The IHAT-GUT Iron Supplementation Trial in Rural Gambia: Barriers,Facilitators, and Benefits

Introduction: In most sub-Saharan African countries iron deficiency anaemia remains highly prevalent in children and this has not changed in the last 25 years. Supplementation with iron hydroxide adipate tartrate (IHAT) was being investigated in anaemic children in a phase two clinical trial (termed IHAT-GUT), conducted at the Medical Research Council Unit the Gambia at the London School of Hygiene and Tropical Medicine (LSHTM) (abbreviated as MRCG hereof). This qualitative study aimed to explore the personal perceptions of the trial staff in relation to conducting a clinical trial in such settings in order to highlight the health system specific needs and strengths in the rural, resource-poor setting of the Upper River Region in the Gambia. Methods: Individual interviews (n = 17) were conducted with local trial staff of the IHAT-GUT trial. Data were analysed using inductive thematic analysis. Results: Potential barriers and facilitators to conducting this clinical trial were identified at the patient, staff, and trial management levels. Several challenges, such as the rural location and cultural context, were identified but noted as not being long-term inhibitors. Participants believed the facilitators and benefits outnumbered the barriers, and included the impact on education and healthcare, the ambitious and knowledgeable locally recruited staff, and the local partnership. Conclusions: While facilitators and barriers were identified to conducting this clinical trial in a rural, resource-poor setting, the overall impact was perceived as beneficial, and this study is a useful example of community involvement and partnership for further health improvement programs. To effectively implement a nutrition intervention, the local health systems and context must be carefully considered through qualitative research beforehand.     

Multiple Micronutrients,Including Zinc,Selenium and Iron,Are Positively Associated with Anemia in New Zealand Aged Care Residents

Anemia is a significant comorbidity for older adults not fully attributable to iron deficiency. Low-grade inflammation and other micronutrient deficiencies also contribute. This cross-sectional study examined the relationships between nutrient and non-nutrient factors with hemoglobin and anemia in 285 residents (>65 years) of 16 New Zealand aged-care facilities. Blood samples were analyzed for hemoglobin, ferritin, sTfR, hepcidin, zinc, selenium, and interleukin-6 (IL-6), (with ferritin, sTfR, zinc and selenium adjusted for inflammation). Linear regression models examined the relationships between micronutrient biomarkers (iron, zinc, selenium, vitamin B-12 and D), age, sex, and health factors with hemoglobin. Thirty-two percent of participants exhibited anemia, although <2% had either depleted iron stores or iron deficiency. Plasma zinc and selenium deficiencies were present in 72% and 38% of participants, respectively. Plasma zinc and total body iron (TBI) were positively associated (p < 0.05) with hemoglobin, while gastric acid suppressing medications, hepcidin, and interleukin-6 were inversely associated. These relationships were maintained after the application of anemia cut-offs. These findings emphasize the importance of considering multiple micronutrient deficiencies as risk factors for anemia.     

Zinc Nutritional Status in a Series of Children with Chronic Diseases: A Cross-Sectional Study

Background: Zinc is an essential trace element for the normal growth and development of human beings. The main objective was to evaluate the nutritional status of zinc and its association with nutritional indicators in a series of children with chronic diseases. Methods: The prevalence of patients with dietary zinc deficiency or deficit zinc intake (<80% DRI: dietary reference intake) was analyzed through prospective 72 h dietary surveys, and serum zinc deficiency or hypozincemia (≤70 µg/dL in children under 10 years of age in both sexes and in females older than 10 years and <74 μg/dL in males older than 10 years) was measured through atomic absorption spectrophotometry. The participants were classified according to their nutritional status by body mass index (BMI). Results: Mean serum zinc level in obese (87 µg/dL), undernourished (85 µg/dL), and eutrophic children (88 µg/dL) were normal, but in the undernutrition (60% DRI) and eutrophic (67% DRI) groups the mean dietary zinc intake was low compared to that in the obesity group (81% DRI). There were different associations between nutritional parameters, dietary zinc intake, and serum zinc. All patients with hypozincemia had dietary zinc deficiency. Conclusions: In the whole series, 69% of participants showed a zinc intake lower than recommended and might be at high risk of zinc deficiency.     

Postnatal Iron Supplementation with Ferrous Sulfate vs. Ferrous Bis-Glycinate Chelate: Effects on Iron Metabolism,Growth, and Central Nervous System Development in Sprague Dawley Rat Pups

Iron-fortified formulas and iron drops (both usually ferrous sulfate, FS) prevent early life iron deficiency, but may delay growth and adversely affect neurodevelopment by providing excess iron. We used a rat pup model to investigate iron status, growth, and development outcomes following daily iron supplementation (10 mg iron/kg body weight, representative of iron-fortified formula levels) with FS or an alternative, bioavailable form of iron, ferrous bis-glycinate chelate (FC). On postnatal day (PD) 2, sex-matched rat litters (n = 3 litters, 10 pups each) were randomly assigned to receive FS, FC, or vehicle control until PD 14. On PD 15, we evaluated systemic iron regulation and CNS mineral interactions and we interrogated iron loading outcomes in the hippocampus, in search of mechanisms by which iron may influence neurodevelopment. Body iron stores were elevated substantially in iron-supplemented pups. All pups gained weight normally, but brain size on PD 15 was dependent on iron source. This may have been associated with reduced hippocampal oxidative stress but was not associated with CNS mineral interactions, iron regulation, or myelination, as these were unchanged with iron supplementation. Additional studies are warranted to investigate iron form effects on neurodevelopment so that iron recommendations can be optimized for all infants.     

Multi-Nutrient Fortified Dairy-Based Drink Reduces Anaemia without Observed Adverse Effects on Gut Microbiota in Anaemic Malnourished Nigerian Toddlers: A Randomised Dose–Response Study

Prevalence of anaemia among Nigerian toddlers is reported to be high, and may cause significant morbidity, affects brain development and function, and results in weakness and fatigue. Although, iron fortification can reduce anaemia, yet the effect on gut microbiota is unclear. This open-label randomised study in anaemic malnourished Nigerian toddlers aimed to decrease anaemia without affecting pathogenic gut bacteria using a multi-nutrient fortified dairy-based drink. The test product was provided daily in different amounts (200, 400 or 600 mL, supplying 2.24, 4.48 and 6.72 mg of elemental iron, respectively) for 6 months. Haemoglobin, ferritin, and C-reactive protein concentrations were measured to determine anaemia, iron deficiency (ID) and iron deficiency anaemia (IDA) prevalence. Faecal samples were collected to analyse gut microbiota composition. All three dosages reduced anaemia prevalence, to 47%, 27% and 18%, respectively. ID and IDA prevalence was low and did not significantly decrease over time. Regarding gut microbiota, Enterobacteriaceae decreased over time without differences between groups, whereas Bifidobacteriaceae and pathogenic E. coli were not affected. In conclusion, the multi-nutrient fortified dairy-based drink reduced anaemia in a dose-dependent way, without stimulating intestinal potential pathogenic bacteria, and thus appears to be safe and effective in treating anaemia in Nigerian toddlers.     

High Prevalence of Stunting and Anaemia Is Associated with Multiple Micronutrient Deficiencies in School Children of Small-Scale Farmers from Chamwino and Kilosa Districts,Tanzania

Inadequate macro- and micronutrient nutrition and its consequences, such as anaemia, iron and vitamin deficiency, and growth retardation, could particularly affect children of small-scale farmers. In the present cross-sectional study, 666 school children aged 5–10 years from villages of Chamwino and Kilosa districts were studied for associations between nutritional and micronutrient status and dietary intake. The overall prevalence of stunting, underweight, and overweight was 28.1, 14.4, and 5%, while that of anaemia and deficiency of iron (ID), vitamin A (VAD), and zinc (ZnD) was 42.9, 29.3, 24.9, and 26.4%, respectively. Dietary recalls (24h) revealed that, except of iron (74%), only small proportions of children reached the recommended daily micronutrient intakes: 4% for zinc, 19% for vitamin A, and 14–46% for B vitamins. Stunting was highly associated with wasting in both districts and with VAD in Chamwino. Anaemia was predicted by ID, VAD, and ZnD in Chamwino and by elevated infection markers, C-reactive protein (CRP) and α-1 glycoprotein (AGP), in Kilosa. Overall, elevated CRP and/or AGP increased the risk while higher serum carotenoids indicating a diet of more fruit and vegetables reduced the risk of VAD. The significantly lower prevalence of anaemia and ID in Chamwino was related to higher iron and vitamin A intake and the consumption of mainly bulrush millet with dark green leafy vegetables compared to maize or rice with legumes in Kilosa. Nutrition and hygiene education integrated with home and school garden programmes could reduce the multiple burdens of anaemia; micronutrient deficiencies and infections; and, in the long term, the prevalence of stunting.     

Oral Administration of Ginger-Derived Lipid Nanoparticles and Dmt1 siRNA Potentiates the Effect of Dietary Iron Restriction and Mitigates Pre-Existing Iron Overload in Hamp KO Mice

Intestinal iron transport requires an iron importer (Dmt1) and an iron exporter (Fpn1). The hormone hepcidin regulates iron absorption by modulating Fpn1 protein levels on the basolateral surface of duodenal enterocytes. In the genetic, iron-loading disorder hereditary hemochromatosis (HH), hepcidin production is low and Fpn1 protein expression is elevated. High Fpn1-mediated iron export depletes intracellular iron, causing a paradoxical increase in Dmt1-mediated iron import. Increased activity of both transporters causes excessive iron absorption, thus initiating body iron loading. Logically then, silencing of intestinal Dmt1 or Fpn1 could be an effective therapeutic intervention in HH. It was previously established that Dmt1 knock down prevented iron-loading in weanling Hamp (encoding hepcidin) KO mice (modeling type 2B HH). Here, we tested the hypothesis that Dmt1 silencing combined with dietary iron restriction (which may be recommended for HH patients) will mitigate iron loading once already established. Accordingly, adult Hamp KO mice were switched to a low-iron (LFe) diet and (non-toxic) folic acid-coupled, ginger nanoparticle-derived lipid vectors (FA-GDLVs) were used to deliver negative-control (NC) or Dmt1 siRNA by oral, intragastric gavage daily for 21 days. The LFe diet reduced body iron burden, and experimental interventions potentiated iron losses. For example, Dmt1 siRNA treatment suppressed duodenal Dmt1 mRNA expression (by ~50%) and reduced serum and liver non-heme iron levels (by ~60% and >85%, respectively). Interestingly, some iron-related parameters were repressed similarly by FA-GDLVs carrying either siRNA, including ⁵⁹Fe (as FeCl₃) absorption (~20% lower), pancreatic non-heme iron (reduced by ~65%), and serum ferritin (decreased 40–50%). Ginger may thus contain bioactive lipids that also influence iron homeostasis. In conclusion, the combinatorial approach of FA-GDLV and Dmt1 siRNA treatment, with dietary iron restriction, mitigated pre-existing iron overload in a murine model of HH.     

缺铁性贫血婴幼儿智能行为发育研究

目的 探讨缺铁性贫血对婴幼儿智能行为发育的影响。方法 对264名儿童进行0－36个月的生长发育纵向监测,定期对其智力发育指数（MDI）、精神运动发育指数（PDI）以及行为进行测试,根据2岁时有无缺铁性贫血分为两组：①贫血组（96名）,②非贫血组（168名）,建立数据库,用SPSS软件进行统计学分析。结果 2岁时贫血组MDI、PDI均低于对照组,且这种改变在2．5岁贫血完全被纠正时仍未安全消除;2岁缺铁性贫血患儿血红蛋白水平与其MDI和PDI分值呈正相关;缺铁性贫血组儿童2－3岁期间行为问题发生率明显高于对照组,突出表现在社交退缩和躯体诉述两个行为因子上。结论 缺铁性贫血对婴幼儿智能行为发育均产生重要影响,鉴于对智能发育的不利影响是长期的,积极防治婴幼儿期缺铁性贫血对于保证儿童正常生长发育具有重要意义。     

94例缺铁性贫血患者的病因分析

目的 :通过对确诊为缺铁性贫血的病例进行病因学分析 ,探讨多病变和恶性肿瘤在缺铁性贫血发病中的重要性。方法 :确诊为缺铁性贫血 (IDA)的患者 94例 ,行大便虫卵检查 ,胃镜、结肠镜或钡餐、钡灌肠 ,腹腔B超 ,女性加做妇科检查及盆腔B超检查 ,找出IDA病因。将 94例患者按病因分类分为单一病因组和多病变组 ,用t检验对两组的Hb、SF值进行比较 ;再分为良性病变组和恶性肿瘤组 ,两组间的Hb、SF值也以t检验进行比较。结果 :94例IDA患者的病因中 ,由单一病因致病者 75 .5 % ,以消化性溃疡 (2 7.7% )和慢性胃炎 (17.0 % )为主 ,月经失血过多(2 0 .2 % )仍是女性患者的主要病因 ;多病变致病者 2 4.5 %。良性病变占 86 .2 % ,消化道恶性肿瘤占 13.8%。各组间Hb值均无显著差别 (P >0 .0 5 ) ,但恶性肿瘤组SF值明显高于良性病变组 (P <0 .0 1)。结论 :良性消化道出血性病变仍是导致IDA的主要原因 ,其次为女性月经过多。但多病变导致缺铁 ,尤其是上下消化道多个失血灶同时存在者 (14.9% )也不少见。恶性肿瘤在IDA病因中有增多趋势。恶性肿瘤致IDA的患者SF较高。     

强氧酸性离子水毒性试验研究

目的 了解新型消毒剂强氧酸性离子水的毒性。方法 采用一次性限量灌胃法测定急性经口ＬＤ５０;采用剂量递增蓄积系数法测定蓄积毒性;采用取样前３０小时、６小时两次给予受试物法测定其对小鼠骨髓嗜多染红细胞微核形成的影响;用斑贴法测定其对动物的皮肤刺激强度;用棉条浸入法测定其对大鼠阴道粘膜的刺激强度。结果急性经口ＬＤ５０大于２１５００ｍｇ／ｋｇ·ｂｗ,属实际无毒物,蓄积试验属弱蓄积性,对小鼠骨髓微核细胞未见损伤作用,对家兔皮肤和大鼠阴道粘膜无刺激。结论 强氧酸性离子水是一种安全的消毒剂。