Anaemia is a frequent condition during pregnancy, particularly among women from developing countries who have insufficient iron intake to meet increased iron needs of both the mother and the fetus.Traditionally, gestational anaemia has been prevented with the provision of daily iron supplements throughout pregnancy, but adherence to this regimen due to side effects, interrupted supply of the supplements, and concerns about safety among women with an adequate iron intake, have limited the use of this intervention. Intermittent (i.e. one, two or three times a week on non-consecutive days) supplementation with iron alone or in combination with folic acid or other vitamins and minerals has recently been proposed as an alternative to daily supplementation.
To assess the benefits and harms of intermittent supplementation with iron alone or in combination with folic acid or other vitamins and minerals to pregnant women on neonatal and pregnancy outcomes.
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (23 March 2012). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) for ongoing studies and contacted relevant organisations for the identification of ongoing and unpublished studies (23 March 2012).
Randomised or quasi-randomised trials.
Data collection and analysis
We assessed the methodological quality of trials using standard Cochrane criteria. Two review authors independently assessed trial eligibility, extracted data and conducted checks for accuracy.
This review includes 21 trials from 13 different countries, but only 18 trials (with 4072 women) reported on our outcomes of interest and contributed data to the review. All of these studies compared daily versus intermittent iron supplementation.
Three studies provided iron alone, 12 iron+folic acid and three more iron plus multiple vitamins and minerals. Their methodological quality was mixed and most had high levels of attrition. Overall, there was no clear evidence of differences between groups for infant primary outcomes: low birthweight (average risk ratio (RR) 0.96; 95% confidence interval (CI) 0.61 to 1.52, seven studies), infant birthweight (mean difference MD -8.62 g; 95% CI -52.76 g to 35.52 g, eight studies), premature birth (average RR 1.82; 95% CI 0.75 to 4.40, four studies). None of the studies reported neonatal deaths or congenital anomalies.
For maternal outcomes, there was no clear evidence of differences between groups for anaemia at term (average RR 1.22; 95% CI 0.84 to 1.80, four studies) and women receiving intermittent supplementation had less side effects (average RR 0.56; 95% CI 0.37 to 0.84, 11 studies) than those receiving daily supplements. Women receiving intermittent supplements were also at lower risk of having high haemoglobin (Hb) concentrations (greater than 130 g/L) during the second or third trimester of pregnancy (average RR 0.48; 95% CI 0.35 to 0.67, 13 studies). There were no significant differences in iron-deficiency anaemia between women receiving intermittent or daily iron+folic acid supplementation (average RR 0.71; 95% CI 0.08 to 6.63, 1 study). There were no maternal deaths (six studies) or women with severe anaemia in pregnancy (six studies). None of the studies reported on iron deficiency at term or infections during pregnancy.
Where sufficient data were available for primary outcomes, we set up subgroups to look for possible differences between studies in terms of earlier or later supplementation; women’s anaemia status at the start of supplementation; higher and lower weekly doses of iron; and the malarial status of the region in which the trials were conducted. There was no clear effect of these variables on the results of the review.
The present systematic review is the most comprehensive summary of the evidence assessing the benefits and harms of intermittent iron supplementation regimens in pregnant women on haematological and pregnancy outcomes. The findings suggest that intermittent iron+folic acid regimens produce similar maternal and infant outcomes at birth as daily supplementation but are associated with fewer side effects. Women receiving daily supplements had increased risk of developing high levels of Hb in mid and late pregnancy but were less likely to present mild anaemia near term. Although the evidence is limited and the quality of the trials was low or very low, intermittent may be a feasible alternative to daily iron supplementation among those pregnant women who are not anaemic and have adequate antenatal care.
Plain language summary
Intermittent regimens of iron supplementation during pregnancy
Anaemia is a frequent condition during pregnancy, particularly among women from developing countries who have insufficient iron intake to meet increased iron needs. Traditionally, pregnancy anaemia has been prevented with the provision of daily iron supplements, however, it has recently been proposed that if women take supplements less often, such as once or twice weekly rather than daily, this might reduce side effects and increase acceptance and adherence to supplementation. In this review we assess the benefits and harms of intermittent (i.e. one, two or three times a week on non-consecutive days) oral supplementation with iron or iron+folic acid or iron+vitamins and minerals for pregnant women.
We included 21 randomised controlled trials, but only 18 trials involving 4072 women, had information on the outcomes we evaluated. Three studies looked at intermittent iron alone versus daily iron alone; there did not appear to be differences in the effects of two types of regimens when women were followed up.The other studies included in the review compared intermittent iron+folic acid versus daily iron+folic acid. Two of these studies looked at intermittent versus daily iron+folic acid in women who were also advised to take daily calcium supplements.There was no clear evidence of differences between groups for most of the outcomes we examined including infant birthweight, premature birth, perinatal death, and anaemia, haemoglobin concentration and iron deficiency in women at the end of pregnancy. However, women receiving intermittent rather than daily iron supplements were less likely to report side effects (such as constipation and nausea). In addition, intermittent supplementation appeared to decrease the number of women with high haemoglobin concentrations during mid and late pregnancy compared with daily regimens. High haemoglobin concentrations may be harmful as they may be associated with an increased risk of having a premature birth and low birthweight baby. There were no other clear differences between groups for other outcomes examined.
Source: Cochrane Library.