Iron supplementation used during pregnancy alone or in combination with folic acid supplementation may reduce maternal anaemia by 70% and iron deficiency at term by 57%.
Photo by: Stanislas Fradelizi
Why is iron supplementation during prenancy important?
- Anaemia in pregnant women is common, affecting over 38% of women globally. Iron deficiency, acute and chronic infections, deficiencies of other vitamins, and genetics are some causes for anaemia. Iron supplementation helps cover iron intake requirements and is recommended for pregnant women to meet their daily iron needs. Folic acid supplementation, an essential B-vitamin, is often used in combination with iron supplementation for pregnant women to meet their daily nutrient requirements.
Do iron supplements work for women?
- Iron supplementation alone or in combination with folic acid used during pregnancy may reduce maternal anaemia by 70% and iron deficiency at term by 57%, however, it may increase the risk of infection.
- It is uncertain whether iron supplementation alone or in combination with folic acid reduces maternal death, adverse effects, and severe anaemia during the second and third trimester.
Equity: Do iron supplements work in the disadvantaged?
- Eleven studies of the included studies were conducted in low- or middle-income countries. However, the benefits of iron supplementation would likely be similar in other countries.
- Twenty-three studies were conducted in countries that are considered malaria endemic areas. Two studies reported placental malaria, however, there is no evidence that suggests iron supplementation increases this outcome.
- The included studies assess non-anaemic and mild or moderately anaemic women. Evidence is unclear for individuals with severe anaemia.
Intervention delivery
- All studies assessed daily or weekly oral supplementation (ex. tablets, capsules) containing iron, iron and folic acid, or iron and other vitamins/minerals.
- Most dosages ranged from 9 mg to 900 mg of elemental iron for the duration of the participant's pregnancy.
- One trial reported a daily dose of 0.6 g ferrous sulphate.
- One trial reported a daily dose of 1 g iron salt.
- Most dosages of folic acid ranged from 10 µg to 5000 µg used in combination with iron supplementation for the duration of the participant's pregnancy.
Population and setting
- The 61 included studies took place in 30 countries: Australia, Belgium, Canada, China, Denmark, Ecuador, Finland, France, Gambia, Hong Kong, Indonesia, Iran, Ireland, Italy, Jamaica, Myanmar, Nepal, Netherlands, Niger, Nigeria, Norway, Philippines, South Africa, South Korea, Sweden, Thailand, Turkey, United Kingdom, United States, and Vietnam.
- Included participants were non-anaemic, mild or moderately anaemic pregnant women of any gestational age and parity.
Summary of Findings [SOF] Table: (Infant outcomes) Any supplements containing iron compared with same supplements without iron or no treatment/placeno (no iron or placebo) for pregnant women.
Population: pregnant women of any gestational age and parity
Setting: hospital or community-based antenatal clinic
Intervention: any supplement containing iron
Comparison: same supplements without iron or no treatment/placebo (no iron or placebo)
| Outcomes | Anticipated absolute effects | Relative effect (95% CI) | No of participants (studies) | Quality of evidence (GRADE) | |
| Risk with same supplement without iron or no treatment/placebo | Risk with any supplement containing iron | ||||
| Low birthweight (less than 2500 g) | 59 per 1000 | 8 fewer per 1000 (from 18 fewer to 2 more) | RR 0.84 (0.69-1.03) | 17,613 (11) | Low1, 2 |
| Birthweight (g) | The mean birthweight (g) in the intervention group was 23.75 higher (3.02 lower to 50.51 higher) | 18,590 (15) | Moderate1 | ||
| Preterm birth (less than 37 weeks of gestation) | 73 per 1000 | 6 fewer per 1000 (from 12 fewer to 2 more) | RR 0.93 (0.84-1.03) | 19,286 (13) | Moderate1 |
| Neonatal death (within 28 days after delivery) | 15 per 1000 | 2 fewer per 1000 (from 4 fewer to 3 more) | RR 0.91 (0.71-1.18) | 16,603 (4) | Low1, 2 |
| Congenital anomalies | 7 per 1000 | 1 fewer per 1000 (from 3 fewer to 2 more) | RR 0.88 (0.58-1.33) | 14,636 (4) | Low1, 2 |
About quality of evidence (GRADE)
High quality (HIgh): Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality (Moderate): Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality (Low): Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality (Very low): We are uncertain about the estimate.
1 Several studies contributing data had design limitations
2 Wide 95% CI crossing the line of no effect
Summary of Findings [SOF] Table: (Maternal outcomes) Any supplements containing iron compared with same supplements without iron or no treatment/placebo (no iron or placebo) for pregnant women
Population: pregnant women of any gestational age and parity
Setting: hospital or community-based antenatal clinic
Intervention: any supplement containing iron
Comparison: same supplement without iron or no treatment/placebo (no iron or placebo)
| Outcomes | Anticipated absolute effects | Relative effect (95% CI) | No of participants (studies) | Quality of evidence (GRADE) | |
| Risk with same supplement without iron or no treatment/placebo | Risk with any supplement containing iron | ||||
| Maternal anaemia at term (Hb less than 110 g/L at 37 weeks' gestation or more) | 357 per 1000 | 226 fewer per 1000 (from 193-289 fewer) | RR 0.30 (0.19-0.46) | 2199 (14) | Low1, 2 |
| Maternal iron deficiency at term (as defined by trialists, based on any indicator of iron status at 37 weeks' gestation or more) | 513 per 1000 | 228 fewer per 1000 (from 174-374 fewer) | RR 0.43 (0.27-0.66) | 1256 (7) | Low2, 3 |
| Maternal death (death while pregnant or within 42 days of termination of pregnancy) | 16 per 100,000 | 16 fewer per 100,000 (from 16 fewer to 115 more) | RR 0.33 (0.01-8.19) | 12,560 (2) | Very low4, 5 |
| Side effects (any reported throughout the intervention period) | 180 per 1000 | 36 more per 1000 (from 31 fewer to 184 more) | RR 1.29 (0.83-2.02) | 2423 (11) | Very low2, 3, 6 |
| Maternal severe anaemia at any time during second and third trimester (Hb less than 70 g/L) | 23 per 1000 | 20 fewer per 1000 (from 23 fewer to 51 more) | RR 0.22 (0.01-3.20) | 2125 (9) | Very low3, 6, 7 |
| Infection during pregnancy (including urinary tract infections) | 11 per 1000 | 3 more per 1000 (from 4 fewer to 38 more) | RR 1.21 (0.33-4.46) | 727 (1) | Low5 |
About quality of evidence (GRADE)
High quality (HIgh): Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality (Moderate): Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality (Low): Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality (Very low): We are uncertain about the estimate.
1 Several studies contributing data had design limitations and one had serious design limitations
2 High heterogeneity I2 > 80%
3 Several studies contributing data had design limitations
4 One of the studies contributing data had design limitations
5 Wide 95% CI crossing the line of no effect. Low event rate.
6 Wide 95% CI crossing the line of no effect.
7 High heterogeneity I2 = 69%
Summary of Findings [SOF] Table: (Infant outcomes) Any supplements containing iron and folic acid compared with same supplements without iron nor folic acid (no iron nor folic acid or placebo) for pregnant women
Population: pregnant women of any gestational age and parity
Setting: hospital or community-based antenatal clinic
Intervention: any supplement containing iron and folic acid
Comparison: same supplement without iron nor folic acid (no iron nor folic acid or placebo)
| Outcomes | Anticipated absolute effects (95% CI) | Relative effect (95% CI) | No of participants (studies) | Quality of evidence (GRADE) | |
| Risk with same supplement without iron and folic acid treatment/placebo | Risk with any supplement containing iron and folic acid | ||||
| Low birthweight (less than 2500 g) | 402 per 1000 | 68 more per 1000 (from 277 fewer to 1101 more) | RR 1.07 (0.31-3.74) | 1311 (2) | Low1, 2 |
| Birthweight | The mean birthweight (g) in the intervention group was 57.73 higher (7.66 higher to 107.79 higher) | 1365 (2) | Moderate1 | ||
| Preterm birth (less than 37 weeks' of gestation) | 192 per 1000 | 2 more per 1000 (from 115 fewer to 960 more) | RR 1.55 (0.40-6.00) | 1497 (3) | Low2, 3 |
| Neonatal death (within 28 days after delivery) | 42 per 1000 | 6 fewer per 1000 (from 21 fewer to 13 more) | RR 0.81 (0.51-1.30) | 1793 (3) | Low2, 3 |
| Congenital anomalies | 24 per 1000 | 7 fewer per 1000 (from 18 fewer to 10 more) | RR 0.70 (0.35-1.40) | 1652 (1) | Low2, 4 |
About quality of evidence (GRADE)
High quality (HIgh): Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality (Moderate): Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality (Low): Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality (Very low): We are uncertain about the estimate.
1 Both studies contributing data had design limitations.
2 Wide 95% CI crossing the line of no effect.
3 All studies contributing data had design limitations
4 Study contributing data had design limitations
Summary of Findings [SOF] Table: (Maternal outcomes) Any supplement containing iron and folic acid compared with same supplements without iron nor folic acid (no iron nor folic acid or placebo) for pregnancy women
Population: pregnant women of any gestational age and parity
Setting: hospital or community-based antenatal clinic
Intervention: any supplement containing iron and folic acid
Comparison: same supplement without iron nor folic acid (no iron nor folic acid or placebo)
| Outcomes | Anticipated absolute effects (95% CI) | Relative effect (95% CI) | No of participants (studies) | Quality of evidence (GRADE) | |
| Risk with same supplement without iron and folic acid treatment/placebo | Risk with any supplement containing iron and folic acid | ||||
| Maternal anaemia at term (Hb less than 110 g/L at 37 weeks' gestation or more) | 283 per 1000 | 211 fewer per 1000 (from 130-224 fewer) | RR 0.34 (0.21-0.54) | 346 (3) | Moderate1 |
| Maternal iron deficiency at term (as defined by trialists, based on any indicator of iron status at 37 weeks' gestation or more) | 150 per 1000 | 114 fewer per 1000 (from 2-141 fewer) | RR 0.24 (0.06-0.99) | 131 (1) | Low2, 3 |
| Maternal death (death while pregnant or within 42 days of termination of pregnancy) | 0 per 1000 | 0 per 1000 | Not estimable | 131 (1) | Low2, 4 |
| Side effects (any reported throughout the intervention period) | 0 per 1000 | 210 more per 1000 | RR 44.32 (2.77-709.09) | 456 (1) | Moderate2 |
| Maternal severe anaemia at any time during second and third trimester (Hb less than 70 g/L) | 6 per 1000 | 2 fewer per 1000 (from 2-6 fewer) | RR 0.12 (0.02-0.63) | 506 (4) | Very low1, 5 |
| Infection during pregnancy (including urinary tract infection) | 83 per 1000 | 0 fewer per 1000 (from 71 fewer to 459 more) | RR 1.00 (0.15-6.53) | 48 (1) | Very low2, 6 |
About quality of evidence (GRADE)
High quality (HIgh): Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality (Moderate): Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality (Low): Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality (Very low): We are uncertain about the estimate.
1 Studies contributing data had design limitations
2 Study contributing data had design limitations
3 Estimate based on small sample size
4 Small sample size and no events
5 Wide 95% CI interval crossing the line of no effect and low effect rate
6 Wide 95% CI interval crossing the line of no effet, small sample size and low event rate.
Relevance of the review for disadvantaged communities
| Findings | Interpretation |
| Equity - Which of the PROGRESS groups examined | |
| Included studies were conducted in low-, middle-, and high-income countries. | Further research is required to understand the efficiency of iron supplementation used alone or in combination with folic acid. |
| Several included studies were conducted in malaria endemic areas to complement measures used to prevent, diagnose, and treat malaria. | It is unclear whether iron supplementation interventions are applicable to other infection-related anaemia such as HIV and vaginosis. |
| Equity Applicability | |
| All participants were non-anaemic and mild or moderately anaemic women. | Further research is required to understand the effects of iron supplementation used alone or in combination with folic acid on women with severe anaemia. |
| Cost-equity | |
| Two excluded studies provided supplementation to participants free of cost. | There is no mention of the cost to provide supplementation and follow-up appointments. Additional research is needed to determine the cost of this intervention to understand its feasibility and accessibility within their settings. |
| Monitoring & Evaluation for PROGRESS groups | |
| Iron supplementation may have benefits, however, may also increase risk of infection. | Although iron supplementation may reduce anaemia during pregnancy, it is important to consider the risks when implementing this intervention. A patient's background risks and adherence to the intervention will affect its results. |
Comments on this summary? Please contact Jennifer Petkovic
This summary was prepared by Chaeyon Lee