Long-lasting mRNA-encoded interleukin-2 restores CD8+ T cell neoantigen immunity in MHC class I-deficient cancers.

Major histocompatibility complex (MHC) class I antigen presentation deficiency is a common cancer immune escape mechanism, but the mechanistic implications and potential strategies to address this challenge remain poorly understood. Studying ß2-microglobulin (B2M) deficient mouse tumor models, we find that MHC class I loss leads to a substantial immune desertification of the tumor microenvironment (TME) and broad resistance to immune-, chemo-, and radiotherapy. We show that treatment with long-lasting mRNA-encoded interleukin-2 (IL-2) restores an immune cell infiltrated, IFNγ-promoted, highly proinflammatory TME signature, and when combined with a tumor-targeting monoclonal antibody (mAB), can overcome therapeutic resistance. Unexpectedly, the effectiveness of this treatment is driven by IFNγ-releasing CD8+ T cells that recognize neoantigens cross-presented by TME-resident activated macrophages. These macrophages acquire augmented antigen presentation proficiency and other M1-phenotype-associated features under IL-2 treatment. Our findings highlight the importance of restoring neoantigen-specific immune responses in the treatment of cancers with MHC class I deficiencies.

Iron Deficiency is Related to Depressive Symptoms in United States Nonpregnant Women of Reproductive Age: A Cross-Sectional Analysis of NHANES 2005-2010.

BACKGROUND: Findings of the association between iron status and depressive symptoms in nonpregnant women of reproductive age (WRA) are equivocal, limited by a small sample size, or did not consistently control for confounders. OBJECTIVE: We tested the association between iron status and depressive symptoms in WRA with the NHANES data (2005-2010). METHODS: Nonpregnant WRA (20-44 y) with complete data on iron (ferritin and transferrin receptor (TfR)) and anemia (hemoglobin) biomarkers, depressive symptoms (Patient Health Questionnaire-9), and sociodemographic variables were included. Logistic and negative binomial regressions were used to estimate presence (odds ratios) and magnitude (prevalence ratios), respectively, for depressive symptoms by iron deficiency (ID)/anemia/ID anemia in the total sample and stratified by poverty:income ratio (≤ 1.85 or >1.85). RESULTS: Among 2516 females, the prevalence of ID was 8 to 16% (depending on the iron biomarker used), of anemia 8%, of which 52 to 65% were also ID. The prevalence of depressive symptoms was 10%. Crude logistic models showed that females with ID (TfR ≥ 8.3 mg/L or body iron <0 mg/kg) from the total sample had 1.82 (95% confidence interval [CI]: 1.24, 2.68) and 1.62 (95% CI: 1.05, 2.48), respectively, higher odds of depressive symptoms than females with iron sufficiency; these associations were attenuated after adjustments for confounders. Adjusted negative binomial models showed that females with ID (TfR ≥ 8.3 mg/L) from the total and low-income samples showed 1.19 (95% CI: 1:00, 1.40) and 1.27 (95% CI: 1.03, 1.58), respectively, higher prevalence ratios of depressive symptoms scores than females with iron sufficiency. CONCLUSIONS: These nationally representative data indicate that nonpregnant WRA with ID (based on high TfR) in the United States have higher prevalence of somatic depressive symptoms scores than those with iron sufficiency, especially if they are of low income.

Iron status, development, and behavior in young children in the Pennsylvania foster care system.

BACKGROUND: Children in foster care are classified as a highly vulnerable population and struggle with both physical and mental health problems. Medical conditions, like poor nutritional status, remain understudied in children in foster care. To our knowledge, few studies in children in U.S. foster care have quantified the prevalence of anemia, and no studies have examined the association between anemia status and relevant developmental and behavioral outcomes. OBJECTIVE/AIMS: (1) To determine the prevalence of anemia among children in or adopted from Pennsylvania foster care, between the ages of six months to ten years and (2) To examine if a child's anemia status is associated with greater odds of relevant developmental and behavioral diagnoses. METHODS: We conducted a secondary data analysis utilizing the Medicaid Analytic eXtract database between 2010-2015. Children six months-ten years were included in the analysis if they were in or had been adopted from Pennsylvania foster care. Logistic regression was used to calculate adjusted odds ratios (AOR) with 95% confidence intervals for the association between iron status and health outcomes. RESULTS: A total of 50,311 children were included in our sample, of which 1,365 children (2.7%) were diagnosed with anemia. Children diagnosed with anemia had greater odds of delayed milestones (AOR: 2.38 [1.64-3.45]), specific delays in development (AOR: 1.59 [1.23-2.07]), adjustment disorder (AOR: 1.59 [1.06-2.39]), and irritability (AOR: 10.57 [3.36-33.25]), than children not diagnosed with anemia. CONCLUSION: The prevalence of anemia among children between six months-ten years in or adopted from the Pennsylvania foster care system is within the national rate of U.S. childhood anemia. Odds of several relevant developmental and behavioral diagnoses were greater among children diagnosed with anemia than children who were not.

Modeling relationships between iron status, behavior, and brain electrophysiology: evidence from a randomized study involving a biofortified grain in Indian adolescents.

BACKGROUND: Iron deficiency (ID) and iron deficiency anemia (IDA) are highly-prevalent nutrient deficiencies and have been shown to have a range of negative effects on cognition and brain function. Human intervention studies including measures at three levels-blood, brain, and behavior-are rare and our objective was to model the relationships among measures at these three levels in school-going Indian adolescents. METHODS: Male and female adolescents in rural India were screened for ID/IDA. Subjects consumed 2 meals/day for 6 months; half were randomly assigned to consume meals made from a standard grain (pearl millet) and half consumed meals made from an iron biofortified pearl millet (BPM). Prior to and then at the conclusion of the feeding trial, they completed a set of cognitive tests with concurrent electroencephalography (EEG). RESULTS: Overall, serum ferritin (sFt) levels improved over the course of the study. Ten of 21 possible measures of cognition showed improvements from baseline (BL) to endline (EL) that were larger for those consuming BPM than for those consuming the comparison pearl millet (CPM). Critically, the best model for the relationship between change in iron status and change in cognition had change in brain measures as a mediating factor, with both change in serum ferritin as a primary predictor and change in hemoglobin as a moderator. CONCLUSIONS: A dietary intervention involving a biofortified staple grain was shown to be efficacious in improving blood iron biomarkers, behavioral measures of cognition, and EEG measures of brain function. Modeling the relationships among these variables strongly suggests multiple mechanisms by which blood iron level affects brain function and cognition. TRIAL REGISTRATION: Registered at ClinicalTrials.gov, NCT02152150 , 02 June 2014.

Full breastfeeding protection against common enteric bacteria and viruses: results from the MAL-ED cohort study.

BACKGROUND: Breastfeeding is known to reduce the risk of enteropathogen infections, but protection from specific enteropathogens is not well characterized. OBJECTIVE: The aim was to estimate the association between full breastfeeding (days fed breast milk exclusively or with nonnutritive liquids) and enteropathogen detection. METHODS: A total of 2145 newborns were enrolled at 8 sites, of whom 1712 had breastfeeding and key enteropathogen data through 6 mo. We focused on 11 enteropathogens: adenovirus 40/41, norovirus, sapovirus, astrovirus, and rotavirus, enterotoxigenic Escherichia coli (ETEC), Campylobacter spp., and typical enteropathogenic E. coli as well as entero-aggregative E. coli, Shigella and Cryptosporidium. Logistic regression was used to estimate the risk of enteropathogen detection in stools and survival analysis was used to estimate the timing of first detection of an enteropathogen. RESULTS: Infants with 10% more days of full breastfeeding within the preceding 30 d of a stool sample were less likely to have the 3 E. coli and Campylobacter spp. detected in their stool (mean odds: 0.92-0.99) but equally likely (0.99-1.02) to have the viral pathogens detected in their stool. A 10% longer period of full breastfeeding from birth was associated with later first detection of the 3 E. coli, Campylobacter, adenovirus, astrovirus, and rotavirus (mean HRs of 0.52-0.75). The hazards declined and point estimates were not statistically significant at 3 mo. CONCLUSIONS: In this large multicenter cohort study, full breastfeeding was associated with lower likelihood of detecting 4 important enteric pathogens in the first 6 mo of life. These results also show that full breastfeeding is related to delays in the first detection of some bacterial and viral pathogens in the stool. As several of these pathogens are risk factors for poor growth during childhood, this work underscores the importance of exclusive or full breastfeeding during the first 6 mo of life to optimize early health.

The prevalence of anemia and iron deficiency among pregnant Ghanaian women, a longitudinal study.

BACKGROUND: Gestational iron deficiency (ID) can be deleterious to mother and fetus. However, iron status is not routinely measured during pregnancy in Ghana. Therefore, the scope of ID in this population is unknown. OBJECTIVE: To determine the prevalence of anemia and ID across pregnancy in the Central Region of Ghana. METHODS: Women were recruited during their 1st trimester of pregnancy (< 13 weeks; n = 116) and followed through to their 2nd (n = 71) and 3rd (n = 71) trimesters. Data on socio-demographic variables, weekly intake of iron-rich foods and vitamin C-rich fruits were collected. Blood samples were drawn and the concentrations of hemoglobin (Hb), ferritin (Ft), serum iron (sFe), total iron binding capacity (TIBC), were measured; transferrin saturation (TSAT) was calculated. Repeated measures ANOVA was used to determine change in anemia and iron variables over time with groups categorized by 1st trimester iron status. RESULTS: Participants were 27.1 ± 5.2 years, on average. Prevalence of anemia (Hb <11.0 g/dL) was 37%, 63%, 58%; ID (Ft <15 µg/L) was 16%, 20%, 38%; and iron deficiency anemia (IDA; based on low Ft and Hb) was 6%, 12%, 25% in 1st, 2nd and 3rd trimesters, respectively. Significant changes in Hb, Ft and TIBC occurred across time. Iron status at 1st trimester had a significant effect on 2nd but not 3rd trimester iron status. CONCLUSIONS: ID is prevalent in pregnant Ghanaian women, especially during the 3rd trimester. Anemia is a major public health problem during pregnancy in Ghana with a significant proportion due to factors other than ID.

Net benefit and cost-effectiveness of universal iron-containing multiple micronutrient powders for young children in 78 countries: a microsimulation study.

BACKGROUND: Universal home fortification of complementary foods with iron-containing multiple micronutrient powders (MNPs) is a key intervention to prevent anaemia in young children in low-income and middle-income countries. However, evidence that MNPs might promote infection raises uncertainty about whether MNPs give net health benefits and are cost-effective. We aimed to determined country-specific net benefit or harm and cost-effectiveness of universal provision of MNPs to children aged 6 months. METHODS: We developed a microsimulation model to estimate net country-specific disability-adjusted life-years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) due to anaemia, malaria, and diarrhoea averted (or increased) by provision of a 6-month course of MNPs to children aged 6 months, compared with no intervention, who would be followed up for an additional 6 months (ie, to age 18 months). Anaemia prevalence was derived from Demographic and Health Surveys or similar national surveys, and malaria and diarrhoea incidence were sourced from the Global Burden of Disease Study. Programme and health-care costs were modelled to determine cost per DALY averted (US$). Additionally, we explored the effects of reduced MNP coverage in a sensitivity analysis. FINDINGS: 78 countries (46 countries in Africa, 20 in Asia or the Middle East, and 12 in Latin America) were included in the analysis, and we simulated 5 million children per country. 6 months of universal distribution of daily MNPs, assuming 100% coverage, produced a net benefit (DALYs averted) in 54 countries (24 in Africa, 19 in Asia and the Middle East, 11 in Latin America) and net harm in 24 countries (22 in Africa, one in Asia, and one in Latin America). MNP intervention provided a benefit on YLDs associated with anaemia, but these gains were attenuated and sometimes reversed by increases in YLLs associated with malaria and diarrhoea, reducing the benefits seen for DALYs. In the 54 countries where MNP provision was beneficial, the median benefit was 28·1 DALYs averted per 10 000 children receiving MNPs (IQR 20·6-40·4), and median cost per DALY averted was $3576 (IQR 2474-4918). DALY effects positively correlated with moderate and severe anaemia prevalence in Asia, the Middle East, and Latin America, but correlated inversely in Africa. Suboptimal coverage markedly reduced DALYs averted and cost-effectiveness. INTERPRETATION: Net health benefits of MNPs vary between countries, are highest where prevalence of moderate and severe anaemia is greatest but infection prevalence is smallest, and are ameliorated when coverage of the intervention is poor. Our data provide country-specific guidance to national policy makers. FUNDING: International Union of Nutrition Sciences.

Why Do Children in Slums Suffer from Anemia, Iron, Zinc, and Vitamin A Deficiency? Results from a Birth Cohort Study in Dhaka.

Considering the high burden of micronutrient deficiencies in Bangladeshi children, this analysis aimed to identify the factors associated with micronutrient deficiencies and association of plasma micronutrient concentration trajectories from 7 to 24 months with the concentrations at 60 months of age. Plasma samples were collected at 7, 15, 24, and 60 months of age, and hemoglobin, ferritin, zinc, and retinol concentrations of 155, 153, 154, and 155 children were measured, respectively. A generalized estimating equation was used to identify the factors associated with micronutrient deficiencies, while latent class growth modeling identified the trajectories of plasma micronutrients from 7 to 24 months and its association with the concentrations of micronutrients at 60 months was examined using multiple linear regression modeling. Early (AOR = 2.21, p < 0.05) and late convalescence (AOR = 1.65, p < 0.05) stage of an infection, low ferritin (AOR = 3.04, p < 0.05), and low retinol (AOR = 2.07, p < 0.05) were associated with increased anemia prevalence. Wasting at enrollment was associated with zinc deficiency (AOR = 1.8, p < 0.05) and birth weight was associated with ferritin deficiency (AOR = 0.58, p < 0.05). Treatment of drinking water was found protective against vitamin A deficiency (AOR = 0.57, p < 0.05). Higher trajectories for ferritin and retinol during 7-24 months were positively associated with plasma ferritin (ß = 13.72, p < 0.05) and plasma retinol (ß = 3.99, p < 0.05) at 60 months.

Changes in Iron Status Are Related to Changes in Brain Activity and Behavior in Rwandan Female University Students: Results from a Randomized Controlled Efficacy Trial Involving Iron-Biofortified Beans.

BACKGROUND: Evidence suggests that iron deficiency (ID) affects cognitive performance, as measured in behavior. Although such effects must be mediated by changes in the brain, very few studies have included measures of brain activity to assess this relation. OBJECTIVE: We tested the hypothesis that provision of iron-biofortified beans would result in improvements in measures of iron status, brain dynamics, and behavior. METHODS: A double-blind, randomized, intervention study was conducted in 55 women aged 18-27 y with low iron status (serum ferritin <20 µg/L). Women were randomly assigned to consume iron-biofortified (86.1 ppm iron) or comparison beans (50.1 ppm iron) daily for 18 wk. Iron status was assessed by hemoglobin, ferritin, transferrin receptor, and body iron; cognitive performance with 5 computerized tasks; and brain dynamics by concurrent electroencephalography (EEG). All measures were taken at baseline and endline. RESULTS: The groups did not differ on any measures at baseline. Intention-to-treat analyses revealed significant (all P < 0.05) improvements in hemoglobin (partial effect size attributable to the independent variable, η2 = 0.16), ferritin (η2 = 0.17), and body iron (η2 = 0.10), speed of responding in attentional and mnemonic tasks (η2 = 0.04-0.29), sensitivity and efficiency of memory retrieval (η2 = 0.12-0.55), and measures of EEG amplitude and spectral power (η2 = 0.08 to 0.49). Mediation models provided evidence in support of the hypothesis that changes in iron status produce changes in behavior by way of changes in brain activity. CONCLUSIONS: Behavioral performance and brain activity, as measured by EEG, are sensitive to iron status, and the consumption of iron-biofortified beans for 18 wk resulted in improvements in measures of both, relative to what was obtained with a comparison bean, in a sample of female university students. Furthermore, the results support the conclusion that changes in brain activity resulting from consumption of biofortified beans mediate the relations between changes in iron biomarkers and changes in cognition. Clinical trial registry: ClinicalTrials.gov Reg No. NCT01594359.

Iron status at opposite ends of the menstrual function spectrum.

OBJECTIVES: Although exercising women are at high risk of poor iron status, it is unknown how non-pathological, physiological menstrual function affects iron status. As such, this study investigates the association between menstrual function and iron status in exercising women with amenorrhea and exercising women with ovulatory, eumenorrheic menstrual cycles. DESIGN: Cross-sectional analysis of iron depletion prevalence, iron status indices, exercise parameters, and diet composition. METHODS: Women aged 18-35 years performing at least 2 h per week of aerobic exercise were recruited. Women with amenorrhea (AMEN) were defined by the absence of menses for at least 90 days or less than 6 menses in the past 12 months (n = 82). Women with ovulatory, eumenorrheic menstrual cycles (OvEU) were defined by the presence of ovulatory cycles of 26-35 days in length for the past 6 months (n = 109). Group differences in serum ferritin (Ft), soluble transferrin receptor (sTfR), total body iron (TBI), hemoglobin (Hb), hematocrit (Hct), iron depletion prevalence (Ft <15 µg/L), peak oxygen consumption (VO2peak), exercise minutes per week, and diet logs were assessed. RESULTS: The prevalence of iron depletion was greater in OvEU when compared to AMEN (26% vs. 15%, p = 0.04). No significant differences were observed between AMEN and OvEU in Ft (30.2 ± 2.2 vs. 24.9 ± 2.6 µg/L; p = 0.62), sTfR (5.2 ± 1.4 vs. 4.9 ± 1.5 mg/L; p = 0.95), TBI (5.3 ± 2.7 vs. 4.8 ± 3.7 mg/kg; p = 0.42), Hb (13.2 ± 0.4 vs. 13.4 ± 0.6 g/dL; p = 0.80), Hct (39.5 ± 0.8% vs. 39.8 ± 4.1%; p = 0.93), or exercise parameters. AMEN consumed more vitamin C than OvEU (269 ± 180 vs. 129 ± 141 mg/day, p < 0.001), but all other dietary factors were similar between AMEN and OvEU. CONCLUSION: Exercising women with ovulatory, eumenorrheic cycles are at a greater risk of iron depletion than exercising, amenorrheic women. Thus, menstrual function must be considered when screening for poor iron status in exercising women.

Effect of iron deficiency on simultaneous measures of behavior, brain activity, and energy expenditure in the performance of a cognitive task.

OBJECTIVES: Iron deficiency (ID) - the highly prevalent nutritional deficiency - has been shown to have deleterious effects on measures of cognitive performance and brain activity. Many of these results are suggestive of the impact of ID on neurotransmitter regulation and myelination. A third critical potential effect of ID on brain function is at the level of brain energy expenditure; however, to date there has not been any method for indirectly estimating the impact of ID on energy expenditure in humans in the context of cognitive work. METHODS: We report here a study comparing ID and iron sufficient (IS) college students in which simultaneous behavioral, encephelographic (EEG), and metabolic data were collected in a task designed as a cognitive analog to standard physical exertion tasks. RESULTS: We show that increases in cognitive demands produced decrements in behavioral measures of performance, and increases in EEG and metabolic measures of work. Critically, we found that the magnitudes of those changes were directly related to iron levels. DISCUSSION: We find support for the idea that brain activity mediates the relationship between cognitive demands and energy expenditure, with ferritin and hemoglobin moderating those relationships in distinct ways. Finally, we show that levels of energy expenditure can be indirectly estimated by measures of EEG spectral power.

Cognitive Performance in Indian School-Going Adolescents Is Positively Affected by Consumption of Iron-Biofortified Pearl Millet: A 6-Month Randomized Controlled Efficacy Trial.

BACKGROUND: Iron deficiency remains the most prevalent micronutrient deficiency globally, but few studies have examined how iron status relates to cognition in adolescents. Iron biofortification of staple food crops is being scaled up, yet it is unknown whether consuming biofortified crops can benefit cognition. Objective: Our objective was to determine the efficacy of iron-biofortified pearl millet in improving attention and memory in Indian school-going adolescents. Methods: A double-blind, randomized, intervention study was conducted in 140 Indian boys and girls, aged 12-16 y, who were assigned to consume iron-biofortified [Fe = 86 parts per million (ppm)] or conventional (Fe = 21-52 ppm) pearl millet. Hemoglobin, ferritin, and transferrin receptor (TfR) were measured and body iron (BI) was calculated at baseline and after 4 and 6 mo. Five measures of cognitive function were obtained at baseline and 6 mo: simple reaction time (SRT), Go/No-Go (GNG) task, Attentional Network Task (ANT), Composite Face Effect (CFE) task, and Cued Recognition Task (CRT). Intention-to-treat analysis was used. Results: Daily iron intake from pearl millet was higher in those consuming biofortified compared with conventional pearl millet (19.6 compared with 4.8 mg/d). Effects on ferritin, TfR, and BI at 4 mo, and on TfR at 6 mo (all P < 0.05), indicated efficacy of biofortified pearl millet over conventional pearl millet in improving iron status. Compared with conventional pearl millet, the consumption of biofortified pearl millet resulted in greater improvement in attention (SRT, GNG, and ANT) and memory (CFE and CRT). Reaction time decreased twice as much from 0 to 6 mo in those consuming biofortified compared with conventional pearl millet on attention tasks (SRT: -123 compared with -63 ms; GNG: -67 compared with -30 ms; ANT double cue: -74 compared with -32 ms; all P < 0.01). Conclusion: Consuming iron-biofortified pearl millet improves iron status and some measures of cognitive performance in Indian adolescents. This trial was registered at http://www.clinicaltrials.gov as NCT02152150.

Association Between Non-Iron-Deficient Anemia and Insomnia Symptoms in Community-Dwelling Older Adults: The Baltimore Longitudinal Study of Aging.

Background: Anemia is associated with poorer sleep in children, and clinically, anemia is linked to insomnia. However, the association between anemia and insomnia in older adults is understudied. Methods: We examined the cross-sectional association between anemia and insomnia in 1,053 adults (71.4 ± 10.6 years) in the Baltimore Longitudinal Study of Aging. Participants were classified as nonanemic, non-iron-deficient anemic, or iron-deficient anemic based on hemoglobin, ferritin, transferrin saturation, and mean cell volume. Insomnia symptoms were evaluated by the Women's Health Initiative Insomnia Rating Scale (WHIIRS). A total score (range 0-20) was generated, and participants were also classified as having 0, 1, or 2+ symptoms. Results: Overall, 10.5% of participants had non-iron-deficient anemia, 0.9% had iron-deficient anemia, and 88.5% had no anemia. Due to its low prevalence, the iron-deficient anemic group was dropped from analyses. In models adjusted for demographics, number of medical conditions, and Center for Epidemiologic Studies Depression Scale score, non-iron-deficient anemic individuals had significantly higher WHIIRS total scores, indicating greater insomnia severity, compared to those without anemia (predicted adjusted mean WHIIRS of 7.24 [95% confidence interval (CI): 6.40-8.08] vs 5.92 [95% CI: 5.65-6.19]). They also had twice the risk of reporting ≥2 insomnia symptoms (vs 0 symptoms; relative risk ratio = 2.20, 95% CI: 1.25-3.89). Conclusions: Results suggest that individuals with non-iron-deficient anemia are more likely to experience insomnia symptoms than those who are nonanemic. These results may have implications for insomnia treatment or the identification of underlying frailty in individuals with sleep problems.

Consumption of Iron-Biofortified Beans Positively Affects Cognitive Performance in 18- to 27-Year-Old Rwandan Female College Students in an 18-Week Randomized Controlled Efficacy Trial.

Background: Evidence shows that iron deficiency in adulthood may affect cognitive performance, possibly by disrupting neurotransmitter regulation or brain energy metabolism. Women of reproductive age (WRA) are among those who are most vulnerable to iron deficiency; however, they have been largely ignored in the literature relating iron status to cognition.Objective: Our aim was to determine the efficacy of iron-biofortified beans in improving cognition in WRA compared with control beans.Methods: A double-blind, randomized intervention study was conducted in 150 women aged 18-27 y with low iron status (ferritin <20 µg/L). Women were randomly assigned to consume iron-biofortified beans (86.1 ppm iron) or control beans (50.1 ppm iron) daily for 18 wk. Iron status was assessed based on hemoglobin, ferritin, transferrin receptor, and body iron values and on cognitive performance on 5 computerized tasks at baseline and endline.Results: Groups did not differ on any variables at baseline. Per protocol analyses revealed that consumption of the biofortified beans resulted in a 17% larger improvement in the speed of spatial selective attention; a nearly 7-fold larger improvement in the speed, a 68% greater improvement in the efficiency, and a >2-fold greater improvement in the specificity of memory retrieval; and a >2-fold larger improvement in the speed and a >3-fold larger improvement in the efficiency of memory search-all of which are relative to consumption of the control beans (P < 0.01 for all comparisons).Conclusions: Cognitive performance is sensitive to iron status, and consumption of iron-biofortified beans for 18 wk improved cognitive performance, especially the efficiency of search and the speed of retrieval on memory tasks, in young adult women. This trial was registered at clinicaltrials.gov as NCT01594359.

Double Fortified Salt Intervention Improved Iron Intake But Not Energy and Other Nutrient Intakes in Female Tea Plantation Workers From West Bengal, India.

BACKGROUND: Iron deficiency is a global public health concern and has implications on the health status of women in reproductive age. OBJECTIVE: We hypothesized that improving iron intake with double fortified salt would improve food intake, resulting in higher energy, nutrient intakes, and weight indicators of female tea plantation workers. METHODS: In this randomized double-masked study, the participants (n = 245) were assigned to receive salt double fortified with iron and iodine (DFS; treatment) or salt fortified with iodine (control) and followed for 7.5 to 9 months. Dietary intakes were measured at three time points, baseline, midpoint, and end line using (1) food frequency questionnaire, (2) 24-hour recall, and (3) weighed lunch intake. Anthropometric measures of height (cm), weight (kg), and mid-upper arm circumference (cm) were also recorded at three time points. Mixed-model repeated-measures approach was used to detect group differences across time. RESULTS: Double fortified salt improved dietary iron intake in the treatment group compared to the control group ( P < .001). No other dietary or anthropometric differences could be attributed to treatment. Significant effect of time was observed in the intake frequency of major food groups and calcium, vitamin A and C ( P <.001 for all), suggesting an equal effect of seasonality in both the groups. CONCLUSION: Addition of DFS in the diet improved dietary iron intake but did not affect the intake of energy, other nutrients, or nutritional status indicators. The improvement observed in the dietary iron intake demonstrates that fortification is an effective strategy to address iron deficiency in at-risk populations.

Association between menarche and iron deficiency in non-anemic young women.

BACKGROUND: The prevalence of iron deficiency (ID) among non-pregnant, reproductive-age US women significantly exceeds rates among males. In clinical practice ID screening relies on hemoglobin, a late-stage indicator of ID. As a single, low-cost laboratory test to diagnose ID before anemia develops is lacking, the study objective was to improve ID screening by identifying risk factors among non-anemic, iron-deficient reproductive age women. METHODS: Cross-sectional data were from the National Health and Nutrition Examination Survey (NHANES) 2003-2010. Hemoglobin identified non-anemic women. ID was defined using the body iron formula, requiring ferritin and transferrin receptor values. Logistic regression assessed the association of sociodemographic, behavioral, and reproductive risk factors in an anemia-based conceptual framework with non-anemic reproductive age women (12-49 years) with ID, as well as subsets of younger (12-21 years) and older (22-49 years) women, recognizing that risks may differ by age. RESULTS: Among 6216 women, 494 had ID (prevalence was 8.0%, 95% CI 7.3%, 8.6%). Among non-anemic younger women, 250 (8.7%, 95% CI 7.7%, 9.8%) had ID, compared to 244 (7.3%, 95% CI 6.4%, 8.2%) older women. Among younger women, menstruation for over 3 years was the only variable significantly associated with non-anemic ID (risk ratio 3.18, 95% CI 2.03, 4.96). No other significant risk factors were identified. CONCLUSION: Menstrual years was the only risk factor significantly associated with ID among non-anemic younger women. The negative results suggest ID risk factors among non-anemic women may need to be considered separately from those associated with ID anemia.

Risk-Based Questionnaires Fail to Detect Adolescent Iron Deficiency and Anemia.

OBJECTIVE: To evaluate the predictive ability of screening questionnaires to identify adolescent women at high-risk for iron deficiency or iron deficiency anemia who warrant objective laboratory testing. STUDY DESIGN: Cross-sectional study of 96 female individuals 12-21 years old seen at an academic medical center. Participants completed an iron deficiency risk assessment questionnaire including the 4 Bright Futures Adolescent Previsit Questionnaire anemia questions, along with depression, attention, food insecurity, and daytime sleepiness screens. Multiple linear regression controlling for age, race, and hormonal contraception use compared the predictive ability of 2 models for adolescent iron deficiency (defined as ferritin <12 mcg/L) and anemia (hemoglobin <12 g/dL). Model 1, the Bright Futures questions, was compared with model 2, which included the 4 aforementioned screens and body mass index percentile. RESULTS: Among participants, 18% (17/96) had iron deficiency and 5% (5/96) had iron deficiency anemia. Model 1 (Bright Futures) poorly predicted ferritin and hemoglobin values (R2 = 0.03 and 0.08, respectively). Model 2 demonstrated similarly poor predictive ability (R2 = 0.05 and 0.06, respectively). Mean differences for depressive symptoms (0.3, 95% CI -0.2, 0.8), attention difficulty (-0.1, 95% CI -0.5, 0.4), food insecurity (0.04, 95% CI -0.5, 0.6), daytime sleepiness (0.1, 95% CI -0.1, 0.3), and body mass index percentile (-0.04, 95% CI -0.3, 0.2) were not significantly associated with ferritin in model 2. Mean differences for hemoglobin were also nonsignificant. CONCLUSIONS: Risk-based surveys poorly predict objective measures of iron status using ferritin and hemoglobin. Next steps are to establish the optimal timing for objective assessment of adolescent iron deficiency and anemia.