Noélia L. Lima

Prolonged Episodes of Acute Diarrhea Reduce Growth and Increase Risk of Persistent Diarrhea in Children

BACKGROUND & AIMS Prolonged episodes of acute diarrhea (ProD; duration 7-13 days) or persistent diarrhea (PD; duration ≥14 days) are important causes of undernutrition, yet the epidemiology and nutritional impact of ProD are poorly understood. METHODS We conducted a 10-year cohort study of 414 children from a Brazilian shantytown who were followed from birth; data were collected on diarrhea, enteric pathogens, and anthropometry. RESULTS During 1276 child-years of observation, we recorded 3257 diarrheal episodes. ProD was twice as common as PD (12% and 5% of episodes, respectively); ProD and PD together accounted for 50% of all days with diarrhea. ProD was more common in infants whose mothers had not completed primary school (relative risk [RR], 2.1; 95% confidence interval: 1.02-2.78). Early weaning was associated with earlier onset of ProD (Spearman ρ = 0.309; P = .005). Infants with ProD were twice as likely to develop PD in later childhood (log rank, P = .002) compared with infants with only acute diarrhea (AD; duration <7 days), even after controlling for confounders. Childrens growth was more severely stunted before their first episode of ProD, compared with AD (mean height-for-age Z score (HAZ) -0.81 vs -0.51, respectively, P < .05, unpaired t test). Following ProD, HAZ (ΔHAZ = -0.232) and weight-for-age (ΔWAZ = -0.26) significantly decreased (P < .005 in paired t tests). ProD was associated with Cryptosporidium and Shigella infections. CONCLUSIONS ProD accounts for significant morbidity and identifies children at risk of a vicious cycle of diarrhea and malnutrition. Further studies are needed to address the recognition and control of ProD and its consequences in resource-limited settings and assess its role in PD pathogenesis.

Intestinal barrier function and weight gain in malnourished children taking glutamine supplemented enteral formula.

Objective: We examined the effect of standard formula and glutamine or glycine supplemented enteral formula on intestinal permeability and weight gain in children with malnutrition. Methods: 80 children aged 2 to 60 months with a weight-for-age z-score less than −2 were studied. From December 1996 to April 1999, 27 study patients received nonsupplemented formula. From June 2001 to June 2002 an additional 53 patients were randomly assigned to receive formula supplemented with glutamine or glycine (isosmolar concentrations) for 10 days. Lactulose/mannitol excretion ratio was used as a measure of intestinal permeability and was performed before and after 10 days of nutritional rehabilitation. Weight was measured before and after treatment. Results: Patients were similar on admission with regard to age, sex, nutritional status and lactulose/mannitol ratio. The lactulose/mannitol ratio significantly improved (decreased) in children receiving formula supplemented with glutamine for 10 days but not in those receiving glycine or nonsupplemented formula. Weight gain occurred during therapy in all groups and was not statistically different among groups. Conclusion: Formula supplemented with glutamine improves intestinal barrier function compared with nonsupplemented formula but does not augment weight gain.

Wasting and intestinal barrier function in children taking alanyl-glutamine-supplemented enteral formula.

Objective: We examined the effect of a diet supplemented with alanyl-glutamine (AG) or placebo glycine (G) on intestinal barrier function and growth in children in northeastern Brazil. Patients and Methods: One hundred seven children ages 7.9 to 82.2 months with a weight-for-age (WAZ), height-for-age (HAZ), or weight-for-height (WHZ) z-score less than −1 were studied. From July 2003 to November 2004, 51 study patients received AG (24 g/d) and 56 received G (25 g/d; isonitrogenic concentration) control for 10 days. Lactulose/mannitol excretion ratio was used as a measure of intestinal permeability and was performed on days 1 and 10 of nutritional supplementation. Weight and height were measured on days 1, 10, 30, and 120 of the protocol. Results: The patients were similar on admission with regard to age, sex, birth weight, nutritional status, lactulose/mannitol ratio, and serum concentrations of glutamine and arginine. The percentage of lactulose urinary excretion significantly improved (decreased) in children receiving AG for 10 days but not in those receiving glycine controls. AG significantly increased cumulative change over 120 days in WHZ and WAZ scores but not HAZ scores after adjustment for age and season in comparison with the placebo glycine group. Conclusions: Children tolerated AG-supplemented enteral formula well, and it significantly improved cumulative WHZ and WAZ over 120 days in comparison with children in the placebo glycine group. The data also suggested a beneficial effect of AG in the barrier function paracellular pathway, albeit with reduced mannitol excretion. Thus, although the effect of AG on reduced mannitol concentration requires clarification, AG appears to improve nutrition and barrier function.

Effects of vitamin A supplementation on intestinal barrier function, growth, total parasitic, and specific Giardia spp. infections in Brazilian children: a prospective randomized, double-blind, placebo-controlled trial.

Background: This study evaluates the effects of retinol on intestinal barrier function, growth, total parasites, and Giardia spp infections in children in northeastern Brazil. Subjects and Methods: The study was a double-blind, randomized placebo-controlled trial (http://clinicaltrials.gov; register no. #NCT00133406) involving 79 children who received vitamin A 100,000–200,000 IU (n = 39) or placebo (n = 40) at enrollment, 4, and 8 months and were followed for 36 months. Intestinal barrier function was evaluated using the lactulose:mannitol ratio test. Stool lactoferrin was used as a marker for intestinal inflammation. Results: The groups were similar with regard to age, sex, nutritional parameters (z scores), serum retinol concentrations, proportion of lactoferrin-positive stool samples, and intestinal barrier function. The lactulose:mannitol ratio did not change during the same time of follow-up (P > 0.05). The proportion of lactoferrin-positive samples evaluated at 1 month did not change between groups (P > 0.05). Total intestinal parasitic, specifically new, infections were significantly lower in the vitamin A treatment compared with control group; these were accounted for entirely by significantly fewer new Giardia infections in the vitamin A treatment group. The cumulative z scores for weight-for-length or height, length or height-for-age z scores, and weight-for-age did not change significantly with vitamin A intervention for 36 months of follow-up. Conclusions: These data showed that total parasitic infection and Giardia spp infections were significantly lower in the vitamin A treatment group when compared with the placebo group, suggesting that vitamin A improves the hosts defenses against Giardia infections.

Campylobacter jejuni and Campylobacter coli in children from communities in Northeastern Brazil: molecular detection and relation to nutritional status

This study determined the prevalence of Campylobacter jejuni/coli and its relation with nutritional status in children from Northeastern Brazil. This was a case-control study design. Stool samples were evaluated for hipO (C. jejuni), ask (C. coli), and cdtABC (C. jejunis cytolethal distending toxin) genes. The nutritional status from these children was assessed by anthropometric measures and z-scores. C. jejuni and C. coli were detected in 9.6% (8/83) and 6.0% (5/83) in the diarrhea group and in 7.2% (6/83) and 1.2% (1/83) of the nondiarrhea group, respectively. Children with positive molecular detection of C. jejuni showed significantly lower z-scores than children without C. jejuni. The cdtABC operon was found in 57% of hipO(+) samples. C. jejuni/coli prevalence was similar in diarrhea and nondiarrhea groups. There was a significant association of C. jejuni infection with lower nutritional status.

Geography, Population, Demography, Socioeconomic, Anthropometry, and Environmental Status in the MAL-ED Cohort and Case-Control Study Sites in Fortaleza, Ceará, Brazil

The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort in the studys Fortaleza, Brazil, catchment area has a population of approximately 82 300 inhabitants. Most of the households (87%) have access to clean water, 98% have electricity, and 69% have access to improved toilet/sanitation. Most childbirths occur at the hospital, and the under-5 mortality rate is 20 per 1000 live births. The MAL-ED case-control study population, identified through the Institute for the Promotion of Nutrition and Human Development (IPREDE), serves 600 000 inhabitants from areas totaling about 42% of the city of Fortaleza. IPREDE receives referrals from throughout the state of Ceará for infant nutrition, and provides services including teaching activities and the training of graduate students and health professionals, while supporting research projects on child nutrition and health. In this article, we describe the geographic, demographic, socioeconomic, anthropometric, and environmental status of the MAL-ED cohort and case-control study populations in Fortaleza, Brazil.

Urinary N -methylnicotinamide and β-aminoisobutyric acid predict catch-up growth in undernourished Brazilian children

Enteric infections, enteropathy and undernutrition in early childhood are preventable risk factors for child deaths, impaired neurodevelopment, and later life metabolic diseases. However, the mechanisms linking these exposures and outcomes remain to be elucidated, as do biomarkers for identifying children at risk. By examining the urinary metabolic phenotypes of nourished and undernourished children participating in a case-control study in Semi-Arid Brazil, we identified key differences with potential relevance to mechanisms, biomarkers and outcomes. Undernutrition was found to perturb several biochemical pathways, including choline and tryptophan metabolism, while also increasing the proteolytic activity of the gut microbiome. Furthermore, a metabolic adaptation was observed in the undernourished children to reduce energy expenditure, reflected by increased N-methylnicotinamide and reduced β-aminoisobutyric acid excretion. Interestingly, accelerated catch-up growth was observed in those undernourished children displaying a more robust metabolic adaptation several months earlier. Hence, urinary N-methylnicotinamide and β-aminoisobutyric acid represent promising biomarkers for predicting short-term growth outcomes in undernourished children and for identifying children destined for further growth shortfalls. These findings have important implications for understanding contributors to long-term sequelae of early undernutrition, including cognitive, growth, and metabolic functions.

Selective surveillance for nosocomial infections in a Brazilian hospital.

OBJECTIVE To devise a system for surveying the frequency of nosocomial infections in a tertiary care hospital in a developing country. DESIGN Prospective selective surveillance by nurses of the charts of patients at high risk for nosocomial infections, as identified by a form completed by resident physicians. The sensitivity, specificity, and predictive value of this method of selective surveillance were compared with those for total prospective chart review by two infectious disease specialists. SETTING A university hospital in northeastern Brazil. PATIENTS All patients hospitalized for more than 72 hours with an identified risk factor for nosocomial infection. RESULTS The ratio of nosocomial infections to 100 discharges was 13.4 and the incidence density was 11.2/1,000 patient days. The surveillance method demonstrated a sensitivity of 74% and a specificity of 99.7%. Positive predictive value was 93%, negative predictive value was 99%, and overall accuracy was 98%. CONCLUSIONS This method of selective surveillance for nosocomial infections based on risk factors identified by physicians demonstrated excellent predictive value and overall accuracy and may be of use to other hospitals that lack a nursing care plan book such as the Kardex. The relative frequency of nosocomial infections significantly exceeded the rates reported from hospitals in developed countries.

Zinc, vitamin A, and glutamine supplementation in Brazilian shantytown children at risk for diarrhea results in sex-specific improvements in verbal learning

OBJECTIVE: To identify the impact of supplemental zinc, vitamin A, and glutamine, alone or in combination, on long-term cognitive outcomes among Brazilian shantytown children with low median height-for-age z-scores. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in children aged three months to nine years old from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for cognitive testing (total of 167 children) were: (1) placebo, n = 25; (2) glutamine, n = 23; (3) zinc, n = 18; (4) vitamin A, n = 19; (5) glutamine+zinc, n = 20; (6) glutamine+vitamin A, n = 21; (7) zinc+vitamin A, n = 23; and (8) glutamine+zinc+vitamin A, n = 18. Neuropsychological tests were administered for the cognitive domains of non-verbal intelligence and abstraction, psychomotor speed, verbal memory and recall ability, and semantic and phonetic verbal fluency. Statistical analyses were performed using SPSS, version 16.0. ClinicalTrials.gov: NCT00133406. RESULTS: Girls receiving a combination of glutamine, zinc, and vitamin A had higher mean age-adjusted verbal learning scores than girls receiving only placebo (9.5 versus 6.4, p = 0.007) and girls receiving zinc+vitamin A (9.5 versus 6.5, p = 0.006). Similar group differences were not found between male study children. CONCLUSIONS: The findings suggest that combination therapy offers a sex-specific advantage on tests of verbal learning, similar to that seen among female patients following traumatic brain injury.

Effects of glutamine alone or in combination with zinc and vitamin A on growth, intestinal barrier function, stress and satiety-related hormones in Brazilian shantytown children

OBJECTIVE: To determine the impact of supplemental zinc, vitamin A, and glutamine alone or in combination on growth, intestinal barrier function, stress and satiety-related hormones among Brazilian shantytown children with low median height-for-age z-scores. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in children aged two months to nine years from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for testing (a total of 120 children) were as follows: (1) glutamine alone, n = 38; (2) glutamine plus vitamin A plus zinc, n = 37; and a placebo (zinc plus vitamin A vehicle) plus glycine (isonitrogenous to glutamine) control treatment, n = 38. Leptin, adiponectin, insulin-like growth factor (IGF-1), and plasma levels of cortisol were measured with immune-enzymatic assays; urinary lactulose/mannitol and serum amino acids were measured with high-performance liquid chromatography. ClinicalTrials.gov: NCT00133406. RESULTS: Glutamine treatment significantly improved weight-for-height z-scores compared to the placebo-glycine control treatment. Either glutamine alone or all nutrients combined prevented disruption of the intestinal barrier function, as measured by the percentage of lactulose urinary excretion and the lactulose:mannitol absorption ratio. Plasma leptin was negatively correlated with plasma glutamine (p = 0.002) and arginine (p = 0.001) levels at baseline. After glutamine treatment, leptin was correlated with weight-for-age (WAZ) and weight-for-height z-scores (WHZ) (p≤0.002) at a 4-month follow-up. In addition, glutamine and all combined nutrients (glutamine, vitamin A, and zinc) improved the intestinal barrier function in these children. CONCLUSION: Taken together, these findings reveal the benefits of glutamine alone or in combination with other gut-trophic nutrients in growing children via interactions with leptin.