| 1. |
- Berglund, Staffan, 1975-
(författare)
-
Effects of iron supplementation on iron status, health and neurological development in marginally low birth weight infants.
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Due to small iron stores and rapid growth during the first months of life, infants with low birth weight (LBW) are at risk of iron deficiency (ID). ID in infancy is associated with irreversible impaired neurodevelopment. Preventive iron supplementation may reduce the risk of ID and benefit neurodevelopment, but there is also a possible risk of adverse effects. More than 50% of all LBW infants are born with marginally LBW (MLBW, 2000-2500g), and it is not known if they benefit from iron supplementation. Methods We randomized 285 healthy, Swedish, MLBW infants to receive 3 different doses of oral iron supplements; 0 (Placebo), 1, and 2 mg/kg/day from six weeks to six months of age. Iron status, during and after the intervention was assessed and so was the prevalence of ID and ID anemia (IDA), growth, morbidity and the interplay with iron and the erythropoetic hormones hepcidin and erythropoietin (EPO). As a proxy for conduction speed in the developing brain, auditory brainstem response (ABR) was analyzed at six months. In a follow up at 3.5 years of age, the children were assessed with a cognitive test (WPPSI-III) and a validated parental checklist of behavioral problems (CBCL), and compared to a matched reference group of 95 children born with normal birth weight. Results At six months of age, the prevalence of ID and IDA was significantly higher in the placebo group compared to the iron supplemented infants. 36% had ID in the placebo group, compared to 8% and 4 % in the 1 and 2mg/kg/day-groups, respectively. The prevalence of IDA was 10%, 3% and 0%, respectively. ABR-latencies did not correlate with the iron intake and was not increased in infants with ID or IDA. ABR wave V latencies were similar in all three groups. Hepcidin correlated to ferritin and increased in supplemented infants while EPO, which was negatively correlated to iron status indicators, decreased. At follow up there were no differences in cognitive scores between the groups but the prevalence of behavioral problems was significantly higher in the placebo group compared to those supplemented and to controls. The relative risk increase of CBCL-scores above a validated cutoff was 4.5 (1.4 – 14.2) in the placebo-group compared to supplemented children. There was no detected difference in growth or morbidity at any age. Conclusion MLBW infants are at risk of ID in infancy and behavioral problems at 3 years of age. Iron supplementation at a dose of 1-2 mg/kg/day from six weeks to six months of age reduces the risks with no adverse effects, suggesting both short and long term benefit. MLBW infants should be included in general iron supplementation programs during their first six months of life.
|
|
| 2. |
- Bergström, Erik, 1944-
(författare)
-
Cardiovascular risk indicators in adolescents : the Umeå youth study
- 1995
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atherosclerotic cardiovascular diseases (CVD), particularly coronary heart disease (CHD) and cerebrovascular disease, are today major causes of death in the industrialised parts of the world. There are evidence to suggest that the atherosclerotic process starts in childhood, implying that preventive measures should be implemented already in children and adolescents.The aim of this study was to examine CVD risk indicators and their determinants in healthy Swedish adolescents. The study population comprised 14- and 17-year-old boys and girls (n=1032), in the dty and surroundings of Umeå in northern Sweden.Biochemical, anthropometric, and physiological parameters associated to CVD (s- lipoproteins and s-apolipoproteins, s-insulin, s-ferritin, anthropometric measurements, blood pressure, and physical fitness) were evaluated in relation to family history of CVD, weight and length at birth, infant feeding regimen, physical growth during infancy and childhood, current diet, physical activity, smoking, and educational level and occupation of the parents.The main findings of the study were that, on average, total serum cholesterol (TC) values in boys and girls were at the same level as reported from other European countries. A family history of CVD, short duration of breast feeding, low attained height during infancy and childhood, high body mass index (BMI), and low physical fitness were all associated with an unfavourable serum lipid profile. The findings also showed that features typical of the insulin resistance syndrome are present already in adolescents. In boys, iron stores, estimated by serum ferritin, were related to BMI and physical fitness, in a similar way as well established CVD risk indicators. Compared to previous dietary studies in Sweden, mean relative (energy %) fat intake had decreased substantially although the mean relative intake of saturated fat was still rather high. For both boys and girls, reported relative energy intake (energy intake/estimated energy expenditure) decreased with increasing level of BMI. Furthermore, daily smoking was more common among adolescents from families with low socio-economic status (SES) but was most strongly associated to smoking in peers. Tobacco use was considerably higher among adolescents attending vocational programs at secondary high school as compared to theoretical programs. Daily smokers had a more unfavourable serum lipid profile compared to non-smokers. Low socio-economic status of the parents was related to higher BMI and low educational level to higher dietary fat intake in both boys and girls.In conclusion, the findings of the study show that parameters linked to adult CVD when examined in adolescents, are related to family history, infant nutrition, previous physical growth, current body composition, physical fitness, physical activity, smoking, and social status and educational level of the parents.
|
|
| 3. |
- Björmsjö, Maria, 1978-
(författare)
-
Clinical effects of reduced iron content and fortification with bovine lactoferrin in infant formula
- 2023
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Breast milk, with its complex, individual and over time adapting composition, is considered the optimal source of nutrition for infants during the first months of life. Two possible contributing factors to the benefits of breastfeeding compared to infant formula-feeding are the differences in iron and lactoferrin (Lf) concentrations between breast milk and infant formula. The overall purpose of the LIME (a Swedish acronym) study was to add knowledge on how to reduce the gap in health and development between breastfed and formula-fed infants. The aim of this double-blinded controlled trial, and doctoral thesis, was to investigate how added bovine lactoferrin and reduced iron concentration in infant formula affect health and development.Methods: Recruitment took place from June 2014 to June 2018. With equal gender distribution, healthy term Swedish formula-fed infants (n=180) were randomly assigned, from 6 weeks to 6 months of age, to receive a low iron formula (2 mg/L) with bovine Lf (1.0 g/L) (Lf+, n=72), a low iron formula without Lf (Lf-, n=72) or a control standard formula with 8 mg/L iron and no Lf (CF, n=36). Additionally, 72 breastfed infants were recruited as a reference (BF) group. Blood samples were drawn at 4, 6, and 12 months. Primary outcomes were cytokine levels and iron status. Secondary outcomes were growth, gastrointestinal symptoms, infection-related morbidity and treatments, antibody response to vaccines and cognitive development.Findings: All explored outcomes were unaffected by Lf fortification and the two low iron groups (Lf+ and Lf-) were combined and compared to the CF group. At 6 months of age the TGF-β2 levels were lower among the low iron groups and more similar to the BF infants. No other significant differences in cytokine levels were observed. There was a trend of lower geometric mean of ferritin at 4, 6, and 12 months for the combined low iron groups compared to the CF group (67.7 vs 88.7, 39.5 vs 50.9, and 20.5 vs 25.1 μg/L, respectively, p=0.054, p=0.056, and p=0.082). No similar trends or significant differences were found for any of the other iron status indicators, except for hepcidin at 12 months with lower levels in the low iron group compared to CF (37.8 vs 49.4 ng/mL, p=0.027). Overall, infants fed low iron formula had iron status indicators closer to the breastfed reference group and the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) was generally low with no significant differences among the intervention groups.There were no clinically relevant effects of the interventions on growth, gastrointestinal symptoms, infection-related morbidity, vaccine antibody response or neurocognitive development.In secondary analyses, the present study confirmed previous results of higher cognitive scores among breastfed infants compared to formula-fed and observed an unexpected lower IgG response to vaccines against Hib and Diphtheria.Conclusion: Adding bovine lactoferrin did not affect any of the clinical outcomes explored. Lowering infant formula iron concentration from 8 to 2 mg/L minimally reduced iron stores to levels closer to breastfed infants but did not increase the risk of ID/IDA during the first year of life. Consequently, 2 mg/L is a sufficient level of iron fortification during the first six months of life in a population with low risk of ID. Both adjustments are considered safe with no observed adverse effects.
|
|
| 4. |
|
|
| 5. |
- Hernell, Olle, 1945-
(författare)
-
Den humana mjölkens lipaser : egenskaper och fysiologiska aspekter
- 1974
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- I avhandlingen visas att: Human mjölk innehåller två lipaser. Det ena är ett serum-stimulerat lipas (lipoprotein lipas). Lipoprotein lipaser är enzymer som har en central roll i den normala katabolismen av de triglyceridrika plasma- lipoproteinerna. Lipaset har sannolikt inte någon fysiologisk funktion i mjölken. En metod beskrivs med vilken lipaset har renats ca 9 500 gånger från mjölk. Det serum-stimulerade lipaset från human mjölk har de klassiska egenskaperna för ett serum-stimulerat lipas (lipoprotein lipas). Med en immunologisk metod visas att lipaset korsreagerar med motsvarande lipaser i bovin mjölk och human postheparin plasma. Slutsatsen är att det serum-stimulerade lipaset i human mjölk är väl värt att studera eftersom det mycket väl kan ha många egenskaper gemensamma med de fysiologiskt aktiva och viktiga humana serum-stimulerade lipaserna. Det andra lipaset i human mjölk, det gallsalt-stimulerade lipaset, har en låg substratspecificitet. Gallsalter stimulerar enzymaktiviteten mot alla substrat som testats. Mot mjölkens egna triglycerider är lipaset helt inaktivt i frånvaro av gallsalter. I närvaro av gall- salter spjälkar lipaset alla tre esterbindningarna i triglycerid- molekylen så att slutprodukterna blir fria fettsyror och glycerol. Gallsalter skyddar lipaset mot olika typer av inaktivering, t ex mot inaktivering av tarmens proteinnedbrytande enzymer. Det är sannolikt att gallsalternas effekt beror på att de direkt interagerar med enzymproteinet. Lipaset visas ha sådana egenskaper att det väsentligt skulle kunna bidraga till den spjälkning av mjölktriglyceriderna som sker i tarmen hos den nyfödde.
|
|
| 6. |
- Karlsson Videhult, Frida, 1980-
(författare)
-
Effects of early probiotic supplementation in a pediatric setting : Focus on body composition, metabolism and inflammation
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- We aimed to determine the short- and long-term effects on growth, body composition, metabolic and inflammatory markers following supplementation with the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) during weaning. Methods: One-hundred and seventy-nine healthy, infants in Umeå city, Västerbotten County were randomised to daily intake of cereals with (n=89) or without (n=90) LF19 108 colony-forming units from 4 to 13 months of age. Weight, length, head circumference and body composition, assessed by skinfold thickness, were examined at 4, 5.5, 6.5, 9, 12 and 13 months of age. Venous blood was drawn at 5.5 and 13 months. In all, 171 infants completed the intervention and were invited to a follow-up at 8-9 years of age between 2009 and 2011, 120 children participated. Weight, height, sagittal abdominal diameter and body composition (using Dual Energy X-ray Absorptiometry-scan) were measured. Data on weight and height at 4 years were collected from medical records. The families filled out a 4-day food record and a food frequency questionnaire, physical activity was assessed using a pedometer for 7 days. At 5.5, 13 months and 8-9 years of age we analysed the serum blood lipid profile. At 8-9 years fasting glucose, insulin, aspartate and alanine transaminases were analysed in serum. Homeostatic Model Assessment index was calculated. At follow-up serum adiponectin, high-sensitivity C-reactive protein and plasma C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide 1, glucagon, insulin, leptin, plasminogen activator inhibitor-1, resistin and visfatin were analysed. For characterisation of the plasma metabolome, a subgroup (n=40) was analysed at 5.5 and 13 months of age by gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) analysis and in all (n=112) children at the follow-up using untargeted GC-GC/MS. Results: There were no differences between the LF19 and placebo group regarding body weight, length/height at any assessment from 4 months to 8-9 years of age; nor were there any differences between the groups in body composition. In the LF19 group 19 % were overweight/obese, the corresponding number was 21 % in the placebo group (p=0.78). Analysed metabolic and inflammatory markers, both during the intervention and the follow-up did not differ between the two groups. At 13 months of age lower levels of palmitic acid and palmitoleic acid (both p<0.04) and higher levels of putrescine (p<0.01) were seen in the LF19 compared to the placebo group. These differences did not persist at 8-9 years of age. At that age, we found statistically stronger models when comparing overweight/obese and normal weight children as well as in relation to sex. Conclusion: Early intervention with the probiotic LF19 at the time of weaning exerted transient effects on the metabolome. In a long-term perspective, we found neither benefit nor harm on growth, body composition, metabolic or inflammatory markers following supplementation with LF19 during weaning.
|
|
| 7. |
- Sjöberg, Veronika, 1980-
(författare)
-
Immune response of the small intestinal mucosa in children with celiac disease : impact of two environmental factors, resident microbiota and oats
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Celiac disease (CD) is an immune-mediated enteropathy caused by permanent intolerance to dietary gliadin in wheat gluten and related prolamines in barley and rye. The pathogenesis of CD is still unknown and several different environmental factors have been associated with CD, such as dysbiosis of the microflora. In this translational study we investigated the immune status and the interplay of T-cells and Tregs in the mucosa of children with CD and controls, as well as the immune status in treated CD patients, provoked by either dietary oats, CD associated bacteria or gluten.The major findings in the studies were: First, indicators of extrathymic T-cells maturation (ETCM), i.e., the RAG1 enzyme required for recombination of the T cell receptor (TCR) genes and the preTα-surrogate chain in the immature TCR, were both expressed at lower levels in CD patients compared to controls. In addition, IELs expressing RAG1 were less abundant in CD patients compared to controls. The levels of these two indicators stayed low in treated CD patients as well, suggesting that impaired capacity of ETCM is an inherent feature of CD patients. Second, IL-17A, a cytokine involved in both inflammation and anti-bacterial responses was increased in active CD. The major cellular source was CD8+IELs. Furthermore, ex vivo challenge of biopsies from treated CD patients with gluten and with CD-associated bacteria induced an IL-17A response. The CD-associated bacteria also influenced the magnitude of the IL-17A response to gluten. Third, we investigated the effect of dietary oats on local immune status in the intestinal mucosa by comparing CD patients receiving GFD with and without oats. 22 different mRNAs for immunity effector molecules and tight junction proteins were analyzed. We found that expression of two down-regulatory cytokines, two activating NK-receptors and the tight-junction protein claudin-4 normalized in patients on a standard GFD while they did not normalize in patients on a GFD with oats. Fourth, we analyzed the expression level of mRNAs for chemokines, cytotoxic effector molecules, NK-receptors and their ligands in IELs and epithelial cells. Expression levels of several of these genes follow disease activity, suggesting massive recruitment of immune cells by both cell types accompanied by increased IEL-mediated cytotoxicity in the epithelium of inflamed mucosa.In this thesis we have identified three potential risk factors for development of CD: 1) an inherent lower level of ETCM in the small intestinal mucosa than in controls. This could lead to decreased generation of regulatory T cells and less capacity to tolerate gluten and adapt to the local milieu in the mucosa. 2) Dysbiosis of the resident microbiota with increased IL-17A production that could promote local inflammation and immune cell infiltration as well as antibacterial reactions. 3) Dietary oats may provoke a local immune response in a sub-population of CD patients. These patients should probably avoid oats in their GFD but larger studies are needed.
|
|
| 8. |
- Timby, Niklas, 1973-
(författare)
-
Effects of feeding term infants low energy low protein formula supplemented with bovine milk fat globule membranes
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Observational studies have shown that early nutrition influences short- and long-term health of infants. Formula-fed infants have higher protein and energy intakes and lower intakes of several biologically active components present in human milk. Some of these are present in the milk fat globule membrane (MFGM). The aim of the present study was to examine the effects of feeding term infants an experimental low energy low protein formula supplemented with bovine milk fat globule membranes. Our hypothesis was that infants fed experimental formula (EF), compared to infants fed standard formula (SF), would have outcomes more similar to a breast-fed reference (BFR) group.Methods In a double-blinded randomized controlled trial, 160 exclusively formula-fed, healthy, term infants were randomized to receive EF or SF from <2 to 6 months of age. A BFR group consisted of 80 breast-fed infants. Measurements were made at baseline, 4, 6 and 12 months of age. The EF had lower energy (60 vs. 66 kcal/100 mL) and protein (1.20 vs. 1.27 g/100 mL) concentrations, and was supplemented with a bovine MFGM concentrate.Results At 12 months of age, the EF group performed better than the SF group in the cognitive domain of Bayley Scales of Infant Development, 3rd Ed. During the intervention, the EF group had a lower incidence of acute otitis media than the SF group, less use of antipyretics and the EF and SF groups differed in concentrations of s-IgG against pneumococci. The formula-fed infants regulated their intakes by increasing meal volumes. Thus, there were no differences between the EF and SF groups in energy or protein intakes, blood urea nitrogen, insulin or growth including body fat percent until 12 months of age. Pressure-to-eat score at 12 months of age was reported lower by parents of formula-fed infants than by parents of breast-fed infants, indicating a low level of parental control of feeding in the formula-fed groups. Neither high pressure-to-eat score nor high restrictive score was associated with formula feeding. During the intervention, the EF group gradually reached higher serum cholesterol concentrations than the SF group, and closer to the BFR group. At 4 months of age, there was no significant difference in the prevalence of lactobacilli in saliva between the EF and SF groups.Conclusions Supplementation of infant formula with a bovine MFGM fraction enhanced both cognitive and immunological development in formula-fed infants. Further, the intervention narrowed the gap in serum cholesterol concentrations between formula-fed and breast-fed infants. The lower energy and protein concentrations of the EF were totally compensated for by a high level of self-regulation of intake which might, at least partly, be explained by a low level of parental control of feeding in the study population. The findings are of importance for further development of infant formulas and may contribute to improved short- and long-term health outcomes for formula-fed infants.
|
|
| 9. |
- West, Christina, 1969-
(författare)
-
Feeding Lactobacillus paracasei ssp. paracasei strain F19 to infants during weaning : effects on adaptive immunity and gut microbial function
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Gut microbial composition has been associated with immune-mediated diseases. Breastfeeding yields a microbiota rich in bifidobacteria and promotes colonization by lactobacilli. Bifidobacteria and lactobacilli are considered health-promoting and are used as probiotics, i.e. live microbial food supplements which when ingested in adequate amounts confer a beneficial effect on the host. During weaning the developing gut immune system is exposed to an increasing variety of antigens from both foods and gut microbiota.Aims: We aimed to determine if daily feeding of 1x108 colony-forming units (CFU) of the probiotic Lactobacillus paracasei ssp. paracasei strain F19 (LF19) to healthy term infants from 4 to 13 months of age could maintain some of the beneficial effects conferred by breastfeeding on gut microbial composition, with possible effects on gut microbial function, T cell function, Th1/Th2 immune balance and eczema incidence.Study design: Infants were randomized to daily intake of cereals with (n=89) or without LF19 (n=90) from 4-13 months of age. Clinical outcome measures were monitored by diaries and a questionnaire. Stool and blood samples were obtained at 4, 6½, 9, 13 and 5½, 6½, 12 and 13 months of age, respectively. Stool samples were analyzed for lactobacilli counts by conventional culture methods and the presence of LF19 was verified by randomly amplified polymerase chain reaction (RAPD-PCR). Fecal short-chain fatty acid (SCFA) pattern, a proxy for gut microbial function, was determined by gas-liquid chromatography. After polyclonal or specific activation of T cells, the cytokine mRNA expression levels [interleukin 2 (IL2), IFN-, IL4 and IL10] were determined on isolated mRNA by quantitative real time reverse transcriptase-PCR. Serum concentrations of total and specific IgE antibodies, Haemophilus influenzae type b, diphtheria and tetanus toxoid specific IgG antibodies were analyzed by enzyme immunoassay.Results: Feeding LF19 maintained high fecal lactobacilli counts during weaning. Persistent colonization with LF19 induced differences in the fecal SCFA pattern. The cumulative incidence of eczema was lower in the probiotic group, in conjunction with a higher IFN-γ/IL4 mRNA ratio in polyclonally activated T cells. Even though there was an effect by LF19 on Th1/Th2 immune balance, there was no effect on IgE sensitization. Infants in both groups increased their capacity to express both Th1 and Th2 cytokines during the second half of infancy but the expression was still lower than that of adults. Infants in the probiotic group had lower IL2 levels after polyclonal T cell activation at 13 months of age compared with infants in the placebo group. Infants fed LF19 did not have fewer infections, but had fewer days with antibiotic prescription compared with infants fed placebo. In addition, compared to placebo, persistent colonization by LF19 enhanced specific vaccine responses to protein antigens during the course of vaccination.Conclusions: We conclude that feeding LF19 was safe, based on no observed adverse effects in our study. Infants in both groups demonstrated maturation of adaptive immune responses during weaning. Adding probiotics in complementary foods during weaning reduced the risk of eczema by 50%, with a concomitant shift towards an enhanced Th1/Th2 ratio. The reduction of eczema might be explained by probiotic effects on both T cell-mediated immune responses and reinforced gut microbial function.
|
|
| 10. |
- Öhlund, Inger, 1954-
(författare)
-
Health implications of dietary intake in infancy and early childhood
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Swedish children are the healthiest in Europe. Through regular visits to well-baby clinics, infants and young children are checked and parents given information and advice on diet and other relevant matters for their child. For a long time, adequate nutrition during infancy and childhood has been focused on encouraging proper nutrition, preventing malnutrition and deficiency states, and obtaining optimal growth. Today, malnutrition and deficiency states in infants and children are rare. But other public health problems have arisen. Nutrition early in life is now thought to influence health and diseases even in adulthood. Thus promotion of a healthy diet in early life is important for preventing public health diseases such as iron deficiency, cardiovascular disease, obesity, and dental caries. Aims: This study investigates health implications of dietary intake in infancy and early childhood. More specific focus was on the associations between dietary fat intake and serum lipid levels in infants, early dietary intake, iron status, dental caries, and Body Mass Index (BMI) at 4 years of age. In addition, hereditary factors and changes over time were evaluated. Methods: Before 6 month of age, 300 healthy infants were recruited from well-baby clinics in Umeå. This thesis is based on secondary analysis of a prospective study in these infants run from 6-18 months and a follow-up of 127 of the children at 4 years. Between 6-18 months and at 4 years, dietary intakes were assessed, anthropometric measures performed, and venous blood samples taken. At 4 years, a dental examination was also performed and anthropometric data and blood samples were collected from parents and included in the study. Results: All but two infants were ever breastfed and at 6 months 73% were still breastfed. The quality of dietary fat was not within national recommendations. At 4 years, intake of vitamin D and selenium were below and intake of sugar and sweet products above the recommendations. In girls, but not boys, higher polyunsaturated fatty acid intake was associated with lower levels of total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B levels. Iron status of the children was generally good and no child had iron deficiency anaemia (IDA). Children’s haemoglobin (Hb) levels tracked from infancy to 4 years and correlated with their mother’s Hb. Fortified infant products and meat were important sources of iron at both 12 months and 4 years. Children with frequent intake of cheese had less caries in this population with low caries prevalence. We found higher protein intake over time to be associated with higher Body Mass Index (BMI) at 4 years and high BMI at 4 years was associated with high BMI at 6 mo. There was also an association between the BMI of the child and that of its parents. Conclusions: BMI of the child and parents (especially the father), and iron status at 6 months were predictors of these variables at 4 years of age. The quality rather than the quantity of dietary fat in infancy affected serum lipid values. Even in a healthy and well-nourished group of Swedish infants and young children, quality of food and intake of nutrients are important for current and later health of the child.
|
|
