Iron supplementation alone or in combination with folic acid has been associated with the well being of the mother and fetus. It leads to a significant reduction in anemia incidence during pregnancy and, thus, plays a vital role in reducing maternal morbidity and mortality. The results of our review were consistent with those of an earlier Cochrane review by Pena Rosas and Viteri [2
] that also showed a significant reduction in incidence of anemia and iron deficiency anemia at term with daily iron supplementation and that of anemia at term due to daily iron-folate supplementation versus no intervention/placebo.
The pooled analysis of effect of daily iron supplementation vs. control had a high heterogeneity (fig ). The most likely explanation of this substantial statistical heterogeneity (I2
=73 %) is the variable effect size of the studies which in turn depend on the baseline anemia status of the study population. An important observation to make is that the direction effect in all the studies was in the same direction. We can expect that biologic effect of iron supplementation would differ based on prevalence of anemia in the study population. To further elaborate on this observation, we conducted a post hoc subgroup analysis based on baseline anemia status of the study population (data not shown). There were seven studies that included only non-anemic pregnant women based on laboratory evidence of absence of anemia (hemoglobin < 110 g/L) [21
] and in other seven studies, population was that of mixed status [17
]. Pooled estimates for non-anemic women were less heterogeneous (I2
=47%) and size of summary estimate was less prominent (RR 0.31, 95 % CI 0.19-0.52) compared to that of mixed population that had more heterogeneous (I2
=83%) and more prominent results (RR 0.22, 95 % CI 0.11-0.47). This shows a strong biologic effect in favor of the intervention and also indicates that effect of Iron supplementation would depend on degree of baseline anemia in the study population.
CHERG rules were applied to the collective outcomes of anemia for recommendation of iron deficiency anemia into the LiST model. Daily supplementation with iron led to 73% reduction in incidence of anemia at term as compared to no supplementation. This intervention had a ‘moderate’ quality evidence owing to some limitations in included studies like unclear [17
] or inadequate sequence generation [19
], and high loss to follow up [17
]. Another limitation was that all the studies in the pooled analysis were not conducted in developing countries. In any case, based on strong biologic plausibility and consistent direction of effect across the studies, we recommend a 73 % reduction in anemia at term with iron supplementation during pregnancy, for inclusion in the LiST model. Daily supplementation with iron and folate led to 73% reduction in incidence of anemia at term when compared with no supplementation. We recommend this estimate for reduction in anemia at term for inclusion in the LiST model. The quality of evidence regarding this intervention had to be down-graded from ‘high’ to moderate due to some limitations like high loss to follow up [17
] and unclear sequence generation [21
] and also the fact that all the studies were not conducted in developing countries.
Our results show that there was not much difference in effect between iron alone and iron-folate combined. The effect sizes were similar for both the analyses but CIs were wider for that of iron/folate, mainly due to less number of studies in the pooled analysis. This shows that we can expect a similar biological effect when the iron is supplemented alone or in combination with folate. We did a subgroup for developing and developed countries. There were not sufficient studies from developing countries for all the analyses. An important observation to make in figure is that even though there were two studies from developing countries, the results were very consistent (I2
=0%). Even though there are not a lot of randomized trials conducted in developing countries but we can suggest that iron supplementation would be much effective in developing world by looking at biological plausibility of the intervention. The populations that are most at risk for iron deficiency and IDA are young children and women of reproductive age, especially during pregnancy. The global estimates on prevalence of anemia showed that more than half the pregnant women and young children are anemic in Southeast Asia, West Pacific and Africa [48
]. This shows that amount of effect would be substantially high in developing countries however more efficacy trials are required to determine the conduct of the intervention.
Weekly iron and folic acid supplementation (WIFS) is a relatively new phenomenon, and there is very little data at the moment comparing weekly supplementation with daily dosage. Weekly iron and folic acid supplementation, in synchrony with the turnover of mucosal cells, may be a promising substitute for daily iron supplementation and has been proposed as a more efficient preventive approach in public health programs [49
]. The WHO says that WIFS should be considered a strategy for prevention of iron deficiency in population groups where the prevalence of anemia is above 20% among women of reproductive age and mass fortification programs of staple foods with iron and folic acid are unlikely to be implemented within 1-2 years. However, conclusive data regarding its efficacy as compared to the daily regimen are not yet available. Weekly dosage may have benefits of reduced side effects and increased compliance, but more field randomized controlled trials are needed to establish the efficacy of weekly supplementation compared to daily regimen.