The benefits and harms of oral iron supplementation in non-anaemic pregnant women: A systematic review and meta-analysis.

Objective: Iron deficiency during pregnancy poses a significant risk to both maternal and foetal health. Despite increased iron requirements during pregnancy, current UK NICE guidelines do not give clear advice on antenatal iron supplementation for non-anaemic women. We aimed to assess whether the benefits of routine antenatal supplementation outweigh potential harms for non-anaemic women. Methods: The Cochrane Library, MEDLINE, Embase and clinical trial registries were searched for randomised control trials (RCTs) and observational studies comparing oral iron supplementation with placebo or no supplement in non-anaemic pregnant women. The relevant data were extracted, and the risk of bias for included studies was assessed using the Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale. Where appropriate, meta analysis was conducted using R. Results: 23 eligible studies were identified including 4492 non-anaemic women who were followed through pregnancy. Haemoglobin and ferritin levels were consistently higher in individuals receiving iron compared with control groups, although both findings were associated with a high degree of heterogeneity (I2 = 92% and 87% respectively) and therefore did not warrant a pooled analysis. Iron supplementation was associated with a significant reduction in rate of maternal anaemia (OR = 0.36; 95% CI = 0.22 - 0.61, p<.001; I2 = 54%; moderate certainty, NNT 8). There was no significant effect of intervention on birth weight (MD = 22.97g, 95% CI = -56.27 to 102.22, p = 0.57; I2 = 64%; very low certainty). Of the 18 studies reporting adverse effects, none found a significant influence of supplementation on GI disturbance, caesarean sections or preterm births. Conclusions: Prophylactic iron supplementation reduces the risk of maternal anaemia in pregnancy. Limited evidence was found relating to the harms of supplementation in non-anaemic pregnant women, highlighting the need for further research to inform practice guidelines and support clinical decision making. Registration: The study protocol was registered on the Open Science Framework (DOI 10.17605/OSF.IO/HKZ4C).