Dissertations / Theses on the topic 'Micronutrient supplementation'

Pregnancy is a state of constant physiological compensation, processes that simultaneously account for the physical needs of both mother and foetus. These changes create a complex and continuously evolving environment, one which depends on essential elements for continued optimal function. While these processes are vital to the maintenance of pregnancy, they are also pivotal to parturition, a process which relies on the actions of numerous micronutrients for essential endocrine and inflammatory pathways. As such, proper maternal nutrition is pivotal to optimal birth outcomes. Global, national and state agencies address nutrition within theoretical and conceptual frameworks; these interact with governance, clinical, and consumer factors to create complexities individuals must navigate when making nutrition-related decisions. This decision-making becomes more complicated during pregnancy due to social influences, such as advertising and peer pressure, and cultural factors such as food avoidance, traditions and beliefs. The confluence of these determinants influences each woman’s nutrition state, with the potential to result in transgenerational health consequences. Malnutrition is associated with suboptimal perinatal outcomes, a situation not restricted to low and middle-income countries. Although outcomes in these regions have improved with supplement interventions, research is yet to determine the efficacy of supplementation in high-income countries. However, despite the lack of evidence surrounding their safety and efficacy, and recommendations relating to the use of supplements during pregnancy, the pregnancy supplement market is estimated to reach a value of $673.8 million by the year 2025. This quantitative research explored data collected from three cross-sectional cohorts in order to explore the associations between micronutrient supplementation and birth outcomes in South-East Queensland women. The first of these datasets – the Environments for Healthy Living cohort - was a longitudinal birth cohort study with self-reported perinatal data collection undertaken between 2006 and 2011. The second was the Gold Coast Health and Hospital Service Maternity Information System cohort; a clinician controlled digital perinatal database with data available from 2014 to 2017. The third was the Maternal Outcomes and Nutrition Tool database, a cohort recruited explicitly for this study between 2016 and 2018, self-declaring data using a specially designed digital data collection tool. Collectively, these three cohorts examine the relationships between demographics, socio-cultural factors, micronutrition status, supplement use, dietary decision-making and their influence on the birth outcomes of 9300 women from South-East Queensland over the twelve years from 2006 to 2018. Six research aims informed three formative enquiries addressing the central research question. These aims examined evidence informing current recommendations regarding micronutrient supplements during pregnancy in Australia, determined if evidence of benefit exists regarding micronutrient supplements and birth outcomes in South-East Queensland women and explored the human factors affecting nutrition-related decision making in the study population. This research aimed to determine relationships between socio-cultural determinants of health, micronutrition, supplement use and birth outcomes in pregnant women of South-East Queensland. A literature review was conducted, highlighting current limitations and knowledge gaps relating to the influence of supplementation in nutritionally replete and high-income populations. Furthermore, current data collections were found to exhibit significant limitations inhibiting accurate determination of causal relationships. As such evidence informing current recommendations during pregnancy was determined to be neither robust nor contemporary. Driving dietary decision making were several social, health, cultural and economic factors. These include smoking, income, education, cultural and linguistic diversity, access to maternity care models, the range of maternity care models and providers, and health service resources. In particular, women from low-socioeconomic backgrounds - including women who smoke and women from cultural and linguistically diverse backgrounds - reported nutrition motives that position health factors as a low priority. While these women did not demonstrate evidence of benefit from micronutrient supplements, they did declare nutrition decision-making behaviours that would benefit from dietary counselling and support strategies. The synthesis of information afforded by this research has determined that micronutrient supplementation is not appropriate in pregnant women of South-East Queensland. Further, supplementation did not improve birth outcomes in either the general population or in women from demographic groups considered to be at risk for suboptimal outcomes. Conversely, non-therapeutic use demonstrated the capacity for detrimental effects across all three cohorts, particularly concerning the effect of micronutrient supplements on overweight women and the incidence of prolonged pregnancy. Determination of what constitutes sustainable, safe and effective nutrition interventions in women at risk of suboptimal birth outcomes requires further empirical research.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Griffith Health
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This thesis describes a randomized, double-blind, placebo-controlled, clinical trial investigating the effect of a multiple micronutrient supplement in patients with stable chronic heart failure. Seventy-nine patients with chronic stable heart failure were recruited and randomized to treatment with a multiple micronutrient supplement or placebo. The primary end-point of the study was left ventricular ejection fraction (LVEF), assessed using cardiovascular magnetic resonance imaging or 3·dimensional echocardiography. The secondary end·points were quality of life (assessed using the Minnesota Living With Heart Failure Questionnaire), physical functioning (assessed using six-minute walk test distance), blood levels of N·terminal prohormone of brain natriuretic peptide, blood levels of Creactive protein, blood • levels of pro· and anti-inflammatory cytokines (tumour necrosis factor alpha. interleukin·6 and mterleukin-10) and urinary levels of a marker of oxidative stress (8· iso·prostagtandin F2 alpha). All end-points were assessed at baseline and after 12 months of treatment with the study medication . Compliance with the study med ication was assessed by measuring blood levels of a number of micro nutrients contained within the multiple micronutrient supplement. There was evidence of good compliance with the study medication in nearly all subjects. With respect to the primary end-point , complete follow-up data were available for 68 subjects (35 patients in th~ placebo group and 33 patients in the multiple micronutrient supplement group). There was no evidence of a significant effect of multiple micronutrient supplementation on LVEF In addition, there was no evidence of a significant effect of multiple micronutrient supplementation on any of the secondary end·points. This study, therefore, provides no evidence to support the routine treatment with a multiple micronutrient supplement of such patients with chronic stable heart failure.

The PhD thesis investigates the long-term effects of antenatal multiple micronutrient (MMN) supplementation. A growing body of evidence suggests that changes in early-life environment can have lasting effects on health and disease. To investigate this, we followed up children from a double-blind randomised controlled trial of MMN in pregnancy. The trial found that the intervention group were a mean 77 g heavier at birth and 204 g at 2.5 years, with a 2.5 mmHg lower mean blood pressure. The project described in the thesis set out to investigate the role of antenatal MMN intervention in the programming of future health and disease risk factors in mid-childhood. It sought to determine whether the differences in anthropometry previously present were sustained into mid-childhood and if this was due to an increase in lean mass or fat mass. It also looked at whether antenatal MMN supplementation resulted in an improvement in lung function in the children. Finally, two secondary analyses were conducted to investigate the association between socioeconomic status and growth, and air pollution and asthma. We measured anthropometry, body composition using bioelectrical impedance (with population specific isotope calibration), blood pressure, kidney dimensions by ultrasound and lung function. Data were also collected on potential confounders: socieconomic status, food security and personal air pollution exposure estimates. We assessed 841 children (422 controls, 419 intervention) at a mean age 8.5 years. Other than maternal education and residence, children lost to follow-up were no different. The unadjusted differences (intervention minus control), were 0.05 z-scores (95% CI -0.09, 0.19) for weight-for-age, 0.02 z-scores (95% CI -0.10, 0.15) for height, -0.08 z scores (95% CI - 0.19, 0.04) for forced expiratory volume in the first second, and -0.05 (95% CI -0.17, 0.06) for forced vital capacity. There was no difference in blood pressure, body circumferences, lean mass, skinfold thicknesses or kidney measurements. The adjusted differences were similar for all outcomes. When considered together, just over half the children had low weight-for-age, and approximately one-third had stunting and low body mass index. Only 1.4% of the children were overweight and mean fat mass proportion was 14.5%. When lung function was expressed in relation to predicted values for Caucasian children, FEV1 was 14% lower and FVC 12% lower. Our measures of socioeconomic status produced a multidimensional poverty index score of 0.155 and approximately one in ten households were considered food insecure in the previous year. The air pollution data showed a mean 24 hour time-weighted average of 168 μg/m3. We found an overall low prevalence of asthma, with air pollution associated with cough at night in boys only (odds ratio 1.15 per 10 μg/m3 increase in air pollution; 95% CI 1.05, 1.26). Socioeconomic status was associated with the growth of children when families owned more expensive assets and appeared to have the greatest effect on skeletal growth in early life. Differences in phenotype, body composition and lung function between children born to mothers who received antenatal MMN supplements and children whose mothers received iron and folate were not apparent at 8.5 years. While generally poor, households were comparable to those in more affluent regions of the country and were relatively food secure. The air pollution data showed that the children were exposed to levels much higher than national and international recommendations.

Undernutrition and oxidative stress in fetal life and infancy may lead to adverse health outcomes in the offspring. We studied nutrition and oxidative parameters in pregnancy and their associations with birth anthropometry and metabolic status in the children. In Matlab in rural Bangladesh, women were randomized to either early (Early) invitation to food supplementation or to start at their own liking (Usual). Women were also allocated to either; 1) 60 mg iron and 400 µg folic acid (Fe60F), 2) multiple micronutrients including 30 mg iron and folic acid (MMS), or 3) 30 mg iron and folic acid (Fe30F). Micronutrients (hemoglobin, iron, zinc, folic acid, vitamin B-12) were assessed in pregnancy week 14, lipid peroxidation in week 14 and 30, and DNA oxidation in week 19. The offspring were assessed for anthropometric measurements at birth and metabolic status at 4.5 years. Micronutrient deficiencies were common with zinc and vitamin B-12 deficiency being most prevalent. Anemia was present in approximately one third of women, however, iron deficiency was uncommon seen in only 2%. Maternal Early food supplementation group resulted in an improved lipid status in the children at 4.5 years compared to Usual food group. Prenatal use of MMS lowered the children’s glucose, insulin, HOMA-IR, and growth factors compared to Fe60F.   Lipid peroxidation in early pregnancy was associated with size at birth and insulin and HOMA-IR levels in the children. Lipid peroxidation in late pregnancy, however, was associated with the children’s lipid status. Both increasing lipid peroxidation and increasing DNA oxidation was associated with decreasing IGF-1 levels.  The beneficial effects of an Early start of food supplementation show that an improved prenatal nutrition may have lasting effects in the offspring and highlights the importance of early timing food supplementation. Use of MMS, however, resulted in lower insulin levels, which, considering the already low level of insulin in these children, may be a cause of concern. MMS also resulted in growth factors indicative of slower growth and further research appears to be needed before scaling up the use of MMS. Oxidative parameters in pregnancy were associated with longer-term outcomes in the offspring, suggesting that oxidative stress may be involved in the development of later metabolic disease.

Micronutrients are increasingly appreciated as potent immunomodulators. Long used to 'treat' measles virus (MeV), vitamin A was recently shown to act through RIG-I to up-regulate type 1 interferons. Similar actions are seen with some (mumps virus and CDV) but not all members of the Paramyxoviridae. However, children infected with respiratory syncytial virus (RSV), a close relative of MeV, do worse when given pharmacological doses of vitamin A. RSV is known to elicit a pathologic Th2-biased response. Vitamin A also has a strong Th2-deviating influence. Our primary objective was to develop a small animal model of vitamin A deficiency and sufficiency in which we could assess the impact of vitamin A status and supplementation on RSV infection in vivo. Such a model will be of great use to characterize the mechanism of action of retinoids in this infection. We succeeded in the development of this model by restricting dietary retinol through 2 generations of BALB/c mice (ie: deficiency state) and introducing novel means to reliably attain a state of consistent vitamin A supplementation (ie: reconstituted & excess states). Preliminary data using this model suggested that there were marked differences in RSV pathology between deficient and sufficient mouse groups. Like the apparent situation in humans, infection in the vitamin A deficient mice was paradoxically less severe than in mice with a positive vitamin A status. This model and the data generated with it may be of particular interest in regions with diets high in vitamin A (North America in particular). Historically, very little attention has been given to possible negative effects of micronutrient 'over-nutrition'. The limited human data and the preliminary data from our new model brings into question whether or not we are 'priming' ourselves for more severe RSV infection than would otherwise occur. The data generated in this model may also be highly relevant to guide supplementation efforts in regions of the world that currently have less access to vitamin A.
Les micronutriments sont des plus appréciés comme immunomodulateurs puissants. Longtemps utilisé pour traiter measles virus (MeV), la vitamine A a été récemment montré à agir par le biais de RIG-I pour réguler les interférons de type 1. Des actions similaires sont observés avec certains (canine distemper virus, CDV), mais pas tous les membres du Paramyxoviridae. Cependant, les enfants infectés par des voies respiratoire, respiratory syncycial virus (RSV), un proche cousine de MeV, faire pire lorsqu'il est administré des doses pharmacologiques de vitamine A. Le RSV est connu pour induire une résponse pathologique biaisée au Th2. La vitamine A est également une forte influence pour la Th2 déviation. Notre principal objectif était de développer un modèle animal de la carence en vitamine A et la suffisance dans lesquels nous pourrions évaluer l'impact du statut en vitamine A et de la supplémentation sur l'infection à RSV in vivo. Un tel modèle sera d'une grande utilité pour caractériser le mécanisme d'action des rétinoïdes dans cette infection. Nous avons réussi dans le développement de ce modèle en limitant le rétinol alimentaires grâce à deux générations de souris BALB / c (ie: état de carence) et en introduisant de nouveaux moyens de atteindre un état fiable de vitamine A cohérente supplémentation (ie: les Etats reconstitué & excès). Les données préliminaires utilisant ce modèle suggéré qu'il y avait des différences marquées dans la pathologie du RSV entre les groupes de souris déficientes et suffisante. Comme la situation apparente dans les humains, l'infection dans la vitamine A des souris déficientes en était paradoxalement moins sévère que dans les souris avec une vitamine positifs d'un statut. Ce modèle et les données générées avec elle peut être d'un intérêt particulier dans les régions où les régimes son riches en vitamine A (Amérique du Nord en particulier). Historiquement, très peu d'attention a été accordée aux effets négatifs possibles des micronutriments sur-nutrition. Les données humaines limitées et les données préliminaires de notre nouveau modèle remet en question si oui ou non nous sommes d'amorçage nous-mêmes pour l'infection à VRS plus sévères que se produirait autrement. Les données générées dans ce modèle peut également être très pertinentes pour guider les efforts de la supplémentation dans les régions du monde qui ont actuellement un accès moindre à la vitamine A.

Objectives: To study the effects of prenatal zinc and vitamin A supplementation on birthsize, neonatal morbidity, infant mortality, and growth in children up to two years of age. Subjects and Methods: From September 1995 to December 1999 pregnant women inPurworejo District, Central Java, Indonesia with gestational age <17 weeks (n=2173) wererecruited to and participated in a community-based, individually randomized, placebo controlled,double blinded study aiming to evaluate the impact of supplementation (vitamin A,zinc, vitamin A + zinc) during pregnancy on maternal morbidity and pregnancy outcomes. Weanalyzed secondary data from that study regarding birth size, neonatal morbidity and infantmortality of the 1956 infants born alive. A subsample of infants (n=343) was followed until 2years of age concerning growth, feeding practices and morbidity. Outcomes were tested usingthe chi-square test, ANOVA, ANCOVA, and Cox’s proportional hazard function. Results: Birth weights in the zinc [mean ±Standard deviation (SD): 3.16 ± 0.52 kg], vitaminA (3.08 ± 0.46 kg) or the combined vitamin A and zinc (3.10 ± 0.59) groups did not differ fromplacebo (3.09 ± 0.50 kg) after adjustment for maternal pre-pregnancy weight, weight gainduring pregnancy, and parity (P=0.70). Birth lengths of infants born to mothers supplementedwith zinc or vitamin A were in average 0.3 cm and 0.2 cm longer than those in the placebogroup after adjustment for maternal height, pre-pregnancy weight, weight gain during pregnancy,and parity (P=0.04). The impact of prenatal supplementation on infant mortality andneonatal morbidity was not significant. There was a small effect of prenatal vitamin A supplementationon postnatal growth in height-for-age z-score (HAZ). The absolute differencesbetween the vitamin A only and vitamin A + zinc groups at 3 and 9 months were 0.34 SD and0.37 SD, respectively, and the absolute difference between the vitamin A only and zinc onlygroups at 18 months was 0.31 SD. Defining growth faltering as downward crossing of ≥2 majorpercentile lines, 50-75% of the children were faltering within 9 months of age, whereas 17%and 8% were <-2 SD for growth in weight-for-age z-score (WAZ) and HAZ, respectively.Prenatal supplementation did not reduce the prevalence of growth faltering. Conclusions: Prenatal vitamin A and zinc demonstrates a small but significant impact onbirth length, but it does not have any protective effect on infant mortality and neonatal morbidity.Prenatal vitamin A supplementation had a small but significant effect on postnatallength growth until 18 months of age, but no effect on weight gain, growth rate and it did notreduce the prevalence of growth faltering.
Tujuan: meneliti pengaruh suplementasi zink dan vitamin A pada masa prenatal terhadapukuran tubuh bayi baru lahir, morbiditas neonatal, kematian bayi, dan pertumbuhan anaksampai dengan umur dua tahun Subjek dan Metode: Dari bulan September 1995 sampai dengan Desember 1999 ibu hamildi Kabupaten Purworejo, Jawa Tengah, Indonesia dengan umur kehamilan <17 minggu(n=2173) diikutsertakan ke dalam penelitian berbasis komunitas, teracak, menggunakankontrol plasebo dan buta ganda yang bertujuan mengevaluasi pengaruh suplementasi vitaminA, zink, dan kombinasi vitamin A dan zink selama kehamilan terhadap morbididitas ibu danhasil kehamilan. Kami menganalisis data sekunder dari penelitian ini dan mengevaluasi ukurantubuh bayi waktu lahir, morbiditas neonatal, dan kematian bayi dari 1956 bayi yang lahirhidup. Sebagian dari subjek (n=343) diikuti sampai dengan umur dua tahun untuk mengetahuipertumbuhan, cara pemberian makan, dan morbiditasnya. Data dianalisis dengan chi-squaretest, ANOVA, ANCOVA, dan Cox’s proportional hazard function. Hasil: Berat badan lahir pada kelompok zink [mean ±standar deviasi (SD): 3.16 ± 0.52 kg],vitamin A (3.08 ± 0.46 kg) atau kombinasi vitamin A dan zink (3.10 ± 0.59) tidak berbedasecara bermakna dibandingkan dengan plasebo (3.09 ± 0.50 kg) setelah dikontrol oleh beratbadan ibu sebelum hamil, pertambahan berat badan selama hamil, dan paritas (P=0,70).Panjang lahir dari kelompok ibu yang disuplementasi dengan vitamin A atau zink 0,2 cm danrata-rata 0,3 cm lebih panjang dibanding kelompok plasebo setelah dikontrol oleh tinggi badanibu, berat badan ibu sebelum hamil, pertambahan berat selama hamil, dan paritas (P=0,04). Pengaruh suplementasi selama masa prenatal terhadap kematian bayi dan morbiditas neonataltidak bermakna. Suplementasi masa prenatal mempunyai efek yang lemah terhadap pertumbuhanyang diukur dengan indikator tinggi badan menurut umur (HAZ). Perbedaan absolutpanjang badan anak antara kelompok vitamin A dan kombinasi vitamin A dan zink pada umur3 dan 9 bulan adalah 0,34 SD dan 0,37 SD; dan perbedaan absolut antara kelompok vitaminA dengan zink pada umur 18 bulan adalah 0,31 SD. Dengan menggunakan kriteria growthfaltering sebagai penurunan garis pertumbuhan memotong ≥ 2 persentil major, 50-75% anakmengalami growth faltering pada umur 9 bulan, dan hanya 17% dan 8% yang terdeksi mengalamigrowth faltering bila digunakan kriteria WAZ dan HAZ <- 2SD. Suplementasi vitaminA dan zink pada masa prenatal tidak menurunkan prevalensi growth faltering. Kesimpulan: Suplementasi vitamin A dan zink pada masa prenatal menunjukkan adanyapengaruh lemah tetapi bermakna terhadap panjang lahir, tetapi tidak menunjukkan efekprotektif terhadap kematian bayi dan morbiditas neonatal. Suplementasi vitamin A pada masaprenatal mempunyai efek lemah tetapi bermakna terhadap pertumbuhan panjang badansampai dengan umur 18 bulan, tetapi tidak disertai pengaruh terhadap kenaikan berat badan,laju pertumbuhan dan tidak menurunkan prevalensi growth faltering.

There is a growing body of research into the effects of micronutrients on human mental health. There is evidence that multi-ingredient formulas are beneficial especially in relation to serious mental health disorders such as mood and anxiety disorders, attention-deficit hyperactivity disorder and obsessive-compulsive disorders. However there is almost no scientific research which looks at the effects of these formulas in an animal population. Therefore the aim of this study was to investigate the effects of a micronutrient formula, EMPowerplus, on anxiety behaviour in rats, and whether there is a relationship between dose and anxiolytic effect. In order to investigate this 40 male and 40 female rats received a diet consisting of either 0%, 1.25%, 2.5% or 5% EMP+ from when they were weaned (post natal day 30) until the end of testing 141 days later. Animals were tested in a Y maze, a light-dark emergence box and an open field at mid-adulthood (PND 136-138) and late adulthood (PND 186-188). Results found that animals receiving the 5% supplemented diet occupied the centre squares the most, occupied the corner squares the least and ambulated the most in the open field compared to the other experimental groups and control groups. No significant differences were found in the Y maze or Light-dark box. Animals were found to display more anxiety-like behaviour at time 2 than at time 1 regardless of receiving a supplemented diet or not. Overall a higher dose of EMP+ was associated with the greatest reduction in anxiety related behaviour. Due to the impact of the September 4th, 2010 Canterbury Earthquake caution should be taken when interpreting these results.

Maternal nutrition is closely linked to child health and survival. In Bangladesh there is a high prevalence of undernutrition in the form of chronic energy deficiency [CED, Body Mass Index <18.5 (kg/m2)] in women and low birth weight. The aims of this thesis are to explore women’s perceptions of maternal undernutrition, to analyse the association between prenatal food supplementation and birth weight (BW), to analyse whether food- and multiple micronutrient interventions generate pro-disadvantaged equity in child survival, and to examine whether an early prenatal invitation to food supplementation and multiple micronutrient supplements (MMS) represents value for money in infant survival compared to invitation to food supplementation at usual time combined with 60 mg iron and 400 µg folic acid (standard practice). The study on women’s perceptions (n=236) was nested into the MINIMat randomized trial where women (n=4436) were allocated to early (E), or usual (U) time of invitation to prenatal food supplementation and 30 mg iron with 400 µg folic acid, or 60 mg iron with 400 µg folic acid, or MMS. Live births (n=3625) were followed-up. The analyses of equity and cost-effectiveness were based on this trial. A cohort design (n=619) was employed for the analysis of food supplements and BW. Women perceived maternal undernutrition as a serious health problem and attached very low scores to CED in pregnancy. An average of four months of prenatal food supplementation increased BW by 118 g. An early invitation to prenatal food supplementation and MMS lowered mortality in children before the age of five years and reduced social disparity in child survival chances. An increment from standard practice to E-MMS averted one extra infant death at a cost of US$797 to US$907, and saved one extra life year at a cost of US$27 to US$30. High priority should be given to the nutritional status of pregnant women in societies where undernutrition and food insecurity occurs. Prenatal food supplementation has the potential to significantly increase BW, and an early initiation of prenatal food supplementation combined with MMS was considered cost-effective in lowering infant mortality and increase social equity in child survival chances.

Background: The prevalence of low birth weight (LBW) is high in developing countries and is estimated to be 30% (UNICEF, 2001) in Bangladesh. Maternal under nutrition is an important cause of LBW is also highly prevalent in Bangladesh 50 % (March of Dimes, 2002). Public health programs of food-supplementation during pregnancy have been mounted to address the issue and it is important to determine the most effective way of providing the food. In addition it has been suggested that supplementation with multiple micronutrients may be more beneficial than supplementing with iron and folic acid alone, which is the present practise. Most studies of pregnancy supplementation have focused on the effect on birth outcomes whereas there is extremely little data on the effects on the offspring's' development. A large randomized-trial of the effect of 2 types of nutritional supplementation (food and micronutrients) in pregnant women on birth-outcomes was conducted in the Matlab field-site of ICDDR,B: Centre for Health and Population Research, Bangladesh. We took the opportunity to evaluate the effect of the supplements on children's development.;Aims: We aimed to determine the effect of giving pregnant women early (around 10 week of gestation) versus late (around 17 week of gestation) food-supplementation and multi-micronutrients or 30mg iron + 400 fig folate or 60mg iron + 400 fig folate on their infants' development.;Methods: A sub-sample of all singletons (n=2853) born between May 2002 and December 2003 in the main trial was selected to have developmental assessments at 7 months of age. The children were assessed using 2 problem-solving tests (cover and support), the Bayley motor-scale (PDI) and Wolke's behaviour ratings assessing approach, activity, emotionality, co-operation and vocalization during the test procedure. The children were also assessed for the age of attainment of motor milestones.;Intervention: 2 nutritional interventions were given: Food supplementation: Women were randomly assigned to begin the food supplementation program (a) immediately after diagnosis of pregnancy (early care) or (b) at the time of their choosing (usual care). Micronutrient supplementation: Within each food group, women were randomly assigned to receive a pill that contained (a) 30 mg iron and 400 Lig folate or (b) 60 mg iron and 400 Hg folate (usual care) or (c) 30 mg iron, 400 U-g folate and 13 additional micronutrients (UN1CEF/WHO/UNU, 1999 formulation of 15-micronutrients).;Results: There is no overall benefit of prenatal supplementation with early food or multiple-micronutrients compared with late food or iron and folate supplementation on any of the tests of children's development when assessed at 7 months of age. However infants of thin mothers (body mass index < 18.5 kg/m ) showed a small but statistically significant benefit from both early food and multiple-micronutrients supplements whereas the children of better nourished mothers did not. Early food supplementation benefited children of malnourished mothers in the problem solving tests, support (BMI x early food p < 0.03) and cover (BMI x early food p < 0.05) and behaviour. The children were less fussy (BMI x early food p < 0.04), more cooperative with the test situation (BMI x early food p < 0.04) and vocalised more often (BMI x early food p < 0.04) than children of similar mothers given late food supplementation. Small but significant benefits on motor development (BMI x micronutrients p=0.05) and activity (BMI x micronutrients p < 0.05) were also observed among the infants of malnourished mothers who received multiple-micronutrient supplements. Mothers' BMI had an independent effect on children's development. Conclusions: Early food and multiple micronutrient supplementation benefited development in children of undernourished mothers but not children of better nourished mothers. The findings support current practices in Bangladesh of targeting thin mothers and suggest that early food supplementation may be more beneficial than later supplementation. The findings also suggest that multiple micronutrients may be more beneficial to the child than iron and folate. However, the effect sizes were very small and their clinical and public health importance are not clear and can only be determined with longer follow-up. As there was no placebo group, the benefit of giving food supplementation throughout pregnancy could not be assessed. The relationship between mothers BMI and children's development emphasises the importance of maternal nutrition.

Background: Dietary zinc recommendations vary widely across Europe. The EURRECA (European Micronutrient Recommendations Aligned) Network of Excellence was brought together to harmonise the approach to setting micronutrient recommendations. The overall aim was to produce a set of guidelines and an extensive database that may be of use to expert panels in underpinning future micronutrient recommendations, based on a series of systematic reviews and meta-analysis of published data. A secondary aim was to identify gaps in knowledge regarding micronutrient status, intake and health outcomes for future research. A third aim, coming from the result of the secondary aim, was to investigate the long term effect of supplementation on cognition. Objectives: The objectives of this thesis were: (1) To adapt the methodology for undertaking a systematic review and meta-analysis developed by EURRECA for zinc in all population groups (infants, children, adolescents, pregnant and lactating women and adults and elderly). (2) To identify knowledge gaps in the research through the assessment of the interrelationships between zinc intake, status and health outcomes. (3) To design and implement a study to explore the intake-status-health relationships between micronutrient supplementation and cognitive function in Peruvian children. Methods: Phase 1: The EURRECA systematic review. Database searches were conducted in MEDLINE, Embase and the Cochrane library, from inception to March 2014. For the assessment of the intake-status relationship, an intake-status regression coefficient (^) was estimated for each individual study and the overall pooled ^ and SE ^ was calculated using random effect meta-analysis on a double log scale. The systematic review included randomized controlled trials, cohort studies, cross sectional studies and nested case-control studies in healthy children and adult populations that measured zinc intake (diet and supplements) and zinc status (serum/plasma zinc) in association health outcomes that included cognitive function and psychomotor development. Phase 2: Empirical study. This included the assessment of multiple micronutrients (MMN) supplementation and cognitive development in Peruvian children when compared with giving iron supplements alone. These tests were considered to reflect theoretical dimensions of working memory (Nine boxes), and inhibitory control (Day/Night stroop task). Intelligence Quotient (IQ) was measured using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI); social-emotional behaviour was assessed via the Brief Infant–Toddler Social and Emotional Assessment (BITSEA) and reasoning through the theory of mind test. Results: Meta-analysis of data reporting zinc intake and status revealed that doubling intake increased plasma zinc concentration by 9% in children, by 3% during pregnancy, by 1% during lactation and by 6% in adults and elderly. The systematic review of zinc and health outcomes highlighted the need for further research on the relationship between micronutrients and cognitive function. The empirical study was therefore designed and undertaken. The results revealed that there were no significant differences between the iron and the MMN supplemented groups for all cognitive tests, with the exception of the vocabulary WPPSI subtest in girls (mean±SD), (MMN, 6.83±2.05; iron 5.78±1.59, p = 0.028) and no significant differences were found for plasma zinc and haemoglobin concentrations between the two groups. Conclusions: The systematic reviews provided novel dose-response estimates between zinc intake-status that could be used either qualitatively or quantitatively with balance studies when setting future zinc recommendations. Following an assessment of the impact of micronutrient supplementation on cognitive and social-emotional development in Peruvian preschool children, it can be concluded that MMN supplements had no long term additional effects on cognitive function compared with iron alone, however the timing of the supplement for maximal potential benefit needs to be explored further.

Anemia and micronutrient deficiencies in infancy are common in low-income settings. These are partly due to maternal malnutrition and may impair child health and development. We studied the impact of maternal food and micronutrient supplementation, duration of exclusive breastfeeding (EBF), growth and infection on infant anemia and micronutrient status. In the MINIMat trial in Matlab, Bangladesh, pregnant women were randomized to Early or Usual promotion of enrolment in a food supplementation program and to one of three daily micronutrient supplements. Capsules containing 400µg folic acid and (a) 30 mg iron (Fe30Fol), (b) 60 mg iron (Fe60Fol), (c) 30 mg iron and other micronutrients (MMS) were provided from week 14 of gestation. Capsule intake was assessed with the eDEM device recording supplement container openings. Blood samples (n=2377) from women at week 14 and 30 were analyzed for hemoglobin (Hb). Duration of EBF and infant morbidity was based on monthly maternal recalls. Infants were weighed and measured monthly. Blood samples (n=1066) from 6-months-old infants were analyzed for Hb and plasma ferritin, zinc, retinol, vitamin B12 and folate. In women, Hb increase per capsule reached a plateau at 60 Fe60Fol capsules, indicating that nine weeks of daily supplementation produced maximum Hb response. Anemia was common (36%) at capsule intakes >60 indicating other causes of anemia than iron deficiency. In infants, vitamin B12 deficiency prevalence was lower in the MMS (26.1%) than in the Fe30Fol group (36.5%), (p=0.003) and zinc deficiency prevalence was lower in the Usual than in the Early group. There were no other differential effects of food or micronutrient supplementation on infant anemia or micronutrient status. Infants exclusively breast-fed for 4-6 months had a higher mean plasma zinc concentration (9.9±2.3 µmol/L) than infants exclusively breast-fed for <4 months (9.5±2.0 µmol/L), (p< 0.01). No other differences in anemia, iron or zinc status were observed between EBF categories. Infection, low birth weight and iron deficiency were independent risk factors for infant anemia. Regardless of studied interventions, prevalence of anemia (43%), deficiency of zinc (56%), vitamin B12, vitamin A (19%) and iron (22%) in infancy was high and further preventive strategies are needed.
MINIMat

Background Anaemia is a public health concern in Bangladesh, affecting 30-50% of the children under-5 years of age. Iron deficiency (ID) is thought to be the primary cause of anaemia in the country. However, a national micronutrient survey revealed that the prevalence of ID in under-five children is quite low (10.7%) and drinking iron-containing groundwater from tube wells was reported to be linked with low ID. Despite the low burden of ID, due to the high prevalence of anaemia, the national policy for childhood anaemia prevention recommended iron supplementation through distributing micronutrient powder (MNP) containing 12.5 mg of iron. The MNP programmes have been implemented over the decades to prevent anaemia in children. Physiologically, in an iron-replete state, usage of iron supplement (MNP) might induce side effects such as, diarrhoea, nausea, and vomiting is common. Hence, the present study was conducted in Bangladeshi children drinking from groundwater with high level of iron to assess the effect of the low iron MNP (5 mg iron) against the standard MNP (12.5 mg iron) on haemoglobin concentration and to compare the relative side-effects of the competing MNP treatments. Methods: The RCT was conducted in children 2-5 years old who drank water from groundwater with a high concentration of iron (≥2 mg/L) in Belkuchi—a rural district of Bangladesh. A total of 435 children were screened for eligibility, with 327 enrolled in the trial and randomly allocated to receive either the standard MNP (12.5 mg iron per sachet) or the low-iron MNP (5 mg iron per sachet). The trial assessed if low-iron MNP, after consumption of one sachet every day for 60 days, was non-inferior to the standard MNP in regard to haemoglobin concentration of the children. A priori non-inferior margin (-0.5 g/dl) was set; and non-inferiority was concluded if the lower bound of the one-sided 95% CI for the difference in the treatment effect of the low iron MNP was higher than the non-inferiority margin. The treatment effect of the low iron MNP on haemoglobin was examined by Generalized Linear Modelling through controlling for the pertinent baseline covariates. Furthermore, the study assessed the comparative incidence of iron-induced side effect such as diarrhoea, loose stools, nausea, fever, and vomiting between the treatment groups. Incidence Rate Ratio (IRR) which compares incidence rates of an event between two groups was calculated using the poisson regression to assess the incidence of the side effects in the groups. On a subsample (n=53) of the enrolled children representing both MNP groups, gut microbiome was assessed by sequencing of 16sRNA at baseline and the endpoint. The effects of the intake of MNPs on the composition of gut microbiota were compared between the groups and between endpoint and baseline. Additionally, to assess the effect of thalassaemia in the background of high groundwater iron and MNP consumption, a sub-sample analysis from the trial was conducted to compare haemoglobin and ferritin status among the thalassaemia carriers and non-carriers. Another sub-study was conducted to examine the haemoglobin status of the children whose drinking groundwater contained low level of iron (0--<2 mg/) for hypothesizing the utility of the low iron MNP in the low groundwater iron setting. Further, the trial was preceded by three sub studies leading up to the preparation of the trial—such as the taste-rating of the groundwater sample for semi quantitative assessment of iron content (annex 1); validation of a semi quantitative food frequency questionnaire (annex 2); and assessment of temporal concentration of groundwater iron (annex 3). Results: The results of the RCT revealed that the low-dose iron MNP was non-inferior to the standard MNP on haemoglobin outcome (β = −0.14, 95% CI: −0.30, 0.013; p = 0.07). The lower bound of the 95% CI for the difference in the treatment effect on haemoglobin was higher than -0.5 g/dl, thus confirming the non-inferiority of the low iron MNP. It resulted in a lower incidence of diarrhoea (IRR = 0.29, p = 0.01, 95% CI: 0.11–0.77), nausea (IRR = 0.24, p = 0.002, 95% CI: 0.09–0.59) and fever (IRR = 0.26, p < 0.001, 95% CI: 0.15–0.43) compared to the standard MNP. The 16sRNA sequencing revealed that overall; there was no significant treatment effect of the low-iron MNP on microbiota compared to the standard MNP. However, an apparent treatment effect was observed in children with a relative adultlike microbiota, with a higher relative abundance of potentially pathogenic Enterobacteriaceae after receiving the standard MNP compared to the low-iron MNP (p=0.07). The results of the sub-sample of the thalassaemia carriers showed that the haemoglobin concentration of the children with thalassaemia at the end-point remained unchanged relative to the baseline value; 11.56±0.59 (Endpoint) vs. 11.6±0.54 (Baseline), p=0.83. In the children without thalassaemia haemoglobin tended to increase; 12.54±0.72 (Endpoint) vs. 12.41±0.72 (baseline), p=0.06. Baseline reserve of body iron was significantly higher in the thalassaemia carriers compared to their non-carrier peers; 594 mg vs. 558 mg; p=0.03. The increase of the infection adjusted ferritin level from baseline to the endpoint was 7.37% (p=0.7) and 10.17% (p=0.009) in the carrier and non-carrier groups respectively. The sub-study examining the effect of the low iron MNP in a low groundwater iron setting revealed that the ccombined intake of iron from dietary, groundwater and low-iron MNP in children was 5.8±2.0 and 6.9±2.5 mg/day comprising 193% and 169% of the Estimated Average Requirement in the 2-3 year-old and 4-5 year-old subgroups, respectively. The mean concentration of haemoglobin in children exposed to groundwater concentration 0.8-<2.0 mg/L and 0.0-<0.8 mg/L subgroups was 12.17±0.94 mg/dl and 11.91±0.91 mg/dl (p=0.30) respectively. Conclusion: The low iron MNP (5 mg iron) was non-inferior to the standard MNP (12.5 mg) in preventing the low level of haemoglobin in Bangladeshi children exposed to high content of iron from drinking groundwater. It caused fewer incidence of side effects, such as diarrhoea, nausea and fever. Overall, there was no treatment effect of the low iron MNP on composition of gut microbiota. Further, a low iron MNP can be potentially beneficial to the thalassaemia carriers. Low iron MNP has the potential to curb the childhood anaemia in settings where groundwater iron is low. The combined findings of the trial and the sub studies demonstrated beneficial role of the low iron MNP in Bangladesh to control childhood anaemia.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medicine & Dentistry
Griffith Health
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A obesidade é uma desordem multifatorial que envolve agentes hereditários, ambientais e estilo de vida, e suas consequências não são apenas sociais ou psicológicas, mas estão também relacionadas à presença de comorbidades como hipertensão arterial, diabetes tipo 2, doenças cardiovasculares e vários tipos de câncer. Considerando que as alterações genéticas relacionadas à obesidade não são totalmente conhecidas, assim como não se sabe a possível ação da suplementação nutricional sobre tais alterações, o presente estudo teve como objetivo avaliar a relação entre a ingestão de micronutrientes, alterações genéticas e perfil inflamatório em um grupo de 30 mulheres com obesidade mórbida, com idade entre 20 e 45 anos e submetidas à cirurgia bariátrica. A suplementação nutricional consistiu da ingestão (pó diluído em água) de vitaminas e micronutrientes correspondentes a duas DRIs (Ingestão Dietética de Referência) por dia, durante 10 semanas antes e 24 após a cirurgia bariátrica. O total de 30 mulheres eutróficas saudáveis, não fumantes e pareadas por idade às obesas, constituiu o grupo de referência. Todos os parâmetros avaliados nas mulheres obesas foram mensurados em três momentos: antes da suplementação nutricional (M1); 8 semanas após o início da suplementação e uma semana antes da cirurgia bariátrica (M2); e seis meses após o procedimento cirúrgico (M3). Os testes do cometa e do micronúcleo foram utilizados para medir, respectivamente, os níveis de danos primários no DNA e as frequências de alterações citogenéticas em células do sangue periférico. As mulheres obesas, nos três momentos mensurados, apresentaram maiores níveis (p < 0,05) de danos no DNA que as eutróficas (grupo controle). No entanto, seis meses após a cirurgia bariátrica, foi significativa a redução dos danos, quando consideradas apenas as obesas, muito embora os níveis não voltassem a atingir valores próximos ao do grupo controle. Frequências aumentadas de células micronucleadas foram detectas nas mulheres obesas antes da cirurgia bariátrica em relação as eutróficas. Contudo, seis meses após a cirurgia a frequência diminuiu significativamente, ficando semelhante à do grupo controle. Diminuições significativas de citocinas inflamatórias foram observadas nas mulheres obesas, tanto após o início da suplementação de micronutrientes, como após a cirurgia. A avaliação do perfil de expressão gênica pela técnica de microarranjos de DNA mostrou que as mulheres obesas, antes da suplementação nutricional, apresentavam hiperexpressão de genes relacionados a vias de metabolismo energético e lipídico e perfil inflamatório. Após a suplementação, foram observadas modificações no perfil de expressão desses genes, além da modulação de genes de vias como viabilidade celular e reparo de DNA. Por outro lado, após o procedimento cirúrgico e a concomitante suplementação nutricional ocorreu modulação de genes envolvidos em vias de metabolismo energético e processos inflamatórios, possivelmente devido à significativa perda de peso e consequente diminuição do IMC. Concluindo, do ponto de vista genético, este estudo demonstrou a importância da suplementação nutricional em mulheres com obesidade mórbida, antes e após a cirurgia bariátrica, embora não tivesse sido possível discriminar a extensão dos seus efeitos frente à perda de peso ocorrida após o procedimento cirúrgico.
Obesity is a complex disease that originates from a combination of social, environmental and genetic factors. Furthermore, it is associated with comorbidities such as hypertension, type 2 diabetes, heart disease and various types of cancers. Since the relationship among genetic alterations, nutritional supplementation and obesity are not fully understood, this study aimed to evaluate the effects of micronutrient intake on genetic and inflammatory profile in a group of 30 morbidly obese women, aged between 20 and 45 years and undergoing bariatric surgery. The nutritional intervention consisted of two recommended dietary allowance (RDA) of vitamins and micronutrients per day, for 10 weeks before and 24 after the bariatric surgery. A total of 30 healthy normal-weight, non-smokers and matched for age to the obese women were recruited as a control group. All the checked endpoints in obese the women were measured at three moments: before nutritional supplementation (M1); 8 weeks after beginning of supplementation and one week before bariatric surgery (M2); and six months after surgery with simultaneous nutritional supplementation (M3). The comet and micronucleus tests were used to measure the levels of primary DNA damage and the frequency of cytogenetic changes in peripheral blood cells, respectively. Obese women at the three measured moments, presented higher levels (p <0.05) of DNA damage than the control group. However, six months after the bariatric surgery the genetic damage was significantly reduced compared to the obese women before nutritional supplementation, but the amount did not reached the control group level. Similarly, increased frequencies of micronucleated cells were detected in obese women before bariatric surgery compared to the control group. However, six months after surgery this frequency decreased significantly, being similar to that in the control group. Significant reduction of inflammatory cytokines was observed in obese women after four weeks after the beginning of nutritional, as well as after surgery. Gene expression profiling was investigated using DNA microarrays. Data showed upregulation of genes related to energy and lipid metabolism, and also to inflammatory pathways in obese women before nutritional supplementation. Changes in these gene expression and also modulation of gene associated to cell viability and DNA repair pathways were observed after the nutritional supplementation. Six month after the surgical procedure and nutritional supplementation genes involved in energy metabolism and inflammatory pathways were modulated, probably due to the significant weight loss. In conclusion, this study showed the importance of nutritional supplementation, both before and after bariatric surgery. However, it was not possible to distinguish the extension of its effects after surgery because of the weight loss.

Orientador: João Paulo de Castro Marcondes
Resumo: A obesidade é uma desordem multifatorial que envolve agentes hereditários, ambientais e estilo de vida, e suas consequências não são apenas sociais ou psicológicas, mas estão também relacionadas à presença de comorbidades como hipertensão arterial, diabetes tipo 2, doenças cardiovasculares e vários tipos de câncer. Considerando que as alterações genéticas relacionadas à obesidade não são totalmente conhecidas, assim como não se sabe a possível ação da suplementação nutricional sobre tais alterações, o presente estudo teve como objetivo avaliar a relação entre a ingestão de micronutrientes, alterações genéticas e perfil inflamatório em um grupo de 30 mulheres com obesidade mórbida, com idade entre 20 e 45 anos e submetidas à cirurgia bariátrica. A suplementação nutricional consistiu da ingestão (pó diluído em água) de vitaminas e micronutrientes correspondentes a duas DRIs (Ingestão Dietética de Referência) por dia, durante 10 semanas antes e 24 após a cirurgia bariátrica. O total de 30 mulheres eutróficas saudáveis, não fumantes e pareadas por idade às obesas, constituiu o grupo de referência. Todos os parâmetros avaliados nas mulheres obesas foram mensurados em três momentos: antes da suplementação nutricional (M1); 8 semanas após o início da suplementação e uma semana antes da cirurgia bariátrica (M2); e seis meses após o procedimento cirúrgico (M3). Os testes do cometa e do micronúcleo foram utilizados para medir, respectivamente, os níveis de danos primários no DNA e as f... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Obesity is a complex disease that originates from a combination of social, environmental and genetic factors. Furthermore, it is associated with comorbidities such as hypertension, type 2 diabetes, heart disease and various types of cancers. Since the relationship among genetic alterations, nutritional supplementation and obesity are not fully understood, this study aimed to evaluate the effects of micronutrient intake on genetic and inflammatory profile in a group of 30 morbidly obese women, aged between 20 and 45 years and undergoing bariatric surgery. The nutritional intervention consisted of two recommended dietary allowance (RDA) of vitamins and micronutrients per day, for 10 weeks before and 24 after the bariatric surgery. A total of 30 healthy normal-weight, non-smokers and matched for age to the obese women were recruited as a control group. All the checked endpoints in obese the women were measured at three moments: before nutritional supplementation (M1); 8 weeks after beginning of supplementation and one week before bariatric surgery (M2); and six months after surgery with simultaneous nutritional supplementation (M3). The comet and micronucleus tests were used to measure the levels of primary DNA damage and the frequency of cytogenetic changes in peripheral blood cells, respectively. Obese women at the three measured moments, presented higher levels (p <0.05) of DNA damage than the control group. However, six months after the bariatric surgery the genetic damage w... (Complete abstract click electronic access below)
Doutor

Nutritional insults and conditions in fetal life and infancy may influence later growth and body composition as well as the development of chronic diseases in adult life. We studied the effects of maternal food and micronutrient supplementation and exclusive breast-feeding counseling on offspring growth 0-54 months and body composition at 54 months of age. We also validated and developed equations for a leg-to-leg bioimpedance analyzer in order to assess body composition of Bangladeshi children aged 4-10 years. In the MINIMat trial in Matlab, Bangladesh, pregnant women were randomized to Early (around 9 weeks) or a Usual invitation (around 20 weeks) to food supplementation and to one of three daily micronutrient supplementations with capsules of either 30 mg Fe and 400 µg folic acid, or 60 mg Fe and 400 µg folic acid, or multiple micronutrient supplements (MMS) (15 micronutrients including 30 mg Fe and 400 µg folic acid). They were also randomized to exclusive breastfeeding counseling (EBC) or to usual health messages (UHM). Growth of their children was measured from birth to 54 months, when body composition also was assessed. There were no differences in background characteristics across the different intervention groups. There was no differential effect by prenatal interventions on birth weight or length. Early invitation to food supplementation reduced stunting from early infancy up to 54 months for boys (average difference 6.5 percent units, 95% CI=1.7 to 11.3, p=0.01), but not for girls (average difference 2.4 percent units, 95% CI=-2.2 to 7.0, p=0.31). MMS resulted in more stunting than standard Fe60F (average difference 4.8 percent units, 95% CI=0.8 to 8.9, p=0.02). Breast-feeding counseling prolonged the duration of exclusive breastfeeding (difference 35.0 days, 95% CI 30.6-39.5, p<0.001). Neither the pregnancy interventions nor the breast-feeding counseling influenced body composition at 54 months. Early food supplementation in pregnancy reduced the occurrence of stunting in boys 0-54 months, while prenatal MMS increased the proportion of stunting. Early food and multiple micronutrient supplementation or exclusive breastfeeding intervention provided to rural Bangladeshi women during pregnancy did not affect offspring body composition at 54 months of age. The effects on postnatal growth suggest programming effects in early fetal life.

L'etude min-vit-aox avait pour objectif d'evaluer chez des sujets ages institutionnalises, l'impact d'une supplementation en vitamines et/ou en mineraux antioxydants a doses nutritionnelles, durant deux annees, sur le metabolisme oxydatif, l'etat immunitaire, la morbidite et la mortalite. 756 sujets ages repartis en quatre groupes de traitement recevaient soit des vitamines (6 mg de beta-carotene, 15 mg de dl alpha-tocopherol, 120 mg de vitamine c) soit des mineraux (20 mg de sulfate de zinc, 100 g de selenite de sodium), soit l'association vitamines et mineraux aux doses precedemment citees, soit un placebo. Un bilan biologique a ete realise a l'inclusion, au 6#e#m#e mois et apres une annee de supplementation. L'analyse du statut vitaminique et mineral a l'inclusion confirme la prevalence elevee de sujets presentant des stigmates biochimiques evocateurs de deficiences en certains micronutriments, en particulier en vitamine c, zinc et selenium. L'analyse longitudinale a montre qu'un apport nutritionnel induisait des le 6#e#m#e mois une augmentation des taux seriques en ces micronutriments avec disparition quasi totale des stigmates biochimiques evocateurs d'une deficience, excepte pour le zinc. L'activite erythrocytaire de la glutathion peroxydase et la production d'il1 par les monocytes ont ete modifiees au cours de la supplementation. Ces resultats pose le probleme de l'eventuel non reversibilite de certains dommages et l'interet d'optimiser le potentiel antiradicalaire avant la derniere periode de la vie. L'analyse des consequences cliniques de la supplementation objectivera les benefices eventuels de telles modifications

It has been generally recognised that sick children have an increased risk on malnutrition. An activated immune system requires more nutrients while illness is often associated with a lower absorption and decreased consumption because of lack of appetite. When these increased needs are not balanced with an adequate availability of nutrients, the sick child is at higher risk of developing malnutrition.Médecins Sans Frontières investigated the question whether this process is mitigated by simple short term nutritional supplementation given to sick children alongside medical treatment. Three Randomised Controlled Trials (RCT’s) were conducted. The first, in Democratic Republic of Congo, was a pilot; 180 children with malaria were randomised in 2 arms: 1 group receiving 2 weeks of ready to use therapeutic food (RUTF) and a control group. The children were followed for a period of 4 weeks. Children in the RUTF group showed a higher weight gain in the first 14 days compared to the control group, at day 28 the weight gain in both groups was similar.Thereafter, 2 RCT’s were implemented in Uganda and Nigeria using a similar methodology. Children with malaria, lower respiratory tract infection or diarrhoea (sample size of 2202) were randomised in three groups: supplemented with 2 weeks of RUTF, supplemented with 2 weeks of micronutrient powder (MNP), and not receiving supplementation after each disease episode. The incidence of malnutrition was compared after an observation period of 6 months. The trial in Uganda showed a reduction in malnutrition in the RUITF group with 31%, while in Nigeria, there was no significant reduction in the RUTF group. The MNP group did not show reduction in malnutrition in any site. In the group of moderate malnourished children the RUTF and MNP supplementations were not effective in preventing deterioration to severe malnutrition. However, when the studies were combined the RUTF group showed a lower mortality compared to the MNP group.Multi-variate analysis did not show a reduction of incidence of malnutrition in the supplementation groups. A strong association with morbidity was found. A higher frequency of diarrhoea was associated with an increased incidence of malnutrition. The association with malaria episodes was mixed; it was associated with a higher incidence of malnutrition in Kaabong, but in Goronyo a higher frequency of malaria decreased the incidence of malnutrition. In addition, a more frequent monitoring of the children and treatment of their illnesses was associated with a decreased incidence of malnutrition.The difference in effectiveness of supplementation between the sites can be explained by differences in food security and level of morbidity. It is argued that the fragile food security in Kaabong limits the supply of nutrients, and therefore supplementation with RUTF was effective. In Goronyo the high frequency of morbidity limits convalescence and therefore supplementation was not effective.It is likely that malnutrition is more effectively prevented when several interventions are combined like water and sanitation to prevent diarrhoea, malaria chemoprophylaxis and preventative and curative health and nutrition interventions.This dissertation will present the background, the methods of the trials and the results, followed by a discussion on the implications for programming and research.
Doctorat en Santé Publique
info:eu-repo/semantics/nonPublished

碩士
弘光科技大學
營養醫學研究所
96
Asthma is a chronic respiratory tract disease and the prevalence increases gradually. Global professionals always look for and renew the therapeutic guidelines of asthma. The purpose of the present theme examined the micronutrients status, immune function, oxidative stress, pulmonary function, and life quality in asthma patients comparison with the values in healthy control subjects, and further to evaluate the improvement after the intervention of nutrition supplements. From January to April of 2007, a total of 30 asthma patients ( 9 males and 21 females, average 37.5 ± 11.2 y ) enrolled in this study （IRB：HP060007, Cheng-Ching Hospital, Taichung, Taiwan, ROC）. First, they took the 「SF-36 generic health survey」and「asthma control test」questionnaires, pulmonary function test, blood sampling with total IgE, immune markers (CD3+、CD19+), anti-oxidative micronutrients status (Vitamin C , E , β-carotene , zinc , cupper , selenium) , n-3 fatty acids (EPA and DHA) , and oxidative stress markers (glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase enzyme activities, and MDA products). In a addition, 20 healthy subjects (9 males and 11 females, average 34.3 ± 5.9 y) randomly selected from health examination center referred to control group. The study was divided into two parts. At the first part, the questionnaires, pulmonary function, and blood sampling were taken before, during and after the intervention. It was found that asthma patients have higher significantly total IgE, CD19+ and lower CD3+ (p < 0.05). And asthma group also have higher MDA, Copper, serum copper/zinc ratio, and markedly lower glutathione peroxidase, Glutathione reductase, catalase, superoxide dismutase enzyme activities, vitamin C, E, β-carotene, selenium, and zinc levels than that in control group. Moreover, plasma EPA and DHA percentage in asthma group is also lower than the values in control group. At second part of the present theme, after 2 months’ nutritional intervention for asthma group, the MDA, serum copper, copper/zinc ratio significantly decreased than that at before and month 1 during. In addition, higher glutathione peroxidase, glutathione reductase, catalase , superoxide dismutase enzyme activities, and vitamin C, E , β-carotene, selenium, and zinc levels, as well as plasma concentrations of EPA and DHA were also noted obviously. Even total IgE have declined tendency. In the SF-36 survey, data showed that physical dimension in asthma group are lower than the control group, but mental dimension is no different between two groups. After nutritional intervention for asthma group, all the dimensions improved except physical functioning, which means the quality of life in asthma are improved greatly after nutritional intervention. In the asthma control test, the percentage of ‘totally controlled’ add‘ controlled well’ increase from 23.3% to 66.7% after intervention, which indicate more improvement from patient. The pulmonary function was also mildly improvement after intervention（p > 0.05）. Asthma patients have a higher allergic immune index, imbalance between B cell and T cell, lower anti-inflammatory n-3 polyunsaturated fatty acid, higher oxidative stress and anti-oxidative stress micronutrients status. After nutrition intervention for asthma, the anti-oxidative micronutrients status, the oxidative stress, the anti-inflammatory n-3 polyunsaturated fatty acid, and balance the immune status between B cell and T cell were recovered. The results suggested that nutritional supplements bring reduced oxidative stress, elevated the anti-oxidative capacity, and further help modulation of the immune function and improvement of life quality in patients with asthma. It can be the complementary and integrated therapy for asthma.