› Author Affiliations Funding None.
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Abstract

Objective Little data are available regarding erythropoietin (Epo) utilization patterns within neonatal intensive care units (NICUs). We sought to describe the trends in Epo utilization across a large cohort of U.S. NICUs.

Study Design This is a retrospective cohort study of infants discharged from 2008 to 2017 using the Pediatrix Clinical Data Warehouse.

Results We identified 704,159 eligible infants from 358 sites, of whom 9,749 (1.4%) had Epo exposure. For extremely low gestational age newborns (ELGANs), Epo exposure ranged from 7.6 to 13.5%. We found significant site variability in Epo utilization in ELGANs. Among the 299 NICUs caring for ELGANs during the study period, 184 (61.5%) never used Epo for this population, whereas 21 (7%) utilized Epo in 50% or more of eligible infants. Epo was initiated at a median of 25 days in ELGANs. For infants with hypoxic–ischemic encephalopathy (HIE), Epo exposure remained ≤1% through 2014 then increased fourfold to 3.4% by 2017. The median day of Epo initiation was the day of birth for infants diagnosed with HIE.

Conclusion Epo is utilized in ELGANs more commonly than for other NICU populations. Utilization patterns appear to indicate the treatment of established anemia for ELGANs and more recently for neuroprotection in patients diagnosed with HIE.

Keywords

erythropoietin - hypoxic–ischemic encephalopathy - neuroprotection - prematurity - ELGAN


Publication History

Received: 16 July 2019

Accepted: 19 October 2019

Article published online:
13 December 2019

© 2019. Thieme. All rights reserved.

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  • References

  • 1 Shannon KM, Mentzer WC, Abels RI. et al. Recombinant human erythropoietin in the anemia of prematurity: results of a placebo-controlled pilot study. J Pediatr 1991; 118 (06) 949-955
    CrossrefPubMedGoogle Scholar
  • 2 Ohls RK, Christensen RD. Recombinant erythropoietin compared with erythrocyte transfusion in the treatment of anemia of prematurity. J Pediatr 1991; 119 (05) 781-788
    CrossrefPubMedGoogle Scholar
  • 3 Emmerson AJ, Coles HJ, Stern CM, Pearson TC. Double blind trial of recombinant human erythropoietin in preterm infants. Arch Dis Child 1993; 68 (3 Spec No): 291-296
    CrossrefPubMedGoogle Scholar
  • 4 Ohls RK, Hunter DD, Christensen RD. A randomized, double-blind, placebo-controlled trial of recombinant erythropoietin in treatment of the anemia of bronchopulmonary dysplasia. J Pediatr 1993; 123 (06) 996-1000
    CrossrefPubMedGoogle Scholar
  • 5 Maier RF, Obladen M, Scigalla P. et al; European Multicentre Erythropoietin Study Group. The effect of epoetin beta (recombinant human erythropoietin) on the need for transfusion in very-low-birth-weight infants. N Engl J Med 1994; 330 (17) 1173-1178
    CrossrefPubMedGoogle Scholar
  • 6 Shannon KM, Keith III JF, Mentzer WC. et al. Recombinant human erythropoietin stimulates erythropoiesis and reduces erythrocyte transfusions in very low birth weight preterm infants. Pediatrics 1995; 95 (01) 1-8
    CrossrefPubMedGoogle Scholar
  • 7 Fauchère JC, Koller BM, Tschopp A, Dame C, Ruegger C, Bucher HU. Swiss Erythropoietin Neuroprotection Trial Group. Safety of early high-dose recombinant erythropoietin for neuroprotection in very preterm infants. J Pediatr 2015; 167 (01) 52-57
    CrossrefPubMedGoogle Scholar
  • 8 Natalucci G, Latal B, Koller B. et al; Swiss EPO Neuroprotection Trial Group. Effect of early prophylactic high-dose recombinant human erythropoietin in very preterm infants on neurodevelopmental outcome at 2 years: a randomized clinical trial. JAMA 2016; 315 (19) 2079-2085
    CrossrefPubMedGoogle Scholar
  • 9 Ohls RK, Cannon DC, Phillips J. et al. Preschool assessment of preterm infants treated with darbepoetin and erythropoietin. Pediatrics 2016; 137 (03) e20153859
    CrossrefPubMedGoogle Scholar
  • 10 Song J, Sun H, Xu F. et al. Recombinant human erythropoietin improves neurological outcomes in very preterm infants. Ann Neurol 2016; 80 (01) 24-34
    CrossrefPubMedGoogle Scholar
  • 11 Lowe JR, Rieger RE, Moss NC. et al. Impact of erythropoiesis-stimulating agents on behavioral measures in children born preterm. J Pediatr 2017; 184: 75-80
    CrossrefPubMedGoogle Scholar
  • 12 Wu YW, Bauer LA, Ballard RA. et al. Erythropoietin for neuroprotection in neonatal encephalopathy: safety and pharmacokinetics. Pediatrics 2012; 130 (04) 683-691
    CrossrefPubMedGoogle Scholar
  • 13 Leuchter RH, Gui L, Poncet A. et al. Association between early administration of high-dose erythropoietin in preterm infants and brain MRI abnormality at term-equivalent age. JAMA 2014; 312 (08) 817-824
    CrossrefPubMedGoogle Scholar
  • 14 Rogers EE, Bonifacio SL, Glass HC. et al. Erythropoietin and hypothermia for hypoxic-ischemic encephalopathy. Pediatr Neurol 2014; 51 (05) 657-662
    CrossrefPubMedGoogle Scholar
  • 15 Wu YW, Mathur AM, Chang T. et al. High-dose erythropoietin and hypothermia for hypoxic-ischemic encephalopathy: a phase II trial. Pediatrics 2016; 137 (06) e20160191-e20160191
    CrossrefPubMedGoogle Scholar
  • 16 Mulkey SB, Ramakrishnaiah RH, McKinstry RC. et al. Erythropoietin and brain magnetic resonance imaging findings in hypoxic-ischemic encephalopathy: volume of acute brain injury and 1-year neurodevelopmental outcome. J Pediatr 2017; 186: 196-199
    CrossrefPubMedGoogle Scholar
  • 17 Juul SE, Mayock DE, Comstock BA, Heagerty PJ. Neuroprotective potential of erythropoietin in neonates; design of a randomized trial. Matern Health Neonatol Perinatol 2015; 1: 27
    CrossrefPubMedGoogle Scholar
  • 18 Juul SE, Comstock BA, Heagerty PJ. et al. High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL): a randomized controlled trial - background, aims, and study protocol. Neonatology 2018; 113 (04) 331-338
    CrossrefPubMedGoogle Scholar
  • 19 ClinicalTrials.gov. PAEAN - Erythropoietin for Hypoxic Ischaemic Encephalopathy in Newborns (PAEAN). Accessed July 1, 2019 at: https://clinicaltrials.gov/ct2/show/NCT03079167
    PubMedGoogle Scholar
  • 20 Spitzer AR, Ellsbury DL, Handler D, Clark RH. The Pediatrix BabySteps Data Warehouse and the Pediatrix QualitySteps improvement project system--tools for “meaningful use” in continuous quality improvement. Clin Perinatol 2010; 37 (01) 49-70
    CrossrefPubMedGoogle Scholar
  • 21 Ohlsson A, Aher SM. Early erythropoiesis-stimulating agents in preterm or low birth weight infants. Cochrane Database Syst Rev 2017; 11: CD004863
    PubMedGoogle Scholar
  • 22 Aher SM, Ohlsson A. Late erythropoiesis-stimulating agents to prevent red blood cell transfusion in preterm or low birth weight infants. Cochrane Database Syst Rev 2019; 2: CD004868
    PubMedGoogle Scholar
  • 23 Hsieh EM, Hornik CP, Clark RH, Laughon MM, Benjamin Jr DK, Smith PB. Best Pharmaceuticals for Children Act—Pediatric Trials Network. Medication use in the neonatal intensive care unit. Am J Perinatol 2014; 31 (09) 811-821
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Juul S. Erythropoietin in anemia of prematurity. J Matern Fetal Neonatal Med 2012; 25 (Suppl. 05) 80-84
    CrossrefPubMedGoogle Scholar
  • 25 Guillén U, Cummings JJ, Bell EF. et al. International survey of transfusion practices for extremely premature infants. Semin Perinatol 2012; 36 (04) 244-247
    CrossrefPubMedGoogle Scholar
  • 26 Zhu C, Kang W, Xu F. et al. Erythropoietin improved neurologic outcomes in newborns with hypoxic-ischemic encephalopathy. Pediatrics 2009; 124 (02) e218-e226
    CrossrefPubMedGoogle Scholar
  • 27 Elmahdy H, El-Mashad A-R, El-Bahrawy H, El-Gohary T, El-Barbary A, Aly H. Human recombinant erythropoietin in asphyxia neonatorum: pilot trial. Pediatrics 2010; 125 (05) e1135-e1142
    CrossrefPubMedGoogle Scholar
  • 28 Malla RR, Bhat MA. Erythropoietin monotherapy in perinatal asphyxia with moderate to severe encephalopathy: a randomized placebo-controlled trial. J Perinatol 2018; 38 (03) 294-294
    CrossrefPubMedGoogle Scholar
  • 29 Mayock DE, Comstock BA, Heagerty P, Juul SE. PENUT Trial Study Group. The relationship between retinopathy of prematurity and erythropoietin in extremely low gestational age neonates. Paper presented at the 2019 Pediatric Academic Society Meetings, Baltimore, MD, April 28, 2019
    PubMedGoogle Scholar
  • 30 Westfall JM, Mold J, Fagnan L. Practice-based research--“Blue Highways” on the NIH roadmap. JAMA 2007; 297 (04) 403-406
    CrossrefPubMedGoogle Scholar
  • 31 Morris ZS, Wooding S, Grant J. The answer is 17 years, what is the question: understanding time lags in translational research. J R Soc Med 2011; 104 (12) 510-520
    CrossrefPubMedGoogle Scholar
  • 32 Hanney SR, Castle-Clarke S, Grant J. et al. How long does biomedical research take? Studying the time taken between biomedical and health research and its translation into products, policy, and practice. Health Res Policy Syst 2015; 13: 1
    CrossrefPubMedGoogle Scholar
  • 33 Grant J, Green L, Mason B. Basic research and health: a reassessment of the scientific basis for the support of biomedical science. Res Eval 2003; 12: 217-224
    CrossrefPubMedGoogle Scholar
  • 34 Tolia VN, Murthy K, McKinley PS, Bennett MM, Clark RH. The effect of the national shortage of vitamin A on death or chronic lung disease in extremely low-birth-weight infants. JAMA Pediatr 2014; 168 (11) 1039-1044
    CrossrefPubMedGoogle Scholar
  • 35 Laughon MM, Chantala K, Aliaga S. et al. Diuretic exposure in premature infants from 1997 to 2011. Am J Perinatol 2015; 32 (01) 49-56
    PubMedGoogle Scholar
  • 36 Ellsworth MA, Harris MN, Carey WA, Spitzer AR, Clark RH. Off-label use of inhaled nitric oxide after release of NIH consensus statement. Pediatrics 2015; 135 (04) 643-648
    CrossrefPubMedGoogle Scholar
  • 37 Carey WA, Weaver AL, Mara KC, Clark RH. Inhaled nitric oxide in extremely premature neonates with respiratory distress syndrome. Pediatrics 2018; 141 (03) e20173108
    CrossrefPubMedGoogle Scholar
  • 38 Bixler GM, Powers GC, Clark RH, Walker MW, Tolia VN. Changes in the diagnosis and management of patent ductus arteriosus from 2006 to 2015 in United States neonatal intensive care units. J Pediatr 2017; 189: 105-112
    CrossrefPubMedGoogle Scholar