Treatment for women with iron deficiency anaemia after childbirth

Anaemia is a condition where the blood contains less than normal haemoglobin (low blood count), as shown in blood tests. Haemoglobin is the molecule within red blood cells that requires iron to carry oxygen. Insufficient iron intake/uptake and iron loss (bleeding) can cause iron deficiency anaemia. Anaemia symptoms include tiredness, shortness of breath and dizziness. Women may bleed severely at childbirth and many pregnant women already have anaemia, which can worsen as a result of bleeding. Severe anaemia can be linked to maternal deaths. Iron deficiency anaemia after childbirth is more likely to occur in low-income countries.

Treatment for iron deficiency anaemia includes iron tablets or a solution injected into a vein (intravenously). Another option is to restore red blood cells through transfusion with blood from a blood donor or to boost red blood cell formation with erythropoietin. It is important to investigate if one treatment is better than another in relieving anaemia symptoms, and whether the treatment options are safe.

We included 22 randomised controlled studies with 2858 women and performed 13 comparisons, many of which were based on few studies involving small numbers of women. The overall quality of evidence was low. Most trials were conducted in high-income countries.

Ten studies, including 1553 women, compared intravenous iron with oral iron. Only one study showed a temporary positive effect on fatigue for intravenous iron. Other anaemia symptoms were not reported. One woman died from heart complications in the intravenous group. Only two studies reported on maternal deaths. Allergic reactions occurred in three women, and heart complications in two women in the intravenous group. Gastrointestinal symptoms were frequent in the oral group and caused some participants to abandon treatment.

One study compared red blood cell transfusion with no transfusion. Some (but not all) fatigue scores temporarily improved in the transfused women. Maternal mortality was not reported.

When comparing oral iron to placebo (three studies), anaemia symptoms were not reported. It remains unknown whether benefits of oral iron outweigh documented gastrointestinal harms.

Other treatment options were compared in other studies, which did not investigate fatigue.

Very few studies reported on relief of anaemia symptoms, although this is perhaps the most important purpose of treatment.

The body of evidence did not allow us to fully evaluate the efficacy of the treatments on iron deficiency anaemia after childbirth and further research is needed.

Authors' conclusions: 

The body of evidence did not allow us to reach a clear conclusion regarding the efficacy of the interventions on postpartum iron deficiency anaemia. The quality of evidence was low.

Clinical outcomes were rarely reported. Laboratory values may not be reliable indicators for efficacy, as they do not always correlate with clinical treatment effects. It remains unclear which treatment modality is most effective in alleviating symptoms of postpartum anaemia.

Intravenous iron was superior regarding gastrointestinal harms, however anaphylaxis and cardiac events occurred and more data are needed to establish whether this was caused by intravenous iron.

The clinical significance of some temporarily improved fatigue scores in women treated with blood transfusion is uncertain and this modest effect should be balanced against known risks, e.g. maternal mortality (not reported) and maternal immunological sensitisation, which can potentially harm future pregnancies.

When comparing oral iron to placebo it remains unknown whether efficacy (relief of anaemia symptoms) outweighs the documented gastrointestinal harms.

We could not draw conclusions regarding erythropoietin treatment due to lack of evidence.

Further research should evaluate treatment effect through clinical outcomes, i.e. presence and severity of anaemia symptoms balanced against harms, i.e. survival and severe morbidity.

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Background: 

Postpartum iron deficiency anaemia is caused by bleeding or inadequate dietary iron intake/uptake. This condition is defined by iron deficiency accompanied by a lower than normal blood haemoglobin concentration, although this can be affected by factors other than anaemia and must be interpreted in the light of any concurrent symptoms. Symptoms include fatigue, breathlessness, and dizziness. Treatment options include oral or intravenous iron, erythropoietin which stimulates red blood cell production, and substitution by red blood cell transfusion.

Objectives: 

To assess the efficacy and harms of the available treatment modalities for women with postpartum iron deficiency anaemia.

Search strategy: 

The Cochrane Pregnancy and Childbirth Group’s Trials Register (9 April 2015); the WHO International Clinical Trials Registry Portal (ICTRP), and the Latin-American and Caribbean Health Sciences Literature database (LILACS) (8 April 2015) and reference lists of retrieved studies.

Selection criteria: 

We included published, unpublished and ongoing randomised controlled trials that compared a treatment for postpartum iron deficiency anaemia with placebo, no treatment, or another treatment for postpartum iron deficiency anaemia, including trials described in abstracts only. Cluster-randomised trials were eligible for inclusion. We included both open-label trials and blinded trials, regardless of who was blinded. The participants were women with a postpartum haemoglobin of 120 g per litre (g/L) or less, for which treatment was initiated within six weeks after childbirth.

Non-randomised trials, quasi-randomised trials and trials using a cross-over design were excluded.

Data collection and analysis: 

Two review authors independently assessed studies for inclusion, quality, and extracted data. We contacted study authors and pharmaceutical companies for additional information.

Main results: 

We included 22 randomised controlled trials (2858 women), most of which had high risk of bias in several domains. We performed 13 comparisons. Many comparisons are based on a small number of studies with small sample sizes. No analysis of our primary outcomes contained more than two studies.

Intravenous iron was compared to oral iron in 10 studies (1553 women). Fatigue was reported in two studies and improved significantly favouring the intravenously treated group in one of the studies. Other anaemia symptoms were not reported. One woman died from cardiomyopathy (risk ratio (RR) 2.95; 95% confidence interval (CI) 0.12 to 71.96; two studies; one event; 374 women; low quality evidence). One woman developed arrhythmia. Both cardiac complications occurred in the intravenously treated group. Allergic reactions occurred in three women treated with intravenous iron, not statistically significant (average RR 2.78; 95% CI 0.31 to 24.92; eight studies; 1454 women; I² = 0%; low quality evidence). Gastrointestinal events were less frequent in the intravenously treated group (average RR 0.31; 95% CI 0.20 to 0.47; eight studies; 169 events; 1307 women; I² = 0%; very low quality evidence).

One study evaluated red blood cell transfusion versus non-intervention. General fatigue improved significantly more in the transfusion group at three days (MD -0.80; 95% CI -1.53 to -0.07; women 388; low quality evidence), but no difference between groups was seen at six weeks. Maternal mortality was not reported.

The remaining comparisons evaluated oral iron (with or without other food substances) versus placebo (three studies), intravenous iron with oral iron versus oral iron (two studies) and erythropoietin (alone or combined with iron) versus placebo or iron (seven studies). These studies did not investigate fatigue. Maternal mortality was rarely reported.

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