Table 1 Summary effect of nutritional vitamins supplements on status of vitamin A human milk composition

Ayah [18]

maternal vitamin A (400 000 IU) or placebo,24 h postpartum

435 mothers infant pairs.

A randomised, placebo-controlled, double blind, two-by-two factorial trial

To assess the effects of high-dose postpartum maternal supplementation with 400,000 IU and infant supplementation with 100,000 IU at 14 weeks of age, on maternal and infant vitamin A status in the 6-month postpartum period.

Retinol

Maternal serum retinol was not different between groups, but milk retinol was higher in the vitamin A group. Vitamin A supplementation was associated with significantly higher milk retinol per volume at 4, 14 and 26 weeks postpartum and higher milk retinol expressed per gram fat at week 4, but not at weeks 14 and 26.

5/5

Africa (AFRO)

Bahl [19]

Single dose of 60 mg vitamin A or placebo at enrolment.

A total of 9424 mother-infant pairs were enrolled in the trial, 18–28 d postpartum in India and Peru and 21–42 d after delivery in Ghana.

Multicenter randomized, double-blind, placebo-controlled trial

To determine the effect of maternal vitamin A supplementation on breast milk retinol and of maternal and infant supplementation on infant vitamin A status.

Retinol

Maternal supplementation resulted in higher breast milk retinol at 2 mo postpartum. At 6 and 9 mo, maternal supplementation did not affect breast milk retinol or the proportion of mothers with low breast milk retinol.

At the doses used, maternal supplementation improved breast milk retinol status at 2 mo (P = 0.001) and maternal and infant supplementation modestly increased (P = 0.03) infant vitamin A status at 6 mo of age.

3/5

(SEARO), (AMRO), (AFRO)

Basu [20]

A single oral dose of 209 μmol of retinol (200,000 IU of vitamin A)

300 mothers, 150 in control and 150 in treatment group. Mean age: 24.6 and 25.2 years respectively.

A randomised controlled prospective study

To evaluate the effect of a single oral mega dose of vitamin A on the breast milk concentration.

Retinol

After supplementation, the treatment group showed a rise in mean breast milk retinol content (12.08 v 2.96 μmol/l) which remained significantly higher for four months. The breast milk retinol concentration increased significantly in the test population within 24 h of supplementation.

1/5

South East Asia (SEARO)

Bezerra [21]

retinyl palmitate consisted of a single dose of 200,000 IU (experimental group) and zero IU (control group).

113 healthy women aged 18–40 years.

randomised clinical trial

To evaluate the effect of maternal supplementation with a single dose of retinyl palmitate during the postpartum period, in order to supply vitamin A to the infant at the concentration of retinol in maternal milk.

Retinol

There was a significant increase in mean retinol levels in the colostrums of the supplemented group: 3.22 (sd = 1.81) μmol/l and 5.76 (sd = 2.80) μmol/l (p < 0.0001), between time zero and 24 h, respectively. This increase did not occur in the control group (p = 0.69).

2/5

Americas (AMRO)

Bezerra [22]

Participants were randomly allocated to 3 groups and supplemented in the postpartum period with a single retinyl palmitate dose of 200,000 IU (S1), a double dose of 200,000 IU 24 h apart (S2), or no supplementation (C).

199 healthy women within 16 h postpartum, aged between 18 and 40 years.

randomised clinical trial

To assess the effect of 2 different mega doses of retinyl palmitate on the level of retinol in the breast milk of healthy women.

retinol

The retinol content in mature milk differed between no supplementation group and groups S1 and S2 (P < .05). The double dose of vitamin A did not significantly increase the retinol content of milk at 4 weeks postpartum in comparison to a single dose.

3/5

Americas (AMRO)

Bhaskaram [23]

vitamin A supplementation (200,000 IV)

102 women who did not receive any vitamin A supplements during pregnancy and have full term normal deliveries

a double blind controlled prospective study

To investigate the vitamin A status of breast fed infants, extent of cornea1 lesions and the impact of postnatal maternal vitamin A supplementation on their growth and vitamin A status.

Retinol

The mean values were significantly higher at 10 and 30 days in supplemented mothers compared to control group.

2/5

South East Asia (SEARO)

Canfield [24]

Mothers in Group I received 90 mg β-carotene as red palm oil concentrate.

Mothers in Group II received capsules containing 90 mg purified β-carotene (BASF) and Group III mothers received placebo capsules identical in appearance to those containing β-carotene.

Ninety-eight mothers mean age: 26.0 ± 6.5

randomised clinical trial

To investigate the effect of β- carotene added to the diets of mothers as red palm oil or supplements on the vitamin A status of mothers and their nursing infants in a marginal barrio of Tegucigalpa, Honduras.

Carotenoids and retinol

Changes in milk concentrations of α-carotene (P < 0.01) and β-carotene (P < 0.02) before and after supplementation were significantly different between the three experimental groups. Increases in β- carotene concentrations were greater for the palm oil group (2.5 fold, p < 0.0001) than for the β-carotene supplement group (1.6 fold, p < 0.006) relative to placebo.

2/5

Americas (AMRO)

Canfield [25]

B-carotene beadlets (30-mg capsules)

Forty-four lactating mothers who had vitamin-A–poor diets. Mean age 23.7 ± 6.4 years.

randomised clinical trial

Investigation the effect of short-term b-carotene supplementation of lactating mothers on maternal milk.

Milk retinol and carotenoids

B-Carotene supplementation markedly elevated maternal serum and milk b-carotene concentrations (nine- and sevenfold, respectively). Maternal serum and milk retinol were unchanged in response to the treatment.

2/5

Americas (AMRO)

Darboe [26]

vitamin A as retinyl palmitate

197 mothers With a child weighing more than 2200 g and delivering over 37 weeks

Randomised, double blind, placebo controlled trial.

To compare the efficacy of the International Vitamin A Consultative Group early high-dose protocol with that of the WHO protocol by the assessment of adverse events at dosing, maternal and infant vitamin A concentrations, mucosal integrity, growth and morbidity patterns, and measurements of infant immunity.

vitamin A

At 1 month postpartum, there was a non-significant trend towards higher levels of breast milk retinol in the high dose group than in the WHO group.

4/5

Africa (AFRO)

Dijkhuizen [27]

All women received iron and folic acid (30mgiron as ferrous fumarate/d and 0.4 mg pteroylglutamic acid/d). In addition, one group of women received β –carotene (4.5 mg as water-soluble granulate/d; β-carotene group), one group received zinc (30 mg zinc as sulfate/d; zinc group), one group received β –carotene plus zinc (4.5 mg β –carotene and 30 mg zinc/d; β –carotene zinc group), and one group received only iron and folic acid (control group).

Pregnant women (n = 170). Mean age 25.1 ± 5.6 years.

A double-blind, placebo-controlled study

To investigates whether supplementing women during pregnancy with β-carotene and zinc, in addition to the standard supplementation with iron and folic acid, can improve vitamin A and zinc status of mothers and newborns 1 and 6 months postpartum.

Breast-milk b-carotene

Retinol

Zinc

Breast-milk β-carotene concentrations were higher in all women supplemented with β –carotene, but breast-milk retinol concentrations were higher only in women who received β –carotene + zinc. Zinc concentrations did not differ among groups in mothers and infants. Six months postpartum, plasma retinol concentrations were higher in the women who received zinc during pregnancy than in women who did not.

4/5

South East Asia (SEARO)

Garcia-Guerra [28]

100 to 150% of the recommended dietary vitamin A

249 mothers with 23.0 ± 5.2 years.

A randomized controlled trial

To assess the impact of daily supplementation with multiple micronutrients during pregnancy on zinc, vitamin A and folate status during pregnancy and 1 month postpartum, zinc and vitamin A in cord blood, and breast milk retinol concentration at one month postpartum.

Retinol

Breast milk retinol concentration at one month postpartum didn’t differ between groups.

4/5

Americas (AMRO)

Gossage [29]

All mothers were randomly assigned to 4 weeks of supplementation with either β carotene (30 mg/d; n = 11) or placebo (n = 10) beginning on day 4 postpartum (day 0 of the study).

Twenty-one pregnant women who had breast-fed at least one infant, did not smoke, had not taken prenatal supplements.

randomized controlled trial

To investigate the effects of β -carotene supplementation on human milk composition.

Milk concentrations of β -carotene, the other carotenoids, retinol, or α-tocopherol.

Β carotene supplementation did not significantly change the milk concentrations of β -carotene, the other carotenoids, retinol, or α tocopherol.

2/5

Americas (AMRO)

Grilo [30]

A mega dose of 200,000 IU of retinyl palmitate.

33 voluntary postpartum women aged 18 to 35 years

quasi-experimental study

To investigate the effect of vitamin A supplementation on the retinol concentration in colostrums under fasting and postprandial conditions

retinol

After supplementation, the values were 89.5 (32.9–264.2) g/dL and 102.7 (37.3–378.3) g/dL in fasting and postprandial conditions in breast milk, respectively (p < 0.05), representing an increase of 14.7%.

3/5

Americas (AMRO)

Grilo [31]

The supplemented group received 200,000 IU of retinyl palmitate after the first colostrum collection.

Healthy puerperal women were randomly distributed into a control group (n = 44) and a supplemented group (n = 44).

prospective, controlled, randomised and parallel-design trial

To assess the influence of maternal retinyl palmitate supplementation on the levels of retinol and a-tocopherol in the colostrum and mature milk of healthy lactating women.

Retinol a-tocopherol

The colostrum retinol levels of the supplemented group increased significantly 24 h after the intervention (P < 0.001). However, the retinol levels in the mature milk of both groups did not differ (P > 0.05). Moreover, after maternal supplementation with vitamin A, the colostrums a-tocopherol level decreased by 16.4%, which is a significant reduction (P < 0.05). However, vitamin A supplementation did not affect the a-tocopherol level of mature milk (P > 0.05).

3/5

Americas (AMRO)

Idindili [32]

60,000 g vitamin A palmitate

780 newborn infants and their mothers

Randomised, double blind, placebo controlled trial.

To compare the safety and efficacy of the previously tested low-dose regimen 25,000 IU vitamin A palmitate on breast milk.

Vitamin A

There were no significant difference in breast milk concentration of vitamin A in high and low dose group.

5/5

Africa (AFRO)

Johnson [33]

Participants were given either seven doses of a placebo (n = 4) or seven doses of naturally occurring BC (n = 8).

Twelve healthy lactating women (1–8 months postpartum, 18–40 years old).

randomized controlled trial

To determine effect of continuous oral doses of b-Caroten on breast Milk composition.

Carotenoids b-Caroten isomers

In the experimental group, the mean maternal milk concentration of all-trans b-carotene significantly increased to seven times the baseline level by the end of the supplementation period. The maternal milk concentration of 9-cis b-carotene significantly increased to three times the baseline level by the end of the supplementation period.

2/5

Americas (AMRO)

Klevor [34]

Women were randomly assigned to receive either the multiple-micronutrient supplement (MMN) providing 18 micronutrients, including 800 mg retinol equivalents of vitamin A, or the lipid-based nutrient supplement (LNS) with the same nutrients as the MMN group, plus 4 minerals and macronutrients, until 6 mo postpartum; a control group received iron and folic acid during pregnancy and a placebo (calcium tablet) during the first 6 months postpartum.

1320 women during pregnancy (≤20 wk. of gestation to delivery) and the first 6 mo postpartum.

A randomized, partially double-blind, controlled trial

Assessing effect of daily supplementation with approximately the recommended daily intake of vitamin A in LNS or a multiple-micronutrient supplement (MMN) during pregnancy and the first 6 mo postpartum on breast milk retinol concentration at 6 mo postpartum.

Breast milk vitamin A

There were no significant differences in any of these outcomes among intervention groups and results did not change after controlling for significant covariates. We found no significant effect of daily low-dose vitamin A provided in LNS or MMN during pregnancy and the first 6 mo postpartum on breast milk retinol concentration at 6 mo postpartum.

5/5

Africa (AFRO)

Lietz [35]

control group (n = 30), the sunflower oil group (n = 30), and the red palm oil

group (n = 30)

Ninety rural, pregnant Tanzanian women from 3 randomly selected villages were recruited during their third trimester.

randomized controlled trial

To efficacy of red palm oil in increasing retinol and provitamin A status in pregnant and lactating women.

carotenoid and retinol

Supplementation with red palm oil, which is rich in provitamin A, increased α- and β- carotene concentrations significantly in both plasma and breast milk. The difference in change in breast-milk retinol concentration between the red palm oil group and the control group was significant.

2/5

Africa (AFRO)

Lietz [36]

Red Palm Oil

56 Pregnant women (in their 3rd trimester, aged 18–45 years).

quasi-experimental study

To investigate the effect of maternal red palm oil supplementation throughout the 3rd trimester of pregnancy and the first 3 mo postpartum on carotenoid pattern in both plasma and breast milk.

Xanthophyll and Hydrocarbon Carotenoid

Red palm oil supplementation increases the milk concentrations of provitamin A carotenes without decreasing the milk concentrations of xanthophylls.

2/5

Africa (AFRO)

Martins [37]

a single dose of 200,000 IU vitamin A (retinyl palmitate)

66 mother–infant pairs, 33 mothers in control and 33 mothers in intervention group.

A double blind, placebo-controlled randomized clinical assay

Assess the impact of maternal supplementation with a single dose of retinyl palmitate on the vitamin A status of mother, breast milk and infant.

Serum and milk retinol

Reduction in breast milk retinol was observed in the control group compared with the pre-supplementation levels (1.93 and 1.34 mmol/l, respectively; P ≤ 0.0001) and to the post-supplementation levels of the supplemented group (1.56 mmol/l; P = 0.0003). There was significant difference in the prevalence of VAD in breast milk after supplementation, 55.6% (15/27) in the control group and 16.1% (5/31) in the supplemented group (P = 0.002).

3/5

Americas (AMRO)

Muslimatun [38]

One group received (n 5 88) a weekly supplement of iron (120 mg Fe as FeSO4) and folic acid (500 mg) and another (n 5 82) the same amount of iron and folic acid plus vitamin A [4800 retinol equivalents (RE)].

170 women with age 17–35 years.

A randomized double-blind, community-based trial

To investigate whether retinol and iron variables in breast milk and in serum postpartum were enhanced more with weekly vitamin A and iron supplementation during pregnancy than with weekly iron supplementation alone.

Fat, iron and vitamin A

Compared with the weekly iron group, the weekly vitamin A and iron group had a greater (P < 0.05) concentration of retinol in transitional milk (as mmol/L) and in mature milk (as mmol/g fat). However, no positive effects were observed on iron status and iron concentration in breast milk.

3/5

South East Asia (SEARO)

Nagayama [39]

Chlorella tablets.

Twenty healthy pregnant women (age range, 24–39 years.

randomized controlled trial

Investigation the effect of maternal supplementation with Chlorella on the carotenoid concentrations of breast milk.

carotenoids

Among the carotenoids detected in breast milk, lutein, zeaxanthin and b-carotene concentrations in the Chlorella group were 2.6-fold (p = 0.001), 2.7-fold (p = 0.001) and 1.7-fold (p = 0.049) higher, respectively, than those in the control group.

2/5

WPRO (Western Pacific Regional Office)

Rice [40]

a single dose of 200,000 international units [60,000 retinol equivalents (RE)] vitamin A followed by daily placebos (n = 74), (2) daily doses of b-carotene [7.8 mg (1300 RE)] (n = 73) or (3) daily placebos (n = 73) until 9 mo postpartum

220 women in three treatment group.

b-carotene Vs Placebo Vs Vitamin A

Randomized double blinded clinical trial

To investigate the the effects of maternal postpartum vitamin A or b-carotene supplementation on maternal and infant serum retinol concentrations and breast milk vitamin A concentrations.

Vitamin A

Compared to placebos, vitamin A supplementation resulted higher milk vitamin A concentrations at 3 mo, but these improvements were not sustained. Women receiving b-carotene supplements produced breast milk with increasingly higher vitamin A concentrations from 3 to 9 mo, but the concentration was significantly different from the placebo group only at 9 mo.

5/5

South East Asia (SEARO)

Roy [41]

209 mmol retinol.

50 pregnant women in their last trimester aged 16 ± 35 year.

Randomized clinical trial

To evaluate the effect of vitamin A supplementation 24 h after delivery on breast milk retinol concentration.

serum retinol, Breast milk retinol

Mean serum retinol levels increased in the supplemented mothers at 2.77 (2.3, 3.2) compared to 1.15 (0.9, 1.4) mmol/l in controls (P < 0.05) and remained at a significantly higher level of 1.59 (1.4, 1.8) mmul/l compared to 1.33 (1.8, 1.5) mmol/l in the control group (P < 0.001) up to a period of three months.

2/5

Eastern Mediterranean (EMRO)

Stoltzfus [42]

300,000 IU vitamin A as retinyl palmitate (n = 77) 2. Mother received placebo (n = 76).

153 mothers and their infants. Mother received supplement (n = 77) mother received placebo (n = 76).

Randomised, double blind, placebo controlled trial.

To measure the effects of supplementing mothers postpartum with vitamin A and effects on their milks.

breast milk retinol concentration

The milk retinol concentrations of the vitamin A group were higher than those of the placebo group (P < 0.05).

5/5

South East Asia (SEARO)

Tomiya [43]

Group 1 e received one 200,000 IU (retinol palmitate) capsule 40 mg of vitamin E orally immediately after delivery and, 10 days after delivery, the second 200,000 IU (retinol palmitate) capsule 40 mg of vitamin E were given.

Group 2 e received one 200,000 IU (retinol palmitate) capsule 40 mg of vitamin E orally immediately after delivery and, 10 days after delivery, the second “placebo” capsule containing 40 mg of vitamin E diluted in soybean oil were given.

158 women from 13 to 42 years of age.

A randomized, controlled, triple blind and hospital based clinical trial.

To determine if the 400,000 IU supplementation with retinol palmitate, immediately after delivery, promotes an additional effect in the concentrations of retinol in the human milk, when compared to the 200,000 IU supplementation.

Retinol

There was no significant difference between retinol concentrations in breast milk between treatment groups (400,000 IU vs 200,000 IU) in the studied period: 2 months (p = 0.790) and 4 months (p = 0.279).

5/5

Americas (AMRO)