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).

Key Points What is this research focused on exploring, validating, or solving?

Antenatal iron supplementation is known to benefit pregnant women with iron deficiency anaemia, resulting in improved maternal and foetal outcomes. We explored whether these beneficial effects extend to non-anaemic pregnant women and whether they outweigh potential harms of supplementation.

What conclusions did this research draw through design, method, and analysis?

We have shown that supplementation of non-anaemic women helps prevent maternal anaemia and increases maternal haemoglobin. We have also identified a significant paucity in available evidence surrounding side effects of iron supplementation.

What is the value, meaning and impact of your research? Is there any followup study based on this research?

By clarifying the benefits of supplementation, we hope to assist decision making in primary care. This is particularly relevant given the current discrepancies in international guidelines. Our findings strengthen the evidence base in favour of universal supplementation, but focused research into side effects is still required to better qualify risk.

The authors have declared no competing interest.

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This study did not receive any funding

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