Temporal and long-term gut microbiota variation in allergic disease: A prospective study from infancy to school age.

BACKGROUND: Compositional changes in the early-life gut microbiota have been implicated in IgE-associated allergic diseases, but there is lack of longitudinal studies. We examined gut microbiota development from infancy to school age in relation to onset of IgE-associated allergic diseases. At 8 years of age, we also examined the relationship between gut microbiota and T-cell regulation, estimated as responses to polyclonal T-cell activation. METHODS: Stool samples were collected from 93 children at 4, 6, 13 months, and 8 years of age. The gut microbiota was profiled using 16S rRNA gene sequencing. Peripheral blood was drawn from all children, and mononuclear cells were polyclonally activated. Levels of IL-10 and FOXP3 mRNA copies were determined using real-time quantitative reverse transcriptase-PCR. RESULTS: At 8 years of age, 21 children were diagnosed with IgE-associated allergic disease and 90% displayed allergic comorbidity. Seventy-two children were nonallergic and nonsensitized. Statistical tests with multiple testing corrections demonstrated temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella, and Coprococcus in allergic compared to nonallergic children from infancy to school age. The gut microbiota of the allergic 8-year-olds was enriched in Bifidobacterium and depleted of Lactobacillus, Enterococcus, and Lachnospira. In allergic 8-year-olds, Faecalibacterium correlated with IL-10 mRNA levels (rs  = 0.49, Padj  = 0.02) with the same trend for FOXP3 (rs  = 0.39, Padj  = 0.08). CONCLUSIONS: We identified both temporal and long-term variation in the differential abundance of specific bacterial genera in children developing IgE-associated allergic disease. Improved dietary interventions aiming at expanding immune-modulatory taxa could be studied for prevention of allergic disease.

Probiotics in primary prevention of allergic disease--follow-up at 8-9 years of age.

BACKGROUND: Long-term effects of probiotics in primary prevention of allergic disease need further evaluation. We previously reported a reduced cumulative incidence of infant eczema by feeding Lactobacillus paracasei ssp paracasei F19 (LF19) during weaning. Therefore, we assessed effects of LF19 on the prevalence of allergic disease at school age. METHODS: In a double-blind placebo-controlled trial infants were randomized to daily intake of cereals with (n = 89) or without LF19 10(8) CFU (n = 90) from 4-13 months of age. At age 8-9, we evaluated the prevalence of allergic disease (eczema, allergic rhinitis, asthma, and food allergy) by clinical examination and validated questionnaires. IgE sensitization was assessed by skin prick test (inhalant allergens) and specific IgE levels (food allergens). Lung function was evaluated by a spirometry reversibility test. Fractional exhaled nitric oxide (FENO ) was measured. RESULTS: Of 171 children that completed the intervention, 121 were assessed at age 8-9. In the probiotic group, 15/59 (25%) were diagnosed with any allergic disease vs 22/62 (35%) in the placebo group [OR (95% CI) 0.62 (0.28-1.36)]. Corresponding numbers for IgE-associated allergic disease were 9/53 (17%) vs 12/59 (20%) [0.80 (0.31-2.09)]. Median (25th-75th percentile) FENO was 9 (8-12) in the probiotic vs 8 (7-12) ppb in the placebo group (P > 0.05). There was no effect of LF19 on lung function measures (P > 0.05). CONCLUSIONS: There was no long-term effect of LF19 on any diagnosed allergic disease, airway inflammation or IgE sensitization. This suggests delayed eczema onset but to fully examine long-term benefits a larger study population had been needed.

Probiotic effects on T-cell maturation in infants during weaning.

BACKGROUND: We previously reported that feeding the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) during weaning reduced the cumulative incidence of eczema. OBJECTIVE: To investigate the impact of feeding LF19 on T-cell maturation. METHODS: One hundred and seventy-nine healthy, term infants with no prior allergic manifestations were randomized to daily intake of cereals with (n = 89) or without (n = 90) the addition of LF19 10(8 ) colony forming units per serving from 4 to 13 months of age. Venous blood was drawn at 5.5 and 13 months of age. We used the cytokine response to polyclonal T-cell stimulation by anti-CD3 plus anti-CD28 monoclonal antibodies, and in vitro stimulation with the vaccine tetanus toxoid (TT) as measures of global adaptive immunity and capacity to raise a specific T-cell response, respectively. Expression levels of IL-2, IFN-γ, IL-4, IL-17A and IL-10 messenger RNAs (mRNAs) were used as proxies for general T-cell stimulation and naive Th0 cells, Th1-, Th2-, Th17- and T regulatory lineages. RESULTS: There was no difference between the two groups at 5.5 months of age. At 13 months, the polyclonal IL-2 response was higher in the placebo group (P < 0.05), whereas the IFN-γ/IL-2 (P < 0.01) and IL-17A/IL-2 (P < 0.05) ratios after polyclonal stimulation were higher in the probiotic group, as was the TT-specific IL17-A response (P < 0.001). In both groups, the IFN-γ and IL-4 responses increased from 5.5 to 13 months upon both polyclonal and specific stimulation (P < 0.01), whereas the IL-10 response remained low (P > 0.05). CONCLUSION AND CLINICAL RELEVANCE: Our findings suggest modest effects by probiotics on T-cell maturation following 9 months of probiotic intake. Future studies should address if specific probiotics may drive immune development with possible preventive effects on the development of allergic disease.

Mode of birth delivery affects oral microbiota in infants.

Establishment of the microbiota of the gut has been shown to differ between infants delivered by Caesarian section (C-section) and those delivered vaginally. The aim of the present study was to compare the oral microbiota in infants delivered by these different routes. The oral biofilm was assayed by the Human Oral Microbe Identification Microarray (HOMIM) in healthy three-month-old infants, 38 infants born by C-section, and 25 infants delivered vaginally. Among over 300 bacterial taxa targeted by the HOMIM microarray, Slackia exigua was detected only in infants delivered by C-section. Further, significantly more bacterial taxa were detected in the infants delivered vaginally (79 species/species clusters) compared with infants delivered by C-section (54 species/species clusters). Multivariate modeling revealed a strong model that separated the microbiota of C-section and vaginally delivered infants into two distinct colonization patterns. In conclusion, our study indicated differences in the oral microbiota in infants due to mode of delivery, with vaginally delivered infants having a higher number of taxa detected by the HOMIM microarray.

Serum lipid and apolipoprotein levels in 4-year-old children are associated with parental levels and track over time.

BACKGROUND/OBJECTIVES: There are only a few studies linking dietary fat intake to serum lipid levels in young children. Our objective was to prospectively evaluate serum lipid levels from infancy to early childhood, and to explore their possible association with dietary, growth and parental factors. SUBJECTS/METHODS: Children (n=127) followed from early infancy were examined for serum lipid levels, anthropometry and dietary intake at 4 years of age. We also studied possible associations with parental anthropometric and blood biochemistry data collected from 122 mothers' and 118 fathers' when children were 4 years of age. RESULTS: Serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and the apolipoprotein B/apolipoprotein A-1 ratio (apo B/apo A-1) showed significant tracking from infancy to 4 years. Furthermore, children's TC levels correlated with paternal TC level from 6 months to 4 years, but with maternal only at 4 years. In girls, both LDLC and HDLC correlated with parental LDLC and HDLC. In all children, intake of saturated fatty acids (SAFAs) was higher than recommended, and in 90% of the children polyunsaturated fatty acid (PUFA) intake was lower than recommended. CONCLUSIONS: Serum lipid levels values tracked from infancy to 4 years and were associated with parental values. Higher serum lipid levels at 4 years compared with 6-18 months of age may result from changes in the quality of dietary fat. We therefore suggest that intake of dietary fat in 4-year-old children should be more focused on quality. Furthermore, as there were strong associations between the child and parental serum lipid levels this supports the view that family-based rather than individual intervention is preferable.

Dietary shortcomings in children on a gluten-free diet.

BACKGROUND: Coeliac disease (CD), or permanent gluten intolerance, is one of the most common chronic food-related diseases among children in Europe and the USA. The treatment is lifelong gluten-free diet (GFD) (i.e. the exclusion of wheat, rye and barley from the diet, which are important sources particularly of iron, dietary fibre and vitamin B). The present study aimed to evaluate dietary intakes of energy and nutrients in children and adolescents on GFD and compare these with intake of comparable age groups on a normal diet as well as current recommendations. METHODS: Thirty children, 4-17 years of age with confirmed CD and on GFD were agreed to participate in this study at the Department of Pediatrics, Umeå University Hospital. Weight and height were used to calculate individual energy requirement according to Nordic Nutrition Recommendations 2004 (NNR-04). Dietary intake was assessed using 5-day food records and household measures were used for quantities. Twenty-five children completed their dietary record. RESULTS: Thirteen of the 25 children did not meet the recommended energy intake and the dietary intakes were inadequate regarding quality of macronutrients and quantity of minerals and vitamins. The mean intakes of sucrose and saturated fatty acids were above and the intakes of dietary fibre, vitamin D, magnesium and selenium below the NNR-04. High intakes of sucrose and saturated fat and a low intake of dietary fibre were also noted in a previous national survey on healthy children on a normal diet. The nutrient density of vitamin D, riboflavin, niacin, thiamine, magnesium and selenium were lower among CD children than healthy children but, for iron and calcium, it was higher in CD children. CONCLUSIONS: Children on GFD appear to follow the same trends as healthy children on a normal diet, with high intakes of saturated fat and sucrose and low intakes of dietary fibre, vitamin D and magnesium compared to recommendations.

BMI at 4 years of age is associated with previous and current protein intake and with paternal BMI.

OBJECTIVES: To evaluate possible associations between body mass index (BMI) at 4 years of age, current and previous dietary intakes and parental BMI. METHODS: A follow-up of dietary intake and anthropometry in 127 4-year-old children corresponding to 54% of children who completed an initial intervention study at 18 months of age. RESULTS: Fourteen percent of the girls and 13% of the boys were overweight (age-adjusted BMI> or =25) and 2% of the girls and 3% of the boys were obese (age-adjusted BMI> or =30). Thirty-four percent and 9% of the fathers and 19 and 7% of the mothers were overweight and obese, respectively. BMI at 6-18 months was a strong predictor of BMI at 4 years. Univariate regression analyses revealed that intake of protein in particular, and also of total energy and carbohydrates at 17/18 months and at 4 years, was positively associated with BMI at 4 years. Although BMI at 6-18 months was the strongest predictor of BMI at 4 years, in the final multivariate models of the child's BMI, protein intake at 17-18 months and at 4 years, energy intake at 4 years and the father's-but not the mother's-BMI were also independent contributing factors. CONCLUSIONS: Among these healthy children, BMI at 4 years of age tracked from 6 to 18 months of age and were associated with previous and current protein intake as well as parental BMI, particularly that of the father.

Human milk compounds inhibiting adhesion of mutans streptococci to host ligand-coated hydroxyapatite in vitro.

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.

Aberrant extrathymic T cell receptor gene rearrangement in the small intestinal mucosa: a risk factor for coeliac disease?

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.

Dietary fat in infancy should be more focused on quality than on quantity.

OBJECTIVE: The primary aim was to assess, the association of the quantity and quality of dietary fat intake from 6 to 12 months of age and serum lipids at 12 months. SUBJECTS/METHODS: Three hundred healthy term Swedish infants were recruited in a longitudinal prospective study at the age of 6 months; 276 remained in the study at 12 months. Food records and anthropometric data were collected monthly from 6 to 12 months; serum lipids were analysed at 6 and 12 months. RESULTS: Swedish infants had a total fat intake within the Nordic recommendations, but intake of polyunsaturated fatty acids (PUFA) was low (5.6 percent of total energy (E%)) and intake of saturated fatty acids (SAFA) was high (15.1 E%). Higher PUFA intake was associated with lower total serum cholesterol (TC, B=-0.13, P=0.003), lower low-density-lipoprotein cholesterol (LDL-C, B=-0.12, P=0.004) and apolipoprotein B (B=-0.03) (P=0.034) in girls but not in boys. When data from the present study were compared to data from similar studies in Finland and Iceland, it appears that the quality of the dietary fat has greater impact on serum lipid levels than the quantity of fat in the diet. CONCLUSIONS: Higher PUFA and lower SAFA intakes may reduce TC and LDL-C early in life, particularly in girls. Further, with respect to lowering serum lipid concentrations in early childhood it seems appropriate to set focus on fat quality rather than the quantity. SPONSORSHIPS: Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas), Swedish Research Council, Medicine, Stiftelsen Oskar Foundation, Sven Jerring Foundation, Samariten Foundation, Stiftelsen Goljes minne and Semper AB.

Pasteurization of mother's own milk reduces fat absorption and growth in preterm infants.

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 < or =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.

Depot-specific messenger RNA expression of 11 beta-hydroxysteroid dehydrogenase type 1 and leptin in adipose tissue of children and adults.

OBJECTIVE: To compare expression of messenger RNA (mRNA) coding for the cortisol regenerating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), and the adipocytokines leptin and resistin in paired biopsies of subcutaneous adipose tissue (SC) and omental adipose tissue (OM) from children. DESIGN: Paired biopsies (SC and OM) were obtained from 54 children (age 0.17-16 years, body mass index (BMI) 12.5-28.3 kg/m(2), BMI standard deviation score (SDS) -2.5-4.5) and 16 adults (age 27-79 years, BMI 19-46 kg/m(2)) undergoing open abdominal surgery. mRNA levels of 11beta-HSD1, leptin and resistin were measured using quantitative real-time polymerase chain reaction (PCR). RESULTS: 11beta-HSD1 mRNA level was higher in OM than in SC (P<0.05), whereas leptin mRNA was higher in SC than in OM (P<0.001). There was no difference in the resistin mRNA level between SC and OM. These results were consistent in children and adults. In children, 11beta-HSD1 mRNA in SC was positively associated with BMI SDS (P<0.05), whereas in OM it was positively associated with age (P<0.05). The association between 11beta-HSD1 expression and age remained significant after adjustment for BMI SDS and gender. Leptin mRNA was positively associated with BMI SDS (SC: P<0.001, OM: P<0.001) but not with age in children. In multiple regression analyses, including anthropometric variables and age, BMI SDS was independently associated with mRNA levels of 11beta-HSD1 (P<0.05) and leptin (P<0.001) in SC. When normal weight and overweight children were analyzed separately, 11beta-HSD1 mRNA levels were positively associated with leptin in OM in the overweight group (P<0.05). CONCLUSION: There are depot-specific differences in mRNA levels of 11beta-HSD1 and leptin in children and adults. The positive association of 11beta-HSD1 mRNA in OM with age may reflect a causal role in visceral fat accumulation during growth. Increasing 11beta-HSD1 and leptin mRNA in SC with increasing BMI SDS could suggest that the risk of metabolic consequences of obesity may be established early in life.

Diet intake and caries prevalence in four-year-old children living in a low-prevalence country.

Preventive measures have dramatically decreased the prevalence of dental caries in children. However, risk factors for the disease in children living in low-prevalence areas remain elusive. In the present study we evaluated associations between dental caries, saliva levels of mutans streptococci and lactobacilli, and diet with special emphasis on the intake of fermentable carbohydrates and dairy products in 4-year-old children living in an area where the overall caries prevalence was low. Dietary intake was recorded in 234 infants as part of the Study of Infant Nutrition in Umeå, Sweden (SINUS). Of these the parents of 124 children gave consent to participate in a follow-up at 4 years of age. Dietary intake, height and weight, dental caries, oral hygiene, including tooth brushing habits, presence of plaque and gingival inflammation, fluoride habits and numbers of mutans streptococci and lactobacilli in saliva were recorded. Using multivariate stepwise logistic regression, caries experience was negatively associated with intake frequency of cheese (OR = 0.67; 95% CI = 0.44-0.98) and positively associated with the salivary level of mutans streptococci (OR = 1.57; 95% CI = 1.21-2.03). Caries experience was not correlated with intake frequency or amounts of carbohydrate-containing foods, with any other particular food, or with daily intake of energy, carbohydrate or any other macro- or micronutrient. We conclude that cheese intake may have a caries-protective effect in childhood populations where the overall caries prevalence and caries experience are low and the children are regularly exposed to fluoride from toothpaste.

Effects of human milk on adhesion of Streptococcus mutans to saliva-coated hydroxyapatite in vitro.

Adhesion of bacteria to pellicle-coated tooth surfaces is the first step in biofilm formation on teeth. The aim of this study was to explore whether human milk prevents or promotes adhesion of cariogenic Streptococcus mutans to saliva-coated hydroxyapatite (HA) using an in vitro model system. S. mutans binding to HA coated with human parotid saliva (s-HA) or human milk was studied, in addition to binding inhibition to s-HA by human milk. S. mutans did not bind to HA coated with milk. S. mutans binding to s-HA was inhibited by milk from 15 (71 %) of 21 women, whereas milk from the remaining 6 mothers enhanced binding of S. mutans to s-HA. Inhibition of S. mutans binding correlated with bacterial binding to s-HA (r = 0.76). Human milk does not mediate adhesion of S. mutans to HA in vitro, but affects adhesion in an individually varying fashion. Phenotypic variations in milk and saliva glycosylation may explain the inhibitory capacity and possibly affect susceptibility to colonization by S. mutans in childhood.

From innovation to implementation.

Requirements for the safety and nutritional adequacy of infant formula are set by legislation and aim for the best possible substitute for human milk with regard to growth, development and biological effects. This is, however, a continuous process and has to be supported by science-driven innovative activities of manufacturers and be confirmed by adequate clinical studies performed according to agreed standards.

Is iron deficiency in infants and young children common in Scandinavia and is there a need for enforced primary prevention?

A significant problem in diagnosing infants and young children with iron deficiency (ID) and iron deficiency anemia (IDA) is that it is not clear how the biochemical markers used correspond to physiological outcomes such as growth, neurodevelopment and morbidity. Thus, the prevalence of iron deficiency and iron deficiency anemia in infants and young children is difficult to assess and therefore not really known. Recent studies have shown that iron metabolism is subjected to developmental changes during infancy, which affect indicators of iron status. Hence, better defined cut-off values for the indicators used are needed and, in particular, how they are correlated to functional outcomes.

Expression of cellular inhibitor of apoptosis protein-2 in human subcutaneous and omental adipose tissue.

OBJECTIVE: In the current study, we addressed the question if there is depot-specific expression of cellular inhibitor of apoptosis protein-2 (cIAP2) already in childhood and if the relative expression changes with age in parallel with increasing risk of developing visceral adiposity. SUBJECTS: Paired samples of human omental (OM) and subcutaneous (SC) adipose tissue were obtained from 23 patients (12 children and 11 adults). METHOD: mRNA level of cIAP2 was determined using reverse transcription-polymerase chain reaction (RT-PCR) and protein expression confirmed by Western blotting. Apoptosis indices were determined by terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick-end labelling (TUNEL). RESULTS: cIAP2 mRNA was 1.51-fold higher in OM compared with SC adipose tissue (OM>SC in 20 of 23 subjects; P<0.001). Western blots were in agreement with mRNA expression (OM>SC in nine of 10 subjects, P<0.01). Subgroup analyses showed depot difference in both children (P<0.01) and adults (P<0.05). Contrary to the hypothesis, depot-specific difference in mRNA expression of cIAP2 was significantly higher in children compared with adults (P<0.05). We were unable to demonstrate any difference in the basal apoptosis rate between adipocytes from the two depots. There was no significant association between cIAP2 mRNA expression and BMI or sex. CONCLUSIONS: The results demonstrated for the first time that depot-specific difference in cIAP2 expression is consistent in children and adults. This suggests that the higher expression of cIAP2 in OM than in SC adipose tissue may be due to inherent properties of cells from the two depots. The more pronounced depot-specific difference in children than in adults may reflect a net gain in visceral adipose tissue during growth.

Effects of weaning cereals with different phytate content on growth, development and morbidity: a randomized intervention trial in infants from 6 to 12 months of age.

BACKGROUND: Phytate decreases iron and zinc bioavailability and contributes to deficiencies of iron and zinc, potentially causing anaemia, poor psychomotor development, impaired growth and increased risk of diarrhoea and respiratory infections. AIM: To investigate whether a reduced dietary intake of phytate, either via extensively phytate-reduced infant cereals [milk cereal drinks (MCDs) and porridge] or a milk-based infant formula, would improve growth and development and reduce morbidity in infants. DESIGN: Infants (n = 300) were, in a double-blind design, randomized to three diet intervention groups from 6 to 12 mo of age-commercial MCD and porridge (CC group), phytate-reduced MCD and phytate-reduced porridge (PR group), or milkbased infant formula and porridge with regular phytate content (IF group)-then followed until 18 mo. Dietary intake, anthropometry, development (Bayley Scales of Infant Development) and episodes of infectious diseases were registered. RESULTS: There were no significant differences between study groups in growth, development or morbidity until 12 mo of age. The IF group had a 77% higher risk (95% CI: 1.05-2.97) of diarrhoea compared to the PR group during the 12-17-mo period. Infants with haemoglobin concentration (Hb) < 110 g/l at 12 mo had lower attained weight at 18 mo (11.14 kg vs 11.73 kg, p = 0.012). Infants with serum zinc (S-Zn) <10.7 pmol/l at 12 mo had higher risk of respiratory infections (RR = 1.74, 95% CI: 1.19-2.56) compared to controls. CONCLUSION: Phytate reduction had no effect on growth, development or incidence of diarrhoeal or respiratory infections. Infants with low Hb or low S-Zn may be at higher risk of poor growth and respiratory infections, even in this high-income population.

Total energy expenditure and physical activity level in healthy young Swedish children 9 or 14 months of age.

OBJECTIVES: To measure total energy expenditure (TEE) and total body water (TBW) in healthy Swedish children 9 or 14 months of age. To compare their TEE with current recommendations for energy intake. To define their body composition and relate this to energy expenditure. DESIGN: : Children were investigated at 9 or 14 months. The following variables were measured: TEE and TBW (by the doubly labelled water method), weight and length. Total body fat (TBF), sleeping metabolic rate, activity energy expenditure and physical activity level (PAL) were calculated. SUBJECTS: Thirty infants 9 months of age and 29 children 14 months of age. RESULTS: : TEE was 323+/-38, 322+/-29, 313+/-23 and 331+/-28 kJ/kg/day in 9-month-old girls, 9-month-old boys, 14-month-old girls and 14-month-old boys, respectively. At 9 months of age girls and boys contained 29.6+/-4.8 and 29.7+/-4.5% TBF, respectively. At 14 months the corresponding figures were 29.1+/-4.3 and 28.2+/-4.3%. There was a significant negative relationship between PAL and %TBF (r=-0.81, P<0.001, n=59). CONCLUSIONS: Measured TEE plus calculated energy cost of growth confirm previous estimates that the physiological energy requirements of children 9 and 14 months of age are 15-20% lower than current recommendations for energy intake. One possible interpretation of the relationship between PAL and %TBF is that children with a high TBF content are less physically active than children with less TBF. However, this relationship needs further studies.