Table 1 Characteristics of randomized controlled trials comparing the effectiveness and safety of interventions for postpartum anaemia
First author, year, country | Main eligibility criteria | Age (years) mean (SD) | Intervention n Control n Baseline Hb (g/dL), | Intervention: dosing and duration of exposure | Control: dosing and duration of exposure | Period of patient recruitment, and duration of follow-up | Primary Outcome |
|---|---|---|---|---|---|---|---|
Bhandal 2006 United Kingdom [33] | Hb < 9 g/dL ferritin < 15 mcg/L | IV Iron: 29 (3.7) Oral iron: 28 (4.1) | IV Iron: n = 22 7.5 (0.8) Oral iron: n = 21 7.3 (0.9) | IV Ferric Sucrose, 200 mg D2 and D4 Total dose 400 mg | Oral ferrous sulphate 200 mg bd for 6 wks Mean total dose NR | 24–48 h postpartum 6 wks | Hb, Hct, ferritin and serum iron on D5, D14 and D40 |
Breymann 2008 Switzerland, Russia, & Romania [34] | Hb < 105 g/L | IV Iron: 27.7 (5.5) Oral iron: 27.5 (5.4) | IV Iron: n = 227 9.7 (1.5) Oral iron: n = 117 9.7 (1.5) | IV FCM, up to 3 weekly doses (maximum 1000 mg per dose) Mean total dose 1346.7 g | Oral ferrous sulphate 100 mg bd for 12 wks Mean total dose NR | Up to 7 days postpartum 12 wks | Hb change at 12 wk |
Damineni 2016 India [35] | Hb 7–10 g/dL | IV Iron: 28.0 Oral iron: 27.4 | IV Iron: n = 45 8.7 (0.8) Oral iron: n = 45 8.9 (0.6) | IV FCM, single 1000 mg dose | Oral ferrous ascorbate 100 mg bd for 6 wks Mean total dose NR | D1 postpartum 6 wks | % to achieve a Hb ≥ 3 g/dL at 6 wks |
Froessler 2013 Australia [36] | Hb < 11 g/dL and ferritin < 12 mcg/L | IV Iron: 28 (26–32) Oral iron: 30 (26–34) | IV Iron: n = 31 9.6a (8.7–10.2) g/dL Oral iron: n = 43 9.5a (8.9–10.6) g/dL | IV Ferric Sucrose, two 200 mg doses over 2 days at least 24 h apart Total dose 400 mg Folic acid 600 mcg daily for 6 weeks | Oral Ferrous sulphate 250 mg with 600 mcg folic acid bd for 6 wks Mean total dose NR | Within 72 h postpartum 6 wks | Hb and ferritin on D14 and 42 |
Guerra Merino 2011 Spain [37] | Hb 7–10 g/dL and ferritin < 15mcg/L | IV Iron: 34 Oral iron: 30 | IV Iron: n = 6 8.9 (0.9) g/dL Oral iron: n = 7 8.6 (1.0) g/dL | IV Ferric Sucrose 200 mg D2 and D4 Total dose 400 mg | Oral ferrous sulphate 200 mg bd for 6 wks Mean total dose NR | 24–48 h postpartum 6 wks | Hb, Hct, ferritin and serum iron on D7, D14 and D42 |
Hamm 2020 America [50] | Requires RBC-T, Hb < 7 g/dL or > 7 g/dL + signs or symptoms of anaemia | Single-unit RBC-T: 29 (6) Multiple-unit RBC-T: 29 (6) | Single-unit: n = 33 6.8 (0.6) g/dL Multiple Unit: n = 33 7.0 (0.6) g/dL | Single-Unit RBC-T Number of units of RBC-T: 1.2 (0.5) | Multiple-Unit RBC-T Number of units of RBCs: 2.1 (0.4) | Up to 4 days postpartum 4–9 wks postpartum | Total units of RBC-T |
Holm 2017a Denmark [38] | PPH > 1000 mL and Hb 5.6—8.1 g/dL | IV-Iron: 30.4 (2.6) RBC-T: 34.5 (3.5) | IV-Iron: n = 7 6.80 (6.4–7.6) g/dL RBC-T: n = 6 6.80 (6.4–7.6) g/dL | IV-iron Isomaltoside Single 1500 mg dose Total dose 1500 mg | RBC-T units calculated from baseline Hb Five received 1-unit RBC-T, one received 2-units |  ≥ 12 h postpartum 12 wks | Change in physical fatigue score within 12 weeks |
Holm 2017b Denmark [49] | PPH ≥ 700 mL and ≤ 1000 mL or PPH > 1000 mL and Hb > 6.5 g/dL | IV-Iron: 32.2 (4.4) Oral iron: 32.6 (4.5) | IV-Iron: n = 97 9.71 g/dL Oral iron: n = 90 9.71 g/dL | IV-iron Isomaltoside Single 1200mg dose | Variable oral iron dosing and timing. Formulation not stated Mean total dose 4784 mg (4309) |  ≥ 12 h postpartum 12 wks | Change in physical fatigue score within 12 weeks |
Jain 2013 India [39] | Hb < 8 g/dL within 48 h postpartum | IV Iron: 24 (3.5) Oral iron: 25 (2.7) | IV Iron: n = 21 6.7 (0.3) Oral iron: n = 20 6.8 (0.2) | IV iron sucrose 100–200 mg three times in one week Total dose 300–600 mg | Oral ferrous fumarate 300 mg for 2 wks Mean total dose NR | 24–48 h postpartum 2 wks | Change in Hb on D7 and D14 |
Mumtaz 2011 India [40] | Hb < 9 g/dL, ferritin < 15 mcg/L | IV Iron: 24.6 (3.7) Oral iron: 25.1 (3.3) | IV Iron: n = 40 8.4 (0.3) Oral iron: n = 40 8.1 (0.5) | IV-iron sucrose Two 200 mg doses on D2 and D4 Total dose 400 mg | Oral ferrous sulphate 200 mg bd for 6 wks Mean total dose NR | 24–48 h postpartum 40 days | Hb, Hct, red-cell indices, ferritin and serum iron on D7, D14 and D40 |
Perello 2014 Spain [47] | Hb 6.0–8.0 g/dL | IV and oral iron: 29.5 (5.8) Oral iron and placebo: 29.9 (5.3) | IV and oral iron: n = 31 7.2 (0.5) g/dL Oral iron and placebo: n = 29 7.3 (0.5) g/dL | IV-iron sucrose & oral ferrous sulphate 525 mg Two × 200 mg of IV-iron on consecutive days, & bd oral iron for 30 days Mean total dose NR | Placebo and oral ferrous sulphate 525 mg Placebo and bd oral iron for 30 days Mean total dose NR |  ≤ 48 h postpartum 6 wks | Change in Hb and Hct at 6 wks |
Prick 2014 Netherlands [12] | PPH ≥ 1000 mL and/or Hb drop ≥ 1.9 g/d/L, and Hb 4.8–7.9 g/dL | RBC-T: 30.7 (5.0) Non-intervention: 30.9 (5.3) | RBC-T: n = 258 7.3 (6.8–7.7) Non-intervention: n = 261 7.4 (6.8–7.7) | RBC-T At least one unit of RBC-T | Non-intervention (n = 261) Oral and IV iron according to local protocol. RBC-T if severe symptoms | 12–24 h postpartum 6 wks | Physical fatigue at D3 postpartum |
Rathod 2015 India [32] | Hb < 10 g/dL | IV-iron FCM: 25.9 (3.6) IV-iron sucrose: 26.0 (3.7) Oral iron: 25.4 (3.1) | IV-iron FCM: n = 100, 7.71 (1.17) IV-iron sucrose: n = 100, 8.05 (1.07) Oral iron: n = 100 8.23 (1.01) | IV-iron FCM Calculated dose not more than once a week Mean total dose NR IV-iron sucrose Calculated dose on alternate days Mean total dose NR | Oral ferrous ascorbate 100 mg od Duration of exposure unclear Mean total dose NR | Recruitment period unclear 6 wks | Changes in Hb and ferritin levels at 2 wks and 6 wks |
Razzaq 2017 Pakistan [41] | Postpartum anaemia (not defined) | IV-Iron: 26.36 (4.3) Oral iron: 26.31 (4.7) | IV-Iron: n = 41 Stratified by baselinec Hb ≤ 7: 53% Hb 71–99: 47% Oral iron: n = 41 Hb ≤ 7: 44% Hb 71–99: 56% | IV-iron formulation unclear Up to 1000 mg given, repeated weekly Mean total dose NR | Oral Ferrous sulphate 325 mg tds for 6 wks Mean total dose NR | Recruitment period unclear for 6 wks | % to achieve Hb rise > 3.5 g/dL at 6 wks |
Seid 2008 USA [42] | Hb < 10.0 g/dL within 10 days of birth | IV-Iron: 26.39 (5.97) Oral iron: 26.49 (5.55) | IV-iron: n = 139 8.91 (0.89) g/dL Oral iron group: n = 147 8.88 (0.89) g/dL | IV-iron FCM Given up to 2500 mg in divided weekly doses (maximum 1000 mg per dose) Mean dose 1503.5 mg | Oral Ferrous sulphate 325 mg tds for 6 wks Mean dose 7906.1 mg |  ≤ 10 days postpartum for 6 wks | % to achieve Hb > 12 g/dL |
Seid 2017b USA [43] | Hb ≤ 11.0 g/dL | IV-Iron: 31.2 (9.36) Oral iron: 31.4 (8.98) | IV-iron: n = 606 10.2 (1.16) g/dL Standard Medical Care: n = 623 10.11 (1.19) g/dL | IV-iron FCM Single dose up to 1000mg Mean dose 926 mg | Standard medical care for 30 days using oral ferrous sulphate 325 mg tablets if given Mean total dose NR |  ≥ 18 h postpartum 30 days | Incidence of serious AEs, including death, hospitalization, disability, congenital anomaly/birth defect, and life-threatening events |
Vanobberghen 2021 Tanzania [46] | Hb < 11.0 g/dL and ferritin < 50 mcg/L | IV-Iron: 26a(22–30) Oral iron: 26 (22–31) | IV Iron: n = 114 9.8 (8.6–10.5) g/dL Oral iron: n = 116 9.2 (8.5–10.3) g/dL | IV-iron FCM Total dose calculated Mean total dose NR | Oral ferrous sulphate 200 mg tablets & 5 mg folic acid tds until 3 months after correction of anaemia Mean total dose NR |  ≤ 14 days postpartum 12 months | % to achieve a Hb > 11.5 g/dL at 6 weeks |
Van Wyck 2007 USA & Mexico [44] | Hb ≤ 10 g/dL | IV-Iron: 26.9 (6.4) Oral iron: 26.1 (6.0) | IV Iron: n = 174 9.0 (0.9) g/dL Oral iron: n = 178 9.0 (1.0) g/dL | IV FCM Total dose up to 2500 mg, maximum 1000 mg per dose given weekly Mean dose 1403.1 mg | Oral ferrous sulphate 325 mg tds for 6 wks Mean dose 6764 mg |  ≤ 10 days postpartum 6 wks | % to achieve a Hb rise ≥ 2 g/dL |
Verma 2011 India [45] | Hb < 8 g/dL | IV-Iron: 25 (2.0) Oral iron: 24 (3.0) | IV-iron: n = 75 7.58 g/dL Oral iron: n = 75 7.42 g/dL | IV-iron sucrose 600–800 mg in three 200 mg doses on alternate days Mean total dose NR | Oral ferrous sulphate 200mg bd for 4 wks Mean total dose NR |  ≤ 24 h postpartum 4 wks | Change in Hb |
Westad 2008 Norway [48] | Hb ≥ 6.5 to ≤ 8.5 | IV-Iron: 29.5 (4.1) Oral iron: 29.6 (4.5) | IV and oral iron: n = 58 7.91 (6.9) g/dL Oral iron: n = 70 7.72 (8.4) g/dL | IV-iron sucrose 600 mg in three 200 mg doses After 4 wks, bd oral ferrous sulphate 100 mg Mean total dose NR | Oral ferrous sulphate 100 mg bd for 12 wks Mean total dose NR |  ≤ 48 h postpartum 12 wks | Change in Hb at 4 wks |