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.     

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.     

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.     

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.     

Vitamin A status of preterm infants during infancy

Plasma retinol and retinol-binding protein (RBP) were measured in 67 enterally fed preterm infants (750-1398 g) at 33 +/- 2 wk postconceptional age (PCA), and at regular intervals during infancy. Retinol and RBP declined by 35 +/- 2 wk PCA and remained low at 38 wk after discharge, with the infants fed a term-infant formula. At 38 +/- 2 wk PCA, 48% (32 of 67) of these infants had plasma retinol concentrations less than 0.35 mumol/L. Mean retinol and RBP rose over the next 7 mo, but large numbers of infants (26 of 59 at 48 wk, 10 of 61 at 57 wk) had hyporetinolemia (0.35-0.67 mumol/L). Plasma RBP leveled off at 57 +/- 2 wk PCA and remained low (less than 0.95 mumol/L) in many infants throughout the first year of life. Lower plasma retinol and RBP concentrations at 33 and 38 wk correlated with longer periods of intravenous nutrition. At 57 and 69 wk, lower retinol and RBP correlated with higher birth order. Suboptimal vitamin A status may occur for many months after preterm infants are discharged from the hospital.     

Randomized controlled safety and efficacy trial of 2 vitamin A supplementation schedules in Tanzanian infants

BACKGROUND: Vitamin A supplementation reduces morbidity and mortality in children living in areas endemic for vitamin A deficiency. Routine vitamin A supplementation usually starts only at age 9 mo, but high rates of illness and mortality are seen in the first months of life. OBJECTIVE: The objective of the study was to evaluate the safety and efficacy of vitamin A supplementation at the same time as routine vaccination in infants aged 1-3 mo. DESIGN: We recruited 780 newborn infants and their mothers to a randomized double-blind controlled trial in Ifakara in southern Tanzania. In one group, mothers received 60,000 microg vitamin A palmitate shortly after delivery, and their infants received 7500 microg at the same time as vaccinations given at approximately 1, 2, and 3 mo of age. In the other group, mothers received a second 60,000-microg dose when their infant was aged 1 mo, and their infants received 15,000 microg at the same time as the routine vaccinations. VAD was defined as a modified relative dose-response test result of >or=0.060. RESULTS: High-dose vitamin A supplementation was well tolerated. The relative risk of VAD at 6 mo in the high-dose group compared with the lower dose group was 0.91 (95% CI: 0.76, 1.09; P=0.32). Serum retinol and incidence of illness did not differ significantly between the 2 groups. Some vitamin A capsules degraded toward the end of the study. CONCLUSIONS: Doubling the doses of vitamin A to mothers and their young infants is safe but unlikely to reduce short-term morbidity or to substantially enhance the biochemical vitamin A status of infants at age 6 mo. The stability of vitamin A capsules merits further investigation.     

The concentration of free holo-retinol binding protein is higher in vitamin A-sufficient than in deficient Nepalese women in late pregnancy

Free holo-retinol binding protein (RBP) [i.e., unbound to transthyretin (TTR)] plays a role in transporting vitamin A across the placenta during pregnancy. In a cross-sectional study of clinically healthy urban women, we assessed the association among clinical and biochemical factors on estimated concentrations of free holo-RBP during the last trimester of pregnancy. Serum samples obtained from a subsample of women (n = 259), who had participated in the Night Vision Threshold Test study in Nepal, were analyzed for determinations of retinol by HPLC, and RBP, TTR, and alpha-1 acid glycoprotein by radial immunodiffusion. Free holo-RBP concentrations were calculated using dissociation constants for free holo- and apo-RBP. Among these women, 30% were vitamin A deficient based on either the RBP:TTR index < or = 0.36 or serum retinol < 1.05 micromol/L. Using stepwise regression analyses, the RBP:TTR index explained 75% of the variance in free holo-RBP concentrations, whereas retinol explained only 14%. Women were classified as vitamin A sufficient (n = 185) or deficient (n = 74) using the RBP:TTR index and were stratified into 3 gestational groups (I: 24-28 wk, II: 29-33 wk, III: >33 wk). Concentrations of free holo-RBP were higher in vitamin A-sufficient women than in vitamin A-deficient women (mean +/- SEM, 48.1 +/- 1.2 vs. 27.6 +/- 0.8 nmol/L; P < 0.001), and in a 3 x 2 factorial analysis, the interaction between gestational group and vitamin A status was significant. These results demonstrate that the RBP:TTR index is a useful proxy for free holo-RBP concentration and that vitamin A status affects its distribution.     

Genetic hemoglobin disorders, infection, and deficiencies of iron and vitamin A determine anemia in young Cambodian children

In Cambodia, many factors may complicate the detection of iron deficiency. In a cross-sectional survey, we assessed the role of genetic hemoglobin (Hb) disorders, iron deficiency, vitamin A deficiency, infections, and other factors on Hb in young Cambodian children. Data on sociodemographic status, morbidity, and growth were collected from children (n = 3124) aged 6 to 59 mo selected from 3 rural provinces and Phnom Penh municipality. Blood samples were collected (n = 2695) for complete blood count, Hb type (by DNA analysis), ferritin, soluble transferrin receptor (sTfR), retinol-binding protein (RBP), C-reactive protein, and α(1)-acid glycoprotein (AGP). Genetic Hb disorders, anemia, and vitamin A deficiency were more common in rural than in urban provinces (P < 0.001): 60.0 vs. 40.0%, 58.2 vs. 32.7%, and 7.4 vs. 3.1%, respectively. Major determinants of Hb were age group, Hb type, ferritin, sTfR, RBP, AGP >1.0 g/L (P < 0.001), and rural setting (P < 0.05). Age group, Hb type, RBP, elevated AGP, and rural setting also influenced ferritin and sTfR (P < 0.02). Multiple factors affected anemia status, including the following: age groups 6-11.99 mo (OR: 6.1; 95% CI: 4.3, 8.7) and 12-23.99 mo (OR: 2.7; 95% CI: 2.1, 3.6); Hb type, notably Hb EE (OR: 18.5; 95% CI: 8.5, 40.4); low ferritin (OR: 3.2; 95% CI: 2.2, 4.7); elevated AGP (OR: 1.4; 95% CI: 1.2,1.7); rural setting (OR: 2.3; 95% CI: 1.7, 3.1); low RBP (OR: 3.6; 95% CI: 2.2, 5.9); and elevated sTfR (OR: 2.1; 95% CI: 1.7, 2.7). In Cambodia, where a high prevalence of genetic Hb disorders exists, ferritin and sTfR are of limited use for assessing the prevalence of iron deficiency. New low-cost methods for detecting genetic Hb disorders are urgently required.     

Effect of high-dose vitamin A supplementation on the immune response to Bacille Calmette-Guerin vaccine

BACKGROUND: Vitamin A supplementation (VAS) at birth has been associated with decreased mortality in Asia. Bacille Calmette-Guérin (BCG) vaccine is given at birth in tuberculosis-endemic countries. Previous studies suggest that VAS may influence the immune response to vaccines. OBJECTIVE: Our objective was to examine whether VAS influences the immune response to simultaneously administered BCG vaccine. DESIGN: Within a randomized trial of 50,000 IU vitamin A or placebo given with BCG vaccine at birth in Guinea-Bissau, 2710 infants were examined for BCG scar formation and delayed-type hypersensitivity (DTH) to purified protein derivative of Mycobacterium tuberculosis (PPD) at 2 and 6 mo of age. The ex vivo cytokine response to PPD was measured in 607 infants. RESULTS: At 2 mo of age, 39% (43% of the boys and 34% of the girls) responded to PPD. The prevalence ratio of a measurable PPD reaction for VAS compared with placebo recipients was 0.90 (95% CI: 0.80, 1.02) for all infants, 0.81 (95% CI: 0.69, 0.95) for boys, and 1.04 (95% CI: 0.86, 1.26) for girls. At 6 mo of age, 42% of the infants responded to PPD. No difference was observed between VAS and placebo recipients. The prevalence of BCG scar was not affected by VAS. The ex vivo interferon-gamma response to PPD was increased by VAS (means ratio: 1.40; 95% CI: 1.03, 1.91). CONCLUSIONS: VAS with BCG vaccination does not appear to interfere with the long-term immune response to BCG. However, VAS temporarily altered the DTH reaction to PPD in boys at 2 mo of age, suggesting sex differences in the immunologic response to VAS given with BCG. This trial was registered at www.clinicaltrials.gov as #NCT00168597.     

Liver concentrations of vitamin A and carotenoids, as a function of age and other parameters, of American children who died of various causes

To assess the age-dependent vitamin A status of children, liver samples taken at autopsy from 170 American children 0-15 yr of age were analyzed for vitamin A and carotenoids. The median liver vitamin A concentration at birth was low (11 micrograms retinol/g), remained constant to 3 mo, rapidly increased to 4 yr (130 micrograms/g) and then remained constant into adolescence. In contrast the vitamin A status of premature infants deteriorated after birth. Of infants less than 3 mo, approximately one-fourth and two-thirds showed liver vitamin A concentrations less than or equal to 5 micrograms retinol/g and less than or equal to 20 micrograms/g, respectively. On the other hand, essentially all infants greater than or equal to 6 months showed an adequate vitamin A status, defined as liver stores greater than 20 micrograms retinol/g liver. Liver carotenoid concentrations did not meaningfully correlate with age or with vitamin A concentrations. Parameters that did not significantly affect the vitamin A concentration were: 1) height and weight in infants less than 1 mo, except in the highest weight-height groups, 2) sex, although values of females were slightly higher than males, and 3) causes of death.     

A randomized, 4-month mango and fat supplementation trial improved vitamin A status among young Gambian children

Supplementation with carotene-rich fruits may be an effective and sustainable approach to prevent vitamin A deficiency. To test the effectiveness of mango supplementation, 176 Gambian children, aged 2 to 7 y, were randomly assigned to one of four treatments: 75 g of dried mango containing approximately 150 micro g retinol activity equivalents with (MF) or without (M) 5 g of fat, 5 d/wk for 4 mo or 60,000 micro g of vitamin A (A) or placebo (P) capsule at baseline. After 4 mo, plasma beta-carotene was greater in both the M (P < 0.05) and MF (P = 0.07) groups compared with the P group. After controlling for baseline plasma retinol, elevated acute phase proteins and age, plasma retinol concentrations in the A and MF, but not M, groups were higher than in the P group at the end of the study (P < 0.01). Increases in retinol concentrations, however, were small in both groups. These results support the use of dietary supplementation with dried mangoes and a source of fat as one of several concurrent strategies that can be used to help maintain vitamin A status of children in developing countries where there is a severe seasonal shortage of carotenoid-rich foods.     

Vitamin A supplementation in iodine-deficient African children decreases thyrotropin stimulation of the thyroid and reduces the goiter rate

BACKGROUND: Vitamin A (VA) deficiency (VAD) and iodine deficiency (ID) often coexist in children in Africa. VAD may affect thyroid function and the response to iodine prophylaxis. OBJECTIVE: The aim was to investigate the effects of supplementation with iodine or VA alone, and in combination, in children with concurrent VAD and ID. DESIGN: A 6-mo randomized, double-blind, 2 x 2 intervention trial was conducted in 5-14 y-old South African children (n = 404), who, on average, had mild-to-moderate VAD and ID. At baseline and after 3 mo, children received 1) iodine (191 mg I as oral iodized oil) + placebo (IS group), 2) VA (200000 IU VA as retinyl palmitate) + placebo (VAS group), 3) both iodine and VA (IS+VAS group), or 4) placebo. At baseline, 3 mo, and 6 mo, urinary iodine (UI), thyroid volume, thyrotropin (thyroid-stimulating hormone; TSH), total thyroxine (TT(4)), thyroglobulin, serum retinol (SR), and retinol-binding protein (RBP) were measured. RESULTS: SR and RBP increased significantly with VA supplementation (P < 0.05). For UI, SR, and RBP, there were no significant treatment interactions between iodine and vitamin A. The 3-factor and all three 2-factor interactions were significant for thyroid volume, TSH, and thyroglobulin (P < 0.001), whereas none of these interactions were significant for TT(4). There was a clear effect of VAS without IS on TSH, thyroglobulin, and thyroid volume; all 3 variables decreased significantly (P < 0.05). CONCLUSIONS: Iodine prophylaxis is effective in controlling ID in areas of poor vitamin A status. VA supplements are effective in treating VAD in areas of mild ID and have an additional benefit-through suppression of the pituitary TSHbeta gene, VAS can decrease excess TSH stimulation of the thyroid and thereby reduce the risk of goiter and its sequelae.     

Preconception homocysteine and B vitamin status and birth outcomes in Chinese women

BACKGROUND: The associations between homocysteine, B vitamin status, and pregnancy outcomes have not been examined prospectively. OBJECTIVE: We assessed the associations of preconception homocysteine and B vitamin status with preterm birth and birth of low-birth-weight (LBW) and small-for-gestational-age (SGA) infants in Chinese women. DESIGN: This was a case-control study of women aged 21-34 y. Preterm cases (n = 29) delivered living infants at <37 wk gestation; term controls (n = 405) delivered infants at > or =37 wk. LBW cases (n = 33) had infants weighing <2500 g; normal-birth-weight controls (n = 390) had infants weighing > or =2500 g. SGA cases (n = 65) had infants below the 10th percentile of weight-for-gestational-age; appropriate-for-gestational-age controls (n = 358) had infants above this cutoff. Nonfasting plasma concentrations of homocysteine, folate, and vitamins B-6 and B-12 were measured before conception. RESULTS: Elevated homocysteine (> or =12.4 micro mol/L) was associated with a nearly 4-fold higher risk of preterm birth (OR: 3.6; 95% CI: 1.3, 10.0; P < 0.05). The risk of preterm birth was 60% lower among women with vitamin B-12 > or =258 pmol/L than among vitamin B-12-deficient women (OR: 0.4; 95% CI: 0.2, 0.9; P < 0.05) and was 50% lower among women with vitamin B-6 > or =30 nmol/L than among vitamin B-6-deficient women (OR: 0.5; 95% CI: 0.2, 1.2; NS). Folate status was not associated with preterm birth, and homocysteine and B vitamin status were not associated with LBW or SGA status. CONCLUSIONS: Elevated homocysteine and suboptimal vitamin B-12 and B-6 status may increase the risk of preterm birth. These results need to be confirmed in larger prospective studies.     

Dietary vitamin A intake and nondietary factors are associated with reversal of stunting in children

We examined prospectively the associations between dietary vitamin A intake, nondietary factors and growth in 8174 Sudanese children ages 6-72 mo who were stunted at the start of follow-up. All subjects were weighed and measured at baseline and at 6-mo intervals for 18 mo of follow-up. Dietary vitamin A intake during the prior 24 h was assessed using recall of vitamin A-containing foods at baseline and 6-mo intervals. We examined the association of dietary vitamin A intake with growth and the incidence of recovery of stunting after controlling for age, sex, breast-feeding status and socioeconomic variables. We found that carotenoid intake was associated with a greater incidence of reversal of stunting. Children in the highest quintile grew 13 mm more during the study period than children in the lowest quintile [95% confidence interval (CI): 0-25 mm] in multivariate analyses. The relative risk (RR) of recovery associated with vitamin A intake was greater in infants up to 1 y old (RR = 3.3, CI: 0.9-11.7) than in children > or =3 y of age (RR = 1.0, CI: 0.8-1. 3) (P:-value for interaction = 0.08). Diets rich in carotenoids may increase the rate of recovery from stunting in children. Dietary effects on growth might be strongest among very young children and those who have been most malnourished. Age, sex, breast-feeding status, socioeconomic status and severity of baseline stunting also were associated with reversal of stunting in this population.     

Vitamin A supplementation in children with poor vitamin A and iron status increases erythropoietin and hemoglobin concentrations without changing total body iron

BACKGROUND: Vitamin A deficiency impairs iron metabolism; vitamin A supplementation of vitamin A-deficient populations may reduce anemia. The mechanism of these effects is unclear. In vitro and in animal models, vitamin A treatment increases the production of erythropoietin (EPO), a stimulant of erythropoiesis. OBJECTIVE: We measured the effect of vitamin A supplementation on hemoglobin, iron status, and circulating EPO concentrations in children with poor iron and vitamin A status. DESIGN: In a double-blind, randomized trial, Moroccan schoolchildren (n = 81) were given either vitamin A (200,000 IU) or placebo at baseline and at 5 mo. At baseline, 5 mo, and 10 mo, hemoglobin, indicators of iron and vitamin A status, and EPO were measured. RESULTS: At baseline, 54% of children were anemic; 77% had low vitamin A status. In the vitamin A group at 10 mo, serum retinol improved significantly compared with the control group (P < 0.02). Vitamin A treatment increased mean hemoglobin by 7 g/L (P < 0.02) and reduced the prevalence of anemia from 54% to 38% (P < 0.01). Vitamin A treatment increased mean corpuscular volume (P < 0.001) and decreased serum transferrin receptor (P < 0.001), indicating improved iron-deficient erythropoiesis. Vitamin A decreased serum ferritin (P < 0.02), suggesting mobilization of hepatic iron stores. Calculated from the ratio of transferrin receptor to serum ferritin, overall body iron stores remained unchanged. In the vitamin A group at 10 mo, we observed an increase in EPO (P < 0.05) and a decrease in the slope of the regression line of log10(EPO) on hemoglobin (P < 0.01). CONCLUSION: In children deficient in vitamin A and iron, vitamin A supplementation mobilizes iron from existing stores to support increased erythropoiesis, an effect likely mediated by increases in circulating EPO.     

Subclinical vitamin A deficiency in Israeli-Bedouin toddlers

OBJECTIVE: This study was designed to estimate the prevalence of and evaluate risk factors for subclinical vitamin A deficiency in Arab-Bedouin children at age 18 months, followed from birth. DESIGN: Community-based, prospective, cohort study conducted in Rahat, a large Arab-Bedouin township, located near the city of Beer Sheva in the Negev region of southern Israel. SUBJECTS: Healthy Bedouin infants (n=117) from the township, born at Soroka University Medical Center (SUMC) in Beer Sheva, were randomly recruited at birth. Enrollment was restricted to well infants born weighing >2500 g at birth. RESULTS: More than 15% of the children had serum retinol concentrations below 0.7 micromol/l. Male sex (odds ratio (OR) 4.17 [1.14-15.32], P=0.031), stunting at age 12 months (OR 10.09 [2.00-50.97], P=0.05) and warm season at age 18 months (OR 6.20 [1.36-28.28], P=0.018) were associated with vitamin A deficiency. Maternal education decreased the risk of vitamin A deficiency (OR 0.81 [0.68-0.95], P=0.011). CONCLUSIONS: Study results indicate a significant vitamin A deficiency problem among Bedouin children. Deficiency may be prevented by increasing dietary intake of vitamin A, especially during the warm season. Other interventions include preventing and controlling diarrheal diseases in order to avert nutritional stunting, and providing nutritional education to women of childbearing age. SPONSORSHIP: This study received financial support from the National Institute of Allergy and Infectious Diseases (AI-26497), the US-Israel Bi-national Science Foundation (BSF 90-00257), and the National Academy of Sciences/Institute of Medicine (AID/ANE 0158-G-SS-9035-00).     

Plasma retinol-binding protein predicts plasma retinol concentration in both infected and uninfected Cameroonian women and children

Variation in the relationship between plasma retinol-binding protein (RBP) and retinol (ROH) has implications for vitamin A (VA) status assessment using RBP. Our objectives were to identify factors affecting the RBP:ROH relationship and to derive and evaluate population-specific RBP cutoffs for VA deficiency (VAD) in Cameroon. Plasma RBP, C-reactive protein (CRP), α1-acid-glycoprotein (AGP), and ROH concentrations were compared in a subsample of women 15-49 y (n = 121) and children 12-59 mo (n = 123) included in a national survey conducted in 2009. Plasma RBP and ROH were highly correlated (r = 0.94 for women; r = 0.96 for children; P < 0.001). Pregnancy and lactation altered the RBP:ROH relationship in women, but obesity, elevated CRP and AGP, age, and VA status did not. Among children, age altered the RBP:ROH relationship, but sex, stunting, VA status, and elevated CRP and AGP did not. Cutoffs for VAD derived using regression analysis were <1.17 μmol RBP/L for women (corresponding to <1.05 μmol ROH/L) and <0.83 μmol RBP/L for children (corresponding to <0.70 μmol ROH/L). The sensitivity and specificity of derived cutoffs were 81.8 and 93.0% for women and 94.7 and 88.9% for children, respectively. The infection-adjusted prevalence of low VA status (<1.17 μmol RBP/L) was 21.9% (95% CI = 18.7-25.0%) among women. Among children, the infection-adjusted prevalence of VAD (<0.83 μmol RBP/L) was 35.0% (95% CI = 31.1-39.0%). In conclusion, VAD remains a public health problem in Cameroon. The RBP:ROH relationship should be considered in surveys using RBP to assess VA status, and use of population-specific cutoffs may be advisable.     

Regulation of metabolism of retinol-binding protein by vitamin A status in children with biliary atresia

Regulation of retinol-binding protein (RBP) by vitamin A status was studied in 43 children; 25 had biliary atresia and vitamin A deficiency, 15 had biliary atresia treated by vitamin A, and 9 control children had normal liver and vitamin A status. Vitamin A and RBP were assayed and the two forms of RBP, holo-RBP and apo-RBP, were separated in both liver and plasma. No difference in liver RBP concentrations was found between the three groups; apo-RBP was the most abundant form. Plasma RBP concentrations and the ratio of retinol to RBP were lower for vitamin A-deficient than for vitamin A-treated children. Two models could be proposed: 1) a preferential secretion of holo-RBP with variations in RBP catabolism or synthesis in vitamin A-deficient liver and 2) a continuous secretion of RBP by the liver with a rapid clearance of plasma apo-RBP in vitamin A deficiency.     

Vitamin A, retinol binding protein and lipids in type 1 diabetes mellitus

OBJECTIVE: A case-control study was conducted to evaluate the effects of type 1 diabetes mellitus (IDDM) on plasma levels of vitamin A (retinol) and serum levels of retinol-binding protein (RBP) and their relationship with the atherogenic indicators. SUBJECTS: A total of 47 randomised IDDM children were recruited from those treated at the Endocrinology Unit of the University Hospital of Granada (Spain). They were matched for age and sex with 16 healthy children. METHODS: The following parameters were measured in all patients: serum concentrations of total cholesterol, triglycerides, high (HDL, spectrophotometry), very low (VLDL) and low (LDL) density lipoprotein cholesterol (Friedewald's formula); serum levels of RBP (kinetic nephelometry); plasma vitamin A and glycosilated haemoglobin (HbA1c; high performance chromatography). RESULTS: Higher RBP concentrations in IDDM children (P=0.05), lower retinol levels (P=0.05) and lower vitamin A/cholesterol ratio (P=0.02) than in the control group were found; no differences in the atherogenic indicators were observed. There was a correlation between RBP and vitamin A (P=0.0001). Relationships between retinol, RBP and atherogenic indicators were demonstrated in the IDDM group (A-LDLc/HDLc (P=0.01); A-(VLDL+LDL)c/HDLc (P=0.007); RBP-LDLc/HDLc (P=0.05); RBP-(VLDL+LDL)c/HDLc (P=0.02)), and an inverse relationship was found between the vitamin A/TG ratio and HbA1c (P=0.004). The children with HbA1c>8% showed increased atherogenic indicators and lower vitamin A/CHOL and vitamin A/TG ratios than those with good control of the illness. CONCLUSIONS: The IDDM children with poor metabolic control face a higher atherogenic risk and vitamin A 'relative deficiency' risk than those with good metabolic control of their illness. Relationships between retinol and RBP with atherogenic indicators were found. The results suggest that vitamin A therapeutic supplements in IDDM children may reduce or prevent atherogenic risk.     

A multi-micronutrient beverage enhances the vitamin A and zinc status of Nigerian primary schoolchildren

Schoolchildren in Nigeria are rarely targeted by micronutrient interventions. We completed a 6-mo, double-blind, placebo-controlled trial to determine the effects of a multi-micronutrient beverage on biochemical and anthropometric indicators of nutritional status among schoolchildren participating in a pilot school feeding program in Nasarawa State, Nigeria. Children received 1 of 2 interventions 5 d/wk during school hours: 1) 250 mL/d of a multi-micronutrient beverage that included vitamin A, iron, and zinc (micronutrient); or 2) an isoenergetic control beverage (control). At baseline, 566 children 5-13 y old were randomized to groups (micronutrient: n = 288; control: n = 278). Height, weight, hemoglobin, and serum concentrations of C-reactive protein, ferritin, retinol, and zinc were measured at baseline and at the end of the study. A total of 270 children in the micronutrient group and 264 children in the control group completed the study. Self-reports of vomiting increased in both groups at 6 mo; however, the prevalence tended to be greater in the micronutrient group (21%) compared to the control group (14%) (P = 0.06). Biochemical changes were greater in the micronutrient group compared to control for serum retinol (0.10 ± 0.02 μmol/L vs. 0.02 ± 0.02 μmol/L; P = 0.016) and zinc (1.0 ± 0.2 μmol/L vs. 0.6 ± 0.2 μmol/L; P = 0.031). The intervention did not significantly affect hemoglobin or serum ferritin concentrations. The cost effectiveness of the intervention needs to be further evaluated, as does the efficacy of the beverage on anemia and indicators of iron status.