CD003094_Anaemia Review 2007

Treatments for iron deficiency anaemia in pregnancy (Review) Cuervo LG, Mahomed K

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2007, Issue 1 http://www.thecochranelibrary.com

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

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TABLE OF CONTENTS ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW . . . . . . . . . . . . . . . . .

SEARCH METHODS FOR IDENTIFICATION OF STUDIES . . . . . . . . . . . . . . . . . .

METHODS OF THE REVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

DESCRIPTION OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

METHODOLOGICAL QUALITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

POTENTIAL CONFLICT OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . .

ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Characteristics of included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Characteristics of excluded studies . . . . . . . . . . . . . . . . . . . . . . . . . . . .

ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Comparison 01. Oral iron vs placebo . . . . . . . . . . . . . . . . . . . . . . . . . . .

Comparison 02. Oral iron with vitamin A vs placebo . . . . . . . . . . . . . . . . . . . . .

Comparison 03. Oral iron + vitamin A vs oral iron . . . . . . . . . . . . . . . . . . . . . .

Comparison 04. Controlled release oral iron vs regular oral iron . . . . . . . . . . . . . . . . . .

Comparison 05. Intramuscular iron sorbito-citric acid vs intramuscular dextran . . . . . . . . . . . .

Comparison 06. Intramuscular iron dextran vs intravenous iron dextran . . . . . . . . . . . . . . .

Comparison 07. Intramuscular iron sorbitol citric acid vs intravenous iron dextran . . . . . . . . . . .

Comparison 08. Intravenous iron vs placebo . . . . . . . . . . . . . . . . . . . . . . . .

Comparison 09. Intravenous iron vs regular oral iron . . . . . . . . . . . . . . . . . . . . .

Comparison 10. Intravenous iron vs controlled release oral iron . . . . . . . . . . . . . . . . . .

Comparison 11. Intravenous iron + hydrocortisone vs intravenous iron . . . . . . . . . . . . . . .

Comparison 12. 2/3 dose intravenous iron vs full dose intravenous iron . . . . . . . . . . . . . . .

INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

COVER SHEET . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

GRAPHS AND OTHER TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 01.01. Comparison 01 Oral iron vs placebo, Outcome 01 Anaemic during 2nd trimester. . . . . . .

Analysis 01.02. Comparison 01 Oral iron vs placebo, Outcome 02 Haemoglobin levels (g/dl) . . . . . . .

Analysis 01.03. Comparison 01 Oral iron vs placebo, Outcome 03 Ferritin levels (ln ug/l) . . . . . . . . .

Analysis 01.04. Comparison 01 Oral iron vs placebo, Outcome 04 Serum iron (mg/l) . . . . . . . . . .

Analysis 01.05. Comparison 01 Oral iron vs placebo, Outcome 05 Side effects . . . . . . . . . . . . .

Analysis 01.06. Comparison 01 Oral iron vs placebo, Outcome 06 Nausea and vomiting . . . . . . . . .

Analysis 01.07. Comparison 01 Oral iron vs placebo, Outcome 07 Constipation . . . . . . . . . . . .

Analysis 01.08. Comparison 01 Oral iron vs placebo, Outcome 08 Abdominal cramps . . . . . . . . . .

Analysis 02.01. Comparison 02 Oral iron with vitamin A vs placebo, Outcome 01 Anaemic during 2nd trimester.

Analysis 02.02. Comparison 02 Oral iron with vitamin A vs placebo, Outcome 02 Haemoglobin levels (g/dl) . .

Analysis 02.03. Comparison 02 Oral iron with vitamin A vs placebo, Outcome 03 Ferritin levels (ln ug/l) . . .

Analysis 02.04. Comparison 02 Oral iron with vitamin A vs placebo, Outcome 04 Serum iron (mg/l) . . . . .

Analysis 03.01. Comparison 03 Oral iron + vitamin A vs oral iron, Outcome 01 Anaemia during second trimester Analysis 03.02. Comparison 03 Oral iron + vitamin A vs oral iron, Outcome 02 Haemoglobin levels (g/dl) . . .

Analysis 03.03. Comparison 03 Oral iron + vitamin A vs oral iron, Outcome 03 Ferritin (ln ug/l) . . . . . .

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

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Analysis 03.04. Comparison 03 Oral iron + vitamin A vs oral iron, Outcome 04 Serum iron (mg/l) . . . . . .

Analysis 04.01. Comparison 04 Controlled release oral iron vs regular oral iron, Outcome 01 Side effects . . . .

Analysis 04.02. Comparison 04 Controlled release oral iron vs regular oral iron, Outcome 02 Nausea and vomiting .

Analysis 04.03. Comparison 04 Controlled release oral iron vs regular oral iron, Outcome 03 Constipation . . . .

Analysis 04.04. Comparison 04 Controlled release oral iron vs regular oral iron, Outcome 04 Abdominal cramps . .

Analysis 05.01. Comparison 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran, Outcome 01 Pain at injection site . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 05.02. Comparison 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran, Outcome 02 Skin discolouration at injection site . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 05.03. Comparison 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran, Outcome 03 Venous thrombosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 05.04. Comparison 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran, Outcome 04 Nausea or vomiting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 05.05. Comparison 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran, Outcome 05 Headaches Analysis 05.06. Comparison 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran, Outcome 06 Shivering Analysis 05.07. Comparison 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran, Outcome 07 Itching Analysis 05.08. Comparison 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran, Outcome 08 Metallic taste in mouth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 06.01. Comparison 06 Intramuscular iron dextran vs intravenous iron dextran, Outcome 01 Pain at injection site . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 06.02. Comparison 06 Intramuscular iron dextran vs intravenous iron dextran, Outcome 02 Skin discolouration at injection site . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 06.03. Comparison 06 Intramuscular iron dextran vs intravenous iron dextran, Outcome 03 Venous thrombosis Analysis 06.04. Comparison 06 Intramuscular iron dextran vs intravenous iron dextran, Outcome 04 Nausea or vomiting Analysis 06.05. Comparison 06 Intramuscular iron dextran vs intravenous iron dextran, Outcome 05 Headaches . .

Analysis 06.06. Comparison 06 Intramuscular iron dextran vs intravenous iron dextran, Outcome 06 Shivering . .

Analysis 06.07. Comparison 06 Intramuscular iron dextran vs intravenous iron dextran, Outcome 07 Itching . . .

Analysis 06.08. Comparison 06 Intramuscular iron dextran vs intravenous iron dextran, Outcome 08 Metallic taste in mouth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 07.01. Comparison 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran, Outcome 01 Pain at injection site . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 07.02. Comparison 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran, Outcome 02 Skin discolouration at injection site . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 07.03. Comparison 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran, Outcome 03 Venous thrombosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 07.04. Comparison 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran, Outcome 04 Nausea or vomiting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 07.05. Comparison 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran, Outcome 05 Headaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 07.06. Comparison 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran, Outcome 06 Shivering Analysis 07.07. Comparison 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran, Outcome 07 Itching Analysis 07.08. Comparison 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran, Outcome 08 Metallic taste in mouth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 08.01. Comparison 08 Intravenous iron vs placebo, Outcome 01 Side effects . . . . . . . . . . .

Analysis 08.02. Comparison 08 Intravenous iron vs placebo, Outcome 02 Nausea or vomiting . . . . . . . .

Analysis 08.03. Comparison 08 Intravenous iron vs placebo, Outcome 03 Constipation . . . . . . . . . .

Analysis 08.04. Comparison 08 Intravenous iron vs placebo, Outcome 04 Abdominal cramps . . . . . . . .

Analysis 09.01. Comparison 09 Intravenous iron vs regular oral iron, Outcome 01 Side effects . . . . . . . .

Analysis 09.02. Comparison 09 Intravenous iron vs regular oral iron, Outcome 02 Nausea or vomiting . . . . .

Analysis 09.03. Comparison 09 Intravenous iron vs regular oral iron, Outcome 03 Constipation . . . . . . .

Analysis 09.04. Comparison 09 Intravenous iron vs regular oral iron, Outcome 04 Abdominal cramps . . . . .

Analysis 09.05. Comparison 09 Intravenous iron vs regular oral iron, Outcome 05 Diarrhoea . . . . . . . .

Analysis 09.06. Comparison 09 Intravenous iron vs regular oral iron, Outcome 06 Haemoglobin at 36 weeks . . .

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

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Analysis 09.09. Comparison 09 Intravenous iron vs regular oral iron, Outcome 09 Maternal haemoglobin at delivery Analysis 09.10. Comparison 09 Intravenous iron vs regular oral iron, Outcome 10 Maternal haemoglobin at 6 weeks Analysis 09.13. Comparison 09 Intravenous iron vs regular oral iron, Outcome 13 Maternal mortality . . . . .

Analysis 09.14. Comparison 09 Intravenous iron vs regular oral iron, Outcome 14 Preterm labour . . . . . . .

Analysis 09.15. Comparison 09 Intravenous iron vs regular oral iron, Outcome 15 Caesarean section . . . . . .

Analysis 09.16. Comparison 09 Intravenous iron vs regular oral iron, Outcome 16 Operative vaginal delivery . . .

Analysis 09.17. Comparison 09 Intravenous iron vs regular oral iron, Outcome 17 Postpartum haemorrhage . . .

Analysis 09.18. Comparison 09 Intravenous iron vs regular oral iron, Outcome 18 Low birth weight (under 2,500g) Analysis 09.19. Comparison 09 Intravenous iron vs regular oral iron, Outcome 19 Neonatal birth weight . . . .

Analysis 09.20. Comparison 09 Intravenous iron vs regular oral iron, Outcome 20 Small for gestational age . . .

Analysis 09.21. Comparison 09 Intravenous iron vs regular oral iron, Outcome 21 Five minute Apgar score under seven Analysis 09.22. Comparison 09 Intravenous iron vs regular oral iron, Outcome 22 Neonatal mortality . . . . .

Analysis 10.01. Comparison 10 Intravenous iron vs controlled release oral iron, Outcome 01 Side effects . . . .

Analysis 10.02. Comparison 10 Intravenous iron vs controlled release oral iron, Outcome 02 Nausea or vomiting .

Analysis 10.03. Comparison 10 Intravenous iron vs controlled release oral iron, Outcome 03 Constipation . . . .

Analysis 10.04. Comparison 10 Intravenous iron vs controlled release oral iron, Outcome 04 Abdominal cramps . .

Analysis 11.01. Comparison 11 Intravenous iron + hydrocortisone vs intravenous iron, Outcome 01 Tenderness or erythema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 11.02. Comparison 11 Intravenous iron + hydrocortisone vs intravenous iron, Outcome 02 Venous thrombosis Analysis 12.01. Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 01 Allergic reaction during infusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 12.02. Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 02 Allergic reaction after infusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 12.03. Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 03 Life threatening allergic reaction during infusion . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 12.04. Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 04 Discomfort needing analgesics after infusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 12.05. Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 05 Immobilised by painful joints . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 12.06. Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 06 Non-live births Analysis 12.07. Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 07 Neonatal death Analysis 12.08. Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 08 Stillbirth . .

Analysis 12.09. Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 09 Spontaneous abortion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

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Treatments for iron deficiency anaemia in pregnancy (Review) Cuervo LG, Mahomed K

This record should be cited as: Cuervo LG, Mahomed K. Treatments for iron deficiency anaemia in pregnancy. Cochrane Database of Systematic Reviews 2001, Issue 2. Art. No.: CD003094. DOI: 10.1002/14651858.CD003094.

This version first published online: 23 April 2001 in Issue 2, 2001.

Date of most recent substantive amendment: 31 January 2001

ABSTRACT Background Iron deficiency is the most common cause of anaemia in pregnancy worldwide. Iron treatment can be given by mouth, intramuscular or intravenous injection. Alternatively, blood transfusions and recombinant erythropoietin are also used.

Objectives To assess the effectiveness of different treatments for iron deficiency anaemia in pregnancy (defined as haemoglobin less than 11 g/dl) on maternal and neonatal morbidity and mortality.

Search strategy Cochrane Pregnancy and Childbirth Group Specialised Register of Trial was searched. Date of last search: December 2000.

Selection criteria Randomised controlled trials comparing treatments for iron deficiency anaemia in pregnancy.

Data collection and analysis The search identified 54 trials. Five trials, involving approximately 1234 women, met the inclusion criteria. Trial quality was assessed.

Study authors were contacted for additional information.

Main results Oral iron treatment in pregnancy was assessed in one small trial (n=125), where it was compared with placebo. This showed a reduction in the number of women with haemoglobins under 11g/dl (odds ratio (OR) 0.12, 95% confidence interval (CI) 0.06 to 0.24) and a greater mean haemoglobin level 11.3g/dl compared to 10.5 g/dl (weighted mean difference 0.80, 95% CI 0.62 to 0.98). However, there were no data on clinically relevant outcomes. When comparing different iron treatments, the intravenous (IV) route of administration was associated with an increased risk of venous thrombosis (1 trial, n=74. Iron dextran intramuscularly (IM) versus IV (n=49) OR 0.13, 95% CI 0.02-1.02. IM iron sorbitol-citric acid versus IV iron dextran, OR 0.12, 95% CI 0.02-0.94). Intravenous iron treatments were compared with placebo in one trial (n=54) but only scarce data on adverse outcomes were suitable for inclusion in this review.

Authors’ conclusions This review provides inconclusive evidence on the effects of treating iron deficiency anaemia in pregnancy due to the shortage of good quality trials.

PLAIN LANGUAGE SUMMARY Not enough evidence to know the best way to treat iron deficiency anaemia in pregnancy Anaemia happens when there are not enough red cells in the blood to carry oxygen to the tissues. Anaemia can be due to a number of causes, including certain diseases or a shortage of iron, folic acid or vitamin B12. The most common cause of anaemia in pregnancy is due to iron shortage. Iron treatment can be given by mouth, an injection into the muscle or into the vein, or by giving a blood Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

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transfusion. There are not enough studies to show which way is best for women with anaemia in pregnancy but the route into the vein can cause blockages in the veins. More research is needed.

BACKGROUND Anaemia is the reduction in the normal number of red blood cells and quantity of haemoglobin in the blood. Anaemia in pregnancy is defined by the World Health Organisation as a haemoglobin value below 11 g/dl (WHO 1992). Haemoglobin is the protein in the red blood cell which carries oxygen to the tissues. However, the estimation of the haemoglobin concentration in the blood is not a particularly sensitive indicator of anaemia because the delivery of oxygen to the tissues depends on the concentration of haemoglobin in the blood, the capacity of haemoglobin to bind oxygen and the blood flow through the tissue. A high haemoglobin concentration causes increased blood viscosity which decreases the blood flow through the tissues. In some cases, for example in pre-eclampsia, increased haemoglobin concentration is caused by poor increase in plasma volume which is under independent control from the red cell mass.

The common causes of anaemia include iron deficiency, folate deficiency, vitamin B12 deficiency, bone marrow suppression, haemolytic diseases (sickle cell disease and malaria), chronic blood loss (e.g. hook worm infestation) and underlying malignancies (WHO 1992), with iron deficiency anaemia being the most common cause of anaemia in pregnant women worldwide (Williams 1992; Lops 1995; Goroll 1997). However, neither blood haemoglobin concentration nor serum iron are thought to be good indicators of anaemia because there can be depletion of body iron stores in the presence of normal haemoglobin levels and serum iron fluctuates depending on recent iron intake. Serum ferritin may be a better indicator of iron status as the examination of iron stores in the bone marrow is impractical. However, historically, blood haemoglobin levels have been used, the test being simple and inexpensive to undertake and the WHO define anaemia in pregnancy as haemoglobin levels less than 11 g/dl.

During pregnancy there is an increase in both red cell mass and plasma volume to accommodate the needs of the growing uterus and fetus. The plasma volume increases more than the red cell mass leading to a fall in the concentration of haemoglobin in the blood, despite the increase in the total number of red cells. This drop in haemoglobin concentration decreases the blood viscosity and it is thought this enhances the placental perfusion providing a better maternal-fetal gas and nutrient exchange (Mani 1995).

There is controversy around the significance for women and their babies of this physiological haemodilution of pregnancy and at what level of haemoglobin women and babies would benefit from iron treatment. As discussed below, some studies suggest that the physiological decrease in haemoglobin is associated with improved outcomes for the baby (Steer 1995; Mahomed 1989), whilst others

have identified adverse long term outcomes for the baby (Walter 1994).

Anaemia has been associated with general weakness, tiredness and dizziness but the level of haemoglobin associated with these symptoms in pregnancy is unknown. It is suggested that the iron stores of the woman’s body become reduced during pregnancy (as a result of the increased red cell mass and the demands of the fetus exceeding iron intake), and that this can take place in the presence of normal blood haemoglobin levels. Some will argue that this is a well designed mechanism to continue to deliver oxygen to the tissues in the presence of lowered iron stores. An observational study done in London UK found that low levels of haemoglobin, commonly considered as mild anaemia, were associated with a better prognosis for the fetus, although figures did not appear to be corrected for women with pre-eclampsia (Steer 1995). However, others argue that reduced iron stores are a health problem for pregnant women and their babies (Letsky 2001). Several studies considered anaemia (haemoglobin levels between 7 g/dl and 10 g/dl) as a risk factor for fetal death, premature delivery, low birth weight and other adverse outcomes (Williams 1992). Some suggest a link between maternal anaemia in pregnancy on the later developmental problems of the children (Williams 1992; Letsky 2001). There is evidence that when maternal haemoglobin levels are under 7 g/dl, there is a higher risk in the mother of developing cardiac heart failure which has adverse consequences on the mother and fetus (WHO 1992; Williams 1992; Lops 1995). The suggestion that low iron stores in the mother during pregnancy may affect the child’s later development, means that long term outcomes on the baby should be outcome measures in any study on the treatment of anaemia in pregnancy. There is also a strong case for studying separately physiological anaemia, mild anaemia and severe anaemia in pregnancy.

In developing countries anaemia in pregnancy is high and this is attributed to poor nutrition and the high incidence of diseases, and it can be associated with increased problems including postpartum haemorrhage which is a major contributor to maternal mortality in many developing countries (WHO 1992). However, anaemia may only be a marker of various social and nutritional conditions, and the changes on haemoglobin levels could have a minor effect on morbidity or mortality if other conditions are not changed (Goroll 1997).

There are various possible forms of treatment for iron deficiency anaemia. Iron can be given by mouth, by intramuscular injection or intravenous injection. It is also possible to give iron by giving a blood transfusion, and recombinant erythropoietin in conjunction with iron is a further possibility. Anecdotal evidence suggests

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

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that oral iron given to anaemic pregnant and non-pregnant women is associated with the gastrointestinal side effects of nausea and constipation. Intramuscular or intravenous iron is thought to be associated with allergic reactions and anaphylactic shock as well as venous thrombosis and occasionally cardiac arrest and death.

Blood transfusion runs the risk of possible parasitic or viral infection transmissions such as HIV and hepatitis, despite screening.

There is also the possibility of bovine spongioform encephalitis (BSE) and as yet unknown viral infections. Oral iron is often the choice of route of administration for mild anaemia, with intramuscular and intravenous routes used in cases of extreme anaemia where side effects may need to be balanced against the possibility of cardiac failure due to severe anaemia. Recommendations for the treatment of anaemia are currently based on expert opinions rather than systematic reviews of randomised clinical trials, and may not take into account possible side effects of the treatment such as allergic reactions, viral or parasitic transmission from blood transfusions and discomfort generated by common side effects of iron.

The aim of this review is, therefore, to search systematically for, and combine the evidence from all relevant randomised controlled trials of iron treatment for anaemia due to iron deficiency in pregnancy, in order to provide the best reliable and valid evidence to guide clinical practice.

OBJECTIVES The principal objective was to determine the overall effect of iron therapy on iron deficiency anaemia in pregnancy, measuring neonatal and maternal morbidity and mortality, haematological parameters and side effects of treatment. The review also compared different forms of iron therapy for iron deficiency anaemia on neonatal and maternal morbidity and mortality, haematological parameters and side effects on mothers and babies.

The review did not discuss the need for iron supplementation of non-anaemic women since this issue has been addressed in another review (Mahomed 2000). Similarly, it did not focus on vitamin A, vitamin B12, folate deficiency, infectious or genetic anaemia, which will be covered in other reviews.

CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW Types of studies Randomised controlled trials related to the treatment of iron deficiency anaemia in pregnancy were considered for this review.

When information was not clear or complete in the abstract, the ’materials and methods’ of the reports were reviewed. Quasi-random studies were not eligible for this review.

Iron deficiency anaemia definitions may be problematic due to the controversy about which diagnostic tests are sufficient and reliable enough to rule out other causes of anaemia, and to the fact that anaemia causes are frequently combined. Therefore, for this review we accepted the authors’ definition of iron deficiency anaemia.

Types of participants Pregnant women with a diagnosis of anaemia (haemoglobin levels under 11 g/dl) attributed to iron deficiency.

Types of intervention (1) All types of iron preparations versus placebo/no treatment.

(2) Different forms of oral iron preparations used for the treatment of anaemia.

(3) Oral iron in combination with other haematinics versus regular oral iron.

(4) Oral iron in combination with substances that could increase its absorption versus regular oral iron.

(5) Slow release preparations versus regular oral iron.

(6) Intramuscular iron versus regular oral iron.

(7) Intravenous iron versus regular oral iron.

(8) Intravenous versus intramuscular iron therapies.

(9) Different dosages of above combinations.

(10) Blood transfusion versus oral iron therapy.

(11) Blood transfusion versus parenteral iron.

(12) Recombinant erythropoietin versus oral iron therapy.

(13) Recombinant erythropoietin versus parenteral iron therapy.

(14) Parenteral iron versus oral iron. * For the purpose of this review, regular oral iron will include preparations different from controlled release oral iron.

Types of outcome measures 1. Women 1.1Clinical Outcomes 1.1.1 Mortality 1.1.2 Morbidity 1.1.2.1 Preterm labour 1.1.2.2 Premature delivery 1.1.2.3 Puerperal sepsis 1.1.2.4 Systemic bacterial infection after delivery 1.1.2.5 Fever 1.1.2.6 Pneumonia 1.1.2.7 Postpartum haemorrhage (equal to or more than 500 ml) 1.1.2.8 Heart failure 1.1.2.9 Incapacity to work due to disease 1.1.2.10 Days in intensive care unit (ICU) 1.1.2.11 Days hospitalized during pregnancy 1.1.2.12 Hypertensive disorders of pregnancy 1.1.2.13 Malaria 1.1.2.14 Urinary tract infection 1.2 Haematological outcomes 1.2.1 Maternal serum ferritin 1.2.2 Maternal serum iron

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1.2.3 Haemoglobin levels 1.3 Long term haematological outcomes (not pre-specified in original protocol) 2 Newborn 2.1 Clinical Outcomes 2.1.1 Mortality 2.1.2 Morbidity 2.1.2.1 Low birth weight (less than 2,500 g) 2.1.2.2 Jaundice requiring hospital admission or plasmapheresis 2.1.2.3 Respiratory disease requiring ventilation 2.1.2.4 Admission to neonatal intensive care unit 2.1.2.5 Five minute Apgar score under seven 2.1.2.6 Days hospitalized 2.1.2.7 Small for gestational age 2.1.3 Haematological outcomes 2.1.3.1 Cord serum ferritin 2.1.3.2 Cord haemoglobin 2.1.4 Long term outcomes (not pre-specified in original protocol) 2.1.4.1 Haemoglobin levels at 1 year (not pre-specified in original protocol) 2.1.4.2 Serum ferritin at 1 year (not pre-specified in original protocol) 2.1.4.3 Neurological development at 1 year (not pre-specified in original protocol) 3. Maternal side effects 3.1 Gastrointestinal effects 3.1.1 Nausea 3.1.2 Vomiting 3.1.3 Diarrhoea 3.1.4 Epigastric pain 3.1.5 Constipation 3.2 Local symptoms 3.2.1 Pain or tenderness 3.2.2 Discolouration 3.2.3 Pigmentation or staining of injection site 3.2.4 Erythema 3.3 Systemic symptoms 3.3.1 Myalgia 3.3.2 Arthralgia 3.3.3 Abscess formation at injection site 3.3.4 Fever following treatment (> 37.5ºC) 3.3.5 Allergic reactions 3.3.6 Anaphylactic shock 3.4 Incapacity to work due to an adverse effect of medication.

SEARCH METHODS FOR IDENTIFICATION OF STUDIES See: methods used in reviews.

The following sources of information were used initially:

This review has drawn on the search strategy developed for the Cochrane Pregnancy and Childbirth Group as a whole. The full list of journals and conference proceedings, as well as the search strategies for the electronic databases, which are searched by the Group on behalf of its reviewers, is given in detail in the ’Search strategies for the identification of studies’ section within the editorial information about the Cochrane Pregnancy and Childbirth Group. Briefly, the Group’s electronic searches include MEDLINE and the Cochrane Controlled Trials Register.

Date of last search: December 2000.

Relevant trials, which are identified through the Group’s search strategy, are entered into the Group’s Specialised Register of Controlled Trials. Please see Review Group’s details for more information.

In addition, MEDLINE on PubMed was searched in September 1998, for the period 1966 to September 1998, using the following terms: (Randomized-controlled-trial:PT OR Randomized-clinicaltrials:PT) AND (Pregnancy in Mesh OR Prenatal care in Mesh) (Anemia, Hypochromic/drug therapy in MESH OR Anemia, Hypochromic/prevention and control in MESH OR Anemia, Hypochromic/therapy in MESH OR Anemia, Iron deficiency/drug therapy in MESH OR Anemia, Iron deficiency/prevention and control in MESH OR Anemia, Iron deficiency/therapy in MESH) Iron/therapeutic use Pregnancy complications/prevention and control Haematinics/adverse effects.

References in published material were checked.

METHODS OF THE REVIEW Trials under consideration were evaluated for methodological quality and appropriateness for inclusion without consideration of their results. Data from included trials were processed as described in The Cochrane Collaboration Handbook (Clarke 2000). The papers that passed this first screening were appraised using the strategy proposed by Sackett (Sackett 1997).

When flaws in the study compromised validity, these flaws were described and the study was excluded. Specifically, studies were excluded if there was more than 20% of participants lost to followup (with no explanation of cause) or if there was a difference in the percentage lost to follow-up between compared groups of more than 15%. Trials that combined anaemic with non-anaemic women were excluded when more that 40% of the women were non-anaemic and there was no significant difference in the baseline

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distribution. Inclusion and exclusion criteria were established prior to the initiation of the review.

DESCRIPTION OF STUDIES From the search, 54 trials were identified: two unpublished trials, two congress abstracts and 50 published trials. Twenty eight were excluded after first review as they were not randomised clinical trials, included mostly non-anaemic women, evaluated postpartum iron treatments or were focused on non iron deficiency anaemia.

Sixteen were excluded after critical appraisal due to methodological flaws that compromised validity. Only 10 studies were eligible for inclusion, but seven provided insufficient information so their authors were actively searched and mailed, using data provided in the paper and through active search of the Internet. Authors for the papers by Singh (Singapore 1998), Visca (Visca 1996) and Suharno (West Java 1993) were contacted through active Internet search. The authors for the papers by Visca and Suharno responded to the queries. The authors of papers by Al Momen (Al Momen 1996) were faxed but no reply was received. Authors for the paper by Stein (Stein 1991) were not contactable.

Five trials were included in the review (Australia 1969; Singapore 1998; Tanzania 1988; UK 1965; West Java 1993). Most papers focused on laboratory values rather than on clinical outcomes.

Clinical outcomes were assessed by Singh although these data were unpublished; these data were provided by the author and have been incorporated into this review.

METHODOLOGICAL QUALITY We found studies that had both valid information and also data with validity problems. Withdrawal rates were high, therefore, data for some outcomes were incomplete. We used only the information that fulfilled our pre-stated inclusion criteria.

The paper from West Java (West Java 1993) evaluated results at the end of treatment during the second trimester of pregnancy.

We consider that this information would have been much more valuable if outcomes had been evaluated at term or at least in the third trimester, since positive increments in outcomes could subsequently disappear. This study provided information of good randomisation process with concealment of allocation (other papers lacked detail on this issue). This was the only paper that provided sample size considerations. Its overall quality was good. There were concerns about the clinical significance of the outcomes evaluated after eight weeks of treatment, long before delivery was due.

Women were not followed until delivery and clinical outcomes were not published.

The study in Singapore (Singapore 1998) provided data on haematological measurements done at some clinically important ’milestones’ such as the end of pregnancy, at delivery and in the post-

partum period. The authors also provided unpublished information on relevant clinical outcomes. The overall quality of the paper was graded as good. No sample size considerations were provided and masking was not possible because the control group did not receive a placebo. Information on randomisation was insufficient in the published paper, but additional details were provided by the authors upon request. This trial had no withdrawals. Published baseline data suggest that the compared groups were similar at baseline except for the mean haemoglobin level which was lower for the parenteral iron group. However, we decided to include this study in the review because such a difference would act to lower the effect for the parenteral therapy, so the effects found may be underestimated rather than overestimated.

The study in Tanzania (Tanzania 1988) provided insufficient information about the randomisation procedure. There was a high rate of dropouts for most outcomes so the only information used was that on side effects.

In a similar way, the study in the United Kingdom (UK 1965) had inappropriate randomisation strategies and no care was taken to conceal the allocation of interventions. It had high rates of women who did not have follow-up. The study was used to obtain data on side effects of interventions.

The study in Australia (Australia 1969) had some methodological flaws that made the inclusion of two of the four analysis groups inappropriate. Researchers masked two intervention groups and kept unmasked the other two groups for one month. Afterwards they unmasked the whole trial. We used only data obtained during the first month of treatment in the two masked groups. Useful data were restricted to side effects. The authors provided insufficient data to incorporate other outcomes in the analysis and overall it was also a study with methodological flaws that compromised the validity of other data.

RESULTS The search identified 54 trials. Five trials, involving approximately 1234 women, met the inclusion criteria. Globally, results for included outcomes were unsatisfactory and susceptible to bias due to the fact that most of them were extracted from one or two trials and these trials had small sample sizes.

When oral treatments were compared with placebo, data provided from one trial showed that the risk of being anaemic during the second trimester would be reduced for women receiving iron (odds ratio (OR) 0.12, 95% confidence interval (CI) 0.06-0.24) . In the iron-treated group, the mean haemoglobin level was greater, 11.3 g/dl compared to 10.5g/dl (weighted mean difference (WMD) 0.80, 95% CI 0.62-0.98), as was the mean serum ferritin level.

There were trends towards increased side effects (nausea, vomiting, constipation and abdominal cramps) but numbers were too

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small to be of value. There were no measurements of other clinical outcomes, so the possible benefits to women and babies are unclear. Also, conclusions should be approached with care as they are drawn from a small population of participants (n=125). Furthermore, one trial assessed outcomes during the second trimester (West Java 1993) and we cannot be sure that those women sustained similar haemoglobin status during the rest of their pregnancy. There was no assessment of the haematological condition of the women at delivery. For the population considered in that same trial, the addition of vitamin A to regular iron improved the results of iron therapy. This is an interesting result that could be taken as the best evidence available, but should be applied only to populations of similar characteristics. Results may not apply to other populations with different nutritional status, or with appropriate vitamin A intake in the diet.

Controlled release oral iron compared with other iron preparations was assessed in only one trial (Australia 1969). This trial provided data on side effects but data on effectiveness were not included due to high withdrawal rates. It found no differences between controlled release iron and regular oral iron. This could be explained by a real absence of clinically relevant differences or because this small trial may have had insufficient power to find such differences.

When comparing two intramuscular preparations, women receiving intramuscular iron-sorbitol complex had lower rates of skin discoloration at injection sites (one trial, n=48, OR 0.14, 95% CI 0.04-0.48) and headaches (one trial, n=48, OR 0.16, 95% CI 0.03 -0.70) when compared with intramuscular iron dextran. As in previous studies, results should be interpreted with care as they come from a single small trial but, in this particular case, random allocation and concealment were appropriately done.

Comparing intramuscular treatments with intravenous treatment, the intramuscular route produced more frequent pain at the injection site. The relevant trial had a factorial design, where data from active treatments were compared to a single control group. No adjustments for multiple comparisons were done. Skin discoloration was more frequently observed in people receiving intramuscular iron-dextran.

a higher risk of nausea or vomiting compared with intravenous infusion.

Comparing oral and intravenous treatments, the review found a significantly higher risk of having constipation with regular oral treatments when compared with intravenous treatments. Statistical significant differences were not found when the comparison was made against controlled release iron. Data for this comparison were obtained from a single trial. One trial (Singapore 1998) found higher haemoglobin values at the end of gestation were obtained with intravenous treatments than with oral treatments. The study population were mostly Malayan and Chinese women. No maternal or neonatal deaths were recorded in the trial, the only one assessing such outcomes in women receiving oral or intravenous therapies.

When a comparison was made between iron-dextran infusion and iron-dextran with an added dose of hydrocortisone, the addition of hydrocortisone lowered the risk for venous thrombosis (UK 1965).

Two different doses of intravenous iron-dextran were compared (Tanzania 1988). The lower dose had a statistically significant lower rate of allergic reactions after the infusion had ended. Life threatening allergic reactions were more frequent in the low dose group, but this difference did not reach statistical significance.

Data required to evaluate effectiveness were not obtained from this trial because it did not fulfil our quality criteria.

DISCUSSION The objective of this review was to address the effects of anaemia treatments on maternal and neonatal morbidity and mortality.

Also, intravenous iron treatment was associated with a higher risk of venous thrombosis compared with intramuscular iron. These data were obtained from one trial done in United Kingdom (UK 1965). The same trial showed that headaches were more frequent with iron-dextran when injected intramuscularly than when given by intravenous infusion (n=49, OR 4.42, 95% CI 1.05-18.54).

Few of the included trials in this review considered those outcomes and no important differences were found with the data provided.

Moreover, the available data were unlikely to give a different result, as the number of people with available data on these outcomes was so small that even if the treatments are effective, it is improbable that differences would have shown up in such small groups. The evidence found suggests that gastrointestinal side effects are more common with oral iron treatments than with other preparations.

Iron treatments seem to increase haematological values. There is inconclusive evidence on the benefits of controlled release iron preparations compared with standard oral preparations, except for a diminished frequency of constipation.

Women complained of nausea more frequently when given oral iron than when receiving intravenous preparations. This was found in two different trials and, in both, the magnitude of the effect was similar. The Australian trial (Australia 1969) compared controlled release preparations with regular intravenous preparations and obtained similar results to those for regular oral iron preparations -

Intravenous treatments were associated with a higher risk of venous thrombosis and a lower risk of changes in skin pigmentation. The risk of venous thrombosis may be modified by the addition of hydrocortisone to the infusion but there are no data to address if this alters the effectiveness of the iron therapy. Evidence of a relationship between doses of intravenous iron and risk of adverse

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allergic reactions is inconclusive. No effectiveness measurements were done for the compared doses.

None of the included trials were designed to evaluate time-toresolution of anaemia.

There is poor quality evidence from randomised trials to support advice on whether clinical outcomes may be modified using available treatments in women with iron deficiency anaemia during pregnancy.

the Pontificia Universidad Javeriana in Bogota, Colombia. Kassam Mahomed worked with the Obstetrics and Gyneacology Department at the University of Zimbabwe. During the second semester of 2000, when the search was updated, Luis Gabriel Cuervo moved to London, where he works for the British Medical Association and Kassam Mahomed moved to Australia where he works for the University of Adelaide.

POTENTIAL CONFLICT OF INTEREST

AUTHORS’ CONCLUSIONS

None known.

Implications for practice With the available data, we are unable to give evidence-based advice on whether, or how, to treat iron deficiency anaemia. While it seems sensible to treat severe iron deficiency anaemia in pregnancy with clinical symptoms, there is no good evidence to support any specific treatment, except that the intravenous route is associated with venous thrombosis. Whether to treat pregnant women with mild anaemia remains controversial.

Implications for research Severe iron deficiency anaemia affects a large number of pregnant women in developing countries and may have considerable impact on maternal and neonatal health. Considerable resources are used to treat this condition, however, available evidence is insufficient to prove that the effort is worthwhile. This review is an invitation for researchers in developing countries to initiate relevant, high quality research that will fill the knowledge gaps about this common condition, particularly looking at different degrees of anaemia and measuring long term effects on both mothers and babies.

ACKNOWLEDGEMENTS Accommodation and financial support were provided by the Cochrane Pregnancy and Childbirth Group in Liverpool (UK) and the Pontificia Universidad Javeriana in Bogota (Colombia).

Special thanks to Prof Jim Neilson for his academic support and to Sonja Henderson, Lynn Hampson and Claire Winterbottom for their support as well. Also, thanks to Elizabeth Letsky and Gill Gyte for commenting on draft manuscripts.

SOURCES OF SUPPORT External sources of support • Financial support was given by HRP-UNDP/UNFPA/WHO/World Bank Special Programme in Human Reproduction, Geneva. SWITZERLAND

NOTES

• Cochrane Pregnancy and Childbirth Group UK

This study was done in its majority while Luis Gabriel Cuervo worked as assistant professor at the Clinical Epidemiology Unit of

Internal sources of support • Pontificia Universidad Javeriana at Bogota COLOMBIA

REFERENCES

References to studies included in this review Australia 1969 {published data only} Symonds E, Radden H, Cellier K. Controlled-release iron therapy in pregnancy. Aust NZ J Obstet Gynaecol 1969;9(1):21–5. [MedLine: 1969188811].

Tanzania 1988 {published data only} Kaisi M, Ngwalle EWK, Runyoro DE, Rogers J. Evaluation of tolerance of and response to iron dextran (Imferon) adminisered by total dose infusion to pregnant women with iron deficiency anemia. Int J Gynecol Obstet 1988;26(2):235–43. [MedLine: 1988255482].

Singapore 1998 {published and unpublished data} Singh K, Fong YF, Kuperan P. A comparison between intravenous iron polymaltose complex (Ferrum Hausmann) and oral ferrous fumarate in the treatment of iron deficiency anaemia in pregnancy. Eur J Haematol 1998;60:119–24. [MedLine: 1998167778].

UK 1965 {published data only} Dawson D, Goldthorp W, Spencer D. Parenteral iron therapy in pregnancy. J Obstet Gynaecol Br Cmmwlth 1965;72:89–93.

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West Java 1993 {published data only} Suharno D, West CE, Muhilal, Karyadi D, Hautvast JG. Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia. Lancet 1993;342:1325–8. [MedLine: 1994048760].

References to studies excluded from this review Al Momen 1996 Al-Momen A, Al-Meshari A, Al-Nuaim L, Saddique A, Abotalib Z, Khashogji T, et al.Intravenous iron sucrose complex in the treatment of iron deficiency anemia during pregnancy. Eur J Obstet Gynecol Reprod Biol 1996;69:121–4. [MedLine: 1997058115].

Allaire 1961 Allaire B, Campagna F. Iron-deficiency anemia in pregnancy. Evaluation of diagnosis and therapy by bone marrow hemosiderin. Obstet Gynecol 1961;17:605–10.

Bare 1960 Bare W, Sullivan A. Comparison of intravenous saccharated iron oxide and whole blood in treatment of hypochromic anemia of pregnancy. Am J Obstet Gynecol 1960;79:279–85.

Barrada 1991 Barrada M, Pateisky N, Schatten C, Salzer H, Vavra N, Spona J, et al.Ferritin levels in newborn after prepartal iron medication. Geburtshilfe Frauenheilkd 1991;51(5):366–8. [MedLine: 1991331243].

and chemicals in Tropical Africa. Proceedings of the 1973 Annual Scientific Conference of the East African Research Council. Nairobi: East African Literature Bureau, 1973:463–6.

Hampel 1974 Hampel K, Roetz R. Influence of a long-time substitution with folate-iron combination in pregnancy on serum folate and serum iron and on hematological parameters. Geburtshilfe Frauenheilkd 1974; 34:409–17. [MedLine: 1974293872].

Hawkins 1970 Hawkins DF. Relative efficacy of sustained release iron and iron with folic acid treatment in pregnancy. Personal communication 1987.

Holly 1955 Holly R. Anemia in pregnancy. Obstet Gynecol 1955;5:562–9.

Izak 1973 Izak G, Levy S, Rachmilewitz M, Grossowicz N. The effect of iron and folic acid therapy on combined iron and folate deficiency anaemia: the results of a clinical trial. Scand J Haematol 1973;11(3): 236–40. [MedLine: 1974063093].

Jackson 1982 Jackson RT, Latham MC. Anemia of pregnancy in Liberia, West Africa: a therapeutic trial. Am J Clin Nutr 1982;35:710–4. [MedLine: 1982179371].

Jaud 1979 Jaud W. Folate- and iron- deficiency in pregnancy. Geburtshilfe Frauenheilkd 1979;39(4):317–23. [MedLine: 1979170627].

Barrada M, Salzer H, Schatten C, Pateisky N, Vavra N, Spona J, et al.Influence of prepartal iron-medication on newborns. Proceedings of the 13th World Congress of Gynaecology and Obstetrics (FIGO); 1991; Singapore, 1991:38.

Mahale 1993 Mahale AR, Shah SH. New schedule of intramuscular iron administration for pregnant women. Asia Oceania J Obstet Gynaecol 1993; 19:141–4. [MedLine: 1993393475].

Basu 1973 Basu RN, Sood SK, Ramachandan K, Mathur M, Ramalingaswami V. Ethiopathogenesis of nutritional anemia in pregnancy: a therapeutic approach. Am J Clin Nutr 1973;26(6):591–4. [MedLine: 1973186956].

Preziosi 1997 Preziosi P, Prual A, Galan P, Daouda H, Boureima H, Hercberg S. Effect of iron supplementation on the iron status of pregnant women: consequences for newborns. Am J Clin Nutr 1997;66:1178– 82. [MedLine: 1998019349].

Breymann 1998 Breymann C. rhEPO/parenteral iron vs parenteral iron only in the treatment of severe pregnancy anemia. Personal communication 1999.

Sood 1975 Sood SK, Ramachandran K, Mathur M, Gupta K, Ramalingaswami V, Swarnabai C, et al.WHO sponsored collaborative studies on nutritional anaemia in India. 1. The effects of supplemental oral iron administration to pregnant women. Q J Med 1975;44:241–58. [MedLine: 1976053828].

Breymann C, Visca E, Huch R, Huch A. Recombinant human erythropoietin (rhEPO) for the therapy of severe iron deficiency anaemia during pregnancy. 21st Conference of the Swiss Society of Gynecology and Obstetrics, 1998:24.

Chanarin 1965 Chanarin I, Rothman D. Response to folic and folinic acid in megaloblastic anaemia in pregnancy. Journal of Obstetrics and Gynaecology of the British Commonwealth 1965;72:374–5.

Stein 1991 Stein ML, Gunston KD, May RM. Iron dextran in the treatment of iron-deficiency anaemia of pregnancy. Haematological response and incidence of side-effects. S Afr Med J 1991;79:195–6. [MedLine: 1991142847].

Steiner 1977 Steiner H, Hilgarth M. Treatment of anemia in pregnancy [translation]. Fortschr Med 1977;95:753–6. [MedLine: 1977163809].

Fochi 1985 Fochi F, Ciampini M, Ceccarelli G. Efficacy of iron therapy: a comparative evaluation of four iron preparations administered to anaemic pregnant women. J Int Med Res 1985;13(1):1–11. [MedLine: 1985154970].

Valli Rani 1995 Valli Rani N, Pandey J, Das B, Shruti, Talib VH, Singh K, et al.Pregnancy associated anemia and iron: a pilot study. Indian J Pathol Microbiol 1995;38(3):293–7. [MedLine: 1996416871].

Hamilton 1973 Hamilton PJS, Gebbie DAM. Antenatal clinics as trial units in evaluating treatment of anaemia in pregnancy. The use and abuse of drugs

Visca 1996 Visca E, Breymann CC, Huch R, Huch A. Recombinant erythropoietin (rhEPO) and iron vs. parenteral iron only for the treatment

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of pregnancy anemia; a prospective and randomised study. The 15th European Congress of Perinatal Medicine; 1996 September 10-13; Glasgow, Scotland, UK, 1996:184.

References to studies awaiting assessment Christiansen 1961 Christiansen TC, Koszewski BJ, Grier ME. Evaluation of a new cobalt chelate with iron in pregnancy anemia. American Journal of Obstetrics and Gynecology 1961;82:213–8.

Dommisse 1982 Dommisse J, Du Toit ED, Nicholson N. Folic acid - has it a role in the treatment of severe iron deficiency anaemia in pregnancy?. South African Medical Journal 1982;61:831–2.

Ridwan 1996 Ridwan E, Schultink W, Dillon D, Gross R. Effects of weekly iron supplementation on pregnant indonesian women are similar to those of daily supplementation. American Journal of Clinical Nutrition 1996;63:884–90.

Von Peiker 1986 Van Peiker G, Muller B, Schwarz A, Dawczynski H, Linke E. Diagnosis and treatment of iron deficiency anemia in pregnancy. Zentralblatt fur Gynakologie 1986;108:1487–92.

Additional references Clarke 2000 Clarke M, Oxman AD. Cochrane Reviewers’ Handbook 4.1 [updated June 2000]. Review Manager (RevMan) [Computer program].

Verson 4.1. Oxford, England: The Cochrane Collaboration, 2000.

Goroll 1997 Goroll H, May LA, Mulley AG. Primary care medicine on CD. Lippincott Raven Publishers. Vol 1 Number 1.

Gülmezoglu 1998 Gülmezoglu AM, Garner P. Malaria in pregnancy in endemic areas (Cochrane Review). In: The Cochrane Library, 3, 1998.Oxford: Update Software.

Letsky 2001 Letsky EA. Maternal anaemia in pregnancy, iron and pregnancy a haematologist’s viewpoint. Fetal and Maternal Medicine Review 2001 In press.

Lops 1995 Lops VR, Hunter LP, Dixon LR. Anemia in pregnancy. Am Fam Physician 1995;51:1189–97. [MedLine: 1995225250].

Mahomed 2000 Mahomed K. Iron supplementation in pregnancy (Cochrane Review). In: The Cochrane Library, 3, 2000.Oxford: Update Software.10.1002/14651858.CD000117.pub2 Mahomed 1989 Mahomed K, Hytten F. Iron and folate supplementation in pregnancy. In: ChalmersI, EnkinM, KeirseMJNC editor(s). Effective Care in Pregnancy and Childbirth. Vol. 1, Oxford: Oxford University Press, 1989:301–17.

Mani 1995 Mani S, Duffy TP. Anemia of pregnancy. Perinatal Hematology 1995; 22(3):593–607.

Sackett 1997 Sackett DL, Richardson WS, Rosenberg W, Haynes RB. Evidence based medicine - How to teach and practice EBM. New York: Churchill Livingston, 1997.

Steer 1995 Steer P, Alam MA, Wadsworth J, Welch A. Relation between maternal haemoglobin concentration and birth weight in different ethnic groups. BMJ 1995;310(6978):489–91.

Walter 1994 Walter T. Effect of iron-deficiency anaemia on cognitive skills in infancy and childhood. Baillieres Clinical Haematology 1994;7:815– 27.

WHO 1992 World Health Organization, Maternal Health and Safe Motherhood Programme, Division of Family Health. The prevalence of anaemia in women: a tabulation of available information. WHO 1992. 2nd Edition. Geneva. (WHO/MCH/MSM/92).

Williams 1992 Williams MD, Wheby MS. Anemia in pregnancy. Med Clin North Am 1992;76:631–47. [MedLine: 1992252444].

TABLES

Characteristics of included studies Study

Australia 1969

Methods

Women were assigned randomly although the method is not clearly specified. Baseline data for the four groups compared are very similar.

Participants

Women attending the Queen Elizabeth Hospital in Woodville, Australia. Inclusion criteria were a gestational age of 32 weeks or less and a haemoglobin level of 10.8 g/dl or less.

Interventions

Four treatment groups were assembled:

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Characteristics of included studies (Continued ) 1. Ferrous gluconate 108 mg of elemental iron daily divided in three doses given orally throughout pregnancy.

2. Ferrogradumet tablets (controlled release) iron tablets with 105 mg elemental iron given once daily throughout pregnancy 3. Placebo for the controlled release iron tablets provided by the same pharmaceutical laboratory.

4. Intravenous iron -dextran 2% solution. Initial test dose of 2 ml IV followed by 5 injections of 5 ml (100mg).

Participants received controlled release iron or placebo for the first month. After that time side effects were evaluated, and then all participants were given a daily dose of active controlled release oral iron. The trial was masked only the first two months and only for these two groups.

Outcomes

For this review side effects were considered. The other data were incomplete, without reported standard deviations of mean values and irrelevant due to important flaws in the design of the study.

Notes

Haemoglobin results were presented as increases in haemoglobin. Since standard deviations for the values cannot be added to baseline data, the data was not included.

Allocation concealment

B – Unclear

Study

Singapore 1998

Methods

Women were allocated using sealed envelopes with consecutive numbers.

Participants

The first 100 women with diagnosed iron deficiency anaemia while attending for antenatal care at the National University Hospital, Singapore. Data provided by one of the authors reveals that compared groups had similar age distribution, parity, mean total income, weight, height, history of anaemia in previous pregnancies, history of intrauterine growth retardation in previous pregnancies and similar time-gap between pregnancies.

Races were distributed as follows: Chinese (10% parenteral and 6% of oral iron therapy), Malayan (46% and 78% in the same order), Indian (16 and 8%). History of preterm delivery was seen in 16% of the parenteral treatment group and 12% of oral iron group.

Interventions

Total dose iron infusion vs oral therapy with iron fumarate. The dose was determined according to the body weight and estimated iron deficiency.

Outcomes

This paper provided data at 36 weeks, delivery and 6 weeks postpartum. The paper provided haematological outcomes. In addition, the publication mentioned some side effects and similar clinical outcomes in both groups. The authors were contacted and provided precise data on clinical outcomes and side effects that were included too.

Dr. Kuldip Singh at the National University Hospital - University of Singapore was the contacted author.

Contact was established through a search on Internet. Further contact is being undertaken to check the units used for serum iron and ferritin estimations, then further comparison tables can be added to this review.

Notes

Allocation concealment

A – Adequate

Study

Tanzania 1988

Methods

A randomisation list was used to generate the randomisation sequence.

Participants

The study was done in a population of indigenous women. Inclusion criteria were: 1. Diagnosis of iron deficiency anaemia defined as haemoglobin under 10 g/dl; MCHC under 32%; hypochromia; poikilocytosis and anisocytosis.

2. Age 16 years and above.

3. Gestational age under 36 wks.

Exclusion criteria were: 1. History of reaction to parenteral iron 2. Hypersensitivity to iron dextran 3. Asthma history 4. Allergic conditions 5. Hepatic impairment 6. Renal impairment

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Characteristics of included studies (Continued ) 7. Rheumatoid arthritis.

8. Fever.

314 women received the full dose while 309 women received the 2/3 dose. Age, gravidity, parity, duration of pregnancy and basal haemoglobin levels were similar for the groups. Nearly one forth of the women had haemoglobin levels under 7.0 g/dl in both groups.

Interventions

The dose of the two studied treatments was determined according to the recommendations of providers. In the intervention group patients received 2/3 of the total dose calculated of iron dextran “Imferon” while in the control group they received the total dose of iron dextran plus 10 additional ml as suggested for pregnant women. The iron dextran was diluted in 500 ml of 5% dextrose and infused at a steady rate of 40 drops per minute. A test dose was given at the start of each infusion. This test dose was administered at a rate of 5 drops per minute over 10 minutes.

Outcomes

Women were followed up regularly throughout the remaining part of their pregnancy, during delivery and for 16 weeks post-partum. Infants were examined at the time of birth. Maternal haemoglobin levels were assessed at each visit to the antenatal clinic and 6 and 16 weeks after delivery. Cord haemoglobin was measured as well.

Women were analysed by intention to treat. Loss to follow-up for haemoglobin result was 47% so these results were not included in this review. For other clinical outcomes, loss to follow up was 18% and 20% so they were included.

Notes

Allocation concealment

B – Unclear

Study

UK 1965

Methods

Method of allocation was a random number table. It is not clearly stated how allocation was concealed.

Participants

Pregnant women in the third trimester with haemoglobin with less than 10 g/dl, MCHC under 30 % and a marrow aspiration indicating iron deficiency. Patients with toxemia, infection or ante-partum haemorrhage were excluded. All women received prophylactic folate and oral iron was stopped prior to randomisation.

Women were followed for 8 weeks and outcomes assessed at admission, 2, 4 and 8 weeks. Side effects were assessed during the treatment period.

Interventions

Iron sorbitrol-citric acid complex (Jectofer) IM 25 women Iron dextran (Imferon) IM 23 women Iron dextran (Imferon) IV 26 women Dosages of all preparations were calculated to replace iron stores.

Outcomes

Side effects: 1. Pain at injection site 2. Skin discoloration 3. Venous thrombosis 4. Nausea or vomiting 5. Headaches 6. Shivering 7. Itching 8 Metallic taste in mouth

Notes

Other outcomes were not considered due to a high drop-out rate. Haemoglobin level data are not included due to 81% drop-outs at pre-delivery. The authors made an additional trial of iron dextran IV vs iron dextran + 50 mg of hydrocortisone in the infusion to assess if this had any effect on the rate of side effects.

Allocation concealment

B – Unclear

Study

West Java 1993

Methods

Allocation was done using a random number list from 1 to 305 and allocating patients sequentially in the list. The manufacturers of the active treatments provided placebos. An independent researcher randomly

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

11

labelled the active and placebo preparations. Coding colours were given to the preparations and these codes were opened once the data for all analyses had been entered in the computer and cleaned.

Participants

The study was conducted from April to September 1992 in 20 rural villages in three sub-districts of Bogor, West Java. Participants came from middle and low socio-economic groups. They were aged between 17 and 35 years, with parity in the ranges of 0 to 4 and gestational age of 16 to 25 weeks.

572 women met inclusion criteria. 305 participated in the study.

Haemoglobin levels of participants were in the range of 8.0 to 10.9 g/dl. Women receiving iron or Vitamin A treatments or supplements in the 6 months prior to study were excluded. Outcomes were assessed 2 and 7 days after the last dose of treatment was given (24 to 33 weeks). Participants had similar age, height, weight, pregnancies, parity and gestational age at admission.

Interventions

Four different groups received two active treatments at most (factorial design). All preparations were given daily for eight weeks: 1. 60 mg elemental oral iron (as Ferrous sulphate) + Vitamin A (2.4 mg of retinol as retinyl palmitate).

2. 60 mg elemental oral iron (as Ferrous sulphate ) + Placebo of Vitamin A 3. Placebo of oral iron + Vitamin A (2.4 mg of retinol as retinyl palmitate).

4. Placebo or oral iron + Placebo or Vitamin A Haemoglobin, ferritin and serum iron mean values and standard deviations were extracted for this review from the published paper. Percentage of women that became non-anaemic (Hb >10.9g/dl) was counted as a dichotomic variable. Numbers needed to treat were calculated by the authors of this review.

Outcomes

Notes

Results for Vitamin A + placebo were not considered since this is part of a different review. Vitamin A combined with iron was included in this review. Serum iron levels were given in umol/l and converted to mg/l by the authors (umol/l x 0.056 = mg/l). Loss to follow-up accounted for 17% of the women. Analysis was done by intention to treat.

Allocation concealment

A – Adequate

Abbreviations: IV - intravenous MCHC - mean corpuscular haemoglobin concentration vs - versus

Characteristics of excluded studies Study

Reason for exclusion

Al Momen 1996

Not a randomised controlled trial. Sequential allocation.

Allaire 1961

Loss to follow-up of 56%. Used quasi-random allocation.

Bare 1960

They allocated patients using alternate order. This is not considered random.

Barrada 1991

Insufficient information for critical appraisal was provided. There are no explicit inclusion or exclusion criteria.

Basu 1973

Randomisation method not posed. No information is provided regarding blinding or number of women that completed the trial or that were accounted for each result.

Breymann 1998

Randomised open label trial.

Chanarin 1965

This study addressed megaloblastic anaemia.

Fochi 1985

Randomisation is not well balanced. The paper does not explain unbalanced groups.

Hamilton 1973

Allocation was done using a haphazard strategy, not a random one.

Hampel 1974

Used a haphazard allocation method (day of diagnosis).

Hawkins 1970

The study evaluates the use of medication in women with hemoglobin levels over 10.5 g/dl and uses non random strategy for allocation.

Holly 1955

The study is in women with haemoglobin levels over 10 g/dl. Treatment allocation was not random.

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

12

Characteristics of excluded studies (Continued ) Izak 1973

Although the authors state that allocation was random, the groups are very different (184, 76 and 22). The authors used an inappropriate control group of healthy women. They do not explain the randomisation method.

Jackson 1982

More than 50% of their women were lost to follow-up.

Jaud 1979

Used open randomisation list. We tried to contact to verify data but it was impossible. Open randomisation lists are considered inadequate since there is no concealment and it is prone to bias.

Mahale 1993

This study has drop-outs that surpasses the limit established for this review.

Preziosi 1997

No fundamental data to assess validity.

Sood 1975

This study has a high proportion of women lost to follow-up exceding the cut-off point established for this review.

Stein 1991

No fundamental data to assess validity.

Steiner 1977

No information regarding random allocation or allocation concealment. Insufficient baseline data provided.

Valli Rani 1995

They used sequential strategy for allocation and not a random one.

Visca 1996

No fundamental data to assess validity.

ANALYSES

Comparison 01. Oral iron vs placebo Outcome title 01 Anaemic during 2nd trimester.

02 Haemoglobin levels (g/dl) 03 Ferritin levels (ln ug/l) 04 Serum iron (mg/l) 05 Side effects 06 Nausea and vomiting 07 Constipation 08 Abdominal cramps

No. of studies

No. of participants

1 1 1 1 1 1 1 1

125 125 125 125 51 51 51 51

Statistical method Peto Odds Ratio 95% CI Weighted Mean Difference (Fixed) 95% CI Weighted Mean Difference (Fixed) 95% CI Weighted Mean Difference (Fixed) 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI

Effect size 0.12 [0.06, 0.24] 0.80 [0.62, 0.98] 0.70 [0.52, 0.88] 0.04 [0.03, 0.05] 2.30 [0.61, 8.63] 4.21 [0.67, 26.26] 1.15 [0.26, 5.13] 8.74 [0.53, 144.48]

Comparison 02. Oral iron with vitamin A vs placebo Outcome title 01 Anaemic during 2nd trimester.

02 Haemoglobin levels (g/dl) 03 Ferritin levels (ln ug/l) 04 Serum iron (mg/l)

No. of studies

No. of participants

1 1 1 1

125 125 125 125

Statistical method Peto Odds Ratio 95% CI Weighted Mean Difference (Fixed) 95% CI Weighted Mean Difference (Fixed) 95% CI Weighted Mean Difference (Fixed) 95% CI

Effect size 0.04 [0.02, 0.08] 1.30 [1.11, 1.49] 0.70 [0.52, 0.88] 0.08 [0.07, 0.09]

Comparison 03. Oral iron + vitamin A vs oral iron Outcome title 01 Anaemia during second trimester 02 Haemoglobin levels (g/dl) 03 Ferritin (ln ug/l) 04 Serum iron (mg/l)

No. of studies

No. of participants

1

126

Peto Odds Ratio 95% CI

0.14 [0.06, 0.35]

1 1 1

126 126 126

Weighted Mean Difference (Fixed) 95% CI Weighted Mean Difference (Fixed) 95% CI Weighted Mean Difference (Fixed) 95% CI

0.50 [0.31, 0.69] 0.00 [-0.17, 0.17] 0.04 [0.03, 0.05]

Statistical method

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

Effect size

13

Comparison 04. Controlled release oral iron vs regular oral iron

Outcome title 01 Side effects 02 Nausea and vomiting 03 Constipation 04 Abdominal cramps

No. of studies

No. of participants

1 1 1 1

49 49 49 49

Statistical method Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI

Effect size 0.95 [0.28, 3.23] 0.95 [0.21, 4.27] 0.26 [0.04, 1.61] 0.48 [0.05, 4.82]

Comparison 05. Intramuscular iron sorbito-citric acid vs intramuscular dextran

Outcome title 01 Pain at injection site 02 Skin discolouration at injection site 03 Venous thrombosis 04 Nausea or vomiting 05 Headaches 06 Shivering 07 Itching 08 Metallic taste in mouth

No. of studies

No. of participants

1 1

48 48

Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI

0.99 [0.32, 3.05] 0.14 [0.04, 0.46]

1 1 1 1 1 1

48 48 48 48 48 48

Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI

Not estimable 0.92 [0.06, 15.16] 0.16 [0.03, 0.70] 0.12 [0.00, 6.27] 0.91 [0.20, 4.08] 3.40 [0.54, 21.26]

Statistical method

Effect size

Comparison 06. Intramuscular iron dextran vs intravenous iron dextran

Outcome title 01 Pain at injection site 02 Skin discolouration at injection site 03 Venous thrombosis 04 Nausea or vomiting 05 Headaches 06 Shivering 07 Itching 08 Metallic taste in mouth

No. of studies

No. of participants

1 1

49 49

Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI

6.51 [1.95, 21.73] 12.53 [3.67, 42.85]

1 1 1 1 1 1

49 49 49 49 49 49

Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI

0.13 [0.02, 1.02] 0.57 [0.06, 5.73] 4.42 [1.05, 18.54] 0.57 [0.06, 5.73] 1.60 [0.33, 7.81] 1.13 [0.07, 18.76]

Statistical method

Effect size

Comparison 07. Intramuscular iron sorbitol citric acid vs intravenous iron dextran

Outcome title 01 Pain at injection site 02 Skin discolouration at injection site 03 Venous thrombosis 04 Nausea or vomiting 05 Headaches 06 Shivering 07 Itching 08 Metallic taste in mouth

No. of studies

No. of participants

1 1

51 51

Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI

6.31 [1.96, 20.37] 3.02 [0.40, 22.83]

1 1 1 1 1 1

51 51 51 51 51 51

Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI

0.12 [0.02, 0.94] 0.52 [0.05, 5.24] 0.52 [0.05, 5.24] 0.14 [0.01, 2.22] 1.45 [0.30, 7.02] 3.85 [0.62, 23.94]

Statistical method

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

Effect size

14

Comparison 08. Intravenous iron vs placebo

Outcome title 01 Side effects 02 Nausea or vomiting 03 Constipation 04 Abdominal cramps

No. of studies

No. of participants

1 1 1 1

54 54 54 54

Statistical method Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI

Effect size 0.72 [0.15, 3.49] 0.14 [0.00, 6.82] 0.27 [0.04, 1.69] Not estimable

Comparison 09. Intravenous iron vs regular oral iron

Outcome title 01 Side effects 02 Nausea or vomiting 03 Constipation 04 Abdominal cramps 05 Diarrhoea 06 Haemoglobin at 36 weeks 09 Maternal haemoglobin at delivery 10 Maternal haemoglobin at 6 weeks 13 Maternal mortality 14 Preterm labour 15 Caesarean section 16 Operative vaginal delivery 17 Postpartum haemorrhage 18 Low birth weight (under 2,500g) 19 Neonatal birth weight 20 Small for gestational age 21 Five minute Apgar score under seven 22 Neonatal mortality

No. of studies

No. of participants

1 2 2 1 1 1 1

51 154 151 51 100 100 100

Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Weighted Mean Difference (Fixed) 95% CI Weighted Mean Difference (Fixed) 95% CI

0.33 [0.08, 1.28] 0.12 [0.03, 0.56] 0.13 [0.05, 0.35] 0.11 [0.01, 1.89] 0.13 [0.01, 1.28] 1.10 [1.09, 1.11] 0.60 [0.59, 0.61]

1

100

Weighted Mean Difference (Fixed) 95% CI

0.60 [0.59, 0.61]

1 1 1 1 1 1

100 100 100 100 100 100

Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI

Not estimable Not estimable 1.27 [0.33, 4.98] 1.52 [0.25, 9.08] 0.84 [0.26, 2.68] Not estimable

1

100

Weighted Mean Difference (Fixed) 95% CI

1 1

100 100

Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI

-119.30 [-312.10, 73.50] 1.69 [0.53, 5.39] 1.00 [0.06, 16.21]

1

100

Peto Odds Ratio 95% CI

Not estimable

Statistical method

Effect size

Comparison 10. Intravenous iron vs controlled release oral iron

Outcome title 01 Side effects 02 Nausea or vomiting 03 Constipation 04 Abdominal cramps

No. of studies

No. of participants

1 1 1 1

52 52 52 52

Statistical method Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

Effect size 0.34 [0.09, 1.35] 0.11 [0.01, 0.83] 0.92 [0.06, 15.22] 0.12 [0.00, 6.31] 15

Comparison 11. Intravenous iron + hydrocortisone vs intravenous iron Outcome title 01 Tenderness or erythema 02 Venous thrombosis

No. of studies 1 1

No. of participants 30 30

Statistical method Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI

Effect size 7.94 [0.47, 133.26] 0.10 [0.01, 0.65]

Comparison 12. 2/3 dose intravenous iron vs full dose intravenous iron Outcome title 01 Allergic reaction during infusion 02 Allergic reaction after infusion 03 Life threatening allergic reaction during infusion 04 Discomfort needing analgesics after infusion 05 Immobilised by painful joints 06 Non-live births 07 Neonatal death 08 Stillbirth 09 Spontaneous abortion

No. of studies 1

No. of participants 623

Peto Odds Ratio 95% CI

0.65 [0.34, 1.25]

1 1

623 623

Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI

0.56 [0.38, 0.83] 2.42 [0.54, 10.70]

1

623

Peto Odds Ratio 95% CI

0.48 [0.26, 0.88]

1 1 1 1 1

623 507 507 507 507

Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI Peto Odds Ratio 95% CI

0.79 [0.29, 2.12] 0.85 [0.35, 2.08] 0.53 [0.14, 1.98] 0.69 [0.25, 1.93] 2.86 [0.40, 20.42]

Statistical method

Effect size

INDEX TERMS Medical Subject Headings (MeSH) Anemia, Iron-Deficiency [∗ therapy]; Iron [∗ administration & dosage]; Pregnancy Complications, Hematologic [∗ therapy]; Randomized Controlled Trials MeSH check words Female; Humans; Pregnancy

COVER SHEET Title

Treatments for iron deficiency anaemia in pregnancy

Authors

Cuervo LG, Mahomed K

Contribution of author(s)

Both reviewers appraised the papers independently. Luis Gabriel Cuervo took the lead on writing the review with Kassam Mahomed providing comments on the various drafts.

Issue protocol first published

1999/4

Review first published

2001/2

Date of most recent amendment

02 March 2001

Date of most recent SUBSTANTIVE amendment

31 January 2001

What’s New

This review was done in 1998 and updated for publication on January 2000.

Date new studies sought but none found

Information not supplied by author

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

16

Date new studies found but not yet included/excluded

Information not supplied by author

Date new studies found and included/excluded

Information not supplied by author

Date authors’ conclusions section amended

Information not supplied by author

Contact address

A/Prof Luis Gabriel Cuervo-Amore Research Promotion and Development Unit (IKM/RC) Pan American Health Organization 525 23rd St NW Washington DC 20037-2895 USA E-mail: cuervolu@paho.org Tel: +1 202 9743135

DOI

10.1002/14651858.CD003094

Cochrane Library number

CD003094

Editorial group

Cochrane Pregnancy and Childbirth Group

Editorial group code

HM-PREG GRAPHS AND OTHER TABLES

Analysis 01.01.

Review:

Comparison 01 Oral iron vs placebo, Outcome 01 Anaemic during 2nd trimester.

Treatments for iron deficiency anaemia in pregnancy

Comparison: 01 Oral iron vs placebo Outcome: 01 Anaemic during 2nd trimester.

Study

West Java 1993 Total (95% CI)

Oral iron

Placebo

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

20/63

52/62

100.0

0.12 [ 0.06, 0.24 ]

63

62

100.0

0.12 [ 0.06, 0.24 ]

Total events: 20 (Oral iron), 52 (Placebo) Test for heterogeneity: not applicable Test for overall effect z=5.87

p<0.00001

0.1 0.2

0.5

Oral Iron Better

1

2

5

10

Oral Iron Worse

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

17

Analysis 01.02.

Review:

Comparison 01 Oral iron vs placebo, Outcome 02 Haemoglobin levels (g/dl)

Treatments for iron deficiency anaemia in pregnancy

Comparison: 01 Oral iron vs placebo Outcome: 02 Haemoglobin levels (g/dl) Study

Oral iron

West Java 1993 Total (95% CI)

Placebo

N

Mean(SD)

N

Mean(SD)

63

11.30 (0.52)

62

10.50 (0.51)

63

Weighted Mean Difference (Fixed)

Weight

95% CI

(%)

62

Weighted Mean Difference (Fixed) 95% CI

100.0

0.80 [ 0.62, 0.98 ]

100.0

0.80 [ 0.62, 0.98 ]

Test for heterogeneity: not applicable Test for overall effect z=8.68

p<0.00001

-10.0

-5.0

0

Oral iron worse

Analysis 01.03.

Review:

5.0

10.0

Oral iron better

Comparison 01 Oral iron vs placebo, Outcome 03 Ferritin levels (ln ug/l)

Treatments for iron deficiency anaemia in pregnancy

Comparison: 01 Oral iron vs placebo Outcome: 03 Ferritin levels (ln ug/l) Study

Oral iron

West Java 1993 Total (95% CI)

Placebo

N

Mean(SD)

N

Mean(SD)

63

3.30 (0.50)

62

2.60 (0.50)

63

Weighted Mean Difference (Fixed)

Weight

Weighted Mean Difference (Fixed)

95% CI

(%)

95% CI

62

100.0

0.70 [ 0.52, 0.88 ]

100.0

0.70 [ 0.52, 0.88 ]

Test for heterogeneity: not applicable Test for overall effect z=7.83

p<0.00001

-10.0

-5.0

0

Oral iron worse

Analysis 01.04.

Review:

5.0

10.0

Oral iron better

Comparison 01 Oral iron vs placebo, Outcome 04 Serum iron (mg/l)

Treatments for iron deficiency anaemia in pregnancy

Comparison: 01 Oral iron vs placebo Outcome: 04 Serum iron (mg/l) Study

West Java 1993 Total (95% CI)

Oral iron

Placebo

N

Mean(SD)

N

Mean(SD)

63

0.43 (0.04)

62

0.39 (0.02)

63

Weighted Mean Difference (Fixed)

Weight

Weighted Mean Difference (Fixed)

95% CI

(%)

95% CI

62

100.0

0.04 [ 0.03, 0.05 ]

100.0

0.04 [ 0.03, 0.05 ]

Test for heterogeneity: not applicable Test for overall effect z=7.09

p<0.00001

-10.0

-5.0

Oral iron worse

0

5.0

10.0

Oral iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

18

Analysis 01.05.

Review:

Comparison 01 Oral iron vs placebo, Outcome 05 Side effects

Treatments for iron deficiency anaemia in pregnancy

Comparison: 01 Oral iron vs placebo Outcome: 05 Side effects Study

Australia 1969 Total (95% CI)

Oral iron

Placebo

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

7/24

4/27

100.0

2.30 [ 0.61, 8.63 ]

24

27

100.0

2.30 [ 0.61, 8.63 ]

Total events: 7 (Oral iron), 4 (Placebo) Test for heterogeneity: not applicable Test for overall effect z=1.23

p=0.2

0.1 0.2

0.5

1

Oral iron better

Analysis 01.06.

Review:

2

5

10

Oral iron worse

Comparison 01 Oral iron vs placebo, Outcome 06 Nausea and vomiting

Treatments for iron deficiency anaemia in pregnancy

Comparison: 01 Oral iron vs placebo Outcome: 06 Nausea and vomiting Study

Australia 1969 Total (95% CI)

Oral iron

Placebo

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

4/24

1/27

100.0

4.21 [ 0.67, 26.26 ]

24

27

100.0

4.21 [ 0.67, 26.26 ]

Total events: 4 (Oral iron), 1 (Placebo) Test for heterogeneity: not applicable Test for overall effect z=1.54

p=0.1

0.1 0.2

0.5

Oral iron better

1

2

5

10

Oral iron worse

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

19

Analysis 01.07.

Review:

Comparison 01 Oral iron vs placebo, Outcome 07 Constipation

Treatments for iron deficiency anaemia in pregnancy

Comparison: 01 Oral iron vs placebo Outcome: 07 Constipation Study

Australia 1969 Total (95% CI)

Oral iron

Placebo

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

4/24

4/27

100.0

1.15 [ 0.26, 5.13 ]

24

27

100.0

1.15 [ 0.26, 5.13 ]

Total events: 4 (Oral iron), 4 (Placebo) Test for heterogeneity: not applicable Test for overall effect z=0.18

p=0.9

0.1 0.2

0.5

1

Oral iron better

Analysis 01.08.

Review:

2

5

10

Oral iron worse

Comparison 01 Oral iron vs placebo, Outcome 08 Abdominal cramps

Treatments for iron deficiency anaemia in pregnancy

Comparison: 01 Oral iron vs placebo Outcome: 08 Abdominal cramps Study

Australia 1969 Total (95% CI)

Oral iron

Placebo

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

2/24

0/27

100.0

8.74 [ 0.53, 144.48 ]

24

27

100.0

8.74 [ 0.53, 144.48 ]

Total events: 2 (Oral iron), 0 (Placebo) Test for heterogeneity: not applicable Test for overall effect z=1.52

p=0.1

0.1 0.2

0.5

Oral iron better

1

2

5

10

Oral iron worse

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

20

Analysis 02.01.

Review:

Comparison 02 Oral iron with vitamin A vs placebo, Outcome 01 Anaemic during 2nd trimester.

Treatments for iron deficiency anaemia in pregnancy

Comparison: 02 Oral iron with vitamin A vs placebo Outcome: 01 Anaemic during 2nd trimester.

Study

West Java 1993 Total (95% CI)

Oral iron + Vit A

Placebo

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

2/63

52/62

100.0

0.04 [ 0.02, 0.08 ]

63

62

100.0

0.04 [ 0.02, 0.08 ]

Total events: 2 (Oral iron + Vit A), 52 (Placebo) Test for heterogeneity: not applicable Test for overall effect z=9.07

p<0.00001

0.1 0.2

0.5

1

Iron + Vit A better

Analysis 02.02.

Review:

2

5

10

Iron + Vit A worse

Comparison 02 Oral iron with vitamin A vs placebo, Outcome 02 Haemoglobin levels (g/dl)

Treatments for iron deficiency anaemia in pregnancy

Comparison: 02 Oral iron with vitamin A vs placebo Outcome: 02 Haemoglobin levels (g/dl) Study

West Java 1993 Total (95% CI)

Oral iron + Vit A

Placebo

N

Mean(SD)

N

Mean(SD)

63

11.80 (0.55)

62

10.50 (0.51)

63

Weighted Mean Difference (Fixed)

Weight

95% CI

(%)

62

Weighted Mean Difference (Fixed) 95% CI

100.0

1.30 [ 1.11, 1.49 ]

100.0

1.30 [ 1.11, 1.49 ]

Test for heterogeneity: not applicable Test for overall effect z=13.71

p<0.00001

-10.0

-5.0

0

Iron + Vit A worse

Analysis 02.03.

Review:

5.0

10.0

Iron + Vit A better

Comparison 02 Oral iron with vitamin A vs placebo, Outcome 03 Ferritin levels (ln ug/l)

Treatments for iron deficiency anaemia in pregnancy

Comparison: 02 Oral iron with vitamin A vs placebo Outcome: 03 Ferritin levels (ln ug/l) Study

West Java 1993 Total (95% CI)

Oral iron + Vit A

Placebo

N

Mean(SD)

N

Mean(SD)

63

3.30 (0.50)

62

2.60 (0.50)

63

Weighted Mean Difference (Fixed)

Weight

Weighted Mean Difference (Fixed)

95% CI

(%)

95% CI

62

100.0

0.70 [ 0.52, 0.88 ]

100.0

0.70 [ 0.52, 0.88 ]

Test for heterogeneity: not applicable Test for overall effect z=7.83

p<0.00001

-10.0

-5.0

Iron + Vit A worse

0

5.0

10.0

Iron + Vit A better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

21

Analysis 02.04.

Review:

Comparison 02 Oral iron with vitamin A vs placebo, Outcome 04 Serum iron (mg/l)

Treatments for iron deficiency anaemia in pregnancy

Comparison: 02 Oral iron with vitamin A vs placebo Outcome: 04 Serum iron (mg/l) Study

West Java 1993 Total (95% CI)

Oral iron + Vit A

Placebo

N

Mean(SD)

N

Mean(SD)

63

0.47 (0.04)

62

0.39 (0.02)

63

Weighted Mean Difference (Fixed)

Weight

95% CI

(%)

62

Weighted Mean Difference (Fixed) 95% CI

100.0

0.08 [ 0.07, 0.09 ]

100.0

0.08 [ 0.07, 0.09 ]

Test for heterogeneity: not applicable Test for overall effect z=14.18

p<0.00001

-10.0

-5.0

0

5.0

Iron + Vit A worse

Analysis 03.01.

Review:

10.0

Iron + Vit A better

Comparison 03 Oral iron + vitamin A vs oral iron, Outcome 01 Anaemia during second trimester

Treatments for iron deficiency anaemia in pregnancy

Comparison: 03 Oral iron + vitamin A vs oral iron Outcome: 01 Anaemia during second trimester Study

West Java 1993 Total (95% CI)

oral iron + vit A

oral iron

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

2/63

20/63

100.0

0.14 [ 0.06, 0.35 ]

63

63

100.0

0.14 [ 0.06, 0.35 ]

Total events: 2 (oral iron + vit A), 20 (oral iron) Test for heterogeneity: not applicable Test for overall effect z=4.21

p=0.00003

0.1 0.2

0.5

1

Iron + Vit A better

Analysis 03.02.

Review:

2

5

10

Iron + Vit A worse

Comparison 03 Oral iron + vitamin A vs oral iron, Outcome 02 Haemoglobin levels (g/dl)

Treatments for iron deficiency anaemia in pregnancy

Comparison: 03 Oral iron + vitamin A vs oral iron Outcome: 02 Haemoglobin levels (g/dl) Study

West Java 1993 Total (95% CI)

Oral iron + Vit A

Oral iron

N

Mean(SD)

N

Mean(SD)

63

11.80 (0.55)

63

11.30 (0.52)

63

Weighted Mean Difference (Fixed)

Weight

Weighted Mean Difference (Fixed)

95% CI

(%)

95% CI

63

100.0

0.50 [ 0.31, 0.69 ]

100.0

0.50 [ 0.31, 0.69 ]

Test for heterogeneity: not applicable Test for overall effect z=5.24

p<0.00001

-10.0

-5.0

Iron + Vit A worse

0

5.0

10.0

Iron + Vit A better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

22

Analysis 03.03.

Review:

Comparison 03 Oral iron + vitamin A vs oral iron, Outcome 03 Ferritin (ln ug/l)

Treatments for iron deficiency anaemia in pregnancy

Comparison: 03 Oral iron + vitamin A vs oral iron Outcome: 03 Ferritin (ln ug/l) Study

West Java 1993 Total (95% CI)

Oral iron + Vit A

Oral iron

N

Mean(SD)

N

Mean(SD)

63

3.30 (0.50)

63

3.30 (0.50)

63

Weighted Mean Difference (Fixed)

Weight

95% CI

(%)

63

Weighted Mean Difference (Fixed) 95% CI

100.0

0.00 [ -0.17, 0.17 ]

100.0

0.00 [ -0.17, 0.17 ]

Test for heterogeneity: not applicable Test for overall effect z=0.00

p=1

-10.0

-5.0

0

Iron + Vit A worse

Analysis 03.04.

Review:

5.0

10.0

Iron + Vit A better

Comparison 03 Oral iron + vitamin A vs oral iron, Outcome 04 Serum iron (mg/l)

Treatments for iron deficiency anaemia in pregnancy

Comparison: 03 Oral iron + vitamin A vs oral iron Outcome: 04 Serum iron (mg/l) Study

West Java 1993 Total (95% CI)

Oral iron + Vit A

Oral iron

N

Mean(SD)

N

Mean(SD)

63

0.47 (0.04)

63

0.43 (0.04)

63

Weighted Mean Difference (Fixed)

Weight

Weighted Mean Difference (Fixed)

95% CI

(%)

95% CI

63

100.0

0.04 [ 0.03, 0.05 ]

100.0

0.04 [ 0.03, 0.05 ]

Test for heterogeneity: not applicable Test for overall effect z=5.61

p<0.00001

-10.0

-5.0

0

Iron + Vit A worse

Analysis 04.01.

Review:

5.0

10.0

Iron + Vit A better

Comparison 04 Controlled release oral iron vs regular oral iron, Outcome 01 Side effects

Treatments for iron deficiency anaemia in pregnancy

Comparison: 04 Controlled release oral iron vs regular oral iron Outcome: 01 Side effects Study

Australia 1969 Total (95% CI)

Ctrl release iron

Regular oral iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

7/25

7/24

100.0

0.95 [ 0.28, 3.23 ]

25

24

100.0

0.95 [ 0.28, 3.23 ]

Total events: 7 (Ctrl release iron), 7 (Regular oral iron) Test for heterogeneity: not applicable Test for overall effect z=0.09

p=0.9

0.1 0.2

0.5

Ctrl rel iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

1

2

5

10

Ctrl rel iron worse

23

Analysis 04.02.

Review:

Comparison 04 Controlled release oral iron vs regular oral iron, Outcome 02 Nausea and vomiting

Treatments for iron deficiency anaemia in pregnancy

Comparison: 04 Controlled release oral iron vs regular oral iron Outcome: 02 Nausea and vomiting Study

Australia 1969 Total (95% CI)

Ctrl release iron

Regular oral iron

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

4/25

4/24

100.0

0.95 [ 0.21, 4.27 ]

25

24

100.0

0.95 [ 0.21, 4.27 ]

Total events: 4 (Ctrl release iron), 4 (Regular oral iron) Test for heterogeneity: not applicable Test for overall effect z=0.06

p=1

0.1 0.2

0.5

1

Ctrl rel iron better

Analysis 04.03.

Review:

2

5

10

Ctrl rel iron worse

Comparison 04 Controlled release oral iron vs regular oral iron, Outcome 03 Constipation

Treatments for iron deficiency anaemia in pregnancy

Comparison: 04 Controlled release oral iron vs regular oral iron Outcome: 03 Constipation Study

Australia 1969 Total (95% CI)

Ctrl release iron

Regular oral iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

1/25

4/24

100.0

0.26 [ 0.04, 1.61 ]

25

24

100.0

0.26 [ 0.04, 1.61 ]

Total events: 1 (Ctrl release iron), 4 (Regular oral iron) Test for heterogeneity: not applicable Test for overall effect z=1.45

p=0.1

0.1 0.2

0.5

Ctrl rel iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

1

2

5

10

Ctrl rel iron worse

24

Analysis 04.04.

Review:

Comparison 04 Controlled release oral iron vs regular oral iron, Outcome 04 Abdominal cramps

Treatments for iron deficiency anaemia in pregnancy

Comparison: 04 Controlled release oral iron vs regular oral iron Outcome: 04 Abdominal cramps Study

Australia 1969 Total (95% CI)

Ctrl release iron

Regular oral iron

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

1/25

2/24

100.0

0.48 [ 0.05, 4.82 ]

25

24

100.0

0.48 [ 0.05, 4.82 ]

Total events: 1 (Ctrl release iron), 2 (Regular oral iron) Test for heterogeneity: not applicable Test for overall effect z=0.63

p=0.5

0.1 0.2

0.5

1

Ctrl rel iron better

Analysis 05.01.

Review:

2

5

10

Ctrl rel iron worse

Comparison 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran, Outcome 01 Pain at injection site

Treatments for iron deficiency anaemia in pregnancy

Comparison: 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran Outcome: 01 Pain at injection site Study

UK 1965 Total (95% CI)

Iron sorb-cit acid

Iron dextran

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

13/25

12/23

100.0

0.99 [ 0.32, 3.05 ]

25

23

100.0

0.99 [ 0.32, 3.05 ]

Total events: 13 (Iron sorb-cit acid), 12 (Iron dextran) Test for heterogeneity: not applicable Test for overall effect z=0.01

p=1

0.1 0.2

0.5

1

Iron sorb-cit better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

Iron sorb-cit worse

25

Analysis 05.02.

Review:

Comparison 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran, Outcome 02 Skin discolouration at injection site

Treatments for iron deficiency anaemia in pregnancy

Comparison: 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran Outcome: 02 Skin discolouration at injection site Study

UK 1965 Total (95% CI)

Iron sorb-cit acid

Iron dextran

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

3/25

13/23

100.0

0.14 [ 0.04, 0.46 ]

25

23

100.0

0.14 [ 0.04, 0.46 ]

Total events: 3 (Iron sorb-cit acid), 13 (Iron dextran) Test for heterogeneity: not applicable Test for overall effect z=3.23

p=0.001

0.1 0.2

0.5

1

2

Iron sorb-cit better

Analysis 05.03.

Review:

5

10

Iron sorb-cit worse

Comparison 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran, Outcome 03 Venous thrombosis

Treatments for iron deficiency anaemia in pregnancy

Comparison: 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran Outcome: 03 Venous thrombosis Study

Iron sorb-cit acid

Iron dextran

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

x UK 1965

0/25

0/23

0.0

Not estimable

Total (95% CI)

25

23

0.0

Not estimable

Total events: 0 (Iron sorb-cit acid), 0 (Iron dextran) Test for heterogeneity: not applicable Test for overall effect: not applicable

0.1 0.2

0.5

Iron sorb-cit better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

1

2

5

10

Iron sorb-cit worse

26

Analysis 05.04.

Review:

Comparison 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran, Outcome 04 Nausea or vomiting

Treatments for iron deficiency anaemia in pregnancy

Comparison: 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran Outcome: 04 Nausea or vomiting Study

UK 1965 Total (95% CI)

Iron sorb-cit acid

Iron dextran

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

1/25

1/23

100.0

0.92 [ 0.06, 15.16 ]

25

23

100.0

0.92 [ 0.06, 15.16 ]

Total events: 1 (Iron sorb-cit acid), 1 (Iron dextran) Test for heterogeneity: not applicable Test for overall effect z=0.06

p=1

0.1 0.2

0.5

1

Iron sorb-cit better

Analysis 05.05.

Review:

2

5

10

Iron sorb-cit worse

Comparison 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran, Outcome 05 Headaches

Treatments for iron deficiency anaemia in pregnancy

Comparison: 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran Outcome: 05 Headaches Study

UK 1965 Total (95% CI)

Iron sorb-cit acid

Iron dextran

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

1/25

7/23

100.0

0.16 [ 0.03, 0.70 ]

25

23

100.0

0.16 [ 0.03, 0.70 ]

Total events: 1 (Iron sorb-cit acid), 7 (Iron dextran) Test for heterogeneity: not applicable Test for overall effect z=2.43

p=0.02

0.1 0.2

0.5

1

Iron sorb-cit better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

Iron sorb-cit worse

27

Analysis 05.06.

Review:

Comparison 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran, Outcome 06 Shivering

Treatments for iron deficiency anaemia in pregnancy

Comparison: 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran Outcome: 06 Shivering Study

UK 1965 Total (95% CI)

Iron sorb-cit acid

Iron dextran

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

0/25

1/23

100.0

0.12 [ 0.00, 6.27 ]

25

23

100.0

0.12 [ 0.00, 6.27 ]

Total events: 0 (Iron sorb-cit acid), 1 (Iron dextran) Test for heterogeneity: not applicable Test for overall effect z=1.04

p=0.3

0.1 0.2

0.5

1

Iron sorb-cit better

Analysis 05.07.

Review:

2

5

10

Iron sorb-cit worse

Comparison 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran, Outcome 07 Itching

Treatments for iron deficiency anaemia in pregnancy

Comparison: 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran Outcome: 07 Itching Study

UK 1965 Total (95% CI)

Iron sorb-cit acid

Iron dextran

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

4/25

4/23

100.0

0.91 [ 0.20, 4.08 ]

25

23

100.0

0.91 [ 0.20, 4.08 ]

Total events: 4 (Iron sorb-cit acid), 4 (Iron dextran) Test for heterogeneity: not applicable Test for overall effect z=0.13

p=0.9

0.1 0.2

0.5

1

Iron sorb-cit better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

Iron sorb-cit worse

28

Analysis 05.08.

Review:

Comparison 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran, Outcome 08 Metallic taste in mouth

Treatments for iron deficiency anaemia in pregnancy

Comparison: 05 Intramuscular iron sorbito-citric acid vs intramuscular dextran Outcome: 08 Metallic taste in mouth Study

UK 1965 Total (95% CI)

Iron sorb-cit acid

Iron dextran

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

4/25

1/23

100.0

3.40 [ 0.54, 21.26 ]

25

23

100.0

3.40 [ 0.54, 21.26 ]

Total events: 4 (Iron sorb-cit acid), 1 (Iron dextran) Test for heterogeneity: not applicable Test for overall effect z=1.31

p=0.2

0.1 0.2

0.5

1

Iron sorb-cit better

Analysis 06.01.

Review:

2

5

10

Iron sorb-cit worse

Comparison 06 Intramuscular iron dextran vs intravenous iron dextran, Outcome 01 Pain at injection site

Treatments for iron deficiency anaemia in pregnancy

Comparison: 06 Intramuscular iron dextran vs intravenous iron dextran Outcome: 01 Pain at injection site Study

UK 1965 Total (95% CI)

IM iron dextran

IV iron dextran

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

12/23

3/26

100.0

6.51 [ 1.95, 21.73 ]

23

26

100.0

6.51 [ 1.95, 21.73 ]

Total events: 12 (IM iron dextran), 3 (IV iron dextran) Test for heterogeneity: not applicable Test for overall effect z=3.05

p=0.002

0.1 0.2

0.5

1

IM Iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IM iron worse

29

Analysis 06.02.

Review:

Comparison 06 Intramuscular iron dextran vs intravenous iron dextran, Outcome 02 Skin discolouration at injection site

Treatments for iron deficiency anaemia in pregnancy

Comparison: 06 Intramuscular iron dextran vs intravenous iron dextran Outcome: 02 Skin discolouration at injection site Study

UK 1965 Total (95% CI)

IM iron dextran

IV iron dextran

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

13/23

1/26

100.0

12.53 [ 3.67, 42.85 ]

23

26

100.0

12.53 [ 3.67, 42.85 ]

Total events: 13 (IM iron dextran), 1 (IV iron dextran) Test for heterogeneity: not applicable Test for overall effect z=4.03

p=0.00006

0.1 0.2

0.5

1

2

IM iron better

Analysis 06.03.

Review:

5

10

IM iron worse

Comparison 06 Intramuscular iron dextran vs intravenous iron dextran, Outcome 03 Venous thrombosis

Treatments for iron deficiency anaemia in pregnancy

Comparison: 06 Intramuscular iron dextran vs intravenous iron dextran Outcome: 03 Venous thrombosis Study

UK 1965 Total (95% CI)

IM iron dextran

IV iron dextran

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

0/23

4/26

100.0

0.13 [ 0.02, 1.02 ]

23

26

100.0

0.13 [ 0.02, 1.02 ]

Total events: 0 (IM iron dextran), 4 (IV iron dextran) Test for heterogeneity: not applicable Test for overall effect z=1.94

p=0.05

0.1 0.2

0.5

1

IM iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IM iron worse

30

Analysis 06.04.

Review:

Comparison 06 Intramuscular iron dextran vs intravenous iron dextran, Outcome 04 Nausea or vomiting

Treatments for iron deficiency anaemia in pregnancy

Comparison: 06 Intramuscular iron dextran vs intravenous iron dextran Outcome: 04 Nausea or vomiting Study

UK 1965 Total (95% CI)

IM iron dextran

IV iron dextran

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

1/23

2/26

100.0

0.57 [ 0.06, 5.73 ]

23

26

100.0

0.57 [ 0.06, 5.73 ]

Total events: 1 (IM iron dextran), 2 (IV iron dextran) Test for heterogeneity: not applicable Test for overall effect z=0.48

p=0.6

0.1 0.2

0.5

1

IM iron better

Analysis 06.05.

Review:

2

5

10

IM iron worse

Comparison 06 Intramuscular iron dextran vs intravenous iron dextran, Outcome 05 Headaches

Treatments for iron deficiency anaemia in pregnancy

Comparison: 06 Intramuscular iron dextran vs intravenous iron dextran Outcome: 05 Headaches Study

UK 1965 Total (95% CI)

IM iron dextran

IV iron dextran

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

7/23

2/26

100.0

4.42 [ 1.05, 18.54 ]

23

26

100.0

4.42 [ 1.05, 18.54 ]

Total events: 7 (IM iron dextran), 2 (IV iron dextran) Test for heterogeneity: not applicable Test for overall effect z=2.03

p=0.04

0.1 0.2

0.5

1

IM iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IM iron worse

31

Analysis 06.06.

Review:

Comparison 06 Intramuscular iron dextran vs intravenous iron dextran, Outcome 06 Shivering

Treatments for iron deficiency anaemia in pregnancy

Comparison: 06 Intramuscular iron dextran vs intravenous iron dextran Outcome: 06 Shivering Study

UK 1965 Total (95% CI)

IM iron dextran

IV iron dextran

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

1/23

2/26

100.0

0.57 [ 0.06, 5.73 ]

23

26

100.0

0.57 [ 0.06, 5.73 ]

Total events: 1 (IM iron dextran), 2 (IV iron dextran) Test for heterogeneity: not applicable Test for overall effect z=0.48

p=0.6

0.1 0.2

0.5

1

IM iron better

Analysis 06.07.

Review:

2

5

10

IM iron worse

Comparison 06 Intramuscular iron dextran vs intravenous iron dextran, Outcome 07 Itching

Treatments for iron deficiency anaemia in pregnancy

Comparison: 06 Intramuscular iron dextran vs intravenous iron dextran Outcome: 07 Itching Study

UK 1965 Total (95% CI)

IM iron dextran

IV iron dextran

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

4/23

3/26

100.0

1.60 [ 0.33, 7.81 ]

23

26

100.0

1.60 [ 0.33, 7.81 ]

Total events: 4 (IM iron dextran), 3 (IV iron dextran) Test for heterogeneity: not applicable Test for overall effect z=0.58

p=0.6

0.1 0.2

0.5

1

IM iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IM iron worse

32

Analysis 06.08.

Review:

Comparison 06 Intramuscular iron dextran vs intravenous iron dextran, Outcome 08 Metallic taste in mouth

Treatments for iron deficiency anaemia in pregnancy

Comparison: 06 Intramuscular iron dextran vs intravenous iron dextran Outcome: 08 Metallic taste in mouth Study

UK 1965 Total (95% CI)

IM iron dextran

IV iron dextran

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

1/23

1/26

100.0

1.13 [ 0.07, 18.76 ]

23

26

100.0

1.13 [ 0.07, 18.76 ]

Total events: 1 (IM iron dextran), 1 (IV iron dextran) Test for heterogeneity: not applicable Test for overall effect z=0.09

p=0.9

0.1 0.2

0.5

1

IM iron better

Analysis 07.01.

Review:

2

5

10

IM iron worse

Comparison 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran, Outcome 01 Pain at injection site

Treatments for iron deficiency anaemia in pregnancy

Comparison: 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran Outcome: 01 Pain at injection site Study

UK 1965 Total (95% CI)

IM iron sorb-cit

IV iron dextran

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

13/25

3/26

100.0

6.31 [ 1.96, 20.37 ]

25

26

100.0

6.31 [ 1.96, 20.37 ]

Total events: 13 (IM iron sorb-cit), 3 (IV iron dextran) Test for heterogeneity: not applicable Test for overall effect z=3.08

p=0.002

0.1 0.2

0.5

1

IM sorb-cit better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IM sorb-cit worse

33

Analysis 07.02.

Review:

Comparison 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran, Outcome 02 Skin discolouration at injection site

Treatments for iron deficiency anaemia in pregnancy

Comparison: 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran Outcome: 02 Skin discolouration at injection site Study

UK 1965 Total (95% CI)

IM iron sorb-cit

IV iron dextran

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

3/25

1/26

100.0

3.02 [ 0.40, 22.83 ]

25

26

100.0

3.02 [ 0.40, 22.83 ]

Total events: 3 (IM iron sorb-cit), 1 (IV iron dextran) Test for heterogeneity: not applicable Test for overall effect z=1.07

p=0.3

0.1 0.2

0.5

1

IM sorb-cit better

Analysis 07.03.

Review:

2

5

10

IM sorb-cit worse

Comparison 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran, Outcome 03 Venous thrombosis

Treatments for iron deficiency anaemia in pregnancy

Comparison: 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran Outcome: 03 Venous thrombosis Study

UK 1965 Total (95% CI)

IM iron sorb-cit

IV iron dextran

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

0/25

4/26

100.0

0.12 [ 0.02, 0.94 ]

25

26

100.0

0.12 [ 0.02, 0.94 ]

Total events: 0 (IM iron sorb-cit), 4 (IV iron dextran) Test for heterogeneity: not applicable Test for overall effect z=2.02

p=0.04

0.1 0.2

0.5

1

IM sorb-cit better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IM sorb-cit worse

34

Analysis 07.04.

Review:

Comparison 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran, Outcome 04 Nausea or vomiting

Treatments for iron deficiency anaemia in pregnancy

Comparison: 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran Outcome: 04 Nausea or vomiting Study

UK 1965 Total (95% CI)

IM iron sorb-cit

IV iron dextran

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

1/25

2/26

100.0

0.52 [ 0.05, 5.24 ]

25

26

100.0

0.52 [ 0.05, 5.24 ]

Total events: 1 (IM iron sorb-cit), 2 (IV iron dextran) Test for heterogeneity: not applicable Test for overall effect z=0.55

p=0.6

0.1 0.2

0.5

1

IM sorb-cit better

Analysis 07.05.

Review:

2

5

10

IM sorb-cit worse

Comparison 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran, Outcome 05 Headaches

Treatments for iron deficiency anaemia in pregnancy

Comparison: 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran Outcome: 05 Headaches Study

UK 1965 Total (95% CI)

IM iron sorb-cit

IV iron dextran

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

1/25

2/26

100.0

0.52 [ 0.05, 5.24 ]

25

26

100.0

0.52 [ 0.05, 5.24 ]

Total events: 1 (IM iron sorb-cit), 2 (IV iron dextran) Test for heterogeneity: not applicable Test for overall effect z=0.55

p=0.6

0.1 0.2

0.5

1

IM sorb-cit better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IM sorb-cit worse

35

Analysis 07.06.

Review:

Comparison 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran, Outcome 06 Shivering

Treatments for iron deficiency anaemia in pregnancy

Comparison: 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran Outcome: 06 Shivering Study

UK 1965 Total (95% CI)

IM iron sorb-cit

IV iron dextran

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

0/25

2/26

100.0

0.14 [ 0.01, 2.22 ]

25

26

100.0

0.14 [ 0.01, 2.22 ]

Total events: 0 (IM iron sorb-cit), 2 (IV iron dextran) Test for heterogeneity: not applicable Test for overall effect z=1.40

p=0.2

0.1 0.2

0.5

1

IM sorb-cit better

Analysis 07.07.

Review:

2

5

10

IM sorb-cit worse

Comparison 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran, Outcome 07 Itching

Treatments for iron deficiency anaemia in pregnancy

Comparison: 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran Outcome: 07 Itching Study

UK 1965 Total (95% CI)

IM iron sorb-cit

IV iron dextran

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

4/25

3/26

100.0

1.45 [ 0.30, 7.02 ]

25

26

100.0

1.45 [ 0.30, 7.02 ]

Total events: 4 (IM iron sorb-cit), 3 (IV iron dextran) Test for heterogeneity: not applicable Test for overall effect z=0.46

p=0.6

0.1 0.2

0.5

1

IM sorb-cit better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IM sorb-cit worse

36

Analysis 07.08.

Review:

Comparison 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran, Outcome 08 Metallic taste in mouth

Treatments for iron deficiency anaemia in pregnancy

Comparison: 07 Intramuscular iron sorbitol citric acid vs intravenous iron dextran Outcome: 08 Metallic taste in mouth Study

UK 1965 Total (95% CI)

IM iron sorb-cit

IV iron dextran

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

4/25

1/26

100.0

3.85 [ 0.62, 23.94 ]

25

26

100.0

3.85 [ 0.62, 23.94 ]

Total events: 4 (IM iron sorb-cit), 1 (IV iron dextran) Test for heterogeneity: not applicable Test for overall effect z=1.44

p=0.1

0.1 0.2

0.5

1

IM sorb-cit better

Analysis 08.01.

Review:

2

5

10

IM sorb-cit worse

Comparison 08 Intravenous iron vs placebo, Outcome 01 Side effects

Treatments for iron deficiency anaemia in pregnancy

Comparison: 08 Intravenous iron vs placebo Outcome: 01 Side effects Study

Australia 1969 Total (95% CI)

Intravenous iron

Placebo

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

3/27

4/27

100.0

0.72 [ 0.15, 3.49 ]

27

27

100.0

0.72 [ 0.15, 3.49 ]

Total events: 3 (Intravenous iron), 4 (Placebo) Test for heterogeneity: not applicable Test for overall effect z=0.40

p=0.7

0.1 0.2

0.5

1

IV iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IV iron worse

37

Analysis 08.02.

Review:

Comparison 08 Intravenous iron vs placebo, Outcome 02 Nausea or vomiting

Treatments for iron deficiency anaemia in pregnancy

Comparison: 08 Intravenous iron vs placebo Outcome: 02 Nausea or vomiting Study

Australia 1969 Total (95% CI)

Intravenous iron

Placebo

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

0/27

1/27

100.0

0.14 [ 0.00, 6.82 ]

27

27

100.0

0.14 [ 0.00, 6.82 ]

Total events: 0 (Intravenous iron), 1 (Placebo) Test for heterogeneity: not applicable Test for overall effect z=1.00

p=0.3

0.1 0.2

0.5

1

IV iron better

Analysis 08.03.

Review:

2

5

10

IV iron worse

Comparison 08 Intravenous iron vs placebo, Outcome 03 Constipation

Treatments for iron deficiency anaemia in pregnancy

Comparison: 08 Intravenous iron vs placebo Outcome: 03 Constipation Study

Australia 1969 Total (95% CI)

Intravenous iron

Placebo

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

1/27

4/27

100.0

0.27 [ 0.04, 1.69 ]

27

27

100.0

0.27 [ 0.04, 1.69 ]

Total events: 1 (Intravenous iron), 4 (Placebo) Test for heterogeneity: not applicable Test for overall effect z=1.40

p=0.2

0.1 0.2

0.5

1

IV iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IV iron worse

38

Analysis 08.04.

Review:

Comparison 08 Intravenous iron vs placebo, Outcome 04 Abdominal cramps

Treatments for iron deficiency anaemia in pregnancy

Comparison: 08 Intravenous iron vs placebo Outcome: 04 Abdominal cramps Study

Intravenous iron

Placebo

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

x Australia 1969

0/27

0/27

0.0

Not estimable

Total (95% CI)

27

27

0.0

Not estimable

Total events: 0 (Intravenous iron), 0 (Placebo) Test for heterogeneity: not applicable Test for overall effect: not applicable

0.1 0.2

0.5

1

IV iron better

Analysis 09.01.

Review:

2

5

10

IV iron worse

Comparison 09 Intravenous iron vs regular oral iron, Outcome 01 Side effects

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 01 Side effects Study

Australia 1969 Total (95% CI)

IV iron

Oral regular iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

3/27

7/24

100.0

0.33 [ 0.08, 1.28 ]

27

24

100.0

0.33 [ 0.08, 1.28 ]

Total events: 3 (IV iron), 7 (Oral regular iron) Test for heterogeneity: not applicable Test for overall effect z=1.61

p=0.1

0.1 0.2

0.5

1

IV iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IV iron worse

39

Analysis 09.02.

Review:

Comparison 09 Intravenous iron vs regular oral iron, Outcome 02 Nausea or vomiting

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 02 Nausea or vomiting Study

IV iron

Oral regular iron

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

Australia 1969

0/27

4/27

56.2

0.12 [ 0.02, 0.90 ]

Singapore 1998

0/50

3/50

43.8

0.13 [ 0.01, 1.28 ]

77

77

100.0

0.12 [ 0.03, 0.56 ]

Total (95% CI)

Total events: 0 (IV iron), 7 (Oral regular iron) Test for heterogeneity chi-square=0.00 df=1 p=0.96 I =0.0% Test for overall effect z=2.70

p=0.007

0.1 0.2

0.5

1

IV iron better

Analysis 09.03.

Review:

2

5

10

IV iron worse

Comparison 09 Intravenous iron vs regular oral iron, Outcome 03 Constipation

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 03 Constipation Study

IV iron

Oral regular iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

Australia 1969

1/27

4/24

28.6

0.24 [ 0.04, 1.48 ]

Singapore 1998

0/50

13/50

71.4

0.10 [ 0.03, 0.33 ]

77

74

100.0

0.13 [ 0.05, 0.35 ]

Total (95% CI)

Total events: 1 (IV iron), 17 (Oral regular iron) Test for heterogeneity chi-square=0.58 df=1 p=0.45 I =0.0% Test for overall effect z=4.07

p=0.00005

0.1 0.2

0.5

1

IV iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IV iron worse

40

Analysis 09.04.

Review:

Comparison 09 Intravenous iron vs regular oral iron, Outcome 04 Abdominal cramps

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 04 Abdominal cramps Study

Australia 1969 Total (95% CI)

IV iron

Oral regular iron

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

0/27

2/24

100.0

0.11 [ 0.01, 1.89 ]

27

24

100.0

0.11 [ 0.01, 1.89 ]

Total events: 0 (IV iron), 2 (Oral regular iron) Test for heterogeneity: not applicable Test for overall effect z=1.52

p=0.1

0.1 0.2

0.5

1

2

IV iron better

Analysis 09.05.

Review:

5

10

IV iron worse

Comparison 09 Intravenous iron vs regular oral iron, Outcome 05 Diarrhoea

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 05 Diarrhoea Study

Singapore 1998 Total (95% CI)

IV iron

Oral regular iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

0/50

3/50

100.0

0.13 [ 0.01, 1.28 ]

50

50

100.0

0.13 [ 0.01, 1.28 ]

Total events: 0 (IV iron), 3 (Oral regular iron) Test for heterogeneity: not applicable Test for overall effect z=1.75

p=0.08

0.1 0.2

0.5

1

IV iron better

Analysis 09.06.

Review:

2

5

10

IV iron worse

Comparison 09 Intravenous iron vs regular oral iron, Outcome 06 Haemoglobin at 36 weeks

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 06 Haemoglobin at 36 weeks Study

Singapore 1998 Total (95% CI)

IV iron

Oral regular iron

N

Mean(SD)

N

Mean(SD)

50

11.00 (0.01)

50

9.90 (0.02)

50

Weighted Mean Difference (Fixed)

Weight

Weighted Mean Difference (Fixed)

95% CI

(%)

95% CI

50

100.0

1.10 [ 1.09, 1.11 ]

100.0

1.10 [ 1.09, 1.11 ]

Test for heterogeneity: not applicable Test for overall effect z=347.85

p<0.00001

-10.0

-5.0

IV iron worse

0

5.0

10.0

IV iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

41

Analysis 09.09.

Review:

Comparison 09 Intravenous iron vs regular oral iron, Outcome 09 Maternal haemoglobin at delivery

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 09 Maternal haemoglobin at delivery Study

Singapore 1998 Total (95% CI)

IV iron

Oral regular iron

N

Mean(SD)

N

Mean(SD)

50

11.80 (0.02)

50

11.20 (0.02)

50

Weighted Mean Difference (Fixed)

Weight

Weighted Mean Difference (Fixed)

95% CI

(%)

95% CI

50

100.0

0.60 [ 0.59, 0.61 ]

100.0

0.60 [ 0.59, 0.61 ]

Test for heterogeneity: not applicable Test for overall effect z=150.00

p<0.00001

-10.0

-5.0

0

IV iron worse

Analysis 09.10.

Review:

5.0

10.0

IV iron better

Comparison 09 Intravenous iron vs regular oral iron, Outcome 10 Maternal haemoglobin at 6 weeks

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 10 Maternal haemoglobin at 6 weeks Study

Singapore 1998 Total (95% CI)

IV iron

Oral regular iron

N

Mean(SD)

N

Mean(SD)

50

12.50 (0.01)

50

11.90 (0.02)

50

Weighted Mean Difference (Fixed)

Weight

Weighted Mean Difference (Fixed)

95% CI

(%)

95% CI

50

100.0

0.60 [ 0.59, 0.61 ]

100.0

0.60 [ 0.59, 0.61 ]

Test for heterogeneity: not applicable Test for overall effect z=189.74

p<0.00001

-10.0

-5.0

IV iron worse

Analysis 09.13.

Review:

0

5.0

10.0

IV iron better

Comparison 09 Intravenous iron vs regular oral iron, Outcome 13 Maternal mortality

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 13 Maternal mortality Study

IV iron

Oral regular iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

x Singapore 1998

0/50

0/50

0.0

Not estimable

Total (95% CI)

50

50

0.0

Not estimable

Total events: 0 (IV iron), 0 (Oral regular iron) Test for heterogeneity: not applicable Test for overall effect: not applicable

0.1 0.2

0.5

IV iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

1

2

5

10

IV iron worse

42

Analysis 09.14.

Review:

Comparison 09 Intravenous iron vs regular oral iron, Outcome 14 Preterm labour

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 14 Preterm labour Study

IV iron

Oral regular iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

x Singapore 1998

0/50

0/50

0.0

Not estimable

Total (95% CI)

50

50

0.0

Not estimable

Total events: 0 (IV iron), 0 (Oral regular iron) Test for heterogeneity: not applicable Test for overall effect: not applicable

0.1 0.2

0.5

1

2

IV iron better

Analysis 09.15.

Review:

5

10

IV iron worse

Comparison 09 Intravenous iron vs regular oral iron, Outcome 15 Caesarean section

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 15 Caesarean section Study

Singapore 1998 Total (95% CI)

IV iron

Oral regular iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

5/50

4/50

100.0

1.27 [ 0.33, 4.98 ]

50

50

100.0

1.27 [ 0.33, 4.98 ]

Total events: 5 (IV iron), 4 (Oral regular iron) Test for heterogeneity: not applicable Test for overall effect z=0.35

p=0.7

0.1 0.2

0.5

1

IV iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IV iron worse

43

Analysis 09.16.

Review:

Comparison 09 Intravenous iron vs regular oral iron, Outcome 16 Operative vaginal delivery

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 16 Operative vaginal delivery Study

Singapore 1998 Total (95% CI)

IV iron

Oral regular iron

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

3/50

2/50

100.0

1.52 [ 0.25, 9.08 ]

50

50

100.0

1.52 [ 0.25, 9.08 ]

Total events: 3 (IV iron), 2 (Oral regular iron) Test for heterogeneity: not applicable Test for overall effect z=0.46

p=0.6

0.1 0.2

0.5

1

IV iron better

Analysis 09.17.

Review:

2

5

10

IV iron worse

Comparison 09 Intravenous iron vs regular oral iron, Outcome 17 Postpartum haemorrhage

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 17 Postpartum haemorrhage Study

Singapore 1998 Total (95% CI)

IV iron

Oral regular iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

6/50

7/50

100.0

0.84 [ 0.26, 2.68 ]

50

50

100.0

0.84 [ 0.26, 2.68 ]

Total events: 6 (IV iron), 7 (Oral regular iron) Test for heterogeneity: not applicable Test for overall effect z=0.30

p=0.8

0.1 0.2

0.5

1

IV iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IV iron worse

44

Analysis 09.18.

Review:

Comparison 09 Intravenous iron vs regular oral iron, Outcome 18 Low birth weight (under 2,500g)

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 18 Low birth weight (under 2,500g) Study

IV iron

Oral regular iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

x Singapore 1998

0/50

0/50

0.0

Not estimable

Total (95% CI)

50

50

0.0

Not estimable

Total events: 0 (IV iron), 0 (Oral regular iron) Test for heterogeneity: not applicable Test for overall effect: not applicable

0.1 0.2

0.5

IV iron better

Analysis 09.19.

Review:

1

2

5

10

IV iron worse

Comparison 09 Intravenous iron vs regular oral iron, Outcome 19 Neonatal birth weight

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 19 Neonatal birth weight Study

Singapore 1998 Total (95% CI)

IV iron

Oral regular iron

N

Mean(SD)

N

Mean(SD)

50

2966.70 (540.90)

50

3086.00 (437.30)

50

Weighted Mean Difference (Fixed)

Weight

Weighted Mean Difference (Fixed)

95% CI

(%)

95% CI

50

100.0

-119.30 [ -312.10, 73.50 ]

100.0

-119.30 [ -312.10, 73.50 ]

Test for heterogeneity: not applicable Test for overall effect z=1.21

p=0.2

-10.0

-5.0

0

IV iron worse

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

5.0

10.0

IV iron better

45

Analysis 09.20.

Review:

Comparison 09 Intravenous iron vs regular oral iron, Outcome 20 Small for gestational age

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 20 Small for gestational age Study

Singapore 1998 Total (95% CI)

IV iron

Oral regular iron

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

8/50

5/50

100.0

1.69 [ 0.53, 5.39 ]

50

50

100.0

1.69 [ 0.53, 5.39 ]

Total events: 8 (IV iron), 5 (Oral regular iron) Test for heterogeneity: not applicable Test for overall effect z=0.89

p=0.4

0.1 0.2

0.5

1

IV iron better

Analysis 09.21.

Review:

2

5

10

IV iron worse

Comparison 09 Intravenous iron vs regular oral iron, Outcome 21 Five minute Apgar score under seven

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 21 Five minute Apgar score under seven Study

Singapore 1998 Total (95% CI)

IV iron

Oral regular iron

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

1/50

1/50

100.0

1.00 [ 0.06, 16.21 ]

50

50

100.0

1.00 [ 0.06, 16.21 ]

Total events: 1 (IV iron), 1 (Oral regular iron) Test for heterogeneity: not applicable Test for overall effect z=0.00

p=1

0.1 0.2

0.5

1

IV iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IV iron worse

46

Analysis 09.22.

Review:

Comparison 09 Intravenous iron vs regular oral iron, Outcome 22 Neonatal mortality

Treatments for iron deficiency anaemia in pregnancy

Comparison: 09 Intravenous iron vs regular oral iron Outcome: 22 Neonatal mortality Study

IV iron

Oral regular iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

x Singapore 1998

0/50

0/50

0.0

Not estimable

Total (95% CI)

50

50

0.0

Not estimable

Total events: 0 (IV iron), 0 (Oral regular iron) Test for heterogeneity: not applicable Test for overall effect: not applicable

0.1 0.2

0.5

1

IV iron better

Analysis 10.01.

Review:

2

5

10

IV iron worse

Comparison 10 Intravenous iron vs controlled release oral iron, Outcome 01 Side effects

Treatments for iron deficiency anaemia in pregnancy

Comparison: 10 Intravenous iron vs controlled release oral iron Outcome: 01 Side effects Study

Australia 1969 Total (95% CI)

IV iron

Control release iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

3/27

7/25

100.0

0.34 [ 0.09, 1.35 ]

27

25

100.0

0.34 [ 0.09, 1.35 ]

Total events: 3 (IV iron), 7 (Control release iron) Test for heterogeneity: not applicable Test for overall effect z=1.53

p=0.1

0.1 0.2

0.5

1

IV iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IV iron worse

47

Analysis 10.02.

Review:

Comparison 10 Intravenous iron vs controlled release oral iron, Outcome 02 Nausea or vomiting

Treatments for iron deficiency anaemia in pregnancy

Comparison: 10 Intravenous iron vs controlled release oral iron Outcome: 02 Nausea or vomiting Study

Australia 1969 Total (95% CI)

IV iron

Oral regular iron

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

0/27

4/25

100.0

0.11 [ 0.01, 0.83 ]

27

25

100.0

0.11 [ 0.01, 0.83 ]

Total events: 0 (IV iron), 4 (Oral regular iron) Test for heterogeneity: not applicable Test for overall effect z=2.14

p=0.03

0.1 0.2

0.5

1

IV iron better

Analysis 10.03.

Review:

2

5

10

IV iron worse

Comparison 10 Intravenous iron vs controlled release oral iron, Outcome 03 Constipation

Treatments for iron deficiency anaemia in pregnancy

Comparison: 10 Intravenous iron vs controlled release oral iron Outcome: 03 Constipation Study

Australia 1969 Total (95% CI)

IV iron

Oral regular iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

1/27

1/25

100.0

0.92 [ 0.06, 15.22 ]

27

25

100.0

0.92 [ 0.06, 15.22 ]

Total events: 1 (IV iron), 1 (Oral regular iron) Test for heterogeneity: not applicable Test for overall effect z=0.05

p=1

0.1 0.2

0.5

1

IV iron better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

IV iron worse

48

Analysis 10.04.

Review:

Comparison 10 Intravenous iron vs controlled release oral iron, Outcome 04 Abdominal cramps

Treatments for iron deficiency anaemia in pregnancy

Comparison: 10 Intravenous iron vs controlled release oral iron Outcome: 04 Abdominal cramps Study

Australia 1969 Total (95% CI)

IV iron

Oral regular iron

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

0/27

1/25

100.0

0.12 [ 0.00, 6.31 ]

27

25

100.0

0.12 [ 0.00, 6.31 ]

Total events: 0 (IV iron), 1 (Oral regular iron) Test for heterogeneity: not applicable Test for overall effect z=1.04

p=0.3

0.1 0.2

0.5

1

2

IV iron better

Analysis 11.01.

Review:

5

10

IV iron worse

Comparison 11 Intravenous iron + hydrocortisone vs intravenous iron, Outcome 01 Tenderness or erythema

Treatments for iron deficiency anaemia in pregnancy

Comparison: 11 Intravenous iron + hydrocortisone vs intravenous iron Outcome: 01 Tenderness or erythema Study

UK 1965 Total (95% CI)

IV iron + hydrocort

IV iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

2/15

0/15

100.0

7.94 [ 0.47, 133.26 ]

15

15

100.0

7.94 [ 0.47, 133.26 ]

Total events: 2 (IV iron + hydrocort), 0 (IV iron) Test for heterogeneity: not applicable Test for overall effect z=1.44

p=0.2

0.1 0.2

0.5

IV iron + hc better

1

2

5

10

IV iron + hc worse

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

49

Analysis 11.02.

Review:

Comparison 11 Intravenous iron + hydrocortisone vs intravenous iron, Outcome 02 Venous thrombosis

Treatments for iron deficiency anaemia in pregnancy

Comparison: 11 Intravenous iron + hydrocortisone vs intravenous iron Outcome: 02 Venous thrombosis Study

UK 1965 Total (95% CI)

IV iron + hydrocort

IV iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

0/15

5/15

100.0

0.10 [ 0.01, 0.65 ]

15

15

100.0

0.10 [ 0.01, 0.65 ]

Total events: 0 (IV iron + hydrocort), 5 (IV iron) Test for heterogeneity: not applicable Test for overall effect z=2.41

p=0.02

0.1 0.2

0.5

1

IV iron + hc better

Analysis 12.01.

Review:

2

5

10

IV iron + hc

worse

Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 01 Allergic reaction during infusion

Treatments for iron deficiency anaemia in pregnancy

Comparison: 12 2/3 dose intravenous iron vs full dose intravenous iron Outcome: 01 Allergic reaction during infusion Study

Tanzania 1988 Total (95% CI)

2/3 dose IV iron

Full dose IV iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

15/309

23/314

100.0

0.65 [ 0.34, 1.25 ]

309

314

100.0

0.65 [ 0.34, 1.25 ]

Total events: 15 (2/3 dose IV iron), 23 (Full dose IV iron) Test for heterogeneity: not applicable Test for overall effect z=1.29

p=0.2

0.1 0.2

0.5

2/3 dose better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

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2

5

10

2/3 dose worse

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Analysis 12.02.

Review:

Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 02 Allergic reaction after infusion

Treatments for iron deficiency anaemia in pregnancy

Comparison: 12 2/3 dose intravenous iron vs full dose intravenous iron Outcome: 02 Allergic reaction after infusion Study

Tanzania 1988 Total (95% CI)

2/3 dose IV iron

Full dose IV iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

47/309

77/314

100.0

0.56 [ 0.38, 0.83 ]

309

314

100.0

0.56 [ 0.38, 0.83 ]

Total events: 47 (2/3 dose IV iron), 77 (Full dose IV iron) Test for heterogeneity: not applicable Test for overall effect z=2.91

p=0.004

0.1 0.2

0.5

1

2/3 dose better

Analysis 12.03.

Review:

2

5

10

2/3 dose worse

Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 03 Life threatening allergic reaction during infusion

Treatments for iron deficiency anaemia in pregnancy

Comparison: 12 2/3 dose intravenous iron vs full dose intravenous iron Outcome: 03 Life threatening allergic reaction during infusion Study

Tanzania 1988 Total (95% CI)

2/3 dose IV iron

Full dose IV iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

5/309

2/314

100.0

2.42 [ 0.54, 10.70 ]

309

314

100.0

2.42 [ 0.54, 10.70 ]

Total events: 5 (2/3 dose IV iron), 2 (Full dose IV iron) Test for heterogeneity: not applicable Test for overall effect z=1.16

p=0.2

0.1 0.2

0.5

2/3 dose better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

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2

5

10

2/3 dose worse

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Analysis 12.04.

Review:

Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 04 Discomfort needing analgesics after infusion

Treatments for iron deficiency anaemia in pregnancy

Comparison: 12 2/3 dose intravenous iron vs full dose intravenous iron Outcome: 04 Discomfort needing analgesics after infusion Study

Tanzania 1988 Total (95% CI)

2/3 dose IV iron

Full dose IV iron

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

15/309

31/314

100.0

0.48 [ 0.26, 0.88 ]

309

314

100.0

0.48 [ 0.26, 0.88 ]

Total events: 15 (2/3 dose IV iron), 31 (Full dose IV iron) Test for heterogeneity: not applicable Test for overall effect z=2.39

p=0.02

0.1 0.2

0.5

1

2/3 dose better

Analysis 12.05.

Review:

2

5

10

2/3 dose worse

Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 05 Immobilised by painful joints

Treatments for iron deficiency anaemia in pregnancy

Comparison: 12 2/3 dose intravenous iron vs full dose intravenous iron Outcome: 05 Immobilised by painful joints Study

Tanzania 1988 Total (95% CI)

2/3 dose IV iron

Full dose IV iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

7/309

9/314

100.0

0.79 [ 0.29, 2.12 ]

309

314

100.0

0.79 [ 0.29, 2.12 ]

Total events: 7 (2/3 dose IV iron), 9 (Full dose IV iron) Test for heterogeneity: not applicable Test for overall effect z=0.47

p=0.6

0.1 0.2

0.5

2/3 dose better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

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2

5

10

2/3 dose worse

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Analysis 12.06.

Review:

Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 06 Non-live births

Treatments for iron deficiency anaemia in pregnancy

Comparison: 12 2/3 dose intravenous iron vs full dose intravenous iron Outcome: 06 Non-live births Study

Tanzania 1988 Total (95% CI)

2/3 dose IV iron

Full dose IV iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

9/248

11/259

100.0

0.85 [ 0.35, 2.08 ]

248

259

100.0

0.85 [ 0.35, 2.08 ]

Total events: 9 (2/3 dose IV iron), 11 (Full dose IV iron) Test for heterogeneity: not applicable Test for overall effect z=0.36

p=0.7

0.1 0.2

0.5

1

2/3 dose better

Analysis 12.07.

Review:

2

5

10

2/3 dose worse

Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 07 Neonatal death

Treatments for iron deficiency anaemia in pregnancy

Comparison: 12 2/3 dose intravenous iron vs full dose intravenous iron Outcome: 07 Neonatal death Study

Tanzania 1988 Total (95% CI)

2/3 dose IV iron

Full dose IV iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

3/248

6/259

100.0

0.53 [ 0.14, 1.98 ]

248

259

100.0

0.53 [ 0.14, 1.98 ]

Total events: 3 (2/3 dose IV iron), 6 (Full dose IV iron) Test for heterogeneity: not applicable Test for overall effect z=0.94

p=0.3

0.1 0.2

0.5

2/3 dose better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

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5

10

2/3 dose worse

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Analysis 12.08.

Review:

Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 08 Stillbirth

Treatments for iron deficiency anaemia in pregnancy

Comparison: 12 2/3 dose intravenous iron vs full dose intravenous iron Outcome: 08 Stillbirth Study

Tanzania 1988 Total (95% CI)

2/3 dose IV iron

Full dose IV iron

Peto Odds Ratio

Weight

n/N

n/N

95% CI

(%)

Peto Odds Ratio 95% CI

6/248

9/259

100.0

0.69 [ 0.25, 1.93 ]

248

259

100.0

0.69 [ 0.25, 1.93 ]

Total events: 6 (2/3 dose IV iron), 9 (Full dose IV iron) Test for heterogeneity: not applicable Test for overall effect z=0.70

p=0.5

0.1 0.2

0.5

1

2/3 dose better

Analysis 12.09.

Review:

2

5

10

2/3 dose worse

Comparison 12 2/3 dose intravenous iron vs full dose intravenous iron, Outcome 09 Spontaneous abortion

Treatments for iron deficiency anaemia in pregnancy

Comparison: 12 2/3 dose intravenous iron vs full dose intravenous iron Outcome: 09 Spontaneous abortion Study

Tanzania 1988 Total (95% CI)

2/3 dose IV iron

Full dose IV iron

Peto Odds Ratio

Weight

Peto Odds Ratio

n/N

n/N

95% CI

(%)

95% CI

3/248

1/259

100.0

2.86 [ 0.40, 20.42 ]

248

259

100.0

2.86 [ 0.40, 20.42 ]

Total events: 3 (2/3 dose IV iron), 1 (Full dose IV iron) Test for heterogeneity: not applicable Test for overall effect z=1.05

p=0.3

0.1 0.2

0.5

2/3 dose better

Treatments for iron deficiency anaemia in pregnancy (Review) Copyright Š 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

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2

5

10

2/3 dose worse

54