Prashanth Thankachan

An analysis of the etiology of anemia and iron deficiency in young women of low socioeconomic status in Bangalore, India

Background Anemia and iron deficiency are significant public health problems in India, particularly among women and children. Recent figures suggest that nearly 50% of young Indian women are anemic. Objectives Few studies have comprehensively assessed etiologic factors contributing to anemia and iron deficiency in India. Hence, this study assessed the relative importance of various factors contributing to these problems in young women of low socioeconomic status in Bangalore, India. Methods A random sample of 100 nonpregnant, nonlactating women 18 to 35 years of age, selected from among 511 women living in a poor urban settlement, participated in this study. Data were obtained on demography, socioeconomic status, anthropometry, three-day dietary intake, blood hemoglobin, hemoglobinopathies, serum ferritin, serum C-reactive protein, and stool parasites. Results The prevalence rates of anemia and iron deficiency were 39% and 62%, respectively; 95% of the anemic women were iron deficient. The mean dietary iron intake was 9.5 mg per day, predominantly from the consumption of cereals, pulses, and vegetables (77%). The estimated bioavailability of nonheme iron in this diet was 2.8%. Dietary intakes were suboptimal for several nutrients. Blood hemoglobin was significantly correlated with dietary intake of fat, riboflavin, milk and yogurt, and coffee. Serum ferritin was significantly correlated with intake of niacin, vitamin B12, and selenium. Parasitic infestation was low. Conclusions An inadequate intake of dietary iron, its poor bioavailability, and concurrent inadequate intake of dietary micronutrients appear to be the primary factors responsible for the high prevalence of anemia and iron deficiency in this population.

Iron Fortification of Whole Wheat Flour Reduces Iron Deficiency and Iron Deficiency Anemia and Increases Body Iron Stores in Indian School-Aged Children

Wheat is the primary staple food for nearly one-third of the worlds population. NaFeEDTA is the only iron (Fe) compound suitable for fortifying high extraction flours. We tested the hypothesis that NaFeEDTA-fortified, whole wheat flour reduces Fe deficiency (ID) and improves body Fe stores (BIS) and cognitive performance in Indian children. In a randomized, double-blind, controlled, school feeding trial, 6- to 15-y-old, Fe-depleted children (n = 401) were randomly assigned to either a daily wheat-based lunch meal fortified with 6 mg of Fe as NaFeEDTA or an otherwise identical unfortified control meal. Hemoglobin (Hb) and Fe status were measured at baseline, 3.5 mo, and 7 mo. Cognitive performance was evaluated at baseline and 7 mo in children (n = 170) at one of the study sites. After 7 mo, the prevalence of ID and ID anemia in the treatment group significantly decreased from 62 to 21% and 18 to 9%, respectively. There was a time x treatment interaction for Hb, serum ferritin, transferrin receptor, zinc protoporphyrin, and BIS (all P < 0.0001). Changes in BIS differed between the groups; it increased in the treatment group (0.04 ± 0.04 mmol/kg body weight) and decreased in the control group (-0.02 ± 0.04 mmol/kg body weight) (P < 0.0001). In sensory tests, NaFeEDTA-fortified flour could not be differentiated from unfortified flour. There were no significant differences in cognitive performance tests between the groups. NaFeEDTA-fortified wheat flour markedly improved BIS and reduced ID in Fe-depleted children. It may be recommended for wider use in national school feeding programs.

Low anemia prevalence in school-aged children in Bangalore, South India : possible effect of school health initiatives

Objective:Anemia is a serious public health problem in Indian school children. Since 2003, simple health intervention programs such as antihelminthic treatment and vitamin A supplementation have been implemented in primary schools in the Bangalore region, Karnataka, India. This study examines the prevalence of anemia in school children who are beneficiaries of this program.Design:Cross-sectional survey.Setting:Bangalore district, South India.Subjects:A total of 2030 boys and girls, aged 5–15 years, attending schools in the Bangalore district.Interventions:School-based, twice yearly intervention: deworming (albendazole 400 mg, single oral dose) and vitamin A supplementation (200 000 IU, single oral dose).Main outcome measures:Anemia prevalence based on measure of blood hemoglobin (Hb).Results:Mean age and blood Hb concentration of all children were 9.5±2.6 years and 12.6±1.1 g/dl (range 5.6–16.7), respectively. The overall anemia prevalence in this group was 13.6%. Anemia prevalence was lower in boys than girls (12.0%; n=1037 vs 15.3%; n=993 respectively, P<0.05). There was no significant difference in anemia prevalence between children in urban and rural locations (14.6 and 12.3%, respectively).Conclusions:The current low anemia prevalence in Bangalore could be due to the impact of school-based intervention programs that have been in place since 2003. The beneficial interactions of deworming and vitamin A supplementation could have widespread implications for current preventive public health initiatives. There is now need for the development of clear policy guidelines based on these simple and integrated interventions.Sponsorship:This research was supported by the Micronutrient Initiative, Ottawa, Canada, and Unilever Food and Health Research Institute, Vlaardingen, The Netherlands.

Multiple Micronutrient-Fortified Rice Affects Physical Performance and Plasma Vitamin B-12 and Homocysteine Concentrations of Indian School Children

Fortifying rice with multiple micronutrients could be a promising strategy for combat micronutrient deficiencies in developing countries. We determined the efficacy of extruded rice grains fortified with multiple micronutrients on the prevalence of anemia, micronutrient status, and physical and cognitive performance in 6- to 12-y-old, low-income school children in Bangalore, India. In a randomized, double-blind, controlled trial, 258 children were assigned to 1 of 3 intervention groups to receive rice-based lunch meals fortified with multiple micronutrients with either low-iron (6.25 mg) or high-iron (12.5 mg) concentrations or identical meals with unfortified rice. The meals were provided 6 d/wk for 6 mo. Anthropometric, biochemical, physical performance, and cognitive assessments were taken at baseline and endpoint. At baseline, study groups were comparable, with 61% of the children being anemic. However, only <10% were deficient in iron, vitamin A, and zinc. After 6 mo, plasma vitamin B-12 and homocysteine concentrations (both P < 0.001) as well as physical performance (P < 0.05) significantly improved in the intervention arms. No between-group differences were observed in hemoglobin concentration, anemia, and deficiencies of other micronutrients or cognitive function after 6 mo, but paired analyses revealed a small reduction in anemia prevalence in children in the low-iron group. The fortified rice was efficacious in improving vitamin B-12 status and physical performance in Indian school children.

Catch-up growth does not associate with cognitive development in Indian school-age children

Background/objectives:Stunting is significantly associated with lifetime morbidity and poorer cognitive outcomes in children. Although several studies have examined the relationship between stunting, catch-up growth and cognitive performance in young populations, this relationship has not yet been explored in school-aged children. In this study, we used data from three different nutritional intervention studies conducted over a 4-year period on school-age children in Bangalore, India to assess these relationships.Subjects/methods:A battery of cognitive tests was conducted before each intervention to determine whether stunting status at baseline was related to cognitive performance across four separate domains, and repeated after a 6-month period to assess whether changes to stunting status is related to cognitive advancement.Results:Results of independent t-tests showed that while stunted children had significantly poorer performance on short-term memory, retrieval ability and visuospatial ability tests (P=0.023, 0.026 and 0.028, respectively), there was no significant difference in the change in cognitive scores following nutritional interventions over a 6-month period between those who remained stunted and those who were no longer stunted (P>0.10).Conclusions:Evidently, stunting remains associated with cognitive ability in school-age children; however, the reversal of these effects in this age group may be quite difficult.

Efficacy of a multi micronutrient-fortified drink in improving iron and micronutrient status among schoolchildren with low iron stores in India: a randomised, double-masked placebo-controlled trial

Background/Objectives:A multiple micronutrient-fortified drink could be an effective strategy to combating micronutrient deficiencies in school going children. To assess the efficacy of a multiple micronutrient-fortified drink in reducing iron deficiency (ID), ID anemia (IDA), anemia and improving micronutrient status among schoolchildren with low iron stores. The study employed a school-based, randomized, double-blind, placebo-controlled design.Subjects/Methods:Schoolchildren with low serum ferritin (SF <20 μg/l) (n=246), aged 6–12 years were randomly assigned to receive either a multi-micronutrient fortified or an unfortified identical control drink. The drinks were provided 6 days/week for 8 weeks. Anthropometric and biochemical assessments were taken at baseline and endline.Results:Study groups at baseline were comparable, and compliance to the intervention was similar. The overall prevalence of ID, IDA and anemia was 64%, 19% and 24%, respectively. The prevalence of ID, IDA, vitamin C and vitamin B12 deficiencies significantly reduced by 42%, 18%, 21% and 5%, respectively, in the intervention arm (P<0.01) as compared with the control arm at the end of the study. Similarly, the concentration of hemoglobin, SF, vitamin A, vitamin B12, vitamin C and body iron stores were significantly higher in the intervention arm in comparison to the control arm (P<0.001). Red cell folate levels also improved significantly in the intervention arm (P=0.04), however, serum zinc status did not change in either of the study arms. Children who had received the fortified drink had significantly lower odds of being ID (0.15; 95% confidence interval (CI): 0.09–0.27), IDA (0.14; 95% CI: 0.04–0.52), vitamin B12 deficient (0.36; 95% CI: 0.18–0.73) and vitamin C deficient (0.24; 95% CI: 0.13–0.46), after adjusting for baseline age, gender and weight.Conclusions:The multi micronutrient-fortified drink was efficacious in reducing the prevalence of ID, IDA, vitamin C and vitamin B12 deficiency and improved micronutrient status in schoolchildren.

Helicobacter pylori infection does not influence the efficacy of iron and vitamin B 12 fortification in marginally nourished Indian children

Background/Objectives:Helicobacter pylori infection and iron and vitamin B12 deficiencies are widespread in economically disadvantaged populations. There is emerging evidence that H. pylori infection has a negative effect on the absorption of these micronutrients. The aim of this study was to evaluate the effect of H. pylori infection on the efficacy of micronutrient (including iron and vitamin B12)-fortified foods supplied for 1 year in marginally nourished children.Subjects/Methods:In all, 543 Indian children, aged 6–10 years, participated in a double-blind, randomized controlled intervention trial, receiving foods fortified with either high (100% Recommended Dietary Allowances (RDA)) or low (15% RDA) amounts of iron, vitamin B12 and other micronutrients. The presence of H. pylori infection was diagnosed by the 13C-labeled urea breath test at 11 months after the start of the intervention. Blood hemoglobin, serum ferritin (SF), total body iron and plasma vitamin B12 were estimated at baseline and 12 months, and differences between these time points were assessed using an independent t-test.Results:Overall, the prevalence of H. pylori infection in this group of children was 79%. Baseline hemoglobin, SF, body iron and vitamin B12 concentrations were not associated with H. pylori infection. The response to the intervention (either high or low amounts of iron and vitamin B12 fortification) in terms of change in iron markers and vitamin B12 status did not differ between children with and without H. pylori infection.Conclusions:This study shows that the presence of H. pylori infection did not affect the efficacy of long-term iron and vitamin B12 fortification in these marginally nourished children.

Inhibition of Iron Absorption by Calcium Is Modest in an Iron-Fortified, Casein- and Whey-Based Drink in Indian Children and Is Easily Compensated for by Addition of Ascorbic Acid

BACKGROUND Calcium inhibits and ascorbic acid (AA) enhances iron absorption from iron-fortified foods. Absorption efficiency depends on iron status, although the interaction is unclear. OBJECTIVE We investigated the ability of AA to overcome calcium-induced inhibition of iron absorption in children differing in iron status. METHODS The effect of calcium (0, 100, and 200 mg/test meal) on iron absorption in the absence and presence of AA (0, 42.5, and 85 mg/test meal) from a casein/whey-based drink fortified with ferrous sulfate was assessed in a series of randomized crossover studies both in iron-replete (IR) Indian schoolchildren and in children with iron deficiency anemia (IDA) (6-11 y; n = 14-16/group) by using stable isotopes. RESULTS In the absence of calcium and AA, iron absorption from the casein/whey-based drink was 20% lower in IR children than in children with IDA. The addition of calcium reduced mean iron absorption by 18-27%, with the effect being stronger for high added calcium (P < 0.01). AA at a 2:1 or 4:1 molar ratio enhanced iron absorption by a factor of 2-4 and greatly overcompensated for the inhibitory effect of calcium on iron absorption in a dose-dependent manner (P < 0.001). The dose-response effect tended to be stronger (P < 0.1) in the IDA group, and iron status was of far less influence on iron absorption than the enhancing effect of AA. CONCLUSION When adding AA to iron-fortified milk products, care should be taken not to provide absorbable iron in excess of needs.

Breast milk zinc transfer and early post-natal growth among urban South Indian term infants using measures of breast milk volume and breast milk zinc concentrations

Zinc (Zn) deficiency in infancy and early childhood is of public health concern in developing countries. This study aimed to longitudinally assess Zn intake of urban South Indian term infants in the first 6 months of life using measures of breast milk (BM) volume and BM Zn concentrations and, additionally, to study the effect of BM Zn intake on infant length and weight gain. BM intake by the deuterium dilution technique, BM Zn concentration at months 1, 3 and 6, as well as serum Zn level at months 3 and 6 were assessed in 50 mother-infant pairs. BM intake significantly declined from 627 mL day(-1) at month 1 to 608 mL day(-1) at month 6 (P < 0.01). BM Zn concentration and intake significantly declined from month 1 to month 6 (P < 0.001 for both). Mean infant serum Zn level at months 3 and 6 were 93.0 ± 27.1 and 99.6 ± 30.1 µg dL(-1), respectively. Infant BM Zn intake at months 1 and 3 was not associated with the weight and length gain between 1-3 and 3-6 months, respectively. Zn intake from BM, maternal BM Zn content and serum Zn levels were not significantly different between small-for-gestational age and appropriate-for-gestational age infants. Therefore, among urban south Indian term infants less than 6 months of age, BM Zn intakes were low, owing to low volumes of BM intake, despite BM Zn concentrations being in the normal range. Promotion of breastfeeding and thereby increasing the volumes of milk produced is a first important step towards improving Zn intake among infants.

Beneficiary effect of nanosizing ferric pyrophosphate as food fortificant in iron deficiency anemia: evaluation of bioavailability, toxicity and plasma biomarker

Iron deficiency anemia is a global health issue affecting a significant population worldwide. Fortification of food with iron compounds is a widely used strategy to prevent iron deficiency anemia. To overcome sensory effects, water insoluble and white colored compounds, like ferric pyrophosphate, are used to fortify infant cereals. Ferric pyrophosphate is poorly bioavailable due to its low solubility even in an acid medium. Nanosized iron salts find potential applications in food fortification, since solubility increases with decrease in the particle size. However, limited knowledge exists about the effect of nanoparticles in a biological system. The present study addresses the efficacy of synthesized ferric pyrophosphate in its nano form (10–30 nm) as a potential food fortificant in iron deficiency anemia and measures its toxicity in a rat model. Additionally, the effect of the nanoparticle in vivo has been explored using a mass-spectrometry-based plasma proteomics approach. The relative bioavailability of ferric pyrophosphate nanoparticle, calculated using hemoglobin regeneration efficiency was found to be 103.02% with respect to the reference salt, ferrous sulphate. Histopathological examinations of different organs did not show any significant toxicity attributable to nanoparticle ferric pyrophosphate. However, plasma proteomics analysis showed a decreasing trend in Fetuin-B concentration with increasing dose levels of nanoparticle ferric pyrophosphate. In conclusion, the nanoparticle ferric pyrophosphate could be a promising food fortificant in combating iron deficiency anemia, while Fetuin-B, a negative acute phase protein, might be a potential candidate for detecting biological responses to the nanoparticle exposure in vivo.