title: Practice points - Neonatal Intensive Care Drug Manual
text: Prior to prescription of iron, consider factors including (1) whether delayed cord clamping was performed with current haematocrit and or haemoglobin, (2) iron being received from the diet, (3) amount of blood loss through bloodletting or haemorrhage and (4) any packed red cell transfusions received .
  Common 0–6 month cow’s milk infant formulas in Australia containing 5–8 mg/L provide an average 1 mg/kg/day of iron and therefore require supplemental iron in preterm and low birthweight infants.
  The current iron supplementation and blood transfusions policies in tertiary neonatal intensive care units are less likely to result in iron deficiency during their NICU stay as was evident in a study by Park SH et al 2015. However, iron deficiency is likely post-discharge in preterm infants<37 weeks or low birthweight infants <2.5 Kg if iron intakes are inadequate.3
  National blood authority defines iron deficiency anaemia in infancy as low haemoglobin for the age plus low serum ferritin (<20 microg/L or <50 microg/L in the presence of systemic infection, chronic disease, liver disease).8
  ESPGHAN 2019 recommendations in preterm infants, particularly birthweight <1800 g: (1) Iron intakes of <2 mg/kg/day are likely to result in iron deficiency in preterm infants, at least in those with birth weights <1800 g. (2) Because high enteral iron intakes have been associated with possible adverse effects, an intake of 2 to 3 mg/kg/day is recommended. (3) Prophylactic enteral iron supplementation (given as a separate iron supplement, in preterm formula or in fortified human milk) should be started at 2 to 6 weeks of age (2–4 weeks in extremely-low-birthweight infants). (4) Infants who receive erythropoietin treatment and infants who have had significant, uncompensated blood losses may initially need a higher dose, requiring a separate iron supplement in addition to preterm formula or fortified human milk. (5) Enteral iron doses >5 mg/kg/day should be avoided in preterm infants because of the possible risk of retinopathy of prematurity. (6) Iron supplementation should be delayed in infants who have received multiple blood transfusions and have high serum ferritin concentrations.9
  ESPGHAN 2014 recommendations for birthweights 2000–2500 g – 1–2 mg/kg/day for up to 6 months of age.24
  American Academy of Pediatrics (AAP) recommendations: Supplementation of preterm neonates recommended at 2 mg/kg/ day of enteral iron, either as an iron mixture, or in the form of iron-fortified formula. It is recommended that this supplementation commence within two months of birth and be continued until 12 months of age.33
  ESPGHAN 2018 recommendations: Preterm and term infants need parenteral iron 200–250 microgram/kg/day and 50–100 microgram/kg/day respectively during long-term PN >4 weeks duration.14
  ESPGHAN 2014 summary on iron requirements in infants and toddlers:24
  General prevalence of IDA (defined as serum ferritin <10–12 microgram/L) in European infants and toddlers is <2% before 6 months, 2–3% at 6–9 months and 3–9% at 1–3 years of age
  If low before 6 months of age; 0.9–1.3 mg/kg/day at 6–12 months; 0.5–0.8 mg/kg/day at 1–3 years
  Breastfed infants <6 months: Iron supplementation do not reduce iron deficiency anaemia in populations with already low (<5–10%) prevalence of IDA at 6 months
  In low-birthweight infants <6 months, iron supplements (1–3 mg/kg/day depending on birthweight) prevent IDA and possibly improve neurodevelopment
  Iron supplements at 4–12 months prevent IDA and may improve neurodevelopment but only in populations with high (>10%) prevalence of IDA at 6–12 months of age
  1 g of haemoglobin contains 3.5 mg of iron. Based on these numbers, 1 mL of bloodletting with an average 150 g/L of haemoglobin results in net iron loss of 0.5 mg of iron. Packed red cells, on average, contain 180 g/L (48 g in a 260 mL adult red cell pack) of haemoglobin and haematocrit of 0.50–0.70.1 1 mL of packed red cells contain 0.6 mg (0.5–1 mg) of iron.
  The amount of iron lost through blood collection can be calculated using the following formula:
  Blood Iron (mg) = Hb (g/dL) x 3.5 (mg/mL) x blood loss (mL).35
  The term infant with normal iron stores at birth, who benefitted from delayed cord clamping, is breastfed, and is growing at a rate consistent with the World Health Organization standard growth curves, requires no additional iron beyond what is found in human milk until 4–6 months of age.47
  Serum ferritin concentrations: Umbilical cord serum ferritin concentrations increased with advancing gestational age, from a mean of 63 microg/L at 23 weeks to 171 microg/L at 41 weeks gestation (p <0.001).25 Higher ferritin concentrations were reported in preterm infants who received intrauterine transfusion, recipients of twin-twin transfusions or received transfusions of more than 100 mL of packed red cells.26-28 Lundström, et al studied ferritin concentrations in LBW infants receiving iron supplementation who did not receive transfusion. By age 2 months ferritin concentrations averaged 60–70 microg/L and remained between 20 and 40 microg/L up to 6 months of age.29
  Parenteral iron therapy for iron deficiency: Surico et al38 compared intramuscular and intravenous administration in 33 children with severe iron deficiency who failed to respond to oral iron. Mean age was 3.1 years (range 0.7–13.5). Intravenous iron (iron saccharate) was given daily as a 2-hour infusion in a normal saline solution, at an average dose of 28 mg/kg (range 10–50) depending on haemoglobin values, administered over an average time of 6.5 days (range 3–10). The infusion was preceded by a 10-min infusion test dose. Intramuscular iron (iron polymaltose complex) was given twice per week at an average dose of 20 mg/kg (range 8.5–40), depending on haemoglobin values at diagnosis, over an average period of 26 days (range 14–56). Parenteral iron doses have been calculated taking into account haemoglobin values and weight of children at diagnosis, according to the following formula:
  Total iron dose (mg) = (desired Hb – observed Hb) x 80 mL x BW x 0.03438
  A non-neonatal age group study by Martini et al used IV iron saccharate to treat iron deficiency anaemia in children with juvenile chronic arthritis using the formula:
  Total iron dose (mg) = (12.5 – haemoglobin(g/dL) x body weight x 3.4 x 1.4
  In this formula, 12.5 is the ideal haemoglobin, 3.4 is the milligrams of iron in 1 g haemoglobin and 1.4 a multiplication factor accounting for iron stores.15
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