Table 4.
Characteristics of the included studies and their main findings for the primary and secondary outcomes (n=19)
| Study name | Age (years) | Study location | Baseline hemoglobin (mean ± SD) | Intervention group (n) | Comparison group (n) | Source of sample | Type of participants | Type of Intervention | Duration of intervention | Comparison group | Blinding procedure | Randomization method and level | Primary outcome measure* | Secondary outcome measure** | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Intervention group | Control group | ||||||||||||||
| Mumtaz et al. (2000) [43] | 17 to 35 years | Peri-urban and rural Northern Pakistan | 9.2 ± 1.4 | 9.5 ± 1.0 | 100 | 91 | Tertiary care hospital | > 20 weeks of gestation | Daily iron supplementation capsules comprise 200 mg ferrous sulfate (60 mg elemental iron) | 12 weeks of gestation | Twice-weekly iron supplementation capsules comprised of 200 mg ferrous sulfate (60 mg elemental iron) | Double-blind | Random number generation | Mean hemoglobin level was significantly higher in the intervention group (p < 0.001) | Serum Ferritin levels significantly increased in the intervention group |
| Zavaleta et al. (2000) [44] | 15 to 35 years | Villa El Salvador/Lima/Peru | 11.6 ± 1.2 | 11.5 ± 1.4 | 325 | 320 | Hospital-based | 10 to 24 weeks of gestation | Daily oral supplements of 60 mg Fe (ferrous sulfate) and 250 mg folic acid | 10 to 24 weeks, 28 to 30 weeks 37to 38 weeks, 4 weeks postpartum | The same amount of iron and folic acid along with 15 mg Zn (as zinc sulfate) | Double-blind | Random assignment and stratification | Mean hemoglobin level was not significantly different in both the groups (p > 0.005) | No statistically significant difference was found in S. ferritin level and prevalence of anemia in both the groups |
| Ekström et al. (2002) [45] | Not mentioned | Rural areas/Mymensingh thana (subdistrict), Bangladesh | 11.2 ± 1.3 | 11.0 ± 1.2 | 74 | 66 | Antenatal center | 18 to 24 weeks of gestation | Women received weekly 2 doses of supplements/tablets comprised of 60 mg Fe and 250 μg folic acid | 12 weeks of gestation | Women received daily 1 dose of supplements/tablet comprised of 60 mg Fe and 250 μg folic acid | Not specified | Not specified | No significant difference was found in hemoglobin concentration between the two groups (p = 0.422) | No statistically significant difference was found in the prevalence of anemia between the two groups |
| Thuy et al. (2003) [46] | 17 to 49 years | Vietnam | 11.1 ± 0.8 | 11.0 ± 0.8 | 64 | 72 | Factory setting | Non-pregnant women | Women received daily 10 mL of Iron-fortified fish sauce fortified with 10 mg Fe | 6 months (26 weeks) | Women received daily 10 mL of non-fortified fish sauce | Double-blind | Not specified | Mean hemoglobin level was significantly higher in the intervention group (p < 0.0001) | S. Ferritin was statistically significantly higher in the intervention group. The prevalence of anemia was statistically significantly lower in the intervention group. S. transferrin receptor was statistically significantly lower in the intervention group |
| Makola et al. (2003) [47] | Not mentioned | Tanzania | 10.5 ± 1.4 | 10.5 ± 1.5 | 127 | 132 | Antenatal center | 12 to 34 weeks of gestation | Micronutrient-fortified with 11 micronutrients including Fe | 8 weeks of gestation | Non -fortified beverage (placebo) | Double-blind | Block randomization | Mean hemoglobin level was significantly increased in the intervention group (p = 0.015) | A statically significant increase in S. Ferritin was found in the intervention group |
| Mukhopadhyay et al. (2004) [48, 49] | Not mentioned | India | 11.3 ± 1.4 | 11.6 ± 0.9 | 40 | 40 | Antenatal clinic | < 20 weeks of gestation | Daily oral tablet of 100 mg elemental iron and 500 mg folic acid | 32 to 34 weeks gestation | Weekly oral tablet of 200 mg elemental iron and 1000 mg folic acid | Single-blinded | Block randomization | Mean Hemoglobin level was not significantly different between two groups (p = 0.11) | No secondary outcome was assessed |
| Mukhopadhyay et al. (2004) [48, 49] | Not mentioned | New Delhi, India | 11.6 ± 0.9 | 11.3 ± 1.0 | 40 | 40 | Antenatal clinic | < 20 weeks of gestation | 200 mg elemental iron tablets weekly | 32 to 34 weeks of gestation | 100 mg elemental iron tablets daily | Not specified | Block randomization | Mean hemoglobin level was not significantly differed in both the groups (p < 0.05) | Statistically significant decrease in S. Ferritin level in the intervention group and decrease in the prevalence of anemia in the control group |
| Sharma et al. (2004) [50] | 18 to 40 years | New Delhi, India | 9.4 ± 0.94 | 9.6 ± 0.87 | 100 | 100 | Antenatal clinic | 18 to 24 weeks of gestation | Three intramuscular doses of 250 mg elemental Fe as iron dextran at 1 month intervals plus oral doses of 5 mg folic acid twice weekly | 37 to 41 weeks of gestation | Daily oral dose of 100 mg elemental Fe and 500 µg folic acid | Not specified | Partial randomization | Mean hemoglobin was improved in both the groups but the difference was insignificant (p > 0.005) | Statistically significant increase in S. Ferritin level in the intervention group. Statistical significant improvement in Serum iron in both the groups |
| Kumar et al. (2005) [51] | Not mentioned | India | 9.89 ± 0.75 | 9.60 ± 0.77 | 75 | 75 | Antenatal Clinic | 16 to 24 weeks of gestation | Daily oral iron therapy of 100 mg of elemental iron | 36 weeks of gestation | Overall, intramuscularly 2 doses of 250 mg of iron sorbitol with an interval of 4 to 6 weeks | Not specified | Not specified | Mean Hemoglobin was improved in the intervention group but the difference between the two groups was not statistically significant (p > 0.05) | S. Ferritin was statistically significantly increasing in control (parenteral iron) group. No significant difference was found in S. iron between the two groups |
| Saha et al. (2007) [52] | 20 to 40 years | Chandigarh, India | 8.47 ± 0.72 | 8.39 ± 0.74 | 48 | 52 | Tertiary care hospital | 14 to 27 weeks of gestation | One tablet once daily of Iron polymaltose Complex 100 mg elemental iron + folic acid 500 mcg for 8 weeks | 27 weeks gestation | One tablet orally twice daily of Ferrous Sulphate 60 mg elemental iron + folic acid 500 mcg for 8 weeks | Double-blind | Not specified | Significant increase in the mean hemoglobin in both groups (p < 0.05) | Statistically significant increase in S. Ferritin level in both the groups |
| Bhutta et al. (2009) [53] | 15 to 49 years | Urban and rural Sindh/Pakistan | 10.7 ± 1.6 | 10.8 ± 1.5 | 466 | 522 | Community-based | < 24 weeks of gestation | Multiple micronutrient supplements contained iron 30 mg (ferrous fumarate) and folic acid (400 μg), retinol (800 μg), zinc (15 mg), 2 mg of copper, 65 μg of selenium, and 150 μg of iodine, vitamins: D (200 IU), E (10 mg), C (70 mg), B1 (1.4 mg), B3 (18 mg), B2 (1.4 mg), B6 (1.9 mg), B12 (2.6 μg) | Post-natal visit | Iron (60 mg) and folic acid (400 μg) supplementation tablets | Double-blind | Block randomization | Mean hemoglobin level was not significantly different between the two groups (p = 0.27) | Statistically, significant improvement was found in S. Ferritin level in the intervention group |
| Wijaya-Erhardt et al. (2011) [54] | 15 to 49 years | Karanganyar and Demak, of Central Java Province, Indonesia | 12.5 ± 1.14 | 11.8 ± 1.14 | 110 | 117 | Community-based | 12 to 20 weeks of gestation | Optimized food was given 6 days per week comprised 600 g of tempeh, 30 g of meat, 350 g of guava, 300 g of papaya, and 100 g of orange along with tablets containing 60 mg of Fe and 250 mg of folic acid | 36 weeks of gestation | Received tablets containing 60 mg of Fe and 250 mg of folic acid | Not specified | Cluster level | Mean hemoglobin level was decreased in both the groups (p < 0.05) | Statistically significant decrease in S. Ferritin level and S. Iron (Fe) level, a significant increase in transferrin receptor in both the groups |
| Choudhury et al. (2012) [55] | Not mentioned | Rural/ Central Bangladesh | 10.9 ± 1.4 | 11.1 ± 1.3 | 207 | 198 | Antenatal care centers | 14 to 22 weeks of gestation | Micronutrient powder (contains 60 mg of elemental iron, 400 μg of folic acid, 30 mg of vitamin C, and 5 mg of zinc) | 32 weeks of gestation | Iron and folic acid tablets (60 mg of elemental iron and 400 μg of folic acid) | Not specified | Cluster level | Mean hemoglobin was not significantly different in the intervention group (p = 0.106) | The prevalence of anemia improved in the intervention group but was statistically insignificant |
| Magon et al. (2014) [56] | 18 to 35 years | Rajasthan/India | 8.83 ± 1.7 | 8.38 ± 1.4 | 45 | 47 | Community-based | 14 to 16 weeks of gestation | Weekly distribution of leaf concentrate fortified ready-to-eat (lcRTE) snack in a dried powdered form fortified with 7 g Leaf concentrate | 35–36 weeks of gestation | Weekly distribution of standard ready-to-eat (sRTE) snack contained 102 g wheat flour and 18 g soya flour | Single-blind | Consecutively numbered sealed envelopes along with block randomization | Mean hemoglobin level was improved in the intervention group significantly (p < 0.001) | - |
| Kamdi et al. (2015) [57] | 18 to 30 years | Maharashtra and Gujarat, India | 8.38 ± 1.41 | 8.27 ± 1.20 | 26 | 24 | Health care facility based | 12 to 26 weeks of gestation | A single daily dose of tablet ferrous asparto glycinate (FAG) (contains 100 mg of elemental iron + 300 μg of L-methyl folate + 500 μg of methylcobalamin) | 28 days (4 weeks) of gestation | The single daily dose of tablet ferrous ascorbate (contains100 mg of elemental iron + 1.1 mg of folic acid) | Double-blind | Stratification and matching | Mean higher levels of hemoglobin in the intervention group (p < 0.01) | Statistically significant rise in S. Ferritin level in the intervention group |
| Mehta et al. (2017) [58] | 18 to 35 years | India | 10.5 ± 1.2 | 10.5 ± 1.3 | 65 | 71 | Healthcare facility based | Non-pregnant women | One non-heme iron supplement bar (contain 14 mg Fe)/day (termed as GudNeSs bars) | 90 days (13 weeks) | No intervention (No placebo either) | None | Cluster level | Mean hemoglobin level increased among intervention group (p < 0.001) | The prevalence of anemia became significantly lower in intervention group |
| Not mentioned | India | 9.38 ± 1 | 9.49 ± 1 | 184 | 184 | Community based setting | 12 to 16 weeks of gestation | Directly observed Iron Folic Acid (IFA) supplementation tablets once or twice daily | 100 days(14 weeks) of gestation | Unobserved IFA supplementation tablets daily | Open-label | Block randomization | Mean hemoglobin level was higher in the intervention group (p < 0.001) | Serum ferritin and reduction of anemia in the intervention group was higher but not significant | |
| 16 to 45 years | Nigeria | 11.1 ± 0.9 | 11.0 ± 0.7 | 84 | 80 | Antenatal clinic | 14 to 24 weeks of gestation | Once daily FeSO4 200 mg supplements in tablets form (contains 65 mg elemental Fe) | 37 weeks gestation | Twice daily FeSO4 200 mg supplements in tablets form (contain 130 mg of elemental iron) | Double blind | Balloting | Serum Hemoglobin was found to be lower among those on once daily dose as compared to twice daily (p = 0.002) | No difference in the serum ferritin levels between two groups | |
| Jose et al. (2019) [59] | Not mentioned | India | 8.57 ± 0.9 | 8.67 ± 0.8 | 50 | 50 | Tertiary care hospital | 16 to 36 weeks of gestation | Intravenous Ferric Carboxymaltose (FCM) | 12 weeks gestation | Intravenous Iron sucrose complex (ISC) | Open-label | Computer generated block randomization | Mean rise in hemoglobin found in FCM group (p < 0.001) | No significant difference was found in S. Ferritin and S. Iron (Fe) level in both the groups |
*Primary outcome measure was defined as change in Hemoglobin (Hb) level
** Secondary outcome measures were defined as changes in the mean ferritin level, serum transferrin receptor, iron status, and iron deficiency