Treatment for women with postpartum iron deficiency anaemia

Veronika Markova; Astrid Norgaard; Karsten Juhl Jørgensen; Jens Langhoff‐Roos

doi:10.1002/14651858.CD010861.pub2

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Figure 1

Study flow diagram.

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Figure 2

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 3

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

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Analysis 1.1

Comparison 1 Intravenous iron versus oral iron, Outcome 1 Maternal mortality.

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Analysis 1.2

Comparison 1 Intravenous iron versus oral iron, Outcome 2 Fatigue ‐ 14 days.

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Analysis 1.3

Comparison 1 Intravenous iron versus oral iron, Outcome 3 Fatigue ‐ 42 days.

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Analysis 1.4

Comparison 1 Intravenous iron versus oral iron, Outcome 4 SF‐36: Physical F(x) ‐ 14 days.

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Analysis 1.5

Comparison 1 Intravenous iron versus oral iron, Outcome 5 SF‐36: Physical role ‐ 14 days.

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Analysis 1.6

Comparison 1 Intravenous iron versus oral iron, Outcome 6 SF‐36: Bodily pain ‐ day 14.

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Analysis 1.7

Comparison 1 Intravenous iron versus oral iron, Outcome 7 SF‐36: General health ‐ 14 days.

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Analysis 1.8

Comparison 1 Intravenous iron versus oral iron, Outcome 8 SF‐36: Vitality ‐ 14 days.

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Analysis 1.9

Comparison 1 Intravenous iron versus oral iron, Outcome 9 SF‐36: Emotional role ‐ 14 days.

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Analysis 1.10

Comparison 1 Intravenous iron versus oral iron, Outcome 10 SF‐36: Social function ‐ 14 days.

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Analysis 1.11

Comparison 1 Intravenous iron versus oral iron, Outcome 11 SF‐36: Mental health ‐ 14 days.

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Analysis 1.12

Comparison 1 Intravenous iron versus oral iron, Outcome 12 Depression.

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Analysis 1.13

Comparison 1 Intravenous iron versus oral iron, Outcome 13 Infections.

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Analysis 1.14

Comparison 1 Intravenous iron versus oral iron, Outcome 14 Compliance to treatment.

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Analysis 1.15

Comparison 1 Intravenous iron versus oral iron, Outcome 15 All gastrointestinal symptoms.

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Analysis 1.16

Comparison 1 Intravenous iron versus oral iron, Outcome 16 Constipation.

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Analysis 1.17

Comparison 1 Intravenous iron versus oral iron, Outcome 17 Nausea.

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Analysis 1.18

Comparison 1 Intravenous iron versus oral iron, Outcome 18 Gastrointestinal pain.

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Analysis 1.19

Comparison 1 Intravenous iron versus oral iron, Outcome 19 Diarrhoea.

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Analysis 1.20

Comparison 1 Intravenous iron versus oral iron, Outcome 20 Vomiting.

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Analysis 1.21

Comparison 1 Intravenous iron versus oral iron, Outcome 21 Dyspepsia.

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Analysis 1.22

Comparison 1 Intravenous iron versus oral iron, Outcome 22 Dysgeusia.

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Analysis 1.23

Comparison 1 Intravenous iron versus oral iron, Outcome 23 Headache.

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Analysis 1.24

Comparison 1 Intravenous iron versus oral iron, Outcome 24 Hepatic involvement.

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Analysis 1.25

Comparison 1 Intravenous iron versus oral iron, Outcome 25 Injection site discomfort.

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Analysis 1.26

Comparison 1 Intravenous iron versus oral iron, Outcome 26 Skin rash.

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Analysis 1.27

Comparison 1 Intravenous iron versus oral iron, Outcome 27 Urticaria.

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Analysis 1.28

Comparison 1 Intravenous iron versus oral iron, Outcome 28 Flush.

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Analysis 1.29

Comparison 1 Intravenous iron versus oral iron, Outcome 29 Muscle cramp.

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Analysis 1.30

Comparison 1 Intravenous iron versus oral iron, Outcome 30 Pain (not specified).

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Analysis 1.31

Comparison 1 Intravenous iron versus oral iron, Outcome 31 Seriouse adverse events (not specified).

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Analysis 1.32

Comparison 1 Intravenous iron versus oral iron, Outcome 32 Anaphylaxis or evidence of hypersensitivity.

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Analysis 1.33

Comparison 1 Intravenous iron versus oral iron, Outcome 33 Arythmia.

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Analysis 1.34

Comparison 1 Intravenous iron versus oral iron, Outcome 34 Red blood cell transfusion.

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Analysis 2.1

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 1 General fatigue ‐ 3 days.

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Analysis 2.2

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 2 General fatigue ‐ 6 weeks.

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Analysis 2.3

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 3 SF‐36: Physical functioning ‐ 1 week.

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Analysis 2.4

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 4 SF‐36: Social function ‐ 1 week.

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Analysis 2.5

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 5 SF‐36: Physical role ‐ 1 week.

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Analysis 2.6

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 6 SF‐36: Bodily pain ‐ 1 week.

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Analysis 2.7

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 7 SF‐36: General health ‐ 1 week.

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Analysis 2.8

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 8 SF‐36: Vitality ‐ 1 week.

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Analysis 2.9

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 9 SF‐36: Emotional role ‐ 1 week.

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Analysis 2.10

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 10 SF‐36: Mental health ‐ 1 week.

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Analysis 2.11

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 11 Infections.

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Analysis 2.12

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 12 Compliance to treatment.

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Analysis 2.13

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 13 Breastfeeding at six weeks.

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Analysis 2.14

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 14 Erythrocyte alloantibody formation.

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Analysis 2.15

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 15 Rash.

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Analysis 2.16

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 16 Fever.

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Analysis 2.17

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 17 Thromboembolic events.

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Analysis 2.18

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 18 Parenteral iron intolerance.

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Analysis 2.19

Comparison 2 Red blood cell transfusion versus no transfusion, Outcome 19 Transfusion reactions.

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Analysis 3.1

Comparison 3 Oral iron versus placebo, Outcome 1 Digit Symbol Substitution test ‐ 10 weeks.

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Analysis 3.2

Comparison 3 Oral iron versus placebo, Outcome 2 EPDS ‐ 10 weeks.

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Analysis 3.3

Comparison 3 Oral iron versus placebo, Outcome 3 STAI ‐ 10 weeks.

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Analysis 3.4

Comparison 3 Oral iron versus placebo, Outcome 4 Percieved Stress ‐ 10 weeks.

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Analysis 3.5

Comparison 3 Oral iron versus placebo, Outcome 5 Breastfeeding at two days postpartum.

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Analysis 3.6

Comparison 3 Oral iron versus placebo, Outcome 6 Back pain.

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Analysis 3.7

Comparison 3 Oral iron versus placebo, Outcome 7 All gastrointestinal symptoms.

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Analysis 4.1

Comparison 4 Oral iron, magnesium oxide and yeast extract versus placebo, Outcome 1 All gastrointestinal symptoms.

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Analysis 5.1

Comparison 5 Intravenous iron and oral iron after 4 weeks versus oral iron (week 5‐12), Outcome 1 All gastrointestinal symptoms.

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Analysis 5.2

Comparison 5 Intravenous iron and oral iron after 4 weeks versus oral iron (week 5‐12), Outcome 2 Abdominal pain.

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Analysis 5.3

Comparison 5 Intravenous iron and oral iron after 4 weeks versus oral iron (week 5‐12), Outcome 3 Constipation.

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Analysis 5.4

Comparison 5 Intravenous iron and oral iron after 4 weeks versus oral iron (week 5‐12), Outcome 4 Diarrhoea.

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Analysis 5.5

Comparison 5 Intravenous iron and oral iron after 4 weeks versus oral iron (week 5‐12), Outcome 5 Nausea.

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Analysis 5.6

Comparison 5 Intravenous iron and oral iron after 4 weeks versus oral iron (week 5‐12), Outcome 6 Dysgeusia.

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Analysis 5.7

Comparison 5 Intravenous iron and oral iron after 4 weeks versus oral iron (week 5‐12), Outcome 7 Flatulence.

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Analysis 5.8

Comparison 5 Intravenous iron and oral iron after 4 weeks versus oral iron (week 5‐12), Outcome 8 Melaena.

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Analysis 5.9

Comparison 5 Intravenous iron and oral iron after 4 weeks versus oral iron (week 5‐12), Outcome 9 Headache.

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Analysis 6.1

Comparison 6 Intravenous iron and oral iron versus oral iron, Outcome 1 Persistent anaemia symptoms on a VAS scale: 1 week.

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Analysis 6.2

Comparison 6 Intravenous iron and oral iron versus oral iron, Outcome 2 Persistent anaemia symptoms on a VAS scale: 2 week.

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Analysis 6.3

Comparison 6 Intravenous iron and oral iron versus oral iron, Outcome 3 Persistent anaemia symptoms on a VAS scale: 6 week.

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Analysis 6.4

Comparison 6 Intravenous iron and oral iron versus oral iron, Outcome 4 EPDS ‐ 1 week.

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Analysis 6.5

Comparison 6 Intravenous iron and oral iron versus oral iron, Outcome 5 Length of hospital stay.

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Analysis 6.6

Comparison 6 Intravenous iron and oral iron versus oral iron, Outcome 6 Adverse events (pooled) ‐ 1 week.

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Analysis 6.7

Comparison 6 Intravenous iron and oral iron versus oral iron, Outcome 7 Adverse events (pooled) ‐ 2 weeks.

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Analysis 6.8

Comparison 6 Intravenous iron and oral iron versus oral iron, Outcome 8 Adverse events (pooled) ‐ 6 weeks.

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Analysis 6.9

Comparison 6 Intravenous iron and oral iron versus oral iron, Outcome 9 Red blood cell transfusion.

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Analysis 6.10

Comparison 6 Intravenous iron and oral iron versus oral iron, Outcome 10 Anaphylaxis or evidence of hypersensitivity.

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Analysis 7.1

Comparison 7 Erythropoietin (regardless of route) and intravenous iron versus intravenous iron, Outcome 1 Postpartum depression.

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Analysis 7.2

Comparison 7 Erythropoietin (regardless of route) and intravenous iron versus intravenous iron, Outcome 2 Infections.

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Analysis 7.3

Comparison 7 Erythropoietin (regardless of route) and intravenous iron versus intravenous iron, Outcome 3 Compliance to treatment.

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Analysis 7.4

Comparison 7 Erythropoietin (regardless of route) and intravenous iron versus intravenous iron, Outcome 4 Breasfeeding.

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Analysis 7.5

Comparison 7 Erythropoietin (regardless of route) and intravenous iron versus intravenous iron, Outcome 5 Dysgeusia.

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Analysis 7.6

Comparison 7 Erythropoietin (regardless of route) and intravenous iron versus intravenous iron, Outcome 6 Flush.

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Analysis 7.7

Comparison 7 Erythropoietin (regardless of route) and intravenous iron versus intravenous iron, Outcome 7 Diarrhoea.

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Analysis 7.8

Comparison 7 Erythropoietin (regardless of route) and intravenous iron versus intravenous iron, Outcome 8 Headache.

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Analysis 7.9

Comparison 7 Erythropoietin (regardless of route) and intravenous iron versus intravenous iron, Outcome 9 Itching (including elevated liver enzymes).

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Analysis 7.10

Comparison 7 Erythropoietin (regardless of route) and intravenous iron versus intravenous iron, Outcome 10 Dizziness.

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Analysis 7.11

Comparison 7 Erythropoietin (regardless of route) and intravenous iron versus intravenous iron, Outcome 11 Thrombophlebitis.

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Analysis 7.12

Comparison 7 Erythropoietin (regardless of route) and intravenous iron versus intravenous iron, Outcome 12 Red blood cell transfusion.

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Analysis 8.1

Comparison 8 Subcutaneous EPO 10,000 U two doses and intravenous iron versus intravenous iron, Outcome 1 Postpartum depression.

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Analysis 8.2

Comparison 8 Subcutaneous EPO 10,000 U two doses and intravenous iron versus intravenous iron, Outcome 2 Infections.

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Analysis 8.3

Comparison 8 Subcutaneous EPO 10,000 U two doses and intravenous iron versus intravenous iron, Outcome 3 Headache.

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Analysis 8.4

Comparison 8 Subcutaneous EPO 10,000 U two doses and intravenous iron versus intravenous iron, Outcome 4 Low blood pressure.

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Analysis 8.5

Comparison 8 Subcutaneous EPO 10,000 U two doses and intravenous iron versus intravenous iron, Outcome 5 Diarrhoea.

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Analysis 8.6

Comparison 8 Subcutaneous EPO 10,000 U two doses and intravenous iron versus intravenous iron, Outcome 6 Dizziness.

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Analysis 8.7

Comparison 8 Subcutaneous EPO 10,000 U two doses and intravenous iron versus intravenous iron, Outcome 7 Itching (including elevated liver enzymes).

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Analysis 8.8

Comparison 8 Subcutaneous EPO 10,000 U two doses and intravenous iron versus intravenous iron, Outcome 8 Red blood cell transfusion.

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Analysis 9.1

Comparison 9 Intravenous EPO, intravenous iron and oral iron versus intravenous iron and oral iron, Outcome 1 Leg paraesthesia.

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Analysis 9.2

Comparison 9 Intravenous EPO, intravenous iron and oral iron versus intravenous iron and oral iron, Outcome 2 Red blood cell transfusion.

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Analysis 10.1

Comparison 10 Subcutaneous EPO and oral iron versus oral iron, Outcome 1 Breastfeeding.

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Analysis 10.2

Comparison 10 Subcutaneous EPO and oral iron versus oral iron, Outcome 2 Red blood cell transfusions.

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Analysis 14.1

Comparison 14 Sensitivity analysis, Outcome 1 Heterogeneity ‐ Infections ‐ comparison 1.

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Analysis 14.2

Comparison 14 Sensitivity analysis, Outcome 2 Heterogeneity, fixed effect ‐ Infections ‐ comparison 1.

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Analysis 14.3

Comparison 14 Sensitivity analysis, Outcome 3 Heterogeneity ‐ Hepatic involvement ‐ comparison 1.

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Analysis 14.4

Comparison 14 Sensitivity analysis, Outcome 4 Heterogeneity, fixed effect ‐ Hepatic involvement ‐ comparison 1.

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Summary of findings for the main comparison. Intravenous iron compared with oral iron for women with postpartum iron deficiency anaemia (Comparison 1)

Intravenous iron compared with oral iron for women with postpartum iron deficiency anaemia
Patient or population: women with postpartum iron deficiency anaemia Settings: obstetric care units Intervention: intravenous iron Comparison: oral iron
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Oral iron	Intravenous iron
Maternal mortality Clinical assessment Follow‐up: mean 42 days	Study population		RR 2.95 (0.12 to 71.96)	374 (2 studies)	⊕⊕⊝⊝ low^1,2,3,4	1 maternal death was reported across the included studies.
	0 per 1000	0 per 1000 (0 to 0)
	Moderate
	0 per 1000	0 per 1000 (0 to 0)
Fatigue at 14, 28, and 42 days Fatigue Linear Analog Scale Assessment. Scale from: 0 to 100. Follow‐up: 14‐42 days	See comment	See comment	Not estimable	361 (1 study)	⊕⊝⊝⊝ very low^3,5,6	No statistically significant difference was found at days 14 and 42 days.
Persistent anaemia symptoms ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
Infections Clinical assessment Follow‐up: mean 41 days	Study population		RR 1.7 (0.58 to 5.03)	718 (3 studies)	⊕⊝⊝⊝ very low^1,4,7
	86 per 1000	146 per 1000 (50 to 432)
	Moderate
	34 per 1000	58 per 1000 (20 to 171)
Constipation Reported by the women Follow‐up: mean 46 days	Study population		RR 0.21 (0.11 to 0.39)	1217 (6 studies)	⊕⊝⊝⊝ very low^4,5
	114 per 1000	24 per 1000 (13 to 44)
	Moderate
	112 per 1000	24 per 1000 (12 to 44)
All gastrointestinal symptoms Reported by the women Follow‐up: mean 42 days	Study population		RR 0.31 (0.2 to 0.47)	1307 (8 studies)	⊕⊝⊝⊝ very low^4,5
	216 per 1000	67 per 1000 (43 to 102)
	Moderate
	261 per 1000	81 per 1000 (52 to 123)
Anaphylaxis or evidence of hypersensitivity Clinical assessment Follow‐up: mean 40 days	Study population		RR 2.78 (0.31 to 24.92)	1454 (8 studies)	⊕⊕⊝⊝ low^1,2,4	3 cases of allergic reactions all occurred in the group treated with intravenous iron.
	0 per 1000	0 per 1000 (0 to 0)
	Moderate
	0 per 1000	0 per 1000 (0 to 0)
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ The outcome is unlikely to be influenced by risk of bias and so we did not downgrade the evidence for this outcome: open‐label design combined with a objective outcome measure. ² Downgraded one level due to imprecision: small sample size, few events, broad confidence intervals: likely to lower confidence in effect. ³ Downgraded one level due to risk of bias: at least 1 study suitable for this comparison was terminated by trial sponsors. This trial had fatigue as a pre‐planned outcome. This raises serious concern on the amount of unpublished results which may have been unfavourable to trial sponsors. ⁴ Downgraded one level due to risk of bias: several studies did not report important harms. ⁵ Downgraded two levels due to risk of bias: open‐label design combined with a subjective outcome measure. ⁶ Downgraded one level due to imprecision: broad confidence intervals for raw means and small sample size: likely to lower confidence in effect. ⁷ Downgraded one level due to inconsistency: significant statistical heterogeneity: I² = 72%.

Summary of findings for the main comparison. Intravenous iron compared with oral iron for women with postpartum iron deficiency anaemia (Comparison 1)

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Summary of findings 2. Red blood cell transfusion compared with non‐transfusion (Comparison 2)

Red blood cell transfusion compared with non‐transfusion for postpartum iron deficiency anaemia
Patient or population: patients with postpartum iron deficiency anaemia Settings: obstetric care unit Intervention: red blood cell transfusion Comparison: non‐transfusion
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Non‐transfusion	RBC transfusion
Maternal mortality ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
Fatigue Multidimensional Fatigue Inventory. Scale from: 4 to 20. Follow‐up: 3‐42 days	See comment	See comment		519 (1 study)	⊕⊕⊝⊝ low¹	General fatigue at 3 days was 0.8 lower (1.53 to 0.07) in the transfused group. No statistically significant difference was seen at six weeks.
Persistent anaemia symptoms Reported by the women Follow‐up: mean 42 days	Study population		Not estimable	519 (1 study)	⊕⊝⊝⊝ very low^1,2	The outcome was not systematically registered/reported.
	See comment	See comment
	Moderate

Infections Clinical assessment Follow‐up: mean 42 days	Study population		RR 0.93 (0.53 to 1.61)	519 (1 study)	⊕⊕⊕⊝ moderate³
	92 per 1000	86 per 1000 (49 to 148)
	Moderate
	92 per 1000	86 per 1000 (49 to 148)
Erythrocyte alloantibody formation Laboratory assessment Follow‐up: mean 42 days	Study population		RR 3.03 (0.12 to 74.15)	519 (1 study)	⊕⊝⊝⊝ very low^3,4,5	There was no systematical screening for this outcome in the study population.
	0 per 1000	0 per 1000 (0 to 0)
	Moderate
	0 per 1000	0 per 1000 (0 to 0)
Thromboembolic events Assessment method not described Follow‐up: mean 42 days	Study population		RR 1.01 (0.14 to 7.13)	519 (1 study)	⊕⊕⊝⊝ low^6,7
	8 per 1000	8 per 1000 (1 to 55)
	Moderate
	8 per 1000	8 per 1000 (1 to 57)
Transfusion reactions Clinical assessment Follow‐up: mean 42 days	Study population		RR 7.08 (0.37 to 136.41)	519 (1 study)	⊕⊝⊝⊝ very low^3,5	3 cases of transfusion reactions occurred in the transfusion group.
	0 per 1000	0 per 1000 (0 to 0)
	Moderate
	0 per 1000	0 per 1000 (0 to 0)
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Downgraded two levels due to risk of bias: open‐label design combined with a subjective outcome measure. ² Downgraded one level due to study limitations: the outcome was not systematically registered/reported. ³ The outcome is unlikely to be influenced by risk of bias and so we did not downgrade the evidence for this outcome: open‐label design combined with a objective outcome measure. ⁴ Downgraded one level due to study limitations: the women were not systematically screened for the presence of antibodies. ⁵ Downgraded two levels due to imprecision: very broad confidence interval. ⁶ Downgraded one level due to risk of bias: open‐label study, method for detection not descried. ⁷ Downgraded one level due to imprecision: broad confidence interval.

Summary of findings 2. Red blood cell transfusion compared with non‐transfusion (Comparison 2)

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Summary of findings 3. Oral iron compared with placebo (Comparison 3)

Oral iron compared with placebo for women with postpartum iron deficiency anaemia
Patient or population: women with postpartum iron deficiency anaemia Settings: obstetric care units Intervention: oral iron Comparison: placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Oral iron
Maternal mortality ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
Fatigue ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
Persistent anaemia symptoms Reported by the women Follow‐up: mean 42 days	Study population		Not estimable	(1)	See comment	Symptoms of anaemia were not reported for the anaemic groups separately.
	See comment	See comment
	Moderate

All gastrointestinal symptoms Reported by the patients Follow‐up: mean 30 days	Study population		RR 1 (0.36 to 2.79)	68 (1 study)	⊕⊝⊝⊝ very low^1,2,3
	176 per 1000	176 per 1000 (64 to 492)
	Moderate
	177 per 1000	177 per 1000 (64 to 494)
Constipation ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Downgraded two levels due to risk of bias: open‐label design combined with a subjective outcome measure. ² Downgraded one level due to imprecision: small sample size, single study ‐ likely to lower confidence in effect. ³ Downgraded one level due to study limitations: adverse events not reported separately.

Summary of findings 3. Oral iron compared with placebo (Comparison 3)

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Summary of findings 4. Intravenous iron with oral iron compared with oral iron (Comparison 6)

Intravenous iron with oral iron compared with oral iron for women with postpartum iron deficiency anaemia
Patient or population: women with postpartum iron deficiency anaemia Settings: obstetric care unit Intervention: intravenous iron with oral iron Comparison: oral iron
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Oral iron	Intravenous iron with oral iron
Maternal mortality	See comment	See comment	Not estimable	‐	See comment	In 1 study no maternal deaths were reported. The other study did not report on maternal mortality.
Fatigue ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
Persistent anaemia symptoms ‐ 1 week Visual Analogue Scale ≥ 7 Follow‐up: mean 7 days	Study population		RR 1.75 (0.56 to 5.46)	72 (1 study)	⊕⊝⊝⊝ very low^1,2
	111 per 1000	194 per 1000 (62 to 607)
	Moderate
	111 per 1000	194 per 1000 (62 to 606)
Persistent anaemia symptoms ‐ 2 weeks Visual Analogue Scale ≥ 7 Follow‐up: mean 14 days	Study population		RR 0.6 (0.15 to 2.33)	72 (1 study)	⊕⊝⊝⊝ very low^1,2
	139 per 1000	83 per 1000 (21 to 324)
	Moderate
	139 per 1000	83 per 1000 (21 to 324)
Persistent anaemia symptoms ‐ 6 weeks Visual Analogue Scale ≥ 7 Follow‐up: mean 42 days	Study population		RR 3 (0.33 to 27.5)	72 (1 study)	⊕⊝⊝⊝ very low^1,2
	28 per 1000	83 per 1000 (9 to 764)
	Moderate
	28 per 1000	84 per 1000 (9 to 770)
Infections ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
Anaphylaxis or evidence of hypersensitivity Clinical assessment Follow‐up: mean 28 days	Study population		Not estimable	0 (1 study)	⊕⊕⊝⊝ low¹	1 study reported 0 events, other study pooled adverse events, not reporting allergic reactions separately. Thus the effect was not estimable.
	See comment	See comment
	Moderate

The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Downgraded two levels due to risk of bias: the included study had high risk of attrition and reporting bias. ² Downgraded one level due to imprecision: small sample size, single study.

Summary of findings 4. Intravenous iron with oral iron compared with oral iron (Comparison 6)

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Summary of findings 5. Erythropoietin (regardless of rout) with intravenous iron compared with intravenous iron (Comparison 7)

Erythropoietin (regardless of rout) with intravenous iron compared with intravenous iron for women with postpartum iron deficiency anaemia
Patient or population: women with postpartum iron deficiency anaemia Settings: obstetric care units Intervention: erythropoietin (regardless of rout) with intravenous iron Comparison: intravenous iron
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Intravenous iron	EPO (regardless of rout) with IV iron
Maternal mortality	See comment	See comment	Not estimable	‐	See comment	In 1 study no maternal deaths were reported. The other study did not report on maternal mortality.
Fatigue ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
Thromboembolic events ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
Persistent anaemia symptoms ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

Summary of findings 5. Erythropoietin (regardless of rout) with intravenous iron compared with intravenous iron (Comparison 7)

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Summary of findings 6. Subcutaneous EPO 10,000 U of doses with intravenous iron compared with intravenous iron (Comparison 8)

Subcutaneous EPO 10,000 U of doses with intravenous iron compared with intravenous iron for women with postpartum iron deficiency anaemia
Patient or population: patients with women with postpartum iron deficiency anaemia Settings: obstetric care unit Intervention: subcutaneous EPO of 2 doses of 10,000 U with intravenous iron Comparison: intravenous iron
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Intravenous iron	Erythropoietin 10,000 U 2 doses with intravenous iron
Maternal mortality ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
Fatigue ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
Persistent anaemia symptoms ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
Thromboembolic events ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

Summary of findings 6. Subcutaneous EPO 10,000 U of doses with intravenous iron compared with intravenous iron (Comparison 8)

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Summary of findings 7. Subcutaneous EPO with oral iron compared with oral iron (Comparison 10)

Subcutaneous EPO with oral iron compared with oral iron for women with postpartum iron deficiency anaemia
Patient or population: women with postpartum iron deficiency anaemia Settings: obstetric care unit Intervention: subcutaneous EPO with oral iron Comparison: oral iron
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Oral iron	Subcutaneous EPO with oral iron
Maternal mortality	See comment	See comment	Not estimable	40 (0)	See comment	No maternal deaths were reported.
Fatigue ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
Persistent anaemia symptoms ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
Thromboembolic events ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

Summary of findings 7. Subcutaneous EPO with oral iron compared with oral iron (Comparison 10)

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Summary of findings 8. Subcutaneous EPO with intravenous iron and oral iron compared with intravenous iron with oral iron (Comparison 12)

Subcutaneous EPO with IV iron and oral iron compared with intravenous iron with oral iron for women with postpartum iron deficiency anaemia
Patient or population: women with postpartum iron deficiency anaemia Settings: obstetric care units Intervention: subcutaneous EPO with intravenous iron and oral iron Comparison: intravenous iron with oral iron
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Intravenous iron + oral iron	Subcutaneous EPO + IV iron + oral iron
Maternal mortality ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
Fatigue ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
Persistent anaemia symptoms ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
Thromboembolic events ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not reported.
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

Summary of findings 8. Subcutaneous EPO with intravenous iron and oral iron compared with intravenous iron with oral iron (Comparison 12)

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Comparison 1. Intravenous iron versus oral iron

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Maternal mortality Show forest plot	2	374	Risk Ratio (M‐H, Random, 95% CI)	2.95 [0.12, 71.96]

2 Fatigue ‐ 14 days Show forest plot	1	322	Mean Difference (IV, Fixed, 95% CI)	‐3.30 [‐8.04, 1.44]

3 Fatigue ‐ 42 days Show forest plot	1	329	Mean Difference (IV, Fixed, 95% CI)	‐2.10 [‐6.77, 2.57]

4 SF‐36: Physical F(x) ‐ 14 days Show forest plot	1	320	Mean Difference (IV, Fixed, 95% CI)	0.90 [‐3.84, 5.64]

5 SF‐36: Physical role ‐ 14 days Show forest plot	1	321	Mean Difference (IV, Fixed, 95% CI)	3.50 [‐2.03, 9.03]

6 SF‐36: Bodily pain ‐ day 14 Show forest plot	1	321	Mean Difference (IV, Fixed, 95% CI)	‐0.70 [‐6.00, 4.60]

7 SF‐36: General health ‐ 14 days Show forest plot	1	321	Mean Difference (IV, Fixed, 95% CI)	0.70 [‐3.09, 4.49]

8 SF‐36: Vitality ‐ 14 days Show forest plot	1	321	Mean Difference (IV, Fixed, 95% CI)	0.90 [‐3.64, 5.44]

9 SF‐36: Emotional role ‐ 14 days Show forest plot	1	321	Mean Difference (IV, Fixed, 95% CI)	1.10 [‐4.06, 6.26]

10 SF‐36: Social function ‐ 14 days Show forest plot	1	321	Mean Difference (IV, Fixed, 95% CI)	1.0 [‐4.08, 6.08]

11 SF‐36: Mental health ‐ 14 days Show forest plot	1	321	Mean Difference (IV, Fixed, 95% CI)	‐1.20 [‐4.84, 2.44]

12 Depression Show forest plot	1	361	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.01, 8.00]

13 Infections Show forest plot	3	718	Risk Ratio (M‐H, Random, 95% CI)	1.70 [0.58, 5.03]

14 Compliance to treatment Show forest plot	5	890	Risk Ratio (M‐H, Random, 95% CI)	1.17 [1.01, 1.35]

15 All gastrointestinal symptoms Show forest plot	8	1307	Risk Ratio (M‐H, Random, 95% CI)	0.31 [0.20, 0.47]

16 Constipation Show forest plot	6	1217	Risk Ratio (M‐H, Random, 95% CI)	0.21 [0.11, 0.39]

17 Nausea Show forest plot	4	745	Risk Ratio (M‐H, Random, 95% CI)	0.30 [0.11, 0.81]

18 Gastrointestinal pain Show forest plot	4	543	Risk Ratio (M‐H, Random, 95% CI)	0.18 [0.04, 0.83]

19 Diarrhoea Show forest plot	3	569	Risk Ratio (M‐H, Random, 95% CI)	0.11 [0.02, 0.59]

20 Vomiting Show forest plot	1	128	Risk Ratio (M‐H, Fixed, 95% CI)	0.40 [0.02, 9.66]

21 Dyspepsia Show forest plot	2	93	Risk Ratio (M‐H, Random, 95% CI)	0.36 [0.04, 3.20]

22 Dysgeusia Show forest plot	4	543	Risk Ratio (M‐H, Random, 95% CI)	7.20 [1.63, 31.76]

23 Headache Show forest plot	4	1124	Risk Ratio (M‐H, Random, 95% CI)	1.93 [0.87, 4.29]

24 Hepatic involvement Show forest plot	3	996	Risk Ratio (M‐H, Random, 95% CI)	0.45 [0.12, 1.71]

25 Injection site discomfort Show forest plot	4	702	Risk Ratio (M‐H, Random, 95% CI)	4.72 [1.03, 21.54]

26 Skin rash Show forest plot	2	489	Risk Ratio (M‐H, Random, 95% CI)	2.34 [0.79, 6.97]

27 Urticaria Show forest plot	1	291	Risk Ratio (M‐H, Fixed, 95% CI)	4.14 [0.47, 36.59]

28 Flush Show forest plot	2	124	Risk Ratio (M‐H, Random, 95% CI)	9.00 [1.18, 68.81]

29 Muscle cramp Show forest plot	2	371	Risk Ratio (M‐H, Random, 95% CI)	6.05 [0.74, 49.68]

30 Pain (not specified) Show forest plot	1	128	Risk Ratio (M‐H, Fixed, 95% CI)	8.42 [0.44, 159.82]

31 Seriouse adverse events (not specified) Show forest plot	1	291	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.26, 4.06]

32 Anaphylaxis or evidence of hypersensitivity Show forest plot	8	1454	Risk Ratio (M‐H, Random, 95% CI)	2.78 [0.31, 24.92]

33 Arythmia Show forest plot	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	4.26 [0.18, 101.86]

34 Red blood cell transfusion Show forest plot	4	606	Risk Ratio (M‐H, Random, 95% CI)	0.48 [0.19, 1.23]

Comparison 1. Intravenous iron versus oral iron

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Comparison 2. Red blood cell transfusion versus no transfusion

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 General fatigue ‐ 3 days Show forest plot	1	388	Mean Difference (IV, Fixed, 95% CI)	‐0.80 [‐1.53, ‐0.07]

2 General fatigue ‐ 6 weeks Show forest plot	1	318	Mean Difference (IV, Fixed, 95% CI)	‐0.25 [‐1.22, 0.72]

3 SF‐36: Physical functioning ‐ 1 week Show forest plot	1	368	Mean Difference (IV, Fixed, 95% CI)	5.67 [0.84, 10.50]

4 SF‐36: Social function ‐ 1 week Show forest plot	1	369	Mean Difference (IV, Fixed, 95% CI)	5.34 [0.11, 10.57]

5 SF‐36: Physical role ‐ 1 week Show forest plot	1	366	Mean Difference (IV, Fixed, 95% CI)	4.56 [‐1.41, 10.53]

6 SF‐36: Bodily pain ‐ 1 week Show forest plot	1	368	Mean Difference (IV, Fixed, 95% CI)	‐2.0 [‐5.90, 1.90]

7 SF‐36: General health ‐ 1 week Show forest plot	1	369	Mean Difference (IV, Fixed, 95% CI)	2.18 [‐1.47, 5.83]

8 SF‐36: Vitality ‐ 1 week Show forest plot	1	369	Mean Difference (IV, Fixed, 95% CI)	1.88 [‐2.01, 5.77]

9 SF‐36: Emotional role ‐ 1 week Show forest plot	1	368	Mean Difference (IV, Fixed, 95% CI)	4.37 [‐4.51, 13.25]

10 SF‐36: Mental health ‐ 1 week Show forest plot	1	369	Mean Difference (IV, Fixed, 95% CI)	1.21 [‐2.29, 4.71]

11 Infections Show forest plot	1	519	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.53, 1.61]

12 Compliance to treatment Show forest plot	1	519	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [1.06, 1.17]

13 Breastfeeding at six weeks Show forest plot	1	297	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.78, 1.07]

14 Erythrocyte alloantibody formation Show forest plot	1	519	Risk Ratio (M‐H, Fixed, 95% CI)	3.03 [0.12, 74.15]

15 Rash Show forest plot	1	519	Risk Ratio (M‐H, Fixed, 95% CI)	3.03 [0.12, 74.15]

16 Fever Show forest plot	1	519	Risk Ratio (M‐H, Fixed, 95% CI)	5.06 [0.24, 104.84]

17 Thromboembolic events Show forest plot	1	519	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.14, 7.13]

18 Parenteral iron intolerance Show forest plot	1	519	Risk Ratio (M‐H, Fixed, 95% CI)	0.34 [0.01, 8.24]

19 Transfusion reactions Show forest plot	1	519	Risk Ratio (M‐H, Fixed, 95% CI)	7.08 [0.37, 136.41]

Comparison 2. Red blood cell transfusion versus no transfusion

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Comparison 3. Oral iron versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Digit Symbol Substitution test ‐ 10 weeks Show forest plot	1	51	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐2.76, 2.76]

2 EPDS ‐ 10 weeks Show forest plot	1	51	Mean Difference (IV, Fixed, 95% CI)	0.10 [‐0.86, 1.06]

3 STAI ‐ 10 weeks Show forest plot	1	51	Mean Difference (IV, Fixed, 95% CI)	‐0.40 [‐3.18, 2.38]

4 Percieved Stress ‐ 10 weeks Show forest plot	1	51	Mean Difference (IV, Fixed, 95% CI)	4.1 [1.70, 6.50]

5 Breastfeeding at two days postpartum Show forest plot	1	122	Risk Ratio (M‐H, Fixed, 95% CI)	0.82 [0.58, 1.17]

6 Back pain Show forest plot	1	150	Risk Ratio (M‐H, Fixed, 95% CI)	0.66 [0.42, 1.03]

7 All gastrointestinal symptoms Show forest plot	1	68	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.36, 2.79]

Comparison 3. Oral iron versus placebo

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Comparison 4. Oral iron, magnesium oxide and yeast extract versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All gastrointestinal symptoms Show forest plot	1	67	Risk Ratio (M‐H, Fixed, 95% CI)	2.75 [1.23, 6.16]

Comparison 4. Oral iron, magnesium oxide and yeast extract versus placebo

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Comparison 5. Intravenous iron and oral iron after 4 weeks versus oral iron (week 5‐12)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All gastrointestinal symptoms Show forest plot	1	117	Risk Ratio (M‐H, Fixed, 95% CI)	1.43 [0.83, 2.45]

2 Abdominal pain Show forest plot	1	117	Risk Ratio (M‐H, Fixed, 95% CI)	2.72 [0.55, 13.48]

3 Constipation Show forest plot	1	117	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [0.55, 2.60]

4 Diarrhoea Show forest plot	1	117	Risk Ratio (M‐H, Fixed, 95% CI)	3.27 [0.35, 30.51]

5 Nausea Show forest plot	1	117	Risk Ratio (M‐H, Fixed, 95% CI)	3.26 [0.14, 78.49]

6 Dysgeusia Show forest plot	1	117	Risk Ratio (M‐H, Fixed, 95% CI)	3.26 [0.14, 78.49]

7 Flatulence Show forest plot	1	117	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.02, 8.72]

8 Melaena Show forest plot	1	117	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.02, 8.72]

9 Headache Show forest plot	1	117	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.02, 8.72]

Comparison 5. Intravenous iron and oral iron after 4 weeks versus oral iron (week 5‐12)

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Comparison 6. Intravenous iron and oral iron versus oral iron

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Persistent anaemia symptoms on a VAS scale: 1 week Show forest plot	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	1.75 [0.56, 5.46]

2 Persistent anaemia symptoms on a VAS scale: 2 week Show forest plot	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	0.6 [0.15, 2.33]

3 Persistent anaemia symptoms on a VAS scale: 6 week Show forest plot	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.33, 27.50]

4 EPDS ‐ 1 week Show forest plot	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.65, 13.88]

5 Length of hospital stay Show forest plot	1	72	Mean Difference (IV, Fixed, 95% CI)	‐0.30 [‐1.02, 0.42]

6 Adverse events (pooled) ‐ 1 week Show forest plot	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.21, 2.16]

7 Adverse events (pooled) ‐ 2 weeks Show forest plot	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	0.29 [0.06, 1.28]

8 Adverse events (pooled) ‐ 6 weeks Show forest plot	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	0.4 [0.08, 1.93]

9 Red blood cell transfusion Show forest plot	2	112	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.15, 6.72]

10 Anaphylaxis or evidence of hypersensitivity Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 6. Intravenous iron and oral iron versus oral iron

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Comparison 7. Erythropoietin (regardless of route) and intravenous iron versus intravenous iron

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Postpartum depression Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.01, 7.72]

2 Infections Show forest plot	2	80	Risk Ratio (M‐H, Random, 95% CI)	2.0 [0.72, 5.59]

3 Compliance to treatment Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.91, 1.10]

4 Breasfeeding Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.91, 1.10]

5 Dysgeusia Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.71 [0.27, 1.88]

6 Flush Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.20, 20.33]

7 Diarrhoea Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.01, 7.72]

8 Headache Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.14 [0.01, 2.60]

9 Itching (including elevated liver enzymes) Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.2 [0.01, 3.92]

10 Dizziness Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.01, 7.72]

11 Thrombophlebitis Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.26, 98.00]

12 Red blood cell transfusion Show forest plot	2	80	Risk Ratio (M‐H, Random, 95% CI)	3.0 [0.13, 69.52]

Comparison 7. Erythropoietin (regardless of route) and intravenous iron versus intravenous iron

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Comparison 8. Subcutaneous EPO 10,000 U two doses and intravenous iron versus intravenous iron

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Postpartum depression Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.01, 7.72]

2 Infections Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.75 [0.19, 2.93]

3 Headache Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.12, 3.57]

4 Low blood pressure Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.13, 69.52]

5 Diarrhoea Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.01, 7.72]

6 Dizziness Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.01, 7.72]

7 Itching (including elevated liver enzymes) Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.2 [0.01, 3.92]

8 Red blood cell transfusion Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 8. Subcutaneous EPO 10,000 U two doses and intravenous iron versus intravenous iron

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Comparison 9. Intravenous EPO, intravenous iron and oral iron versus intravenous iron and oral iron

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Leg paraesthesia Show forest plot	2	76	Risk Ratio (M‐H, Random, 95% CI)	0.72 [0.08, 6.65]

2 Red blood cell transfusion Show forest plot	2	100	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Comparison 9. Intravenous EPO, intravenous iron and oral iron versus intravenous iron and oral iron

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Comparison 10. Subcutaneous EPO and oral iron versus oral iron

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Breastfeeding Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	1.9 [1.21, 2.98]

2 Red blood cell transfusions Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.2 [0.01, 3.92]

Comparison 10. Subcutaneous EPO and oral iron versus oral iron

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Comparison 14. Sensitivity analysis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Heterogeneity ‐ Infections ‐ comparison 1 Show forest plot	2	374	Risk Ratio (M‐H, Random, 95% CI)	1.07 [0.62, 1.84]

2 Heterogeneity, fixed effect ‐ Infections ‐ comparison 1 Show forest plot	3	718	Risk Ratio (M‐H, Fixed, 95% CI)	1.49 [0.93, 2.38]

3 Heterogeneity ‐ Hepatic involvement ‐ comparison 1 Show forest plot	2	652	Risk Ratio (M‐H, Random, 95% CI)	0.22 [0.06, 0.75]

4 Heterogeneity, fixed effect ‐ Hepatic involvement ‐ comparison 1 Show forest plot	3	996	Risk Ratio (M‐H, Fixed, 95% CI)	0.47 [0.21, 1.07]

Comparison 14. Sensitivity analysis

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