Female rats consuming an iron and omega-3 fatty acid deficient diet preconception require combined iron and omega-3 fatty acid supplementation for the prevention of bone impairments in offspring.

We previously showed in rats that pre- and postnatal deficiencies in iron and omega-3 (n-3) fatty acids can impair bone development, with additive and potentially irreversible effects when combined. This study aimed to investigate, in female rats consuming a combined iron and n-3 fatty acid deficient (ID + n-3 FAD) diet preconception, whether supplementation with iron and docosahexaenoic/eicosapentaenoic acid (DHA/EPA), alone and in combination, can prevent bone impairments in offspring. Using a 2 × 2 factorial design, female Wistar rats consuming an ID + n-3 FAD diet preconception were randomised to receive an: 1) iron supplemented (Fe + n-3 FAD), 2) DHA/EPA supplemented (ID + DHA/EPA), 3) Fe + DHA/EPA, or 4) ID + n-3 FAD diet from gestational day 10 throughout pregnancy and lactation. Post-weaning, offspring (n = 24/group; male:female = 1:1) remained on the respective experimental diets for three weeks until postnatal day 42-45. Offspring born to female rats consuming a control diet preconception and an Fe+DHA/EPA diet throughout pregnancy and lactation served as non-deficient reference group (Control+Fe+DHA/EPA). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry and bone strength using three-point bending tests. Only offspring in the Fe+DHA/EPA group had significantly higher spine and femur BMD, and higher femur stiffness than offspring in the ID + n-3 FAD group, and had similar spine BMD and femur stiffness as the Control + Fe + DHA/EPA group. Offspring in the Fe + DHA/EPA group further had significantly higher femur strength (ultimate load) than the other experimental groups, and a similar femur strength as the Control + Fe + DHA/EPA group. This study shows that only combined iron and DHA/EPA supplementation can prevent bone impairments in offspring of female rats consuming an iron and n-3 FA deficient diet preconception.

Iron and n-3 fatty acid depletion, alone and in combination, during early development provoke neurochemical changes, anhedonia, anxiety and social dysfunction in rats.

Objectives: Both iron and omega-3 (n-3) fatty acids (FA) play important roles in the development and functioning of the brain. We investigated the effects of n-3 FA and iron deficiencies, alone and in combination, during early development on behaviour and brain monoamines in rats. Methods: Using a 2-factorial design, female Wistar rats were randomly allocated to one of four diet groups: Control, n-3 FA deficient (n-3 FAD), iron deficient (ID), or n-3 FAD + ID. Females received these diets throughout mating, pregnancy and lactation. Offspring (n = 24/group; male:female = 1:1) continued on the same diet until post-natal day 42-45, and underwent a sucrose preference test (SPT), novel object recognition test, elevated plus maze (EPM) and social interaction test (SIT). Results: ID offspring consumed less sucrose in the SPT and spent more time in closed arms and less time in open arms of the EPM than non-ID offspring. In female offspring only, ID and n-3 FAD reduced time approaching and together in the SIT, with an additive effect of ID and n-3 FAD for even less time approaching and spent together in the n-3 FAD + ID group compared to controls. ID offspring had higher striatal dopamine and norepinephrine and lower frontal cortex dopamine concentrations. N-3 FAD and ID affected frontal cortex serotonin concentrations in a sex-specific manner. Conclusions: Our results suggest that ID and n-3 FAD during early development provoke anhedonia, anxiety and social dysfunction in rats, with potential additive and attenuating effects when combined. These effects may in part be attributed to disturbances in brain neurochemistry and may be sex-specific.

A Cross-Sectional Study of the Associations between Biomarkers of Vitamin D, Iron Status, and Hemoglobin in South African Women of Reproductive Age: the Healthy Life Trajectories Initiative, South Africa.

Background: Vitamin D deficiency and anemia impact the health of women of reproductive age. Evidence suggests an inverse relationship between serum vitamin D (25-hydroxyvitamin D [25(OH)D]) and anemia/iron deficiency, but less is known about these associations in women of reproductive age, in particular in a setting with a combined burden of micronutrient deficiency, food insecurity, and obesity. Objective: We aimed to assess the associations between 25(OH)D and biomarkers of iron and anemia in a cohort of women of reproductive age from Soweto, South Africa. The prevalence of vitamin D deficiency was also assessed. Methods: In this cross-sectional substudy of the Healthy Life Trajectories Initiative (HeLTI) South Africa pilot trial, 25(OH)D, iron markers (ferritin and soluble transferrin receptor [sTFR]), and altitude-adjusted hemoglobin (Hb) were measured in 493 women aged 18 to 25 years. Associations between iron deficiency/anemia and vitamin D status were evaluated using multivariable logistic regression, adjusting for confounders including fat mass index (FMI). Structural equation modeling (SEM) was performed to evaluate direct and indirect pathways between 25(OH)D, iron and anemia markers, and covariates. Results: Of 493 participants, 136 (27.6%) had vitamin D insufficiency (25(OH)D ≥12-20 ng/mL), whereas 28 (5.6%) had vitamin D deficiency (<12 ng/mL). Anemia and iron deficiency were not significantly associated with vitamin D category (25(OH)D<20 ng/mL compared with ≥20 ng/mL) in multivariable logistic regression analyses. In SEM, log-transformed 25(OH)D was not significantly associated with Hb, ferritin, or sTFR, but it was significantly associated with season of data collection, hormonal contraceptive use, and FMI (total effects: B = 0.17, 95% CI: 0.104, 0.236, P < 0.001; B: 0.10, 95% CI: 0.041, 0.154, P < 0.001; B: -0.01, 95%CI: -0.016, -0.003, P = 0.003, respectively). Conclusion: No significant association between vitamin D (25(OH)D), anemia (Hb), and iron markers was found. The inverse relationship between FMI and vitamin D status emphasizes the overlap between adiposity and micronutrient deficiencies in young South African women, exacerbating their risk of disease development.

Longer-Term Omega-3 LCPUFA More Effective Adjunct Therapy for Tuberculosis Than Ibuprofen in a C3HeB/FeJ Tuberculosis Mouse Model.

Advancement in the understanding of inflammation regulation during tuberculosis (TB) treatment has led to novel therapeutic approaches being proposed. The use of immune mediators like anti-inflammatory and pro-resolving molecules for such, merits attention. Drug repurposing is a widely used strategy that seeks to identify new targets to treat or manage diseases. The widely explored nonsteroidal anti-inflammatory drug (NSAID) ibuprofen and a more recently explored pharmaconutrition therapy using omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs), have the potential to modulate the immune system and are thus considered potential repurposed drugs in this context. These approaches may be beneficial as supportive therapy to the already existing treatment regimen to improve clinical outcomes. Here, we applied adjunct ibuprofen and n-3 LCPUFA therapy, respectively, with standard anti-TB treatment, in a C3HeB/FeJ murine model of TB. Bacterial loads, lung pathology, lung cytokines/chemokines and lung lipid mediators were measured as outcomes. Lung bacterial load on day 14 post-treatment (PT) was lower in the n-3 LCPUFA, compared to the ibuprofen group (p = 0.039), but was higher in the ibuprofen group than the treated control group (p = 0.0315). Treated control and ibuprofen groups had more free alveolar space initially as compared to the n-3 LCPUFA group (4 days PT, p= 0.0114 and p= 0.002, respectively); however, significantly more alveolar space was present in the n-3 LCPUFA group as compared to the ibuprofen group by end of treatment (14 days PT, p = 0.035). Interleukin 6 (IL-6) was lower in the ibuprofen group as compared to the treated control, EPA/DHA and untreated control groups at 4 days PT (p = 0.019, p = 0.019 and p = 0.002, respectively). Importantly, pro-resolving EPA derived 9-HEPE, 11-HEPE, 12-HEPE and 18-HEPE lipid mediators (LMs) were significantly higher in the EPA/DHA group as compared to the ibuprofen and treated control groups. This suggests that n-3 LCPUFAs do improve pro-resolving and anti-inflammatory properties in TB, and it may be safe and effective to co-administer as adjunct therapy with standard TB treatment, particularly longer-term. Also, our results show host benefits upon short-term co-administration of ibuprofen, but not throughout the entire TB treatment course.

Nutrient density, but not cost of diet, is associated with anemia and iron deficiency in school-age children in South Africa.

OBJECTIVES: This study aimed to investigate the relationship of nutrient density and diet cost with anemia and iron deficiency (ID) in children. METHODS: Dietary intake data of 5- to 12-y-old children (n = 578) from three independent studies in low-income communities were pooled. Nutrient densities were calculated using the Nutrient Rich Foods index and Nutrient Rich Diet index, with higher scores indicating more nutrient-dense foods and diets. Food prices and food intake data were used to calculate ratios of nutrient density to price for foods and diets. Descriptive and correlation analyses examined associations of nutrient density and diet cost with anemia and ID. RESULTS: Most children (>50%) consumed starchy staples (100%), vegetables that are not vitamin A rich (63.9%), and legumes (58.1%), with mean NRF9.3 scores ranging from 31.9 to 56.3. Cheese, eggs, organ meat, fish, dark-green leafy vegetables, and vitamin A-rich vegetables and fruits had mean NRF9.3 scores ranging from 112.6 to 184.7, but each was consumed by less than a third of the children. Children with anemia or ID had lower NRD9.3 scores than children without (P < 0.001 and P = 0.039, respectively). Diet cost did not differ according to anemia and iron status, but nutrient-density-to-price ratio was lower in children with anemia than without (P = 0.001). CONCLUSIONS: Careful selection of nutrient-dense foods as substitutes for foods with lower nutrient density could make it possible for children to consume a diet richer in specific nutrients and help prevent anemia and ID without affecting diet cost.

Effects and Reversibility of Pre- and Post-natal Iron and Omega-3 Fatty Acid Deficiency, Alone and in Combination, on Bone Development in Rats.

Both iron and omega-3 (n-3) polyunsaturated fatty acids may play an important role in bone development. The aim of this study was to investigate the effects of pre- and post-natal iron and n-3 fatty acid deficiency (FAD), alone and in combination, on bone development in rats, and to determine whether effects are reversible when a sufficient diet is provided post-weaning. Using a 2×2-factorial design, 56 female Wistar rats were allocated to one of four diets: (1) control, (2) iron deficient (ID), (3) n-3 FAD or (4) ID and n-3 FAD, and were maintained on the respective diets throughout gestation and lactation. At weaning (post-natal day [PND] 21), offspring (n = 24/group; male:female=1:1) were randomly allocated to either continue with their respective diets or to switch to the control diet until PND 42-45. Bone mineral density (BMD) and bone strength were determined using dual X-ray absorptiometry and three-point bending tests, respectively. Pre- and post-natal ID resulted in significantly lower BMD in the spine and bone strength in the left femur. Both ID and n-3 FAD resulted in lower BMD in the right femur, with an additive reduction in the combined ID and n-3 FAD group vs. controls. While negative effects of pre- and post-natal ID alone were reversed in offspring switched to a control diet post-weaning, lower BMD and bone strength persisted in offspring with combined ID and n-3 FAD during the prenatal and early post-natal period. Effects were not sex-specific. These results indicate that ID during early life may negatively influence bone development, with potential additive effects of n-3 FAD. While the effects of ID alone seem reversible, a combined ID and n-3 FAD may result in irreversible deficits in bone development.

Associations of dietary diversity with anaemia and iron status among 5- to 12-year-old schoolchildren in South Africa.

OBJECTIVE: To examine the associations of dietary diversity with anaemia and iron status among primary school-aged children in South Africa. DESIGN: An analysis was conducted with pooled individual data from the baseline surveys from three previously conducted independent intervention studies. Two different dietary diversity scores (DDS) were calculated based on data from 1-day (1-d) and 3-day (3-d) dietary recall periods, respectively. Logistic regression analysis was performed to examine the associations of dietary diversity with anaemia and iron status. SETTING: KwaZulu-Natal and North West provinces, South Africa. PARTICIPANTS: Children (n 578) 5- to 12-year-old. RESULTS: A DDS ≤ 4 was associated with higher odds of being anaemic (1-d P = 0·001; 3-d P = 0·006) and being iron deficient (ID) (3-d P < 0·001). For both recall periods, consumption of 'vegetables and fruits other than vitamin A-rich' and 'animal-source foods (ASF)' was associated with lower odds of being anaemic (both P = 0·002), and 'organ meats' with lower odds of being ID (1-d P = 0·045; 3-d P < 0·001). Consumption of 'meat, chicken and fish' was associated with lower odds of being anaemic (P = 0·045), and 'vegetables and fruits other than vitamin A-rich', 'legumes, nuts and seeds' and 'ASF' with lower odds of being ID for the 3-d recall period only (P = 0·038, P = 0·020 and P = 0·003, respectively). CONCLUSION: In order to improve anaemia and iron status among primary school-aged children, dietary diversification, with emphasis on consumption of vegetables, fruits and ASF (including organ meats), should be promoted.

Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in Mycobacterium tuberculosis-Infected Mice.

Progressive inflammation and anemia are common in tuberculosis (TB) and linked to poor clinical outcomes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have inflammation-resolving properties, whereas iron supplementation in TB may have limited efficacy and enhance bacterial growth. We investigated effects of iron and EPA/DHA supplementation, alone and in combination, on inflammation, anemia, iron status markers and clinical outcomes in Mycobacterium tuberculosis-infected C3HeB/FeJ mice. One week post-infection, mice received the AIN-93 diet without (control) or with supplemental iron (Fe), EPA/DHA, or Fe+EPA/DHA for 3 weeks. Mice supplemented with Fe or EPA/DHA had lower soluble transferrin receptor, ferritin and hepcidin than controls, but these effects were attenuated in Fe+EPA/DHA mice. EPA/DHA increased inflammation-resolving lipid mediators and lowered lung IL-1α, IFN-γ, plasma IL-1ß, and TNF-α. Fe lowered lung IL-1α, IL-1ß, plasma IL-1ß, TNF-α, and IL-6. However, the cytokine-lowering effects in the lungs were attenuated with Fe+EPA/DHA. Mice supplemented with EPA/DHA had lower lung bacterial loads than controls, but this effect was attenuated in Fe+EPA/DHA mice. Thus, individually, post-infection EPA/DHA and iron supplementation lowered systemic and lung inflammation and mitigated anemia of infection in TB, but not when combined. EPA/DHA also enhanced bactericidal effects and could support inflammation resolution and management of anemia.

Diet and sedentary behaviour in relation to cancer survival. A report from the national health and nutrition examination survey linked to the U.S. mortality registry.

BACKGROUND & AIMS: Cancer is the second most common chronic disease and cause of death in the United States. Our aim was to evaluate the associations of sedentary behavior and nutrient intakes with total and cancer-specific mortality among US cancer survivors. METHODS: Data from 2371 cancer survivors collected by the US National Health and Nutrition Examination Survey between 1999 and 2014 were linked to the US mortality registry. Multivariable adjusted Cox proportional hazard models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and cancer-specific mortality associated with sedentary time and nutrient intakes. The interaction between time spent on sedentary activities and nutrient intake was evaluated on additive and multiplicative scales. RESULTS: During a median observational period of 5.7 years, 532 total deaths occurred among cancer survivors, of which 180 were cancer-specific. A monotonic increasing linear relationship between time spent sitting and all-cause mortality was observed (HR = 1.15, 95% CI = 1.03, 1.28 per one standard deviation increment). The highest versus the lowest tertiles of intakes of dietary fiber, carotene, niacin, thiamine, riboflavin, vitamin B6, vitamin B12, and vitamin C were inversely associated with all-cause and cancer-specific mortality (HRs = 0.48 to 0.75). The inverse associations with all-cause mortality were more pronounced for combinations of low sedentary behaviour and high intakes of dietary fiber, carotenoids, vitamin B12, and vitamin C. CONCLUSION: Our findings support recommendations for cancer survivors to reduce time spent sedentary and to follow a balanced diet with adequate intakes of dietary fiber and micronutrients.

Maternal iron-deficiency is associated with premature birth and higher birth weight despite routine antenatal iron supplementation in an urban South African setting: The NuPED prospective study.

BACKGROUND: Recent studies are suggesting a U-shaped relationship between antenatal iron exposure and birth outcomes. Little is known about the iron status and associated birth outcomes of pregnant women in South Africa. Our aim was to assess iron status at early, mid- and late pregnancy, and to determine associations with gestational age and birth weight in women in Johannesburg, South Africa. METHODS: In this prospective study of 250 pregnant women, we measured haemoglobin, biomarkers of iron status and inflammation at <18, 22 and 36 weeks of gestation, plus birth weight and gestational age at delivery. Associations of anaemia and iron status with birth outcomes were determined using regression models adjusted for confounders. RESULTS: At enrolment, the prevalence of anaemia, iron depletion (ID) and iron deficiency erythropoiesis (IDE) was 29%, 15% and 15%, respectively, and increased significantly with pregnancy progression. Anaemia and ID at 22 weeks, as well as IDE at 36 weeks were associated with higher birth weight (ß = 135.4; 95% CI: 4.8, 266.1 and ß = 205.4; 95% CI: 45.6, 365.1 and ß = 178.0; 95% CI: 47.3, 308.7, respectively). Women in the lowest ferritin quartile at 22 weeks gave birth to babies weighing 312 g (95% CI: 94.8, 528.8) more than those in the highest quartile. In contrast, IDE at 22 weeks was associated with a higher risk for premature birth (OR: 3.57, 95% CI: 1.24, 10.34) and women in lower haemoglobin quartiles at <18 weeks had a shorter gestation by 7 days (ß = -6.9, 95% CI: -13.3, -0.6) compared to those in the highest quartile. CONCLUSION: Anaemia, ID and IDE prevalence increased during pregnancy despite routine iron supplementation. ID and anaemia at mid-pregnancy were associated with higher birth weight, while IDE was associated with premature birth. These results suggest that current antenatal screening and supplementation practices in South Africa need to be revisited.

Substitution of sedentary time with light physical activity is related to increased bone density in U.S. women over 50 years old. An iso-temporal substitution analysis based on the National health and Nutrition Examination Survey.

U.S. women are ageing. This is causing rises in osteoporosis prevalence and risk of fracture with related increases in health care costs. Replacing sedentary time with light physical activity may represent a cost effective public health solution to osteoporosis in elderly women. The National Health and Nutrition Examination Survey conducted over the period 2003-2006 provided cross-sectional data on bone mineral density and objectively assessed physical activity among 1,052 women aged 50-85 years old. Substitution analysis was applied to estimate increased bone mineral density and reduced osteoporosis for those women replacing 30 min of sedentary time with an equivalent amount of light physical activity. Substitution of 30 min of sedentary time with an equal amount of light physical activity was associated with increased bone mineral density of about 3 mg/cm2 and a 12% reduced risk of osteoporosis in the spine. When considering overweight women and women over 65 years of age, this association was reinforced and it extended to the pelvis, legs and trunk, resulting in a consistent bone mineral density increase of about 3-6 mg/cm2. The substitution of 30 min of sedentary time with an equal amount of light physical activity appears a possible primary prevention method to reduce osteoporosis and related increases in risk of fracture, mortality, and health care costs in women over 50 years old.

Nutrient patterns and their relation to anemia and iron status in 5- to 12-y-old children in South Africa.

OBJECTIVE: The aim of this study was to assess nutrient patterns and their relation to anemia and iron status of school children using pooled data from three study populations in South Africa. METHODS: Data from 5- to 12-y-old children (N = 578) from three independent studies conducted in two provinces in South Africa were pooled. Data used in the analysis were dietary intake, hemoglobin, and plasma ferritin concentrations. Nutrient patterns were determined using factor analysis. Logistic regression analysis was performed to determine relationships of nutrient patterns with anemia and iron deficiency. RESULTS: In the pooled group, 13.8% of the children were anemic and 27.7% were iron deficient (ID). More than half of children did not meet the Estimated Average Requirement for various nutrients, including vitamins A, C, B12, folate, and zinc, although only 17.7% of children had an iron intake below the requirements. Median intakes for vitamins A and C were lower for anemic than non-anemic children (P = 0.03 and 0.02, respectively) and for ID versus non-ID children (P = 0.03 and 0.046, respectively). Four nutrient patterns were identified: plant protein, carbohydrate, iron, and B vitamins; animal protein and saturated fat; vitamins A and B12; and calcium and fiber. The vitamin A and B12 nutrient pattern was associated with lower odds of being anemic (odds ratio, 0.63; 95% confidence interval, 0.49-0.91; P = 0.035). CONCLUSION: The present results highlighted the potential role of the combination of dietary vitamin A and B12 in the etiology of nutritional anemia in school-age children in South Africa. Nutrient pattern analysis may improve the understanding of the synergistic role of nutrients related to anemia and may assist in planning intervention strategies.

Effect of small-quantity lipid-based nutrient supplements on growth, psychomotor development, iron status, and morbidity among 6- to 12-mo-old infants in South Africa: a randomized controlled trial.

Background: Evidence on the effect of small-quantity lipid-based nutrient supplements (SQ-LNSs) on early child growth and development is mixed. Objective: This study assessed the effect of daily consumption of 2 different SQ-LNS formulations on linear growth (primary outcome), psychomotor development, iron status (secondary outcomes), and morbidity in infants from age 6 to 12 mo within the context of a maize-based complementary diet. Methods: Infants (n = 750) were randomly assigned to receive SQ-LNS, SQ-LNS-plus, or no supplement. Both SQ-LNS products contained micronutrients and essential fatty acids. SQ-LNS-plus contained, in addition, docosahexaenoic acid, arachidonic acid (important for brain and eye development), lysine (limiting amino acid in maize), phytase (enhances iron absorption), and other nutrients. Infants' weight and length were measured bimonthly. At age 6 and 12 mo, psychomotor development using the Kilifi Developmental Inventory and South African Parent Rating Scale and hemoglobin, plasma ferritin, C-reactive protein, and α1-acid glycoprotein were assessed. WHO Motor Milestone outcomes, adherence, and morbidity were monitored weekly through home visits. Primary analysis was by intention-to-treat, comparing each SQ-LNS group with the control. Results: SQ-LNS-plus had a positive effect on length-for-age zscore at age 8 mo (mean difference: 0.11; 95% CI: 0.01, 0.22; P = 0.032) and 10 mo (0.16; 95% CI: 0.04, 0.27; P = 0.008) but not at 12 mo (0.09; 95% CI: -0.02, 0.21; P = 0.115), locomotor development score (2.05; 95% CI: 0.72, 3.38; P = 0.003), and Parent Rating Score (1.10; 95% CI: 0.14, 2.07; P = 0.025), but no effect for weight-for-age zscore. Both SQ-LNS (P = 0.027) and SQ-LNS-plus (P = 0.005) improved hemoglobin concentration and reduced the risk of anemia, iron deficiency, and iron-deficiency anemia. Both SQ-LNS products reduced longitudinal prevalence of fever, coughing, and wheezing but increased incidence and longitudinal prevalence of diarrhea, vomiting, and rash/sores. Conclusions: Point-of-use fortification with SQ-LNS-plus showed an early transient effect on linear growth and improved locomotor development. Both SQ-LNS products had positive impacts on anemia and iron status. This trial was registered at clinicaltrials.gov as NCT01845610.

Infant Development at the Age of 6 Months in Relation to Feeding Practices, Iron Status, and Growth in a Peri-Urban Community of South Africa.

BACKGROUND: Evidence on the association between feeding practices, iron deficiency, anaemia, stunting, and impaired psychomotor development during infancy is limited. This study assessed the association between psychomotor development with early feeding practices, growth, iron status, and anaemia. METHODS: This was cross-sectional baseline data of a randomised controlled trial which included 6-month-old infants and their mothers or primary caregivers (n = 750) in a peri-urban community in the North West province of South Africa. The Kilifi Developmental Inventory and a parent rating scale were used to assess psychomotor development. Feeding practices and anthropometric measurements were based on the World Health Organisation (WHO) guidelines. Anaemia and iron status were determined by blood sample analysis. RESULTS: Prevalence of anaemia and stunting for the infants were 36.4% and 28.5%, respectively. Multiple regression analysis showed that birth weight was related to combined psychomotor scores (ß = -3.427 (-4.603, 1.891), p < 0.001), as well as parent rating scores (ß = -0.843 (-1.507, -0.180), p = 0.013). Length-for-age z-scores were associated with combined psychomotor scores (ß = -1.419 (-2.466, 0.373), p = 0.008), as well as parent rating scores (ß = -0.747 (-1.483, -0.010), p = 0.047). CONCLUSIONS: In this setting, with high prevalence of anaemia and stunting, important associations between lower psychomotor development scores and birthweight as well as length-for-age z-scores in 6-month-old infants were found. These findings warrant further investigation to develop a greater understanding of factors influencing the association between child growth and psychomotor development within the first 1000 days of life.

Bariatric Surgery to Reduce Mortality in US Adults. A Public Health Perspective from the Analysis of the American National Health and Nutrition Examination Survey Linked to the US Mortality Register.

BACKGROUND: Type II obesity represents a major pandemic and public health threat in high-income countries. Type II obesity increases the risk of all-cause and specific-cause mortality, and it is widely acknowledged that bariatric surgery represents the only effective therapeutic option in these patients. The aim of the present study was to estimate US population attributable risk for all-cause and cause-specific mortality in type II obese subjects undergoing weight loss as resulting from bariatric surgery alone and supplemented with behavioral intervention. METHODS: The American National Health and Nutrition Examination Survey linked to the US death registry updated to 2011 was used to estimate type II obesity prevalence and all-cause and specific cause of death for type II obese adults undergoing weight loss. Multivariate adjusted proportional hazard Cox models were used to estimate mortality risks. Statistical analyses were performed on the most updated version of the database (June 2017). RESULTS: A monotone positive trend for type II obesity was observed during the period 1999-2014 (p < 0.001). According to trend analysis, the rate of type II obesity in US adults is expected to rise up to 8.5%. Two- to sevenfold increased risk of all-cause and specific-cause mortality was observed for type II obese participants when compared to type I obese and overweight participants. Population attributable risk for all-cause and specific-cause mortality for type II obese subjects undergoing weight loss was ranging between 6 and 34%. CONCLUSIONS: Bariatric surgery supplemented with behavioral intervention can result in a relevant reduction of mortality if extensively applied to the US population.

Potential contribution of African green leafy vegetables and maize porridge composite meals to iron and zinc nutrition.

OBJECTIVES: The aim of this study was to determine the mineral nutritive value of different traditional African green leafy vegetable (GLV) dishes and their composite meals with fortified and unfortified maize porridge. METHODS: The mineral (iron, zinc, and calcium) and antinutrient (phytate, total phenolics, and tannins) contents and in vitro bioaccessibility of iron and zinc were analyzed. The iron and zinc contents and bioaccessibilities were used to calculate contribution these dishes and meals could make toward the recommended daily requirements and absolute requirements of vulnerable populations. RESULTS: It was found that the GLV dishes contained average amounts of zinc (2.8-3.2 mg/100 g, dry base [db]), but were high in both iron (12.5-23.4 mg/100 g, db) and antinutrients (phytate 1420-2089 mg/100 g, db; condensed tannins 105-203 mg/100 g, db). The iron bioaccessibility and amount of bioaccessible iron ranged between 6.7% and 45.2% and 0.9 and 5.11 mg/100 g, db, respectively. The zinc bioaccessibility and amount of bioaccessible zinc ranged between 6.4% and 12.7% and 0.63 and 1.63 mg/100 g, db, respectively. CONCLUSION: Importantly, although compositing the GLV dishes with fortified maize porridges decreases the iron and zinc contents, because of the low antinutrient content of the maize meal, the amount of bioaccessible iron and zinc in the meal increases.

n-3 Long-chain PUFAs reduce respiratory morbidity caused by iron supplementation in iron-deficient South African schoolchildren: a randomized, double-blind, placebo-controlled intervention.

BACKGROUND: Although iron supplementation in malaria-free areas mostly reduces infectious morbidity, it can sometimes increase morbidity from infections as a result of the dependence of pathogenic microorganisms on iron. Supplementation with n-3 (ω-3) long-chain polyunsaturated fatty acids (LCPUFAs) improved morbidity in several human studies. However, information on the combined effect of iron and n-3 LCPUFA supplementation on infectious morbidity is limited. OBJECTIVE: We determined whether n-3 LCPUFAs and iron supplementation, alone or in combination, affected absenteeism and illness in iron-deficient schoolchildren with low fish intake. DESIGN: A total of 321 South African children (aged 6-11 y) with iron deficiency (ID) were randomly divided into 4 groups to receive 1) iron plus placebo, 2) a mixture of docosahexaenoic acid and eicosapentaenoic acid (DHA/EPA) plus placebo, 3) iron plus DHA/EPA, or 4) placebo plus placebo as oral supplements 4 times/wk for 8.5 mo. Morbidity was recorded, and iron-status indexes were measured. The total phospholipid fatty acid composition of peripheral blood mononuclear cell membranes was analyzed in a subsample (n = 130). RESULTS: Iron supplementation increased the number of days with illness when all symptoms were considered (B: 0.87; 95% CI: 0.71, 1.03) as well as illness that was specifically caused by respiratory symptoms (B: 1.45; 95% CI: 1.21, 1.70), whereas DHA/EPA reduced the number of days with illness at school (B: -0.96; 95% CI: -1.33, -0.59). The increases caused by iron were reduced to the levels seen in the placebo plus placebo group when iron was provided in combination with DHA/EPA as indicated by significant iron × DHA/EPA interactions (both P < 0.001). CONCLUSION: Iron supplementation increased morbidity (mostly respiratory) in iron-deficient South African schoolchildren with low DHA/EPA intake, but when iron was given in combination with DHA/EPA, this effect was prevented.

Differential ferritin interpretation methods that adjust for inflammation yield discrepant iron deficiency prevalence.

We reassessed the iron deficiency (ID) prevalence in a South African trial that formed part of the International Research on Infant Supplementation study by comparing four methods that account for the high prevalence of acute (28.6%) and chronic (41.8%) inflammation observed in the study. Serum ferritin (SF) was measured as marker of iron status in 192 apparently healthy, 4-13-month-old infants. Alpha-1 glycoprotein and C-reactive protein concentrations were determined to indicate chronic and acute inflammation, respectively. The ID prevalence was obtained by four methods that adjust for inflammation: (1) excluding infants with inflammation; (2) using a higher cut-off (SF < 30 µg L(-1) ); (3) using different cut-offs for infants with vs. without inflammation (SF < 30 µg L(-1) vs. SF < 12 µg L(-1) ); and (4) adjusting SF concentrations with correction factors (CFs) were compared with a reference method (SF < 12 µg L(-1) ) not accounting for inflammation. Using the higher SF cut-off method resulted in the highest ID prevalence (52.1%), followed by using two different cut-offs (31.8%), using CFs (21.9%) and excluding subjects with inflammation (17.6%). The CF method showed the best agreement with the reference method. Disregarding inflammation resulted in a significantly lower ID prevalence (17.2%). ID anaemia (IDA) prevalence ranged from 13.2% to 24.5%, with the lowest prevalence (12.0%) for the reference method. Our analysis highlights the challenge of assessing ID and IDA using only SF as marker of iron status in the presence of inflammation. We demonstrate the importance of measuring inflammation markers to account for their elevating effect on SF.

Long-chain n-3 PUFA supplementation decreases physical activity during class time in iron-deficient South African school children.

Both Fe deficiency and poor n-3 fatty acid status have been associated with behavioural changes in children. In the present study, we investigated the effects of Fe and DHA+EPA supplementation, alone or in combination, on physical activity during school days and on teacher-rated behaviour in healthy Fe-deficient school children. In a 2 × 2 factorial design, children (n 98, 6-11 years) were randomly assigned to receive (1) Fe (50 mg) plus DHA (420 mg)+EPA (80 mg), (2) Fe plus placebo, (3) placebo plus DHA+EPA or (4) placebo plus placebo as oral supplements (4 d/week) for 8.5 months. Physical activity was measured during four school days at baseline and endpoint using accelerometers, and data were stratified into morning class time (08.00-10.29 hours), break time (10.30-11.00 hours) and after-break class time (11.01-12.00 hours) for analysis. Classroom behaviour was assessed at endpoint using Conners' Teacher Rating Scales. DHA+EPA supplementation decreased physical activity counts during morning class time, increased sedentary physical activity, and decreased light- and moderate-intensity physical activities. Consistently, DHA+EPA supplementation increased sedentary physical activity and decreased light-intensity physical activity during after-break class time. Even though there were no treatment effects found on teacher-rated behaviour, lower physical activity during morning class time was associated with lower levels of teacher-rated hyperactivity and oppositional behaviour at endpoint. Despite a positive association between Fe status and physical activity during break time at baseline, Fe supplementation did not affect physical activity during break time and class time. Our findings suggest that DHA+EPA supplementation may decrease physical activity levels during class time, and further indicate that accelerometry might be a useful tool to assess classroom behaviour in healthy children.