Effect of routine iron supplementation with or without folic acid on anemia during pregnancy

Introduction: Iron deficiency is the most prevalent nutrient deficiency in the world, particularly during pregnancy. According to the literature, anemia, particularly severe anemia, is associated with increased risk of maternal mortality. It also puts mothers at risk of multiple perinatal complications. Numerous studies in the past have evaluated the impact of supplementation with iron and iron-folate but data regarding the efficacy and quality of evidence of these interventions are lacking. This article aims to address the impact of iron with and without folate supplementation on maternal anemia and provides outcome specific quality according to the Child Health Epidemiology Reference Group (CHERG) guidelines. Methods: We conducted a systematic review of published randomized and quasi-randomized trials on PubMed and the Cochrane Library as per the CHERG guidelines. The studies selected employed daily supplementation of iron with or without folate compared with no intervention/placebo, and also compared intermittent supplementation with the daily regimen. The studies were abstracted and graded according to study design, limitations, intervention specifics and outcome effects. CHERG rules were then applied to evaluate the impact of these interventions on iron deficiency anemia during pregnancy. Recommendations were made for the Lives Saved Tool (LiST). Results: After screening 3550 titles, 31 studies were selected for assessment using CHERG criteria. Daily iron supplementation resulted in 73% reduction in the incidence of anemia at term (RR = 0.27; 95% CI: 0.17 - 0.42; random effects model) and 67% reduction in iron deficiency anemia at term (RR = 0.33; 95% CI: 0.16 - 0.69; random model) compared to no intervention/placebo. For this intervention, both these outcomes were graded as 'moderate' quality evidence. Daily supplementation with iron-folate was associated with 73% reduction in anemia at term (RR = 0.27; 95% CI: 0.12 - 0.56; random model) with a quality grade of 'moderate'. The effect of the same intervention on iron deficiency anemia was non-significant (RR = 0.43; 95% CI: 0.17 - 1.09; random model) and was graded as 'low' quality evidence. There was no difference in rates of anemia at term with intermittent iron-folate vs. daily iron-folate supplementation (RR = 1.61; 95% CI: 0.82 - 3.14; random model). Conclusion: Applying the CHERG rules, we recommend a 73% reduction in anemia at term with daily iron (alone) supplementation or iron/folate (combined) vs. no intervention or placebo; for inclusion in the LiST model. Given the paucity of studies of intermittent iron or iron-folate supplementation, especially in developing countries, we recommend further evaluation of this intervention in comparison with daily supplementation regimen.