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Guidance for prescribing erythropoiesis stimulating agents (ESAs) and concomitant iron therapy in preterm infants

Guidance for prescribing erythropoiesis stimulating agents (ESAs) and concomitant iron therapy in preterm infants
Medications
  Route Dose and frequency
ESAs*
Darbepoetin alfa (our preferred choice) SUBQ/IV
  • 10 mcg/kg/dose once weekly
Epoetin alfa SUBQ
  • 400 units/kg/dose 3 times per week
Epoetin alfa SUBQ
  • 1200 units/kg/dose once weekly
Epoetin alfa IV
  • 200 units/kg/dose once daily in TPN
IronΔ
Enteral iron (used in neonates tolerating enteral feeds)
  • Ferrous sulfate◊
 PO
  • 6 mg elemental iron/kg once daily
IV iron (an option for neonates not yet tolerating enteral feeds)
  • Iron sucrose
 IV
  • 1 mg/kg daily, or
  • 1.5 mg/kg twice weekly, or
  • 3 to 6 mg/kg once weekly
  • Iron dextran§
 IV
  • 0.5 to 1 mg/kg daily, or
  • 1.5 mg/kg twice weekly, or
  • 3 to 6 mg/kg once weekly
Other supplements¥
Multivitamin PO
  • <2 kg: 0.5 mL once daily
  • ≥2 kg: 1 mL once daily
Monitoring
  • Check HCT or Hgb before starting ESA therapy and check reticulocyte hemoglobin (ret-He) or ferritin and ANC every 2 to 4 weeks while on treatment.
  • Hold ESA if ANC falls below 1000/microL; restart once ANC is in normal range.
  • Discontinue ESA if the neonate develops serious toxicity (thrombosis, hypertension, seizure).
  • Monitor adequacy of iron supplementation with ret-He (if available) or serum ferritin:
    • Check at 14 to 28 days of age, then repeat every 2 to 4 weeks while on treatment.
    • If ferritin >400 ng/mL, discontinue iron.
    • If ret-He is >35 pg or ferritin >300 ng/mL, decrease iron by 2 mg/kg/day.
    • If ret-He is <29 pg or ferritin <50 ng/mL, increase oral iron by 2 mg/kg/day; some UpToDate experts increase to a maximum dose of 12 mg/kg/day. If ret-He or ferritin remains low despite the maximal dose of oral iron, consider a single dose of IV iron.
Treatment discontinuation
  • Criteria for discontinuing ESA and iron therapy include any of the following:
    • HCT ≥50%‡
    • Infant's CGA is ≥35 weeks
    • Serious toxicity (neutropenia, thrombosis, hypertension, seizure)
  • It is not necessary to hold ESA or iron therapy after blood transfusions except in the case of double-volume exchange transfusion for alloimmune hemolytic anemia (in which case ESA and iron are held for 2 weeks)
This table summarizes our suggested approach to prescribing ESAs and concomitant iron and other supplement therapy in preterm infants. The practice of using ESAs is not standardized and varies from center to center. ESAs may be used in infants whose parents/caregivers refuse blood transfusions. Some neonatal centers routinely use ESAs for prophylaxis in at-risk preterm neonates. This includes all ELBW infants and select VLBW infants (ie, infants with alloimmune hemolytic anemia, infants requiring frequent blood draws, and/or infants undergoing surgery). There is considerable practice variation regarding the use of ESAs in this setting and the optimal approach is uncertain. Refer to related UpToDate content on anemia of prematurity for additional details.

ANC: absolute neutrophil count; CGA: corrected gestational age; ELBW: extremely low birth weight (<1000 g); ESA: erythropoiesis stimulating agent; HCT: hematocrit; Hgb: hemoglobin; IV: intravenous; MVI: multi-vitamin infusion; PO: per os (by mouth); ret-He: reticulocyte hemoglobin content; SUBQ: subcutaneous; TPN: total parenteral nutrition; VLBW: very low birth weight (<1500 g).

* We recommend preservative-free medications. If darbepoetin is not available, epoetin alfa is an acceptable alternative.

¶ Parenteral epoetin alfa may be administered with TPN as a 24-hour infusion.

Δ When determining the total dose of iron supplementation, all sources of iron should be accounted for (eg, from human milk or formula, MVI, and direct supplementation with iron).

◊ Ferrous sulfate dosing is expressed in terms of elemental iron. Ferrous sulfate oral liquid preparations contain 20% elemental iron. Multiple product concentrations exist; use caution when ordering and switching between products.

§ A test dose of IV iron dextran is recommended prior to starting maintenance dosing.

¥ Some UpToDate experts administer folate (50 micrograms/day) and either an MVI or vitamin E (15 to 25 IU/day) when infants are no longer receiving TPN. Folate is not included in MVI supplements.

‡ For ELBW infants, ESAs can be discontinued if the Hct is >50% after 2 weeks of age. ESAs should be restarted if the Hct decreases to <30% and the infant is <34 to 36 weeks gestation.

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