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    A double-blind, randomized, clinical trial of the effect of vitamin A and zinc supplementation on diarrheal disease and respiratory tract infections in children in Mexico City, Mexico. Long Kurt Z,Montoya Yura,Hertzmark Ellen,Santos Jose I,Rosado Jorge L The American journal of clinical nutrition BACKGROUND:The efficacy of micronutrient supplementation in improving childhood health and survival in developing countries may be specific to the micronutrient used and health outcome measured. OBJECTIVE:We evaluated the effect of vitamin A and zinc supplementation on overall rates of childhood diarrheal disease and respiratory tract infections and rates stratified by household and personal characteristics. DESIGN:A double-blind, randomized, placebo-controlled trial was carried out in which 736 children aged 6-15 mo living in a periurban area of Mexico City were assigned to receive vitamin A every 2 mo, zinc daily, vitamin A and zinc together, or placebo. Children were followed for 12 mo to determine overall counts of diarrheal episodes and respiratory tract infections. RESULTS:Vitamin A supplementation was associated with a 27% increase in diarrheal disease [risk ratio (RR): 1.27; 95% CI: 1.10, 1.45; P < 0.001] and a 23% increase in cough with fever (RR: 1.23; 95% CI: 1.02, 1.47; P = 0.02), whereas zinc had no effect on these outcomes. Vitamin A supplementation decreased diarrhea in children from households with dirt floors but increased diarrhea in children from households with nondirt floors, piped water, and indoor bathrooms. Zinc supplementation decreased diarrhea in children from households with dirt floors and whose mothers were more educated. Vitamin A supplementation increased cough with fever in children from less-crowded households that lacked indoor bathrooms and in children of less-educated mothers. CONCLUSIONS:Vitamin A increases diarrheal disease and respiratory tract infections in young children in periurban areas of Mexico City. Vitamin A and zinc have more heterogeneous effects in different subgroups of children. 10.1093/ajcn.83.3.693
    Zinc and vitamin A supplementation in Australian Indigenous children with acute diarrhoea: a randomised controlled trial. Valery Patricia C,Torzillo Paul J,Boyce Naomi C,White Andrew V,Stewart Peter A,Wheaton Gavin R,Purdie David M,Wakerman John,Chang Anne B The Medical journal of Australia OBJECTIVE:To evaluate the role of zinc and vitamin A supplementation in the recovery of Indigenous children hospitalised for acute diarrhoea. DESIGN:A randomised controlled 2 by 2 factorial trial of supplementation with zinc and vitamin A. SETTING AND PARTICIPANTS:Aboriginal children (aged < 11 years) hospitalised for acute diarrhoea at Alice Springs Hospital, Northern Territory, April 2001-July 2002. MAIN OUTCOME MEASURES:Duration of diarrhoeal illness; re-admission for diarrhoeal illness within 120 days. RESULTS:Our study involved 392 Aboriginal children with 436 episodes of diarrhoea. Supplementation with zinc, vitamin A, or combined zinc and vitamin A had no significant effect on duration of diarrhoea or rate of re-admission compared with placebo. Median diarrhoea duration after starting supplementation was 3.0 days for the vitamin A and zinc supplemented and placebo groups (P values 0.25 and 0.69, respectively). The number of re-admissions did not differ significantly between those receiving vitamin A or zinc and the relevant placebo groups (relative risk [95% CI], 1.2 [0.7-2.1] and 1.3 [0.8-2.1], respectively). CONCLUSION:Vitamin A and zinc supplementation may not be indicated for in-hospital management of acute diarrhoeal disease in Aboriginal children living in remote areas. This finding may not apply to children with malnutrition, for whom other studies suggest a benefit. Larger trials incorporating more comprehensive data on the vitamin A and zinc status as well as nutritional status of study populations might help to explain the different results in different populations. 10.5694/j.1326-5377.2005.tb00021.x
    Zinc and vitamin A supplementation in Indigenous Australian children hospitalised with lower respiratory tract infection: a randomised controlled trial. Chang Anne B,Torzillo Paul J,Boyce Naomi C,White Andrew V,Stewart Peter M,Wheaton Gavin R,Purdie David M,Wakerman John,Valery Patricia C The Medical journal of Australia OBJECTIVE:To evaluate the efficacy of supplementation with zinc and vitamin A in Indigenous children hospitalised with acute lower respiratory infection (ALRI). DESIGN:Randomised controlled, 2-by-2 factorial trial of supplementation with zinc and vitamin A. SETTING AND PARTICIPANTS:187 Indigenous children aged < 11 years hospitalised with 215 ALRI episodes at Alice Springs Hospital (April 2001 to July 2002). INTERVENTIONS:Vitamin A was administered on Days 1 and 5 of admission at a dose of 50 000 IU (infants under 12 months), or 100 000 IU; and zinc sulfate was administered daily for 5 days at a daily dose of 20 mg (infants under 12 months) or 40 mg. MAIN OUTCOME MEASURE:Time to clinical recovery from fever and tachypnoea, duration of hospitalisation, and readmission for ALRI within 120 days. RESULTS:There was no clinical benefit of supplementation with vitamin A, zinc or the two combined, with no significant difference between zinc and no-zinc, vitamin A and no-vitamin A or zinc + vitamin A and placebo groups in time to resolution of fever or tachypnoea, or duration of hospitalisation. Instead, we found increased morbidity; children given zinc had increased risk of readmission for ALRI within 120 days (relative risk, 2.4; 95% CI, 1.003-6.1). CONCLUSION:This study does not support the use of vitamin A or zinc supplementation in the management of ALRI requiring hospitalisation in Indigenous children living in remote areas. Even in populations with high rates of ALRI and poor living conditions, vitamin A and zinc therapy may not be useful. The effect of supplementation may depend on the prevalence of deficiency of these micronutrients in the population. 10.5694/j.1326-5377.2006.tb00147.x
    Zinc combined with vitamin A reduces upper respiratory tract infection morbidity in a randomised trial in preschool children in Indonesia. Kartasurya Martha I,Ahmed Faruk,Subagio Hertanto W,Rahfiludin Muhammad Z,Marks Geoffrey C The British journal of nutrition Zn supplementation has shown inconsistent effects on respiratory morbidity in young children in developing countries. Few studies have focused on upper respiratory tract infection (URTI), a frequent cause of morbidity in this group, and potential benefit from Zn supplementation or factors that influence its efficacy. We investigated the effects of Zn supplementation on URTI before and after vitamin A supplementation. This randomised double-blinded controlled Zn supplementation study was conducted on 826 children aged 2-5 years. Placebo or Zn (10 mg/d) was given in syrup daily for 4 months, with 200 000 IU vitamin A (60 mg retinol) given to all children at 2 months. Health workers visited children every 3 d for compliance and morbidity information. We found that 84 % of children experienced URTI during the study. Zn supplementation reduced the percentage of days with URTI (12 % reduction; P = 0·09), with greater impact following vitamin A supplementation (20 % reduction; P = 0·01). Vitamin A supplementation was associated with a decreased number but an increased duration of URTI episodes. We conclude that Zn combined with vitamin A supplementation significantly reduced the percentage of days with URTI in a population of preschool Indonesian children with marginal nutritional status. The results suggest that vitamin A status modifies the efficacy of Zn supplementation on URTI. 10.1017/S0007114512000499
    The effect of adding zinc to vitamin A on IGF-1, bone age and linear growth in stunted children. Adriani Merryana,Wirjatmadi Bambang Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) A randomized, double-blind, placebo controlled trial of a single dose of 200,000 I.U. of vitamin A with daily zinc supplementation was conducted with children in Mojo village, Surabaya City. Children aged 48 to 60 months were randomized to receive a single dose of 200,000 I.U. of vitamin A plus zinc sulfate (n=12) or a single dose of 200,000 I.U. of vitamin A (n=12) plus placebo six days a week for six months. Children were evaluated weekly for nutrient intake and for IGF-1, C-reactive protein levels, gamma globulin levels, serum zinc, serum retinol, bone age and the index height for age at six months. At the end of the study, there was a significant increase in the serum retinol level (p<0.03), serum zinc level (p<0.03), IGF-1 hormone (p<0.04) and Z-score height for age (p<0.001), bone age (p<0.01), and gamma globulin level (p<0.04) and a significant decrease in the amount of infection/inflammation measured by CRP level (p<0.001). There was also a significant correlation between CRP level and height for age (p<0.01), and between gamma level and height for age (p<0.01). These results suggest that combined vitamin A and zinc supplementation reduces the risk of infection and increases linear growth among children, and thus may play a key role in controlling infection and stunted growth for children under five years old. 10.1016/j.jtemb.2014.08.007
    The effects of regular consumption of a multiple micronutrient fortified milk beverage on the micronutrient status of school children and on their mental and physical performance. Kuriyan Rebecca,Thankachan Prashanth,Selvam Sumithra,Pauline Maria,Srinivasan K,Kamath-Jha Shilpa,Vinoy Sophie,Misra Situn,Finnegan Yvonne,Kurpad Anura V Clinical nutrition (Edinburgh, Scotland) Multiple micronutrient deficiencies exist in school going children in India and bridging the gap between nutrient intake and requirements is an effective way to combat the deficiencies. This study aimed to test the effect of a multi-micronutrient fortified malt and cocoa based milk beverage on the micronutrient status, cognition, physical performance and nutritional deficiencies of 7-10 years old south Indian children. A randomized, double blind placebo controlled study design was used with normal healthy children from low to middle income families, aged 7-10 years randomly assigned to receive either a multi-micronutrient fortified or an unfortified milk based control drink. The drinks were provided 6 days/week for 5 months. Assessments included anthropometry, blood biochemistry, physical performance and cognition at baseline and endline. The baseline characteristics of the study groups were similar. The changes in body weight and height were similar between the groups at the end of the study. Levels of vitamin B12, red cell folate and vitamin B2 significantly improved in the intervention group, while vitamin D, selenium and body iron showed no difference. The Hemoglobin (Hb) and serum ferritin levels of the control group decreased at endline, while those in the intervention group maintained their levels. The serum transferrin receptor levels increased in both the groups. The prevalence of iron deficiency and Vitamin B2 deficiency were significantly lower in the intervention group at endline. Overall improvement in cognitive and physical performance was seen in both the groups at endline, with no significant differences between the groups. The micronutrient fortified milk based drink was efficacious in improving the micronutrient status of Vitamin B2, Vitamin B12 and red cell folate and in preventing a decline in Hb level compared to an unfortified milk based drink. It also reduced anemia and the risk of deficiencies of iron, and B12, in apparently healthy children. ClinicalTrials.gov IdentifierNCT01415557. Clinical Trial RegistryIndia - REF/2012/12/004332. 10.1016/j.clnu.2015.02.001
    The relationship between cow's milk and stores of vitamin D and iron in early childhood. Maguire Jonathon L,Lebovic Gerald,Kandasamy Sharmilaa,Khovratovich Marina,Mamdani Muhammad,Birken Catherine S,Parkin Patricia C, , Pediatrics OBJECTIVE:To examine the association between cow's milk intake on both vitamin D and iron stores in healthy urban preschoolers. METHODS:Healthy children 2 to 5 years of age were recruited from December 2008 through December 2010 through the TARGet Kids! practice-based research network. Cow's milk intake was measured by parental report. Vitamin D and iron stores were measured by using serum 25-hydroxyvitamin D and ferritin. Bivariate multivariable linear regression was used to examine the effect of cow's milk intake simultaneously on 25-hydroxyvitamin D and serum ferritin. Analyses were stratified by important clinical variables including skin pigmentation, bottle feeding, vitamin D supplementation, and season. RESULTS:Among 1311 children, increasing cow's milk consumption was associated with decreasing serum ferritin (P < .0001) and increasing 25-hydroxyvitamin D (P ≤ .0001). Two cups (500 mL) of cow's milk per day maintained 25-hydroxyvitamin D >75 nmol/L with minimal negative effect on serum ferritin for most children. Children with darker skin pigmentation not receiving vitamin D supplementation during the winter required 3 to 4 cups of cow's milk per day to maintain 25-hydroxyvitamin D >75 nmol/L. Cow's milk intake among children using a bottle did not increase 25-hydroxyvitamin D and resulted in more dramatic decreases in serum ferritin. CONCLUSIONS:There is a trade-off between increasing 25-hydroxyvitamin D and decreasing serum ferritin with increasing milk intake. Two cups of cow's milk per day appears sufficient to maintain healthy vitamin D and iron stores for most children. Wintertime vitamin D supplementation was particularly important among children with darker skin pigmentation. 10.1542/peds.2012-1793
    Vitamin D Status Is Associated with Hepcidin and Hemoglobin Concentrations in Children with Inflammatory Bowel Disease. Syed Sana,Michalski Ellen S,Tangpricha Vin,Chesdachai Supavit,Kumar Archana,Prince Jarod,Ziegler Thomas R,Suchdev Parminder S,Kugathasan Subra Inflammatory bowel diseases BACKGROUND:Anemia, iron deficiency, and hypovitaminosis D are well-known comorbidities in inflammatory bowel disease (IBD). Epidemiologic studies have linked vitamin D deficiency with increased risk of anemia, and in vitro studies suggest that vitamin D may improve iron recycling through downregulatory effects on hepcidin and proinflammatory cytokines. METHODS:We aimed to investigate the association of vitamin D status with inflammation, iron biomarkers, and anemia in pediatric IBD. Cross-sectional data were obtained from N = 69 patients with IBD aged 5 to <19 years. Iron biomarkers (ferritin, soluble transferrin receptor), and 25-hydroxyvitamin D (25(OH)D), inflammatory biomarkers (C-reactive protein and α-1-acid glycoprotein), hepcidin, and hemoglobin were collected. Iron biomarkers were regression corrected for inflammation. Multivariable logistic/linear models were used to examine the associations of 25(OH)D with inflammation, iron status, hepcidin, and anemia. RESULTS:Approximately 50% of subjects were inflamed (C-reactive protein >5 mg/L or α-1-acid glycoprotein >1 g/L). Iron deficiency prevalence (inflammation-corrected ferritin <15 μg/L or soluble transferrin receptor >8.3 mg/L) was 67%; anemia was 36%, and vitamin D insufficiency (25(OH)D <30 ng/mL) was 77%. In linear regression models, vitamin D insufficiency was associated with increased hepcidin levels (β [SE] = 0.6 [0.2], P = 0.01) and reduced hemoglobin (β [SE] = -0.9 [0.5], P = 0.046), controlling for age, sex, race, insurance status, body mass index for age, inflammation, disease diagnosis (ulcerative colitis versus Crohn's disease), and disease duration, compared with 25(OH)D ≥30 ng/mL. CONCLUSIONS:Our results suggest that concentrations of 25(OH)D ≥30 ng/mL are associated with lower hepcidin and higher hemoglobin levels. Further research is needed to clarify the association of vitamin D with inflammation, iron status, and anemia in pediatric IBD. 10.1097/MIB.0000000000001178
    Low vitamin D levels are associated with both iron deficiency and anemia in children and adolescents. Lee Jun Ah,Hwang Jin Soon,Hwang Il Tae,Kim Dong Ho,Seo Ju-Hee,Lim Jung Sub Pediatric hematology and oncology BACKGROUND:We aimed to examine the association between vitamin D deficiency and anemia in a nationally representative sample of Korean children and adolescents. METHODS:Cross-sectional data on 2526 children and adolescents aged 10-20 years from the Korea National Health and Nutrition Examination Survey-V (2010-2012) were used. Anemia was defined according to specifications of the World Health Organization. Iron deficiency was defined as serum ferritin level of <12 ng/mL and transferrin saturation (TSAT) <16%. RESULTS:The prevalence of vitamin D deficiency in Korean children and adolescents was high especially in female (35.7% vs. 50.9%, P < 0.001). The prevalence of anemia was also higher in female (1.1% vs. 6.8%; P < 0.001). In logistic regression, risk factors for anemia were female sex, old age, post-menarche, low household income, vitamin D deficiency, and iron deficiency. The Odds Ratio for anemia, iron deficiency and iron deficiency anemia (IDA) in subjects with vitamin D deficiency (<15 ng/mL) were 1.81(95% CI, 1.13-2.88), 1.94(95% CI, 1.27-2.97), and 2.26 (95% CI, 1.20-4.24) after controlling for other risk factors. However, after examining the sexes separately, only female subjects showed statistical significance. After further controlling for iron deficiency, the risk of anemia was not significant (P = 0.261). CONCLUSIONS:Vitamin D deficiency is associated with increased risk of anemia, especially iron deficiency anemia, in healthy female children and adolescents. However, the association is attenuated after adjustment for iron deficiency. Further studies are needed to determine whether vitamin D deficiency is the cause of anemia, or bystander of nutritional deficiency which cause iron deficiency. 10.3109/08880018.2014.983623
    Poor vitamin D status increases the risk of anemia in school children: National Food and Nutrition Surveillance. Nikooyeh Bahareh,Neyestani Tirang R Nutrition (Burbank, Los Angeles County, Calif.) OBJECTIVES:This study aimed to investigate the association between 25-hydroxyvitamin D (25[OH]D) concentrations and the risk of anemia in a large cohort of children with consideration for the effects of sex, body mass index (BMI), serum intact parathyroid hormone (iPTH) concentrations, and iron level status. METHODS:A total of 937 children (493 boys, 444 girls) ages 9 to 12 y were enrolled in a cross-sectional study. The children underwent various examinations including anthropometric measurements and blood sampling. RESULTS:Overall, 13.3% of the children were anemic and 64.2% and 28.1% of the subjects had a vitamin D deficiency (<25 nmol/L) and insufficiency (25-50 nmol/L), respectively. Approximately 13% of the children had concurrent low hemoglobin and hypovitaminosis D levels. The prevalence of hypovitaminosis D in the group of children with anemia was 96.8% compared with 91.6% in the non-anemic group (P = 0.046). Mean 25(OH)D concentrations were significantly lower in the anemic children compared with the non-anemic children (19.6 ± 13.3 vs. 24.0 ± 23.1 nmol/L; P = 0.003). After controlling for sex and BMI, children with a vitamin D deficiency were almost 3.45 times more likely to be anemic compared with children with a vitamin D sufficiency (95% confidence interval [CI], 1.21-9.81). The increased risk of anemia was found to start significantly at 25(OH)D < 44 nmol/L (17.6 ng/mL; odds ratio: 2.29; 95% CI, 1.07-4.91, P = 0.032). CONCLUSIONS:These findings strongly suggest an association between low circulating concentrations of 25(OH)D and anemia in a large, representative sample of children, even after adjustment for sex, age, BMI, and iPTH. 10.1016/j.nut.2017.09.008
    Compared with Cow Milk, a Growing-Up Milk Increases Vitamin D and Iron Status in Healthy Children at 2 Years of Age: The Growing-Up Milk-Lite (GUMLi) Randomized Controlled Trial. Lovell Amy L,Davies Peter S W,Hill Rebecca J,Milne Tania,Matsuyama Misa,Jiang Yannan,Chen Rachel X,Wouldes Trecia A,Heath Anne-Louise M,Grant Cameron C,Wall Clare R The Journal of nutrition Background:Iron deficiency (ID) and vitamin D deficiency (VDD) are significant pediatric health issues in New Zealand and Australia and remain prevalent micronutrient deficiencies in young children globally. Objective:We aimed to investigate the effect of a micronutrient-fortified, reduced-energy growing-up milk (GUMLi) compared with cow milk (CM) consumed for 1 y on dietary iron and vitamin D intakes and the status of New Zealand and Australian children at 2 y of age. Methods:The GUMLi Trial was a multicenter, double-blind, randomized controlled trial in 160 healthy 1-y-old New Zealand and Australian children conducted in 2015-2017. Participants were randomly assigned 1:1 to receive GUMLi (1.7 mg Fe/100 mL; 1.3 µg cholecalciferol/100 mL) or CM (0.02 mg Fe/100 mL; 0.06 µg cholecalciferol/100 mL) for 12 mo. Secondary outcomes, reported here, included change in dietary iron and vitamin D intakes, iron status, and 25-hydroxyvitamin D [25(OH)D] concentrations from blood samples at age 2 y. All regression models were adjusted for baseline outcome and study center. Results:GUMLi was a large contributor to dietary intakes of iron and vitamin D after 12 mo when compared with intakes from food and CM. The adjusted mean difference between groups for serum ferritin concentrations was 17.8 µg/L (95% CI: 13.6, 22.0 µg/L; P < 0.0001), and for 25(OH)D it was 16.6 nmol/L (95% CI: 9.9, 23.3 nmol/L; P < 0.0001). After 12 mo, ID was present in 16 (24%) participants in the CM group and 5 (7%) participants in the GUMLi group (P = 0.009), and the prevalence of VDD in the CM group increased to 14% (n = 10) and decreased to 3% (n = 2) (P = 0.03) in the GUMLi group. Conclusion:In comparison with CM, GUMLi significantly improved dietary iron and vitamin D intakes and the iron and vitamin D status of healthy children at 2 y of age. This trial was registered with the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12614000918628. 10.1093/jn/nxy167
    A micronutrient-fortified young-child formula improves the iron and vitamin D status of healthy young European children: a randomized, double-blind controlled trial. Akkermans Marjolijn D,Eussen Simone Rbm,van der Horst-Graat Judith M,van Elburg Ruurd M,van Goudoever Johannes B,Brus Frank The American journal of clinical nutrition BACKGROUND:Iron deficiency (ID) and vitamin D deficiency (VDD) are common among young European children because of low dietary intakes and low compliance to vitamin D supplementation policies. Milk is a common drink for young European children. Studies evaluating the effect of milk fortification on iron and vitamin D status in these children are scarce. OBJECTIVE:We aimed to investigate the effect of a micronutrient-fortified young-child formula (YCF) on the iron and vitamin D status of young European children. DESIGN:In this randomized, double-blind controlled trial, healthy German, Dutch, and English children aged 1-3 y were allocated to receive either YCF (1.2 mg Fe/100 mL; 1.7 μg vitamin D/100 mL) or nonfortified cow milk (CM) (0.02 mg Fe/100 mL; no vitamin D) for 20 wk. Blood samples were taken before and after the intervention. The primary and secondary outcomes were change from baseline in serum ferritin (SF) and 25-hydroxyvitamin D [25(OH)D], respectively. ID was defined as SF <12 μg/L in the absence of infection (high-sensitivity C-reactive protein <10 mg/L) and VDD as 25(OH)D <50 nmol/L. Statistical adjustments were made in intention-to-treat analyses for sex, country, age, baseline micronutrient status, and micronutrient intake from food and supplements (and sun exposure in the case of vitamin D outcomes). RESULTS:The study sample consisted of 318 predominantly Caucasian (∼95%) children. The difference in the SF and 25(OH)D change between the treatment groups was 6.6 μg/L (95% CI: 1.4, 11.7 μg/L; P = 0.013) and 16.4 nmol/L (95% CI: 9.5, 21.4 nmol/L; P < 0.001), respectively. The probability of ID (OR 0.42; 95% CI:0.18, 0.95; P = 0.036) and VDD (OR 0.22; 95% CI: 0.01, 0.51; P < 0.001) after the intervention was lower in the YCF group than in the CM group. CONCLUSION:Micronutrient-fortified YCF use for 20 wk preserves iron status and improves vitamin D status in healthy young children in Western Europe. This trial was registered at www.trialregister.nl as NTR3609. 10.3945/ajcn.116.136143
    Low Serum Levels of Vitamins A, D, and E Are Associated with Recurrent Respiratory Tract Infections in Children Living in Northern China: A Case Control Study. Zhang Xuguang,Ding Fengshu,Li Huaining,Zhao Wenfeng,Jing Hong,Yan Yageng,Chen Yanping PloS one BACKGROUND:This study aimed to investigate the association of serum concentrations of vitamin A, D, and E with recurrent respiratory tract infections (RRTIs). METHODS:A total of 1200 children aged at 0.5-14 years were selected via a face-to-face survey in Harbin, China. Among the participants, 600 children with RRTIs comprised the symptomatic group (RRTI group), whereas 600 healthy children were used as controls (control group). Blood samples were collected to measure serum levels of vitamins A and E by HPLC; the serum level of 25-hydroxycholecalciferol (25(OH)D), was measured by HPLC-MS/MS. RESULTS:Serum levels of vitamins A and E, as well as 25(OH)D, were significantly lower in the RRTI group than the control group. The conditional logistic regression model and the receiver-operating characteristic curve showed that the insufficiency or deficiency of vitamins A, D, and E was positively correlated with RRTI occurrence (p < 0.05). CONCLUSIONS:Low serum concentrations of vitamins A, D, and E were associated with RRTIs in children from northern China. 10.1371/journal.pone.0167689
    Comorbidity of Vitamin A and Vitamin D Deficiency Exacerbates the Severity of Atopic Dermatitis in Children. Xiang Juan,Wang Hua,Li Tingyu Dermatology (Basel, Switzerland) BACKGROUND:Several studies have suggested that vitamin D (VD) deficiency (VDD) is associated with atopic dermatitis (AD). However, little is known about the relationship between AD and vitamin A (VA). The interaction between VA and VD on AD requires further study. OBJECTIVE:We detected serum levels of VA and VD in children with AD to explore how VA deficiency (VAD) and VDD affect AD severity. METHODS:We assessed the SCORing Atopic Dermatitis (SCORAD) index, total immunoglobin E levels and peripheral blood eosinophil counts. VA and VD levels were determined with high-performance liquid chromatography. Correlations among variables were investigated with Pearson's correlation analysis. RESULTS:The VD and VA levels were significantly lower in children with AD than in normal children (p < 0.001, p = 0.0423). Both VD and VA levels were negatively correlated with SCORAD scores. The SCORAD scores were significantly higher in AD patients with both VDD and VAD (co-deficiency) than in other AD patients. Significant inverse correlations were observed between peripheral blood eosinophil counts and serum VA and VD levels. CONCLUSIONS:VA and VD co-deficiency may exacerbate AD symptoms in children, but the specific mechanism underlying this relationship requires further study. These findings may indicate the need for studies evaluating the use of VD and VA as potential treatments for AD patients. 10.1159/000496603
    Risk factors for vitamin A and vitamin D deficiencies in children younger than 5 years in the occupied Palestinian territory: a cross-sectional study. Chaudhry Aeysha,Hajat Shakoor,Rizkallah Najwa,Abu-Rub Ala'a Lancet (London, England) BACKGROUND:Vitamin A and vitamin D are essential for a child's growth and development. However, research on micronutrients in the occupied Palestinian territory is scarce. The aim of this study was to ascertain the prevalence and risk factors of vitamin A and vitamin D deficiencies in children living in the occupied Palestinian territory. METHODS:The Palestinian Micronutrient Survey in 2013 measured concentrations of vitamin A in 1054 children (569 children in the West Bank and 485 children in the Gaza Strip) and vitamin D in 150 children (75 children in the West Bank and 75 children in the Gaza Strip). Risk factors for deficiency were assessed in children aged 6-59 months using χ tests and logistic regression with each of the outcome variables of vitamin A and vitamin D deficiencies. A child was considered deficient if serum concentrations were less than 1·05 μmol/L vitamin A or less than 50 nmol/L vitamin D. Multiple logistic regression models were developed to identify independent risk factors. Ethical approval was obtained from the London School of Hygiene & Tropical Medicine. FINDINGS:771 (73%) children in the survey had vitamin A deficiency, and 91 (61%) children had vitamin D deficiency. Compared with children living in the West Bank, children living in the Gaza Strip were more likely to be deficient in vitamin A (odds ratio 1·34, 95% CI 0·78-2·31) and vitamin D (1·96, 0·67-5·71). Vitamin A deficiency was 1·5 more likely in children with anaemia than in children who did not have anaemia (95% CI 1·08-2·10; p=0·047). Vitamin D deficiency was more common in children older than 1 years than in children aged 1 year or younger, and vitamin D deficiency was 2·72 times more likely in girls than in boys (95% CI 1·21-6·01; p=0·037). INTERPRETATION:The study provides an initial assessment of the burden of vitamin A and vitamin D deficiencies in the occupied Palestinian territory. However, due to the small sample size, more robust research is needed. The observed low adherence to the full supplementation regimen warrants further research into methods of effective service delivery by health service providers. FUNDING:None. 10.1016/S0140-6736(18)30369-6
    Correlation of serum vitamin A, D, and E with recurrent respiratory infection in children. Zhang J,Sun R-R,Yan Z-X,Yi W-X,Yue B European review for medical and pharmacological sciences OBJECTIVE:To investigate the correlation of serum vitamin A, D, and E levels with a recurrent respiratory infection (RRI) in children. PATIENTS AND METHODS:The medical records of 422 children with RRI (a study group) in Cangzhou Central Hospital from January 2015 to December 2018 were retrospectively analyzed (the study group was divided into an active group and a stable group). Further 100 healthy children who underwent physical examination at the same time were enrolled as a control group. High-performance liquid chromatography (HPLC) was used to determine vitamin A, D, and E levels, so as to analyze their differences between the groups. RESULTS:Vitamin A, D, and E in the active and stable groups were significantly lower than those in the control group (p < 0.001); in the active group they were significantly lower than those in the stable group (p < 0.001). According to partial correlation analysis, in children with active RRI, vitamin A was respectively positively correlated with vitamin D (r=0.945, p < 0.001), and vitamin E (r=0.988, p < 0.001). Moreover, vitamin E was positively correlated with vitamin D (r=0.959, p < 0.001). CONCLUSIONS:The deficiency of vitamin A, D, and E is positively correlated with the disease activity of children with RRI. Therefore, the supplement of vitamin A, D, and E through dietary adjustment is beneficial to the rehabilitation of the children. 10.26355/eurrev_201909_19033
    [Effect of vitamin A supplements on iron metabolic homeostasis for preschoolers]. Chen Ke,Zhang Lan,Luo Hongyi,Wang Jin,Li Qin,Mao Meng Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] OBJECTIVE:To explore the effect of vitamin A (VA) combined iron supplements on iron metabolic homeostasis for preschoolers. METHODS:About 445 preschoolers with aged 3-6 years old from eight kindergartens in Pixian county, Chengdu were recruited into this trial from March to September, 2011. All subjects met the inclusion criteria were randomly divided into four groups using random number table: sole VA supplementation group (VA group, a single oral dose of VA at about 200 000 units), sole iron supplementation group (FE group, daily oral supplementation with the element iron 1-2 mg·kg(-1)·d(-1) for five days a week, lasting for 6 months), the combined supplementation of VA and iron group (VF group) and control group (CO group, no VA and iron supplementation). The concentration of serum VA, serum ferritin (SF), serum transferring receptor (sTfR), C-reactive protein (CRP) and hemoglobin (Hb) were measured from 3 ml vein blood. The sTfR-SF index (TFR-F index) and total body iron content (TBIC) before and after intervention were calculated. The differences of these indexes between groups before and after intervention were analyzed. RESULTS:The level of sTfR before intervention in VA group ((1.78 ± 0.17) mg/L) was significantly higher than that of after intervention ((1.18 ± 0.11)mg/L) (t = 28.88, P < 0.01). The levels of TFR-F index and TBIC in FE and VF groups before intervention ( (1.59 ± 0.37), (1.63 ± 0.40) and (9.04 ± 2.71), (9.26 ± 2.33) mg/kg, respectively) were all lower than those of after intervention (TFR-F index:(1.84 ± 0.51), (1.87 ± 0.45) and TBIC:(12.42 ± 3.49), (13.01 ± 2.98)mg/kg) (t values were 3.93, 3.78, 7.57 and 9.41, respectively, all P values were <0.01). The incidence of iron deficiency in VA, FE, and VF groups before intervention were 26% (25/95), 31% (30/98) and 31% (28/90) and were 41% (39/95), 10% (10/98) and 18% (16/90) for after intervention, respectively. The difference of this index in VA, FE and VF groups were significant (χ(2) values were 4.59, 12.50 and 4.31, respectively, all the P values were <0.05). CONCLUSION:Combined VA and iron was as effective as VA alone or iron alone in decreasing the iron deficiency, the impact of VA intervention on iron metabolic homeostasis was mainly manifested in iron usage and mobilization, but showed no effect on total body iron content.
    Effect of vitamin A, vitamin A plus iron and multiple micronutrient-fortified seasoning powder on infectious morbidity of preschool children. Chen Ke,Zhang Xuan,Li Ting-yu,Chen Li,Wei Xiao-ping,Qu Ping,Liu You-xue Nutrition (Burbank, Los Angeles County, Calif.) OBJECTIVE:Improvement of hemoglobin and serum retinol and facilitation of the mobilization of iron storage were achieved with a multiple-micronutrient-fortified diet in preschoolers for 6 mo in a suburb of Chongqing, China. We investigated whether fortification with multiple micronutrients in a diet for preschool children results in changes in children's infectious morbidity compared with diets fortified solely with vitamin A and with vitamin A plus iron. METHODS:From December 2005 to June 2006, 226 2- to 6-y-old preschool children were recruited from three nurseries randomly assigned to three different fortified-diet groups for 6 mo. Group I was fortified with vitamin A; groups II and III were fortified with vitamin A plus iron and vitamin A plus iron, thiamine, riboflavin, folic acid, niacinamide, zinc, and calcium, respectively. The secondary functional outcomes, morbidity of diarrhea and respiratory infection, were collected during supplementation. RESULTS:The groups were comparable concerning compliance and loss to follow-up. There was evidence of a lower incidence rate of respiratory-related illnesses, diarrhea-related illness, fewer symptoms of runny nose, cough, and fever, and shorter duration of respiratory-related illnesses and cough for children in group III compared with children in groups I and II. However, there was no significantly or clinically important difference between children in groups I and II. CONCLUSION:The beneficial effects on infectious morbidity over 6 mo, in addition to some biochemical improvements, highlight the potential of this micronutrient-fortified seasoning powder supplied in a diet for preschool children. 10.1016/j.nut.2010.04.004
    Iron deficiency and anemia are associated with low retinol levels in children aged 1 to 5 years. Saraiva Bárbara C A,Soares Michele C C,Santos Luana C dos,Pereira Simone C L,Horta Paula M Jornal de pediatria OBJECTIVE:To analyze the occurrence of anemia and iron deficiency in children aged 1 to 5 years and the association of these events and retinol deficiency. METHODS:This was an observational analytic cross-sectional study conducted in Vitoria, ES, Brazil, between April and August of 2008, with healthy children aged 1 to 5 years (n=692) that lived in areas covered by primary healthcare services. Sociodemographic and economic conditions, dietary intake (energy, protein, iron, and vitamin A ingestion), anthropometric data (body mass index-for-age and height-for-age), and biochemical parameters (ferritin, hemoglobin, and retinol serum) were collected. RESULTS:The prevalence of anemia, iron deficiency, and retinol deficiency was 15.7%, 28.1%, and 24.7%, respectively. Univariate analysis showed a higher prevalence of anemia (PR: 4.62, 95% CI: 3.36, 6.34, p<0.001) and iron deficiency (PR: 4.51, 95% CI: 3.30, 6.17, p<0.001) among children with retinol deficiency. The same results were obtained after adjusting for socioeconomic and demographic conditions, dietary intake, and anthropometric variables. There was a positive association between ferritin vs. retinol serum (r=0.597; p<0.001) and hemoglobin vs. retinol serum (r=0.770; p<0.001). CONCLUSIONS:Anemia and iron deficiency were associated with low levels of serum retinol in children aged 1 to 5 years, and a positive correlation was verified between serum retinol and serum ferritin and hemoglobin levels. These results indicate the importance of initiatives encouraging the development of new treatments and further research regarding retinol deficiency. 10.1016/j.jped.2014.03.003
    Low intake of calcium and vitamin D, but not zinc, iron or vitamin A, is associated with stunting in 2- to 5-year-old children. van Stuijvenberg Martha E,Nel Jana,Schoeman Serina E,Lombard Carl J,du Plessis Lisanne M,Dhansay Muhammad A Nutrition (Burbank, Los Angeles County, Calif.) OBJECTIVES:This cross-sectional study examined the nutritional factors associated with the high levels of stunting in 2- to 5-y-old children in an impoverished South African setting where liver is frequently eaten and vitamin A deficiency known to be absent. METHODS:Children's dietary intake was assessed by a single 24-h recall. Heights and weights were measured and information was obtained on breast-feeding history, the child's habitual milk intake, as well as substance use by the mother during pregnancy (n = 150). RESULTS:The overall prevalence of stunting was 36.9% (CI 29.2, 44.6) and increased with age, being 49% in the 4- to 5-y-old age category. Birth weight correlated significantly with height-for-age z-scores (HAZ; r = 0.250, P = 0.003), and was lower in children whose mothers smoked and used alcohol during pregnancy than in children whose mothers abstained (P < 0.0001). Median intake of energy, carbohydrate and protein was adequate. Median intake for all micronutrients was at least 90% of the estimated average requirement, except for calcium, vitamin D and vitamin E, which was 21%, 15%, and 32%, respectively. Intake of fat, calcium, phosphorous, vitamin D, riboflavin, and vitamin B12 (nutrients that typically occur in milk) was significantly lower in stunted than in non-stunted children (P < 0.05). When excluding children with low birth weight, intake of calcium, vitamin D, and riboflavin were still significantly lower (P < 0.05). HAZ was higher in children who habitually drank milk compared to those who did not (P = 0.003). CONCLUSIONS:Inadequate calcium and vitamin D intake, presumably because of low intake of milk after weaning, may have contributed to stunting in this population. 10.1016/j.nut.2014.12.011
    Effect of simultaneous supplementation of vitamin A and iron on diarrheal and respiratory tract infection in preschool children in Chengdu City, China. Chen Ke,Chen Xin-ran,Zhang Lan,Luo Hong-yi,Gao Ning,Wang Jin,Fu Gui-Ying,Mao Meng Nutrition (Burbank, Los Angeles County, Calif.) OBJECTIVE:The goal of this study was to investigate whether vitamin A combined with iron supplementation for preschool children resulted in improved changes in children's infectious morbidity. METHOD:In this randomized placebo-controlled and blinded field intervention trial, totally 445 preschoolers, ages 3 to 6 y old, were randomly selected. All children were randomly divided into four groups: vitamin A supplement-only group (group I), iron supplement-only group (group II), vitamin A and iron supplement group (group III), and no vitamin A and ferrous sulfate as placebo-control (group IV) for 6 mo. The morbidity of diarrhea and respiratory infections, were collected during supplementation. RESULTS:There was evidence of the lowest incidence rate of respiratory-related illnesses and fewest symptoms of runny nose, cough, and fever for children in group III compared with children in groups I, II and IV (P < 0.05). Moreover, despite the undistinguished incidence rate of vomiting, nausea, and stomach pain, the rate of diarrhea-related illness was significantly lower for children in group III than for those in the other three groups. CONCLUSION:The beneficial affects on infectious morbidity over 6 mo, highlight the potential of vitamin A plus an iron supplement for preschool-aged children. 10.1016/j.nut.2013.03.025
    Effect of single-dose albendazole and vitamin A supplementation on the iron status of pre-school children in Sichuan, China. Chen Ke,Xie Hu Mina,Tian Weizheng,Zheng Xiaoling,Jiang Alice C The British journal of nutrition The aim of this study was to explore the effect of single-dose albendazole and vitamin A intervention on the anaemic status and Fe metabolism of pre-school children. This study was a randomised, placebo-controlled and double-blinded intervention trial. All eligible anaemic pre-school children were randomly divided into three groups: group 1 received no intervention, which served as the control group, group 2 received 400 mg single-dose albendazole administration and group 3 received a 60000 μg vitamin A capsule combined with 400 mg single-dose albendazole at the beginning of the study. The follow-up period was for 6 months. Anthropometry and biochemical index about Fe metabolism were measured before and after intervention. A total of 209 pre-school anaemic children were randomly divided into three intervention groups (sixty-four, sixty-two and sixty for groups 1, 2 and 3, respectively). The mean age of the children in the study was 4·4 (sd 0·7) years and 50·5 % of the children were female (94/186). After a follow-up period of 6 months, the levels of serum retinol, ferritin, transferrin receptor-ferritin index and body total Fe content of children in group 3 were significantly higher compared with children in groups 1 and 2 (P<0·05). Moreover, the proportion of vitamin A deficiency, marginal vitamin A deficiency and Fe deficiency among children in group 3 were markedly lower compared with children in groups 1 and 2 (P<0·05). Albendazole plus vitamin A administration showed more efficacy on the improvement of serum retinol and Fe metabolic status. 10.1017/S0007114516000350
    Undernutrition, Vitamin A and Iron Deficiency Are Associated with Impaired Intestinal Mucosal Permeability in Young Bangladeshi Children Assessed by Lactulose/Mannitol Test. Hossain Md Iqbal,Haque Rashidul,Mondal Dinesh,Mahfuz Mustafa,Ahmed Am Shamsir,Islam M Munirul,Guerrant Richard L,Petri William A,Ahmed Tahmeed PloS one BACKGROUND:Lactulose/mannitol (L:M) test has been used as a non-invasive marker of intestinal mucosal -integrity and -permeability (enteropathy). We investigated the association of enteropathy with anthropometrics, micronutrient- status, and morbidity in children. METHODS:The urine and blood samples were collected from 925 children aged 6-24 months residing in Mirpur slum of Dhaka, Bangladesh during November 2009 to April 2013. L:M test and micronutrient status were assessed in the laboratory of International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b) following standard procedure. RESULTS:Mean±SD age of the children was 13.2±5.2 months and 47.8% were female. Urinary- lactulose recovery was 0.264±0.236, mannitol recovery was 3.423±3.952, and L:M was 0.109±0.158. An overall negative correlation (Spearman's-rho) of L:M was found with age (rs = -0.087; p = 0.004), weight-for-age (rs = -0.077; p = 0.010), weight-for-length (rs = -0.060; p = 0.034), mid-upper-arm-circumference (rs = -0.098; p = 0.001) and plasma-retinol (rs = -0.105; p = 0.002); and a positive correlation with plasma α-1-acid glycoprotein (rs = 0.066; p = 0.027). However, most of the correlations were not very strong. Approximately 44% of children had enteropathy as reflected by L:M of ≥0.09. Logistic regression analysis revealed that younger age (infancy) (adjusted odds ratio (AOR) = 1.35; p = 0.027), diarrhea (AOR = 4.00; p = 0.039) or fever (AOR = 2.18; p = 0.003) within previous three days of L:M test were the risk factors of enteropathy (L:M of ≥0.09). CONCLUSIONS:Enteropathy (high L:M) is associated with younger age, undernutrition, low vitamin A and iron status, and infection particularly diarrhea and fever. 10.1371/journal.pone.0164447
    Effect of vitamin A supplementation on iron status in humans: A systematic review and meta-analysis. da Cunha Marcela de Sá Barreto,Campos Hankins Natália Aboudib,Arruda Sandra Fernandes Critical reviews in food science and nutrition Anemia is a worldwide public health problem that can be related to many causes, including vitamin A deficiency. The aim of this study was to assess and estimate the effect of vitamin A supplementation (VAS) on iron status biomarkers and anemia in humans. Six databases, including Cochrane, EMBASE, LILACS, Pubmed, Scopus and Web of Science, were searched for clinical trials and cohort studies that investigated the effect of vitamin A supplementation alone on iron status and anemia, without time-restriction. The search yielded 23 eligible studies, 21 clinical trials and 2 cohort studies, with children, teenagers, pregnant or lactating women. The meta-analysis of the clinical trials showed that VAS reduces the risk of anemia by 26% and raises hemoglobin levels, compared to non-treated group, independent of the life stage. VAS did not alter the prevalence of iron deficiency among the clinical trials conducted with children and teenagers (RR 0.82, 95% CI 0.60 to 1.12, p = 0.204), whereas a significant increase in serum ferritin levels was observed in trials conducted with pregnant and lactating women (WMD 6.61 μg/L; 95% CI 6.00 to 7.21 μg/L; p < 0.001). Therefore, vitamin A supplementation alone may reduce the risk of anemia, by improving hemoglobin and ferritin levels in individuals with low serum retinol levels. 10.1080/10408398.2018.1427552