DIET AS A PROPHYLACTIC AGENT AGAINST PUERPERAL SEPSIS. Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia. Effect of low-dosage vitamin A and riboflavin on iron-folate supplementation in anaemic pregnant women. Antenatal vitamin A supplementation increases birth weight and decreases anemia among infants born to human immunodeficiency virus-infected women in Malawi. Randomized trial testing the effect of vitamin A supplementation on pregnancy outcomes and early mother-to-child HIV-1 transmission in Durban, South Africa. South African Vitamin A Study Group. Effect of vitamin A supplementation in women of reproductive age on maternal survival in Ghana (ObaapaVitA): a cluster-randomised, placebo-controlled trial. Weekly supplementation with iron and vitamin A during pregnancy increases hemoglobin concentration but decreases serum ferritin concentration in Indonesian pregnant women. Vitamin A and iron status are improved by vitamin A and iron supplementation in pregnant Indonesian women. Double blind, cluster randomised trial of low dose supplementation with vitamin A or beta carotene on mortality related to pregnancy in Nepal. The NNIPS-2 Study Group. Red palm oil supplementation: a feasible diet-based approach to improve the vitamin A status of pregnant women and their infants. Effect of vitamin supplementation to HIV-infected pregnant women on the micronutrient status of their infants. Maternal vitamin A supplementation and immunity to malaria in pregnancy in Ghanaian primigravids. Randomised trial of vitamin A supplementation in pregnant women in rural Malawi found to be anaemic on screening by HemoCue. Inluence of vitamin A on human colostrum and early milk. Impact of vitamin A supplementation on anaemia and plasma erythropoietin concentrations in pregnant women: a controlled clinical trial. Zinc plus beta-carotene supplementation of pregnant women is superior to beta-carotene supplementation alone in improving vitamin A status in both mothers and infants.
nan Nutritional anaemia, thought to be caused by iron deficiency, affects 50-70% of pregnant women in the developing world. The influence of vitamin A and iron supplementation was studied in anaemic pregnant women in West Java, in a randomised, double-masked, placebo-controlled field trial. 251 women aged 17-35 years, parity 0-4, gestation 16-24 weeks, and haemoglobin between 80 and 109 g/L were randomly allocated to four groups: vitamin A (2.4 mg retinol) and placebo iron tablets; iron (60 mg elemental iron) and placebo vitamin A; vitamin A and iron; or both placebos, all daily for 8 weeks. Maximum haemoglobin was achieved with both vitamin A and iron supplementation (12.78 g/L, 95% Cl 10.86 to 14.70), with one-third of the response attributable to vitamin A (3.68 g/L, 2.03 to 5.33) and two-thirds to iron (7.71 g/L, 5.97 to 9.45). After supplementation, the proportion of women who became non-anaemic was 35% in the vitamin-A-supplemented group, 68% in the iron-supplemented group, 97% in the group supplemented with both, and 16% in the placebo group. Improvement in vitamin A status may contribute to the control of anaemic pregnant women. A double-blind, placebo, controlled trial was conducted in Banyudono subdistrict, Boyolali regency, Central Java province, Indonesia. The aim of the study was to determine whether adding low-dosage vitamin A and riboflavin can enhance the effect of iron-folate supplementation in anaemic pregnant women. From July to November 2000, 202 pregnant women were screened for anaemia (haemoglobin < 11.0 g/dL). One hundred and three pregnant women (51%) were found to be anaemic and were then allocated alternately into four groups. Over a period of 60 days, group IF (n = 29) received iron-folate tablets (200 mg FeSO4 and 250 microg folic acid) + 5 mg glucose: group IFR (n = 22) received iron-folate tablets + 5 mg riboflavin; group IFA (n = 29) received iron-folate tablets + 2.75 mg retinyl palmitate (equal to 5000 IU vitamin A); and group IFRA (n = 23) received iron-folate tablets + 5 mg riboflavin + 2.75 mg retinyl palmitate. At the end of the study 19 pregnant women (18.4%) were excluded from the analysis because of various reasons. Statistical analysis was based on 84 women (81.5%): group IF, n = 25; group IFR, n = 22; group IFA, n = 18; and group IFRA, n = 19. Haemoglobin measurements were carried out using the Technicon H1* (cyanmethaemoglobin method). All groups showed a significant increase in haemoglobin concentration (P < 0.05), except group IFA (P > 0.05), with the highest increment being in group FR. Multiple comparisons only showed significant differences between group IFR and group IFA (P < 0.05). It can be concluded that iron-folate supplementation can increase haemoglobin concentrations in anaemic pregnant women. Adding riboflavin tends to enhance the effect of iron-folate supplementation, but this is not the case with adding vitamin A. Vitamin A is essential for immunity and growth. A controlled clinical that involved 697 human immunodeficiency virus (HIV)-infected pregnant women was conducted to determine whether vitamin A prevents anemia, low birth weight, growth failure, HIV transmission, and mortality. Women received daily doses of iron and folate, either alone or combined with vitamin A (3 mg retinol equivalent), from 18-28 weeks' gestation until delivery. In the vitamin A and control groups, respectively, the mean (+/-SE) birth weights were 2895+/-31 g and 2805+/-32 g (P=.05), the proportions of low-birth-weight infants were 14.0% and 21.1% (P=.03), the proportions of anemic infants at 6 weeks postpartum were 23.4% and 40.6% (P<.001), and the respective cumulative proportions of infants who were HIV infected at 6 weeks and 24 months of age were 26.6% and 27.8% (P=.76) and 27.7% and 32.8% (P=.21). Receipt of vitamin A improved birth weight and neonatal growth and reduced anemia, but it did not affect perinatal HIV transmission. Poor vitamin A status has been associated with a higher risk for mother-to-child transmission of HIV-1 and there is contradictory evidence on the impact of vitamin A on perinatal outcome. We therefore assessed the effect of vitamin A supplementation to mothers on birth outcome and mother-to-child transmission of HIV-1.
                In Durban, South Africa 728 pregnant HIV infected women received either vitamin A (368) or placebo (360) in a randomized, double-blind trial. The vitamin A treatment consisted of a daily dose of 5000 IU retinyl palmitate and 30 mg beta-carotene during the third trimester of pregnancy and 200000 IU retinyl palmitate at delivery. HIV infection results were available on 632 children who were included in the Kaplan-Meier transmission analysis. Results are reported on mother-to-child transmission rates up to 3 months of age.
                There was no difference in the risk of HIV infection by 3 months of age between the vitamin A [20.3%; 95% confidence interval (CI), 15.7-24.9] and placebo groups (22.3%; 95% CI, 17.5-27.1), nor were there differences in foetal or infant mortality rates between the two groups. Women receiving vitamin A supplement were, however, less likely to have a preterm delivery (11.4% in the vitamin A and 17.4% in the placebo group; P = 0.03) and among the 80 preterm deliveries, those assigned to the vitamin A group were less likely to be infected (17.9%; 95% CI, 3.5-32.2) than those assigned to the placebo group (33.8%; 95% CI, 19.8-47.8).
                Vitamin A supplementation, a low-cost intervention, does not appear to be effective in reducing overall mother-to-child transmission of HIV; however, its potential for reducing the incidence of preterm births, and the risk of mother-to-child transmission of HIV in these infants needs further investigation. A previous trial in Nepal showed that supplementation with vitamin A or its precursor (betacarotene) in women of reproductive age reduced pregnancy-related mortality by 44% (95% CI 16-63). We assessed the effect of vitamin A supplementation in women in Ghana.
                ObaapaVitA was a cluster-randomised, double-blind, placebo-controlled trial undertaken in seven districts in Brong Ahafo Region in Ghana. The trial area was divided into 1086 small geographical clusters of compounds with fieldwork areas consisting of four contiguous clusters. All women of reproductive age (15-45 years) who gave informed consent and who planned to remain in the area for at least 3 months were recruited. Participants were randomly assigned by cluster of residence to receive a vitamin A supplement (25 000 IU retinol equivalents) or placebo capsule orally once every week. Randomisation was blocked and based on an independent, computer-generated list of numbers, with two clusters in each fieldwork area allocated to vitamin A supplementation and two to placebo. Capsules were distributed during home visits undertaken every 4 weeks, when data were gathered on pregnancies, births, and deaths. Primary outcomes were pregnancy-related mortality and all-cause female mortality. Cause of death was established by verbal post mortems. Analysis was by intention to treat (ITT) with random-effects regression to account for the cluster-randomised design. Adverse events were synonymous with the trial outcomes. This trial is registered with ClinicalTrials.gov, number NCT00211341.
                544 clusters (104 484 women) were randomly assigned to vitamin A supplementation and 542 clusters (103 297 women) were assigned to placebo. The main reason for participant drop out was migration out of the study area. In the ITT analysis, there were 39 601 pregnancies and 138 pregnancy-related deaths in the vitamin A supplementation group (348 deaths per 100 000 pregnancies) compared with 39 234 pregnancies and 148 pregnancy-related deaths in the placebo group (377 per 100 000 pregnancies); adjusted odds ratio 0.92, 95% CI 0.73-1.17; p=0.51. 1326 women died in 292 560 woman-years in the vitamin A supplementation group (453 deaths per 100 000 years) compared with 1298 deaths in 289 310 woman-years in the placebo group (449 per 100 000 years); adjusted rate ratio 1.01, 0.93-1.09; p=0.85.
                The body of evidence, although limited, does not support inclusion of vitamin A supplementation for women in either safe motherhood or child survival strategies.
                UK Department for International Development, and USAID.
                Copyright 2010 Elsevier Ltd. All rights reserved. We investigated whether weekly iron supplementation was as effective as the national daily iron supplementation program in Indonesia in improving iron status at near term in pregnancy. In addition, we examined whether weekly vitamin A and iron supplementation was more efficacious than weekly supplementation with iron alone. One group of pregnant women (n = 122)was supplemented weekly with iron (120 mg Fe as FeSO4) and folic acid (500 microg); another group (n = 121) received the same amount of iron and folic acid plus vitamin A [4800 retinol equivalents (RE)]. A third ("daily") group (n = 123), participating in the national iron plus folic acid supplementation program, was also recruited. Data on subjects with complete biochemical data are reported (n = 190). At near term, hemoglobin concentrations increased, whereas serum ferritin concentrations decreased significantly in the weekly vitamin A and iron group, suggesting that vitamin A improved utilization of iron for hematopoiesis. Iron status in the weekly iron group was not different from that of the "daily" group. However, iron status decreased with daily supplementation if <50 iron tablets were ingested. Serum transferrin receptor concentrations increased in all groups (P < 0.01). Serum retinol concentrations were maintained in the weekly vitamin A and iron group, but decreased in the other two groups (P < 0.01). Thus, delivery of iron supplements on a weekly basis can be as effective as ona daily basis if compliance can be ensured. Addition of vitamin A to the supplement improved hemoglobin concentration. In Indonesia, deficiencies of vitamin A and iron are of public health concern during pregnancy. We sought to determine the effects of vitamin A and iron supplementation on the vitamin A and iron status of pregnant Indonesian women. The women (n = 27) were randomly assigned to four groups. The modified relative dose response (MRDR) test for vitamin A status and hemoglobin, hematocrit and ferritin values were determined at baseline. Thereafter, daily supplements were administered: placebo [Pl] (n = 7), 8.4 micromol vitamin A [A] (n = 7), 1.07 mmol iron [Fe] (n = 5), and 8.4 micromol vitamin A plus 1.07 mmol iron [A + Fe] (n = 8). Post-treatment tests were performed after 8 wk. The MRDR value was reduced, i.e., vitamin A status improved, more markedly by the combination of vitamin A and iron than by either nutrient alone (P = 0.034). The decrease in the MRDR relative to baseline was significant in the A + Fe group (P = 0.008). Iron status was also significantly improved in these women (P < 0.05) with both iron and vitamin A supplementation. The mechanism of the enhancing effect of iron on the vitamin A-induced reduction in the MRDR is not known. To assess the impact on mortality related to pregnancy of supplementing women of reproductive age each week with a recommended dietary allowance of vitamin A, either preformed or as beta carotene.
                Double blind, cluster randomised, placebo controlled field trial.
                Rural southeast central plains of Nepal (Sarlahi district).
                44 646 married women, of whom 20 119 became pregnant 22 189 times.
                270 wards randomised to 3 groups of 90 each for women to receive weekly a single oral supplement of placebo, vitamin A (7000 micrograms retinol equivalents) or beta carotene (42 mg, or 7000 micrograms retinol equivalents) for over 31/2 years.
                All cause mortality in women during pregnancy up to 12 weeks post partum (pregnancy related mortality) and mortality during pregnancy to 6 weeks postpartum, excluding deaths apparently related to injury (maternal mortality).
                Mortality related to pregnancy in the placebo, vitamin A, and beta carotene groups was 704, 426, and 361 deaths per 100 000 pregnancies, yielding relative risks (95% confidence intervals) of 0. 60 (0.37 to 0.97) and 0.51 (0.30 to 0.86). This represented reductions of 40% (P<0.04) and 49% (P<0.01) among those who received vitamin A and beta carotene. Combined, vitamin A or beta carotene lowered mortality by 44% (0.56 (0.37 to 0.84), P<0.005) and reduced the maternal mortality ratio from 645 to 385 deaths per 100 000 live births, or by 40% (P<0.02). Differences in cause of death could not be reliably distinguished between supplemented and placebo groups.
                Supplementation of women with either vitamin A or beta carotene at recommended dietary amounts during childbearing years can lower mortality related to pregnancy in rural, undernourished populations of south Asia. This double-blinded, randomized, controlled study was designed to study the effect of dietary supplementation with red palm oil during pregnancy on maternal and neonatal vitamin A status. A total of 170 women were recruited at 16 to 24 weeks of gestation and randomly assigned to an experimental group that received red palm oil to supply approximately one recommended dietary amount (RDA) (2,400 micrograms) of beta-carotene or to a control group that received an equivalent volume of groundnut oil. The women received the oils for a period of 8 weeks, starting at 26 to 28 weeks of gestation and extending to 34 to 36 weeks of gestation. The mean postintervention (34 to 36 weeks) levels of serum retinol were 1.20 +/- 0.22 (SD) mumol/L (95% CI, 1.15-1.25) in women receiving red palm oil and 0.73 +/- 0.15 mumol/L (95% CI, 0.69-0.77) in their infants; these levels were significantly higher than those in women receiving groundnut oil (1.07 +/- 0.26 mumol/L; 95% CI, 1.01-1.13; p < .01) and their infants (0.62 +/- 0.17 mumol/L; 95% CI, 0.57-0.67; p < .001). A significantly lower proportion of women in the red palm oil group than in the control group had vitamin A deficiency (serum retinol levels < 0.7 mumol/L) after intervention (1.5% vs. 9.7%). The proportion of women having anemia was significantly lower (p < .01) in the red palm oil-supplemented group (80.6%) than in the control group (96.7%). The mean birthweight and gestational age of the infants did not differ significantly between the two groups. An increased risk of low birth-weight (p = .003) and preterm delivery (p = .000) was observed with decreasing serum retinol levels in the third trimester of pregnancy. These results show that red palm oil supplementation significantly improved maternal and neonatal vitamin A status and reduced the prevalence of maternal anemia. Maternal vitamin A status in the later part of pregnancy is significantly associated with fetal growth and maturation. Hence red palm oil, a rich source of bioavailable vitamin A, could be used as a diet-based approach for improving vitamin A status in pregnancy. We examined whether supplementation with vitamin A and/or vitamins B, C, and E to HIV-infected women during pregnancy and lactation is related to increased concentrations of vitamins A, B12, and E in their infants during the first 6 months of life.
                We carried out a randomized clinical trial among 716 mother-infant pairs in Dar-es-Salaam, Tanzania. Women were randomly allocated to receive a daily oral dose of one of four regimens: vitamin A, multivitamins (B, C, and E), multivitamins including A, or placebo. Supplementation started at first prenatal visit and continued after delivery throughout the breastfeeding period. The serum concentration of vitamins A, E and B12 was measured in infants at 6 weeks and 6 months postpartum.
                Maternal vitamin A supplementation increased serum retinol in the infants at 6 weeks (mean difference=0.09 micromol/l, P<0.0001) and 6 months (mean difference=0.06 micromol/l, P=0.0002), and decreased the prevalence of vitamin A deficiency, but had no impact on serum vitamins E or B12. Multivitamins increased serum vitamin B12 at 6 weeks and 6 months (mean differences=176 pmol/l, P<0.0001 and 127 pmol/l, P<0.0001, respectively) and vitamin E (mean differences=1.8 micromol/l, P=0.0008 and 1.1 micromol/l, P=0.004, respectively) and decreased the prevalence of vitamin B12 deficiency.
                Vitamin supplementation to HIV-1-infected women is effective in improving the vitamin status of infants during the first 6 months of age. Vitamin A supplementation is believed to enhance immune responses to infection but few studies have assessed its effects on anti-malarial immunity, especially during pregnancy when women are at increased risk from both vitamin A deficiency and pregnancy-associated malaria. The pathological effects of malaria in pregnancy are believed to be due to the sequestration of parasites in the placenta mediated via binding of variant surface antigens (VSA) expressed on the surface of P. falciparum infected red blood cells to placental chondroitin sulphate A (CSA).
                We conducted a randomized double-blind controlled trial of vitamin A supplementation in 98 primigravid Ghanaian women to investigate the effects of vitamin A supplementation on levels of IgG antibodies binding to VSA of a clinical, P. falciparum placental isolate and to two isolates selected (or not) for adherence to CSA in vitro (anti-VSACSA IgG or anti-VSA IgG). Placental malarial infection was determined by placental blood smear and histology.
                Vitamin A supplementation was non-significantly associated with a decreased risk of active or chronic-active placental malarial infection compared to past, resolved infection at delivery, as determined by histology (OR=0.42, P=0.13--adjusted for level of education). After adjustment for differences in baseline values, levels of anti-VSACSA IgG to a placental, CSA-adherent isolate (EJ-24) but not to two isolates selected for CSA-adhesion in vitro (FCR3CSA and BusuaCSA), were significantly lower in women receiving vitamin A supplementation than in women receiving placebo (P=0.002). There was no apparent effect of vitamin A supplementation to levels of Ab to non-CSA-adherent parasite isolates.
                The data suggest that the reduction in the levels of anti-VSACSA antibodies to the known placental malaria isolate may reflect reduced intensity or duration of placental parasitaemia in women receiving vitamin A supplementation. These observations are of potential public health significance and deserve further investigation. To assess the effects of vitamin A supplementation in women with anaemia during pregnancy.
                Single-centre randomised controlled trial.
                Rural community in southern Malawi, central Africa.
                Seven hundred women with singleton pregnancies at 12-24 weeks measured by ultrasound scan and with haemoglobin <11.0 g/dl by HemoCue screening method. Analysis was by intention to treat. All received iron and folate, and sulphadoxine/pyrimethamine for antimalarial prophylaxis.
                Women were randomised to receive oral supplementation with daily 5000 or 10,000 iu vitamin A, or placebo.
                Anaemia, as assessed by Coulter counter, severe anaemia, iron status and indices of infection.
                Vitamin A deficiency was, in this rural population, less common than predicted. Vitamin A supplementation had no significant impact on anaemia, severe anaemia, iron status and indices of infection. Vitamin A stores were less likely to be depleted at the end of pregnancy in supplemented groups.
                Vitamin A supplementation programmes to reduce anaemia should not be implemented in similar antenatal populations in rural sub-Saharan Africa unless evidence emerges of positive benefit on substantive clinical outcomes. Introducing public health interventions of unknown benefit and with unclear biological mechanisms can divert scarce resources from clinical and social interventions more likely to impact maternal mortality. nan Although studies suggest that vitamin A or its metabolites influence the synthesis of erythropoietin in vitro and in animal models, it is unclear whether vitamin A supplementation increases plasma erythropoietin concentrations in humans.
                To determine whether daily vitamin A supplementation increases plasma erythropoietin concentrations in pregnant women with a high prevalence of anaemia.
                A randomized, double-blind, controlled clinical trial was conducted to examine the effect of daily vitamin A (3000 microg retinol equivalent), iron (30 mg), and folate (400 microg) versus iron (30 mg) and folate (400 microg) (control) on haemoglobin and plasma erythropoietin concentrations in 203 pregnant women in Malawi, Africa.
                Mean gestational age at enrollment was 23 wk, at which time 50% of the women were anaemic (haemoglobin <110 g/L). Mean (+/-SEM) change in haemoglobin from enrollment to 38 wk was 4.7+/-1.6 g/L (p=0.003) and 7.3+/-2.3 g/L (p=0.003) in the vitamin A and control groups, respectively. Mean change in plasma erythropoietin concentrations from enrollment to 38 wk was 2.39+/-5.00 (p=0.63) and -2.87+/-3.92 IU/L (p=0.46) in the vitamin A and controls groups, respectively. There were no significant differences between vitamin A and control groups in the slope of the regression line between log10 erythropoietin and haemoglobin at enrollment or 38 wk, and between enrollment and follow-up within either group.
                Vitamin A supplementation does not appear to increase haemoglobin and plasma erythropoietin concentrations among pregnant women with a high prevalence of anaemia in Malawi. Deficiencies of vitamin A, iron, and zinc are prevalent in women and infants in developing countries. Supplementation during pregnancy can benefit mother and infant.
                We examined whether supplementation during pregnancy with iron and folic acid plus beta-carotene or zinc or both improves the micronutrient status of mothers and infants postpartum.
                Pregnant women (n = 170) were supplemented daily only during pregnancy with beta-carotene (4.5 mg), zinc (30 mg), or both or placebo plus iron (30 mg) and folic acid (0.4 mg) in a randomized, double-blind, placebo-controlled trial. Micronutrient status was assessed 1 and 6 mo postpartum.
                Six months postpartum, plasma retinol concentrations were higher in the women who received zinc during pregnancy than in women who did not. Infants born to mothers supplemented with beta-carotene + zinc had higher plasma retinol concentrations, with the frequency of vitamin A deficiency reduced by >30% compared with the other 3 groups. Breast-milk beta-carotene concentrations were higher in all women supplemented with beta-carotene, but breast-milk retinol concentrations were higher only in women who received beta-carotene + zinc. Zinc concentrations did not differ among groups in mothers and infants.
                Zinc supplementation during pregnancy improved the vitamin A status of mothers and infants postpartum, which indicates a specific role of zinc in vitamin A metabolism. Addition of both beta-carotene and zinc to iron supplements during pregnancy could be effective in improving the vitamin A status of mothers and infants.
The pooled results of two large trials in Nepal and Ghana (with almost 95,000 women) do not currently suggest a role for antenatal vitamin A supplementation to reduce maternal or perinatal mortality. However the populations studied were probably different with regard to baseline vitamin A status and there were problems with follow-up of women. There is good evidence that antenatal vitamin A supplementation reduces maternal anaemia for women who live in areas where vitamin A deficiency is common or who are HIV-positive. In addition the available evidence suggests a reduction in maternal infection, but these data are not of a high quality.