Table 1.
Prenatal intervention studies
| Reference | Sample size analysed, ages at base and endline | Design | Main development outcomes | Quality | ||||
|---|---|---|---|---|---|---|---|---|
| Mental development (mean ± SD) | d | Motor development (mean ± SD) | d | Item ratings | Global rating | |||
| Thilly et al. 1980a DR Congo HDI .304 (Thilly, 1980a,1980b; Thilly, 1981) |
N = 75; INT n = 39; CTRL n = 36 Mothers enrolled in 2nd and 3rd trimester Infants tested at 23 months. |
RCT where Intervention received a single dose of 475‐mg iodine in oil and Control received a placebo. | Brunet‐Lézine: INT (115 ± 18) > CTRL (103 ± 24)** | 0.57 | W, S, S, S, W, W, S, M | Weak | ||
| Joos et al. 1983 Taiwan HDI .699 (Joos et al. 1983) |
N = 198; INT n = 99; CTRL n = 99 Mothers enrolled during lactation of first pregnancy. Infants from second pregnancy tested at 8 m Mean base maternal BMI = 20.4 kg/m2 |
RCT where Intervention received a high calorie and protein supplement (800 kcal and 40‐g protein per day). Control received placebo with 6 kcal or 80 kcal per day. They were in liquid form. A vitamin and mineral pill was given to all women. Supplementation during lactation of first child and continued through interpregnancy, pregnancy and lactation of second child. This analysis used children from the second pregnancy only. | BSID: INT (4.48 ± 1.8) = CTRL (4.39 ± 1.8) | 0.05 | BSID: INT (3.8 ± 1.9) = CTRL (3.31 ± 1.71) | 0.27 | M, S, S, S, W, S, M, S | Moderate |
| Hamadani et al. 2002 Bangladesh HDI .515 (Hamadani et al. 2002) |
N = 168; INT n = 83; CTRL n = 85 Women started supplementation at 4‐m gestation Infants tested at 13 m Mean base maternal BMI = 18.7 kg/m2 |
RCT where Intervention received daily zinc supplementation (30‐mg zinc acetate tablets) and Control received a placebo. | BSID II: INT (99.34 ± 11.2) < CTRL (102.64 ± 10.0)* | −0.31 | BSID II: INT (88.7 ± 17.4) < CTRL (95.7 ± 15.0)** | −0.43 | M, S, S, S, S, M, S, S | Strong |
| Schmidt et al. 2004 Indonesia HDI .629 (Schmidt et al. 2004) |
N = 188; INT n = 94; CTRL n = 94 Women enrolled at 16–20‐wk gestation Infants measured at 12 m Mean base maternal BMI = 22.0 kg/m2 |
RCT where Intervention received weekly supplementation of 120‐mg Fe + 500‐mcg FA + 4800‐mcg retinol in the form of retinyl acetate and Control received 120‐mg Fe + 500‐mcg FA. | BSID: INT (105.4 ± 22.3) = CTRL (104.0 ± 27.1) | 0.06 | BSID: INT (98.3 ± 32.0) = CTRL (102.3 ± 36.8)*** | −0.12 | M, S, S, S, W, S, S, S | Moderate |
| Tofail et al. 2006 Bangladesh HDI .515 (Tofail et al. 2006) |
N = 249; INT n = 125; CTRL n = 124 Mothers supplemented in last trimester Infants tested at 10 m Mean base maternal BMI = 20.3 kg/m2 |
RCT where Intervention received daily supplementation of 4 g of fish oil (containing 1.2 g of docosahexaenoic acid and 1.8 g of eicosapentaenoic acid) and Control received 4 g of daily soy‐oil (containing 2.25 g of linoleic acid and 0.27 g of α‐linolenic acid). | BSID II: INT (102.5 ± 8.0) = CTRL (101.5 ± 7.8) | 0.13 | BSID II: INT (101.7 ± 10.9) = CTRL (100.5 ± 10.1) | 0.11 | M, S, S, S, S, S, S, S | Strong |
| McGrath et al. 2006 Tanzania HDI .476 (McGrath et al. 2006) |
N = 334; Multivitamin n = 93; No multivitamin n = 74; Vitamin A n = 94; No vitamin A n = 73 Mothers enrolled at 12–27‐wk gestation Infants measured at 18 m HIV‐infected mothers |
RCT where Interventions received daily vitamin A (30 mg of β‐carotene + 5000 IU preformed vitamin A), multivitamins with no vitamin A (20‐mg B1, 20‐mg B2, 25‐mg B6, 100‐mg niacin, 50‐mcg B12, 500‐mg vitamin C, 30‐mg vitamin E and 0.8‐mg FA), or multivitamins + vitamin A, and Control received placebo. | BSID II: INT MV (78.4 ± 13.8) = CTRL No MV (82.0 ± 13.5) INT Vit A (80.6 ± 12.5) = CTRL No vit A (79.3 ± 15.4) | −0.26 0.09 | BSID II: INT MV (86.2 ± 14.3) = CTRL No MV (88.5 ± 14.8) INT Vit A (87.4 ± 12.2) = CTRL No vit A (87.0 ± 15.1) | −0.16 0.03 | M, S, S, S, W, S, S, S | Moderate |
| Tofail et al. 2008 Bangladesh HDI .515 (Tofail et al. 2008) |
N = 1407; INT MMN n = 705; CTRL n = 702 Mother enrolled btw 6 and 8 weeks of pregnancy. Infants measured at 7m Mean base maternal BMI = 20.2 kg/m2 |
RCT where Intervention received daily MMN and Control received iron and folate. MMN included 150‐mcg I (potassium iodide), 15‐mg Zn (sulphate), 65‐mcg Se (sodium selenite), 2‐mg Cu (sulphate), 800‐mcg retinyl acetate (RE) vitamin A, 1.4‐mg thiamine mononitrate, 1.4‐mg vitamin riboflavin, 18‐mg vitamin B3 (niacin), 1.9‐mg vitamin B6 (pyridoxine hydrochloride), 2.6‐mcg vitamin B12 (cyanocobalmin), 70‐mg vitamin C, 200 IU vitamin D (vitamin D3) and 10‐mcg vitamin E (α‐tocopherol acetate) in the recommended dietary allowance dose in addition to 60‐mg Fe (fumarate) and 400‐mcg folate. Control received 30‐mg Fe (fumarate) and 400‐mcg folate. | Problem solving test: Support: INT MM (11.3 ± 7.9) = CTRL (11.1 ± 7.5) | 0.03 | BSID II:INT MM (103.66 ± 16.6) = CTRL (102.42 ± 15.4) | 0.08 | S, S, S, W, M, S, S | Moderate |
| Li et al. 2009 China HDI .699 (Li et al. 2009) |
N = 1159; INT Fe/FA n = 393; INT MMN n = 351; CTRL n = 415 Mean gestation age of mothers at enrollment = 97.36 days Infants measured at 12 m Mean base maternal BMI = 20.8 kg/m2 |
Cluster RCT where Interventions received MMN, iron/folic acid or folic acid supplementation. Assume two trimesters of supplementation. Control received folic acid. MMN included 30‐mg iron, 400‐mcg folate, 15‐mg zinc, 2‐mg copper, 65‐mcg selenium, 150‐mcg iodine, 800‐mcg vitamin A, 1.4‐mg vitamin B1, 1.4‐mg vitamin B2, 1.9‐mg vitamin B6, 2.6‐mcg vitamin B12, 5‐mcg vitamin D, 70‐mg vitamin C, 10‐mg vitamin E and 18‐mg niacin. FE/FA included 60‐mg iron and 400‐mcg folic acid. FA included 400‐mcg folic acid. | BSID: INT Fe/FA (102.44 ± 45.26) = CTRL (102.65 ± 49.21) INT MMN (103.65 ± 42.11) = CTRL (102.65 ± 49.21) | 0.04 0.02 | BSID: INT Fe/FA (45.3 ± 22.15) = CTRL (45.39 ± 22.40) INT MMN (45.64 ± 19.83) = CTRL (45.39 ± 22.40) | −0.004 0.01 | S, S, S, S, W, M, S, S | Moderate |
| Chang et al. 2013 China HDI .699 (Chang et al. 2013) |
N = 850; INT Fe/FA n = 238; INT MMN n = 254; CTRL n = 313 Mean gestation age of mothers at enrollment = 97.36 days Infants measured at 24m Mean base maternal BMI = 20.8 kg/m2 |
Cluster RCT where Interventions received MMN, iron/folic acid or folic acid supplementation. Assume two trimesters of supplementation. Control received folic acid. MMN included 30‐mg iron, 400‐mcg folate, 15‐mg zinc, 2‐mg copper, 65‐mcg selenium, 150‐mcg iodine, 800‐mcg vitamin A, 1.4‐mg vitamin B1, 1.4‐mg vitamin B2, 1.9‐mg vitamin B6, 2.6‐mcg vitamin B12, 5‐mcg vitamin D, 70‐mg vitamin C, 10‐mg vitamin E and 18‐mg niacin. FE/FA included 60‐mg iron and 400‐mcg folic acid. FA included 400‐mcg folic acid. | BSID II: INT Fe/FA (90.31 ± 16.1) = CTRL (88.78 ± 17.3) INT MMN (89.67 ± 19.5) = CTRL (88.78 ± 17.3) | 0.09 0.05 | BSID II: INT Fe/FA (104.47 ± 11.7) = CTRL FA (103.89 ± 12.8) INT MMN (103.13 ± 13.0) = CTRL FA (103.89 ± 12.8) | 0.05–0.06 | S, S, S, W, M, S, S | Moderate |
| Hanieh et al. 2013 Viet Nam HDI .617 (Hanieh et al. 2013) |
N = 769; INT n = 381; CTRL n = 388 Mothers enrolled if <16‐wk gestation Infants tested at 6m Mean base maternal BMI = 19.9 kg/m2 |
Cluster RCT where Intervention received MMN twice per week and Control received 60‐mg elemental iron plus 0.4‐mg folic acid daily. MMN contained 15 micronutrients, including 60‐mg iron, 20‐mg zinc, 300‐mcg iodine, 4‐mg copper, 130‐mcg selenium, 1.6‐mg vitamin A, 2.8‐mg thiamine, 2.8‐mg riboflavin, 36‐mg niacin, 3.8‐mg vitamin B6, 5.2‐mcg vitamin B12, 1.5‐mg folic acid, 140‐mg vitamin C, 400 IU vitamin D and 20‐mg vitamin E. | BSID III:INT (101.2 ± 9.9) = CTRL (100.2 ± 11.4) | 0.09 | S, S, S, S, W, S, S, S | Moderate | ||
Note: Assessment of Quality (Item Ratings) with following categories in order: selection bias, study design, confounders, blinding, data collection methods, withdrawals and dropouts, intervention integrity, analysis; HDI, Human Development Index; RCT, Randomized Controlled Trial; m, month; wk, week; INT, Intervention group; CTRL, Control group; BMI, body mass index; BSID, Bayley Scales of Infant Development; effect size d, standardized mean difference; SD, standard deviation; W, weak; M, moderate; S, strong; MMP, multiple micronutrient powder; MMN, multiple micronutrients; MV, multivitamin; Zn, zinc; Fe, iron; FA, folic acid.
p < 0.05;
p < 0.01;
p < 0.001.