29 August 2021
WHO recommendation on daily oral iron and folic acid supplementation
Daily oral iron and folic acid supplementation with 30 mg to 60 mg of elemental iron and 400 g (0.4 mg) of folic acid is recommended for pregnant women to prevent maternal anaemia, puerperal sepsis, low birth weight, and preterm birth.
First published: November 2016
Updated: No update planned
Assessed as up-to-date: November 2016
Anaemia is associated with iron, folate and vitamin A deficiencies. It is estimated to affect 38.2% of pregnant women globally, with the highest prevalence in the WHO regions of South-East Asia (48.7%) and Africa (46.3%), medium prevalence in the Eastern Mediterranean Region (38.9%) and the lowest prevalence in the WHO regions of the Western Pacific (24.3%), the Americas (24.9%) and Europe (25.8%) (7).
Major contributory factors to anaemia include parasitic infections such as malaria, hookworm and schistosomiasis, in areas where these infections are endemic. In addition, chronic infections such as tuberculosis (TB) and HIV, and haemoglobinopathies such as sickle-cell disease, contribute to the prevalence of anaemia. It is estimated that 0.8 million pregnant women globally have severe anaemia (defined as a blood haemoglobin concentration < 70 g/L) (7). In pregnancy, severe anaemia is associated with an increased risk of maternal and infant mortality (8). It is estimated that about half of the anaemia found in pregnant women is amenable to iron supplementation (7); however, this may be quite variable and is likely to be much lower in malaria-endemic areas. In addition to causing anaemia, iron deficiency adversely affects the use of energy sources by muscles and, thus, physical capacity and work performance, and also adversely affects immune status and morbidity from infections (9). Folate (vitamin B9) deficiency, in addition to anaemia it is also linked to fetal neural tube defects (10). Vitamin A deficiency affects about 19 million pregnant women, mostly in Africa and South-East Asia, causing night blindness (11).
The ANC recommendations are intended to inform the development of relevant health-care policies and clinical protocols. These recommendations were developed in accordance with the methods described in the WHO handbook for guideline development (12). In summary, the process included: identification of priority questions and outcomes, retrieval of evidence, assessment and synthesis of the evidence, formulation of recommendations, and planning for the implementation, dissemination, impact evaluation and updating of the guideline.
The quality of the scientific evidence underpinning the recommendations was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) (13) and Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) (14) approaches, for quantitative and qualitative evidence, respectively. Up-to-date systematic reviews were used to prepare evidence profiles for priority questions. The DECIDE (Developing and Evaluating Communication Strategies to support Informed Decisions and Practice based on Evidence) (15) framework, an evidence-to-decision tool that includes intervention effects, values, resources, equity, acceptability and feasibility criteria, was used to guide the formulation and approval of recommendations by the Guideline Development Group (GDG) – an international group of experts assembled for the purpose of developing this guideline – at three Technical Consultations between October 2015 and March 2016.
To ensure that each recommendation is correctly understood and applied in practice, the context of all context-specific recommendations is clearly stated within each recommendation, and the contributing experts provided additional remarks where needed.
In accordance with WHO guideline development standards, these recommendations will be reviewed and updated following the identification of new evidence, with major reviews and updates at least every five years.
Further information on procedures for developing this recommendation are available here.
For this recommendation, we aimed to answer the following question:
For pregnant women (P), does daily iron supplementation (I) (with or without folic acid) compared with no iron supplementation or placebo (C), improve maternal and perinatal outcomes (O)?
The evidence on the effects of daily iron and/or folic acid was derived from a Cochrane review of 61 trials conducted in low-, middle- and high-income countries (16). Twenty-three trials were conducted in countries with some malaria risk, of which two reported malaria outcomes. Overall, 44 trials involving 43274 women contributed data to the review’s meta-analyses. The trials compared daily oral iron supplementation, with or without folic acid or other vitamin and mineral supplements, with various control groups (folic acid only, placebo, no intervention, other vitamin and mineral supplements without iron or folic acid). Most of the evidence was derived from studies comparing iron supplementation with no iron supplementation. In most trials, women began taking supplements before 20 weeks of gestation and continued taking supplements until delivery. The most commonly used dose of elemental iron was 60 mg daily (range: 30–240 mg) and that of folic acid was 400 µg daily.
Anaemia was reported in many different ways and at different time points during pregnancy and the puerperium. Low-certainty evidence shows that daily iron supplementation may reduce the risk of anaemia at term (defined as blood Hb concentration 130 g/L at 34 weeks of gestation or later) (8 trials, 2156 women; RR: 3.07, 95% CI: 1.18–8.02). Regarding maternal morbidity, moderate-certainty evidence shows that daily iron supplementation probably reduces the risk of maternal puerperal infections (4 trials, 4374 women; RR: 0.68, 95% CI: 0.5–0.92).
Low-certainty evidence shows that daily iron supplementation may have little or no effect on pre-eclampsia (4 trials, 1704 women; RR: 1.63, 95% CI: 0.87–3.07) and antepartum haemorrhage (2 trials, 1157 women; RR: 1.48, 95% CI: 0.51–4.31), and moderate-certainty evidence shows that it probably has little or no effect on postpartum haemorrhage (4 trials, 1488 women; RR: 0.93, 95% CI: 0.59–1.49). Evidence on other morbidity outcomes, including placental abruption and blood transfusions, is of very low certainty.
Low-certainty evidence shows that daily iron supplementation may have little or no effect on maternal mortality (2 trials, 12 560 women; RR: 0.33, 95% CI: 0.01–8.19). Women’s satisfaction was evaluated in one small trial (49 women), which found little difference between daily iron and control groups.
Side-effects: Moderate-certainty evidence indicates that daily iron supplementation probably has little or no effect on the risk of experiencing any side-effect (11 trials, 2425 women; RR: 1.29, 95% CI: 0.83–2.02), and that it may have little or no effect on constipation (4 trials, 1495 women; RR: 0.95, 95% CI: 0.62–1.43), heartburn (3 trials, 1323 women; RR: 1.19, 95% CI: 0.86–1.66) and vomiting (4 trials, 1392 women; RR: 0.88, 95% CI: 0.59–1.30). Evidence that daily iron has little or no effect on nausea is of low certainty (4 trials, 1377 women; RR: 1.21, 95% CI: 0.72–2.03). High-certainty evidence shows that diarrhoea is less common with daily iron supplements (3 trials, 1088 women; RR: 0.55, 95% CI: 0.32–0.93).
Fetal and neonatal outcomes
Low-certainty evidence shows that daily iron may reduce the risk of low-birth-weight neonates (< 2500 g) (11 trials, 17 613 neonates; RR: 0.84, 95% CI: 0.69–1.03). High-certainty evidence shows that it does not reduce the risk of preterm birth before 37 weeks of gestation (13 trials, 19 286 women; RR: 0.93, 95% CI: 0.84–1.03), but it does reduce the risk of very preterm birth (i.e. less than 34 weeks of gestation) (5 trials, 3749 women; RR: 0.51, 95% CI: 0.29–0.91).
Low-certainty evidence suggests that daily iron may have little or no effect on congenital anomalies (4 trials, 14 636 neonates; RR: 0.88, 95% CI: 0.58–1.33).
Moderate-certainty evidence indicates that daily iron probably has little or no effect on neonatal deaths (4 trials, 16 603 neonates; RR: 0.91, 95% CI: 0.71–1.18).
Neonatal infections and SGA were not reviewed as outcomes.
Evidence from subgroups tended to be consistent with the overall findings for the main outcomes.
Daily iron and folic acid supplements are relatively low cost, at less than 1 United States dollar (US$ 1) per pregnant woman (17).
Iron deficiency and parasitic infections are more common in LMICs and disadvantaged populations. Poor, rural and least-educated populations also experience the highest maternal, infant and child mortality (18). Increasing coverage of effective nutritional interventions to prevent anaemia, particularly among disadvantaged populations, might help to address maternal and newborn health inequalities.
Qualitative evidence suggests that the availability of iron supplements may actively encourage women to engage with ANC providers (low confidence in the evidence) (19). However, where there are additional costs associated with supplementation or where the supplements may be unavailable (because of resource constraints) women are less likely to engage with ANC services (high confidence in the evidence). Lower doses of iron may be associated with fewer side-effects and therefore may be more acceptable to women than higher doses.
Qualitative evidence about the views of health-care providers suggests that resource constraints, both in terms of the availability of the supplements and the lack of suitably trained staff to deliver them, may limit implementation (high confidence in the evidence) (20).
Further information and considerations related to this recommendation can be found in the WHO guidelines, available at:
The GDG identified these priority questions related to this recommendation
WHO recommendations on antenatal care for a positive pregnancy experience
Citation: WHO Reproductive Health Library. WHO recommendation on daily oral iron and folic acid supplementation (November 2016). The WHO Reproductive Health Library; Geneva: World Health Organization.
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