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To assess the effect of probiotics on diarrhea during in- and outpatient treatment of children with severe acute malnutrition (SAM). A randomized, double-blind, placebo-controlled study was conducted involving 400 children admitted with SAM. Patients received one daily dose of a blend of Bifidobacterium animalis subsp. lactis (BB-12) and Lactobacillus rhamnosus (LGG) (10 billion colony-forming units, 50:50) or placebo during hospitalization followed by an 8-12 week outpatient treatment period, depending on patients' recovery rate. All outcomes were reported for in- and outpatient treatment separately. The primary outcome was number of days with diarrhea during hospitalization. Secondary outcomes included other diarrhea outcomes, pneumonia, weight gain, and recovery. There was no difference in number of days with diarrhea between the probiotic (n = 200) and placebo (n = 200) groups during inpatient treatment (adjusted difference +0.2 days, 95% CI -0.8 to 1.2, p = 0.69), however during outpatient treatment, probiotics reduced days with diarrhea (adjusted difference -2.2 days 95% CI -3.5 to -0.3, p = 0.025). There were no effects of probiotics on diarrhea incidence and severity or pneumonia, weight gain or recovery during in- or outpatient treatment. Twenty-six patients died in the probiotic versus 20 in the placebo group (p = 0.38). BB-12 and LGG had no effect on diarrhea in children with SAM during hospitalization, but reduced the number of days with diarrhea in outpatient treatment by 26%. Probiotics may have a role in follow-up of hospitalized children with SAM or in community based treatment of malnourished children, but further studies are needed to confirm this.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

The aim of the study was the development and validation of a simple stool diary for caretakers collecting data on stool frequency and consistency among young children in a low-income country.Focus group studies evaluated how diarrhea was understood by caregivers (content validity). The sensitivity, reliability, and correlations between dehydration and diary scores (construct validity) were tested in a clinical trial.Caregivers recognized and understood the concept and severity of diarrhea. Stool frequency and liquid consistency decreased in children admitted with diarrhea (P 0.0001 for both), confirming good sensitivity of the diary. High reliability was obtained after a few days of training. The caregiver intracorrelation coefficients were 0.66 (0.55-0.77) and 0.75 (0.66-0.84) after 2 and 7 days of training, respectively, and subjective staff evaluation of caregiver scores showed that ≤6% of caregivers had low scoring abilities after 3 days. The degree of dehydration (4-point score) was correlated with both increasing stool frequency and liquid stool consistency (+0.2 points [0.07-0.3], P = 0.0018 for 6 or more diarrheal stools, compared to 3 or more diarrheal stools per day, and +0.5 points (0.3-0.6), P 0.0001 for diarrheal episodes with 3 or more watery stools/day compared with episodes with 3 or more "watery + abnormally loose + loose" stools per day).The diary showed high validity, good reliability, and high sensitivity. After 3 days of training, caregivers with mainly no or limited education could report stool consistency with good reliability. Stool consistency, which correlated strongly with dehydration, may be considered an important marker of diarrhea severity in future research.

The reported prevalence of malnutrition in pediatric hospitals ranges from 15% to 30% of patients, with an impact on growth, morbidity and mortality. Major deficits in nutrition care have been highlighted in European hospitals, and the implementation of nutrition support teams (NSTs) has been suggested as a means to improve malnutrition diagnosis and nutrition care for hospitalized patients. This comment by the ESPGHAN Committee on Nutrition reviews disease related-mechanisms causing malnutrition and consequences of malnutrition and suggests a framework for implementation of NSTs in pediatric units. The recommendations by the Committee on Nutrition include: 1) Implementation of NSTs in hospitals is recommended to improve nutritional management of sick children; 2) The main tasks of the NST should include screening for nutritional risk, identification of patients who require nutritional support, provision of adequate nutritional management, education and training of hospital staff and audit of practice; 3) The NST should be multidisciplinary, with expertise in all aspects of clinical nutrition care; 4) The funds needed to support NSTs should be raised from the health care system; and 5) Further research is needed to evaluate the effects of NSTs in prevention and management of pediatric nutritional disorders, including cost effectiveness in different settings.

Objective It is assumed that early feeding can affect liver biochemistry because breast-fed infants have a higher risk of hyperbilirubinemia than formula-fed infants. The authors sought to determine how feeding mode affected liver biochemistry in healthy term infants. Methods Healthy term infants were followed up during infancy with a monthly questionnaire about feeding mode. Blood samples were obtained at 2, 6, and 9 months. Liver biochemistry (serum albumin, alkaline phosphatase, lactic dehydrogenase, aspartate aminotransferase [AST], and bilirubin), total insulin-like growth factor 1 (IGF-I), and insulin growth factor binding protein 3 (IGFBP-3) were determined at all ages. Results Mean AST and bilirubin were significantly higher in breast-fed infants at 2 and 6 months. In addition, mean albumin levels were higher in breast-fed infants at 2 months. Alkaline phosphatase, IGF-I, IGFBP-3, and lactic dehydrogenase levels did not differ between the feeding groups. AST levels did not correlate significantly with bilirubin, albumin, alkaline phosphatase, or lactic dehydrogenase values. There was a strong positive association between AST and IGF-I at 2 months (r = 0.47, P = 0.004). Conclusion Cytomegalovirus infection, vitamin K deficiency, and macromolecular forms of AST could be an explanation for a higher AST level among breast-fed infants. However, no other clinical or paraclinical sign of liver disease was seen, all infants were given oral vitamin K, and the AST did not rise to levels comparable to those seen in individuals with macromolecular AST. The authors speculate the most likely explanation of the elevated AST is induction of hepatocytes by factors in human milk. This is supported by the higher albumin levels in breast-fed infants and the positive association between AST and IGF-I.

The connections between gut microbiota, energy homeostasis, and inflammation and its role in the pathogenesis of obesity-related disorders are increasingly recognized. We aimed to investigate the effect of the probiotic strain Lactobacillus salivarius Ls-33 on a series of biomarkers related to inflammation and the metabolic syndrome (MS) in adolescents with obesity.The study was a double-blind placebo-controlled trial including 50 adolescents with obesity randomized to Ls-33 (10 CFU) or placebo daily for 12 weeks.The average body mass index-for-age z-score was 2.6 ± 0.5. There were no differences in biomarkers of inflammation and parameters related to the MS at baseline between the probiotic and placebo groups. Furthermore, there were no differences in changes from baseline to 12-week intervention with regard to any anthropometric measures, blood pressure (systolic and diastolic), fasting glucose and insulin, homeostasis model assessment of insulin resistance, C-peptide, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, free fatty acids, C-reactive protein, interleukin-6, tumor necrosis factor alpha, or fecal calprotectin, despite the increased values of biomarkers of inflammation and of several parameters related to the MS at baseline when compared with normal-weight adolescents. The levels of L salivarius in fecal samples from the probiotic group in the present study were comparable with the levels reported for the other probiotic lactobacilli and bifidobacteria using quantitative polymerase chain reaction.It was not possible to detect any beneficial effect of the probiotic intervention with Ls-33 on inflammatory markers or parameters related to the MS in adolescents with obesity being in a state of low-grade systemic inflammation.

BACKGROUND AND AIM Patients with cystic fibrosis (CF) have low levels of n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) in plasma or red blood cells (RBC), as also seen in other chronic and acute liver diseases. The differences may be more pronounced in CF transmembrane conductance regulator protein (CFTR)-regulated tissues such as granulocytes, monocytes, and lymphocytes. The aim of the present study was to investigate whether patients with CF-related liver disease have lower n-3 LCPUFA level than patients with CF without liver disease. METHODS Twenty patients with known CF-related liver disease were matched with 20 CF patients without. Blood samples were analysed for liver biochemistry and haematology. Granulocytes, mononuclear cells, and RBC were separated by density gradient centrifugation, and fatty acid composition was measured by gas chromatography. Hepatic ultrasound was scored according to Williams et al. Hepatic transit time (HTT) was measured with the ultrasound contrast agent SonoVue. RESULTS No significant differences were seen in either n-6 or n-3 LCPUFAs in any cell line when the 2 groups were compared. In a multiple regression analysis including HTT, age, Pseudomonas aeruginosa infection, diabetes mellitus, treatment with ursodeoxycholic acid, forced expiratory volume in 1 second (% of predicted value), and Williams' ultrasound scoring scale, only n-3 LCPUFA docosahexaenoic acid in mononuclear cell membranes was positively associated with HTT (P = 0.02). The arachidonic acid/docosahexaenoic acid ratio within the mononuclear cells was negatively associated with both HTT (P = 0.003) and Williams' ultrasound scoring scale (P = 0.03). For RBC-LCPUFAs, no significant associations were seen. CONCLUSIONS These findings indicate that in patients with CF, the degree of liver disease was negatively associated with LCPUFA n-3 levels in CFTR-expressing white blood cells but unrelated to those levels in CFTR-negative RBC.

Objectives: The aim of this study was to monitor changes in the fecal microbiota from 9 to 18 months and to investigate the effect of increasing dietary n-3 polyunsaturated fatty acids on the fecal microbiota. Patients and Methods: In a double-blind controlled trial with random allocation to daily supplementation with 5 mL of fish oil (FO) or sunflower oil (SO) from 9 to 18 months of age, stool samples were collected from 132 healthy Danish infants. Molecular fingerprints of the bacterial DNA were obtained by terminal restriction fragment length polymorphism (T-RFLP). Results: The T-RFLP profiles indicated that a few T-RFs became dominant with age (bp100 and 102, both presumed to be Bacteroidetes) concomitantly with an overall increase in the microbial diversity (P = 0.04). Breast-feeding influenced both the T-RFLP profiles at 9 months and the changes from 9 to 18 months, and breast-feeding cessation during the trial modified the response to the dietary oils. In the FO group, the increase in bp102 was significantly reduced among children weaned before compared with those weaned during the trial (P = 0.027), whereas the increase in bp100 was reduced in the preweaned children of the SO group relative to those weaned during the trial (P = 0.004). This was supported by intervention group differences in the changes in bp102 and bp100 among the earlier weaned children (P = 0.06 and P = 0.09, respectively). Conclusions: Cessation of breast-feeding played a dominant role relative to developmental changes in the fecal microbiota from 9 to 18 months. FO compared with SO supplementation affected changes in large bacterial groups, but only among children who had stopped breast-feeding before 9 months of age.

*University of Lancashire, Lancashire, United Kingdom; †University of Milano, Milano, Italy; ‡University of Umea, Umea, Sweden; §Committee Chairman, University of Munich, Munich, Germany; Free University of Amsterdam, Amsterdam, The Netherlands; ¶Committee Secretary, Royal Agricultural and Veterinary University, Fredricksburg, Denmark; #University of Liege, Liege, Belgium; **University of Glasgow, Glasgow, United Kingdom

To investigate whether diet influences the composition of the intestinal microbiota in 10-month-old infants.Fecal samples were collected from sixty-five 10-month-old infants participating in a randomized 2 x 2 intervention study comparing cow's milk (CM) with infant formula (IF) with or without fish oil (FO) supplement. Infants randomized to CM received a daily iron supplement. Bacterial DNA was extracted from the feces. Polymerase chain reaction was performed with primers targeting the V3 and V6-8 region of the 16S rRNA gene and analyzed by denaturing gradient gel electrophoresis (DGGE). Cluster analysis of the DGGE gels was performed by use of the Pearson correlation coefficient.Samples from infants receiving CM clustered differently than did those from the IF group in the V3-based DGGE gels (P0.001) and showed a different distribution with or without FO in the CM group (P = 0.001) but not in the IF group (P = 0.39). Repeat analysis with the V6-8-based DGGE gels showed the same pattern, although the V3 gels had 2.5 times as many bands as the V6-8 gels.Consumption of CM or IF has a decisive influence on the composition of the intestinal microbiota. Supplementation with FO showed an effect on the microbiota only in the CM group. We speculate that these differences could be influenced by the intake of iron and n-3 polyunsaturated fatty acids, respectively.

The consumption of nondigestible carbohydrates is perceived as beneficial by health professionals and the general public, but the translation of this information into dietary practice, public health recommendations, and regulatory policy has proved difficult. Nondiaestible carbohydrates are a heterogeneous entity, and their definition is problematic. Without a means to characterize the dietary components associated with particular health benefits, specific attributions of these cannot be made. Food labeling for "fiber" constituents can be given only in a general context, and the development of health policy, dietary advice, and education, and informed public understanding of nondigestible carbohydrates are limited. There have, however, been several important developments in our thinking about nondigestible carbohydrates during the past few years. The concept of fiber has expanded to include a range of nondigestible carbohydrates. Their fermentation, fate, and effects in the colon have become a defining characteristic; human milk, hitherto regarded as devoid of nondigestible carbo-hydrates, is now recognized as a source for infants, and the inclusion of nondigestible carbohydrates in the diet has been promoted for their "prebiotic" effects. Therefore, a review of the importance of nondigestible carbohydrates in the diets of infants and young children is timely. The aims of this commentary are to clarify the current definitions of nondigestible carbohydrates, to review published evidence for their biochemical, physiologic, nutritional, and clinical effects, and to discuss issues involved in defining dietary guidelines for infants and young children. (C) 2003 Lippincott Williams Wilkins, Inc. (Less)

*University of Lancashire, Lancashire, United Kingdom; †University of Milano, Milano, Italy; ‡University of Lund, Malmo, Sweden; §Hopital des Enfants Malades, Paris, France; Hopital Necker Enfants-Malades, Paris, France, ¶Umea University, Umea, Sweden; #University of Munich, Munich, Germany; **Free University of Amsterdam, Amsterdam, The Netherlands; ††Royal Veterinary and Agricultural University, Frederiksberg, Denmark; ‡‡CHUV University Hospital, Lausanne, Switzerland; §§University of Liege, Liege, Belgium; Medical University of Warsaw, Warsaw, Poland; and ¶¶University of Glasgow, Glasgow, United Kingdom

Background Docosahexaenoic acid (DHA), present in high concentrations in the brain and retina, has a role in visual development. DHA is present in human milk, but not in most infant formulas. It is, however, under discussion whether DHA should be added to formulas intended for term infants. The concentration of DHA in human milk, which is influenced by maternal diet, varies considerably, but it is unknown whether this variation affects visual development in term infants. Methods The authors investigated 39 4-month-old fully breast-fed term infants in a cross-sectional study. Visual acuity was measured by swept visual evoked potentials, milk DHA was determined by gas chromatography, and maternal fish intake was assessed by a frequency questionnaire. Results Frequency of fish intake correlated positively to the DHA level in breast-milk (P = 0.001). Mothers who ate fish the day before sampling had a milk DHA level higher than expected from habitual fish intake (P = 0.002). If this was taken into account, 57% of the variation in milk DHA could be explained by fish intake. Multiple linear regression analysis revealed a significant association between visual acuity and milk DHA (P = 0.02, R2 = 0.09). Conclusion This finding suggests a cause-and-effect relationship between infant milk DHA intake and visual acuity. If these data are confirmed, there is a need to consider the optimal intake of DHA for the lactating mother.

Highly bioavailable dietary iron is needed to ensure optimal iron status in infants during weaning. The purpose of the current study was to examine the effect of increased meat intake on hemoglobin concentration (Hb), serum ferritin (SF), and serum transferrin receptors (TfR) in late infancy.Forty-one healthy, term, partially breast-fed 8-month-old infants were randomized into two groups: a low-meat group (LMG), in which infants received a diet with a mean meat content of 10 g/day and a high-meat group (HMG), in which infants received a diet with a mean meat content of 27 g/day. The intervention lasted for 2 months, and blood samples were drawn on the first and the last days of the intervention.At the beginning of the intervention, no significant differences were found in Hb, SF, TfR values between the two groups. After the intervention, there was a significant (p = 0.008) difference in the change in hemoglobin (delta Hb) concentration. In the LMG delta Hb was -4.9 g/l (range, -12.9-5.6 g/l) and in the HMG -0.6 g/l (range, -12.1-7.3 g/l). There was no significant difference in change in SF or TfR concentrations between the LMG and the HMG. The intake of iron from meat (mean; range) was significantly higher (p = 0.0001) in the HMG (0.4 mg/day; 0.02-0.7 mg/day) than in the LMG (0.1 mg/day; 0.03-0.5 mg/day). However, there was no significant difference in total iron intake between the HMG (3.1 mg/day; 0.4-6.2 mg/day) and the LMG (3.4 mg/day; 1.4-6.1 mg/day).The results suggest that an increase in meat intake can prevent a decrease in Hb in late infancy, probably by enhancing iron absorption. However, there was no effect on iron stores or on cellular iron deficiency, evaluated by SF and TfR levels, respectively.

Protein (P), fat (F), and carbohydrate (C) concentration in expressed human bank milk was determined by infrared analysis of 2,554 samples from 224 mothers. The mean contents of P, F, C, and energy (E, calculated from P, F, and C) were 9.0 g/L, 39.0 g/L, 71.9 g/L, and 696 kcal/L, respectively. There was a large variation in the concentration of energy-yielding macronutrients. The contents of P, F, C, and E in the samples with the highest values (97.5 percentile) were 2.3-, 4.8-, 1.2-, and 2.3-fold, respectively, above the contents in the samples with the lowest values (2.5 percentile). The P content decreased exponentially during the 1st 8 months, followed by an increase during the following months. The F content decreased during the 1st 4 months, followed by an almost linear increase. The possible influence of different maternal characteristics on the macronutrient content of the milk was examined. The main results were as follows: the P and F contents increased slightly with increasing body mass index of the mother, the P content decreased with increasing amounts of milk delivered to the milk bank, and the F content was higher in mothers delivering large amounts of milk. By selecting incoming milk with a high P content, we have developed a "high-protein" milk with a P content of about 12 g/L (true protein) and an E content of about 725 kcal/L. Thus, by continuous monitoring of macronutrient content in human bank milk it is possible to develop a "high-protein" milk with sufficient P and E content to cover the needs of preterm infants with very low birth weights (less than 1,500 g).