Oral Iron Supplementation in Pregnancy: Current Recommendations and Evidence-Based Medicine Suplementação oral de ferro na gravidez: recomendações atuais e medicina baseada na evidência

Duarte, Ana Filipa Moreira; Carneiro, Ana Catarina Simões Viana; Peixoto, Ana Teresa Barbosa Maciel Meira; Montenegro, Daniela Filipa Pereira; Campos, Débora Sofia Carvalho; Alves, Ana Patrícia Ribeiro; Costa, Ana Rita Mota Magalhães; Fino, Andreia Patrícia Machado

doi:10.1055/s-0041-1736144

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Revista Brasileira de Ginecologia e Obstetrícia

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Review Article • Rev. Bras. Ginecol. Obstet. 43 (10) • Oct 2021 • https://doi.org/10.1055/s-0041-1736144 copy

Oral Iron Supplementation in Pregnancy: Current Recommendations and Evidence-Based Medicine Suplementação oral de ferro na gravidez: recomendações atuais e medicina baseada na evidência

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

To review the evidence about universal iron supplementation in pregnancy to prevent maternal anemia.

Methods

Bibliographic research of randomized and controlled clinical trials, meta-analyses, systematic reviews, and clinical guidelines, published between August 2009 and August 2019, using the MeSH terms: iron; therapeutic use; pregnancy; anemia, prevention and control.

Results

We included six clinical guidelines, three meta-analyses and one randomized controlled clinical trial.

Discussion

Most articles point to the improvement of hematological parameters and reduction of maternal anemia risk, with supplementary iron. However, they do not correlate this improvement in pregnant women without previous anemia with the eventual improvement of clinical parameters.

Conclusion

Universal iron supplementation in pregnancy is controversial, so we attribute a SORT C recommendation strength.

Keywords:
iron; dietary supplements; pregnancy; anemia; prenatal care

Reference/Type of study	Findings	LE
Imdad et al. (2012)¹¹11 Imdad A, Bhutta ZA. Routine iron/folate supplementation during pregnancy: effect on maternal anaemia and birth outcomes. Paediatr Perinat Epidemiol. 2012;26(Suppl 1):168-177. Doi: 10.1111/j.1365-3016.2012.01312.x https://doi.org/10.1111/j.1365-3016.2012... MA	• Daily supplementation of iron: ○ 69% reduction in the incidence of anemia at term in the intervention group compared with control (Relative Risk (RR) 0.31; 95% confidence Interval [CI]: 0.22–0.44]); ○ 66% reduction in ferropenic anemia at term (RR 0.44 [95% CI: 0.28–0.68]) compared with no intervention/placebo;• There was no statistically significant difference between intermittent administration of iron/iron-folic acid and daily administration, based on 3 studies. (RR 1.61 [95%CI: 0.82–3.14])	1
Haider et al. (2013)¹²12 Haider BA, Olofin I, Wang M, Spiegelman D, Ezzati M, Fawzi WWNutrition Impact Model Study Group (anaemia) Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis. BMJ. 2013;346:f3443. Doi: 10.1136/bmj.f3443 https://doi.org/10.1136/bmj.f3443... MA	• Daily iron supplementation (effects in the 3^rd trimester and delivery): ○ increased the mean maternal Hb concentration by 4.59 g/L (95%CI: 3.72–5.46) compared with the control group; ○ significantly reduced the risk of anemia (RR 0.50; 95%CI: 0.42–0.59); ○ significantly reduced iron deficiency (RR 0.59, 95%CI: 0.46–0.79) and ferropenic anemia (RR 0.40, 95%CI: 0.26–0.60).• The effects on Hb concentration in the 2^nd trimester were not evaluated by a small number of trials.	2
Peña-Rosas et al. (2015)¹³13 Peña-Rosas JP, De-Regil LM, Garcia-Casal MN, Dowswell T. Daily oral iron supplementation during pregnancy. Cochrane Database Syst Rev. 2015;(07):CD004736. Doi: 10.1002/14651858.CD004736.pub5 https://doi.org/10.1002/14651858.CD00473... SR	• Preventive iron supplementation reduces: ○ maternal anemia at term in 70% (RR 0.30; 95%CI: 0.19–0.46); ○ ferropenic anemia at term (RR 0.33; 95%CI: 0.16–0.69); ○ iron deficit at term by 57% (RR 0.43; 95%CI: 0.27–0.66); ○ Women who received added iron supplement increased risk of hemoconcentration at the end of pregnancy (average RR 3.07; 95%CI: 1.18–8.02)• The implementation of iron supplementation in all pregnant women can lead to heterogeneous results, since the risk of anemia is different between the various populations studied, as well as the level of adherence.	2
Abraha et al. (2019)¹⁴14 Abraha I, Bonacini MI, Montedori A, Di Renzo GC, Angelozzi P, Micheli M, et al. Oral iron-based interventions for prevention of critical outcomes in pregnancy and postnatal care: An overview and update of systematic reviews. J Evid Based Med. 2019;12(02): 155-166. Doi: 10.1111/jebm.12344 https://doi.org/10.1111/jebm.12344... MA	• Any supplement containing iron reduced maternal anemia by 67% (RR 0.32; 95%CI: 0.20–0.49) with significant heterogeneity; ○ the subgroup analysis of studies using doses ≥ 200 mg/day (lower heterogeneity) obtained results consistent with the main analysis (RR 0.15; 95%CI: 0.08–0.28; participants = 360; studies = 5).• Iron-containing supplements reduced the incidence of ferropenic anemia, with no statistically significant difference (RR 0.33; 95%CI: 0.16–0.69);• The supplementation with iron resulted in a higher frequency of side effects compared with the control group (22 versus 18%), but with no statistical difference (RR 1.42; 95%CI: 0.91–2.21).	2
Parisi et al. (2017)¹⁵15 Parisi F, Berti C, Mandò C, Martinelli A, Mazzali C, Cetin I. Effects of different regimens of iron prophylaxis on maternal iron status and pregnancy outcome: a randomized control trial. J Matern Fetal Neonatal Med. 2017;30(15):1787-1792. Doi: 10.1080/14767058.2016.1224841 https://doi.org/10.1080/14767058.2016.12... RCT	• Levels of Hb: ○ Concentration decreased in all groups; less pronounced decrease in liposomal iron groups (positive effect of interaction between time and groups – LI14 p < 0.03 and LI28 p < 0.001); ○ There were no statistically significant differences in Hb values between the control group and the ferrous iron group.• Ferritin levels: ○ statistically significant differences between ferritin concentration between liposomal iron and control groups (LI14 p < 0.02 and LI28 p < 0.001);• High incidence of iron deficit/iron anemia in the control group and with ferrous iron (30%).	2

Reference	Recommendations	SR
U.S. Preventive Services Task Force (2015)²2 Siu ALU.S. Preventive Services Task Force. Screening for iron deficiency anemia and iron supplementation in pregnant women to improve maternal health and birth outcomes: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2015;163(07):529-536. Doi: 10.7326/M15-1707 https://doi.org/10.7326/M15-1707...	Evidence on the effect of universal iron supplementation on asymptomatic pregnant women on maternal clinical parameters is insufficient.More evidence is needed, and the balance between benefits and risks cannot be determined.	C
Direção-Geral da Saúde (2013)⁹9 Direção-Geral da Saúde. Norma No. 030/2013, de 31 de dezembro 2013: abordagem, diagnóstico e tratamento da ferropénia no adulto. Lisboa: Direção-Geral da Saúde; 2013	Supplementation with iron should be individualized, based on clinical-laboratory parameters such as blood count, ferritin and CRP in the first consultation and at 28 weeks.Make the determination of serum ferritin before starting iron, and only prescribe if ferritin < 70 ng/mL.	C
Direção-Geral da Saúde (2015)⁸8 Direção-Geral da Saúde. Serviço Nacional de Saúde. Programa Nacional para a Vigilância da Gravidez de Baixo Risco. Lisboa: Direção-Geral da Saúde; 2015	Start supplementation with 30–60 mg/day of elementary iron between 14 and 16 weeks and 6 days, in the absence of contraindications.	C
National Institute for Health and Care Excellence (2019)¹⁶16 National Institute for Health and Care Excellence. Antenatal care for uncomplicated pregnancies [Internet]. 2019 [cited 2020 Jul 10]. NICE Clinical Guideline (CG62). Available from: https://www.nice.org.uk/guidance/cg62/resources/antenatal-care-for-uncom plicated-pregnancies-pdf-975564597445 https://www.nice.org.uk/guidance/cg62/re...	Iron supplementation should not be offered in a universal way to all pregnant women, since it has no benefits on maternal health and may have unpleasant side effects.	C
Areia et al.¹⁷17 Areia AL, Nogueira-Silva C, Serrano F, Mairos J, Guimarães M, Clode N. Anemia na gravidez e no puerpério: normas de orientação da SPOMMF. Acta Obstet Ginecol Port. 2019;13(02) (2019)	Perform universal screening of anemia in pregnancy, with blood count and ferritin in the preconception and/or 1^st trimester, between 24 and 28 weeks of pregnancy, and in the 3^rd trimester.In women without anemia, supplementation should be initiated in pregnant women with ferritin < 30 ng/mL - daily oral administration of at least 60 mg elemental iron (consider intermittent administration on nonconsecutive days to decrease side effects and increase absorption and adherence).	B
Pavord et al. (2011)⁷7 Pavord S, Daru J, Prasannan N, Robinson S, Stanworth S, Girling JBSH Committee. UK guidelines on the management of iron deficiency in pregnancy. Br J Haematol. 2020;188(06):819-830. Doi: 10.1111/bjh.16221 https://doi.org/10.1111/bjh.16221...	Iron deficiency anemia in pregnancy is common and associated with increased risk of maternal morbidity and mortality.Routine screening with serum ferritin, outside the context of research, to diagnose anemia in pregnancy is not currently recommended.Individual approach, based on the results of anemia screening, as well as identification of women at increased risk.Nonanemic women at risk of iron deficiency should be identified and either started on prophylactic iron empirically (40–80 mg of elemental iron once a day) or have serum ferritin checked first (and iron offered if ferritin < 30 ug/l).	C

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[1] Address for correspondence Ana Filipa Moreira Duarte, Specialist doctor of General and FamilyMedicine, Rua Rodrigo Pereira Pimenta, 60, 4755-558, Vila Seca, Barcelos, Portugal (e-mail: a.filipa.duarte91@gmail.com).