Oral Iron Supplementation in Pregnancy: Current Recommendations and Evidence-Based Medicine

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TL;DR

This narrative review examines evidence on universal oral iron supplementation in pregnancy to prevent maternal anemia. Meta-analyses show iron reduces anemia at term by 67–70%, but clinical guidelines disagree: some recommend universal supplementation from 14 weeks, others advise individualized prescribing based on ferritin levels, and NICE recommends against universal use due to lack of maternal benefit and side effects. The authors conclude that prophylactic iron should not be given universally to asymptomatic pregnant women (SORT C recommendation), citing inconsistent evidence linking improved lab parameters to clinical outcomes.

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**Background:** Gestational anemia is the most common health problem in pregnancy, with global prevalence estimated at 38.2% (26% in Europe, 48.7% in Southeast Asia, 46.3% in Africa). In the USA, iron deficit affects 18.6% of pregnant women, with 16.2% having anemia. In Portugal, the EMPIRE study reported 54.2% prevalence. Ferropenic anemia is associated with increased maternal morbidity including infection, peripartum transfusion, pre-eclampsia, placental abruption, and maternal death. There is inconsistency between Portuguese clinical guidelines: the National Low-Risk Pregnancy Surveillance Program recommends universal iron from 14 weeks, while the DGS guideline on ferropenia recommends serum ferritin testing before prescribing. This review examines evidence on universal oral iron supplementation to prevent maternal anemia.

**Methods:** A bibliographic survey was conducted in August 2019 across PubMed, National Guideline Clearinghouse, Guidelines Finder, Canadian Medical Association Practice Guidelines Infobase, The Cochrane Library, Evidence Based Medicine Online, SciELO, and DGS databases. Search terms included 'iron', 'therapeutic use', 'pregnancy', 'anemia', and 'prevention and control'. Inclusion criteria: studies on asymptomatic pregnant women without established anemia evaluating prevention of maternal anemia through oral iron versus no supplement. Exclusion criteria: articles on already anemic or ferropenic women, twin pregnancies, major comorbidities, non-oral iron, or iron combined with other compounds without matched controls. Level of evidence was graded using the American Family Physician SORT scale (levels 1–3, strengths A–C).

**Key Results:** From 704 initial articles, 11 were included: 6 clinical guidelines, 3 meta-analyses, 1 systematic review, and 1 RCT. The meta-analysis by Imdad et al. (2012) found daily iron reduced anemia at term by 69% (RR 0.31; 95%CI 0.22–0.44) and ferropenic anemia by 66% (RR 0.44; 95%CI 0.28–0.68). Haider et al. (2013) included 48 RCTs (n=17,793) and 44 cohorts (n=1,851,682), finding daily iron increased mean Hb by 4.59 g/L (95%CI 3.72–5.46), reduced anemia risk by 50% (RR 0.50; 95%CI 0.42–0.59), iron deficiency by 41% (RR 0.59; 95%CI 0.46–0.79), and ferropenic anemia by 60% (RR 0.40; 95%CI 0.26–0.60). Peña-Rosas et al. (2015) (Cochrane review, 44 studies, n=43,274) reported 70% reduction in maternal anemia at term (RR 0.30; 95%CI 0.19–0.46), ferropenic anemia (RR 0.33; 95%CI 0.16–0.69), and iron deficit by 57% (RR 0.43; 95%CI 0.27–0.66), but also increased risk of hemoconcentration (RR 3.07; 95%CI 1.18–8.02). Abraha et al. (2019) found any iron-containing supplement reduced anemia by 67% (RR 0.32; 95%CI 0.20–0.49), with subgroup analysis of doses ≥200 mg/day showing RR 0.15 (95%CI 0.08–0.28). Side effects were higher with iron (22% vs 18%) but not statistically significant (RR 1.42; 95%CI 0.91–2.21). The RCT by Parisi et al. (2017) (n=80) compared ferrous iron and liposomal iron versus placebo, finding liposomal iron groups had less pronounced Hb decline (LI14 p<0.03, LI28 p<0.001) and significantly higher ferritin (LI14 p<0.02, LI28 p<0.001), while 30% of the control and ferrous iron groups developed iron deficit or anemia. Clinical guidelines varied: USPSTF (2015) found insufficient evidence for universal supplementation; DGS (2013) recommended individualized prescribing if ferritin <70 ng/mL; DGS (2015) recommended universal 30–60 mg/day from 14–16 weeks; NICE (2019) recommended against universal iron; SPOMMF (2019) recommended screening and supplementation if ferritin <30 ng/mL; British Committee for Standards in Haematology (2011/2019) recommended identifying at-risk nonanemic women for empirical prophylaxis (40–80 mg/day) or ferritin testing.

**Clinical Implications:** The authors conclude that prophylactic iron supplementation in pregnancy is controversial and should not be performed universally in asymptomatic pregnant women (SORT C). They note that existing Portuguese DGS guidelines are inconsistent and need updating, particularly the 70 ng/mL ferritin cutoff which differs from the 30 ng/mL cutoff in the source guideline. High-quality RCTs with homogeneous methodologies are needed to correlate improved laboratory parameters with clinical outcomes. The heterogeneity in anemia prevalence across populations and in study designs limits consensus on universal supplementation.