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BackgroundHuman immunodeficiency virus (HIV) and iron deficiency (ID) affect many African children. Both HIV and iron status interact with gut microbiota composition and related biomarkers. The study's aim was to determine the associations of HIV and iron status with gut microbiota composition, gut inflammation and gut integrity in South African school-age children.MethodsIn this two-way factorial case-control study, 8- to 13-year-old children were enrolled into four groups based on their HIV and iron status: (1) With HIV (HIV+) and ID (n = 43), (2) HIV+ and iron-sufficient nonanaemic (n = 41), (3) without HIV (HIV-) and ID (n = 44) and (4) HIV- and iron-sufficient nonanaemic (n = 38). HIV+ children were virally suppressed (, Journal of Human Nutrition and Dietetics, 36 (3), ISSN:0952-3871, ISSN:1365-277X

Perinatal depression can negatively affect the health of the mother and her offspring. N-3 polyunsaturated fatty acids (PUFA) may play a role in the aetiology of depression. Therefore, we investigated the association of n-3 PUFA status during early pregnancy with perinatal depression among women living in urban Johannesburg, South Africa. For this prospective analysis, we analysed red blood cell (RBC) total phospholipid fatty acid (FA) composition (% of total FA) of 242 pregnant women at, Prostaglandins, Leukotrienes and Essential Fatty Acids, 190, ISSN:0952-3278, ISSN:1532-2823

The WHO Regional Office for Europe and the Federation of International Societies for Pediatric Gastroenterology, Hepatology, and Nutrition held a joint workshop, "Moving Complementary Feeding Forward" at the sixth World Congress Pediatric Gastroenterology, Hepatology, and Nutrition in 2021. Here we summarize workshop presentations and discussions. The workshop covered health implications of complementary feeding (CF) including allergies, challenges to meet dietary needs during the CF period, quality of commercial complementary foods (CFD) and respective marketing practices, national CF guidelines in Europe, a nutrient profiling system for CFD, and global policy perspectives on the standards and regulation of marketing for CFD. Adequate CF practices are of critical importance for short and long-term child health, prevention of nutrient deficiencies, normal growth and development, and reducing the risk of allergies. The workshop identified the need to improve feeding practices, harmonize evidence-based information and develop guidance jointly with various stakeholders, improve the composition and marketing practices of commercial CFD and their transparent labeling based on nutrient profiling. Renewed efforts for collaboration between scientists, public health experts, pediatric associations, national governments, and the WHO are necessary for advancing progress., Journal of Pediatric Gastroenterology and Nutrition, 75 (4), ISSN:0277-2116, ISSN:1536-4801

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.

PURPOSE: Both HIV and oral iron interventions may alter gut microbiota composition and increase gut inflammation. We determined the effect of oral iron supplementation on gut microbiota composition, gut inflammation, and iron status in iron-depleted South Africa school-aged children living with HIV (HIV+) but virally suppressed on antiretroviral therapy and children without HIV (HIV-ve). METHODS: In this before-after intervention study with case-control comparisons, we provided 55 mg elemental iron from ferrous sulphate, once daily for 3 months, to 33 virally suppressed (

Adequate intake of iodine is important during pregnancy because of its essential role in foetal growth and neurodevelopment. Data on iodine status of South African pregnant women are scarce, and the salt reduction policy implemented in 2016 may decrease iodine intake of South Africans. This cross-sectional study assessed the iodine status of pregnant women residing in urban Johannesburg, South Africa. A total of 250 pregnant women were enrolled into the ‘Nutrition during Pregnancy and Early Development’ (NuPED) study and 312 pregnant women into the ‘Assessment of dried blood spot thyroglobulin in pregnant women to redefine the range of median urinary iodine concentration that indicates adequate iodine intake, South Africa’ (STRIPE-SA) study and were included in this analysis. Urinary iodine concentration (UIC) was analysed in a spot urine sample. Thyroglobulin (Tg) was measured in serum, and thyroid-stimulating hormone (TSH) and total thyroxine (tT4) were measured in dried blood spots. The median [interquartile range (IQR)] UIC of pregnant women was 144 (84–234) μg/L. Women in the first (n = 99), second (n = 262) and third (n = 174) trimester had a median UIC of 133 (81–316), 145 (84–236) and 156 (89–245) μg/L, respectively (p = 0.419). Median TSH, tT4 and Tg were 2.7 (2.3–3.2) mU/L, 202 (163–236) nmol/L and 9.2 (5.4–17.9) μg/L, respectively. Based on the median UIC, pregnant women residing in urban Johannesburg may be borderline iodine deficient. These findings highlight the need for ongoing monitoring of iodine status among vulnerable pregnant women, especially considering the recently introduced salt reduction policy in South Africa., Maternal & Child Nutrition, 18 (1), ISSN:1740-8695, ISSN:1740-8709

Both HIV and oral iron interventions may alter gut microbiota composition and increase gut inflammation. We determined the effect of oral iron supplementation on gut microbiota composition, gut inflammation, and iron status in iron-depleted South Africa school-aged children living with HIV (HIV+) but virally suppressed on antiretroviral therapy and children without HIV (HIV-ve).In this before-after intervention study with case-control comparisons, we provided 55 mg elemental iron from ferrous sulphate, once daily for 3 months, to 33 virally suppressed ( 50 HIV RNA copies/mL) HIV+ and 31 HIV-ve children. At baseline and endpoint, we assessed microbial composition of faecal samples (16S rRNA sequencing), and markers of gut inflammation (faecal calprotectin), anaemia (haemoglobin) and iron status (plasma ferritin, soluble transferrin receptor). This study was nested within a larger trial registered at clinicaltrials.gov as NCT03572010.HIV+ (11.3y SD ± 1.8, 46% male) and HIV-ve (11.1y SD ± 1.7, 52% male) groups did not significantly differ in age or sex ratio. Following iron supplementation, improvements were observed in haemoglobin (HIV+ : 118 to 124 g/L, P = 0.003; HIV-ve: 120 to 124 g/L, P = 0.003), plasma ferritin (HIV+ : 15 to 34 µg/L, P 0.001; HIV-ve: 18 to 37 µg/L, P 0.001), and soluble transferrin receptor (HIV+ : 7.1 to 5.9 mg/L, P 0.001; HIV-ve: 6.6 to 5.7 mg/L, P 0.001), with no significant change in the relative abundance of any genera, alpha diversity of the gut microbiota (HIV+ : P = 0.37; HIV-ve: P = 0.77), or faecal calprotectin (HIV+ : P = 0.42; HIV-ve: P = 0.80).Our findings suggest that oral iron supplementation can significantly improve haemoglobin and iron status without increasing pathogenic gut microbial taxa or gut inflammation in iron-depleted virally suppressed HIV+ and HIV-ve school-age children.

Background: The sodium iodide symporter is responsible for the transfer of iodine into breast milk and is encoded for by the SLC5A5 gene. The role of genetic variants in the SLC5A5 gene locus in relation to the transfer of iodine from plasma into breast milk in healthy lactating individuals has, to our knowledge, not been explored. Objective: To identify and characterize possible genetic variants of the SLC5A5 gene in women of African descent living in urban South Africa, and to study associations with breast milk iodine concentrations (BMIC) in lactating women. Methods: This study is affiliated to the Nutrition during Pregnancy and Early Development (NuPED) cohort study (n = 250 enrolled pregnant women). In a randomly selected sub-sample of 32 women, the SLC5A5 gene was sequenced to identify known and novel variants. Of the identified variants, genotyping of selected variants was performed in all pregnant women who gave consent for genetic analyses (n = 246), to determine the frequency of the variants in the study sample. Urinary iodine concentration (UIC) in spot urine samples and BMIC were measured to determine iodine status. Associations of SLC5A5 genetic variants with BMIC were studied in lactating women (n = 55). Results: We identified 27 variants from sequencing of gene exomes and 10 variants were selected for further study. There was a significant difference in BMIC between the genotypes of the rs775249401 variant (P = 0.042), with the homozygous GG group having lower BMIC [86.8 (54.9–167.9) μg/L] compared to the (A) allele carriers rs775249401(AG+AA) [143.9 (122.4–169.3) μg/L] (P = 0.042). Of the rs775249401(GG), 49% had UIC, Frontiers in Nutrition, 8, ISSN:2296-861X

Background/objectives The objective of this study was to investigate the efficacy of small-quantity lipid-based nutrient supplements (SQ-LNS) containing essential fatty acids (EFAs) with or without long-chain polyunsaturated fatty acids (LCPUFAs) in improving LCPUFA status in South African infants fed complementary food. Subjects/methods Six-month-old infants (n = 750) were randomised to receive SQ-LNS, SQ-LNS-plus, or no supplement. Both SQ-LNSs contained micronutrients and EFAs. SQ-LNS-plus additionally contained the LCPUFAs arachidonic acid (AA) and docosahexaenoic acid (DHA), lysine, phytase and other nutrients. Plasma total phospholipid FA composition (% of total FAs) was measured at baseline (n = 353) and at 12 months (n = 293). Results At baseline, geometric mean (95% CI) plasma DHA and AA were 4.1 (4.0–4.3) and 11.5 (11.2–11.8)% respectively, with significantly higher plasma DHA and AA in breastfed than non-breastfed infants. Infants receiving the SQ-LNS-plus had significantly higher plasma DHA (4.52 (4.3–4.9)) at 12 months than the controls (3.8 (3.6–4.0)), with a higher effect size in infants who no longer received breast milk (β = 1.148 (95% CI = 0.597, 1.699)) than in infants who were still breastfeeding (β = 0.544 (95% CI = 0.179, 0.909)). There was no effect of either of the two SQ-LNSs on plasma AA. Consequently, infants receiving the SQ-LNS-plus had a significantly lower plasma n-6 to n-3 PUFA ratio at 12 months than control infants did. Conclusions Our study suggests that the provision of SQ-LNS-plus is efficacious in improving plasma DHA status. Particularly, infants who are no longer breastfed may benefit most from LCPUFA-enriched SQ-LNS

ObjectiveThe 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.MethodsData 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.ResultsIn 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).ConclusionThe 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.

Purpose of review Iron deficiency remains highly prevalent in women and young children in low-income and middle-income countries. To prevent the potentially life-long consequences of iron deficiency when occurring during early life, the WHO recommends iron supplementation of pregnant women and young children. However, increasing evidence of limited efficacy and risk of current iron intervention strategies are cause of concern. This review aims to highlight recent advances and challenges of established and novel intervention strategies for the prevention of iron deficiency during the first 1000 days in low-income and middle-income countries. Recent findings Recent meta-analyses and trials challenged the WHO's current recommendation to provide iron-folic acid rather than multiple micronutrient supplements during routine antenatal care. Furthermore, several studies explored optimal windows for iron supplementation, such as prior to conception. Studies are demonstrating that infectious and noninfectious inflammation is compromising the efficacy of iron interventions in vulnerable groups. Therefore, strategies addressing iron deficiency should focus on targeting infection and inflammation while simultaneously providing additional iron. Furthermore, both iron deficiency and iron supplementation may promote an unfavourable gut microbiota. Recent trials in infants indicate that the provision of a prebiotic together with iron may alleviate the adverse effects of iron on the gut microbiome and gut inflammation, and may even enhance iron absorption. Summary Recent studies highlight the need for and potential of novel intervention strategies that increase the efficacy and limit the potential harm of universal iron supplementation.

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.

Universal salt iodization has been adopted by many countries to address iodine deficiency. More recently, salt-reduction strategies have been widely implemented to meet global salt intake targets of5 g/d. Compatibility of the two policies has yet to be demonstrated. This study compares urinary iodine excretion (UIE) according to 24-h urinary sodium excretion, between South Africa (SA) and Ghana; both countries have implemented universal salt iodization, but in Ghana no salt-reduction legislation has been implemented.Participants from the World Health Organization's Study on Global Ageing and Adult Health Wave 3, with survey and valid 24-h urinary data (Ghana, n = 495; SA, n = 707), comprised the sample. Median 24-h UIE was compared across salt intake categories of5, 5-9 and9 g/d.In Ghana, median sodium excretion indicated a salt intake of 10.7 g/d (interquartile range [IQR] = 7.6), and median UIE was 182.4 µg/L (IQR = 162.5). In SA, both values were lower: median salt = 5.6 g/d (IQR = 5.0), median UIE = 100.2 µg/L (IQR = 129.6). UIE differed significantly across salt intake categories (P0.001) in both countries, with positive correlations observed in both-Ghana: r = 0.1501, P0.0011; South Africa: r = 0.4050, P0.0001. Participants with salt intakes9 g/d in SA did not meet the World Health Organization's recommended iodine intake of 150 µg/d, but this was not the case in Ghana.Monitoring and surveillance of iodine status is recommended in countries that have introduced salt-reduction strategies, in order to prevent reemergence of iodine deficiency.

The etiology of multifactorial morbidities such as undernutrition and anemia in children living with the human immunodeficiency virus (HIV) (HIV+) on antiretroviral therapy (ART) is poorly understood. Our objective was to examine associations of HIV and iron status with nutritional and inflammatory status, anemia, and dietary intake in school-aged South African children. Using a two-way factorial case-control design, we compared four groups of 8 to 13-year-old South African schoolchildren: (1) HIV+ and low iron stores (inflammation-unadjusted serum ferritin ≤40 µg/L), n = 43, (2) HIV+ and iron sufficient non-anemic (inflammation-unadjusted serum ferritin &gt, 40 µg/L, hemoglobin ≥115 g/L), n = 41, (3) children without HIV (HIV-ve) and low iron stores, n = 45, and (4) HIV-ve and iron sufficient non-anemic, n = 45. We assessed height, weight, plasma ferritin (PF), soluble transferrin receptor (sTfR), plasma retinol-binding protein, plasma zinc, C-reactive protein (CRP), α-1-acid glycoprotein (AGP), hemoglobin, mean corpuscular volume, and selected nutrient intakes. Both HIV and low iron stores were associated with lower height-for-age Z-scores (HAZ, p &lt, 0.001 and p = 0.02, respectively), while both HIV and sufficient iron stores were associated with significantly higher CRP and AGP concentrations. HIV+ children with low iron stores had significantly lower HAZ, significantly higher sTfR concentrations, and significantly higher prevalence of subclinical inflammation (CRP 0.05 to 4.99 mg/L) (54%) than both HIV-ve groups. HIV was associated with 2.5-fold higher odds of iron deficient erythropoiesis (sTfR &gt, 8.3 mg/L) (95% CI: 1.03–5.8, p = 0.04), 2.7-fold higher odds of subclinical inflammation (95% CI: 1.4–5.3, p = 0.004), and 12-fold higher odds of macrocytosis (95% CI: 6–27, p &lt, 0.001). Compared to HIV-ve counterparts, HIV+ children reported significantly lower daily intake of animal protein, muscle protein, heme iron, calcium, riboflavin, and vitamin B12, and significantly higher proportions of HIV+ children did not meet vitamin A and fiber requirements. Compared to iron sufficient non-anemic counterparts, children with low iron stores reported significantly higher daily intake of plant protein, lower daily intake of vitamin A, and lower proportions of inadequate fiber intake. Along with best treatment practices for HIV, optimizing dietary intake in HIV+ children could improve nutritional status and anemia in this vulnerable population. This study was registered at clinicaltrials.gov as NCT03572010.

Dietary pattern analyses allow assessment of the diet as a whole. Limited studies include both a priori and a posteriori dietary pattern analyses. This study aimed to explore the diet of pregnant women in urban South Africa through both a priori and a posteriori dietary pattern analyses and associated maternal and household factors. Dietary data were collected during early pregnancy using a quantified food frequency questionnaire from 250 pregnant women enrolled in the Nutrition During Pregnancy and Early Development (NuPED) cohort. A priori dietary patterns were determined using the Diet Quality Index-International (DQI-I), and a posteriori nutrient patterns using exploratory factor analysis. Based on the DQI-I, the study population followed a borderline low-quality diet. Three a posteriori nutrient patterns were identified: Pattern 1 “plant protein, iron, thiamine, and folic acid”, pattern 2 “animal protein, copper, vitamin A, and vitamin B12”, pattern 3 “fatty acids and sodium”. Pattern 1 was associated with higher dietary quality (p &lt, 0.001), lower maternal educational level (p = 0.03) and socioeconomic status (p &lt, 0.001). Pattern 3 was significantly associated with lower dietary quality. The low dietary quality among pregnant women residing in urban South Africa should be addressed to ensure optimal maternal and offspring health outcomes.

In South Africa, haemoglobin (Hb) is measured to screen for iron deficiency (ID). However, low levels of Hb are only a late stage indicator of ID. Furthermore, Hb values are generally not adjusted for altitude even though recommended by WHO. We determined the Hb threshold with the highest combined sensitivity and specificity for detecting ID among South African women living at 1700 m above sea level. In a cross-sectional study of 492 18&ndash, 25-year-old women, we measured Hb and iron status biomarkers. Using receiver operating characteristic curves, we determined the Hb threshold with maximum Youden Index for detecting ID. This threshold of &lt, 12.35 g/dL resulted in a 37.2% anaemia prevalence (20.9% IDA), and sensitivity and specificity of 55.7% and 73.9%, respectively. The WHO altitude-adjusted threshold of &lt, 12.5 g/dL resulted in a 39% anaemia prevalence (21.3% IDA), and sensitivity and specificity of 56.8% and 70.8%, respectively. In contrast, using the unadjusted Hb cut-off of &lt, 12 g/dL resulted in a 18.5% anaemia prevalence (12.6% IDA), and sensitivity and specificity of 35.1% and 88.6%, respectively. In this sample of South African women of reproductive age an Hb threshold &lt, 12.35 g/dL had the highest combined sensitivity and specificity for detecting ID. The diagnostic performance of this Receiver operating characteristic curve-determined threshold was comparable to the altitude-adjusted threshold proposed by WHO. Thus, clinical and public health practice in South Africa should adopt adjustment of Hb for altitude to avoid underestimation of ID and missing women in need for intervention.

Data on breast milk fatty acid (FA) composition in South African lactating women in relation to their FA status, as well as on potential compositional changes within feed, are limited. The aim of this study was to assess the FA composition of breast milk sampled at three time points within feed, and to determine associations with red blood cell (RBC) total phospholipid FA levels in lactating South African mothers of 2–4-month-old breastfed infants. FA composition (% total FAs) was analyzed in RBC total phospholipids, and in fore-, mid-feed and hind-milk samples of lactating mothers (n = 100) of Black African descent living in a peri‑urban township. The mean age of the lactating women was 27.8 ± 6.8 years. Geometric mean (95% CI) breast milk SFA, MUFA and PUFA contents were 37.7 (37.3,38.1), 28.5 (27.9, 28.8), and 23.5 (23.2, 24.5)%, respectively. Breast milk DHA and AA contents were 0.25 (0.24, 3.71) and 0.81 (0.79, 0.83)%, respectively, in fore-, mid- and hind-milk combined. Maternal RBC EPA, DHA and AA levels were 0.37 (0.34, 0.40), 3.8 (3.6, 4.0) and 15.4 (14.8, 16.1)%, respectively. Women who reported to consume fish often (n = 3) had significantly higher RBC EPA levels than women who consumed fish sometimes (n = 56), never (n = 14) or rarely (n = 19). Breast milk DHA positively correlated with maternal RBC DHA, while no correlations were found between breast milk AA and maternal RBC AA. Breast milk ALA and DHA contents were significantly higher in mid-feed [ALA= 0.8 (0.2, 0.2), DHA=0.3 (0.2, 0.3)] and hind-milk [ALA=0.8 (0.8, 0.9), DHA=0.3 (0.3, 0.3)] than foremilk [ALA=0.8 (0.7, 0.9), DHA=0.2 (0.2, 0.3)]. In contrast, LA and AA contents remained constant within feed. In this sample of peri‑urban South African lactating mothers, breast milk was low in DHA and high in AA compared to global means. Breast milk DHA was associated with maternal RBC status, while breast milk AA was not. We further showed that breast milk ALA and DHA increased, while LA and AA remained unchanged within feed. This suggests that n-3 PUFA maybe preferentially transferred to breast milk within feed through biomagnification.

Principal component analysis (PCA) is a popular statistical tool. However, despite numerous advantages, the good practice of imputing missing data before PCA is not common. In the present work, we evaluated the hypothesis that the expectation-maximization (EM) algorithm for missing data imputation is a reliable and advantageous procedure when using PCA to derive biomarker profiles and dietary patterns. To this aim, we used numerical simulations aimed to mimic real data commonly observed in nutritional research. Finally, we showed the advantages and pitfalls of the EM algorithm for missing data imputation applied to plasma fatty acid concentrations and nutrient intakes from real data sets deriving from the US National Health and Nutrition Examination Survey. PCA applied to simulated data having missing values resulted in biased eigenvalues with respect to the original data set without missing values. The bias between the eigenvalues from the original set of data and from the data set with missing values increased with number of missing values and appeared as independent with respect to the correlation structure among variables. On the other hand, when data were imputed, the mean of the eigenvalues over the 10 missing imputation runs overlapped with the ones derived from the PCA applied to the original data set. These results were confirmed when real data sets from the National Health and Nutrition Examination Survey were analyzed. We accept the hypothesis that the EM algorithm for missing data imputation applied before PCA aimed to derive biochemical profiles and dietary patterns is an effective technique especially for relatively small sample sizes.

The objective of this study was to investigate the efficacy of small-quantity lipid-based nutrient supplements (SQ-LNS) containing essential fatty acids (EFAs) with or without long-chain polyunsaturated fatty acids (LCPUFAs) in improving LCPUFA status in South African infants fed complementary food.Six-month-old infants (n = 750) were randomised to receive SQ-LNS, SQ-LNS-plus, or no supplement. Both SQ-LNSs contained micronutrients and EFAs. SQ-LNS-plus additionally contained the LCPUFAs arachidonic acid (AA) and docosahexaenoic acid (DHA), lysine, phytase and other nutrients. Plasma total phospholipid FA composition (% of total FAs) was measured at baseline (n = 353) and at 12 months (n = 293).At baseline, geometric mean (95% CI) plasma DHA and AA were 4.1 (4.0-4.3) and 11.5 (11.2-11.8)% respectively, with significantly higher plasma DHA and AA in breastfed than non-breastfed infants. Infants receiving the SQ-LNS-plus had significantly higher plasma DHA (4.52 (4.3-4.9)) at 12 months than the controls (3.8 (3.6-4.0)), with a higher effect size in infants who no longer received breast milk (β = 1.148 (95% CI = 0.597, 1.699)) than in infants who were still breastfeeding (β = 0.544 (95% CI = 0.179, 0.909)). There was no effect of either of the two SQ-LNSs on plasma AA. Consequently, infants receiving the SQ-LNS-plus had a significantly lower plasma n-6 to n-3 PUFA ratio at 12 months than control infants did.Our study suggests that the provision of SQ-LNS-plus is efficacious in improving plasma DHA status. Particularly, infants who are no longer breastfed may benefit most from LCPUFA-enriched SQ-LNS.

The objective of this study was to assess plasma fatty acid (FA) patterns of 6-month-old South African infants and to determine their association with feeding practices, growth, and psychomotor development. Plasma total phospholipid FA composition (% of total FAs) of 6-month-old infants (n = 353) from a peri-urban township was analysed, and principal component and factor analysis were performed to identify plasma FA patterns. Feeding practices, anthropometric measurements, and psychomotor development scores were determined. Four major plasma phospholipid FA patterns were identified: A plant-based C18 FA, a high n-6 long-chain polyunsaturated fatty acids (LCPUFA), a C16:1 and long-chain saturated fatty acid (SFA), and a high n-3 and low n-6 LCPUFA pattern. Formula feeding was associated with higher, whereas breastfeeding was associated with lower scores for the plant-based C18 FA and C16:1 and long-chain SFA patterns. On the other hand, breastfeeding, the consumption of cow's milk, and the consumption of semisolid foods were associated with higher scores, whereas formula feeding was associated with lower scores for the high n-6 LCPUFA pattern. Breastfeeding and the consumption of semisolids were also associated with higher high n-3 and low n-6 LCPUFA pattern scores. The C16:1 and long-chain SFA and high n-3 and low n-6 LCPUFA patterns were positively associated with psychomotor development scores. In 6-month-old South African infants, we identified distinct plasma FA patterns that presumably represent the FA quality of their diet and that are associated with psychomotor development. Our results suggest that breast milk is an important source of n-6 LCPUFAs and formula-fed infants may be at risk of inadequate LCPUFA intake.

Nutritional transition in Africa is linked with increased blood pressure (BP). We examined 10-year fatty acid status and longitudinal associations between individual long-chain polyunsaturated fatty acids (PUFA), BP and status of hypertension (&ge, 140/90 mmHg and/or medication use) in black South Africans. We included 300 adults (&gt, 30 years) participating in the Prospective Urban Rural Epidemiology study, and analysed data from three consecutive examinations (2005, 2010 and 2015 study years). Fatty acids in plasma phospholipids were analysed by gas chromatography-mass spectrometry. We applied sequential linear mixed models for continuous outcomes and generalized mixed models for the hypertension outcome, in the complete sample and separately in urban and rural subjects. Mean baseline systolic/diastolic BP was 137/89 mmHg. Ten-year hypertension status increased among rural (48.6% to 68.6%, p = 0.001) and tended to decrease among urban subjects (67.5% to 61.9%, p = 0.253). Regardless of urbanisation, n-6 PUFA increased and eicosapentaenoic acid (EPA, C20:5 n-3) decreased over the 10-years. Subjects in the highest tertile of arachidonic acid (C20:4 n-6) had 3.81 mmHg lower systolic (95% confidence interval (CI): &minus, 7.07, &minus, 0.54) and 3.82 mmHg lower diastolic BP (DBP) (95% CI: &minus, 5.70, &minus, 1.95) compared to the reference tertile, irrespective of lifestyle and clinical confounders. Similarly, osbond acid (C22:5 n-6) was inversely associated with DBP. Over the 10-years, subjects in the highest EPA tertile presented with +2.92 and +1.94 mmHg higher SBP and DBP, respectively, and with 1.46 higher odds of being hypertensive. In black South African adults, individual plasma n-6 PUFA were inversely associated with BP, whereas EPA was adversely associated with hypertension, supporting implementation of dietary fat quality in national cardiovascular primary prevention strategies.

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, PLoS ONE, 14 (9), ISSN:1932-6203

We considered the Blom’s transformation, a statistical method aimed to normalise and standardise food intakes before principal component analysis. A simulation study was performed to evaluate the eigenvalue distribution of a correlation matrix under common conditions in food questionnaire analysis. The scree plot visual inspection and the Guttman–Kaiser (GK) criterion were compared to Horn’s parallel analysis to evaluate their efficacy in food pattern identification. The scree plot results as a monotone continuous series when no food patterns are present. In this situation, about 50% of the eigenvalues assume a value higher than one, showing a first fallacy of the GK. When three food patterns are simulated a clear discontinuity appears after the third eigenvalue, showing that the scree-plot visual inspection is a suitable method to identify food patterns. Finally, according to the present work it appears that the GK generates a number of false-positive food patterns.

Animal models are widely used in the field of nutrition research. Scientifically and ethically sound experiments need an adequate number of experimental units. The use of 5-10 units is common, but such sample sizes can be justified for large effect sizes only. We reviewed animal model studies recently published in selected journals in the field of nutrition sciences. We performed a simulation study aimed at determining the adequate sample size for normality assessment. We then performed power calculations for a number of statistical tests commonly found in rodent model studies in nutrition research. Among the selected papers, sample sizes ranged from 6-18 units per group. None of them justified the sample size. However, such sample sizes do not allow for normality testing, thus, graphical approaches should be used. Parametric approaches result in higher statistical power when compared to their non-parametric counterparts. Repeated measures analysis should always be preferred, when possible.

Objective Lactating women and their infants are susceptible to iodine deficiency and iodine excess. In South Africa, no data exist on the iodine status and thyroid function of these vulnerable groups. Methods In a cross-sectional study, urinary iodine concentrations (UIC), thyroid function, and breast-milk iodine concentrations (BMIC) were assessed in 100 lactating women from a South African township and their 2-4-month-old breastfed infants. Potential predictors of UIC, thyroid function, and BMIC, including household salt iodine concentrations (SIC) and maternal sodium excretion, were also investigated. Results The median (25th-75th percentile) UIC was 373 (202-627) μg/L in infants and 118 (67-179) μg/L in mothers. Median household SIC was 44 (27-63) ppm. Household SIC and maternal urinary sodium excretion predicted UIC of lactating mothers. Median BMIC was 179 (126-269) μg/L. Age of infants, SIC, and maternal UIC predicted BMIC. In turn, infant age and BMIC predicted UIC of infants. Forty-two percent of SIC values were within the South African recommended salt iodine fortification level at production of 35-65 ppm, whilst 21% of SIC were >65 ppm. Thyroid-stimulating hormone, total thyroxine, and thyroglobulin concentrations in the dried whole blood spot specimens from the infants were 1.3 (0.8-1.9) mU/L, 128±33 mmol/L, and 77.1 (56.3-105.7) μg/L, respectively, and did not correlate with infant UIC or BMIC. Conclusion Our results suggest that the salt fortification program in South Africa provides adequate iodine to lactating women and indirectly to their infants via breast milk. However, monitoring of salt iodine content of the mandatory salt iodization program in South Africa is important to avoid over-iodization of salt.

Background: Optimal iodine intake during infancy is critical for brain development, but no estimated average requirement (EAR) is available for this age group. Objective: We measured daily iodine intake, excretion, and retention over a range of iodine intakes in early infancy to determine the minimum daily intake required to achieve iodine balance. Design: In a dose-response crossover study, we randomly assigned healthy infants (n = 11; mean ± SD age 13 ± 3 wk) to sequentially consume over 33 d 3 infant formula milks (IFMs) containing 10.5, 19.3, and 38.5 μg I/100 kcal, respectively. Each IFM was consumed for 11 d, consisting of a 6-d run-in period followed by a 4-d balance period and 1 run-out day. Results: Iodine intake (mean ± SD: 54.6 ± 8.1, 142.3 ± 23.1, and 268.4 ± 32.6 μg/d), excretion (55.9 ± 8.6, 121.9 ± 21.7, and 228.7 ± 39.3 μg/d), and retention (−1.6 ± 8.3, 20.6 ± 21.6, and 39.8 ± 34.3 μg/d) differed among the low, middle, and high iodine IFM groups (P < 0.001 for all). There was a linear relation between daily iodine intake and both daily iodine excretion and daily iodine retention. Zero balance (iodine intake = iodine excretion, iodine retention = 0 μg/d) was achieved at a daily iodine intake of 70 μg (95% CI: 60, 80 μg). Conclusion: Our data indicate the iodine requirement in 2- to 5-mo-old infants is 70 μg/d. Adding an allowance for accumulation of thyroidal iodine stores would produce an EAR of 72 μg and a recommended dietary allowance of 80 μg. This trial was registered at clinicaltrials.gov as NCT02045784. ISSN:0002-9165 ISSN:1938-3207

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-1&alpha, IFN-&gamma, plasma IL-1&beta, and TNF-&alpha, Fe lowered lung IL-1&alpha, IL-1&beta, TNF-&alpha, 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.

Background Adequate nutrition during pregnancy is important to ensure optimal birth outcomes, maternal health and offspring development. However, little is known about the dietary intake and nutritional status of pregnant women residing in urban South Africa. Therefore, the Nutrition during Pregnancy and Early Development (NuPED) cohort study was initiated to assess early nutrition-related exposures predictive of early childhood development in urban South Africa. Methods The aims of this prospective cohort study are: 1) to assess dietary intake and nutritional status of urban pregnant women in Johannesburg, South Africa, and 2) to determine associations with birth outcomes, measures of maternal health, as well as measures of offspring health and development. Pregnant women (

The iodine status of populations is conventionally assessed using spot urinary samples to obtain a median urinary iodine concentration (UIC) value, which is assessed against standard reference cut-offs. The assumption that spot UIC reflects daily iodine intake may be flawed because of high day-to-day variability and variable urinary volume outputs. This study aimed to compare iodine status in a sample of South African adults when determined by different approaches using a spot urine sample (median UIC (MUIC), predicted 24 h urinary iodine excretion (PrUIE) using different prediction equations) against measured 24 h urinary iodine excretion (mUIE). Both 24 h and spot urine samples were collected in a subsample of participants (n = 457, median age 55 year, range 18&ndash, 90 year) in the World Health Organization Study on global AGEing and adult health (SAGE) Wave 2 in South Africa, in 2015. Kawasaki, Tanaka, and Mage equations were applied to assess PrUIE from predicted urinary creatinine (PrCr) and spot UIC values. Adequacy of iodine intake was assessed by comparing PrUIE and mUIE to the Estimated Average Requirement of 95 &micro, g/day, while the MUIC cut-off was &lt, 100 &micro, g/L. Bland Altman plots assessed the level of agreement between measured and predicted UIE. Median UIC (130 &micro, g/L) indicated iodine sufficiency. The prediction equations had unacceptable bias for PrUIE compared to measured UIE. In a sample of adult South Africans, the use of spot UIC, presented as a group median value (MUIC) provided similar estimates of inadequate iodine status, overall, when compared to EAR assessed using measured 24 h iodine excretion (mUIE). Continued use of MUIC as a biomarker to assess the adequacy of population iodine intake appears warranted.

Zn status may affect fatty acid (FA) metabolism because it acts as a cofactor in FA desaturase and elongase enzymes. Zn supplementation affects the FA desaturases of Zn-deficient rats, but whether this occurs in humans is unclear. We evaluated the associations between baseline plasma Zn (PZn) concentration and plasma total phospholipid FA composition, as well as the effect of daily consumption of Zn-fortified water on FA status in Beninese children. A 20-week, double-blind randomised controlled trial was conducted in 186 school age children. The children were randomly assigned to receive a daily portion of Zn-fortified, filtered water delivering on average 2·8 mg Zn/d or non-fortified filtered water. Plasma total phospholipid FA composition was determined using capillary GLC and PZn concentrations by atomic absorption spectrometry. At baseline, PZn correlated positively with dihomo-γ-linolenic acid (DGLA,r0·182;P=0·024) and the DGLA:linoleic acid (LA) ratio (r0·293;Pr−0·211;P=0·009) and the arachidonic acid:DGLA ratio (r−0·170;P=0·036). With the intervention, Zn fortification increased nervonic acid (B: 0·109; 95 % CI 0·001, 0·218) in all children (n186) and more so in children who were Zn-deficient (n60) at baseline (B:0·230; 95 % CI 0·023, 0·488). In conclusion, in this study, Zn-fortified filtered water prevented the reduction of nervonic acid composition in the plasma total phospholipids of children, and this effect was stronger in Zn-deficient children. Thus, Zn status may play an important role in FA desaturation and/or elongation.

Accumulating evidence indicates that saturated fat intake is related to mortality risk increase, whereas unsaturated fat intake is associated with reduced mortality risk. The aim of the present study was to estimate the mortality risk reduction related to a dietary change from saturated fat to mono- or polyunsaturated fat intake. The American National Health and Nutrition Examination Surveys conducted between 1999 and 2010 were linked to the 2011 national US death registry resulting in an observational prospective mortality study. Proportional hazards Cox models were used to evaluate the association between saturated, monounsaturated and polyunsaturated fat with all-cause and cause-specific mortality. Substitution analysis was conducted to estimate an iso-energetic substitution of 10 % of the energy from dietary fat intake applied to the substitution of saturated fat with an equal amount of energy from monounsaturated or polyunsaturated fat. The highest tertile intakes of saturated fat resulted in an increased risk (12 %) of all-cause and specific-cause mortality, whereas the highest tertile intakes of polyunsaturated fat resulted in a reduced risk (7 %) of all-cause and specific-cause mortality when compared with the corresponding lowest tertile. Iso-energetic substitution revealed that a substitution of 10 % of energy (from total fat) from saturated fat to an equal amount of energy from monounsaturated or polyunsaturated fat resulted in a significant reduction of the mortality risk ranging from 4 to 8 %. Iso-energetic substitution of saturated fat with monounsaturated and polyunsaturated fat reduced all-cause and specific-cause mortality in US adults.

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

Many children, particularly from low- and middle-income countries, may suffer from both iron deficiency and inadequate omega-3 fatty acid intake due to poor quality diets. Both, iron and omega-3 fatty acids are important for the development and functioning of the brain and immune system. Using a translational research approach, we therefore investigated potential interactive effects of iron and omega-3 fatty acid deficiencies and supplementation on cognition and immune-related outcomes. Our results indicate that in children with iron deficiency and poor omega-3 fatty acid intake, it may be crucial to administer iron in combination with omega-3 long-chain polyunsaturated fatty acids to ensure optimal cognition and immune function.

Purpose of review Children from low- and middle-income countries are particularly vulnerable to develop iron deficiency and iron deficiency anaemia (IDA), which can be prevented or controlled with different iron intervention strategies. However, there is a debate on the efficacy and safety of iron interventions, especially in children from areas with a high infectious disease burden. This review provides an overview of recent trials that investigated the benefits and potential risks of iron interventions in children from low and middle-income countries. Recent findings Recent studies showed that intermittent iron supplementation is a promising strategy in reducing iron deficiency and IDA. Only a few studies investigated the effect of iron interventions on developmental outcomes, such as growth and cognition, and provided mixed results. An increasing number of studies reported that iron intervention increases morbidity and causes unfavourable shifts in the gut microbial composition along with increases in intestinal inflammation, particularly in children with a high infectious disease burden. Summary More studies in children from low and middle-income populations are needed that provide evidence for the beneficial effects of iron interventions on functional outcomes beyond alleviating iron deficiency and IDA, and that explore potential mechanisms underlying the negative effects of iron reported in recent trials.

Introduction Attempting to curb the rising epidemic of hypertension, South Africa implemented legislation in June 2016 mandating maximum sodium levels in a range of manufactured foods that contribute significantly to population salt intake. This natural experiment, comparing two African countries with and without salt legislation, will provide timely information on the impact of legislative approaches addressing the food supply to improve blood pressure in African populations. This article outlines the design of this ongoing prospective nested cohort study. Methods and analysis Baseline sodium intake was assessed in a nested cohort of the WHO Study on global AGEing and adult health (WHO-SAGE) wave 2 (2014–2015), a multinational longitudinal study on the health and well-being of adults and the ageing process. The South African cohort consisted of randomly selected households (n=4030) across the country. Spot and 24-hour urine samples are collected in a random subsample (n=1200) and sodium, potassium, creatinine and iodine analysed. Salt behaviour and sociodemographic data are captured using face-to-face interviews, alongside blood pressure and anthropometric measures. Ghana, the selected control country with no formal salt policy, provided a nested subsample (n=1200) contributing spot and 24-hour urine samples from the SAGE Ghana cohort (n=5000). Follow-up interviews and urine collection (wave 3) in both countries will take place in 2017 (postlegislation) to assess change in population-level sodium intake and blood pressure. Ethics and dissemination SAGE was approved by the WHO Ethics Review Committee (reference number RPC149) with local approval from the North-West University Human Research Ethics Committee and University of the Witwatersrand Human Research Ethics Committee (South Africa), and University of Ghana Medical School Ethics and Protocol Review Committee (Ghana). The results of the study will be published in peer-reviewed international journals, presented at national and international conferences, and summarised as research and policy briefs.

Allergy has been associated with altered fatty acid and inflammatory status. In this cross-sectional study of 321 rural iron deficient (ID) South African children (aged 6–11 years), a subsample (n=111) of children with parent-reported allergy data were divided into an allergic (n=30) and non-allergic (n=81) group and compared. PBMC arachidonic acid (ARA; P=0.010) and the PBMC ARA to dihomo-gamma-linolenic acid (DGLA) ratio (P=0.035) were lower in the allergic children. Plasma 12-hydroxyeicosatetraenoic acid and 17-hydroxydocosahexaenoic acid (17-HDHA) were higher (P=0.040 and 0.020, respectively) in the allergic group. Thus, a fatty acid composition and lipid mediator levels indicative of increased release of ARA from PBMC membranes, increased inflammation as well as the resolving thereof, were associated with parent-reported allergy symptoms. This study used baseline data of an intervention study which was registered at clinicaltrials.gov as NCT01092377.