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

Medications
	Route	Dose and frequency
ESAs (any of the following are acceptable)
Darbepoetin alfa	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 (in TPN)	200 units/kg per 24 hours daily
Iron
Enteral iron (used in neonates tolerating enteral feeds)
Ferrous sulfate*	PO	Initial dose: 6 mg elemental iron/kg once daily Max dose: 12 mg elemental iron/kg/day (for doses ≥8 mg elemental iron/kg/day, divide into 2 daily doses)
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	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
Folate	PO	50 micrograms once daily
Vitamin E	PO	15 international units once daily
Monitoring
Check reticulocyte count, HCT or Hgb, ANC, and ferritin before starting ESA therapy and every 1 to 2 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 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 >200, decrease iron by 2 mg/kg/day If ret-He is <29 pg or ferritin <15 ng/mL, increase oral iron by 2 to 4 mg/kg/day; if ret-He or ferritin remains low despite maximal dose of oral iron, consider single dose of IV iron
Treatment discontinuation
Criteria for discontinuing ESA and iron therapy include ANY of the following: HCT ≥50% Neonate'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 folate therapy in preterm neonates. The practice of using ESAs is not standardized and varies from center to center. ESAs may be used in neonates whose parents/caregivers refuse blood transfusions for religious reasons. In addition, 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 use of ESAs in this setting and the optimal approach is uncertain. Refer to UpToDate's topic on anemia of prematurity for additional detail.

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

* 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.

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