Vitamin B12 supplementation during pregnancy for maternal and child health outcomes.

BACKGROUND: Vitamin B12 deficiency is a major public health problem worldwide, with the highest burden in elderly people, pregnant women, and young children. Due to its role in DNA synthesis and methylation, folate metabolism, and erythropoiesis, vitamin B12 supplementation during pregnancy may confer longer-term benefits to maternal and child health outcomes. OBJECTIVES: To evaluate the benefits and harms of oral vitamin B12 supplementation during pregnancy on maternal and child health outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) on 2 June 2023, and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs, or cluster-RCTs evaluating the effects of oral vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation during pregnancy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Four review authors independently assessed trial eligibility. Two review authors independently extracted data from included studies and conducted checks for accuracy. Three review authors independently assessed the risk of bias of the included studies using the Cochrane RoB 1 tool. We used GRADE to evaluate the certainty of evidence for primary outcomes. MAIN RESULTS: The review included five trials with 984 pregnant women. All trials were conducted in low- and middle-income countries, including India, Bangladesh, South Africa, and Croatia. At enrolment, 26% to 51% of pregnant women had vitamin B12 deficiency (less than 150 pmol/L), and the prevalence of anaemia (haemoglobin less than 11.0 g/dL) ranged from 30% to 46%. The dosage of vitamin B12 supplementation varied from 5 µg/day to 250 µg/day, with administration beginning at 8 to 28 weeks' gestation through to delivery or three months' postpartum, and the duration of supplementation ranged from 8 to 16 weeks to 32 to 38 weeks. Three trials, involving 609 pregnant women, contributed data for meta-analyses of the effects of vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation. Maternal anaemia: there may be little to no difference for maternal anaemia by intervention group, but the evidence is very uncertain (70.9% versus 65.0%; risk ratio (RR) 1.08, 95% confidence interval (CI) 0.93 to 1.26; 2 trials, 284 women; very low-certainty evidence). Maternal vitamin B12 status: vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain (25.9% versus 67.9%; RR 0.38, 95% CI 0.28 to 0.51; 2 trials, 272 women; very low-certainty evidence). Women who received vitamin B12 supplements during pregnancy may have higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (mean difference (MD) 60.89 pmol/L, 95% CI 40.86 to 80.92; 3 trials, 412 women). However, there was substantial heterogeneity (I2 = 85%). Adverse pregnancy outcomes: the evidence is uncertain about the effect on adverse pregnancy outcomes, including preterm birth (RR 0.97, 95% CI 0.55 to 1.74; 2 trials, 340 women; low-certainty evidence), and low birthweight (RR 1.50, 95% CI 0.93 to 2.43; 2 trials, 344 women; low-certainty evidence). Two trials reported data on spontaneous abortion (or miscarriage); however, the trials did not report quantitative data for meta-analysis and there was no clear definition of spontaneous abortion in the study reports. No trials evaluated the effects of vitamin B12 supplementation during pregnancy on neural tube defects. Infant vitamin B12 status: children born to women who received vitamin B12 supplementation had higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (MD 71.89 pmol/L, 95% CI 20.23 to 123.54; 2 trials, 144 children). Child cognitive outcomes: three ancillary analyses of one trial reported child cognitive outcomes; however, data were not reported in a format that could be included in quantitative meta-analyses. In one study, maternal vitamin B12 supplementation did not improve neurodevelopment status (e.g. cognitive, language (receptive and expressive), motor (fine and gross), social-emotional, or adaptive (conceptual, social, practical) domains) in children compared to placebo (9 months, Bayley Scales of Infant and Toddler Development Third Edition (BSID-III); 1 trial; low-certainty evidence) or neurophysiological outcomes (72 months, event-related potential measures; 1 trial; low-certainty evidence), though children born to women who received vitamin B12 supplementation had improved expressive language domain compared to placebo (30 months, BSID-III; 1 trial; low-certainty evidence). AUTHORS' CONCLUSIONS: Oral vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency and may improve maternal vitamin B12 concentrations during pregnancy or postpartum compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain. The effects of vitamin B12 supplementation on other primary outcomes assessed in this review were not reported, or were not reported in a format for inclusion in quantitative analyses. Vitamin B12 supplementation during pregnancy may improve maternal and infant vitamin B12 status, but the potential impact on longer-term clinical and functional maternal and child health outcomes has not yet been established.

A Randomized Trial of Quadruple-Fortified Salt for Anemia and Birth Defects Prevention in Southern India: Protocol Design and Methods.

Background: Women of reproductive age are at an increased risk of anemia and micronutrient deficiencies. Evidence supports the role of periconceptional nutrition in the development of neural tube defects (NTDs) and other pregnancy complications. Vitamin B12 deficiency is a risk factor for NTDs and may modify folate biomarkers that predict NTD risk at the population level. There is an interest in mandatory fortification with vitamin B12 and folic acid for anemia and birth defect prevention. However, there are limited population-representative data needed to inform policy and guidelines. Objectives: This randomized trial will be conducted to evaluate the efficacy of quadruple-fortified salt (QFS; iron, iodine, folic acid, vitamin B12) in 1,000 households in Southern India. Methods: Women 18 to 49 y who are not pregnant or lactating and reside within the catchment area of our community-based research site in Southern India will be screened and invited to participate in the trial. After informed consent, women and their households will be randomized to receive one of the following 4 interventions: 1) double-fortified salt (DFS; iron, iodine), 2) DFS + folic acid (iron, iodine, folic acid), 3) DFS + vitamin B12 (iron, iodine, vitamin B12), or 4) DFS + folic acid and vitamin B12 (QFS; iron, iodine, folic acid, vitamin B12) for 12 mo. Structured interviews will be conducted by trained nurse enumerators to collect sociodemographic, anthropometric, dietary, health, and reproductive history data. Biological samples will be collected at baseline, midpoint, and endpoint. Whole blood will be analyzed for hemoglobin using Coulter Counter. Total vitamin B12 will be measured by chemiluminescence; red blood cell folate and serum folate will be evaluated using the World Health Organization-recommended microbiologic assay. Conclusions: The results of this randomized trial will help to evaluate the efficacy of QFS to prevent anemia and micronutrient deficiencies. Clinical trial registration numbers: NCT03853304 and Clinical Trial Registry of India REF/2019/03/024479. Registration number: NCT03853304 and REF/2019/03/024479.

Strengthening Research that Answers Nutrition Questions of Public Health Importance: Leveraging the Experience of the USDA Nutrition Evidence Systematic Review Team.

The Nutrition Evidence Systematic Review (NESR) team conducts nutrition- and public health-related systematic reviews and is within the USDA's Center for Nutrition Policy and Promotion. NESR has collaborated with scientific experts to conduct systematic reviews on nutrition and public health topics for more than a decade and is uniquely positioned to share recommendations with the research community to strengthen research quality and impact, especially the evidence base that supports public health nutrition guidance, including future editions of the Dietary Guidelines for Americans. Leveraging the expertise of NESR and its systematic review process resulted in the following recommendations for the research community: a) use the strongest study design feasible with sufficient sample size(s); b) enroll study participants who reflect the diversity of the population of interest and report participant characteristics; c) use valid and reliable dietary assessment methods; d) describe the interventions or exposures of interest and use standard definitions to promote consistency; e) use valid and reliable health outcome measures; f) account for variables that may impact the relationship between nutrition-related interventions or exposures and health outcomes; g) carry out studies for a sufficient duration and include repeated measures, as appropriate; and h) report all relevant information to inform accurate interpretation and evaluation of study results. Implementing these recommendations can strengthen nutrition and public health evidence and increase its utility in future public health nutrition systematic reviews. However, implementation will require additional support from the entire research community, including scientific journals and funding agencies.

A randomized trial of iron- and zinc-biofortified pearl millet-based complementary feeding in children aged 12 to 18 months living in urban slums.

BACKGROUND & AIMS: Biofortification of staple crops with higher levels of micronutrients via traditional breeding methods is a sustainable strategy and can possibly complement fortification and other interventions to target micronutrient deficiencies in low resource settings, particularly among vulnerable populations such as children. We aimed to determine if iron- and zinc-biofortified pearl millet (FeZnPM, Dhanashakti, ICTP-8203Fe)-based complementary feeding improves nutritional status, including iron biomarkers and growth, in children living in urban slums of Mumbai. METHODS: We conducted a randomized controlled trial of FeZnPM among 223 children aged 12-18 months who were not severely anemic at baseline (hemoglobin ≥9.0 g/dL). Children were randomized to receive either FeZnPM or conventional non-biofortified pearl millet (CPM) daily for 9 months. Iron status (hemoglobin, serum ferritin), plasma zinc, and anthropometric indicators (length, weight, mid-upper arm circumference, triceps and subscapular skinfolds) were evaluated at enrollment and throughout the trial. World Health Organization (WHO) anthropometric z-scores were calculated using WHO growth standards. Primary outcomes were hemoglobin and serum ferritin concentrations, and growth, defined as WHO z-scores. An intent to treat approach was used for analyses. We used the Hodges-Lehmann-Sen test to assess the change in primary outcomes between baseline and the last visit and report corresponding 95% confidence intervals. RESULTS: At baseline, 67.7% of children were anemic (hemoglobin <11.0 g/dL) and 59.6% were iron deficient (serum ferritin <12.0 µg/L). FeZnPM did not significantly increase iron biomarkers or improve growth, compared to CPM. In subgroup analyses, FeZnPM improved hemoglobin concentrations in male children, and in children with iron deficiency or iron depletion (serum ferritin <25.0 µg/L) at baseline, relative to CPM. CONCLUSIONS: Daily consumption of FeZnPM-based complementary foods did not significantly impact iron and zinc status or growth in children living in Mumbai's urban slums. However, the intervention significantly improved hemoglobin concentrations among male children and among individuals who were iron-deficient or iron-depleted at baseline. TRIAL REGISTRATION: This trial is registered with Clinicaltrials.gov (ID: NCT02233764), and Clinical Trials Registry of India (ID: REF/2014/10/007731).

Omega-3 Fatty Acid Dietary Supplements Consumed During Pregnancy and Lactation and Child Neurodevelopment: A Systematic Review.

BACKGROUND: Maternal nutrition during pregnancy and lactation has profound effects on the development and lifelong health of the child. Long-chain PUFAs are particularly important for myelination and the development of vision during the perinatal period. OBJECTIVES: We conducted a systematic review to examine the relationship between supplementation with omega-3 fatty acids during pregnancy and/or lactation and neurodevelopment in children, to inform the Scientific Report of the 2020 Dietary Guidelines Advisory Committee. METHODS: We identified articles on omega-3 fatty acid supplementation in pregnant and lactating women that included measures of neurodevelopment in their children (0-18 y) by searching PubMed, CENTRAL, Embase, and CINAHL Plus. After dual screening articles for inclusion, we qualitatively synthesized and graded the strength of evidence using pre-established criteria for assessing risk of bias, consistency, directness, precision, and generalizability. RESULTS: We included 33 articles from 15 randomized controlled trials (RCTs) and 1 prospective cohort study. Of the 8 RCTs that delivered omega-3 fatty acid dietary supplements during pregnancy alone (200-2200 mg/d DHA and 0-1100 mg/d EPA for approximately 20 wk), 5 studies reported ≥1 finding that supplementation improved measures of cognitive development in the infant or child by 6%-11% (P < 0.05), but all 8 studies also reported ≥1 nonsignificant (P > 0.05) result. There was inconsistent or insufficient evidence for other outcomes (language, social-emotional, physical, motor, or visual development; academic performance; risks of attention deficit disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, anxiety, or depression) and for supplementation during lactation or both pregnancy and lactation. Populations with a lower socioeconomic status and adolescents were underrepresented and studies lacked racial and ethnic diversity. CONCLUSIONS: Limited evidence suggests that omega-3 fatty acid supplementation during pregnancy may result in favorable cognitive development in the child. There was insufficient evidence to evaluate the effects of omega-3 fatty acid supplementation during pregnancy and/or lactation on other developmental outcomes.

Evaluation of Dietary Patterns and All-Cause Mortality: A Systematic Review.

Importance: The 2020 Dietary Guidelines Advisory Committee conducted a systematic review of existing research on diet and health to inform the current Dietary Guidelines for Americans. The committee answered this public health question: what is the association between dietary patterns consumed and all-cause mortality (ACM)? Objective: To ascertain the association between dietary patterns consumed and ACM. Evidence Review: Guided by an analytical framework and predefined inclusion and exclusion criteria developed by the committee, the US Department of Agriculture's Nutrition Evidence Systematic Review (NESR) team searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase and dual-screened the results to identify articles that were published between January 1, 2000, and October 4, 2019. These studies evaluated dietary patterns and ACM in participants aged 2 years and older. The NESR team extracted data from and assessed risk of bias in included studies. Committee members synthesized the evidence, developed conclusion statements, and graded the strength of the evidence supporting the conclusion statements. Findings: A total of 1 randomized clinical trial and 152 observational studies were included in the review. Studies enrolled adults and older adults (aged 17-84 years at baseline) from 28 countries with high or very high Human Development Index; 53 studies originated from the US. Most studies were well designed, used rigorous methods, and had low or moderate risks of bias. Precision, directness, and generalizability were demonstrated across the body of evidence. Results across studies were highly consistent. Evidence suggested that dietary patterns in adults and older adults that involved higher consumption of vegetables, fruits, legumes, nuts, whole grains, unsaturated vegetable oils, fish, and lean meat or poultry (when meat was included) were associated with a decreased risk of ACM. These healthy patterns were also relatively low in red and processed meat, high-fat dairy, and refined carbohydrates or sweets. Some of these dietary patterns also included intake of alcoholic beverages in moderation. Results based on additional analyses with confounding factors generally confirmed the robustness of main findings. Conclusions and Relevance: In this systematic review, consuming a nutrient-dense dietary pattern was associated with reduced risk of death from all causes.

Breastfeeding and risk of overweight in childhood and beyond: a systematic review with emphasis on sibling-pair and intervention studies.

BACKGROUND: Breastfeeding is associated with a lower risk of subsequent overweight or obesity, but it is uncertain whether this is a causal relation because most studies have not adequately reduced risk of bias due to confounding. OBJECTIVES: The aim of this review was to examine whether 1) ever compared with never consuming human milk and 2) different durations of human milk consumption among infants fed human milk are related to later risk of overweight or obesity, with emphasis on sibling-pair and intervention studies. METHODS: The 2020 Dietary Guidelines Advisory Committee, together with the Nutrition Evidence Systematic Review team, conducted a systematic review of articles relevant to healthy full-term infants in countries with a high or very high level of human development. We searched PubMed, Embase, Cochrane, and CINAHL; dual-screened the results using predetermined criteria; extracted data from and assessed the risk of bias for each included study; qualitatively synthesized the evidence; developed conclusion statements; and graded the strength of the evidence. RESULTS: The review included 42 articles, including 6 cohorts with sibling-pair analyses and 1 randomized controlled trial of a breastfeeding promotion intervention. Moderate evidence suggested that ever, compared with never, consuming human milk is associated with a lower risk of overweight and obesity at ages 2 y and older, particularly if the duration of human milk consumption is >6 mo. However, residual confounding cannot be ruled out. Evidence was insufficient to determine the relation between the duration of any human milk consumption, among infants fed human milk, and overweight and/or obesity at age 2 y and older. CONCLUSIONS: Further research, using strong study designs, is needed to disentangle the complex relation between infant feeding practices and the risk of subsequent overweight or obesity, as well as the biological and behavioral mechanisms if the relation is causal.

Iron status is associated with worker productivity, independent of physical effort in Indian tea estate workers.

Iron deficiency is the most common nutrient deficiency in the world, affecting roughly 40% of women in nonindustrialized countries. Iron is the essential element in hemoglobin, the major carrier of blood oxygen and oxidative metabolism that supports physical and cognitive performance. The relationship between iron and physical work capacity suggests that iron deficient individuals could experience reduced work output. Participants were 138 experienced tea pluckers aged 18-55 years from the Panighatta Tea Estate in Darjeeling District of northern West Bengal, India. Hemoglobin, serum ferritin, and soluble transferrin receptor were measured from venous blood. Energy expenditure was estimated from accelerometry and heart rate, and plucking productivity was measured as amount of tea plucked during the morning work session when temperature and rainfall conditions are optimal. At a given level of energy expenditure, iron deficient, anemic, and iron deficient anemic women plucked less tea during a 3-h period. The results warrant further research as to whether interventions providing supplemental iron might improve worker productivity and work efficiency. Further study should examine evidence of economic incentives for policies and programs targeting nutritional deficiencies. Novelty Anemia predicts up to 2.02 kg (9.1%) less tea plucked per 3 h, or 4.0% lower wage per 3 h, compared with nonanemic women, controlling for physical effort. An increase of 1.0 g/L in hemoglobin concentration predicts 0.71 kg (3.3%) more tea plucked over 3 h. An increase of 1.0 g/L in hemoglobin concentration predicts a 1.6% wage increase.

Predicting potential to benefit from an iron intervention: a randomized controlled trial of double-fortified salt in female Indian tea pluckers.

OBJECTIVE: The present study examines characteristics of those who benefited from a dietary Fe intervention comprised of salt double-fortified with iodine and Fe (DFS). DESIGN: Data from a randomized controlled trial were analysed to identify predictors of improved Fe status and resolution of Fe deficiency (serum ferritin (sFt) < 12 µg/l) and low body Fe (body Fe (BI) < 0·0 mg/kg) using non-parametric estimations and binomial regression models. SETTING: A tea estate in West Bengal, India. PARTICIPANTS: Female tea pluckers, aged 18-55 years. RESULTS: Consuming DFS significantly (P = 0·01) predicted resolution of Fe deficiency (relative risk (RR) = 2·31) and of low BI (RR = 2·78) compared with consuming iodized salt. Baseline sFt (ß = -0·32 (se 0·03), P < 0·001) and treatment group (ß = 0·13 (se 0·03), P < 0·001) significantly predicted change in sFt. The interaction of baseline BI with treatment group (ß = -0·11 (se 0·06), P = 0·08) predicted the change in BI. DFS did not significantly predict change in Hb and marginally predicted resolution of anaemia (Hb < 120 g/l). CONCLUSIONS: Baseline Fe status, as assessed by sFt and BI, and consumption of DFS predict change in Fe status and resolution of Fe deficiency and low BI. Anaemia prevalence and Hb level, although simple and inexpensive to measure, may not be adequate to predict resolution of Fe deficiency in response to an intervention of DFS in similar populations with high prevalence of Fe deficiency and multiple nutritional causes of anaemia. These findings will guide appropriate targeting of future interventions.

Prevalence and Correlates of Undernutrition in Young Children Living in Urban Slums of Mumbai, India: A Cross Sectional Study.

Background: Young children living in urban slums are vulnerable to malnutrition and subsequently poor health outcomes, but data on the correlates of stunting, underweight, wasting, and anemia specifically among 10-18 month-old children in India remain limited. Objective: In this analysis, we sought to describe the prevalence of and examine correlates for different markers of undernutrition, including stunting, underweight, and anemia among 10-18 month-old children living in urban slums, an understudied vulnerable group. Methods: Children and their mothers (n = 323) were screened for anthropometry, demographics, and complete blood counts for hemoglobin concentration between March and November 2017 (Clinicaltrials.gov ID: NCT02233764). Correlates included child and mother's age, sex, birth order, birth weight, illness episodes, hemoglobin concentration, family income, maternal height, and maternal education level. Risk ratios (RR, 95% CI) for binary outcomes (stunting, underweight, wasting and anemia) and mean differences (ß, 95% CI) for continuous outcomes (anthropometric Z-scores, hemoglobin concentration) were calculated using multivariate binomial and linear regression (SAS 9.4). Results: The prevalence of stunting was 31.2%, underweight 25.1%, wasting (9.0%), and anemia (76%) among all children. Male children had a higher prevalence of poor growth indices and lower anthropometric Z-scores than females. Male sex, low birthweight, shorter maternal height, report of ≥1 episodes of illness within the past month, older maternal age, and birth order ≥2 were also associated with poor growth and anemia in multivariate models. Correlates of undernutrition were different among females and males. Female children had a 40% (20, 60%) higher risk of anemia associated with diarrhea, and male children who were firstborn had a 20% (0, 70%) lower risk of anemia. Conclusions: These results show that poor growth and anemia among young children is prevalent in urban slums of Mumbai, and that sex of the child may play an important role in informing interventions to address undernutrition.

Corrigendum: Acceptability of Iron- and Zinc-Biofortified Pearl Millet (ICTP-8203)-Based Complementary Foods among Children in an Urban Slum of Mumbai, India.

[This corrects the article DOI: 10.3389/fnut.2017.00039.].

Effect of iron and zinc-biofortified pearl millet consumption on growth and immune competence in children aged 12-18 months in India: study protocol for a randomised controlled trial.

INTRODUCTION: Biofortified crops represent a sustainable agricultural solution for the widespread micronutrient malnutrition in India and other resource-limited settings. This study aims to investigate the effect of the consumption of foods prepared with iron- and zinc-biofortified pearl millet (FeZn-PM) by children on biomarkers of iron and zinc status, growth, and immune function. METHODS AND ANALYSIS: We will conduct a randomised controlled feeding trial in identified slums of Mumbai, India among 200 children aged between 12 and 18 months. Children will be randomised to receive foods prepared with the biofortified PM (FeZn-PM, ICTP8203-Fe) or non-biofortified PM. Anthropometric and morbidity data will be gathered every month for 9 months. Biological samples will be collected at baseline, midline and endline to assess iron and zinc status, including haemoglobin, serum ferritin, serum transferrin receptor, serum zinc, C-reactive protein and alpha-1 acid glycoprotein. Biological samples will be archived for future analyses. The midline measurement will be a random serial sample between baseline and endline. Immune function will be assessed at each time point by the measurement of T cell counts and vaccine responses in a subset, respectively. ETHICS AND DISSEMINATION: This study has obtained clearance from the Health Ministry Screening Committee of the Indian Council of Medical Research. Ethical clearance has been obtained from Cornell University's Institutional Review Board, the Inter System Biomedica Ethics Committee and St John's Research Institute's Institutional Ethics Review Board. The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Clinical trial registration number NCT02233764. CTRI registration number REF/2014/10/007731.

Acceptability of Iron- and Zinc-Biofortified Pearl Millet (Dhanashakti)-Based [corrected] Complementary Foods among Children in an Urban Slum of Mumbai, India.

Biofortification, a method for increasing micronutrient content of staple crops, is a promising strategy for combating major global health problems, such as iron and zinc deficiency. We examined the acceptability of recipes prepared using iron- and zinc-biofortified pearl millet (FeZnPM) (~80 ppm Fe, ~34 ppm Zn, varietal Dhanashakti), [corrected] compared to conventional pearl millet (CPM) (~20 ppm Fe, ~19 ppm Zn) in preparation for an efficacy trial. Our objective was to examine the acceptability of FeZnPM compared to CPM among young children and mothers living in the urban slums of Mumbai. Standardized traditional feeding program recipes (n = 18) were prepared with either FeZnPM or CPM flour. The weight (g) of each food product was measured before and after consumption by children (n = 125) and the average grams consumed over a 3-day period were recorded. Mothers (n = 60) rated recipes using a 9-point hedonic scale. Mean intakes and hedonic scores of each food product were compared using t-tests across the two types of pearl millet. There were no statistically significant differences in consumption by children (FeZnPM: 25.27 ± 13.0 g; CPM: 21.72 ± 6.90 g) across the food products (P = 0.28). Overall mean hedonic scores for all recipes were between 7 to 9 points. CPM products were rated higher overall (8.22 ± 0.28) compared to FeZnPM products (7.95 ± 0.35) (P = 0.01). FeZnPM and CPM were similarly consumed and had high hedonic scores, demonstrating high acceptability in this population. These results support using these varieties of pearl millet in a proposed trial [http://Clinicaltrials.gov ID: NCT02233764; Clinical Trials Registry of India (CTRI), reference number REF/2014/10/007731, CTRI number CTRI/2015/11/006376] testing the efficacy of FeZnPM for improving iron status and growth.

Consumption of a Double-Fortified Salt Affects Perceptual, Attentional, and Mnemonic Functioning in Women in a Randomized Controlled Trial in India.

Background: Iron deficiency and iron deficiency anemia have been shown to have negative effects on aspects of perception, attention, and memory.Objective: The purpose of this investigation was to assess the extent to which increases in dietary iron consumption are related to improvements in behavioral measures of perceptual, attentional, and mnemonic function.Methods: Women were selected from a randomized, double-blind, controlled food-fortification trial involving ad libitum consumption of either a double-fortified salt (DFS) containing 47 mg potassium iodate/kg and 3.3 mg microencapsulated ferrous fumarate/g (1.1 mg elemental Fe/g) or a control iodized salt. Participants' blood iron status (primary outcomes) and cognitive functioning (secondary outcomes) were assessed at baseline and after 10 mo at endline. The study was performed on a tea plantation in the Darjeeling district of India. Participants (n = 126; 66% iron deficient and 49% anemic at baseline) were otherwise healthy women of reproductive age, 18-55 y.Results: Significant improvements were documented for iron status and for perceptual, attentional, and mnemonic function in the DFS group (percentage of variance accounted for: 16.5%) compared with the control group. In addition, the amount of change in perceptual and cognitive performance was significantly (P < 0.05) related to the amount of change in blood iron markers (mean percentage of variance accounted for: 16.0%) and baseline concentrations of blood iron markers (mean percentage of variance accounted for: 25.0%). Overall, there was evidence that the strongest effects of change in iron status were obtained for perceptual and low-level attentional function.Conclusion: DFS produced measurable and significant improvements in the perceptual, attentional, and mnemonic performance of Indian female tea pickers of reproductive age. This trial was registered at clinicaltrials.gov as NCT01032005.

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.

Vitamin B-12 and Cognition in Children.

Vitamin B-12 is essential for brain development, neural myelination, and cognitive function. Inadequate vitamin B-12 status during pregnancy and early childhood has been associated with adverse child health outcomes, including impaired cognitive development. However, the underlying mechanisms have not been elucidated. This review was conducted to examine the evidence that links vitamin B-12 and cognition in children. The search strategy resulted in 17 studies: 3 cross-sectional, 1 case-control, and 12 cohort studies, and 1 randomized trial. Cognitive processes assessed included attention, memory, and perception. Developmental outcomes, academic performance, and intelligence quotient were also considered. Despite the high prevalence of vitamin B-12 insufficiency and associated risk of adverse cognitive outcomes in children, to our knowledge, no studies to date have been conducted to examine the effects of vitamin B-12 supplementation on cognition in children. The role of vitamin B-12 in the etiology of child cognitive outcomes needs to be elucidated to inform public health interventions.

Double-fortified salt is efficacious in improving indicators of iron deficiency in female Indian tea pickers.

Poor iron status affects 50% of Indian women and compromises work productivity, cognitive performance, and reproduction. Among the many strategies to reduce iron deficiency is the commercial fortification of iodized table salt with iron to produce a double-fortified salt (DFS). The objective of this study was to test the efficacy of DFS in reducing iron deficiency in rural women of reproductive age from northern West Bengal, India. The participants were 212 women between 18 and 55 y of age who worked as full-time tea pickers on a large tea estate. Participants in the randomized, controlled, double-blind study were assigned to use either DFS or a control iodized salt for 7.5 to 9 mo. The DFS was fortified with 3.3-mg ferrous fumarate (1.1-mg elemental iron) per kg of iodized salt, whereas the control salt contained only iodine (47 mg/kg potassium iodate), and both salt varieties were distributed gratis to the families of participants at 0.5 kg/mo for each 2 household members. At baseline, 53% of participants were anemic (hemoglobin <120 g/L), 25% were iron deficient (serum ferritin <12 µg/L), and 23% were iron-deficient anemic. Also, 22% had a transferrin receptor concentration >8.6 mg/L and 22% had negative (<0.0 mg/kg) body iron stores. After 9 mo the participants receiving DFS showed significant improvements compared with controls in hemoglobin (+2.4 g/L), ferritin (+0.13 log10 µg/L), soluble transferrin receptor (-0.59 mg/L), and body iron (+1.43 mg/kg), with change in status analyzed by general linear models controlling for baseline values. This study demonstrated that DFS is an efficacious approach to improving iron status and should be further evaluated for effectiveness in the general population. This trial was registered at clinicaltrials.gov as NCT01032005.

Milk enriched with conjugated linoleic acid fails to alter blood lipids or body composition in moderately overweight, borderline hyperlipidemic individuals.

BACKGROUND: Dietary conjugated linoleic acid (CLA) represents a group of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid. The effects of dietary CLA on blood lipids and body composition in humans remain controversial. OBJECTIVE: To examine whether consumption of milk enriched naturally or synthetically with cis 9, trans 11 (c-9, t-11) and trans 10, cis 12 (t-10, c-12) CLA isomers alters blood lipid indices, including concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triacyglycerol; indices of liver function including plasma alanine transaminase and total bilirubin; C-reactive protein; tumor necrosis factor-alpha; and body weight and composition in moderately overweight, borderline hyperlipidemic humans. DESIGN: A randomized, 3-phase, crossover, single-blind clinical trial was carried out in moderately overweight, borderline hyperlipidemic individuals who consumed (1) milk naturally enriched in CLA (4.2%) containing c-9, t-11 only providing 1.3 g/d of CLA; (2) milk enriched with a 4.2% synthetic mixture of t-10, c-12 and c-9, t-11 CLA isomers providing 1.3 g/d of CLA; or (3) untreated milk as a control providing 0.2 g/d CLA. Dietary phases were each 8 weeks in duration and were separated by 4-week washout periods. Plasma lipid levels were measured in blood samples collected at the beginning and end of each dietary phase. Magnetic resonance imaging was carried out at the beginning and end of each dietary phase to assess any changes in regional body fat composition. RESULTS: Compared with the control intervention, consumption of the two CLA-enriched milks failed to alter plasma total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triacyglycerol concentrations; body weight; or fat composition. CLA consumption did not significantly affect plasma alanine transaminase, total bilirubin, C-reactive protein, or tumor necrosis factor-alpha concentrations. CONCLUSION: Results from this study fail to support the role of milk enriched naturally with CLA containing c-9, t-11 or synthetically with c-9, t-11 and t-10, c-12 CLA isomers in modulation of lipid profiles or body composition in moderately overweight, borderline hyperlipidemic individuals.

The effect of drinking milk containing conjugated linoleic acid on fecal microbiological profile, enzymatic activity, and fecal characteristics in humans.

BACKGROUND: The primary objective was to determine whether consumption of conjugated linoleic acids (CLAs) affected the fecal microbiota composition, fecal enzyme activity or fecal composition. METHODS: Human subjects consumed (1 L/day) cows' milk (4% fat) containing (5 mg/g fat) cis-9, trans-11 CLA (CONT), (32 mg/g fat) cis-9, trans-11 CLA (NAT) and (32 mg/g fat) trans-10, cis-12 CLA and cis-9, trans-11 CLA (SYN) for 8 weeks, in addition to their normal diet. Milk feeding periods were separated by 4 week washout periods. Fecal samples were obtained at the beginning (day 0) and the end (day 56) of each milk feeding period. Fecal samples were analysed for microbiological profile, enzyme activity, pH and short chain fatty acid content. RESULTS: Samples taken at day 0 and day 56 indicated that the numbers of lactobacilli and bifidobacteria significantly decreased after consumption of all experimental milks; total aerobes, total anaerobes, enterobacteria, and enterococci + streptococci did not change. At day 56, the activities of beta-glucosidase, nitroreductase, and urease enzymes had decreased compared to samples taken on day 0 for all treatments. beta-glucuronidase activity did not change. Fecal pH and ammonia content did not change. CONCLUSION: It was concluded that observed changes could have been attributed to increased milk intake; no differences could be attributed to consumption of the different CLAs.