Maternal vitamin A or beta-carotene supplementation in lactating bangladeshi women benefits mothers and infants but does not prevent subclinical deficiency

The effects of maternal postpartum vitamin A or beta-carotene supplementation on maternal and infant serum retinol concentrations, modified relative dose-response (MRDR) ratios and breast milk vitamin A concentrations were assessed during a community-based trial in Matlab, Bangladesh. At 1-3 wk postpartum, women were randomly assigned to receive either (1) 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 beta-carotene [7.8 mg (1300 RE)] (n = 73) or (3) daily placebos (n = 73) until 9 mo postpartum. Compared to placebos, vitamin A supplementation resulted in lower maternal MRDR ratios (i.e., increased liver stores) and higher milk vitamin A concentrations at 3 mo, but these improvements were not sustained. The beta-carotene supplementation acted more slowly, resulting in milk vitamin A concentrations higher than the placebo group only at 9 mo. Irrespective of treatment group, over 50% of women produced milk with low vitamin A concentrations (/=0. 06. We conclude that while both interventions were beneficial, neither was sufficient to correct the underlying subclinical vitamin A deficiency in these women nor to bring their infants into adequate vitamin A status.     

Vitamin A supplementation of women postpartum and of their infants at immunization alters breast milk retinol and infant vitamin A status

Vitamin A supplementation of lactating mothers and of infants at the time of diphtheria-pertussis-tetanus (DPT) and oral polio vaccine (OPV) immunizations have both been suggested as measures to prevent deficiency among infants. This multicenter randomized, double-blind, placebo-controlled trial was conducted in Ghana, India and Peru to determine the effect of maternal vitamin A supplementation on breast milk retinol and of maternal and infant supplementation on infant vitamin A status. Mothers in the intervention group received 60 mg vitamin A (as retinol palmitate) at 18-42 d postpartum; their infants were given 7.5 mg three times, i.e., at 6, 10 and 14 wk of age with DPT and OPV immunizations. Mothers and infants in the comparison group received a placebo. Maternal supplementation resulted in higher breast milk retinol at 2 mo postpartum [difference in means 7.1, 95% confidence interval (CI), 3.4, 10.8 nmol/g fat] and lower proportion of mothers with breast milk retinol < or = 28 nmol/g fat (15.2 vs. 26.6%, 95% CI of difference -16.6, -4.1%). At 6 and 9 mo, maternal supplementation did not affect breast milk retinol or the proportion of mothers with low breast milk retinol. Vitamin A supplementation of the mothers and their infants reduced the proportion of infants with serum retinol < or = 0.7 micro mol/L (30.4 vs. 37%, 95% CI of difference -13.7, 0.6%) and that with low vitamin A stores as indicated by the modified relative dose response (MRDR) > 0.06 (44.2 vs. 52.9%, 95% CI of difference -16.6, -0.9%) at 6 mo. Supplementation had no effect at 9 mo. The beneficial effect of supplementation on breast milk retinol and infants' vitamin A status varied by site. It was greatest in India followed by Ghana and Peru. 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. Additional strategies to improve vitamin A status of 6- to 9-mo-old infants must be considered.     

The effects of maternal and infant vitamin A supplementation on vitamin A status: a randomised trial in Kenya

Postpartum vitamin A supplementation of mothers and infants is recommended, but the efficacy has been questioned. In this double-blind, placebo-controlled trial, Kenyan mother-infant pairs were randomised to maternal vitamin A (400,000 IU) or placebo <24 h postpartum, and infant vitamin A (100,000 IU) or placebo at 14 weeks. Milk retinol was determined at weeks 4, 14 and 26, and maternal and infant serum retinol at weeks 14 and 26. Infant retinol stores were assessed at week 26, using a modified relative dose response (MRDR) test. Among 564 women, serum retinol at 36 weeks gestation was 0.81 (SD 0.21) micromol/l, and 33.3% were<0.7 micromol/l. Maternal serum retinol was not different between groups, but milk retinol was higher in the vitamin A group: (0.67 v. 0.60 micromol/l; 0.52 v. 0.44 micromol/l; 0.50 v. 0.44 micromol/l at 4, 14 and 26 weeks, respectively). When expressed per gram fat, milk retinol was higher in the vitamin A group only at 4 weeks. Infant serum retinol was not different between groups. However, although most infants had deficient vitamin A stores (MRDR>0.06%) at 26 weeks, vitamin A to infants, but not mothers, resulted in a lower proportion of infants with deficient vitamin A stores (69 v. 78 %). High-dose postpartum vitamin A supplementation failed to increase serum retinol and infant stores, despite modest effects on milk retinol. Infant supplementation, however, increased stores. There is a need for a better understanding of factors affecting absorption and metabolism of vitamin A.     

Comparison of the effects of supplemental red palm oil and sunflower oil on maternal vitamin A status

BACKGROUND: Conflicting results have been reported on the ability of dietary carotenoids to improve vitamin A status in lactating women. Red palm oil is one of the richest dietary sources of beta-carotene. OBJECTIVE: We aimed to determine the efficacy of red palm oil in increasing retinol and provitamin A status in pregnant and lactating women. DESIGN: Ninety rural, pregnant Tanzanian women from 3 randomly selected villages were recruited during their third trimester to participate in 3 dietary intervention groups: a control group, who were encouraged to maintain the traditional practice of eating staples with dark-green leafy vegetables, and 2 study groups, who were given either sunflower or red palm oil for use in household food preparations. The intervention lasted 6 mo. Plasma samples were collected at the third trimester and 1 and 3 mo postpartum, and breast-milk samples were collected 1 and 3 mo postpartum. RESULTS: Supplementation with red palm oil, which is rich in provitamin A, increased alpha- and beta-carotene concentrations significantly (P < 0.001) in both plasma and breast milk. Plasma retinol concentrations were similar in all dietary groups. Breast-milk retinol concentrations tended to decrease from 1 to 3 mo postpartum in the control group, but were maintained in both oil groups. The difference in change in breast-milk retinol concentration between the red palm oil group and the control group was significant (P = 0.041). CONCLUSIONS: Consumption of red palm oil increases concentrations of alpha- and beta-carotene in both breast milk and serum and maintains breast-milk retinol concentrations. Sunflower oil consumption seems to conserve breast-milk retinol similarly to consumption of red palm oil. Breast-milk retinol might be maintained through increased dietary intake of these vegetable oils and use of mild cooking preparation methods (such as the addition of oil at the end of cooking and avoidance of frying).     

Weekly vitamin A and iron supplementation during pregnancy increases vitamin A concentration of breast milk but not iron status in Indonesian lactating women

Studies on the effect of vitamin A and iron supplementation during pregnancy on maternal iron and vitamin A status postpartum are scarce. We investigated 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. During pregnancy, subjects were randomly allocated to two groups and received either (n = 88) a weekly supplement of iron (120 mg Fe as FeSO(4)) and folic acid (500 microg) or (n = 82) the same amount of iron and folic acid plus vitamin A [4800 retinol equivalents (RE)]. Transitional milk (4-7 d postpartum) had higher (P < 0.001) concentrations of retinol and iron than mature milk (3 mo postpartum). 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 micromol/L) and in mature milk (as micromol/g fat). Although serum retinol concentrations approximately 4 mo postpartum did not differ significantly, the weekly vitamin A and iron group had significantly fewer (P < 0.01) subjects with serum retinol concentrations < or = 0.70 micromol/L than the weekly iron group. Iron status and concentrations of iron in transitional and mature milk did not differ between groups. We have shown that weekly vitamin A and iron supplementation during pregnancy enhanced concentrations of retinol in breast milk although not in serum by approximately 4 mo postpartum. However, no positive effects were observed on iron status and iron concentration in breast milk.     

Breast milk immune factors in Bangladeshi women supplemented postpartum with retinol or beta-carotene

BACKGROUND: Vitamin A supplementation of mothers postpartum may improve infant health, not only by increasing vitamin A delivery to the infant through breast milk but also by increasing delivery of milk immune factors. Our hypothesis was that postpartum supplementation with vitamin A increases milk concentrations of certain soluble immune factors. DESIGN: In a double-blind trial conducted in Matlab, Bangladesh, women at 1-3 wk postpartum were randomly assigned to receive until 9 mo postpartum 1) a single dose of 60 mg retinol as retinyl palmitate followed by daily placebos (n = 69), 2) daily doses of 7.6 mg beta-carotene (n = 72), or 3) daily placebos (n = 71). Milk samples collected at baseline and 3 mo postpartum were analyzed by enzyme-linked immunosorbent assay for secretory immunoglobulin A, lactoferrin, lysozyme, and interleukin 8; by HPLC for total retinol; and by atomic absorption spectroscopy for sodium and potassium. RESULTS: After mammary epithelial permeability (defined as an elevated Na:K) and baseline immune factor concentrations were controlled for, there were no significant treatment effects on immune factors at 3 mo. Increased mammary permeability was common (25% of women at baseline and 12% at 3 mo) and was associated with higher concentrations of milk immune factors. Low body vitamin A stores at baseline, as assessed by the modified-relative-dose-response test, were associated with a higher Na:K, but neither retinol nor beta-carotene supplementation affected the prevalence of increased mammary permeability. CONCLUSIONS: Postpartum vitamin A supplementation does not increase milk concentrations of immune factors. The causes of increased mammary epithelial permeability in this population require further study.     

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

BACKGROUND: Deficiencies of vitamin A, iron, and zinc are prevalent in women and infants in developing countries. Supplementation during pregnancy can benefit mother and infant. OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.     

Evaluation of vitamin A supplementation regimens in Ghanaian postpartum mothers with the use of the modified-relative-dose-response test

BACKGROUND: Vitamin A deficiency is an important public health problem in many developing countries. Women of childbearing age and children are documented as the most affected groups. OBJECTIVE: The objective was to determine the length of time mothers are protected postpartum against vitamin A depletion after receiving either 400,000 IU vitamin A in 2 divided doses or 200,000 IU as a single dose plus a placebo 24 h apart. DESIGN: Mothers (n = 168) were recruited by trained fieldworkers 7-10 d after delivery. Modified-relative-dose-response (MRDR) tests were performed at baseline in 167 women, and vitamin A was administered within 6 wk after delivery. The women were randomly assigned to 2 main treatment groups, and each treatment group was divided into 3 follow-up subgroups. Each subgroup was invited back once at month 1, 3, or 5 for a second MRDR test. RESULTS: The serum retinol concentration and the MRDR value were 1.4 +/- 0.5 micromol/L and 0.048 +/- 0.037, respectively, at baseline. A significant improvement in vitamin A status occurred after vitamin A treatment as assessed by the MRDR test (P < 0.0001). Serum retinol concentrations were not different after vitamin A treatment (P = 0.87). CONCLUSIONS: The mothers had marginally depleted liver reserves of vitamin A at baseline on the basis of MRDR test results. Liver reserves of vitamin A significantly improved in both treatment groups, and the improvement was maintained for >or= 5 mo.     

Breast milk vitamin B-12 concentrations in Guatemalan women are correlated with maternal but not infant vitamin B-12 status at 12 months postpartum

In our previous studies, one-third of lactating Guatemalan women, infants, and children had deficient or marginal serum vitamin B-12 concentrations. Relationships among maternal and infant status and breast milk vitamin B-12, however, have not, to our knowledge, been investigated in such populations. Our purpose was to measure breast milk vitamin B-12 in Guatemalan women with a range of serum vitamin B-12 concentrations and explore associations between milk vitamin B-12 concentrations and maternal and infant vitamin B-12 intake and status. Participants were 183 mother-infant pairs breastfeeding at 12 mo postpartum. Exclusion criteria included mother <17 y, infant <11.5 or >12.5 mo, multiple birth, reported health problems in mother or infant, and mother pregnant >3 mo. Data collected on mothers and infants included anthropometry, serum and breast milk vitamin B-12, and dietary vitamin B-12. Serum vitamin B-12 concentrations indicated deficiency (<150 pmol/L) in 35% of mothers and 27% of infants and marginal status (150-220 pmol/L) in 35% of mothers and 17% of infants. In a multiple regression analysis, breast milk vitamin B-12 concentration was associated (P < 0.05) with both maternal vitamin B-12 intake (r = 0.26) and maternal serum vitamin B-12 (r = 0.30). Controlling for the number of breastfeeds per day and vitamin B-12 intake from complementary foods, infant serum vitamin B-12 was associated with maternal serum vitamin B-12 (r = 0.31; P < 0.001) but not breast milk vitamin B-12, implicating a long-term effect of pregnancy status on infant vitamin B-12 status at 12 mo postpartum.     

Impact of Maternal Daily Oral Low-Dose Vitamin A Supplementation on the Mother-Infant Pair: A Randomised Placebo-Controlled Trial in China

Background: The nutritional status of vitamin A in lactating mothers and infants is still not optimistic. Due to the dietary habits and dietary restrictions of postpartum customs in China, vitamin A supplementation has been advocated as a potential strategy to improve vitamin A status of lactating mothers with inadequate dietary vitamin A intake. Existing clinical trials are limited to single or double high-dose maternal administrations. However, in China, vitamin A supplements are readily available in the form of daily oral low-dose supplements, and the effect of these is unknown. This study aimed to evaluate the effects of daily oral low-dose vitamin A supplementation on the retinol levels in the serum and breast milk of lactating mothers and the health status of infants in China. Methods: Lactating mothers who met the inclusion criteria and planned to continue exclusive breastfeeding were randomly assigned to receive either daily oral vitamin A and D drops (one soft capsule of 1800 IU vitamin A and 600 IU vitamin D₂), or a matching placebo for 2 months. Before and after the intervention, dietary intake was investigated by instant photography, and the retinol concentration in maternal serum and breast milk was determined by ultra-high performance liquid chromatography-tandem mass spectrometry. During the trial, the health status of infants was diagnosed by a paediatrician or reported by lactating mothers. A total of 245 participants completed the study, with 117 in the supplementation group and 128 in the control group. Results: After the 2-month intervention, maternal serum retinol concentrations increased in the supplementation group with no change in the control group. Although breast milk retinol concentrations decreased significantly in both groups, the decrease in the supplementation group was significantly lower than that in the control group. However, maternal vitamin A supplementation was not associated with a lower risk of infant febrile illness, respiratory tract infection, diarrhoea, and eczema. Conclusions: Daily oral low-dose vitamin A supplementation is helpful in improving maternal vitamin A status, despite having no effect on infant health status through breast milk.     

Breast-milk vitamin A as an indicator of the vitamin A status of women and infants.

This article reviews the evidence for using breast-milk vitamin A as an indicator of vitamin A status and provides technical information for researchers who want to use this indicator to assess the vitamin A status of women and breast-fed children. Breast-milk vitamin A is a unique indicator for assessing the vitamin A status of lactating women and their breast-fed infants, and has recently been recommended by WHO for use in monitoring global elimination of vitamin A deficiency. Assessing breast-milk vitamin A is less invasive than alternative approaches for assessing a mother''s vitamin A status and not at all invasive for her infant. Collection of milk samples in the field is generally feasible and acceptable. Breast-milk vitamin A appears to be an especially good indicator for measuring the impact of vitamin A interventions on women and infants, and for this purpose, it is more responsive than other indicators.     

Maternal low-dose vitamin A or beta-carotene supplementation has no effect on fetal loss and early infant mortality: a randomized cluster trial in Nepal

BACKGROUND: The effect of vitamin A supplementation on the survival of infants aged <6 mo is unclear. Because most infant deaths occur in the first few month of life, maternal supplementation may improve infant survival. OBJECTIVES: The objective was to assess the effect of maternal vitamin A or beta-carotene supplementation on fetal loss and survival of infants <6 mo of age. DESIGN: Married women of reproductive age in 270 wards of Sarlahi district, Nepal, were eligible to participate. Wards were randomly assigned to have women receive weekly doses of 7000 microg retinol equivalents as retinyl palmitate (vitamin A), 42 mg all-trans-beta-carotene, or placebo. Pregnancies were followed until miscarriage, stillbirth, maternal death, or live birth of one or more infants, who were followed through 24 wk of age. RESULTS: A total of 43559 women were enrolled; 15832 contributed 17373 pregnancies and 15987 live born infants to the trial. The rate of fetal loss was 92.0/1000 pregnancies in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.06 (95% CI: 0.91, 1.25) and 1.03 (95% CI: 0.87, 1.19), respectively. The 24-wk mortality rate was 70.8/1000 live births in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.05 (95% CI: 0.87, 1.25) and 1.03 (95% CI: 0.86, 1.22), respectively. CONCLUSIONS: Small weekly doses of vitamin A or beta-carotene given to women before conception, during pregnancy, and through 24 wk postpartum did not improve fetal or early infant survival in Nepal.     

Validity of the relative-dose-response test and the modified-relative-dose-response test as indicators of vitamin A stores in liver

BACKGROUND: Our group and many others have used the relative-dose-response (RDR) test and the modified-RDR (MRDR) test as proxy indicators of liver stores of vitamin A. However, we have become concerned about the validity of these indicators. OBJECTIVE: Simulation models were used to assess effects of random variations in serum retinol concentration on the RDR and to assess effects of group differences in serum retinol concentration on the distribution of RDR and MRDR values. DESIGN: Random and independent samples were drawn from normally distributed, computer-generated numbers whose distributions simulated serum concentrations of retinol and 3,4-didehydroretinol as obtained from published reports. The resulting data sets were used to compute surrogate RDR or MRDR values. In model 1, the relation between serum concentrations of retinol and RDR was examined within a fictitious population. In models 2 and 3, fictitious populations with different distributions of serum retinol concentration were compared with respect to their RDR and MRDR values. RESULTS: Simulated RDR values and serum retinol concentrations were negatively related. Models 2 and 3 showed that group differences in serum retinol concentrations necessarily produced group differences in mean RDR or MRDR values. A mathematical artifact may explain the negative relation reported between MRDR and serum retinol concentration, and it dictates that this relation will necessarily vary between populations with different degrees of vitamin A deficiency. CONCLUSION: A continued search for alternative blood indicators of liver stores of vitamin A is needed.     

Use of the retinol-binding protein: transthyretin ratio for assessment of vitamin A status during the acute-phase response

The ratio plasma retinol-binding protein (RBP):transthyretin (TTR) has been proposed as a means to improve the assessment of vitamin A status of individuals with concurrent infection or inflammation. We have measured RBP and TTR in stored sera from South African children who had accidentally ingested kerosene. Samples were collected from these children in hospital when suffering acute inflammation and respiratory distress, and from them and neighbourhood control children 3 months later. Vitamin A status was defined by modified relative dose response (MRDR) tests of liver retinol stores at 3 months and by serum retinol concentration both when children were ill and when they were well. Illness was defined as either being in hospital or, at follow-up, as having a raised plasma alpha 1-acid glycoprotein (AGP) level. The RBP:TTR value was significantly decreased by both illness and low liver retinol stores. When the effects on RBP:TTR of illness and vitamin A stores were considered together for the 3-month follow-up samples, only vitamin A status significantly decreased the value. We calculated sensitivity and specificity of the RBP:TTR ratio against established measures of vitamin A status using a cut-off value of 0.3 for RBP:TTR and standard cut-off values for MRDR (0.06) and plasma retinol (0.7 mumol/l). Compared with MRDR, RBP:TTR had sensitivities of 76% and 43% and specificities of 22% and 81% to detect vitamin A deficiency in hospitalized and well children respectively. Compared with plasma retinol, sensitivities were 88% and 44% and specificities were 55% and 64% in hospitalized and well children respectively. Only for the case of clinically well children with biochemical evidence of subclinical inflammation did sensitivity (62% and 100% against MRDR and plasma retinol respectively) and specificity (100% and 60% against MRDR and retinol) approach useful levels for an assessment tool. Overall, although a trend supporting the theory behind the use of the RBP:TTR for assessment of vitamin A status in infection was observed in the current study, the ratio did not provide adequate sensitivity and specificity to be a useful assessment tool.     

Vitamin A and iron supplementation of Indonesian pregnant women benefits vitamin A status of their infants.

Many Indonesian infants have an inadequate nutritional status, which may be due in part to inadequate maternal nutrition during pregnancy. This study was designed to investigate whether infant nutritional status could be improved by maternal vitamin A and Fe supplementation during gestation. Mothers of these infants from five villages had been randomly assigned on an individual basis, supervised and double-blind, to receive supplementation once weekly from approximately 18 weeks of pregnancy until delivery. Supplementation comprised 120 mg Fe and 500 microg folic acid with or without 4800 retinol equivalent vitamin A. Mothers of infants from four other villages who participated in the national Fe and folic acid supplementation programme were also recruited; intake of tablets was not supervised. Anthropometric and biochemical parameters of infants and their mothers were assessed approximately 4 months after delivery. Infants of mothers supplemented with vitamin A plus Fe had higher serum retinol concentrations than infants of mothers supplemented with Fe alone. However, the proportion of infants with serum retinol concentrations <0.70 micromol/l was >70 % in all groups. Maternal and infant serum retinol concentrations were correlated. Fe status, weight and length of infants were similar in all groups. Fe status of girls was better than that of boys, but boys were heavier and longer. We conclude that supplementation with vitamin A in conjunction with Fe supplementation of women during pregnancy benefits vitamin A status of their infants. However, considering the large proportion of infants with marginal serum retinol concentrations, it may still be necessary to increase their vitamin A intake.     

Contribution of breastfeeding to vitamin A nutrition of infants: a simulation model

OBJECTIVE: To provide information on the potential contribution to vitamin A nutrition in infants of strategies for improving maternal vitamin A status and increasing the consumption of breast milk. METHODS: The contribution of breastfeeding to the vitamin A nutrition of children in eight age groups between 0 and 24 months was simulated under four sets of conditions involving two levels of breast milk consumption with or without maternal vitamin A supplementation. FINDINGS: During the first 6 months, optimal breastfeeding on its own (compared with withholding colostrum and then partially breastfeeding after the first week) was as effective as postpartum maternal supplementation alone, retinol intakes being increased by 59 micrograms per day and 68 micrograms per day, respectively. Combined in synergy, these strategies increase retinol intake by 144 micrograms per day, or 36% of the recommended intake. After 6 months, partial breastfeeding continued to provide a significant proportion of the recommended intakes: 42% from 6-12 months and 61% during the second year. CONCLUSION: Maternal supplementation with a high dose of vitamin A at the time of delivery and the promotion of optimal breastfeeding practices are highly effective strategies for improving vitamin A nutrition in infants and should be strengthened as key components of comprehensive child survival programmes.     

Efficacy of a vitamin A-fortified wheat-flour bun on the vitamin A status of Filipino schoolchildren

BACKGROUND: Wheat flour is a possible food vehicle for vitamin A fortification. OBJECTIVE: This study assessed the efficacy of consumption of a vitamin A-fortified wheat-flour bun (pandesal) on the vitamin A status of school-age children. DESIGN: This was a double-masked clinical trial conducted in 396 and 439 children aged 6-13 y attending 4 rural schools in the Philippines. The children were randomly assigned to a vitamin A-fortified (experimental) or nonfortified (control) group. A 60-g vitamin A-fortified pandesal (containing approximately 133 microg retinol equivalents) or a nonfortified pandesal was consumed by the children 5 d/wk for 30 wk. Vitamin A status, hemoglobin concentration, anthropometric status, morbidity, and dietary intake were assessed at baseline and 30 wk later. A modified relative dose response (MRDR) was assessed in a subsample of 20% of the children ( approximately 75/group) with the lowest initial serum retinol concentration at the 30-wk follow-up. RESULTS: Baseline serum retinol significantly modified the effect of the intervention. The fortified group, whose initial serum retinol concentrations were below the median, had a 0.07 +/- 0.03-micromol/L greater improvement in serum retinol at the 30-wk follow-up than did the control group (P: = 0.02). Improved vitamin A status was also evident in the MRDR subsample. End-of-study differences in the MRDR showed that vitamin A- fortified pandesal intake decreased the percentage of children with inadequate liver vitamin A stores by 50% (15.3% compared with 28.6%; P: = 0.05). CONCLUSIONS: Daily consumption of vitamin A-fortified pandesal significantly improved the vitamin A status of Filipino school-age children with marginal-to-low initial serum retinol concentrations.     

Circulating levels of retinol, tocopherol and carotenoid in Nepali pregnant and postpartum women following long-term beta-carotene and vitamin A supplementation

OBJECTIVE: To characterize circulating carotenoid and tocopherol levels in Nepali women during pregnancy and post-partum and to determine the effects of beta-carotene and vitamin A supplementation on their concentration in serum. DESIGN: Randomized community supplementation trial. SETTING: The study was carried out from 1994 to 1997 in the Southern, rural plains District of Sarlahi, Nepal. SUBJECTS: A total of 1431 married women had an ascertained pregnancy, of whom 1186 (83%) provided an analyzable serum sample during pregnancy; 1098 (77%) provided an analyzable 3-4 months post-partum serum sample. INTERVENTIONS: Women received a weekly dose of vitamin A (7000 microg RE), beta-carotene (42 mg) or placebo before, during and after pregnancy. Serum was analyzed for retinol, alpha-tocopherol, gamma-tocopherol, beta-carotene, alpha-carotene, lycopene, lutein + zeaxanthin, and beta-cryptoxanthin concentrations during mid-pregnancy and at approximately 3 months post-partum. RESULTS: Compared to placebo, serum retinol, beta-carotene, gamma-tocopherol, beta-cryptoxanthin and lutein + zeaxanthin concentrations were higher among beta-carotene recipients during pregnancy and, except for beta-cryptoxanthin, at postpartum. In the vitamin A group, serum retinol and beta-cryptoxanthin were higher during pregnancy, and retinol and gamma-tocopherol higher at postpartum. Lutein + zeaxanthin was the dominant carotenoid, regardless of treatment group, followed by serum beta-carotene. Serum lycopene level was lowest, and very low compared to the US population. Serum retinol was higher, and carotenoid and alpha-tocopherol lower, at postpartum than during pregnancy in all groups. CONCLUSIONS: Pregnant and lactating Nepali women have lower serum carotenoid and tocopherol levels than well-nourished populations. beta-carotene supplementation appeared to increase levels of tocopherol and other carotenoids in this population.     

Nutritional vitamin A status in northeast Brazilian lactating mothers

Background: Vitamin A deficiency is the major cause of morbidity and mortality among children and in women of reproductive age in developing countries. The present study aimed to assess maternal nutritional vitamin A status, as well as analyse the association of preformed vitamin A and pro‐vitamin A consumption on the nutritional status of nursing mothers, based on serum retinol and retinol colostrum concentrations coupled with dietary intake. Methods: Serum and colostrums were collected from 86 healthy parturients, recruited within 16 h postpartum. Blood samples were obtained, the morning after an overnight fast. Retinol was analysed by high‐performance liquid chromatography. Dietary vitamin A was assessed using a food frequency questionnaire and the women were separated into two groups according to the predominant dietary source of vitamin A: group A, >50% preformed vitamin A (n = 37); and group B >50% pro‐vitamin A carotenoids, (n = 49). Results: Serum retinol and total vitamin A ingestion (mean ± SD) were higher in group A than in group B (1.4 ± 0.4 μmol L^?1 and 2072.0 ± 1465.9 μg retinol activity equivalent (RAE) day^?1 versus 1.2 ± 0.6 μmol L^?1 and 1051.6 ± 920.4 μg RAE day^?1, respectively (P < 0.05), but colostrum retinol (3.4 ± 1.7 μmol L^?1 and 3.6 ± 1.9 μmol L^?1) was similar in both groups. In group B, 36.7% (n = 18) of the nursing mothers presented a risk of developing vitamin A deficiency, based on their dietary intake. Conclusions: On the basis of the intake of the pro‐vitamin A carotenoids, some women may be at risk of vitamin A deficiency. However, their status is currently normal, as indicated by serum and milk retinol concentrations.     

Cigarette smoking during pregnancy in rural Nepal. Risk factors and effects of beta-carotene and vitamin A supplementation

OBJECTIVE: We examined risk factors of smoking and the association between smoking and pregnancy-related and 6-month infant mortality in rural Nepal, where 30% women reported smoking during pregnancy. DESIGN: Cross-sectional analysis of risk factors associated with smoking status and health consequences of smoking, using prospective data collected as part of a randomized community trial to examine the effect of maternal vitamin A or beta-carotene supplementation on maternal mortality. SETTING: Rural, southeastern plains of Nepal. SUBJECTS AND METHODS: A total of 17 767 women contributed at least one pregnancy during 3.5 y of the study. Data on cigarette or bidi (rolled tobacco) smoking were collected using a 7-day recall, twice during pregnancy. Associations between smoking status and maternal diet, morbidity profile, household socioeconomic status and serum concentration of retinol, carotenoids and tocopherols were examined. Further, relative risk (RR) and 95% confidence intervals (CI) were calculated to estimate supplement effects on pregnancy-related mortality, stratified by smoking status during pregnancy. RESULTS: Smokers were more likely to be older, illiterate and poor compared to nonsmokers. Fruit and vegetable consumption among smokers and nonsmokers did not vary. However, smokers were more likely to consume meat/fish/eggs and less likely to consume milk than nonsmokers. They were also more likely to report symptoms of vaginal bleeding, edema, severe headache and convulsions during pregnancy relative to nonsmokers. Mortality per 100,000 pregnancies appeared to be higher among smokers than nonsmokers in the placebo group (915 vs 584, RR=1.57, 95% CI: 0.80-3.08). beta-Carotene supplementation reduced pregnancy-related mortality both among smokers (RR=0.31 95% CI: 0.11-0.89) and nonsmokers (RR=0.41, 95% CI: 0.19-0.89). Similar results obtained with vitamin A supplementation were not statistically significant. Infant mortality up to 6 months was approximately 30% higher among smokers compared to nonsmokers in the placebo group both before and after adjusting for confounding factors. Neither supplement given to women reduced infant mortality. CONCLUSIONS: Cigarette smoking during pregnancy is associated with an increased risk of maternal and infant mortality in rural Nepal. beta-Carotene and to some extent vitamin A may reduce the risk of pregnancy-related mortality, but not infant mortality, among both smokers and nonsmokers.