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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.