Main results
This review includes 27 trials from 15 countries, but only 21 trials (with 5490 women) contributed data to the review. All studies
compared daily versus intermittent iron supplementation. The methodological quality of included studies was mixed and most had
high levels of attrition.The overall assessment of the quality of the evidence for primary infant outcomes was low and for maternal
outcomes very low.
Of the 21 trials contributing data, three studies provided intermittent iron alone, 14 intermittent iron + folic acid and four intermittent
iron plus multiple vitamins and minerals in comparison with the same composition of supplements provided in a daily regimen.
Overall, for women receiving any intermittent iron regimen (with or without other vitamins and minerals) compared with a daily
regimen there was no clear evidence of differences between groups for any infant primary outcomes: low birthweight (average risk ratio
(RR) 0.82; 95% confidence interval (CI) 0.55 to 1.22; participants = 1898; studies = eight; low quality evidence), infant birthweight
(mean difference (MD) 5.13 g; 95% CI -29.46 to 39.72; participants = 1939; studies = nine; low quality evidence), premature birth
(average RR 1.03; 95% CI 0.76 to 1.39; participants = 1177; studies = five; low quality evidence), or neonatal death (average RR 0.49;
95% CI 0.04 to 5.42; participants = 795; studies = one; very low quality). None of the studies reported 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; participants = 676; studies = four; I² = 10%; very low quality). Women receiving intermittent supplementation had
fewer side effects (average RR 0.56; 95% CI 0.37 to 0.84; participants = 1777; studies = 11; I² = 87%; very low quality) and were at
lower risk of having high haemoglobin (Hb) concentrations (greater than 130 g/L) during the second or third trimester of pregnancy
(average RR 0.53; 95% CI 0.38 to 0.74; participants = 2616; studies = 15; I² = 52%; (this was not a primary outcome)) compared with
women receiving daily supplements. There were no significant differences in iron-deficiency anaemia at term between women receiving
intermittent or daily iron + folic acid supplementation (average RR 0.71; 95% CI 0.08 to 6.63; participants = 156; studies = one).
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.
Most of the studies included in the review (14/21 contributing data) compared intermittent oral iron + folic acid supplementation
compared with daily oral iron + folic acid supplementation (4653 women) and findings for this comparison broadly reflect findings
for the main comparison (any intermittent versus any daily regimen).
Three studies with 464 women examined supplementation with intermittent oral iron alone compared with daily oral iron alone.
There were no clear differences between groups for mean birthweight, preterm birth, maternal anaemia or maternal side effects. Other
primary outcomes were not reported.
Four studies with a combined sample size of 412 women compared intermittent oral iron + vitamins and minerals supplementation
with daily oral iron + vitamins and minerals supplementation. Results were not reported for any of the review’s infant primary outcomes.
One study reported fewer maternal side effects in the intermittent iron group, and two studies that more women were anaemic at term
compared with those receiving daily supplementation.
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 results.