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  • 1. Aggett, P J
    et al.
    Haschke, F
    Heine, W
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Koletzko, B
    Launiala, K
    Rey, J
    Rubino, A
    Schöch,
    Senterre, J
    Comment on the content and composition of lipids in infant formulas. ESPGAN Committee on Nutrition.1991In: Acta paediatrica Scandinavica, ISSN 0001-656X, Vol. 80, no 8-9, p. 887-96Article in journal (Refereed)
  • 2. Aggett, P J
    et al.
    Haschke, F
    Heine, W
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Koletzko, B
    Rey, J
    Rubino, A
    Schöch, G
    Senterre, J
    Strobel, S
    Comment on antigen-reduced infant formulae. ESPGAN Committee on Nutrition.1993In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 82, no 3, p. 314-9Article in journal (Refereed)
  • 3. Aggett, P J
    et al.
    Haschke, F
    Heine, W
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Launiala, K
    Rey, J
    Rubino, A
    Schöch, G
    Senterre, J
    Tormo, R
    Comment on the composition of soy protein based infant and follow-up formulas. ESPGAN Committee on Nutrition.1990In: Acta paediatrica Scandinavica, ISSN 0001-656X, Vol. 79, no 10, p. 1001-5Article in journal (Refereed)
  • 4. Aggett, Peter J
    et al.
    Agostoni, Carlo
    Axelsson, Irene
    De Curtis, Mario
    Goulet, Olivier
    Hernell, Olle
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Koletzko, Berthold
    Lafeber, Harry N
    Michaelsen, Kim F
    Puntis, John W L
    Rigo, Jacques
    Shamir, Raanan
    Szajewska, Hania
    Turck, Dominique
    Weaver, Lawrence T
    Feeding preterm infants after hospital discharge: a commentary by the ESPGHAN Committee on Nutrition.2006In: Journal of pediatric gastroenterology and nutrition, ISSN 1536-4801, Vol. 42, no 5, p. 596-603Article in journal (Refereed)
    Abstract [en]

    Survival of small premature infants has markedly improved during the last few decades. These infants are discharged from hospital care with body weight below the usual birth weight of healthy term infants. Early nutrition support of preterm infants influences long-term health outcomes. Therefore, the ESPGHAN Committee on Nutrition has reviewed available evidence on feeding preterm infants after hospital discharge. Close monitoring of growth during hospital stay and after discharge is recommended to enable the provision of adequate nutrition support. Measurements of length and head circumference, in addition to weight, must be used to identify those preterm infants with poor growth that may need additional nutrition support. Infants with an appropriate weight for postconceptional age at discharge should be breast-fed when possible. When formula-fed, such infants should be fed regular infant formula with provision of long-chain polyunsaturated fatty acids. Infants discharged with a subnormal weight for postconceptional age are at increased risk of long-term growth failure, and the human milk they consume should be supplemented, for example, with a human milk fortifier to provide an adequate nutrient supply. If formula-fed, such infants should receive special postdischarge formula with high contents of protein, minerals and trace elements as well as an long-chain polyunsaturated fatty acid supply, at least until a postconceptional age of 40 weeks, but possibly until about 52 weeks postconceptional age. Continued growth monitoring is required to adapt feeding choices to the needs of individual infants and to avoid underfeeding or overfeeding

  • 5. Aminoff, Anna
    et al.
    Gunnar, Erika
    Barbaro, Michela
    Mannila, Maria Nastase
    Duponchel, Christiane
    Tosi, Mario
    Robinson, Kristina Lagerstedt
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Ehrenborg, Ewa
    Novel mutations in microsomal triglyceride transfer protein including maternal uniparental disomy in two patients with abetalipoproteinemia2012In: Clinical Genetics, ISSN 0009-9163, E-ISSN 1399-0004, Vol. 82, no 2, p. 197-200Article in journal (Refereed)
  • 6.
    Andersson, Eva-Lotta
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bläckberg, Lars
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Fält, Helen
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lindquist, Susanne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bile salt-stimulated lipase and pancreatic lipase-related protein 2: key enzymes for lipid digestion in the newborn examined using the Caco-2 cell line2011In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 52, no 11, p. 1949-1956Article in journal (Refereed)
    Abstract [en]

    In rodents, bile salt-stimulated lipase (BSSL) and pancreatic lipase-related protein 2 (PLRP2) are the dominant lipases expressed in the exocrine pancreas in early life, when milk is the main food. The aim of the present study was to evaluate if BSSL and PLRP2 are also key enzymes in neonatal intestinal fat digestion. Using Caco-2 cells as a model for the small intestinal epithelium, purified human enzymes were incubated in the apical chamber with substrates and bile salt concentrations resembling the milieu of the small intestine of newborn infants. BSSL and PLRP2 hydrolyzed triglycerides (TG) to free fatty acids (FA) and glycerol. The cells took up the FA, which were reesterfied to TG. Together, BSSL and PLRP2 have a synergistic effect, increasing cellular uptake 4-fold compared to the sum of each lipase alone. A synergistic effect was also observed with retinyl ester as a substrate. PLRP2 hydrolyzed cholesteryl ester but not as efficiently as BSSL, and the two had an additive rather than synergistic effect. We conclude the key enzymes in intestinal fat digestion are different in newborns than later in life. Further studies are needed to fully understand this difference and its implication for designing optimal neonatal nutrition.

  • 7.
    Andersson, Y
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Sävman, K
    Bläckberg, L
    Hernell, O
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Pasteurization of mother's own milk reduces fat absorption and growth in preterm infants.2007In: Acta paediatrica, ISSN 0803-5253, Vol. 96, no 10, p. 1445-9Article in journal (Refereed)
    Abstract [en]

    Aim: A randomized study was conducted to evaluate whether pasteurized milk (Holder pasteurization 62.5 degrees C, 30 min) reduces fat absorption and growth in preterm infants. Methods: Preterm infants (825-1325 g) born with gestational age </=30 weeks were randomized into two groups, of which one started with pasteurized own mother's milk for 1 week and continued with raw milk the following week, and a second group was fed in reverse order. By using this design the infants served as their own controls. At the end of each week, a 72-h fat balance was performed and growth was monitored. Results: We found, on an average, 17% higher fat absorption with raw as compared to pasteurized milk. Infants gained more weight and linear growth assessed as knee-heel length was also greater during the week they were fed raw milk as compared to the week they were fed pasteurized milk. Conclusion: Feeding preterm infants pasteurized as compared to raw own mother's milk reduced fat absorption. When the infants were fed raw milk, they gained more in knee-heel length compared to when they were fed pasteurized milk.

  • 8.
    Andersson, Yvonne
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Lönnerdal, Bo
    Department of Nutrition, University of California, Davis, CA 95616.
    Graverholt, Gitte
    Arla Foods Ingredients, Aarhus, Denmark.
    Fält, Helen
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Formula feeding skews immune cell composition toward adaptive immunity compared to breastfeeding2009In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 183, no 7, p. 4322-4328Article in journal (Refereed)
    Abstract [en]

    The ontogeny of the immune system and the effect thereon by type of infant feeding is incompletely understood. We analyzed frequencies and composition of immune cells in blood of breastfed (BF) and formula-fed (FF) infants at 1.5, 4, and 6 mo of age. Three formulas with the same protein concentration but with varying levels of alpha-lactalbumin and caseinoglycomacropeptide were compared. Twenty-nine exclusively BF infants served as reference, and 17 infants in each formula group completed the study. Whole blood and PBMCs were analyzed by flow cytometry and immunoflow cytometry, respectively. Leukocyte count of BF infants increased with time due to increased frequency of neutrophils. Lymphocyte count was high at 1.5 mo and was unchanged over time, as were the relative proportions of CD4+ alphabetaT cells, CD8+ alphabetaT cells, B cells, NK cells, and gammadeltaT cells. Most CD45R0+CD3+ cells were HLA-DR- and hence memory cells. Compared with breastfeeding, formula feeding resulted in a significant decrease in proportion of NK cells, but a significant increase in naive CD4+ alphabetaT cells and an elevated CD4-to-CD8 ratio, that is, 3.3 in the combined FF groups compared with 2.6 in the BF group. No significant differences were found between the three groups of FF infants. In conclusion, blood cells of lymphoid lineage did not change significantly in frequencies or composition from 1.5 to 6 mo of age in BF infants. In contrast, FF infants displayed an ongoing maturation of adaptive immunity cells and a delayed recruitment of innate immunity cells as compared with BF infants.

  • 9.
    Andersson, Yvonne
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lindquist, Susanne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bergström, S
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Three variants of parathyroid hormone-related protein messenger RNA are expressed in human mammary gland.1997In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 41, no 3, p. 380-3Article in journal (Refereed)
    Abstract [en]

    PTH-related protein (PTHrP) is found in a variety of tissues; particularly high levels are present in human milk. The structure of the human PTHrP gene is complex, and alternative splicing allows expression of three different variants PTHrP139, PTHrP173, and PTHrP141, respectively. To determine which of the variants are expressed in human mammary gland a reverse transcriptase polymerase chain reaction (RT-PCR) method was elaborated, distinguishing the three variants. mRNA isolated from human milk cells, human mammary epithelial cells (HMEC) and human nonlactating mammary gland cells were analyzed. The RT-PCR experiments resulted in amplification of DNA fragments corresponding to all three variants for all three cell sources tested. The nucleotide sequences of the PCR fragments were determined and verified to be identical to the reported sequences. Hence, it is concluded that human mammary gland epithelial cells express three variants of PTHrP. Whether these have different physiologic effects in the mammary gland or in the breast fed infant remain to be explored.

  • 10.
    Andersson, Yvonne
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lindquist, Susanne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lagerqvist, Carina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lactoferrin is responsible for the fungistatic effect of human milk.2000In: Early Human Development, ISSN 0378-3782, E-ISSN 1872-6232, Vol. 59, no 2, p. 95-105Article in journal (Refereed)
    Abstract [en]

    Human milk has recognized anti-microbial effects and it has been repeatedly shown that breast-fed infants have fewer and less severe infections than formula-fed infants. While most studies have focused on anti-bacterial and anti-viral activities few have focused on the anti-fungal effect of human milk. Dermal and other infections caused by fungi are common in very low birth weight (VLBW) infants. Using a liquid culturing method and Candida albicans and Rhodotorula rubra as representative fungi, we studied the anti-fungal effect of human milk and certain human milk proteins. In vitro, human milk showed potent inhibitory effect on fungal growth. Most, if not all of this effect was caused by lactoferrin via its iron-binding capacity; increasing the iron content of the incubation medium abolished the inhibitory effect. In contrast, other human milk proteins with known or suggested anti-microbial effects rather increased fungal growth. Viability test and electron microscopy revealed that the growth inhibitory effect of human milk, i.e. mediated by lactoferrin, is fungistatic rather than fungicidal.

  • 11. Ascher, H
    et al.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Kristiansson, B
    Lindberg, T
    Stenhammar, L
    [Infant food and celiac disease. Risk of increase when changing the diet]1994In: Lakartidningen, ISSN 0023-7205, Vol. 91, no 49, p. 4641-3Article in journal (Other academic)
  • 12. Axelsson, Irene
    et al.
    Finkel, Yigael
    Michaelsen, Kim Fleischer
    Gebre-Medhin, Mehari
    Hernell, Olle
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Jakobsson, Iréne
    Perlhagen, John
    Jansson, Martina
    [Complementary food to breastfed infants. Introduction can wait until the age of six months but not longer]2004In: Lakartidningen, ISSN 0023-7205, Vol. 101, no 3, p. 195-7Article in journal (Other academic)
    Abstract [sv]

    [Article in Swedish]

  • 13.
    Bas, A
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Forsberg, G
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Sjöberg, Veronika
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Aberrant extrathymic T cell receptor gene rearrangement in the small intestinal mucosa: a risk factor for coeliac disease?2009In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 58, no 2, p. 189-195Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Coeliac disease is a small intestine enteropathy caused by permanent intolerance to wheat gluten. Gluten intake by patients with coeliac disease provokes a strong reaction by intestinal intraepithelial lymphocytes (IELs), which normalises on a gluten-free diet. AIM: To investigate whether impaired extrathymic T cell maturation and/or secondary T cell receptor (TCR) gene recombination in IELs are features of coeliac disease which could contribute to the failure of establishing tolerance to gluten.

    METHODS: Expression levels of the four splice-forms of recombination activating gene-1 (RAG1) mRNA and preT alpha-chain (preTalpha) mRNA were determined in IEL-subsets of children with coeliac disease and controls. Frequencies of RAG1 expressing IELs were determined by immunomorphometry.

    RESULTS: In controls, the RAG1-1A/2 splice-form selectively expressed outside the thymus, was dominant and expressed in both mature (TCR(+)) and immature (CD2(+)CD7(+)TCR(-)) IELs ( approximately 8 mRNA copies/18S rRNA U). PreTalpha was expressed almost exclusively in CD2(+)CD7(+)TCR(-) IELs ( approximately 40 mRNA copies/18S rRNA U). By contrast, RAG1 and preTalpha mRNA levels were low in patients with coeliac disease compared to controls, both with active disease and with inactive, symptom-free disease on a gluten-free diet (p values <0.01 for mature and <0.05 for immature IELs). Similarly, the frequencies of RAG1+ IELs were significantly lower in patients with coeliac disease compared to controls (p<0.001).

    CONCLUSIONS: Patients with coeliac disease appear to have an impaired capacity for extrathymic TCR gene rearrangement. This is an inherent feature, which probably plays a pivotal role in the failure to efficiently downregulate the T cell response to gluten.

  • 14.
    Berglund, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Björn
    Division of Neonatology, Department of Women and Child Health, Karolinska Institute, Stockholm, Sweden.
    Hägglöf, Bruno
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effects of iron supplementation of LBW infants on cognition and behavior at 3 years2013In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 131, p. 47-55Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Low birth weight (LBW) infants are at increased risk of cognitive and behavioral problems and at risk for iron deficiency, which is associated with impaired neurodevelopment. We hypothesized that iron supplementation of LBW infants would improve cognitive scores and reduce behavioral problems. METHODS: In a randomized controlled trial, 285 marginally LBW (2000-2500 g) infants received 0, 1, or 2 mg/kg/day of iron supplements from 6 weeks to 6 months of age. At 3.5 years of age, these infants and 95 normal birth weight controls were assessed with a psychometric test (Wechsler Preschool and Primary Scale of Intelligence) and a questionnaire of behavioral problems (Child Behavior Checklist; CBCL). RESULTS: There were no significant differences in IQ between the LBW groups or LBW infants versus controls. Mean (SD) full-scale IQ was 105.2 (14.5), 104.2 (14.7), and 104.5 (12.7) in the placebo, 1 mg, and 2 mg groups, respectively (P = .924). However, for behavioral problems, there was a significant effect of intervention. The prevalence of children with CBCL scores above the US subclinical cutoff was 12.7%, 2.9%, and 2.7% in the placebo, 1-mg, and 2-mg groups, respectively (P = .027), compared with 3.2% in controls. Relative risk (95% confidence interval) for CBCL score above cutoff in placebo-treated children versus supplemented was 4.5 (1.4-14.2). CONCLUSIONS: Early iron supplementation of marginally LBW infants does not affect cognitive functions at 3.5 years of age but significantly reduces the prevalence of behavioral problems. The study suggests a causal relation between infant iron deficiency and later behavioral problems.

  • 15.
    Bergström, E
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Hernell, O
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Obesity and insulin resistance in childhood and adolescence.2005In: From Preventive Nutrition: The Comprehensive Guide for Health Professionals, third ed, Humana Press Inc. Totowa, NJ , 2005, p. 293-316Chapter in book (Other academic)
  • 16.
    Bergström, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, B
    Persson, L A
    Sex differences in iron stores of adolescents: what is normal?1995In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 20, no 2, p. 215-24Article in journal (Refereed)
    Abstract [en]

    We evaluated iron status and its determinants in healthy adolescents. Fasting morning blood samples from a school-based cross-sectional study were analyzed for serum ferritin (SF), serum iron, total iron-binding capacity, and circulating transferrin receptors. Physical development, chronic disease, medication, dietary intake, and physical activity were assessed using clinical examination, questionnaires, and 7-day records. The risk of having low serum ferritin values was estimated using bivariate and multivariate regression. Subjects were 867 healthy Swedish adolescents, 14- and 17-year-olds (472 boys and 395 girls). SF values increased with pubertal stage in boys but not in girls. Five percent of the boys and 15% of the girls had SF values < 12 micrograms/L. Of the 17-year-old boys, 7% compared to 1% of the 17-year-old girls had SF values > 100 micrograms/L. Forty-one percent of cases with SF values > 12 micrograms/L had serum iron values < 15 microM, and 22% had transferrin saturation values < 16%. Mean total iron intakes of the boys were high [1.6 times recommended daily allowance (RDA)] and mean intakes of the girls were adequate (0.9 times RDA). Low heme iron intakes increased the risk of low iron stores (< 12 micrograms/L) in girls but not in boys. Total iron intake or other dietary factors, physical development, or level of physical activity did not influence the risk of low SF. The findings of this study suggest that the differences in iron status between boys and girls in adolescence results primarily from biological differences other than menstrual bleeding or insufficient iron intake. Furthermore, the results question the role of SF as an indicator of iron deficiency in adolescence, in particular if age and sex are not taken into consideration. We suggest that different reference values for SF, including the cut-off limit for low SF, adjusted for age and sex, should be considered. The high iron intakes and corresponding high SF values found in the older boys are noticeable in light of the possible negative health consequences of iron overload.

  • 17.
    Bergström, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Persson, L A
    Dietary changes in Swedish adolescents.1993In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 82, no 5, p. 472-80Article in journal (Refereed)
    Abstract [en]

    A school-based dietary survey, using seven-day records, was performed in two cohorts of Swedish adolescents; 14- and 17-year-olds. The study comprised 366 boys and 365 girls. When compared to previous studies in Sweden, a striking finding was a decrease in dietary fat intake and an increase in carbohydrate intake. However, the relative intake of saturated fat had not changed (15% of total energy). The dietary change was mainly due to an increased consumption of cereal products. There were no major differences in dietary habits or nutrient density of the food between the two age groups, or between boys and girls. The mean intakes of protein, fat and carbohydrate, expressed as a percentage of the total energy intake, were 15, 33 and 52%, respectively. The mean intakes of vitamins and minerals were low only for selenium. The boys had a high iron intake (1.5 and 1.7 times the recommended intake for 14- and 17-year-olds, respectively) while the mean iron intake for girls was 0.9 times the recommended dietary allowances in both age groups. The intake of dietary salt was higher in boys than in girls (7.7 g and 9.0 g per day in 14- and 17-year-old boys, respectively, and 5.8 g per day in both 14- and 17-year-old girls). In a long-term health perspective, this positive change in nutrient intake in adolescents may contribute to a reduction in the incidence of diet-related diseases in Sweden.(ABSTRACT TRUNCATED AT 250 WORDS)

  • 18.
    Bergström, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Persson, L A
    Vessby, B
    Serum lipid values in adolescents are related to family history, infant feeding, and physical growth.1995In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 117, no 1, p. 1-13Article in journal (Refereed)
    Abstract [en]

    Total serum cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), and lipoprotein (a) (Lp(a)) were analysed in 879 14- and 17-year-old healthy adolescents (477 boys and 402 girls), and related to family history of cardiovascular disease, early feeding, weight and length at birth, and physical growth during infancy and childhood. Mean TC was significantly higher in girls than in boys (4.4 and 4.2 mmol/l, respectively, both age-groups together). High TC values ( > 5.2 mmol/l) were more prevalent in girls than in boys: 14% and 17% compared to 6% and 12% in 14- and 17-year-old girls and boys, respectively. Mean TC and LDL-C values were lower during mid-puberty in both boys and girls while, in boys but not in girls, mean HDL-C values decreased and TG values increased successively with increasing pubertal stage. Girls who were taking oral contraceptives had higher mean values of TC (4.91/4.39 mmol/l), TG (1.32/0.83 mmol/l), and apo B (0.89/0.73 g/l). Boys with a family history of early deaths ( < 55 years) from myocardial infarction and girls with a family history of cerebral haemorrhage/thrombosis in fathers had higher mean values of TC (4.55/4.17 and 5.03/4.40 mmol/l, for boys and girls, respectively), LDL-C (2.84/2.47 and 3.08/2.56 mmol/l), and apo B (0.73/0.70 and 0.86/0.73 g/l). Adolescents with short duration of breast feeding ( < 6 months), or early introduction of infant formula, had higher mean values of TC (4.29/4.14 mmol/l) and apo B (0.72/0.68 g/l). There were no significant correlations between serum lipid values and body weight or length at birth, but adolescents with high LDL-C (upper quartile) seemed to have lower attained heights during infancy and childhood. In conclusion, this study shows that serum lipids in adolescence are primarily related to age and sex but also to early determinants like family history of cardiovascular diseases, infant feeding, and early physical growth.

  • 19. Bergström, S
    et al.
    Hansson, L
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, B
    Nilsson, A K
    Strömqvist, M
    Cloning and sequencing of human kappa-casein cDNA.1992In: DNA Sequence, ISSN 1042-5179, E-ISSN 1029-2365, Vol. 3, no 4, p. 245-6Article in journal (Refereed)
    Abstract [en]

    A cDNA encoding kappa-casein of human milk was cloned and sequenced. The kappa-casein cDNA was isolated from a lambda gt11 library generated from mRNA prepared from a mammary gland biopsy obtained from a lactating woman. The library was screened with polyclonal rabbit antibodies raised against purified native kappa-casein. The obtained nucleotide sequence contained an ORF sufficient to encode the entire amino acid sequence of a kappa-casein precursor protein consisting of 182 amino acids. This includes a tentative signal peptide of 20 amino acids and a processed protein of 162 amino acids.

  • 20. Bernbäck, S
    et al.
    Bläckberg, Lars
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Fatty acids generated by gastric lipase promote human milk triacylglycerol digestion by pancreatic colipase-dependent lipase.1989In: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 1001, no 3, p. 286-93Article in journal (Refereed)
    Abstract [en]

    The concerted action of purified bovine gastric lipase and human pancreatic colipase-dependent lipase and colipase, or crude human pancreatic juice, in the digestion of human milk triacylglycerols was explored in vitro. Gastric lipase hydrolyzed milk triacylglycerol with an initially high rate but became severely inhibited already at low concentration of released fatty acid. In contrast, colipase-dependent lipase could not, by itself, hydrolyze milk triacylglycerol. However, a short preincubation of milk with gastric lipase, resulting in a limited lipolysis, made the milk fat triacylglycerol available for an immediate and rapid hydrolysis by pancreatic juice, and also for purified colipase-dependent lipase, provided colipase and bile salts were present. The same effect was obtained when incubation with gastric lipase was replaced by addition of long-chain fatty acid. Long-chain fatty acid increased the binding of colipase-dependent lipase to the milk fat globule. Binding was efficient only in the presence of both fatty acid and colipase. We conclude that a limited gastric lipolysis of human milk triacylglycerol, resulting in a release of a low concentration of long-chain fatty acids, is of major importance for the subsequent hydrolysis by colipase-dependent lipase in the duodenum.

  • 21. Bernbäck, S
    et al.
    Bläckberg, Lars
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    The complete digestion of human milk triacylglycerol in vitro requires gastric lipase, pancreatic colipase-dependent lipase, and bile salt-stimulated lipase.1990In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 85, no 4, p. 1221-6Article in journal (Refereed)
    Abstract [en]

    Gastric lipase, pancreatic colipase-dependent lipase, and bile salt-stimulated lipase all have potential roles in digestion of human milk triacylglycerol. To reveal the function of each lipase, an in vitro study was carried out with purified lipases and cofactors, and with human milk as substrate. Conditions were chosen to resemble those of the physiologic environment in the gastrointestinal tract of breast-fed infants. Gastric lipase was unique in its ability to initiate hydrolysis of milk triacylglycerol. Activated bile salt-stimulated lipase could not on its own hydrolyze native milk fat globule triacylglycerol, whereas a limited hydrolysis by gastric lipase triggered hydrolysis by bile salt-stimulated lipase. Gastric lipase and colipase-dependent lipase, in combination, hydrolyzed about two thirds of total ester bonds, with monoacylglycerol and fatty acids being the end products. Addition of bile salt-stimulated lipase resulted in hydrolysis also of monoacylglycerol. When acting together with colipase-dependent lipase, bile salt-stimulated lipase contributed also to digestion of tri- and diacylglycerol. We conclude that digestion of human milk triacylglycerol depends on three lipases with unique, only partly overlapping, functions. Their concerted action results in complete digestion with free glycerol and fatty acids as final products.

  • 22. Bernbäck, S
    et al.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bläckberg, Lars
    Bovine pregastric lipase: a model for the human enzyme with respect to properties relevant to its site of action.1987In: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 922, no 2, p. 206-13Article in journal (Refereed)
    Abstract [en]

    Preduodenal lipolysis is considered to promote efficient lipid digestion in the neonatal period. The lipase(s) responsible may be of pregastric or gastric origin depending upon the species. We have previously reported on purification and molecular characterization of a pregastric lipase from calf. Antibodies to this bovine enzyme crossreact with a protein of similar size in human gastric contents and also inhibit its lipolytic activity. Since the bovine and human enzymes also have similar kinetic properties, the view is favoured that the bovine enzyme can be used as a model for physiological studies relevant to human neonates. In contrast to the lipases operating in the small intestine pregastric lipase has the unique property of initiating the hydrolysis of human milk fat globule triacylglycerol. In order to do this no cofactor is required. Pregastric lipase was stable at low pH and had an acid-pH optimum. Furthermore, it was extremely resistant to pepsin. In contrast, pancreatic proteinases, i.e. trypsin and chymotrypsin, inactivated the enzyme. The rate of inactivation was increased in the presence of bile salts which by themselves could inhibit enzyme activity. Thus, pregastric lipase is ideally suited for activity in the stomach but will not, under healthy conditions, contribute to lipid digestion in the duodenum.

  • 23. Björkstén, B
    et al.
    Burman, L G
    De Château, P
    Fredrikzon, B
    Gothefors, Leif
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Collecting and banking human milk: to heat or not to heat?1980In: British medical journal, ISSN 0007-1447, Vol. 281, no 6243, p. 765-9Article in journal (Refereed)
    Abstract [en]

    Data on human breast milk and its handling when fed to babies who cannot be breast-fed were reviewed to determine whether the method of processing and storage affected the properties of the milk. Breast milk is normally contaminated by potential pathogens, which seem to produce no ill effects, but it also contains antimicrobial properties which protect against infection. The evidence suggests that pasteurisation not only eliminates pathogenic bacteria but also damages bacteriostatic mechanisms, so making the milk more susceptible to later contamination. Pasteurisation also affects the nutritional properties of milk. Freezing has little effect on milk proteins, while a study on the effect of refrigeration showed that there was little bacterial growth at temperatures below 8 degrees C. Several years' experience of feeding donated raw milk to newborn infants has confirmed that it produces no ill effects. These findings suggest that pasteurisation of donated breastmilk is unnecessary, and it is not recommended, while the decision whether or not to freeze the milk may be made on practical grounds. Raw breast milk can be safely stored at 4-6 degrees C for 72 hours.

  • 24.
    Björmsjö, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Ekström, Nina
    Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland.
    Silfverdal, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Department of Nutrition, University of California, Davis, USA.
    Berglund, Staffan K.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Vaccine IgG antibody response is higher in formula-fedcompared to breastfed infants but not affected by added bovine lactoferrin or lowered iron content: results from a randomized controlled trialManuscript (preprint) (Other academic)
  • 25.
    Björmsjö, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Department of Nutrition, University of California, Davis, CA.
    Berglund, Staffan K.
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Immunological Effects of Adding Bovine Lactoferrin and Reducing Iron in Infant Formula: A Randomized Controlled Trial2022In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 74, no 3, p. e65-e72Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Compared to formula-fed infants, breastfed infants have a lower risk of infections. Two possible reasons for this are the presence of the anti-infective and anti-inflammatory protein lactoferrin and the lower level of iron in breast milk. We explored how adding bovine lactoferrin and reducing the iron concentration in infant formula affect immunology and risk of infections in healthy infants.

    METHODS: In a double-blind controlled trial, term formula-fed (FF) Swedish infants (n = 180) were randomized to receive, from 6 weeks to 6 months of age, a low-iron formula (2 mg/L) with added bovine lactoferrin (1.0 g/L) (Lf+; n = 72); low-iron formula with no added lactoferrin (Lf-; n = 72); and standard formula at 8 mg/L iron and no added lactoferrin (control formula [CF]; n = 36). Cytokines, infections, and infection related treatments were assessed until 12 months of age.

    RESULTS: No adverse effects were observed. There were no apparent effects on transforming growth factor beta (TGF-β)1, TGF-β2, tumor necrosis factor alfa (TNF-α) or interleukin2 (IL-2) at 4, 6, or 12 months, except of higher TGF-β2 at 6 months in the CF group in comparison to the low iron groups combined (P = 0.033). No significant differences in otitis, respiratory infections, gastroenteritis, or other monitored infections and treatments were detected for any of the study feeding groups during the first 6 months and only a few and diverging effects were observed between 6 and 12 months.

    CONCLUSIONS: Adding bovine lactoferrin and reducing iron from 8 to 2 mg/L in infant formula was safe. No clinically relevant effects on cytokines or infection related morbidity were observed in this well-nourished and healthy population.

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  • 26.
    Björmsjö, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Department of Nutrition, University of California, Davis, USA.
    Berglund, Staffan K.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Reducing infant formula iron fortification to 2 mg/L does not increase the risk of iron deficiency or impact neurocognitive development at 12 months: a randomized controlled trialManuscript (preprint) (Other academic)
  • 27.
    Björmsjö, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Berglund, Staffan K.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Reducing Iron Content in Infant Formula from 8 to 2 mg/L Does Not Increase the Risk of Iron Deficiency at 4 or 6 Months of Age: A Randomized Controlled Trial2021In: Nutrients, E-ISSN 2072-6643, Vol. 13, no 1, article id 3Article in journal (Refereed)
    Abstract [en]

    Many infant formulas are fortified with iron at 8-14 mg/L whereas breast milk contains about 0.3 mg/L. Another major difference between breast milk and infant formula is its high concentration of lactoferrin, a bioactive iron-binding protein. The aim of the present study was to investigate how reducing the iron content and adding bovine lactoferrin to infant formula affects iron status, health and development. Swedish healthy full-term formula-fed infants (n = 180) were randomized in a double-blind controlled trial. From 6 weeks to 6 months of age, 72 infants received low-iron formula (2 mg/L) fortified with bovine lactoferrin (1.0 g/L) (Lf+), 72 received low-iron formula un-fortified with lactoferrin (Lf-) and 36 received standard formula with 8 mg of iron/L and no lactoferrin fortification as controls (CF). Iron status and prevalence of iron deficiency (ID) were assessed at 4 and 6 months. All iron status indicators were unaffected by lactoferrin. At 4 and 6 months, the geometric means of ferritin for the combined low-iron groups compared to the CF-group were 67.7 vs. 88.7 and 39.5 vs. 50.9 mu g/L, respectively (p = 0.054 and p = 0.056). No significant differences were found for other iron status indicators. In the low-iron group only one infant (0.7%) at 4 months and none at 6 months developed ID. Conclusion: Iron fortification of 2 mg/L is an adequate level during the first half of infancy for healthy term infants in a well-nourished population. Adding lactoferrin does not affect iron status.

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  • 28.
    Blind, Per Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Bläckberg, Lars
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Carboxylic ester hydrolase: a serum marker of acute pancreatitis1987In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 2, no 5, p. 597-603Article in journal (Refereed)
    Abstract [en]

    By use of an enzyme-linked immunosorbent assay we established serum reference values of carboxylic ester hydrolase, a pancreatic secretory lipolytic enzyme, and explored to see if a raised serum level is indicative of acute pancreatitis. Postoperative elevation of carboxylic ester hydrolase was observed in seven out of ten patients who underwent pancreatic surgery. Serum levels of carboxylic ester hydrolase and amylase were determined in 129 patients admitted due to abdominal emergency conditions. Amylase was elevated in 27 patients, and in 20 of these raised carboxylic ester hydrolase levels affirmed the diagnosis acute pancreatitis. In five out of the seven patients with elevated amylase alone no etiologic factor of acute pancreatitis was found. Another 11 patients had raised carboxylic ester hydrolase levels without concomitant elevation of amylase. In all these patients, a likely cause of pancreatic inflammation was identifiable. Hence, a raised carboxylic ester hydrolase level, even in presence of normal amylase, could be indicative of acute pancreatic inflammation.

  • 29. Blind, Per-Jonas
    et al.
    Büchler, M
    Bläckberg, Lars
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Andersson, Yvonne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Uhl, W
    Beger, H G
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Carboxylic ester hydrolase. A sensitive serum marker and indicator of severity of acute pancreatitis.1991In: International journal of Pancreatology, ISSN 0169-4197, Vol. 8, no 1, p. 65-73Article in journal (Refereed)
    Abstract [en]

    When using clinical criteria, both falsely positive and falsely negative diagnoses of acute pancreatitis (AP) are often made. Based on a clinical study, elevated serum levels of the pancreatic lipolytic enzyme carboxylic ester hydrolase (CEH) was recently suggested to be a highly specific marker of acute pancreatitis. To determine the sensitivity of the test for AP, a study on patients with the diagnosis set objectively was necessary. In the present study, AP was diagnosed by contrast-enhanced computed tomography in 64 patients, and histopathological examination of tissue removed at laparotomy in 18 of them. By these criteria, 42 patients suffered from acute interstitial pancreatitis (AIP), and 22 patients from necrotizing pancreatitis (NP). Based on the CEH concentrations in the first serum sample obtained in each patient, the sensitivity of CEH for pancreatitis was 98%. From the second day after admission, CEH levels in patients with NP were significantly higher than in patients with AIP. Furthermore, in patients with NP, CEH values remained at a raised level for the following 10 d, whereas a significant decrease of CEH values was noted in patients with AIP. In contrast, total serum amylase activities were higher in patients suffering of AIP than in patients suffering of NP during the observation period. We conclude, that the sensitivity of the CEH test is very high for AP. CEH concentrations remaining at a high level are suggestive of NP, whereas diminishing CEH levels are suggestive of AIP.

  • 30. Bläckberg, L
    et al.
    Angquist, K A
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bile-salt-stimulated lipase in human milk: evidence for its synthesis in the lactating mammary gland.1987In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 217, no 1, p. 37-41Article in journal (Refereed)
    Abstract [en]

    Human milk contains many enzymes and other biologically active proteins. One of the enzymes, the bile salt-stimulated lipase, constitutes as much as 1% of the milk proteins. Its importance for efficient utilization of milk lipids by the breast-fed infant is now well established. However, whether the lipase protein is a product of protein synthesis within the mammary gland has up till now been an unanswered question. Using biopsy material from lactating human mammary gland we have now demonstrated that the enzyme is synthesized within the gland. This was done by immunoprecipitation of [35S]methionine-labelled protein from tissue pieces. By activity determination we could also determine the amount of enzyme stored in the gland. It was concluded that bile salt-stimulated lipase accounted for 1.3 micrograms/mg tissue protein. Finally, from this figure it could be calculated that about 10-15% of the total protein present in the tissue was milk protein.

  • 31.
    Bläckberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bile salt-stimulated lipase in human milk. Evidence that bile salt induces lipid binding and activation via binding to different sites.1993In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 323, no 3, p. 207-210Article in journal (Refereed)
    Abstract [en]

    Human milk bile salt-stimulated lipase ensures efficient triacylglycerol utilization in breast-fed newborns. For activity against long-chain triacylglycerol, primary bile salts are a prerequisite. Bile salts also protect the enzyme from inactivation by intestinal proteases. We have studied the effect of different bile salts on activation, protease protection, lipid binding, and enzyme inactivation, caused by an arginine modifying agent. Based on the results we propose a model involving two bile salt binding sites; one activation-site specific for primary bile salt, and another, less specific, lipid binding promoting site at which also secondary bile salt binds. Binding to this latter site induces binding of enzyme to emulsified substrates but binding promoting site at which also secondary bile salt binds. Binding to this latter site induces binding of enzyme to emulsified substrates but without subsequent lipolysis.

  • 32.
    Bläckberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Further characterization of the bile salt-stimulated lipase in human milk1983In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 157, no 2, p. 337-341Article in journal (Refereed)
    Abstract [en]

    Bile salt-stimulated lipase is a milk enzyme unique to the higher primates. Its molecular and kinetic characteristics differ greatly from other lipolytic enzymes; e.g., pancreatic lipase and lipoprotein lipase. It has a much higher app. Mr, 310000 on gel filtration and 100000 after denaturation. It requires primary bile salts for optimal activity and bile salts also protect the enzyme from proteolytic and heat inactivation. It may, due to its low substrate specificity, contribute to the utilization of a variety of milk lipids. Since it lacks positional specificity, digestion of milk triglycerides should be complete, which may explain why fat absorption is more efficient in breast-fed than in formula-fed infants.

  • 33. Bruck, Wolfram M
    et al.
    Redgrave, Michele
    Tuohy, Kieran M
    Lönnerdal, Bo
    Graverholt, Gitte
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gibson, Glenn R
    Effects of bovine alpha-lactalbumin and casein glycomacropeptide-enriched infant formulae on faecal microbiota in healthy term infants2006In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 43, no 5, p. 673-679Article in journal (Refereed)
    Abstract [en]

    Objective: Certain milk factors may promote the growth of a host-friendly gastrointestinal microbiota, for example, one that is predominated by bifidobacteria, a perceived healthpromoting genus. This may explain why breast-fed infants experience fewer intestinal infections than their formula-fed counterparts who are believed to have a more diverse microbiota, which is similar to that of adults. The effects of formulas supplemented with 2 such ingredients from bovine milk, a-lactalbumin (alpha-lac) and casein glycomacropeptide (GMP), on gut flora were investigated in this study.

    Patients and Methods: Six-week-old (4-8 wk), healthy term infants were randomised to a standard infant formula or 1 of 2 test formulae enriched in alpha-Jac with higher or lower GMP until 6 months. Faecal bacteriology was determined by the culture-independent procedure fluorescence in situ hybridisation.

    Results: There was a large fluctuation of bacterial counts within groups with no statistically significant differences between groups. Although all groups showed a. predominance of bifidobacteria, breast-fed infants had a small temporary increase in counts. Other bacterial levels varied in formula-fed groups, which overall showed an adult-like faecal microflora.

    Conclusions: It can be speculated that a prebiotic effect for alpha-lac and GMP is achieved only with low starting populations of beneficial microbiota (eg, infants not initially breast-fed).

  • 34.
    Buttner, Barbara E.
    et al.
    Department of Food Science, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Witthoft, Cornelia M.
    Department of Food Science, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effect of type of heat treatment of breastmilk on folate content and pattern2014In: Breastfeeding Medicine, ISSN 1556-8253, E-ISSN 1556-8342, Vol. 9, no 2, p. 86-91Article in journal (Refereed)
    Abstract [en]

    Background: Breastmilk is the recommended aliment for preterm infants. Milk banks provide donated breastmilk for the neonatal care of preterm infants when mother's own milk is not is available. To avoid pathogen transmission, donated breastmilk is heat-treated according to different procedures before administration. There is varying information on the effect of heat treatment on folate in breastmilk. Sufficient folate intake, however, is essential for normal growth and brain development. This study determined and compared the effects of different heat treatments on breastmilk folate content and pattern of individual folate forms. Materials and Methods: Donated Swedish breastmilk samples were heat-treated according to three procedures: two low temperature treatments (57 degrees C, 23 minutes; 62.5 degrees C, 12 minutes) and a rapid high temperature treatment (heating to 73 degrees C in boiling water). The folate content and pattern were determined before and after treatment by high-performance liquid chromatography. Results: The folate content in 38 untreated Swedish breastmilk samples was 15046nmol/L. Two different folate vitamers were detected: 5-methyltetrahydrofolate (78 +/- 7%) and tetrahydrofolate (22 +/- 7%). Heat treatment affected only tetrahydrofolate stability and decreased folate content by 15-24%; however, the effects on folate content did not differ among the investigated heat treatment procedures. Conclusions: Folate losses during heat treatment of human milk were considered acceptable. Yet, native folate content of heat-treated, non-fortified breastmilk supplied only 25% of the recommended daily intake for preterm infants.

  • 35. Bäck, Ove
    et al.
    Blomquist, Hans K Son
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stenberg, Berndt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Does vitamin D intake during infancy promote the development of atopic allergy?2009In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 89, no 1, p. 28-32Article in journal (Refereed)
    Abstract [en]

    The active metabolite of vitamin D, 1,25-(OH)2D3, has immunomodulatory properties in addition to its more established action on bone and calcium metabolism. Recently vitamin D has been proposed as one of several environmental factors responsible for the increase in atopic diseases during the last decades. The objective of this study was to determine whether the estimated dose of dietary vitamin D3 during the first year of life is associated with atopic diseases up to the age of 6 years. In a prospective birth cohort study 123 six-year-old children were investigated for the cumulative incidence of atopic dermatitis, allergic rhinitis or asthma by means of a postal questionnaire. Their vitamin D3 intake during infancy was recorded in a previous study and the relationship between lower or higher vitamin D3 intake and atopic illness later in childhood was assessed. Atopic manifestations were more prevalent in the group with higher intake of vitamin D3. Although small, this study supports previous investigations suggesting a role of vitamin D intake during infancy in the development of atopic allergy later in childhood. If these findings are confirmed in prospective controlled clinical trials, prevention through modified vitamin D3 supplementation in infancy could be discussed to reduce the burden of atopic illnesses.

  • 36.
    Callahan, Emily A.
    et al.
    EAC Health and Nutrition, LLC, VA, United States.
    Chatila, Talal
    Boston Children's Hospital, MA, United States; Harvard Medical School, MA, United States.
    Deckelbaum, Richard J.
    Institute of Human Nutrition and Department of Pediatrics, Columbia University Irving Medical Center, NY, United States.
    Field, Catherine J.
    Department of Agricultural, Food & Nutritional Science, University of Alberta, AB, Canada.
    Greer, Frank R.
    Department of Pediatrics (Emeritus), University of Wisconsin, WI, United States.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Järvinen, Kirsi M.
    Department of Pediatrics, University of Rochester Medical Center, NY, United States.
    Kleinman, Ronald E.
    Harvard Medical School, MA, United States; MassGeneral Hospital for Children, MA, United States; Massachusetts General Hospital, MA, United States.
    Milner, Joshua
    Department of Pediatrics, Columbia University Irving Medical Center, NY, United States.
    Neu, Josef
    Department of Pediatrics, University of Florida, FL, United States.
    Smolen, Kinga K.
    Boston Children's Hospital, MA, United States; Harvard Medical School, MA, United States.
    Wallingford, John C.
    LLC, WA, United States.
    Assessing the safety of bioactive ingredients in infant formula that affect the immune system: recommendations from an expert panel2022In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 115, no 2, p. 570-587Article in journal (Refereed)
    Abstract [en]

    Bioactive ingredients for infant formula have been sought to reduce disparities in health outcomes between breastfed and formula-fed infants. Traditional food safety methodologies have limited ability to assess some bioactive ingredients. It is difficult to assess the effects of nutrition on the infant immune system because of coincident developmental adaptations to birth, establishment of the microbiome and introduction to solid foods, and perinatal environmental factors. An expert panel was convened to review information on immune system development published since the 2004 Institute of Medicine report on evaluating the safety of new infant formula ingredients and to recommend measurements that demonstrate the safety of bioactive ingredients intended for that use. Panel members participated in a 2-d virtual symposium in November 2020 and in follow-up discussions throughout early 2021. Key topics included identification of immune system endpoints from nutritional intervention studies, effects of human milk feeding and human milk substances on infant health outcomes, ontologic development of the infant immune system, and microbial influences on tolerance. The panel explored how "nonnormal" conditions such as preterm birth, allergy, and genetic disorders could help define developmental immune markers for healthy term infants. With consideration of breastfed infants as a reference, ensuring proper control groups, and attention to numerous potential confounders, the panel recommended a set of standard clinical endpoints including growth, response to vaccination, infection and other adverse effects related to inflammation, and allergy and atopic diseases. It compiled a set of candidate markers to characterize stereotypical patterns of immune system development during infancy, but absence of reference ranges, variability in methods and populations, and unreliability of individual markers to predict disease prevented the panel from including many markers as safety endpoints. The panel's findings and recommendations are applicable for industry, regulatory, and academic settings, and will inform safety assessments for immunomodulatory ingredients in foods besides infant formula.

  • 37. Casper, Charlotte
    et al.
    Carnielli, Virgilio P.
    Hascoet, Jean-Michel
    Lapillonne, Alexandre
    Maggio, Luca
    Timdahl, Kristina
    Olsson, Birgitta
    Vagero, Marten
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    rhBSSL Improves Growth and LCPUFA Absorption in Preterm Infants Fed Formula or Pasteurized Breast Milk2014In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 59, no 1, p. 61-69Article in journal (Refereed)
    Abstract [en]

    Objectives: Preterm infants often experience suboptimal growth, which can affect organ development. The aim of this study was to improve growth by treatment with bile salt-stimulated lipase (BSSL), naturally present in breast milk, but lost after pasteurization, and absent in formula. Methods: Two clinical trials were performed with a predefined analysis of combined data to investigate the effects of recombinant human BSSL (rhBSSL) treatment on growth velocity and fat absorption in preterm infants. The studies were randomized and double-blinded comparing 7-day treatment with rhBSSL and placebo, administered in pasteurized breast milk or formula, using a crossover design. Results: Sixty-three infants were evaluated for safety. At randomization, the mean (standard deviation) weight was 1467 (193) g and mean postmenstrual age was 32.6 (0.5) weeks. Sixty and 46 infants were evaluated for growth velocity and fat absorption, respectively. rhBSSL treatment significantly improved mean growth velocity by 2.93 g.kg(-1).day(-1) (P<0.001) compared with placebo (mean 16.86 vs 13.93 g.kg(-1).day(-1)) and significantly decreased the risk of suboptimal growth (<15 g.kg(-1).day(-1)) (30% vs 52%, P = 0.004). rhBSSL significantly increased absorption of the long-chain polyunsaturated fatty acids, docosahexaenoic acid, and arachidonic acid by 5.76% (P = 0.013) and 8.55% (P = 0.001), respectively, but had no significant effect on total fat absorption. The adverse-event profile was similar to placebo. Conclusions: In preterm infants fed pasteurized breast milk or formula, 1 week of treatment with rhBSSL was well tolerated and significantly improved growth and long-chain polyunsaturated fatty acid absorption compared to placebo. This publication presents the first data regarding the use of rhBSSL in preterms and the results have led to further clinical studies.

  • 38. Casper, Charlotte
    et al.
    Hascoet, Jean-Michel
    Ertl, Tibor
    Gadzinowski, Janusz S.
    Carnielli, Virgilio
    Rigo, Jacques
    Lapillonne, Alexandre
    Couce, Maria L.
    Vagero, Marten
    Palmgren, Ingrid
    Timdahl, Kristina
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Recombinant Bile Salt-Stimulated Lipase in Preterm Infant Feeding: A Randomized Phase 3 Study2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 5, article id e0156071Article in journal (Refereed)
    Abstract [en]

    Introduction Feeding strategies are critical for healthy growth in preterm infants. Bile salt-stimulated lipase (BSSL), present in human milk, is important for fat digestion and absorption but is inactivated during pasteurization and absent in formula. This study evaluated if recombinant human BSSL (rhBSSL) improves growth in preterm infants when added to formula or pasteurized breast milk. Patients and Methods LAIF (Lipase Added to Infant Feeding) was a randomized, double-blind, placebo-controlled phase 3 study in infants born before 32 weeks of gestation. The primary efficacy variable was growth velocity (g/kg/day) during 4 weeks intervention. Follow-up visits were at 3 and 12 months. The study was performed at 54 centers in 10 European countries. Results In total 415 patients were randomized (rhBSSL n = 207, placebo n = 208), 410 patients were analyzed (rhBSSL n = 206, placebo n = 204) and 365 patients were followed until 12 months. Overall, there was no significantly improved growth velocity during rhBSSL treatment compared to placebo (16.77 vs. 16.56 g/kg/day, estimated difference 0.21 g/kg/day, 95% CI [-0.40; 0.83]), nor were secondary endpoints met. However, in a predefined subgroup, small for gestational age infants, there was a significant effect on growth in favor of rhBSSL during treatment. The incidence of adverse events was higher in the rhBSSL group during treatment. Conclusions Although this study did not meet its primary endpoint, except in a subgroup of infants small for gestational age, and there was an imbalance in short-term safety, these data provide insights in nutrition, growth and development in preterm infants.

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  • 39. Cederholm, Tommy
    et al.
    Marcus, Claude
    Rössner, Stephan
    Hellénius, Mai-Lis
    Björck, Inger
    Bosaeus, Ingvar
    Forsum, Elisabet
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hulthén, Lena
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Odontology.
    Larsson, Jörgen
    Lissner, Lauren
    Nilsson, Ake
    Nyman, Margareta
    Palmblad, Jan
    Sandberg, Ann-Sofie
    Aman, Per
    Replik till Lars-Erik Holm: Forskaren, samhället och jäv [The researcher, the society and partiality]2008In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, no 16, p. 1206-1207Article in journal (Refereed)
  • 40.
    Chorell, Elin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Karlsson, Frida
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    The impact of feeding Lactobacillus F19 during weaning: a study of the plasma metabolomeManuscript (preprint) (Other academic)
  • 41.
    Chorell, Elin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Videhult, Frida Karlsson
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    West, Christina E
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Impact of probiotic feeding during weaning on the serum lipid profile and plasma metabolome in infants2013In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 110, no 1, p. 116-126Article in journal (Refereed)
    Abstract [en]

    The gut microbiome interacts with the host in the metabolic response to diet, and early microbial aberrancies may be linked to the development of obesity and metabolic disorders later in life. Probiotics have been proposed to affect metabolic programming and blood lipid levels, although studies are lacking in infants. Here, we report on the lipid profile and global metabolic response following daily feeding of probiotics during weaning. A total of 179 healthy, term infants were randomised to daily intake of cereals with (n 89) or without (n 90) the addition of Lactobacillus paracasei ssp. paracasei F19 (LF19) 108 colony-forming units per serving from 4 to 13 months of age. Weight, length and skinfold thickness were monitored. Venous blood was drawn at 5·5 and 13 months of age for analysis of the serum lipid profile. In a subsample, randomly selected from each group, GC-time-of-flight/MS was used to metabolically characterise plasma samples from thirty-seven infants. A combination of multi- and univariate analysis was applied to reveal differences related to LF19 treatment based on 228 putative metabolites, of which ninety-nine were identified or classified. We observed no effects of probiotic feeding on anthropometrics or the serum lipid profile. However, we detected significantly lower levels of palmitoleic acid (16 : 1) (P < 0·05) and significantly higher levels of putrescine (P < 0·01) in LF19-treated infants. Palmitoleic acid is a major MUFA strongly linked to visceral obesity, while putrescine is a polyamine with importance for gut integrity. Whether the observed differences will have long-term health consequences are being followed.

  • 42. Danielsson, L
    et al.
    Stenhammar, L
    Ascher, H
    Cavell, B
    Dannaeus, A
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Lindberg, T
    Lindquist, B
    [Gluten intolerance in children--diagnostic routines in Sweden 1996. Great variations in celiac disease studies]1997In: Lakartidningen, ISSN 0023-7205, Vol. 94, no 37, p. 3165-8Article in journal (Other academic)
  • 43. Danielsson, L
    et al.
    Stenhammar, L
    Ascher, H
    Cavell, B
    Dannaeus, A
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Lindberg, T
    Lindquist, B
    [Proposed criteria for diagnosis of celiac disease in children]1998In: Lakartidningen, ISSN 0023-7205, Vol. 95, no 20, p. 2342-3Article in journal (Other academic)
  • 44.
    Danielsson Niemi, Liza
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Human milk compounds inhibiting adhesion of mutans streptococci to host ligand-coated hydroxyapatite in vitro2009In: Caries Research, ISSN 0008-6568, E-ISSN 1421-976X, Vol. 43, no 3, p. 171-178Article in journal (Refereed)
    Abstract [en]

    Acquisition of mutans streptococci at an early age is a risk factor for later caries development. Following our recent finding that human milk may inhibit adhesion of Streptococcus mutans the aim of the present study was to identify compounds in human milk preventing adhesion of mutans streptococci to saliva- or gp340-coated hydroxyapatite (s-HA and gp340-HA) using an in vitro model system. Superdex 200 fractions of human milk and purified proteins were screened for binding inhibition of the S. mutans strain Ingbritt. Avid inhibition was seen to both s-HA and gp340-HA for caseins, lactoferrin, IgA and IgG, and moderate inhibition for alpha-lactalbumin and bile salt-stimulated lipase, whereas albumin and lysozyme had no effect. The inhibitory epitope in beta-casein was delineated to its C-terminal LLNQELLNPTHQIYPVTQPLAPVHNPISV stretch by use of synthetic peptides. Similarly, a peptide (SCKFDEYFSQSCA) corresponding to the human lactoferrin stretch that is highly homologous to the previously shown inhibitory stretch of bovine lactoferrin was found to inhibit S. mutans Ingbritt binding. Inhibition by human milk, IgA, and the inhibitory beta-casein peptide was universal among 4 strains of S. mutans (Ingbritt, NG8, LT11, JBP) and 2 strains of S. sobrinus (6715 and OMZ176). IgG inhibited 4, alpha-lactalbumin 3 and lactoferrin 2 of these 6 strains. It was also confirmed that none of the milk components coated on HA mediated S. mutans Ingbritt adhesion, which was consistent with the finding that no milk protein was recognized on Western blots by gp340/DMBT1 monoclonal antibodies.

  • 45. Dewey, Kathryn G
    et al.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Cohen, Roberta J
    Landa Rivera, Leonardo
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Iron supplementation affects growth and morbidity of breast-fed infants: results of a randomized trial in Sweden and Honduras.2002In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 132, no 11, p. 3249-3255Article in journal (Refereed)
    Abstract [en]

    Iron supplements are often prescribed during infancy but their benefits and risks have not been well documented. We examined whether iron supplements affect growth or morbidity of breast-fed infants. Full-term infants in Sweden (n = 101) and Honduras (n = 131) were randomly assigned to three groups at 4 mo of age: 1) placebo from 4 to 9 mo; 2) placebo from 4 to 6 mo and iron supplements [1 mg/(kg. d)] from 6 to 9 mo; or 3) iron supplements from 4 to 9 mo. All infants were exclusively or nearly exclusively breast-fed to 6 mo and continued to be breast-fed to at least 9 mo. Growth was measured monthly and morbidity data were collected every 2 wk. Among the Swedish infants, gains in length and head circumference were significantly lower in those who received iron than in those given placebo from 4 to 9 mo. The same effect on length was seen in Honduras, but only at 4-6 mo among those with initial hemoglobin (Hb) > or =110 g/L. There was no significant main effect of iron supplementation on morbidity, nor any significant interaction between iron supplementation and site, but for diarrhea (with both sites combined), there was an interaction between iron supplementation and initial Hb. Among infants with Hb < 110 g/L at 4 mo, diarrhea was less common among those given iron than in those given placebo from 4-9 mo, whereas the opposite was true among those with Hb > or = 110 g/L (P < 0.05). We conclude that routine iron supplementation of breast-fed infants may benefit those with low Hb but may present risks for those with normal Hb.

  • 46.
    Domellöf, Erik
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Timby, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Department of Nutrition, University of California, Davis, USA.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Formula feeding supplemented with milk fat globule membranes  improves cognitive score in term infants at 12 months2013In: Developmental Medicine & Child Neurology, 55 (Suppl. S2): Abstracts of the European Academy of Childhood Disability 25th Annual Meeting, 10-12 October 2013, Newcastle-Gateshead, UK, Mac Keith Press , 2013, p. 50-50Conference paper (Refereed)
    Abstract [en]

    Introduction: Findings of enhanced cognitive development in breast‐fed compared with formula‐fed infants suggest that breast milk contains neurodevelopmentally beneficial components. Animal studies report positive behavioral effects of supplementation with components included in the bovine milkfat globule membrane fraction (MFGM). Behavioral effects of MFGM supplemented formula in human infants have not been studied. This study tested the hypothesis that infants fed an experimental formula (EF) supplemented with a bovine MFGM fraction would display a more favorable neurofunctional development than infants fed a standard formula (SF) at 12 months.

    Participants and Methods: Healthy term formula‐fed infants (n = 160) and a breast‐fed reference (BFR) group (n = 80) were included in a prospective double blind randomized trial before 2 months of age. Formula‐fed infants were randomized to receive EF or SF from inclusion until 6 months. At 12 months, cognitive, motor and verbal functions were tested using the Bayley Scales of Infant and Toddler Development‐III.

    Results: The cognitive score was significantly higher in the EF (105.8 ± 9.2) than SF (101.8 ± 8.0) group, but equal between the EF and BFR groups. No differences were found in motor or verbal score between the formula groups. The BFR group displayed higher verbal but not motor scores than the formula groups.

    Conclusion: In keeping with the hypothesis, feeding infants MFGM supplemented formula resulted in improved cognitive function at 12 months compared with a standard formula. The difference in cognitive score between the EF and SF groups is compliant with calculated differences between formula‐fed and breast‐fed infants in previous studies.

  • 47.
    Domellöf, M
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Dewey, KG
    Lönnerdal, B
    Hernell, O
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Prophylactic iron supplementation in infancy:: Safety issues2006In: Acta Paediatrica, Vol. 95, no 8Article in journal (Other academic)
    Abstract [en]

    No abstract available

  • 48.
    Domellöf, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Cohen, R J
    Dewey, K G
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rivera, L L
    Lönnerdal, B
    Iron supplementation of breast-fed Honduran and Swedish infants from 4 to 9 months of age.2001In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 138, no 5, p. 679-687Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The objective was to study the effects of iron supplementation on hemoglobin and iron status in 2 different populations. Study design: In a randomized, placebo-controlled, masked clinical trial, we assigned term Swedish (n = 101) and Honduran (n = 131) infants to 3 groups at 4 months of age: (1) iron supplements, 1 mg/kg/d, from 4 to 9 months, (2) placebo, 4 to 6 months and iron, 6 to 9 months, and (3) placebo, 4 to 9 months. All infants were breast-fed exclusively to 6 months and partially to 9 months. RESULTS: From 4 to 6 months, the effect of iron (group 1 vs 2 + 3) was significant and similar in both populations for hemoglobin, ferritin, and zinc protoporphyrin. From 6 to 9 months, the effect (group 2 vs group 3) was significant and similar at both sites for all iron status variables except hemoglobin, for which there was a significant effect only in Honduras. In Honduras, the prevalence of iron deficiency anemia at 9 months was 29% in the placebo group and 9% in the supplemented groups. In Sweden, iron supplements caused no reduction in the already low prevalence of iron deficiency anemia at 9 months (<3%). CONCLUSION: Iron supplementation from 4 to 9 months or 6 to 9 months significantly reduced iron deficiency anemia in Honduran breast-fed infants. The unexpected hemoglobin response at 4 to 6 months in both populations suggests that regulation of hemoglobin synthesis is immature at this age.

  • 49.
    Domellöf, Magnus
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Dewey, Kathryn G
    Cohen, Roberta J
    Lönnerdal, Bo
    Hernell, Olle
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Iron supplements reduce erythrocyte copper-zinc superoxide dismutase activity in term, breastfed infants.2005In: Acta Paediatr, ISSN 0803-5253, Vol. 94, no 11, p. 1578-82Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate whether iron supplements compromise copper status in infants. METHODS: 214 healthy, term, breastfed Swedish and Honduran infants were randomized to (1) iron supplements (1 mg/kg/d) from 4-9 mo of age, (2) iron supplements from 6-9 mo, or (3) placebo. Blood samples were obtained at 4, 6, and 9 mo and analyzed for plasma copper (p-Cu) and, at 9 mo, for copper/zinc-dependent superoxide dismutase (CuZn-SOD) activity. RESULTS: P-Cu increased with infant age. At 9 mo, Honduran infants had significantly higher p-Cu (1.40+/-0.29 vs 1.09+/-0.22 mg/l, p<0.001) and CuZn-SOD activity (1.09+/-0.29 vs 0.93+/-0.21 U/mg Hb, p<0.001) than Swedish infants. Infants receiving iron supplements from 4-9 mo had significantly lower CuZn-SOD at 9 mo of age (0.95+/-0.27 vs 1.08+/-0.24 U/mg Hb, p=0.023) than those receiving placebo.CONCLUSION: There is a physiologic increase in p-Cu during the first 9 mo of life. Differences in copper status between Swedish and Honduran infants may be due to genetic or nutritional differences. Iron supplementation decreases CuZn-SOD activity, probably due to a negative effect on copper status. Possible clinical implications remain to be elucidated.

  • 50.
    Domellöf, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Dewey, Kathryn G
    Lönnerdal, Bo
    Cohen, Roberta J
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    The diagnostic criteria for iron deficiency in infants should be reevaluated.2002In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 132, no 12, p. 3680-3686Article in journal (Refereed)
    Abstract [en]

    Diagnostic criteria for iron deficiency (ID) and iron deficiency anemia (IDA) in infants are poorly defined. Our aim was to establish appropriate cut-off values for hemoglobin (Hb), plasma ferritin, erythrocyte mean cell volume (MCV), zinc protoporphyrin (ZPP) and soluble transferrin receptors (TfR) in infancy. Exclusively breast-fed infants (n = 263) in Honduras and Sweden were randomly assigned to receive iron supplementation or placebo, and blood samples were obtained at 4, 6 and 9 mo of age. Reference ranges were determined using three different approaches for defining iron-replete infants. The usefulness of several variables for predicting the Hb response to iron was evaluated. We found the following 2 SD cut-off values in iron-replete infants: Hb <105 g/L at 4-6 mo and <100 g/L at 9 mo; ZPP >75 micro mol/mol heme at 4-6 mo and >90 micro mol/mol heme at 9 mo; ferritin <20 micro g/L at 4 mo, <9 micro g/L at 6 mo and <5 micro g/L at 9 mo; and TfR >11 mg/L at 4-9 mo. The Hb response to iron was not a useful definition of IDA at 4 mo of age. Hb, MCV and ZPP at 6 mo as well as growth variables predicted the Hb response at 6-9 mo, but ferritin and TfR at 6 mo did not. We conclude that there is need for a reevaluation of the definitions of ID and IDA in infants.

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