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Page 1 of 43 Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta- analysis Batool A Haider, Ibironke Olofin, Molin Wang, Donna Spiegelman, Majid Ezzati, Wafaie W Fawzi, on behalf of Nutrition Impact Model Study Group (anaemia) Supplementary figures 1-41

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Page 1 of 43

Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-

analysis

Batool A Haider, Ibironke Olofin, Molin Wang, Donna Spiegelman, Majid Ezzati, Wafaie W Fawzi, on behalf

of Nutrition Impact Model Study Group (anaemia)

Supplementary figures 1-41

Page 2 of 43

Contents: Page number 1. Supplementary fig 1. Forest plot of iron use on mean haemoglobin in postpartum period 3

2. Supplementary fig 2. Forest plot of iron use on mean haemoglobin in second trimester 4

3. Supplementary fig 3. Forest plot of iron use on maternal anaemia in third trimester or

at delivery 5

4. Supplementary fig 4. Funnel plot of maternal anaemia in third trimester or at delivery 6

5. Supplementary fig 5. Forest plot of iron use on iron deficiency 7

6. Supplementary fig 6. Forest plot of iron use on iron deficiency anaemia 8

7. Supplementary fig 7. Forest plot of iron use on birth weight 9

8. Supplementary fig 8. Forest plot of iron use on preterm birth 10

9. Supplementary fig 9. Forest plot of iron use on duration of gestation 11

10. Supplementary fig 10. Forest plot of iron use on SGA birth 12

11. Supplementary fig 11. Forest plot of iron use on birth length 13

12. Supplementary fig 12. Exposure-response relationship between iron dose and

maternal anaemia 14

13. Supplementary fig 13. Exposure-response relationship between iron dose up to 66 mg/day

and maternal anaemia 15

14. Supplementary fig 14. Exposure-response relationship between iron dose up to 66 mg/day

and low birth weight risk 16

15. Supplementary fig 15. Exposure-response relationship between iron dose up to 66 mg/day

and birth weight 17

16. Supplementary fig 16. Exposure-response relationship of haemoglobin difference with

birth weight 18

17. Supplementary fig 17. Exposure-response relationship of haemoglobin difference with

low birth weight risk 19

18. Supplementary fig 18. Exposure-response relationship of haemoglobin difference with

preterm birth risk 20

19. Supplementary fig 19. Forest plot of iron only on mean haemoglobin concentration in third

trimester or at delivery 21

20. Supplementary fig 20. Forest plot of iron only on mean haemoglobin concentration in

postpartum period 22

21. Supplementary fig 21. Forest plot of iron only on maternal anaemia 23

22. Supplementary fig 22. Forest plot of iron only on iron deficiency 24

23. Supplementary fig 23. Forest plot of iron only on iron deficiency anaemia 25

24. Supplementary fig 24. Forest plot of iron only on birth weight 26

25. Supplementary fig 25. Forest plot of iron only on low birth weight 27

26. Supplementary fig 26. Forest plot of iron only on duration of gestation 28

27. Supplementary fig 27. Forest plot of iron only on preterm birth 29

28. Supplementary fig 28. Forest plot of iron only on SGA 30

29. Supplementary fig 29. Forest plot of iron only on birth length 31

30. Supplementary fig 30. Forest plot of iron with folic acid on mean haemoglobin concentration

in third trimester or at delivery 32

31. Supplementary fig 31. Forest plot of iron with folic acid on maternal anaemia in third trimester

or at delivery 33

32. Supplementary fig 32. Forest plot of maternal anaemia on low birth weight (crude estimates) 34

33. Supplementary fig 33. Forest plot of maternal anaemia on low birth weight (adjusted estimates) 35

34. Supplementary fig 34. Forest plot of maternal anaemia on preterm birth (crude estimates) 36

35. Supplementary fig 35. Forest plot of maternal anaemia on preterm birth (adjusted estimates) 37

36. Supplementary fig 36. Forest plot of maternal anaemia on stillbirth (crude estimates) 38

37. Supplementary fig 37. Forest plot of maternal anaemia on duration of gestation 39

38. Supplementary fig 38. Forest plot of maternal anaemia on birth weight 40

39. Supplementary fig 39. Forest plot of maternal anaemia on SGA (crude estimates) 41

40. Supplementary fig 40. Forest plot of maternal anaemia on SGA (adjusted estimates) 42

41. Supplementary fig 41. Forest plot of maternal anaemia on perinatal mortality (crude estimates) 43

Page 3 of 43

Supplementary fig 1. Forest plot of iron use on mean haemoglobin in postpartum period

I-V Overall (I-squared = 0.0%, p = 1.000)

Cantlie 1971

Dawson 1989

Tura 1989 a

D+L Overall

Buytaert 1983

studyid

Lee 2005 a

Christian 2003

Butler 1968

Milman 1991

Taylor 1982

Eskeland 1997 b

Wallenburg 1984

Menendez 1994

6.79 (0.22, 13.36)

14.00 (-80.41, 108.41)

3.34 (-23.66, 30.34)

2.00 (-24.45, 28.45)

6.79 (0.22, 13.36)

-3.22 (-82.75, 76.31)

WMD (95% CI)

10.00 (-29.39, 49.39)

10.00 (-0.33, 20.33)

1.49 (-61.04, 64.02)

5.30 (-42.95, 53.55)

3.40 (-66.62, 73.42)

4.00 (-74.36, 82.36)

0.00 (-93.78, 93.78)

5.00 (-5.59, 15.59)

100.00

0.48

Weight

5.92

6.17

0.68

(I-V)

2.78

%

40.47

1.10

1.85

0.88

0.70

0.49

38.45

6.79 (0.22, 13.36)

14.00 (-80.41, 108.41)

3.34 (-23.66, 30.34)

2.00 (-24.45, 28.45)

6.79 (0.22, 13.36)

-3.22 (-82.75, 76.31)

WMD (95% CI)

10.00 (-29.39, 49.39)

10.00 (-0.33, 20.33)

1.49 (-61.04, 64.02)

5.30 (-42.95, 53.55)

3.40 (-66.62, 73.42)

4.00 (-74.36, 82.36)

0.00 (-93.78, 93.78)

5.00 (-5.59, 15.59)

100.00

0.48

Weight

5.92

6.17

0.68

(I-V)

2.78

%

40.47

1.10

1.85

0.88

0.70

0.49

38.45

Intervention decreases Hb level Intervention increases Hb level 0-10 0 10

Page 4 of 43

Supplementary fig 2. Forest plot of iron use on mean haemoglobin in second trimester

I-V Overall (I-squared = 0.0%, p = 0.988)

Simmons 1993

D+L Overall

Harvey 2007

Lee 2005 b

Dawson 1989

Barton 1994

Lee 2005 a

Milman 1991

Ziaei 2008

studyid

-0.23 (-12.18, 11.72)

6.10 (-37.06, 49.26)

-0.23 (-12.18, 11.72)

6.00 (-113.35, 125.35)

-5.00 (-28.43, 18.43)

3.34 (-23.66, 30.34)

10.10 (-25.86, 46.06)

-10.00 (-36.81, 16.81)

2.50 (-36.27, 41.27)

9.80 (-41.82, 61.42)

WMD (95% CI)

100.00

Weight

7.66

1.00

26.00

19.58

11.04

19.86

9.50

5.36

(I-V)

%

-0.23 (-12.18, 11.72)

6.10 (-37.06, 49.26)

-0.23 (-12.18, 11.72)

6.00 (-113.35, 125.35)

-5.00 (-28.43, 18.43)

3.34 (-23.66, 30.34)

10.10 (-25.86, 46.06)

-10.00 (-36.81, 16.81)

2.50 (-36.27, 41.27)

9.80 (-41.82, 61.42)

WMD (95% CI)

100.00

Weight

7.66

1.00

26.00

19.58

11.04

19.86

9.50

5.36

(I-V)

%

Intervention decreases Hb level Intervention increases Hb level

0-10 0 10

Page 5 of 43

Supplementary fig 3. Forest plot of iron use on maternal anaemia in third trimester or at delivery

I-V Overall (I-squared = 82.9%, p = 0.000)

Zeng 2008

Sood 1975 b

Cogswell 2003

Sood 1975 a

D+L Overall

Romslo 1983

Holly 1955

Makrides 2003

Batu 1976

Ndyomugyenyi 2000

studyid

Puolakka 1980

Preziosi 1997

Siega-Riz 2006

Chisholm 1966

Pritchard 1958

De Benaze 1989

Liu 1996

Milman 1991

Charoenlarp 1988

Christian 2003

Eskeland 1997 b

0.67 (0.64, 0.70)

0.74 (0.70, 0.79)

0.72 (0.65, 0.81)

0.75 (0.35, 1.59)

0.66 (0.56, 0.80)

0.50 (0.42, 0.59)

0.15 (0.02, 1.12)

0.03 (0.00, 0.18)

0.45 (0.25, 0.82)

0.50 (0.35, 0.71)

0.65 (0.47, 0.90)

ES (95% CI)

0.07 (0.00, 1.15)

0.59 (0.45, 0.77)

1.11 (0.71, 1.71)

0.16 (0.08, 0.33)

0.17 (0.08, 0.39)

0.21 (0.06, 0.73)

0.36 (0.25, 0.52)

0.09 (0.02, 0.38)

0.46 (0.37, 0.57)

0.46 (0.37, 0.57)

0.06 (0.00, 1.00)

100.00

54.69

18.30

Weight

0.38

%

6.61

0.05

0.05

0.58

1.67

2.03

(I-V)

0.03

2.98

1.10

0.43

0.31

0.14

1.63

0.11

4.31

4.57

0.03

0.67 (0.64, 0.70)

0.74 (0.70, 0.79)

0.72 (0.65, 0.81)

0.75 (0.35, 1.59)

0.66 (0.56, 0.80)

0.50 (0.42, 0.59)

0.15 (0.02, 1.12)

0.03 (0.00, 0.18)

0.45 (0.25, 0.82)

0.50 (0.35, 0.71)

0.65 (0.47, 0.90)

ES (95% CI)

0.07 (0.00, 1.15)

0.59 (0.45, 0.77)

1.11 (0.71, 1.71)

0.16 (0.08, 0.33)

0.17 (0.08, 0.39)

0.21 (0.06, 0.73)

0.36 (0.25, 0.52)

0.09 (0.02, 0.38)

0.46 (0.37, 0.57)

0.46 (0.37, 0.57)

0.06 (0.00, 1.00)

100.00

54.69

18.30

Weight

0.38

%

6.61

0.05

0.05

0.58

1.67

2.03

(I-V)

0.03

2.98

1.10

0.43

0.31

0.14

1.63

0.11

4.31

4.57

0.03

Intervention decreases anaemia risk Intervention increases anaemia risk

1.1 1 5

Page 6 of 43

Supplementary fig 4. Funnel plot of maternal anaemia in third trimester or at delivery

0.5

11.

5

s.e.

of l

ogrr

-4 -2 0 2logrr

Funnel plot with pseudo 95% confidence limits

Page 7 of 43

Supplementary fig 5. Forest plot of iron use on iron deficiency

I-V Overall (I-squared = 79.4%, p = 0.000)

Romslo 1983

studyid

Siega-Riz 2006

Tura 1989 a

Preziosi 1997

Falahi 2011

D+L Overall

Milman 1991

Makrides 2003

Cogswell 2003

0.73 (0.66, 0.82)

0.06 (0.01, 0.38)

ES (95% CI)

0.81 (0.65, 1.02)

0.92 (0.73, 1.17)

0.34 (0.21, 0.54)

0.35 (0.16, 0.78)

0.59 (0.44, 0.79)

0.16 (0.04, 0.71)

0.60 (0.48, 0.76)

0.87 (0.69, 1.08)

100.00

0.33

(I-V)

22.95

22.45

5.42

1.97

Weight

0.57

22.43

23.89

%

0.73 (0.66, 0.82)

0.06 (0.01, 0.38)

ES (95% CI)

0.81 (0.65, 1.02)

0.92 (0.73, 1.17)

0.34 (0.21, 0.54)

0.35 (0.16, 0.78)

0.59 (0.44, 0.79)

0.16 (0.04, 0.71)

0.60 (0.48, 0.76)

0.87 (0.69, 1.08)

100.00

0.33

(I-V)

22.95

22.45

5.42

1.97

Weight

0.57

22.43

23.89

%

Intervention decreases risk Intervention increases risk 1.1 1 5

Page 8 of 43

Supplementary fig 6. Forest plot of iron use on iron deficiency anaemia

I-V Overall (I-squared = 32.5%, p = 0.180)

Meier 2003 b

Siega-Riz 2006

Cogswell 2003

Makrides 2003

Christian 2003

Meier 2003 a

Milman 1991

studyid

D+L Overall

0.40 (0.29, 0.54)

0.47 (0.16, 1.44)

0.69 (0.33, 1.43)

0.61 (0.32, 1.15)

0.28 (0.12, 0.68)

0.28 (0.17, 0.47)

0.17 (0.02, 1.32)

0.06 (0.00, 0.93)

ES (95% CI)

0.40 (0.26, 0.60)

100.00

7.76

18.03

23.44

12.08

35.21

2.28

1.20

(I-V)

Weight

%

0.40 (0.29, 0.54)

0.47 (0.16, 1.44)

0.69 (0.33, 1.43)

0.61 (0.32, 1.15)

0.28 (0.12, 0.68)

0.28 (0.17, 0.47)

0.17 (0.02, 1.32)

0.06 (0.00, 0.93)

ES (95% CI)

0.40 (0.26, 0.60)

100.00

7.76

18.03

23.44

12.08

35.21

2.28

1.20

(I-V)

Weight

%

Intervention decreases risk Intervention increases risk

1.1 1 5

Page 9 of 43

Supplementary fig 7. Forest plot of iron use on birth weight

I-V Overall (I-squared = 98.9%, p = 0.000)

Sood 1975 b

Makrides 2003

Cogswell 2003

Falahi 2011

Menendez 1994

Taylor 1982

Bloxam 1989

Ziaei 2007

Harvey 2007

Puolakka 1980

Ndyomugyenyi 2000

Zeng 2008

Preziosi 1997

Dawson 1989

Siega-Riz 2006

Ouladsahebmadarek 2011

Christian 2003

D+L Overall

Sood 1975 a

Chan 2009

studyid

Eskeland 1997 b

45.95 (41.95, 49.96)

30.08 (3.43, 56.73)

-43.00 (-65.21, -20.79)

205.00 (172.52, 237.48)

40.00 (6.05, 73.95)

87.00 (67.71, 106.29)

-32.00 (-78.91, 14.91)

470.00 (436.07, 503.93)

10.00 (-4.01, 24.01)

-100.00 (-220.26, 20.26)

-300.00 (-373.90, -226.10)

86.00 (66.36, 105.64)

20.20 (12.36, 28.04)

30.00 (2.07, 57.93)

-220.00 (-241.79, -198.21)

108.00 (83.20, 132.80)

43.22 (29.94, 56.50)

65.00 (52.44, 77.56)

41.21 (1.20, 81.23)

71.00 (28.44, 113.56)

95.40 (85.79, 105.01)

WMD (95% CI)

78.90 (24.45, 133.35)

100.00

2.26

3.26

1.52

1.39

%

4.32

0.73

1.40

8.19

0.11

0.29

4.17

26.16

Weight

2.06

3.39

2.61

9.11

10.19

0.89

17.40

(I-V)

0.54

45.95 (41.95, 49.96)

30.08 (3.43, 56.73)

-43.00 (-65.21, -20.79)

205.00 (172.52, 237.48)

40.00 (6.05, 73.95)

87.00 (67.71, 106.29)

-32.00 (-78.91, 14.91)

470.00 (436.07, 503.93)

10.00 (-4.01, 24.01)

-100.00 (-220.26, 20.26)

-300.00 (-373.90, -226.10)

86.00 (66.36, 105.64)

20.20 (12.36, 28.04)

30.00 (2.07, 57.93)

-220.00 (-241.79, -198.21)

108.00 (83.20, 132.80)

43.22 (29.94, 56.50)

65.00 (52.44, 77.56)

41.21 (1.20, 81.23)

71.00 (28.44, 113.56)

95.40 (85.79, 105.01)

WMD (95% CI)

78.90 (24.45, 133.35)

100.00

2.26

3.26

1.52

1.39

%

4.32

0.73

1.40

8.19

0.11

0.29

4.17

26.16

Weight

2.06

3.39

2.61

9.11

10.19

0.89

17.40

(I-V)

0.54

Intervention decreases birth weight Intervention increases birth weight

0-10010

Page 10 of 43

Supplementary fig 8. Forest plot of iron use on preterm birth

I-V Overall (I-squared = 0.0%, p = 0.676)

D+L Overall

Cogswell 2003

Makrides 2003

Taylor 1982

studyid

Siega-Riz 2006

Ouladsahebmadarek 2011

Chan 2009

Harvey 2007

Falahi 2011

Ziaei 2007

Christian 2003

Eskeland 1997 b

Zeng 2008

0.84 (0.68, 1.03)

0.84 (0.68, 1.03)

1.03 (0.50, 2.09)

0.59 (0.30, 1.19)

7.00 (0.38, 128.61)

ES (95% CI)

0.54 (0.28, 1.02)

0.81 (0.42, 1.56)

0.95 (0.58, 1.57)

1.14 (0.03, 50.40)

0.45 (0.09, 2.22)

1.26 (0.62, 2.56)

1.13 (0.55, 2.30)

0.32 (0.01, 7.48)

0.79 (0.53, 1.18)

100.00

%

Weight

8.44

8.92

0.50

(I-V)

10.34

9.80

16.83

0.30

1.64

8.49

8.38

0.43

25.92

0.84 (0.68, 1.03)

0.84 (0.68, 1.03)

1.03 (0.50, 2.09)

0.59 (0.30, 1.19)

7.00 (0.38, 128.61)

ES (95% CI)

0.54 (0.28, 1.02)

0.81 (0.42, 1.56)

0.95 (0.58, 1.57)

1.14 (0.03, 50.40)

0.45 (0.09, 2.22)

1.26 (0.62, 2.56)

1.13 (0.55, 2.30)

0.32 (0.01, 7.48)

0.79 (0.53, 1.18)

100.00

%

Weight

8.44

8.92

0.50

(I-V)

10.34

9.80

16.83

0.30

1.64

8.49

8.38

0.43

25.92

Intervention decreases risk Intervention increases risk 1.1 1 5

Page 11 of 43

Supplementary fig 9. Forest plot of iron use on duration of gestation

I-V Overall (I-squared = 0.0%, p = 1.000)

Meier 2003 a

Siega-Riz 2006

Falahi 2011

Zeng 2008

studyid

Ziaei 2007

Ouladsahebmadarek 2011

Meier 2003 b

Dawson 1989

Makrides 2003

D+L Overall

Chan 2009

Bloxam 1989

0.11 (-0.35, 0.57)

0.10 (-7.43, 7.63)

0.10 (-15.23, 15.43)

0.10 (-13.18, 13.38)

0.21 (-0.95, 1.37)

WMD (95% CI)

0.00 (-6.78, 6.78)

0.04 (-1.52, 1.60)

-0.30 (-6.92, 6.32)

0.00 (-25.37, 25.37)

0.20 (-11.34, 11.74)

0.11 (-0.35, 0.57)

0.10 (-0.43, 0.63)

0.00 (-4.34, 4.34)

100.00

0.37

0.09

0.12

15.41

(I-V)

0.45

8.62

0.48

0.03

0.16

Weight

73.17

%

1.11

0.11 (-0.35, 0.57)

0.10 (-7.43, 7.63)

0.10 (-15.23, 15.43)

0.10 (-13.18, 13.38)

0.21 (-0.95, 1.37)

WMD (95% CI)

0.00 (-6.78, 6.78)

0.04 (-1.52, 1.60)

-0.30 (-6.92, 6.32)

0.00 (-25.37, 25.37)

0.20 (-11.34, 11.74)

0.11 (-0.35, 0.57)

0.10 (-0.43, 0.63)

0.00 (-4.34, 4.34)

100.00

0.37

0.09

0.12

15.41

(I-V)

0.45

8.62

0.48

0.03

0.16

Weight

73.17

%

1.11

Intervention decreases gest age Intervention increases gest age 0-10 -5 0 5 10

Page 12 of 43

Supplementary fig 10. Forest plot of iron use on SGA birth

I-V Overall (I-squared = 59.4%, p = 0.016)

D+L Overall

Zeng 2008

Dawson 1989

Siega-Riz 2006

Christian 2003

Ouladsahebmadarek 2011

Cogswell 2003

Ziaei 2007

Chan 2009

studyid

0.90 (0.83, 0.98)

0.85 (0.67, 1.07)

1.04 (0.66, 1.63)

1.05 (0.02, 50.43)

0.70 (0.39, 1.25)

0.91 (0.83, 1.00)

0.81 (0.58, 1.12)

0.39 (0.17, 0.86)

1.53 (1.03, 2.26)

0.48 (0.26, 0.87)

ES (95% CI)

100.00

3.46

Weight

0.05

2.07

80.23

6.58

1.10

4.55

1.96

(I-V)

%

0.90 (0.83, 0.98)

0.85 (0.67, 1.07)

1.04 (0.66, 1.63)

1.05 (0.02, 50.43)

0.70 (0.39, 1.25)

0.91 (0.83, 1.00)

0.81 (0.58, 1.12)

0.39 (0.17, 0.86)

1.53 (1.03, 2.26)

0.48 (0.26, 0.87)

ES (95% CI)

100.00

3.46

Weight

0.05

2.07

80.23

6.58

1.10

4.55

1.96

(I-V)

%

Intervention decreases risk Intervention increases risk

1.1 1 5

Page 13 of 43

Supplementary fig 11. Forest plot of iron use on birth length

I-V Overall (I-squared = 0.0%, p = 0.763)

Eskeland 1997 b

D+L Overall

Meier 2003 a

studyid

Cogswell 2003

Zeng 2008

Preziosi 1997

Christian 2003

Falahi 2011

Makrides 2003

Meier 2003 b

-1.08 (-4.96, 2.80)

0.00 (-24.10, 24.10)

-1.08 (-4.96, 2.80)

-1.60 (-30.60, 27.40)

WMD (95% CI)

0.35 (-20.76, 21.46)

0.30 (-5.17, 5.77)

0.70 (-16.62, 18.02)

0.20 (-7.61, 8.01)

-0.20 (-27.91, 27.51)

-15.60 (-29.00, -2.20)

0.60 (-28.13, 29.33)

100.00

Weight

2.59

1.79

(I-V)

3.38

50.35

5.02

24.68

1.96

8.39

1.83

%

-1.08 (-4.96, 2.80)

0.00 (-24.10, 24.10)

-1.08 (-4.96, 2.80)

-1.60 (-30.60, 27.40)

WMD (95% CI)

0.35 (-20.76, 21.46)

0.30 (-5.17, 5.77)

0.70 (-16.62, 18.02)

0.20 (-7.61, 8.01)

-0.20 (-27.91, 27.51)

-15.60 (-29.00, -2.20)

0.60 (-28.13, 29.33)

100.00

Weight

2.59

1.79

(I-V)

3.38

50.35

5.02

24.68

1.96

8.39

1.83

%

Intervention decreases birth length Intervention increases birth length

0-10 0 10

Page 14 of 43

Supplementary fig 12. Exposure-response relationship between iron dose and maternal anaemia

Page 15 of 43

Supplementary fig 13. Exposure-response relationship between iron dose up to 66 mg/day and maternal

anaemia

Page 16 of 43

Supplementary fig 14. Exposure-response relationship between iron dose up to 66 mg/day and low birth

weight risk

Page 17 of 43

Supplementary fig 15. Exposure-response relationship between iron dose up to 66 mg/day and birth

weight

Page 18 of 43

Supplementary fig 16. Exposure-response relationship of haemoglobin difference with birth weight

Page 19 of 43

Supplementary fig 17. Exposure-response relationship of haemoglobin difference with low birth weight

risk

Page 20 of 43

Supplementary fig 18. Exposure-response relationship of haemoglobin difference with preterm birth

risk

Page 21 of 43

Supplementary fig 19. Forest plot of iron only on mean haemoglobin concentration in third trimester or

at delivery

I-V Overall (I-squared = 0.0%, p = 0.967)

Siega-Riz 2006

Dawson 1989

Buytaert 1983

Svanberg 1975Simmons 1993

Romslo 1983

Milman 1991

Chan 2009

Van Eijk 1978Wallenburg 1984

Tanumihardjo 2002 a

De Benaze 1989

Harvey 2007

studyid

D+L Overall

Falahi 2011

Cogswell 2003

Tura 1989

Zeng 2008

Butler 1968 a

Hoa 2005 a

Freire 1989

Batu 1976 b

Menendez 1994

Eskeland 1997 b

McKenna 2003

Tanumihardjo 2002 b

Batu 1976 a

Ziaei 2008

Charoenlarp 1988 c

Cantlie 1971

Makrides 2003

Ziaei 2007

Ouladsahebmadarek 2011Puolakka 1980

4.50 (3.62, 5.39)

0.00 (-22.34, 22.34)

6.67 (-20.05, 33.39)

3.23 (-12.55, 19.01)

5.00 (-71.51, 81.51)10.40 (3.68, 17.12)

13.00 (-46.48, 72.48)

8.50 (-31.53, 48.53)

4.00 (3.04, 4.96)

19.34 (-7.05, 45.73)3.22 (-88.75, 95.19)

10.00 (-93.41, 113.41)

8.00 (-1.82, 17.82)

9.00 (-128.88, 146.88)

WMD (95% CI)

4.50 (3.62, 5.39)

2.30 (-43.45, 48.05)

-0.30 (-7.09, 6.49)

2.00 (-23.97, 27.97)

4.80 (-3.15, 12.75)

1.00 (-117.50, 119.50)

6.90 (-36.97, 50.77)

7.40 (0.53, 14.27)

19.00 (-3.31, 41.31)

9.00 (-0.88, 18.88)

12.90 (-63.07, 88.87)

2.00 (-53.69, 57.69)

14.00 (-100.46, 128.46)

16.00 (3.68, 28.32)

11.00 (-13.59, 35.59)

12.50 (1.11, 23.89)

14.00 (-51.93, 79.93)

7.00 (0.53, 13.47)

7.20 (2.11, 12.29)

9.80 (-9.73, 29.33)21.00 (-52.27, 94.27)

100.00

0.16

0.11

0.31

0.011.72

0.02

Weight

0.05

84.58

0.110.01

0.01

0.81

0.00

(I-V)

0.04

1.69

0.12

1.23

0.01

0.04

1.65

0.16

0.80

0.01

0.03

0.01

0.51

0.13

0.60

0.02

%

1.86

3.00

0.200.01

4.50 (3.62, 5.39)

0.00 (-22.34, 22.34)

6.67 (-20.05, 33.39)

3.23 (-12.55, 19.01)

5.00 (-71.51, 81.51)10.40 (3.68, 17.12)

13.00 (-46.48, 72.48)

8.50 (-31.53, 48.53)

4.00 (3.04, 4.96)

19.34 (-7.05, 45.73)3.22 (-88.75, 95.19)

10.00 (-93.41, 113.41)

8.00 (-1.82, 17.82)

9.00 (-128.88, 146.88)

WMD (95% CI)

4.50 (3.62, 5.39)

2.30 (-43.45, 48.05)

-0.30 (-7.09, 6.49)

2.00 (-23.97, 27.97)

4.80 (-3.15, 12.75)

1.00 (-117.50, 119.50)

6.90 (-36.97, 50.77)

7.40 (0.53, 14.27)

19.00 (-3.31, 41.31)

9.00 (-0.88, 18.88)

12.90 (-63.07, 88.87)

2.00 (-53.69, 57.69)

14.00 (-100.46, 128.46)

16.00 (3.68, 28.32)

11.00 (-13.59, 35.59)

12.50 (1.11, 23.89)

14.00 (-51.93, 79.93)

7.00 (0.53, 13.47)

7.20 (2.11, 12.29)

9.80 (-9.73, 29.33)21.00 (-52.27, 94.27)

100.00

0.16

0.11

0.31

0.011.72

0.02

Weight

0.05

84.58

0.110.01

0.01

0.81

0.00

(I-V)

0.04

1.69

0.12

1.23

0.01

0.04

1.65

0.16

0.80

0.01

0.03

0.01

0.51

0.13

0.60

0.02

%

1.86

3.00

0.200.01

Intervention decreases Hb Intervention increases Hb

0-10 0 10

Page 22 of 43

Supplementary fig 20. Forest plot of iron only on mean haemoglobin concentration in postpartum

period

I-V Overall (I-squared = 0.0%, p = 0.999)

studyid

D+L Overall

Wallenburg 1984

Cantlie 1971

Eskeland 1997 b

Menendez 1994

Buytaert 1983

Dawson 1989

Butler 1968 a

Christian 2003 b

7.01 (0.36, 13.66)

WMD (95% CI)

7.01 (0.36, 13.66)

0.00 (-96.37, 96.37)

14.00 (-83.01, 111.01)

4.00 (-76.63, 84.63)

5.00 (-5.68, 15.68)

-3.22 (-84.50, 78.06)

3.34 (-23.38, 30.06)

2.00 (-69.21, 73.21)

9.20 (-0.03, 18.43)

100.00

(I-V)

0.48

0.47

0.68

38.72

0.67

%

6.19

Weight

0.87

51.92

7.01 (0.36, 13.66)

WMD (95% CI)

7.01 (0.36, 13.66)

0.00 (-96.37, 96.37)

14.00 (-83.01, 111.01)

4.00 (-76.63, 84.63)

5.00 (-5.68, 15.68)

-3.22 (-84.50, 78.06)

3.34 (-23.38, 30.06)

2.00 (-69.21, 73.21)

9.20 (-0.03, 18.43)

100.00

(I-V)

0.48

0.47

0.68

38.72

0.67

%

6.19

Weight

0.87

51.92

Intervention decreases Hb level Intervention increases Hb level

0-10 0 10

Page 23 of 43

Supplementary fig 21. Forest plot of iron only on maternal anaemia

I-V Overall (I-squared = 75.4%, p = 0.000)

Charoenlarp 1988 cChisholm 1966 a

Batu 1976 b

Sood 1975 a

Romslo 1983

Sood 1975 c

Preziosi 1997

Siega-Riz 2006

Sood 1975 b

Puolakka 1980

Cogswell 2003

Zeng 2008

Christian 2003 b

studyid

Makrides 2003Milman 1991

Pritchard 1958

Sood 1975 e

Holly 1955

Sood 1975 d

D+L Overall

De Benaze 1989

Batu 1976 a

Eskeland 1997 b

0.70 (0.66, 0.73)

0.41 (0.27, 0.62)0.15 (0.05, 0.48)

0.41 (0.22, 0.75)

0.66 (0.56, 0.80)

0.15 (0.02, 1.12)

0.85 (0.69, 1.03)

0.59 (0.45, 0.77)

1.11 (0.71, 1.71)

0.80 (0.65, 0.99)

0.07 (0.00, 1.15)

0.75 (0.35, 1.59)

0.74 (0.70, 0.79)

0.43 (0.32, 0.58)

ES (95% CI)

0.45 (0.25, 0.82)0.09 (0.02, 0.38)

0.17 (0.08, 0.39)

0.64 (0.50, 0.82)

0.03 (0.00, 0.18)

0.65 (0.52, 0.81)

0.56 (0.48, 0.65)

0.21 (0.06, 0.73)

0.57 (0.37, 0.88)

0.06 (0.00, 1.00)

100.00

1.32

%

0.17

0.62

7.32

0.06

5.85

3.30

1.22

5.36

0.03

0.42

60.55

2.67

(I-V)

0.650.12

0.35

3.85

0.06

4.63

0.15

Weight

1.27

0.03

0.70 (0.66, 0.73)

0.41 (0.27, 0.62)0.15 (0.05, 0.48)

0.41 (0.22, 0.75)

0.66 (0.56, 0.80)

0.15 (0.02, 1.12)

0.85 (0.69, 1.03)

0.59 (0.45, 0.77)

1.11 (0.71, 1.71)

0.80 (0.65, 0.99)

0.07 (0.00, 1.15)

0.75 (0.35, 1.59)

0.74 (0.70, 0.79)

0.43 (0.32, 0.58)

ES (95% CI)

0.45 (0.25, 0.82)0.09 (0.02, 0.38)

0.17 (0.08, 0.39)

0.64 (0.50, 0.82)

0.03 (0.00, 0.18)

0.65 (0.52, 0.81)

0.56 (0.48, 0.65)

0.21 (0.06, 0.73)

0.57 (0.37, 0.88)

0.06 (0.00, 1.00)

100.00

1.32

%

0.17

0.62

7.32

0.06

5.85

3.30

1.22

5.36

0.03

0.42

60.55

2.67

(I-V)

0.650.12

0.35

3.85

0.06

4.63

0.15

Weight

1.27

0.03

Intervention decreases risk Intervention increases risk 1.1 1 5

Page 24 of 43

Supplementary fig 22. Forest plot of iron only on iron deficiency

I-V Overall (I-squared = 79.4%, p = 0.000)

Cogswell 2003

D+L Overall

Milman 1991

Romslo 1983

Falahi 2011

Makrides 2003

studyid

Siega-Riz 2006

Preziosi 1997

Tura 1989

0.73 (0.66, 0.82)

0.87 (0.69, 1.08)

0.59 (0.44, 0.79)

0.16 (0.04, 0.71)

0.06 (0.01, 0.38)

0.35 (0.16, 0.78)

0.60 (0.48, 0.76)

ES (95% CI)

0.81 (0.65, 1.02)

0.34 (0.21, 0.54)

0.92 (0.73, 1.17)

100.00

Weight

23.89

%

0.57

0.33

1.97

22.43

(I-V)

22.95

5.42

22.45

0.73 (0.66, 0.82)

0.87 (0.69, 1.08)

0.59 (0.44, 0.79)

0.16 (0.04, 0.71)

0.06 (0.01, 0.38)

0.35 (0.16, 0.78)

0.60 (0.48, 0.76)

ES (95% CI)

0.81 (0.65, 1.02)

0.34 (0.21, 0.54)

0.92 (0.73, 1.17)

100.00

Weight

23.89

%

0.57

0.33

1.97

22.43

(I-V)

22.95

5.42

22.45

Intervention decreases anaemia risk Intervention increases anaemia risk 1.1 1 5

Page 25 of 43

Supplementary fig 23. Forest plot of iron only on iron deficiency anaemia

I-V Overall (I-squared = 46.5%, p = 0.082)

Makrides 2003

Siega-Riz 2006

Cogswell 2003

Meier 2003 b

D+L Overall

Meier 2003 a

studyid

Milman 1991

Christian 2003 b

0.37 (0.27, 0.50)

0.28 (0.12, 0.68)

0.69 (0.33, 1.43)

0.61 (0.32, 1.15)

0.47 (0.16, 1.44)

0.37 (0.23, 0.60)

0.17 (0.02, 1.32)

ES (95% CI)

0.06 (0.00, 0.93)

0.24 (0.15, 0.39)

100.00

11.52

Weight

17.20

22.36

7.40

%

2.18

(I-V)

1.14

38.20

0.37 (0.27, 0.50)

0.28 (0.12, 0.68)

0.69 (0.33, 1.43)

0.61 (0.32, 1.15)

0.47 (0.16, 1.44)

0.37 (0.23, 0.60)

0.17 (0.02, 1.32)

ES (95% CI)

0.06 (0.00, 0.93)

0.24 (0.15, 0.39)

100.00

11.52

Weight

17.20

22.36

7.40

%

2.18

(I-V)

1.14

38.20

Intervention decreases anaemia risk Intervention increases anaemia risk

1.1 1 5

Page 26 of 43

Supplementary fig 24. Forest plot of iron only on birth weight

I-V Overall (I-squared = 98.8%, p = 0.000)

Sood 1975 c

Bloxam 1989

Sood 1975 e

Puolakka 1980

Harvey 2007Falahi 2011

D+L Overall

Dawson 1989

Ziaei 2007

Sood 1975 a

Sood 1975 d

Siega-Riz 2006

Makrides 2003

Cogswell 2003

Eskeland 1997 b

Chan 2009

Ouladsahebmadarek 2011

studyid

Sood 1975 b

Menendez 1994

Christian 2003 b

Zeng 2008

Preziosi 1997

45.48 (41.39, 49.58)

-18.40 (-60.66, 23.86)

470.00 (436.41, 503.59)

79.10 (42.14, 116.06)

-300.00 (-375.69, -224.31)

-100.00 (-222.96, 22.96)40.00 (5.26, 74.74)

40.80 (0.97, 80.62)

-220.00 (-241.76, -198.24)

10.00 (-4.30, 24.30)

71.00 (27.54, 114.46)

11.60 (-31.47, 54.67)

108.00 (82.55, 133.45)

-43.00 (-65.88, -20.12)

205.00 (171.59, 238.41)

78.90 (23.09, 134.71)

95.40 (85.65, 105.15)

43.22 (29.58, 56.86)

WMD (95% CI)

44.90 (5.05, 84.75)

87.00 (67.29, 106.71)

65.00 (53.74, 76.26)

20.20 (12.12, 28.28)

30.00 (1.37, 58.63)

100.00

0.94

1.49

1.23

0.29

0.111.39

3.55

8.22

0.89

0.91

2.59

3.21

1.50

0.54

17.68

Weight

9.03

(I-V)

1.06

4.32

13.25

25.75

2.05

%

45.48 (41.39, 49.58)

-18.40 (-60.66, 23.86)

470.00 (436.41, 503.59)

79.10 (42.14, 116.06)

-300.00 (-375.69, -224.31)

-100.00 (-222.96, 22.96)40.00 (5.26, 74.74)

40.80 (0.97, 80.62)

-220.00 (-241.76, -198.24)

10.00 (-4.30, 24.30)

71.00 (27.54, 114.46)

11.60 (-31.47, 54.67)

108.00 (82.55, 133.45)

-43.00 (-65.88, -20.12)

205.00 (171.59, 238.41)

78.90 (23.09, 134.71)

95.40 (85.65, 105.15)

43.22 (29.58, 56.86)

WMD (95% CI)

44.90 (5.05, 84.75)

87.00 (67.29, 106.71)

65.00 (53.74, 76.26)

20.20 (12.12, 28.28)

30.00 (1.37, 58.63)

100.00

0.94

1.49

1.23

0.29

0.111.39

3.55

8.22

0.89

0.91

2.59

3.21

1.50

0.54

17.68

Weight

9.03

(I-V)

1.06

4.32

13.25

25.75

2.05

%

Intervention decreases birthweight Intervention increases birthweight 0-10010

Page 27 of 43

Supplementary fig 25. Forest plot of iron only on low birth weight

I-V Overall (I-squared = 9.3%, p = 0.356)

Meier 2003 b

Meier 2003 a

Christian 2003 b

D+L Overall

Menendez 1994

Makrides 2003

Siega-Riz 2006

Zeng 2008

Falahi 2011

studyid

Dawson 1989

Cogswell 2003

Ziaei 2007

0.81 (0.71, 0.91)

1.89 (0.18, 20.00)

0.81 (0.02, 38.71)

0.82 (0.71, 0.95)

0.78 (0.64, 0.95)

0.55 (0.22, 1.38)

1.30 (0.56, 3.03)

0.51 (0.22, 1.15)

0.81 (0.50, 1.32)

0.45 (0.09, 2.22)

ES (95% CI)

0.35 (0.02, 8.10)

0.26 (0.10, 0.67)

1.21 (0.57, 2.54)

100.00

0.29

0.11

80.65

1.94

Weight

2.28

2.41

6.87

0.63

(I-V)

0.16

1.73

%

2.92

0.81 (0.71, 0.91)

1.89 (0.18, 20.00)

0.81 (0.02, 38.71)

0.82 (0.71, 0.95)

0.78 (0.64, 0.95)

0.55 (0.22, 1.38)

1.30 (0.56, 3.03)

0.51 (0.22, 1.15)

0.81 (0.50, 1.32)

0.45 (0.09, 2.22)

ES (95% CI)

0.35 (0.02, 8.10)

0.26 (0.10, 0.67)

1.21 (0.57, 2.54)

100.00

0.29

0.11

80.65

1.94

Weight

2.28

2.41

6.87

0.63

(I-V)

0.16

1.73

%

2.92

Intervention decreases LBW risk Intervention increases LBW risk 1.1 1 5

Page 28 of 43

Supplementary fig 26. Forest plot of iron only on duration of gestation

I-V Overall (I-squared = 0.0%, p = 1.000)

Ziaei 2007

Meier 2003 a

Ouladsahebmadarek 2011

Bloxam 1989

Falahi 2011

Siega-Riz 2006

Makrides 2003

Meier 2003 b

Zeng 2008

studyid

D+L Overall

Dawson 1989

Chan 2009

0.11 (-0.35, 0.57)

0.00 (-6.78, 6.78)

0.10 (-7.74, 7.94)

0.04 (-1.52, 1.60)

0.00 (-4.34, 4.34)

0.10 (-13.46, 13.66)

0.10 (-15.57, 15.77)

0.20 (-11.43, 11.83)

-0.30 (-7.14, 6.54)

0.21 (-0.99, 1.41)

WMD (95% CI)

0.11 (-0.35, 0.57)

0.00 (-25.90, 25.90)

0.10 (-0.43, 0.63)

100.00

%

0.46

0.34

8.69

1.12

0.11

0.09

0.16

0.45

14.71

(I-V)

0.03

Weight

73.84

0.11 (-0.35, 0.57)

0.00 (-6.78, 6.78)

0.10 (-7.74, 7.94)

0.04 (-1.52, 1.60)

0.00 (-4.34, 4.34)

0.10 (-13.46, 13.66)

0.10 (-15.57, 15.77)

0.20 (-11.43, 11.83)

-0.30 (-7.14, 6.54)

0.21 (-0.99, 1.41)

WMD (95% CI)

0.11 (-0.35, 0.57)

0.00 (-25.90, 25.90)

0.10 (-0.43, 0.63)

100.00

%

0.46

0.34

8.69

1.12

0.11

0.09

0.16

0.45

14.71

(I-V)

0.03

Weight

73.84

Intervention decreases gest age Intervention increases gest age 0-10 -5 0 5 10

Page 29 of 43

Supplementary fig 27. Forest plot of iron only on preterm birth

I-V Overall (I-squared = 0.0%, p = 0.586)

Makrides 2003

studyid

Chan 2009

Ouladsahebmadarek 2011

Siega-Riz 2006

Falahi 2011

Ziaei 2007

Zeng 2008

Harvey 2007

Eskeland 1997 b

Cogswell 2003

Christian 2003 b

D+L Overall

0.92 (0.80, 1.07)

0.59 (0.30, 1.19)

ES (95% CI)

0.95 (0.58, 1.57)

0.81 (0.42, 1.56)

0.54 (0.28, 1.02)

0.45 (0.09, 2.22)

1.26 (0.62, 2.56)

0.79 (0.53, 1.18)

1.14 (0.03, 50.40)

0.32 (0.01, 7.48)

1.03 (0.50, 2.09)

1.04 (0.85, 1.28)

0.92 (0.80, 1.07)

100.00

4.62

(I-V)

Weight

8.73

5.08

5.36

0.85

%

4.40

13.44

0.15

0.22

4.38

52.76

0.92 (0.80, 1.07)

0.59 (0.30, 1.19)

ES (95% CI)

0.95 (0.58, 1.57)

0.81 (0.42, 1.56)

0.54 (0.28, 1.02)

0.45 (0.09, 2.22)

1.26 (0.62, 2.56)

0.79 (0.53, 1.18)

1.14 (0.03, 50.40)

0.32 (0.01, 7.48)

1.03 (0.50, 2.09)

1.04 (0.85, 1.28)

0.92 (0.80, 1.07)

100.00

4.62

(I-V)

Weight

8.73

5.08

5.36

0.85

%

4.40

13.44

0.15

0.22

4.38

52.76

Intervention decreases risk Intervention increases risk 1.1 1 5

Page 30 of 43

Supplementary fig 28. Forest plot of iron only on SGA

I-V Overall (I-squared = 65.0%, p = 0.009)

Ziaei 2007

Cogswell 2003

studyid

Zeng 2008

Siega-Riz 2006

Ouladsahebmadarek 2011

Christian 2003 b

D+L Overall

Chan 2009

0.89 (0.81, 0.97)

1.53 (1.03, 2.26)

0.39 (0.17, 0.86)

ES (95% CI)

1.04 (0.66, 1.63)

0.70 (0.39, 1.25)

0.81 (0.58, 1.12)

0.89 (0.81, 0.99)

0.84 (0.66, 1.07)

0.48 (0.26, 0.87)

100.00

5.15

1.24

(I-V)

3.92

Weight

2.34

7.46

77.66

2.22

%

0.89 (0.81, 0.97)

1.53 (1.03, 2.26)

0.39 (0.17, 0.86)

ES (95% CI)

1.04 (0.66, 1.63)

0.70 (0.39, 1.25)

0.81 (0.58, 1.12)

0.89 (0.81, 0.99)

0.84 (0.66, 1.07)

0.48 (0.26, 0.87)

100.00

5.15

1.24

(I-V)

3.92

Weight

2.34

7.46

77.66

2.22

%

Intervention decreases risk Intervention increases risk

1.1 1 5

Page 31 of 43

Supplementary fig 29. Forest plot of iron only on birth length

I-V Overall (I-squared = 0.0%, p = 0.768)

Meier 2003 a

D+L Overall

Zeng 2008

Falahi 2011

Eskeland 1997 b

Cogswell 2003

Makrides 2003

Preziosi 1997

Meier 2003 b

studyid

Christian 2003 b

-0.93 (-4.76, 2.89)

-1.60 (-30.60, 27.40)

-0.93 (-4.76, 2.89)

0.30 (-5.25, 5.85)

-0.20 (-28.23, 27.83)

0.00 (-24.56, 24.56)

0.35 (-21.25, 21.95)

-15.60 (-29.17, -2.03)

0.70 (-16.90, 18.30)

0.60 (-28.35, 29.55)

WMD (95% CI)

0.50 (-6.62, 7.62)

100.00

1.74

Weight

47.51

1.86

2.43

3.14

7.95

4.72

1.75

(I-V)

28.90

%

-0.93 (-4.76, 2.89)

-1.60 (-30.60, 27.40)

-0.93 (-4.76, 2.89)

0.30 (-5.25, 5.85)

-0.20 (-28.23, 27.83)

0.00 (-24.56, 24.56)

0.35 (-21.25, 21.95)

-15.60 (-29.17, -2.03)

0.70 (-16.90, 18.30)

0.60 (-28.35, 29.55)

WMD (95% CI)

0.50 (-6.62, 7.62)

100.00

1.74

Weight

47.51

1.86

2.43

3.14

7.95

4.72

1.75

(I-V)

28.90

%

Intervention decreases birth length Intervention increases birth length

0-10 0 10

Page 32 of 43

Supplementary fig 30. Forest plot of iron with folic acid on mean haemoglobin concentration in third

trimester or at delivery

I-V Overall (I-squared = 0.0%, p = 0.999)

Ndyomugyenyi 2000

Charoenlarp 1988 a

studyid

Lee 2005 a

Taylor 1982

Charoenlarp 1988 d

Lee 2005 d

Torlesse 2000 a

Batu 1976 c

Hoa 2005 b

D+L Overall

Butler 1968 b

Barton 1994

Torlesse 2000 b

Charoenlarp 1988 b

Charoenlarp 1988 e

Lee 2005 c

Lee 2005 b

10.41 (5.36, 15.46)

4.60 (-4.89, 14.09)

9.20 (-9.30, 27.70)

WMD (95% CI)

14.00 (-15.17, 43.17)

15.30 (-58.53, 89.13)

12.00 (-6.03, 30.03)

15.00 (-16.11, 46.11)

18.40 (0.21, 36.59)

18.00 (-2.98, 38.98)

9.20 (-36.44, 54.84)

10.41 (5.36, 15.46)

-2.00 (-113.41, 109.41)

8.90 (-17.85, 35.65)

10.30 (-4.90, 25.50)

11.70 (-6.97, 30.37)

13.80 (-3.70, 31.30)

4.00 (-29.18, 37.18)

17.00 (-13.50, 47.50)

100.00

%

28.35

Weight

7.45

(I-V)

3.00

0.47

7.85

2.63

7.71

5.80

1.22

0.21

3.56

11.04

7.32

8.33

2.32

2.74

10.41 (5.36, 15.46)

4.60 (-4.89, 14.09)

9.20 (-9.30, 27.70)

WMD (95% CI)

14.00 (-15.17, 43.17)

15.30 (-58.53, 89.13)

12.00 (-6.03, 30.03)

15.00 (-16.11, 46.11)

18.40 (0.21, 36.59)

18.00 (-2.98, 38.98)

9.20 (-36.44, 54.84)

10.41 (5.36, 15.46)

-2.00 (-113.41, 109.41)

8.90 (-17.85, 35.65)

10.30 (-4.90, 25.50)

11.70 (-6.97, 30.37)

13.80 (-3.70, 31.30)

4.00 (-29.18, 37.18)

17.00 (-13.50, 47.50)

100.00

%

28.35

Weight

7.45

(I-V)

3.00

0.47

7.85

2.63

7.71

5.80

1.22

0.21

3.56

11.04

7.32

8.33

2.32

2.74

Intervention decreases Hb level Intervention increases Hb level 0-10 0 10

Page 33 of 43

Supplementary fig 31. Forest plot of iron with folic acid on maternal anaemia in third trimester or at

delivery

I-V Overall (I-squared = 43.8%, p = 0.067)

Charoenlarp 1988 d

Charoenlarp 1988 e

Chisholm 1966 b

Liu 1996 b

Liu 1996 a

Charoenlarp 1988 a

Charoenlarp 1988 b

studyid

Ndyomugyenyi 2000

Christian 2003

Batu 1976 c

D+L Overall

0.46 (0.41, 0.52)

0.45 (0.29, 0.72)

0.32 (0.19, 0.55)

0.17 (0.08, 0.38)

0.41 (0.25, 0.67)

0.32 (0.19, 0.55)

0.61 (0.41, 0.91)

0.47 (0.30, 0.74)

ES (95% CI)

0.65 (0.47, 0.90)

0.46 (0.37, 0.57)

0.39 (0.21, 0.72)

0.44 (0.37, 0.53)

100.00

Weight

7.72

5.42

2.48

6.76

5.59

%

9.90

7.94

(I-V)

15.34

34.47

4.39

0.46 (0.41, 0.52)

0.45 (0.29, 0.72)

0.32 (0.19, 0.55)

0.17 (0.08, 0.38)

0.41 (0.25, 0.67)

0.32 (0.19, 0.55)

0.61 (0.41, 0.91)

0.47 (0.30, 0.74)

ES (95% CI)

0.65 (0.47, 0.90)

0.46 (0.37, 0.57)

0.39 (0.21, 0.72)

0.44 (0.37, 0.53)

100.00

Weight

7.72

5.42

2.48

6.76

5.59

%

9.90

7.94

(I-V)

15.34

34.47

4.39

Supplementation decreases risk Supplementation increases risk

1.1 1 5

Page 34 of 43

Supplementary fig 32. Forest plot of maternal anaemia on low birth weight (crude estimates)

I-V Overall (I-squared = 90.0%, p = 0.000)

Steer 2005

Kumar 2010

D+L Overall

Lee 2006

Xiong 2003

Bhalerao 2011

Murphy 1986

studyid

Bondevik 2001

Williams 1997

Zhou 1998

Vijayalaxmi 2009

Malhotra 2002

Bodeau-Livinec 2011

Marhatta 2007

Ren 2007

Levy 2005

Mola 1999

Abeysena 2010

Knottnerus 1990

Shobeiri 2006

Lone 2004

Chang 2003El Guindi 2004

Scholl 1992

Banhidy 2010

Hamalainen 2003

1.03 (0.99, 1.06)

0.66 (0.61, 0.71)

1.02 (0.83, 1.25)

1.25 (1.08, 1.45)

4.02 (1.46, 11.05)

0.84 (0.60, 1.17)

1.06 (0.71, 1.57)

1.35 (1.07, 1.69)

ES (95% CI)

1.29 (0.97, 1.72)

2.26 (1.14, 4.45)

2.09 (1.05, 4.15)

1.62 (0.84, 3.13)

1.01 (0.62, 1.62)

0.85 (0.57, 1.26)

1.80 (1.21, 2.69)

1.21 (1.08, 1.36)

1.13 (1.07, 1.20)

1.19 (1.09, 1.30)

0.68 (0.24, 1.94)

0.82 (0.40, 1.68)

15.94 (5.33, 47.68)

2.42 (1.38, 4.27)

0.95 (0.37, 2.46)1.71 (0.83, 3.55)

1.42 (0.92, 2.19)

0.85 (0.75, 0.96)

3.19 (1.38, 7.40)

100.00

18.75

2.930.12

1.09

0.77

2.32

(I-V)

%

1.47

0.26

0.26

0.28

0.53

0.77

0.76

9.62

35.37

14.63

0.11

0.23

0.10

0.38

Weight

0.130.23

0.65

8.08

0.17

1.03 (0.99, 1.06)

0.66 (0.61, 0.71)

1.02 (0.83, 1.25)

1.25 (1.08, 1.45)

4.02 (1.46, 11.05)

0.84 (0.60, 1.17)

1.06 (0.71, 1.57)

1.35 (1.07, 1.69)

ES (95% CI)

1.29 (0.97, 1.72)

2.26 (1.14, 4.45)

2.09 (1.05, 4.15)

1.62 (0.84, 3.13)

1.01 (0.62, 1.62)

0.85 (0.57, 1.26)

1.80 (1.21, 2.69)

1.21 (1.08, 1.36)

1.13 (1.07, 1.20)

1.19 (1.09, 1.30)

0.68 (0.24, 1.94)

0.82 (0.40, 1.68)

15.94 (5.33, 47.68)

2.42 (1.38, 4.27)

0.95 (0.37, 2.46)1.71 (0.83, 3.55)

1.42 (0.92, 2.19)

0.85 (0.75, 0.96)

3.19 (1.38, 7.40)

100.00

18.75

2.930.12

1.09

0.77

2.32

(I-V)

%

1.47

0.26

0.26

0.28

0.53

0.77

0.76

9.62

35.37

14.63

0.11

0.23

0.10

0.38

Weight

0.130.23

0.65

8.08

0.17

Exposure decreases odds Exposure increases odds 1.1 1 5

Page 35 of 43

Supplementary fig 33. Forest plot of maternal anaemia on low birth weight (adjusted estimates)

I-V Overall (I-squared = 86.2%, p = 0.000)

Hamalainen 2003

Knottnerus 1990

Levy 2005

Xiong 2003

Abeysena 2010

Scholl 1992

D+L Overall

Banhidy 2010

von Tempelhoff 2008

Ren 2007

studyid

1.19 (1.14, 1.25)

3.14 (1.35, 7.28)

0.82 (0.38, 1.76)

1.10 (1.01, 1.20)

0.75 (0.53, 1.07)

0.56 (0.07, 4.74)

1.55 (0.96, 2.51)

1.13 (0.94, 1.34)

0.85 (0.73, 0.99)

1.44 (1.33, 1.56)

1.16 (1.04, 1.30)

ES (95% CI)

100.00

0.33

0.40

31.17

1.87

%

0.05

1.02

10.15

36.83

Weight

18.18

(I-V)

1.19 (1.14, 1.25)

3.14 (1.35, 7.28)

0.82 (0.38, 1.76)

1.10 (1.01, 1.20)

0.75 (0.53, 1.07)

0.56 (0.07, 4.74)

1.55 (0.96, 2.51)

1.13 (0.94, 1.34)

0.85 (0.73, 0.99)

1.44 (1.33, 1.56)

1.16 (1.04, 1.30)

ES (95% CI)

100.00

0.33

0.40

31.17

1.87

%

0.05

1.02

10.15

36.83

Weight

18.18

(I-V)

Exposure decreases odds Exposure increases odds 1.1 1 5

Page 36 of 43

Supplementary fig 34. Forest plot of maternal anaemia on preterm birth (crude estimates)

I-V Overall (I-squared = 88.9%, p = 0.000)

Levy 2005

Zhou 1998

studyid

Scholl 1992

Kumar 2010

Marhatta 2007

Vijayalaxmi 2009

Banhidy 2010

Lone 2004

D+L Overall

Mau 1977

Knottnerus 1990

Chang 2003

Gonzales 2009

Lee 2006

Hamalainen 2003

Bhalerao 2011

Arbuckle 1989

Steer 2005

Feresu 2004Fareh 2005

Zhang 2009

Bondevik 2001

Malhotra 2002

Ren 2007

Xiong 2003

Abeysena 2010

Murphy 1986

1.06 (1.03, 1.10)

1.20 (1.13, 1.27)

1.74 (1.00, 3.02)

ES (95% CI)

1.59 (1.10, 2.30)

2.50 (0.86, 7.25)

7.60 (1.67, 34.48)

1.67 (0.86, 3.25)

0.99 (0.90, 1.08)

5.00 (2.97, 8.40)

1.28 (1.12, 1.47)

0.71 (0.48, 1.06)

0.86 (0.38, 1.93)

0.71 (0.26, 1.95)

1.21 (1.08, 1.36)

4.46 (1.55, 12.80)

1.81 (0.73, 4.50)

2.48 (1.65, 3.75)

1.22 (0.99, 1.51)

0.73 (0.68, 0.79)

6.50 (2.17, 19.42)9.37 (0.50, 176.43)

1.05 (0.84, 1.30)

0.92 (0.60, 1.42)

1.24 (0.75, 2.07)

1.13 (1.05, 1.22)

1.08 (0.82, 1.42)

0.70 (0.24, 2.00)

1.16 (0.94, 1.44)

100.00

30.38

0.34

Weight(I-V)

0.75

0.09

0.04

0.23

11.71

0.38

0.67

0.16

0.10

7.52

0.09

0.12

0.61

%

2.26

19.36

0.090.01

2.18

0.54

0.40

18.31

1.35

0.09

2.20

1.06 (1.03, 1.10)

1.20 (1.13, 1.27)

1.74 (1.00, 3.02)

ES (95% CI)

1.59 (1.10, 2.30)

2.50 (0.86, 7.25)

7.60 (1.67, 34.48)

1.67 (0.86, 3.25)

0.99 (0.90, 1.08)

5.00 (2.97, 8.40)

1.28 (1.12, 1.47)

0.71 (0.48, 1.06)

0.86 (0.38, 1.93)

0.71 (0.26, 1.95)

1.21 (1.08, 1.36)

4.46 (1.55, 12.80)

1.81 (0.73, 4.50)

2.48 (1.65, 3.75)

1.22 (0.99, 1.51)

0.73 (0.68, 0.79)

6.50 (2.17, 19.42)9.37 (0.50, 176.43)

1.05 (0.84, 1.30)

0.92 (0.60, 1.42)

1.24 (0.75, 2.07)

1.13 (1.05, 1.22)

1.08 (0.82, 1.42)

0.70 (0.24, 2.00)

1.16 (0.94, 1.44)

100.00

30.38

0.34

Weight(I-V)

0.75

0.09

0.04

0.23

11.71

0.38

0.67

0.16

0.10

7.52

0.09

0.12

0.61

%

2.26

19.36

0.090.01

2.18

0.54

0.40

18.31

1.35

0.09

2.20

Exposure decreases odds Exposure increases odds 1.1 1 5

Page 37 of 43

Supplementary fig 35. Forest plot of maternal anaemia on preterm birth (adjusted estimates)

I-V Overall (I-squared = 83.3%, p = 0.000)

Hamalainen 2003

Levy 2005

Klebanoff 1989

Xiong 2003

Ren 2007

Hwang 2010

Feresu 2004

Scanlon 2000

Siega-Riz 1998

studyid

Klebanoff 1989 (Black and white separately)

Banhidy 2010

Scholl 1992

D+L Overall

Gonzales 2009

von Tempelhoff 2008

Abeysena 2010

Knottnerus 1990

1.24 (1.19, 1.30)

1.80 (0.72, 4.49)

(Excluded)

1.10 (0.67, 1.80)

1.01 (0.74, 1.37)

1.17 (1.08, 1.27)

1.70 (1.52, 1.90)

4.12 (1.80, 9.43)

1.29 (1.11, 1.50)

1.05 (0.79, 1.40)

ES (95% CI)

1.60 (1.16, 2.20)

0.97 (0.88, 1.07)

1.30 (0.75, 2.24)

1.28 (1.11, 1.48)

1.43 (1.26, 1.62)

(Excluded)

0.64 (0.08, 5.15)

0.86 (0.36, 2.03)

100.00

0.25

0.00

0.85

2.21

30.59

16.63

Weight

0.30

9.04

2.49

(I-V)

2.03

21.37

0.69

13.22

0.00

0.05

0.28

%

1.24 (1.19, 1.30)

1.80 (0.72, 4.49)

(Excluded)

1.10 (0.67, 1.80)

1.01 (0.74, 1.37)

1.17 (1.08, 1.27)

1.70 (1.52, 1.90)

4.12 (1.80, 9.43)

1.29 (1.11, 1.50)

1.05 (0.79, 1.40)

ES (95% CI)

1.60 (1.16, 2.20)

0.97 (0.88, 1.07)

1.30 (0.75, 2.24)

1.28 (1.11, 1.48)

1.43 (1.26, 1.62)

(Excluded)

0.64 (0.08, 5.15)

0.86 (0.36, 2.03)

100.00

0.25

0.00

0.85

2.21

30.59

16.63

Weight

0.30

9.04

2.49

(I-V)

2.03

21.37

0.69

13.22

0.00

0.05

0.28

%

Exposure decreases odds Exposure increases odds

1.1 1 5

Page 38 of 43

Supplementary fig 36. Forest plot of maternal anaemia on stillbirth (crude estimates)

NOTE: Weights are from random effects analysis

Overall (I-squared = 23.9%, p = 0.209)

Mola 1999

Steer 2005

Conde-Agudelo 2000

Gonzales 2009

Mamun 2006

Bhalerao 2011

Lone 2004

Hamalainen 2003

Levy 2005

studyid

Zhang 2009

Malhotra 2002

Jehan 2007

1.19 (1.09, 1.28)

1.14 (0.93, 1.38)

1.29 (0.94, 1.77)

1.26 (1.17, 1.36)

1.40 (1.15, 1.70)

0.68 (0.41, 1.14)

1.05 (0.49, 2.27)

2.55 (0.49, 13.24)

3.75 (0.23, 61.56)

1.09 (0.96, 1.23)

ES (95% CI)

1.09 (0.90, 1.31)

1.91 (0.09, 40.17)

1.08 (0.33, 3.55)

100.00

11.96

5.61

31.79

12.28

%

2.29

1.07

0.24

0.08

21.29

Weight

12.87

0.07

0.45

1.19 (1.09, 1.28)

1.14 (0.93, 1.38)

1.29 (0.94, 1.77)

1.26 (1.17, 1.36)

1.40 (1.15, 1.70)

0.68 (0.41, 1.14)

1.05 (0.49, 2.27)

2.55 (0.49, 13.24)

3.75 (0.23, 61.56)

1.09 (0.96, 1.23)

ES (95% CI)

1.09 (0.90, 1.31)

1.91 (0.09, 40.17)

1.08 (0.33, 3.55)

100.00

11.96

5.61

31.79

12.28

%

2.29

1.07

0.24

0.08

21.29

Weight

12.87

0.07

0.45

Exposure decreases odds Exposure increases odds 1.1 1 5

Page 39 of 43

Supplementary fig 37. Forest plot of maternal anaemia on duration of gestation

Study or Subgroup

Banhidy 2010

Baraka 2012

Fareh 2005

Lao 2002

Malhotra 2002

Nordenvall 1990

Total (95% CI)

Heterogeneity: Tau² = 0.14; Chi² = 25.93, df = 5 (P < 0.0001); I² = 81%

Test for overall effect: Z = 1.98 (P = 0.05)

Weight

24.6%

10.4%

17.0%

21.0%

12.4%

14.6%

100.0%

IV, Random, 95% CI

0.00 [-0.06, 0.06]

-0.20 [-1.08, 0.68]

-0.70 [-1.21, -0.19]

-0.30 [-0.61, 0.01]

-1.50 [-2.24, -0.76]

0.10 [-0.52, 0.72]

-0.37 [-0.74, -0.00]

Mean Difference Mean Difference

IV, Random, 95% CI

-1 -0.5 0 0.5 1

Favours exposed Favours non-exposed

Page 40 of 43

Supplementary fig 38. Forest plot of maternal anaemia on birth weight

Study or Subgroup

Baraka 2012

Hamalainen 2003

Fareh 2005

Zhou 1998

Malhotra 2002

Lao 2002

Banhidy 2010

Nordenvall 1990

Williams 1997

Total (95% CI)

Heterogeneity: Tau² = 1878.84; Chi² = 26.76, df = 8 (P = 0.0008); I² = 70%

Test for overall effect: Z = 0.97 (P = 0.33)

Weight

2.5%

7.9%

6.1%

18.0%

10.1%

11.5%

22.5%

2.6%

18.7%

100.0%

IV, Random, 95% CI

-276.00 [-518.04, -33.96]

-88.00 [-205.21, 29.21]

-81.00 [-222.47, 60.47]

-51.11 [-95.71, -6.51]

-49.80 [-146.07, 46.47]

-15.00 [-99.93, 69.93]

3.00 [-10.52, 16.52]

21.00 [-215.10, 257.10]

72.00 [31.27, 112.73]

-20.15 [-60.91, 20.61]

Mean Difference Mean Difference

IV, Random, 95% CI

-100 -50 0 50 100

Favours exposed Favours non-exposed

Page 41 of 43

Supplementary fig 39. Forest plot of maternal anaemia on SGA (crude estimates)

NOTE: Weights are from random effects analysis

Overall (I-squared = 92.1%, p = 0.000)

Fareh 2005

studyid

Zhou 1998

Arbuckle 1989

Scholl 1992

Xiong 2003

Mau 1977

Hamalainen 2003

Gonzales 2009

Malhotra 2002

Bhalerao 2011

Lone 2004

Abeysena 2010

Ren 2007

1.04 (0.80, 1.35)

13.83 (0.77, 248.79)

ES (95% CI)

0.98 (0.64, 1.52)

1.06 (0.84, 1.33)

1.54 (0.91, 2.61)

0.80 (0.64, 1.02)

1.17 (0.84, 1.64)

0.94 (0.40, 2.16)

0.58 (0.53, 0.64)

1.27 (0.34, 4.71)

0.70 (0.49, 1.01)

2.50 (1.40, 4.45)

0.88 (0.36, 2.16)

1.17 (1.09, 1.26)

100.00

0.77

Weight

8.70

10.47

7.80

%

10.41

9.58

5.28

11.17

2.99

9.31

7.34

4.93

11.25

1.04 (0.80, 1.35)

13.83 (0.77, 248.79)

ES (95% CI)

0.98 (0.64, 1.52)

1.06 (0.84, 1.33)

1.54 (0.91, 2.61)

0.80 (0.64, 1.02)

1.17 (0.84, 1.64)

0.94 (0.40, 2.16)

0.58 (0.53, 0.64)

1.27 (0.34, 4.71)

0.70 (0.49, 1.01)

2.50 (1.40, 4.45)

0.88 (0.36, 2.16)

1.17 (1.09, 1.26)

100.00

0.77

Weight

8.70

10.47

7.80

%

10.41

9.58

5.28

11.17

2.99

9.31

7.34

4.93

11.25

Exposure decreases odds Exposure increases odds 1.1 1 5

Page 42 of 43

Supplementary fig 40. Forest plot of maternal anaemia on SGA (adjusted estimates)

NOTE: Weights are from random effects analysis

Overall (I-squared = 88.4%, p = 0.000)

Hwang 2010

Xiong 2003

Hamalainen 2003

Scanlon 2000

Ren 2007

Scholl 1992

Abeysena 2010

Gonzales 2009

von Tempelhoff 2008

studyid

1.08 (0.90, 1.29)

1.50 (1.32, 1.70)

0.78 (0.60, 1.01)

0.94 (0.41, 2.17)

0.86 (0.74, 1.00)

1.11 (1.03, 1.20)

1.66 (0.91, 3.04)

0.71 (0.06, 7.94)

0.86 (0.77, 0.96)

1.35 (1.16, 1.57)

ES (95% CI)

100.00

15.53

12.45

3.61

%

15.01

16.28

5.77

0.53

15.80

15.01

Weight

1.08 (0.90, 1.29)

1.50 (1.32, 1.70)

0.78 (0.60, 1.01)

0.94 (0.41, 2.17)

0.86 (0.74, 1.00)

1.11 (1.03, 1.20)

1.66 (0.91, 3.04)

0.71 (0.06, 7.94)

0.86 (0.77, 0.96)

1.35 (1.16, 1.57)

ES (95% CI)

100.00

15.53

12.45

3.61

%

15.01

16.28

5.77

0.53

15.80

15.01

Weight

Exposure decreases odds Exposure increases odds 1.1 1 5

Page 43 of 43

Supplementary fig 41. Forest plot of maternal anaemia on perinatal mortality (crude estimates)

NOTE: Weights are from random effects analysis

Overall (I-squared = 67.3%, p = 0.003)

studyid

Xiong 2003

Mamun 2006

Lone 2004

Murphy 1986

Bhalerao 2011

Steer 2005

Levy 2005

Agarwal1998

1.03 (0.77, 1.37)

ES (95% CI)

1.58 (0.99, 2.52)

0.59 (0.38, 0.92)

3.07 (0.61, 15.32)

1.53 (1.06, 2.20)

1.69 (0.62, 4.66)

0.79 (0.39, 1.61)

0.87 (0.75, 1.02)

0.73 (0.46, 1.15)

100.00

Weight

14.26

14.69

2.85

16.71

6.04

9.67

21.24

14.55

%

1.03 (0.77, 1.37)

ES (95% CI)

1.58 (0.99, 2.52)

0.59 (0.38, 0.92)

3.07 (0.61, 15.32)

1.53 (1.06, 2.20)

1.69 (0.62, 4.66)

0.79 (0.39, 1.61)

0.87 (0.75, 1.02)

0.73 (0.46, 1.15)

100.00

Weight

14.26

14.69

2.85

16.71

6.04

9.67

21.24

14.55

%

Exposure decreases odds Exposure increases odds 1.1 1 5