Vitamin A deficiency remains a nutritional concern in sub-Saharan Africa. Conventionally bred maize hybrids with high provitamin A carotenoid concentrations may have the potential to improve vitamin ...A status in maize-consuming populations.
We evaluated the efficacy of regular provitamin A carotenoid-biofortified "orange" maizemeal (∼15 μg β-carotene/g) consumption in improving vitamin A status and reducing vitamin A deficiency in children.
This was a cluster-randomized controlled trial in the rural farming district of Mkushi, Zambia. All 4- to 8-y-old children in an ∼400-km(2) area were identified and grouped by proximity into clusters of ∼15-25 children. We randomly assigned clusters to 1) orange maizemeal (n = 25), 2) white maizemeal (n = 25), or 3) a parallel, nonintervention group (n = 14). Children in intervention clusters (n = 1024) received 200 g maizemeal for 6 d/wk over 6 mo; the maizemeal was prepared according to standardized recipes and served in cluster-level kitchens. Staff recorded attendance and leftovers. We collected venous blood before and after the intervention to measure serum retinol, β-carotene, C-reactive protein, and α1-acid glycoprotein.
Intervention groups were comparable at baseline, and vitamin A status was better than anticipated (12.1% deficient on the basis of serum retinol <0.7 μmol/L). Although attendance at meals did not differ (85%), median daily maize intake was higher in white (154 g/d) than in orange (142 g/d) maizemeal clusters. At follow-up, mean serum β-carotene was 0.14 μmol/L (95% CI: 0.09, 0.20 μmol/L) higher in orange maizemeal clusters (P < 0.001), but mean serum retinol (1.00 ± 0.33 μmol/L overall) and deficiency prevalence (17.1% overall) did not differ between arms.
In this marginally nourished population, regular biofortified maizemeal consumption increased serum β-carotene concentrations but did not improve serum retinol. This trial was registered at clinicaltrials.gov as NCT01695148.
Antenatal multiple micronutrient (MM) supplementation improves birth outcomes relative to iron–folic acid (IFA) in developing countries, but limited data exist on its impact on pregnancy ...micronutrient status.
We assessed the efficacy of a daily MM (15 nutrients) compared with IFA supplement, each providing approximately 1 RDA of nutrients and given beginning at pregnancy ascertainment, on late pregnancy micronutrient status of women in rural Bangladesh. Secondarily, we explored other contributors to pregnancy micronutrient status.
Within a double-masked trial (JiVitA-3) among 44,500 pregnant women, micronutrient status indicators were assessed in n = 1526 women, allocated by cluster to receive daily MM (n = 749) or IFA (n = 777), at 10 wk (baseline: before supplementation) and 32 wk (during supplementation) gestation. Efficacy of MM supplementation on micronutrient status indicators at 32 wk was assessed, controlling for baseline status and other covariates (e.g., inflammation and season), in regression models.
Baseline status was comparable by intervention. Prevalence of deficiency among all participants was as follows: anemia, 20.6%; iron by ferritin, 4.0%; iron by transferrin receptor, 4.7%; folate, 2.5%; vitamin B-12, 35.4%; vitamin A, 6.7%; vitamin E, 57.7%; vitamin D, 64.0%; zinc, 13.4%; and iodine, 2.6%. At 32 wk gestation, vitamin B-12, A, and D and zinc status indicators were 3.7–13.7% higher, and ferritin, γ-tocopherol, and thyroglobulin indicators were 8.7–16.6% lower, for the MM group compared with the IFA group, with a 15–38% lower prevalence of deficiencies of vitamins B-12, A, and D and zinc (all P < 0.05). However, indicators typically suggested worsening status during pregnancy, even with supplementation, and baseline status or other covariates were more strongly associated with late pregnancy indicators than was MM supplementation.
Rural Bangladeshi women commonly entered pregnancy deficient in micronutrients other than iron and folic acid. Supplementation with MM improved micronutrient status, although deficiencies persisted. Preconception supplementation or higher nutrient doses may be warranted to support nutritional demands of pregnancy in undernourished populations. This trial was registered at clinicaltrials.gov as NCT00860470.
Pregnancy exacerbates vitamin A (VA) deficiency and anaemia among women in developing countries. Improving circulating haemoglobin (Hb) requires erythrocyte production and availability of iron. ...Insulin-like growth factor- 1 (IGF-1) functions in erythropoiesis, but its association with VA status and pregnancy-associated anaemia has not been studied. The aim of this study was to examine the relationship between serum retinol, IGF-1, and Hb among pregnant women in extant samples collected during a placebo-controlled trial of VA and beta-carotene (BC) supplementation in rural Nepal conducted from 1994 to 1997. Mid-pregnancy serum IGF-1 was measured in serum from n=589 randomly selected women of n=1186 in whom anthropometric, VA (retinol) and iron (Hb, erythrocyte zinc protoporphyrin (ZP), and ferritin) status data were available. Associations of IGF-1 with retinol, Hb or anaemia, and iron status were determined using multiple linear and logistic regression. Path analysis was used to explore the role of IGF-1 as a mediator between retinol and Hb, accounting for iron status. A 2.6 g/L increase in IGF-1 was observed per 0.1 mol/L increment in retinol (p<0.0001). Hb increased with each quartile of IGF-1, and odds of anaemia declined 68.8% from the 1st to 4th quartile. Improved iron status indicators explained only 29.1% of the association between IGF-1 and Hb, while IGF-1 explained 25.6% of the association between retinol and Hb. Increasing IGF-1 was likely one mechanism by which retinol improved circulating Hb in pregnant women of rural Nepal, although IGF-1 worked primarily through pathways independent of improved iron status indicators, perhaps by stimulating erythrocyte production.
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Iron status remains difficult to assess in settings where iron deficiency coexists with inflammation, and hepcidin has been proposed as an indicator of the body's iron requirement. ...Hepcidin reduces iron availability in iron sufficiency or inflammation, while low hepcidin may signal the body's need for iron. We sought to identify proteins that may be closely linked to iron metabolism using quantitative proteomics to characterize the plasma proteome in 500 plasma samples, depleted of the 6 most abundant proteins including transferrin, collected from 6–8 year old children in rural Nepal. We related relative abundance of proteins with conventional iron status indicators and hepcidin using linear mixed effects models with an imposed false discovery rate <10%. Among the children, inflammation (by C‐reactive protein, CRP, > 5 mg/L and/or α‐1 acid glycoprotein, AGP, > 1.0 g/L) occurred in 30%, and low iron stores (ferritin < 15 μg/L) were observed in 10% and tissue iron demand (transferrin receptor, TfR, >8.3 mg/L) in 40%. Fifty proteins were associated with hepcidin, 35 with ferritin, and 7 with TfR. A large overlap in the proteomes for hepcidin and ferritin with CRP and AGP, previously characterized, was observed. To further explore for proteins related to iron status independent of inflammation, hepcidin and ferritin were regressed against CRP and AGP, respectively, to generate residuals, to reflect the variability in hepcidin and ferritin unexplained by inflammation indexed by CRP and AGP. Thirty‐seven proteins remained associated with hepcidin, with the majority still associated with the inflammation proteome. These proteins have functions in the immune system (e.g. lipopolysaccharide‐binding protein), complement system (complement component 9 and 8 beta subunit), transcription and translation regulation (RNA polymerase II elongation factor), and glycoprotein formation (mannosyl‐oligosaccharide 1,2‐ α‐mannosidase IA). Nine proteins remained associated with ferritin residuals, but ficolin‐3, with a role in the lectin pathway and complement activation, was the only protein observed in common between hepcidin and ferritin inflammation‐adjusted residuals. Ficolin‐3 may be biologically linked to iron sequestration, given its unique association with hepcidin and ferritin. Plasma proteomics did not reveal new potential markers of iron status per se, but confirmed an extensive and complex association of iron metabolism with inflammation.
Support or Funding Information
Supported by Gates Foundation grants OPPGH5241 and GH614 (Global Control of Micronutrient Deficiency).
Vitamin A deficiency remains a nutritional concern in sub-Saharan Africa. Conventionally bred maize hybrids with high provitamin A carotenoid concentrations may have the potential to improve vitamin ...A status in maize-consuming populations. We evaluated the efficacy of regular provitamin A carotenoid-biofortified "orange" maizemeal (~15 μg β-carotene/g) consumption in improving vitamin A status and reducing vitamin A deficiency in children. This was a cluster-randomized controlled trial in the rural farming district of Mkushi, Zambia. All 4- to 8-y-old children in an ~400-km2 area were identified and grouped by proximity into clusters of ~15-25 children. We randomly assigned clusters to 1) orange maizemeal (n = 25), 2) white maizemeal (n = 25), or 3) a parallel, nonintervention group (n = 14). Children in intervention clusters (n = 1024) received 200 g maizemeal for 6 d/wk over 6 mo; the maizemeal was prepared according to standardized recipes and served in cluster-level kitchens. Staff recorded attendance and leftovers. We collected venous blood before and after the intervention to measure serum retinol, β-carotene, C-reactive protein, and a1-acid glycoprotein. Intervention groups were comparable at baseline, and vitamin A status was better than anticipated (12.1% deficient on the basis of serum retinol <0.7 μmol/L). Although attendance at meals did not differ (85%), median daily maize intake was higher in white (154 g/d) than in orange (142 g/d) maizemeal clusters. At follow-up, mean serum β-carotene was 0.14 μmol/L (95% CI: 0.09, 0.20 μmol/L) higher in orange maizemeal clusters (P < 0.001), but mean serum retinol (1.00 ± 0.33 μmol/L overall) and deficiency prevalence (17.1% overall) did not differ between arms. In this marginally nourished population, regular biofortified maizemeal consumption increased serum β-carotene concentrations but did not improve serum retinol.
Background: Vitamin A deficiency remains a nutritional concern in sub-Saharan Africa. Conventionally bred maize hybrids with high provitamin A carotenoid concentrations may have the potential to ...improve vitamin A status in maize-consuming populations.
Objective: We evaluated the efficacy of regular provitamin A carotenoid–biofortified “orange” maizemeal (∼15 μg β-carotene/g) consumption in improving vitamin A status and reducing vitamin A deficiency in children.
Design: This was a cluster-randomized controlled trial in the rural farming district of Mkushi, Zambia. All 4- to 8-y-old children in an ∼400-km2 area were identified and grouped by proximity into clusters of ∼15–25 children. We randomly assigned clusters to 1) orange maizemeal (n = 25), 2) white maizemeal (n = 25), or 3) a parallel, nonintervention group (n = 14). Children in intervention clusters (n = 1024) received 200 g maizemeal for 6 d/wk over 6 mo; the maizemeal was prepared according to standardized recipes and served in cluster-level kitchens. Staff recorded attendance and leftovers. We collected venous blood before and after the intervention to measure serum retinol, β-carotene, C-reactive protein, and α1-acid glycoprotein.
Results: Intervention groups were comparable at baseline, and vitamin A status was better than anticipated (12.1% deficient on the basis of serum retinol <0.7 μmol/L). Although attendance at meals did not differ (85%), median daily maize intake was higher in white (154 g/d) than in orange (142 g/d) maizemeal clusters. At follow-up, mean serum β-carotene was 0.14 μmol/L (95% CI: 0.09, 0.20 μmol/L) higher in orange maizemeal clusters (P < 0.001), but mean serum retinol (1.00 ± 0.33 μmol/L overall) and deficiency prevalence (17.1% overall) did not differ between arms.
Conclusion: In this marginally nourished population, regular biofortified maizemeal consumption increased serum β-carotene concentrations but did not improve serum retinol. This trial was registered at clinicaltrials.gov as NCT01695148.
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Erythropoiesis is compromised by vitamin A (VA) deficiency, and VA acts on the growth hormone/IGF‐1 axis. Whether VA works through IGF‐1 to enhance erythropoiesis in pregnancy has not ...been explored. We examined associations among mid‐pregnancy retinol, IGF‐1, iron status (ferritin and erythrocyte protoporphyrin) and Hb in 589 rural, pregnant, iron deficient women who participated in a placebo‐controlled VA and β‐carotene supplementation trial in Nepal. Associations of retinol to IGF‐1 and IGF‐1 to Hb or anemia were determined with linear and logistic regression. Path analysis was used to evaluate IGF‐1 as a mediator between retinol and Hb, acting through or independently of iron status indicators. The interventions modestly increased IGF‐1 (P = 0.09 for ANOVA), while each 0.1 μmol/L increment in retinol increased IGF‐1 by 2.4 μg/L (p < 0.0001). Increments of 10 μg/L IGF‐1 were associated with a 0.85 g/L increase in Hb (P < 0.0001) and a 15% reduced risk of moderate‐to‐severe anemia (p = 0.001). IGF‐1 explained ~1/3 of the association between retinol and Hb, while only ~1/3 of the association between IGF‐1 and Hb was explained via iron status indicators. VA may improve Hb in pregnant women by increasing IGF‐1, which may act primarily by enhancing erythrocyte maturation rather than increasing iron availability for erythropoiesis.
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Background
Vitamin A (VA) and beta‐carotene (BC) supplementation reduced pregnancy‐associated mortality and morbidity, as well as oxidative stress levels, in women of rural Nepal. This ...study examines the link between oxidative stress and symptoms of morbidity during pregnancy.
Methods
Serum malondialdehyde (MDA) was measured in a subset (n = 547) of women participating in a maternal VA or BC supplementation trial. Seven‐day frequencies of 21 symptoms were assessed within a month of blood collection. Total number of morbidity symptoms (0, 1, or =2), number of symptom‐days (0, 1‐9, or =10), and symptom clusters were modeled as dependent variables in multivariate logistic regressions.
Results
Serum MDA was lower among women with symptoms <20 weeks gestation, but higher among symptomatic women at =20 weeks. One square‐root unit increase in MDA (μmol/l) was associated with any symptoms (odds ratio OR, 3.17; 95% CI, 1.04‐9.68) and upper gastrointestinal tract infection or nausea and vomiting (OR, 3.67; 95% CI, 1.07‐12.51) at =20 weeks of gestation. MDA was associated with number of symptoms (OR, 3.76; 95% CI, 1.45‐9.73) and symptom‐days (OR, 3.40; 95% CI, 1.36‐8.49). This trend held in three supplementation groups (VA, BC and placebo), but the effects were diminished in the VA group.
Conclusion
Oxidative stress was associated with morbidity symptoms. Supplementing VA/BC may mitigate the illnesses through reducing oxidative stress in this population. Funded by the Bill and Melinda Gates Foundation, Seattle, WA and the US Agency for International Development (USAID).
Four fortified complementary food supplements (CFSs) in a randomized controlled trial (RCT) were found to improve childhood linear growth in rural Bangladesh. We hypothesized children receiving these ...supplements would have improved micronutrient status.
In the RCT, we assessed hemoglobin and serum ferritin, retinol, zinc, C-reactive protein (CRP), and α-1-acid glycoprotein (AGP) at endline (18 mo) in a subsample of children (
= 752). The impact of supplementation on mean concentrations and the prevalence of nutrient deficiency and inflammation were evaluated using adjusted generalized estimating equation (GEE) linear and log-binomial regression models.
In the control arm at age 18 months, 13% of children were anemic (hemoglobin < 110 g/L), and 6% were iron (inflammation-adjusted ferritin < 12 μg/L), 8% vitamin A (inflammation-adjusted retinol < 0.70 μmol/L), and 5% zinc (zinc < 9.9 μmol/L) deficient. The prevalence of inflammation by CRP (>5 mg/L) and AGP (>1 g/L) was 23% and 66%, respectively, in the control group. AGP trended lower in CFS groups (
= 0.04), while CRP did not. Mean ferritin (
< 0.001) and retinol (
= 0.007) were higher in all supplemented groups relative to control, whereas hemoglobin improved with two of the four CFSs (
= 0.001), and zinc was equal or lower in supplemented groups relative to control (
= 0.017).
CFSs improved iron status and vitamin A concentrations and lowered inflammation in a context of low underlying nutrient deficiency but high inflammation.
Prenatal multiple micronutrient (MM) supplementation improves birth weight through increased fetal growth and gestational age, but whether maternal or fetal growth factors are involved is unclear. ...Our objective was to examine the effect of prenatal MM supplementation on intrauterine growth factors and the associations between growth factors and birth outcomes in a rural setting in Bangladesh. In a double-blind, cluster-randomized, controlled trial of MM vs. iron and folic acid (IFA) supplementation, we measured placental growth hormone (PGH) at 10 weeks and PGH and human placental lactogen (hPL) at 32 weeks gestation in maternal plasma (n = 396) and insulin, insulin-like growth factor-1 (IGF-1), and IGF binding protein-1 (IGFBP-1) in cord plasma (n = 325). Birth size and gestational age were also assessed. Early pregnancy mean (SD) BMI was 19.5 (2.4) kg/m2 and birth weight was 2.68 (0.41) kg. There was no effect of MM on concentrations of maternal hPL or PGH, or cord insulin, IGF-1, or IGFBP-1. However, among pregnancies of female offspring, hPL concentration was higher by 1.1 mg/L in the third trimester (95% CI: 0.2, 2.0 mg/L; p = 0.09 for interaction); and among women with height <145 cm, insulin was higher by 59% (95% CI: 3, 115%; p = 0.05 for interaction) in the MM vs. IFA group. Maternal hPL and cord blood insulin and IGF-1 were positively, and IGFBP-1 was negatively, associated with birth weight z score and other measures of birth size (all p<0.05). IGF-1 was inversely associated with gestational age (p<0.05), but other growth factors were not associated with gestational age or preterm birth. Prenatal MM supplementation had no overall impact on intrauterine growth factors. MM supplementation altered some growth factors differentially by maternal early pregnancy nutritional status and sex of the offspring, but this should be examined in other studies.
ClinicalTrials.gov NCT00860470.
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