Effects and safety of preventive oral iron or iron+folic acid supplementation for women during pregnancy

Abstract

Background: Intake of supplements containing iron or a combination of iron and folic acid by pregnant women may improve maternal health and pregnancy outcomes. Recently, intermittent supplementation regimens have been proposed as alternatives to daily regimens.

Objectives: To assess the effectiveness and safety of daily and intermittent use of iron or iron+folic acid supplements by pregnant women.

Search strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (March 2009) and contacted relevant organisations for the identification of ongoing and unpublished studies.

Selection criteria: All randomised or quasi-randomised trials evaluating the effect of supplementation with iron or iron+folic acid during pregnancy.

Data collection and analysis: We assessed the methodological quality of trials using the standard Cochrane criteria. Two authors independently assessed which trials to include in the review and one author extracted data.

Main results: We included 49 trials, involving 23,200 pregnant women. Overall, the results showed significant heterogeneity across most prespecified outcomes and were analysed assuming random-effects. The trials provided limited information related to clinical maternal and infant outcomes.Overall, daily iron supplementation was associated with increased haemoglobin levels in maternal blood both before and after birth and reduced risk of anaemia at term. These effects did not differ significantly between women receiving intermittent or daily iron or iron+folic acid supplementation. Women who received daily prenatal iron supplementation with or without folic acid were less likely to have iron deficiency at term as defined by current cut-off values than those who received no treatment or placebo. Side effects and haemoconcentration (a haemoglobin level greater than 130 g/L) were more common among women who received daily iron or iron+folic acid supplementation than among those who received no treatment or placebo. The risk of haemoconcentration during the second and third trimester was higher among those on a daily regimen of iron supplementation. The clinical significance of haemoconcentration remains uncertain.

Authors' conclusions: Universal prenatal supplementation with iron or iron+folic acid provided either daily or weekly is effective to prevent anaemia and iron deficiency at term. We found no evidence, however, of the significant reduction in substantive maternal and neonatal adverse clinical outcomes (low birthweight, delayed development, preterm birth, infection, postpartum haemorrhage). Associated side effects and particularly haemoconcentration during pregnancy may suggest the need for revising iron doses and schemes of supplementation during pregnancy and adjust preventive iron supplementation recommendations.