The global burden of high fasting plasma glucose associated with zinc deficiency: Results of a systematic review and meta-analysis.

Non-communicable diseases (NCDs) account for the largest share of the global disease burden, and increasing evidence shows that zinc deficiency (ZD) contributes to NCDs by inducing oxidative stress, insulin resistance, and impaired lipid metabolism. A systematic review and meta-analysis was conducted to determine whether ZD was associated with fasting plasma glucose (FPG), a key risk factor for NCDs. A random effects meta-analysis was conducted to determine the strength of the association in the form of an odds ratio (OR) and subsequently the population attributable risk (PAR) with population prevalences of high FPG. The disease burden from high FPG attributable to ZD was expressed as disability adjusted life years (DALYS). Data from seven studies were obtained as part of the systematic review. The meta-analysis shows a significant (p<0.01) inverse relationship between ZD and high FPG (OR = 2.34; 95% CI: 1.16, 4.72). Globally, the PAR of ZD's contribution to high FPG is 6.7%, with approximately 8.2 million high FPG DALYs attributable to ZD. Cardiovascular diseases, diabetes, and chronic kidney diseases account for more than 90% of the total DALYs. Total DALYs attributable to ZD are largest in the "Southeast Asia, East Asia, and Oceania" and "High Income" Super Regions. While the disease burden is highest among populous countries (e.g., China, India, USA), the population-standardized DALYs are highest among island nations, particularly island nations in the South Pacific and Caribbean. While ZD accounts for a small share of the high FPG disease burden, the total number of DALYs far surpasses other estimates of the disease burden attributable to ZD, which focus on diarrheal diseases in childhood. Zinc interventions are urgently needed to help address the increasing disease burden from NCDs, and the double burden of malnutrition.

Factors associated with nutrition intervention adherence: Evidence from a cluster-randomised controlled trial in Kenya.

Nutrition experts point to the importance of a multipronged approach to address high stunting rates in rural areas. This can include nutrition-specific and -sensitive interventions, such as the provision of micronutrient powder, eggs, and chlorine, and nutrition training to improve feeding practices. In 2018, an agricultural nongovernmental organisation initiated a multipronged approach as part of a randomised trial. However, adherence to a programme with so many components can be challenging for participants. The aim of this study is to understand which factors are associated with high adherence in complex multifaceted nutrition-sensitive agricultural programmes. We used a mixed method approach in which we used bivariate and multivariable analyses to estimate the relationship between child and caregiver demographic factors with product adherence. We analyzed data from six focus groups and 120 feedback sessions on barriers to product adherence. We found that the age and sex of the child did not influence product adherence, but caregivers were more likely to adhere to all products if they were not the child's biological mother (most often grandmothers) (0.28 higher adherence score; p < 0.001) and if caregivers were older (0.34 higher adherence score, p < 0.001). A higher monthly training attendance, combining product distribution and interactive training, predicted stronger product adherence. Participants noted that adherence was supported by the early demonstration of positive results, regular reminders, interactive trainings, and the encouragement of family members. These findings underscore the importance of combining product distribution with training and include potentially targeting grandmothers and other caregivers who may demonstrate higher product adherence.

Hepcidin-guided screen-and-treat interventions for young children with iron-deficiency anaemia in The Gambia: an individually randomised, three-arm, double-blind, controlled, proof-of-concept, non-inferiority trial.

BACKGROUND: Iron deficiency is the most prevalent nutritional disorder worldwide. Iron supplementation has modest efficacy, causes gastrointestinal side-effects that limit compliance, and has been associated with serious adverse outcomes in children across low-income settings. We aimed to compare two hepcidin-guided screen-and-treat regimens designed to reduce overall iron dosage by targeting its administration to periods when children were safe and ready to receive iron supplementation, with WHO's recommendation of universal iron supplementation. METHODS: We conducted an individually randomised, three-arm, double-blind, controlled, proof-of-concept, non-inferiority trial in 12 rural communities across The Gambia. Eligible participants were children aged 6-23 months with anaemia. Participants were randomly assigned (1:1:1) to either the WHO recommended regimen of one sachet of multiple micronutrient powder (MMP) daily containing 12·0 mg iron as encapsulated ferrous fumarate (control group); to MMP with 12·0 mg per day iron for the next 7 days if plasma hepcidin concentration was less than 5·5 µg/L, or to MMP without iron for the next 7 days if plasma hepcidin concentration was at least 5·5 µg/L (12 mg screen-and-treat group); or to MMP with 6·0 mg per day iron for the next 7 days if plasma hepcidin concentration was less than 5·5 µg/L, or to MMP without iron for the next 7 days if plasma hepcidin concentration was at least 5·5 µg/L (6 mg screen-and-treat group). Randomisation was done by use of a permuted block design (block size of 9), with stratification by haemoglobin and age, using computer-generated numbers. Participants and the research team (except for the data manager) were masked to group allocation. The primary outcome was haemoglobin concentration, with a non-inferiority margin of -5 g/L. A per-protocol analysis, including only children who had consumed at least 90% of the supplements (ie, supplement intake on ≥75 days during the study), was done to assess non-inferiority of the primary outcome at day 84 using a one-sided t test adjusted for multiple comparisons. Safety was assessed by use of ex-vivo growth tests of Plasmodium falciparum in erythrocytes and three species of sentinel bacteria in plasma samples from participants. This trial is registered with the ISRCTN registry, ISRCTN07210906. FINDINGS: Between April 23, 2014, and Aug 7, 2015, we prescreened 783 children, of whom 407 were enrolled into the study: 135 were randomly assigned to the control group, 136 to the 12 mg screen-and-treat group, and 136 to the 6 mg screen-and-treat group. 345 (85%) children were included in the per-protocol population: 115 in the control group, 116 in the 12 mg screen-and-treat group, and 114 in the 6 mg screen-and-treat group. Directly observed adherence was high across all groups (control group 94·8%, 12 mg screen-and-treat group 95·3%, and 6 mg screen-and-treat group 95·0%). 82 days of iron supplementation increased mean haemoglobin concentration by 7·7 g/L (95% CI 3·2 to 12·2) in the control group. Both screen-and-treat regimens were significantly less efficacious at improving haemoglobin (-5·6 g/L [98·3% CI -9·9 to -1·3] in the 12 mg screen-and-treat group and -7·8 g/L [98·3% CI -12·2 to -3·5] in the 6 mg screen-and-treat group) and neither regimen met the preset non-inferiority margin of -5 g/L. The 12 mg screen-and-treat regimen reduced iron dosage to 6·1 mg per day and the 6 mg screen-and-treat regimen reduced dosage to 3·0 mg per day. 580 adverse events were observed in 316 participants, of which eight were serious adverse events requiring hospitalisation mainly due to diarrhoeal disease (one [1%] participant in the control group, three [2%] in the 12 mg screen-and-treat group, and four [3%] in the 6 mg screen-and-treat group). The most common causes of non-serious adverse events (n=572) were diarrhoea (145 events [25%]), upper respiratory tract infections (194 [34%]), lower respiratory tract infections (62 [11%]), and skin infections (122 [21%]). No adverse events were deemed to be related to the study interventions. INTERPRETATION: The hepcidin-guided screen-and-treat strategy to target iron administration succeeded in reducing overall iron dosage, but was considerably less efficacious at increasing haemoglobin and combating iron deficiency and anaemia than was WHO's standard of care, and showed no differences in morbidity or safety outcomes. FUNDING: Bill & Melinda Gates Foundation and UK Medical Research Council.

Co-Occurrence of Overweight/Obesity, Anemia and Micronutrient Deficiencies among Non-Pregnant Women of Reproductive Age in Ghana: Results from a Nationally Representative Survey.

Overweight/obesity (OWOB) often co-occurs with anemia or micronutrient deficiencies (MNDs) among women of reproductive age (WRA) in Ghana; identifying the risk factors of these conditions is essential for prevention. We aimed to examine the prevalence of OWOB, anemia, and MNDs and their co-occurrence and risk factors among non-pregnant women 15-49 years of age in Ghana. Data were from a 2017 two-stage national survey of 1063 women. We estimated the weighted prevalence of single and co-occurring malnutrition, and used logistic regression to explore risk factors. The prevalence of OWOB, anemia, and ≥1 MND was 39%, 22%, and 62%, respectively; that of OWOB co-occurring with anemia was 6.7%, and OWOB co-occurring with ≥1 MND was 23.6%. There was no significant difference between observed and expected prevalence of co-occurrence OWOB with anemia or MND. Risk factors were: living in southern (vs. northern) belt, high- (vs. low-) wealth household, being ≥ 25 years old, and being married (vs. single) for OWOB, and living in northern (vs. southern) belt and medium- (vs. low-) wealth household for anemia and ≥1 MND, respectively. Different interventions are required for addressing OWOB in WRA than those for anemia and MNDs.

Effectiveness of an integrated agriculture, nutrition-specific, and nutrition-sensitive program on child growth in Western Kenya: a cluster-randomized controlled trial.

BACKGROUND: Stunting rates remain unacceptably high in many regions, including sub-Saharan Africa. Agricultural programs have led to increased yields and household incomes but showed limited success in improving nutritional status. OBJECTIVES: We assessed whether linear growth could be improved through a potentially scalable, integrated program adding nutrition-specific and nutrition-sensitive components to an existing agricultural program. METHODS: In this cluster-randomized controlled trial in rural Western Kenya, we randomized children aged 6-35 months from farming families to an agricultural intervention without (control group) or with a bundle of interventions (intervention group), including distribution of micronutrient powders (MNP), poultry to increase egg consumption, seeds of greens and onions, and soap and chlorine solution, as well as provision of monthly behavior change trainings. The primary outcome was the change in height-for-age z-score (HAZ) over 2 years of follow-up. We assessed safety through active morbidity and passive adverse event monitoring. We conducted an intention-to-treat analysis, followed by per-protocol and prespecified subgroup analyses. RESULTS: From March to April 2018, we enrolled 1927 children from 126 clusters (control, 942 children in 63 clusters; intervention, 985 children in 63 clusters). Data on HAZ were available for 1672 (86.6%) children after 2 years. Adherence was >80% for use of MNP, chlorine, and greens and receipt of soap, and ∼40% for egg and red onion consumption. The intention-to-treat analysis indicated a greater change in HAZ over 2 years in the intervention group (adjusted effect size, 0.11; 95% CI: 0.02-0.19). We found a slightly stronger effect in the per-protocol analysis (adjusted effect size, 0.15; 95% CI: 0.06-0.24). Dietary diversity and consumption of iron-rich foods were improved in the intervention group, and reported instances of fever, lower respiratory tract infections, and diarrheal episodes were lower in the intervention group. CONCLUSIONS: This study found a modest improvement in linear growth, indicating the need for multiple, integrated interventions to achieve benefits. The trial was registered with clinicaltrials.gov as NCT03448484.

Risk factors of stunting and wasting in Somali pre-school age children: results from the 2019 Somalia micronutrient survey.

BACKGROUND: Stunting and wasting in children less than 5 years of age are two key indicators of child malnutrition. Reducing their prevalence is a priority of the global public health community and for Somalia, a country suffering complex humanitarian emergencies such as drought, flooding, conflict and large-scale displacements. METHODS: Data from the nationally representative cross-sectional Somalia Micronutrient Survey (SMS 2019) on 1947 children were analyzed to assess the prevalence and potential risk factors of stunting and wasting. Bivariate and multivariable analyses were conducted separately for children 0-5 months and 6-59 months, and population attributable fractions were calculated using adjusted risk ratios produced by Poisson regression models. RESULTS: Among the 1947 children, the prevalence of stunting and wasting were 17.2% (95% CI: 15.0, 19.6) and 11.0% (95% CI: 9.3, 12.9), respectively. Among children 6-59 months of age, those residing in severely food insecure households had a higher risk of stunting (adjusted risk ratio [aRR] 1.47; CI: 1.12, 1.93) compared to those in food secure households. This risk of stunting was also higher in children with inflammation (aRR 1.75; CI: 1.35, 2.25) and iron deficiency (ID) (aRR 2.09; CI: 1.58, 2.80). For wasting, a dose-response relationship was found with household wealth, with the risk of wasting increasing significantly as the household wealth quintile decreased. On the other hand, the risk of wasting was lower in iron-deficient children (aRR 0.69; CI: 0.49, 0.98) than in iron-replete children. Among children 0-5 months of age no variables remained statistically significantly associated with stunting in the multivariable analysis. Wasting, however, was more common in children with recent diarrhea (aRR 3.51; CI: 1.68, 7.36). CONCLUSIONS: Nutritional status of children in Somalia may be improved by prevention of diarrhea and other infections and improvements in household food security.

Effect of parboiling conditions on zinc and iron retention in biofortified and non-biofortified milled rice.

BACKGROUND: Zinc-biofortified rice could contribute to zinc intake in deficient populations, but processing it into parboiled rice could affect this potential benefit. Zinc and iron true retention (TR) in milled rice produced under conditions resembling household and commercial parboiled methods was evaluated. Zinc and iron TR in milled rice obtained from biofortified and non-biofortified rice subjected to different soaking temperatures during parboiling was also evaluated. RESULTS: Conditions resembling commercial parboiling methods resulted in 52.2-59.7% zinc TR and 55.4-79.1% iron TR, whereas those used for household parboiling resulted in 70.7-79.6% zinc TR and 78.2-119.8% iron TR. Zinc TR in milled (8-16% bran removal) biofortified and non-biofortified parboiled rice was 50.6-66.8% when soaking rough rice at 20 °C and 29.9-56.0% when soaking rough rice at 65 °C; both had lower zinc TR than non-parboiled rice (58.0-80.6%). Iron TR was generally similar between milled non-parboiled and parboiled rice (26.2-67.6%) and between parboiled biofortified and non-biofortified milled rice. CONCLUSION: Parboiling conditions used to obtain milled rice targeted for own household consumption resulted in higher zinc and iron TR compared to parboiling conditions used for milled rice targeted for markets. More zinc from the inner endosperm moved towards the outer layers at high soaking temperature, resulting in lower zinc TR for milled parboiled rice soaked in hotter water. Parboiled rice soaked at temperatures used in households could provide more zinc to diets compared to rice soaked in hotter water commonly used in large rice mills, especially when rice is extensively milled. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Complementary Feeding Indicators in Relation to Micronutrient Status of Ghanaian Children Aged 6-23 Months: Results from a National Survey.

BACKGROUND: Optimal complementary feeding is critical for adequate growth and development in infants and young children. The associations between complementary feeding and growth have been studied well, but less is known about the relationship between complementary feeding and micronutrient status. METHODS: Using data from a national cross-sectional survey conducted in Ghana in 2017, we examined how multiple WHO-recommended complementary feeding indicators relate to anemia and the micronutrient status of children aged 6-23 months. RESULTS: In total, 42%, 38%, and 14% of the children met the criteria for minimum dietary diversity (MDD), minimum meal frequency (MMF), and minimum acceptable diet (MAD), respectively. In addition, 71% and 52% of the children consumed iron-rich foods and vitamin A-rich foods, respectively. The prevalence of anemia, iron deficiency (ID), iron deficiency anemia (IDA) and vitamin A deficiency (VAD) was 46%, 45%, 27%, and 10%, respectively. Inverse associations between MMF and socio-economic status were found, and MMF was associated with an increased risk of ID (55%; p < 0.013) and IDA (38%; p < 0.002). CONCLUSION: The pathways connecting complementary feeding and micronutrient status are complex. Findings related to MMF should be further investigated to ensure that complementary feeding programs account for the potential practice of frequent feeding with nutrient-poor foods.

Prevalence and co-existence of cardiometabolic risk factors and associations with nutrition-related and socioeconomic indicators in a national sample of Gambian women.

Cardiovascular diseases (CVD) are on the rise in Sub-Saharan Africa, and a large proportion of the adult population is thought to suffer from at least one cardiometabolic risk factor. This study assessed cardiometabolic risk factors and the contribution of nutrition-related indicators in Gambian women. The prevalence and co-existence of diabetes (elevated glycated hemoglobin (HbA1c ≥ 6.5%) or prediabetes (HbA1c ≥ 5.7% to < 6.5%), hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg), obesity (body mass index (BMI) ≥ 30.0) and inflammation (C-reactive protein (CRP) > 3 mg/L or alpha-1-acid glycoprotein (AGP) > 1 g/L) and the contribution of nutrition related and socioeconomic indicators were measured in non-pregnant women 15-49 years of age in the Gambia using data from a nationally representative cross-sectional stratified survey. Nationally, 54.5% (95% CI: 47.4, 61.4) of 1407 women had elevated HbA1c. Of these, 14.9% were diabetic and 85.1% were prediabetic. Moreover, 20.8% (95% CI 17.8, 20.0) of 1685 women had hypertension, 11.1% (95% CI 9.0, 13.7) of 1651 were obese and 17.2% (95% CI 5.1, 19.6) of 1401 had inflammation. At least one of the aforementioned cardiometabolic risk factor was present in 68.3% (95% CI 63.0, 73.1) of women. Obesity increased the risk of hypertension (aRR 1.84; 95% CI 1.40, 2.41), diabetes (aRR 1.91; 95% CI 1.29, 2.84), elevated HbA1c (aRR 1.31; 95% CI 1.14, 1.51) and inflammation (aRR 3.47; 95% CI 2.61, 4.61). Inflammation increased the risk of hypertension (aRR 1.42; 95% CI 1.14, 1.78). Aging increased the risk of hypertension, obesity and inflammation. Further, inadequate sanitation increased the risk for diabetes (aRR 1.65; 95% CI 1.17, 2.34) and iron deficiency increased the risk of elevated HbA1c (aRR 1.21; 95% CI 1.09, 1.33). The high prevalence of cardiometabolic risk factors and their co-existence in Gambian women is concerning. Although controlling obesity seems to be key, multifaceted strategies to tackle the risk factors separately are warranted to reduce the prevalence or minimize the risk of CVD.

Malaria is a cause of iron deficiency in African children.

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID1. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria2, as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n = 7,453), but not among individuals living in malaria-free areas (n = 3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%.

Measurement of long-term iron absorption and loss during iron supplementation using a stable isotope of iron (57 Fe).

We report the first measurements of long-term iron absorption and loss during iron supplementation in African children using a stable isotope of iron (57 Fe). After uniform labelling of body iron with 57 Fe, iron absorption is proportional to the rate of decrease in the 57 Fe tracer concentration, while iron loss is proportional to the rate of decrease in the 57 Fe tracer amount. Anaemic Gambian toddlers were given 2 mg 57 Fe orally to equilibrate with total body iron over 8-11 months. After assignment to the positive control arm of the HIGH study, 22 toddlers consumed a micronutrient powder containing 12 mg iron for 12 weeks followed by 12 weeks without iron supplementation. Their daily iron absorption increased 3·8-fold during the iron supplementation period compared to the control period [median (interquartile range, IQR): 1·00 (0·82; 1·28) mg/day vs. 0·26 (0·22; 0·35) mg/day; P = 0·001]. Unexpectedly, during the supplementation period, daily iron loss also increased by 3·4-fold [0·75 (0·55; 0·87) mg/day vs. 0·22 (0·19; 0·29) mg/day; P = 0·005]. Consequently, most (~72%) of the absorbed iron was lost during supplementation. Long-term studies of iron absorption and loss are a promising and accurate method for assessing and quantifying long-term iron balance and may provide a reference method for evaluating iron intervention programs in vulnerable population groups. This study was registered as ISRCTN 0720906.

Risk factors for anaemia among Ghanaian women and children vary by population group and climate zone.

Anaemia has serious effects on human health and has multifactorial aetiologies. This study aimed to determine putative risk factors for anaemia in children 6-59 months and 15- to 49-year-old non-pregnant women living in Ghana. Data from a nationally representative cross-sectional survey were analysed for associations between anaemia and various anaemia risk factors. National and stratum-specific multivariable regressions were constructed separately for children and women to calculate the adjusted prevalence ratio (aPR) for anaemia of variables found to be statistically significantly associated with anaemia in bivariate analysis. Nationally, the aPR for anaemia was greater in children with iron deficiency (ID; aPR 2.20; 95% confidence interval [CI]: 1.88, 2.59), malaria parasitaemia (aPR 1.96; 95% CI: 1.65, 2.32), inflammation (aPR 1.26; 95% CI: 1.08, 1.46), vitamin A deficiency (VAD; aPR 1.38; 95% CI: 1.19, 1.60) and stunting (aPR 1.26; 95% CI: 1.09, 1.46). In women, ID (aPR 4.33; 95% CI: 3.42, 5.49), VAD (aPR 1.61; 95% CI: 1.24, 2.09) and inflammation (aPR 1.59; 95% CI: 1.20, 2.11) were associated with anaemia, whereas overweight and obese women had lower prevalence of anaemia (aPR 0.74; 95% CI: 0.56, 0.97). ID was associated with child anaemia in the Northern and Middle belts, but not in the Southern Belt; conversely, inflammation was associated with anaemia in both children and women in the Southern and Middle belts, but not in the Northern Belt. Anaemia control programmes should be region specific and aim at the prevention of ID, malaria and other drivers of inflammation as they are the main predictors of anaemia in Ghanaian children and women.

Variability in haemoglobin concentration by measurement tool and blood source: an analysis from seven countries.

OBJECTIVE: We explore factors such as the blood sampling site (capillary vs venous), the equipment (HemoCue vs automated haematology analyser) and the model of the HemoCue device (201+ vs 301) that may impact haemoglobin measurements in capillary and venous blood. METHODS: Eleven studies were identified, and bias, concordance and measures of diagnostic performance were assessed within each study. FINDINGS: Our analysis included 11 studies from seven countries (Cambodia, India, The Gambia, Ghana, Laos, Rwanda and USA). Samples came from children, men, non-pregnant women and pregnant women. Mean bias ranged from -8.7 to 2.5 g/L in Cambodian women, 6.2 g/L in Laotian children, 2.4 g/L in Ghanaian women, 0.8 g/L in Gambian children 6-23 months and 1.4 g/L in Rwandan children 6-59 months when comparing capillary blood on a HemoCue to venous blood on a haematology analyser. Bias was 8.3 g/L in Indian non-pregnant women and 2.6 g/L in Laotian children and women and 1.5 g/L in the US population when comparing capillary to venous blood using a HemoCue. For venous blood measured on the HemoCue compared with the automated haematology analyser, bias was 5.3 g/L in Gambian pregnant women 18-45 years and 11.3 g/L in Laotian children 6-59 months. CONCLUSION: Our analysis found large variability in haemoglobin concentration measured on capillary or venous blood and using HemoCue Hb 201+ or Hb 301 or automated haematology analyser. We cannot ascertain whether the variation is due to differences in the equipment, differences in capillary and venous blood, or factors affecting blood collection techniques.

Iron Absorption from Iron-Biofortified Sweetpotato Is Higher Than Regular Sweetpotato in Malawian Women while Iron Absorption from Regular and Iron-Biofortified Potatoes Is High in Peruvian Women.

BACKGROUND: Sweetpotato and potato are fast-maturing staple crops and widely consumed in low- and middle-income countries. Conventional breeding to biofortify these crops with iron could improve iron intakes. To our knowledge, iron absorption from sweetpotato and potato has not been assessed. OBJECTIVE: The aim was to assess iron absorption from regular and iron-biofortified orange-fleshed sweetpotato in Malawi and yellow-fleshed potato and iron-biofortified purple-fleshed potato in Peru. METHODS: We conducted 2 randomized, multiple-meal studies in generally healthy, iron-depleted women of reproductive age. Malawian women (n = 24) received 400 g regular or biofortified sweetpotato test meals and Peruvian women (n = 35) received 500 g regular or biofortified potato test meals. Women consumed the meals at breakfast for 2 wk and were then crossed over to the other variety. We labeled the test meals with 57Fe or 58Fe and measured cumulative erythrocyte incorporation of the labels 14 d after completion of each test-meal sequence to calculate iron absorption. Iron absorption was compared by paired-sample t tests. RESULTS: The regular and biofortified orange-fleshed sweetpotato test meals contained 0.55 and 0.97 mg Fe/100 g. Geometric mean (95% CI) fractional iron absorption (FIA) was 5.82% (3.79%, 8.95%) and 6.02% (4.51%, 8.05%), respectively (P = 0.81), resulting in 1.9-fold higher total iron absorption (TIA) from biofortified sweetpotato (P < 0.001). The regular and biofortified potato test meals contained 0.33 and 0.69 mg Fe/100 g. FIA was 28.4% (23.5%, 34.2%) from the regular yellow-fleshed and 13.3% (10.6%, 16.6%) from the biofortified purple-fleshed potato meals, respectively (P < 0.001), resulting in no significant difference in TIA (P = 0.88). CONCLUSIONS: FIA from regular yellow-fleshed potato was remarkably high, at 28%. Iron absorbed from both potato test meals covered 33% of the daily absorbed iron requirement for women of reproductive age, while the biofortified orange-fleshed sweetpotato test meal covered 18% of this requirement. High polyphenol concentrations were likely the major inhibitors of iron absorption. These trials were registered at www.clinicaltrials.gov as NCT03840031 (Malawi) and NCT04216030 (Peru).

Risk Factors for Anemia and Micronutrient Deficiencies among Women of Reproductive Age-The Impact of the Wheat Flour Fortification Program in Uzbekistan.

Food fortification can be effective in reducing the prevalence of anemia and micronutrient deficiencies. This study assessed risk factors for-and the impact of the wheat flour program in Uzbekistan on-anemia, and iron and folate deficiency (FD) in non-pregnant women (NPW) of reproductive age. National data were analyzed for risk factors using multivariable regression. Additional iron intake from fortified flour was not associated with iron deficiency (ID) and did not result in a significantly different prevalence of anemia regardless of the levels, whereas women with additional folic acid intake had a lower relative risk (RR) of FD (RR: 0.67 [95% CI: 0.53, 0.85]). RR for anemia was greater in women with ID (RR: 4.7; 95% CI: 3.5, 6.5) and vitamin A insufficiency (VAI; RR 1.5; 95% CI: 1.3, 1.9). VAI (RR: 1.4 [95% CI: 1.3, 1.6]) and breastfeeding (RR: 1.1 [95% CI: 0.99, 1.2]) were associated with increased risk of ID, while being underweight reduced the risk (RR: 0.74 [95% CI: 0.58, 0.96]). Breastfeeding (RR: 1.2 [95% CI: 1.1, 1.4]) and inflammation (RR: 1.2 [95% CI: 1.0, 1.3]) increased risk of FD. FD results indicate that the fortification program had potential for impact, but requires higher coverage of adequately fortified wheat flour and a more bioavailable iron fortificant.

Household Coverage with Adequately Iodized Salt and Iodine Status of Nonpregnant and Pregnant Women in Uzbekistan.

Background: Globally, iodine deficiency has been drastically reduced since the introduction of salt iodization programs; nonetheless, many populations remain at-risk for iodine deficiency. This study aimed to assess the iodine status among women of reproductive age in Uzbekistan and to identify factors associated with iodine deficiency, including the availability of adequately iodized salt at the household level. Methods: A cross-sectional household survey was conducted to produce region-specific estimates of the household coverage with adequately iodized salt and iodine status among women for each of the 14 regions in Uzbekistan. Other information, such as socioeconomic status, lactation and pregnancy, residence, age, and consumption of iodine supplements, was also collected. Results: Overall, 36% of 3413 households had adequately iodized salt (iodine concentration >15 ppm [parts per million (mg I/kg salt)]), 20% had inadequately iodized salt (5-14 ppm), and 44% had salt without detectable iodine (<5 ppm). Adequate iodization was found in 33.2% of the 2626 salt samples taken from retail packages labeled as "iodized," 36.5% of the 96 samples taken from retail packages without mention of iodization, and 50.5% of the 674 samples without the original packaging (p < 0.001). The median urinary iodine concentration (UIC) of 140.9 µg/L (95% confidence interval [CI 132.4-150.7]) in nonpregnant nonlactating women indicated adequate iodine status, while for nonpregnant lactating and pregnant women, the median UIC of 112.9 µg/L [CI 99.3-128.4] and 117.3 µg/L [CI 101.8-139.9], respectively, indicated borderline adequacy. Significant differences in UIC (p < 0.001) were found between nonpregnant nonlactating women living in households with adequately iodized salt (UIC 208.9 µg/L), inadequately iodized salt (UIC 139.1 µg/L), and noniodized salt (UIC 89.9 µg/L). Conclusions: Coverage with adequately iodized salt is low in Uzbekistan, and women in households with poorly iodized salt have substantially worse iodine status; claims on packaging about salt iodization do not reflect salt iodine content. This highlights the importance and effectiveness of salt iodization and the need to strengthen this program in Uzbekistan.

Anemia, micronutrient deficiencies, malaria, hemoglobinopathies and malnutrition in young children and non-pregnant women in Ghana: Findings from a national survey.

Nationally representative data on the micronutrient status of Ghanaian women and children are very scarce. We aimed to document the current national prevalence of micronutrient deficiencies, anemia, malaria, inflammation, α-thalassemia, sickle cell disease and trait, and under- and over-nutrition in Ghana. In 2017, a two-stage cross-sectional design was applied to enroll pre-school children (6-59 months) and non-pregnant women (15-49 years) from three strata in Ghana: Northern, Middle and Southern Belt. Household and individual questionnaire data were collected along with blood samples. In total, 2123 households completed the household interviews, 1165 children and 973 women provided blood samples. Nationally, 35.6% (95%CI: 31.7,39.6) of children had anemia, 21.5% (18.4,25.0) had iron deficiency, 12.2% (10.1,14.7) had iron deficiency anemia, and 20.8% (18.1,23.9) had vitamin A deficiency; 20.3%(15.2,26.6) tested positive for malaria, 13.9% (11.1,17.3) for sickle trait plus disease, and 30.7% (27.5,34.2) for α-thalassemia. Anemia and micronutrient deficiencies were more prevalent in rural areas, poor households and in the Northern Belt. Stunting and wasting affected 21.4% (18.0,25.2) and 7.0% (5.1,9.5) of children, respectively. Stunting was more common in rural areas and in poor households. Among non-pregnant women, 21.7% (18.7,25.1) were anemic, 13.7% (11.2,16.6) iron deficient, 8.9% (6.7,11.7) had iron deficiency anemia, and 1.5% (0.8,2.9) were vitamin A deficient, 53.8% (47.6,60.0) were folate deficient, and 6.9% (4.8,9.8) were vitamin B12 deficient. Malaria parasitemia in women [8.4% (5.7,12.2)] was lower than in children, but the prevalence of sickle cell disease or trait and α-thalassemia were similar. Overweight [24.7% (21.0,28.8)] and obesity [14.3% (11.5,17.7)] were more common in wealthier, older, and urban women. Our findings demonstrate that anemia and several micronutrient deficiencies are highly present in Ghana calling for the strengthening of Ghana's food fortification program while overweight and obesity in women are constantly increasing and need to be addressed urgently through governmental policies and programs.

Hepcidin mediates hypoferremia and reduces the growth potential of bacteria in the immediate post-natal period in human neonates.

Septicemia is a leading cause of death among neonates in low-income settings, a situation that is deteriorating due to high levels of antimicrobial resistance. Novel interventions are urgently needed. Iron stimulates the growth of most bacteria and hypoferremia induced by the acute phase response is a key element of innate immunity. Cord blood, which has high levels of hemoglobin, iron and transferrin saturation, has hitherto been used as a proxy for the iron status of neonates. We investigated hepcidin-mediated redistribution of iron in the immediate post-natal period and tested the effect of the observed hypoferremia on the growth of pathogens frequently associated with neonatal sepsis. Healthy, vaginally delivered neonates were enrolled in a cohort study at a single center in rural Gambia (N = 120). Cord blood and two further blood samples up to 96 hours of age were analyzed for markers of iron metabolism. Samples pooled by transferrin saturation were used to conduct ex-vivo growth assays with Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli and Klebsiella pneumonia. A profound reduction in transferrin saturation occurred within the first 12 h of life, from high mean levels in cord blood (47.6% (95% CI 43.7-51.5%)) to levels at the lower end of the normal reference range by 24 h of age (24.4% (21.2-27.6%)). These levels remained suppressed to 48 h of age with some recovery by 96 h. Reductions in serum iron were associated with high hepcidin and IL-6 levels. Ex-vivo growth of all sentinel pathogens was strongly associated with serum transferrin saturation. These results suggest the possibility that the hypoferremia could be augmented (e.g. by mini-hepcidins) as a novel therapeutic option that would not be vulnerable to antimicrobial resistance. Trial registration: The original trial in which this study was nested is registered at ISRCTN, number 93854442.

Hepcidin-guided screen-and-treat interventions against iron-deficiency anaemia in pregnancy: a randomised controlled trial in The Gambia.

BACKGROUND: WHO recommends daily iron supplementation for pregnant women, but adherence is poor because of side-effects, effectiveness is low, and there are concerns about possible harm. The iron-regulatory hormone hepcidin can signal when an individual is ready-and-safe to receive iron. We tested whether a hepcidin-guided screen-and-treat approach to combat iron-deficiency anaemia could achieve equivalent efficacy to universal administration, but with lower exposure to iron. METHODS: We did a three-arm, randomised, double-blind, non-inferiority trial in 19 rural communities in the Jarra West and Kiang East districts of The Gambia. Eligible participants were pregnant women aged 18-45 years at between 14 weeks and 22 weeks of gestation. We randomly allocated women to either WHO's recommended regimen (ie, a daily UN University, UNICEF, and WHO international multiple-micronutrient preparation [UNIMMAP] containing 60 mg iron), a 60 mg screen-and-treat approach (ie, daily UNIMMAP containing 60 mg iron for 7 days if weekly hepcidin was <2·5 µg/L or UNIMMAP without iron if hepcidin was ≥2·5 µg/L), or a 30 mg screen-and-treat approach (ie, daily UNIMMAP containing 30 mg iron for 7 days if weekly hepcidin was <2·5 µg/L or UNIMMAP without iron if hepcidin was ≥2·5 µg/L). We used a block design stratified by amount of haemoglobin at enrolment (above and below the median amount of haemoglobin on every enrolment day) and stage of gestation (14-18 weeks vs 19-22 weeks). Participants and investigators were unaware of the random allocation. The primary outcome was the amount of haemoglobin at day 84 and was measured as the difference in haemoglobin in each screen-and-treat group compared with WHO's recommended regimen; the non-inferiority margin was set at -5·0 g/L. The primary outcome was assessed in the per-protocol population, which comprised all women who completed the study. This trial is registered with the ISRCTN registry, number ISRCTN21955180. FINDINGS: Between June 16, 2014, and March 3, 2016, 498 participants were randomised, of whom 167 were allocated to WHO's recommended regimen, 166 were allocated to the 60 mg per day screen-and-treat approach, and 165 were allocated to the 30 mg per day screen-and-treat approach. 78 participants were withdrawn or lost to follow-up during the study; thus, the per-protocol population comprised 140 women assigned to WHO's recommended regimen, 133 allocated to the 60 mg screen-and-treat approach, and 147 allocated to the 30 mg screen-and-treat approach. The screen-and-treat approaches did not exceed the non-inferiority margin. Compared with WHO's recommended regimen, the difference in the amount of haemoglobin at day 84 was -2·2 g/L (95% CI -4·6 to 0·1) with the 60 mg screen-and-treat approach and -2·7 g/L (-5·0 to -0·5) with the 30 mg screen-and-treat approach. Adherence, reported side-effects, and adverse events were similar between the three groups. The most frequent side-effect was stomachache, which was similar in the 60 mg screen-and-treat group (82 cases per 1906 person-weeks) and with WHO's recommended regimen (81 cases per 1974 person-weeks; effect 1·0, 95% CI 0·7 to 1·6); in the 30 mg screen-and-treat group the frequency of stomachache was slightly lower than with WHO's recommended regimen (58 cases per 2009 person-weeks; effect 0·7, 95% CI 0·5 to 1·1). No participants died during the study. INTERPRETATION: The hepcidin-guided screen-and-treat approaches had no advantages over WHO's recommended regimen in terms of adherence, side-effects, or safety outcomes. Our results suggest that the current WHO policy for iron administration to pregnant women should remain unchanged while more effective approaches continue to be sought. FUNDING: Bill & Melinda Gates Foundation and the UK Medical Research Council.