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Table 1 Characteristics of the studies examining the effects of iron supplementation in low birth weight infants

From: Benefits of Iron supplementation for low birth weight infants: A systematic review

Study Agea Sample Sizeb Eligibility Iron Dose, Duration of
Treatment / Follow-up
Measurements
Hammond et al. 1960[22] 2-3 wks T: 26
C: 22
Premature birth T: 100 mg intramuscular iron-dextran; C: No iron
Treatment: 1 mo; Follow-up: 12 mo
Hematologic: Hb, HCT, PCV, RBC
Brozovic et al. 1974[23] 5 wks 47 GA: 29–37 wks
BW: 920–1870 g
36.3 mg/d oral iron
Treatment and follow-up: 9 mo
Hematologic: Hb, SI, TIBC
Lundstrom et al. 1977[2] 2 wks T: 40
C: 50
BW: 1050–2000 g T: 2 mg/kg/d oral iron; C: No iron
Treatment and follow-up: 6 mo
Hematologic: Hb, MCV, reticulocyte count, SI, SF, TRNSAT, TIBC
Iwai et al. 1986[24] 3 mo Formula: 30
Human milk:15
GA: 30–40 wks
BW: 1000–2499 g
Formula: 8 mg/L oral iron
Treatment: 3 mo; Follow-up: 6 mo
Hematologic: Hb, RBC, SF, iron, TIBC, MCV
Hall et al. 1993[25] 8-10 d High iron: 20
Low iron: 23
Human
milk: 13
GA: < 35 wks
BW: < 1800 g
High: 1.3 mg/kg/d oral iron; Low: 0.3 mg/kg/d oral iron; Milk: 0.3 mg/kg/d iron
Treatment: 25–34 d; Follow-up: ~11-13 wks
Hematologic: Hb, MCV, TRNSAT, SF, HCT, RBC, PLFE
Development: weight, length, head circumference
Griffin et al. 1999[26] 3 d A: 29
B: 34
C: 15
GA: ≥ 32 wks
BW: < 1750 g
A: 0.9 mg/dL iron formula (1.17 mg/kg/d); B: 0.5 mg/dL iron formula (0.81 mg/kg/d); C: 0.9 mg/dL iron formula until term and then 0.5 mg/dL iron formula (0.86 mg/kg/d)
Treatment: 6 mo; Follow-up: 12 mo
Hematologic: Hb, plasma ferritin
Franz et al. 2000[27] 14/61 d T: 68
C: 65
BW: < 1301 g T: 2–4 mg/kg/d oral iron once enteral feeding was tolerated; C: No iron
Treatment and follow-up: Until 61 days of age
Hematologic: SF, TRNAST, HCT, MCV, MCH, RBC, ID
Friel et al. 2001[28] Birth High: 29
Normal: 29
BW: < 2500 g High: 20.7 mg/L iron formula (0.6-5.9 mg/ kg/d); Normal: 13.4 mg/L iron formula (0.6- 3.0 mg/kg/d)
Treatment and follow-up: 12 mo
Hematologic: Hb, HCT, SF, TRN, TRNSAT, MCV, PLFE
Development: WTZ, GDA, HTZ
Oxidative stress: MDA, PLZN, PLCU, FRAG, CAT, SOD, GHSPx
Adverse effects: frequency of infection
Aggarwal et al. 2005[29] 50-80 d T: 37
C: 36
GA: ≥ 37 wks
BW: < 2500 g
T: 3 mg/kg/d oral iron; C: No iron
Treatment and follow-up: 8 wks
Hematologic: Hb, SF, microcytic hypochromic, NCHC, NCNC
Development: weight, length, head circumference
Miller et al. 2006[30] 7-60 d T: 16
C: 16
GA: 24–32 wks T: 3–12 mg/kg/d oral iron; C: No iron
Treatment and follow-up: 2–3 wks
Hematologic: RBC, SI, SF, TIBC, ZnPP/H, sTfR
Adverse effects: blood and urine isoprostanes
Arnon et al. 2007[31] 2 or 4 wks 2 wks: 32
4 wks: 36
GA: < 32 wks 5 mg/kg/d oral iron
Treatment and follow-up: 4–6 wks
Hematologic: SI, SF, sTfR, reticulocyte, Hb
Adverse effects: morbidity
Steinmacher et al. 2007[32] 14/61 d Early: 90
Late: 74
BW: < 1301 g Early (14 d): 2–4 mg/kg/d oral iron;
Late (61 d): 2 mg/kg/d oral iron
Treatment: until BW = 1.6x birth BW; Follow up: 5.3 yrs
Neurologic examination, neurophysiological testing (Gross Motor Functioning Classification Scale, Lincoln-Oseretzky Scale, Kaufmann Assessment Battery for Children, visual impairment, and Child Behavior Check List)
Braekke et al. 2007[33] 5 wks 21 GA: < 32 wks
BW: < 1500 g
9.4 mg/kg/d oral iron
Treatment and follow-up: 1 wk
Hematologic: Hb, reticulocytes, iron, SF, TRNSAT
Oxidative stress: urine isoprostane, urine 2,3 dinor, plasma total hydroperoxides
Plasma antioxidants: AA, TAA, DHAA, alpha tocopherol, FRAP, GGT, total glutathione
Sankar et al. 2009[34] 2 wks T: 22,
C: 24
BW: < 1500 g T: 3–4 mg/kg/d oral iron; C: No iron
Treatment and follow-up: 60 d
Hematologic: SF, Hb
Adverse effects: morbidity
Berglund et al. 2010[35] 6 wks T1: 78
T2: 82
C: 83
BW: 2000–2500 g T1: 1 mg/kg/d oral iron; T2: 2 mg/kg/d oral iron; C: No iron
Treatment: 6 wks to 6 mo of age; Follow-up: up to 6 mo
Hematologic: Hb, SF, MCV, PLFE, TRN, TRNSAT, sTfR, ID, IDA
Development: weight, weight SD score, length, length SD score, head circumference, head circumference SD score, knee-heel length
Adverse effects: morbidity
  1. AA, ascorbic acid; BW, birth weight; C, control; CAT, catalase; CGA, corrected gestational age; d, days; DHAA, dehydroascorbic acid; FRAG, red blood cell fragility; GA, gestational age; GDA, Griffiths’ Development Assessment; GHSPx, glutathione peroxidase; GGT, Gamma-glutamyl transferase; Hb, Hemoglobin; HCT, hematocrit; HTZ, height for age z score; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; ID, iron deficiency; IDA, iron deficiency anemia; MCV, mean corpuscular volume; MDA, malondialdehyde; mo, month; NA, not available; NCHC, normocytic hypochromic; NCNC, normocytic normochromic; PCV, packed cell volume; PLFE, plasma iron; PLCU, plasma copper; PLZN, plasma zinc; RBC, red blood cell; ROP, retinopathy of prematurity; SF, serum ferritin; SI, serum iron; SOD, superoxide dismutase; sTfR, soluble transferrin receptor; T, iron supplementation group; TAA, total ascorbic acid; TIBC, total iron binding capacity; TRN, transferrin; TRNSAT, transferrin saturation; wks, weeks; WTZ, weight for age z score; ZnPP/H, zinc protoporphyrin to heme ratio.
  2. a Age at the start of supplementation.
  3. b Data analysis sample size.