Dietary protein, growth and urea kinetics in severely malnourished children and during recovery

The case mortality for severe malnutrition in childhood remains high, but established best approaches to treatment are not used in practice. The energy and protein content of the diet at different stages of treatment appears important, but remains controversial. The effect on growth, urea kinetics and the urinary excretion of 5-L-oxoproline was compared between a standard infant formula (HP group) provided in different quantities at each stage of treatment and a recommended dietary regimen, which differentiates the requirements of protein and energy during the acute phase of resuscitation (maintenance intake of energy and protein, relatively low protein to energy ratio, LP group) from those during the restoration of a weight deficit (energy and nutrient dense). The energy required to maintain weight was less in the HP than the LP group, but the HP group was not able to achieve as high an energy intake during repletion of wasting because of the high volume which would have had to be consumed. Compared to the LP group, in the HP group during catch-up growth there was significantly greater deposition of lean tissue and higher rates of urea production, hydrolysis and salvage of urea-nitrogen. These, together with higher rates of 5-L-oxoprolinuria, suggest a greater constraint of the formation of adequate amounts of nonessential amino acids, especially glycine, in the face of enhanced demands. Although more effective rehabilitation might be achieved using a standard formula, there is the need to determine the extent to which it might impose metabolic stress compared with the modified formulation.     

Effect of renutrition on humoral and cell-mediated immunity in severely malnourished children

Forty-three Colombian children suffering from either kwashiorkor (21), combined protein-calorie malnutrition (11), or maramus (11) were hospitalized and provided a high protein, high calorie diet for 4 to 5 wk. Improvement in clinical and nutritional status was accompanied by significant increases in levels of serum immunoglobulins G and M and C3 complement and by significant decreases in serum immunoglobulin A concentrations, especially in infants with kwashiorkor. Skin test reactions to purified protein derivative and candidin improved during renutrition. Lymphocyte blastogenesis after stimulation in vitro with phytohemagglutinin and pokeweed mitogen increased rapidly during hospitalization. After 1 yr posttreatment, cell-mediated immune responses, both in vivo and in vitro, had diminished. These results indicate that some aspects of the immune response are affected to a different degree in kwashiorkor, maramus, and combined malnutrition. Short-term nutritional rehabilitation has a differential effect on the long-term restoration of various aspects of immunity.     

Bacteraemia among severely malnourished children in jimma university hospital, ethiopia

Background

Sever acute malnutrition severely suppresses every component of the immune system leading to increased susceptibility and severity to infection. However, symptoms and signs of infections are often unapparent making prompt clinical diagnosis and early treatment very difficult. The aim of the study was to determine the magnitude of bacteraemia and antimicrobial sensitivity among severely malnourished children.

Methods

Severely malnourished children admitted in Jimma University Specialized Hospital were enrolled between October, 2009 to May, 2010. Blood samples were collected, processed and bacterial isolates were identified using standard bacteriological procedures. Then, antibiotic susceptibility pattern of the isolates was determined by using Kirby-Bauer technique.

Results

Bacteraemia was seen in 35 (20.6%) of the 170 study subjects. There were a total of 35 bacterial isolates, Gram positive bacteria constitute 24(68.6%) of the isolates, where Staphylococcus aureus was the leading Gram positive isolate while Klebsiella species were the dominant Gram negative isolates. Twelve (7.1%) children died and 4 (33.3%) of them had bacteraemia. While susceptibility was more than 80% to Gentamicin, Ciprofloxacin and Ceftriaxone, increased level of resistance was documented to commonly used antibiotics, such as Amoxycillin, Co-trimoxazole and Chloramphenicol.

Conclusion

High prevalence of bacteraemia with predominating Gram positive isolates and increased level of resistance to commonly used antibiotics was shown among severely malnourished children in Jimma. Further studies are required to revise the current guideline for antibiotic choice.     

Efficacy of mid-upper arm circumference in identification,follow-up and discharge of malnourished children during nutrition rehabilitation

BACKGROUND/OBJECTIVES

Although it is crucial to identify those children likely to be treated in an appropriate nutrition rehabilitation programme and discharge them at the appropriate time, there is no golden standard for such identification. The current study examined the appropriateness of using Mid-Upper Arm Circumference for the identification, follow-up and discharge of malnourished children. We also assessed its discrepancy with the Weight-for-Height based diagnosis, the rate of recovery, and the discharge criteria of the children during nutrition rehabilitation.

SUBJECTS/METHODS

The study present findings from 156 children (aged 6-59 months) attending a supplementary feeding programme at Makadara and Jericho Health Centres, Eastern District of Nairobi, Kenya. Records of age, weight, height and mid-upper arm circumference were selected at three stages of nutrition rehabilitation: admission, follow-up and discharge. The values obtained were then used to calculate z-scores as defined by WHO Anthro while estimating different diagnostic indices.

RESULTS

Mid-upper arm circumference single cut-off (< 12.5 cm) was found to exhibit high values of sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio at both admission and discharge. Besides, children recorded higher rate of recovery at 86 days, an average increment of 0.98 cm at the rate of 0.14mm/day, and a weight gain of 13.49gm/day, albeit higher in female than their male counterparts. Nevertheless, children admitted on basis of low MUAC had a significantly higher MUAC gain than WH at 0.19mm/day and 0.13mm/day respectively.

CONCLUSIONS

Mid-upper arm circumference can be an appropriate tool for identifying malnourished children for admission to nutrition rehabilitation programs. Our results confirm the appropriateness of this tool for monitoring recovery trends and discharging the children thereafter. In principle the tool has potential to minimize nutrition rehabilitation costs, particularly in community therapeutic centres in developing countries.     

Antibiotics in severely malnourished children: systematic review of efficacy, safety and pharmacokinetics

Objective

To systemically review the evidence in support of World Health Organization guidelines recommending broad-spectrum antibiotics for children with severe acute malnutrition (SAM).

Methods

CENTRAL, MEDLINE, EMBASE, LILACS, POPLINE, CAB Abstracts and ongoing trials registers were searched. Experts were contacted. Conference proceedings and reference lists were manually searched. All study types, except single case reports, were included.

Findings

Two randomized controlled trials (RCTs), one before-and-after study and two retrospective reports on clinical efficacy and safety were retrieved, together with 18 pharmacokinetic studies. Trial quality was generally poor and results could not be pooled due to heterogeneity. Oral amoxicillin for 5 days was as effective as intramuscular ceftriaxone for 2 days (1 RCT). For uncomplicated SAM, amoxicillin showed no benefit over placebo (1 retrospective study). The introduction of a standardized regimen using ampicillin and gentamicin significantly reduced mortality in hospitalized children (odds ratio, OR: 4.0; 95% confidence interval, CI: 1.7–9.8; 1 before-and-after study). Oral chloramphenicol was as effective as trimethoprim-sulfamethoxazole in children with pneumonia (1 RCT). Pharmacokinetic data suggest that normal doses of penicillins, cotrimoxazole and gentamicin are safe in malnourished children, while the dose or frequency of chloramphenicol requires adjustment. Existing evidence is not strong enough to further clarify recommendations for antibiotic treatment in children with SAM.

Conclusion

Large RCTs are needed to define optimal antibiotic treatment in children with SAM with and without complications. Further research into gentamicin and chloramphenicol toxicity and into the pharmacokinetics of ceftriaxone and ciprofloxacin is also required.     

The Kingston project. I. Growth of malnourished children during rehabilitation in the community, given a high energy supplement

Moderate and severely malnourished children referred from public health clinics in Kingston, Jamaica, to a metabolic ward were treated at home for 6 months using community health aides and standard health care similar to that offered by the local health service. A randomly selected subgroup of these children received in addition a daily high energy food supplement of 3.31 MJ for the first 3 months of the 6-month intervention period. Both groups received full nutritional and medical surveillance and care. The supplemented gained significantly more in weight than the unsupplemented children, but the advantage was lost once supplementation ceased. They also gained significantly more in length and this gain was maintained at the end of the intervention period. However, this increase in length, without continuing superior weight gain, left the supplemented children significantly more wasted than the unsupplemented, as measured by a body mass index (weight divided by height squared). These findings remained stable after interactions with morbidity measures had been taken into account. It is concluded that (1) high-energy supplementation assists rehabilitation of malnourished children brought to public health service clinics and treated in the community, and (2) supplementation should be continued until there is catch-up growth to within an acceptable distance from expected length for age.     

Plasma somatomedin-C in Nigerian malnourished children fed a vegetable protein rehabilitation diet

Plasma somatomedin-C (pSm-C) was measured by immunoassay in Nigerian malnourished children treated with a mainly vegetable diet. In oedematous children, the mean intake was 4.31 +/- 0.23 g protein and 611 +/- 46 kJ per kg body weight per day, and in marasmic children 5.22 +/- 0.62 g protein and 795 +/- 131 kJ/kg body weight/d. PSm-C concentration (U/ml) was measured at weekly intervals to determine the response to this rehabilitation diet. By our assay the value for 39 normal children (age range 6-36 months) was 0.315 +/- 0.035 U/ml. The average initial level of pSm-C in the malnourished children was 0.19 +/- 0.03 (n = 24). The values were higher (P less than 0.05) in the 7 marasmic children (0.26 +/- 0.1) than in the 11 with oedema (0.15 +/- 0.02). Eight days after admission pSm-C had risen to 0.20 +/- 0.02 (n = 24) and at discharge after approximately 19 d, pSm-C concentration was normal, 0.30 +/- 0.05. In oedematous malnutrition, pSm-C level at discharge was lower than in marasmus, 0.27 +/- 0.06 (n = 17) compared with 0.37 +/- 0.06 (n = 7) (P less than 0.05). Because the childrens' stay in hospital was short (average 19 d), they were far from attaining normal weight for height by the time of discharge. However, they had gained on average 0.9 kg and their clinical condition was satisfactory. It is concluded that the vegetable-based diet produced satisfactory recovery, at least in the initial stages. Increases in pSm-C compared well with those found in an earlier study with milk-based diets.     

HIV and mortality of mothers and children: evidence from cohort studies in Uganda, Tanzania, and Malawi

BACKGROUND: The steady decline in child mortality observed in most African countries through the 1960s, 1970s, and 1980s has stalled in many countries in the 1990s because of the AIDS epidemic. However, the census and household survey data that generally are used to produce estimates of child mortality do not permit precise measures of the adverse effect of HIV on child mortality. METHODS: To calculate excess risks of child mortality as the result of maternal HIV status, we used pooled data from 3 longitudinal community-based studies that classified births by the mother's HIV status. We also estimated excess risks of child death caused by increased mortality among mothers. The joint effects of maternal HIV status and maternal survival were quantified using multivariate techniques in a survival analysis. RESULTS: Our analysis shows that the excess risk of death associated with having an HIV-positive mother is 2.9 (95% confidence interval = 2.3-3.6), and this effect lasts throughout childhood. The excess risk associated with a maternal death is 3.9 (2.8-5.5) in the 2-year period centered on the mother's death, with children of both infected and uninfected mothers experiencing higher mortality risks at this time. CONCLUSION: HIV impacts on child mortality directly through transmission of the virus to newborns by infected mothers and indirectly through higher child mortality rates associated with a maternal death.     

Declining child mortality in northern Malawi despite high rates of infection with HIV

Objective

To determine whether routine surveys, such as the Demographic and Health Surveys (DHS), have underestimated child mortality in Malawi.

Methods

Rates and causes of child mortality were obtained from a continuous-registration demographic surveillance system (DSS) in Malawi for a population of 32 000. After initial census, births and deaths were reported by village informants and updated monthly by project enumerators. Cause of death was established by verbal autopsy whenever possible. The likely impact of human immunodeficiency virus (HIV) infection on child mortality was also estimated from antenatal clinic surveillance data. Overall and age-specific mortality rates were compared with those from the 2004 Malawi DHS.

Findings

Between August 2002 and February 2006, 38 617 person–years of observation were recorded for 20 388 children aged < 15 years. There were 342 deaths. Re-census data, follow-up visits at 12 months of age and the ratio of stillbirths to neonatal deaths suggested that death registration by the DSS was nearly complete. Infant mortality was 52.7 per 1000 live births, under-5 mortality was 84.8 per 1000 and under-15 mortality was 99.1 per 1000. One-fifth of deaths by age 15 were attributable to HIV infection. Child mortality rates estimated with the DSS were approximately 30% lower than those from national estimates as determined by routine surveys.

Conclusion

The fact that child mortality rates based on the DSS were relatively low in the study population is encouraging and suggests that the low mortality rates estimated nationally are an accurate reflection of decreasing rates.     

Active and passive transport of sodium and potassium ions in erythrocytes of severely malnourished Jamaican children

Erythrocytes of normal and malnourished children, both marasmic and oedematous (kwashiorkor), were equilibrated in standard incubation medium and their ion transport via the Na/K pump and the pathways of passive permeation were measured as unidirectional fluxes of 86Rb (as a congener of K) and 22Na. Cells of children with kwashiorkor exhibited a 65 per cent higher ouabain-sensitive K(Rb) influx ('pump rate') than those of normal or marasmic children. When allowance was made for cytoplasmic Na concentration, the pump rate was slower in younger (12 months and under) normal children than in older children. Judged by the same criterion, cells of older marasmic children also had slower steady-state pump activity. The passive permeation of K through the residual 'leak' pathway (ie, ouabain-and-bumetanide-insensitive influx) and Na permeation (ouabain-and-bumetanide-insensitive Na efflux) were greater in malnourished children than in normal children by a factor of two or more. During treatment for malnutrition, both Na-pump activity and ouabain binding increased rapidly in marasmic children. Passive permeation did not return to normal levels in malnourished children during the period of hospitalization.     

The impact of vitamin A supplementation on mortality inequalities among children in Nepal

OBJECTIVE: This paper examines gender, caste and economic differentials in child mortality in the context of a cluster-randomized trial of vitamin A distribution, in order to determine whether or not the intervention narrowed these differentials. DESIGN: The study involved secondary analysis of data from a placebo-controlled randomized field trial of vitamin A supplements. The study took place between 1989-1991 in rural Sarlahi District of Nepal, with 30,059 children age 6 to 60 months. The main outcome measures were differences in mortality between boys and girls, between highest Hindu castes and others, and between the poorest quintile and the four other quintiles. RESULTS: Without vitamin A, girls in rural Nepal experience 26.1 deaths per 1000, which is 8.3 deaths more than the comparison population of boys. With vitamin A the mortality disadvantage of girls is nearly completely attenuated, at only 1.41 additional deaths per 1000 relative to boys. Vitamin A supplementation also narrowed mortality differentials among Hindu castes, but did not lower the concentration of mortality across quintiles of asset ownership. The vitamin A-related attenuation in mortality disadvantage from gender and caste is statistically significant. CONCLUSIONS: We conclude that universal supplementation with vitamin A narrowed differentials in child death across gender and caste in rural Nepal. Assuring high-coverage vitamin A distribution throughout Nepal could help reduce inequalities in child survival in this population.     

Comparison of the efficacy of a solid ready-to-use food and a liquid,milk-based diet for the rehabilitation of severely malnourished children: a randomized trial

BACKGROUND: The World Health Organization recommends a liquid, milk-based diet (F100) during the rehabilitation phase of the treatment of severe malnutrition. A dry, solid, ready-to-use food (RTUF) that can be eaten without adding water has been proposed to eliminate the risk of bacterial contamination from added water. The efficacies of RTUF and F100 have not been compared. OBJECTIVE: The objective was to compare the efficacy of RTUF and F100 in promoting weight gain in malnourished children. DESIGN: In an open-labeled, randomized trial, 70 severely malnourished Senegalese children aged 6-36 mo were randomly allocated to receive 3 meals containing either F100 (n = 35) or RTUF (n = 35) in addition to the local diet. The data from 30 children in each group were analyzed. RESULTS: The mean (+/- SD) daily energy intake in the RTUF group was 808 +/- 280 (95% CI: 703.8, 912.9) kJ x kg body wt(-1) x d(-1), and that in the F100 group was 573 +/- 201 (95% CI: 497.9, 648.7) kJ. kg body wt(-1) x d(-1) (P < 0.001). The average weight gains in the RTUF and F100 groups were 15.6 (95% CI: 13.4, 17.8) and 10.1 (95% CI: 8.7, 11.4) g x kg body wt(-1) x d(-1), respectively (P < 0.001). The difference in weight gain was greater in the most wasted children (P < 0.05). The average duration of rehabilitation was 17.3 (95% CI: 15.6, 19.0) d in the F100 group and was 13.4 (95% CI: 12.1, 14.7) d in the RTUF group (P < 0.001). CONCLUSIONS: This study indicated that RTUF can be used efficiently for the rehabilitation of severely malnourished children.     

The use of parenteral nutrition in a severely malnourished hemodialysis patient with hypercalcemia.

There is a high prevalence of protein-energy malnutrition (PEM) in chronic dialysis patients. Causes of PEM include the catabolic effects of hemodialysis treatments, acidemia associated with end-stage renal disease, common comorbid conditions, and uremia-induced anorexia. Morbidity and mortality increase with PEM. Before considering parenteral nutrition (PN) as a nutrition intervention in a maintenance dialysis patient, all other efforts to promote optimal nutrition need to be exhausted. The first step is careful evaluation of protein-energy status, followed by intensive nutrition counseling. If necessary, this is followed by oral nutrition supplementation, appetite stimulation, enteral tube feedings, and finally PN. Short-term parenteral nutrition (PN) became a crucial component of the management of a 38-year-old hemodialysis (HD) patient who endured serious complications after kidney transplant rejection. A profound and prolonged malnourished state followed her treatment for necrotizing pancreatitis. She had developed persistent hypercalcemia believed secondary to tertiary hyperparathyroidism (HPT) and immobilization. Later, she developed hungry bone syndrome (HBS) after parathyroidectomy (PTX). She also developed refeeding syndrome after initiation of PN. The patient's persistent, poorly understood hypercalcemia did not resolve even after PTX and removal of all other sources of vitamin D and calcium from her feedings, medications, and dialysis bath. The close communication of the inpatient and outpatient dialysis multidisciplinary teams became a key component to the successful outcome in this complex patient.     

Effect of nucleotide intake and nutritional recovery on insulin-like growth factor I and other hormonal biomarkers in severely malnourished children

The objective of the present study is to demonstrate the effect of nucleotide intake and intensive nutritional support on the concentration of insulin-like growth factor I (IGF-I) and other hormonal biomarkers in severely malnourished children. Twenty-six severely malnourished children < 48 months of age received formula without lactose via enteral feeding for 2 weeks and ad libitum for an additional 2 weeks. Anthropometrical measurements were performed and serum concentrations of IGF-I, insulin-like growth factor binding protein-3 (IGFBP-3), leptin, soluble leptin receptor (sOB-R), as well as the estimated molar excess of sOB-R over leptin were obtained. Two groups were formed. One group received formula with nucleotides (NT+; n 13) and the other without nucleotides (NT-; n 13). A control group was included (n 13). Parametric and non-parametric tests as well as ANOVA models were used. Nutritional recovery, nucleotides intake, type of malnutrition, age and the interaction between gender and malnutrition influenced the concentration of IGF-I (P < 0.001). Nutritional recovery, nucleotides intake, gender and type of malnutrition had an effect on IGFBP-3 (P < 0.001). Nutritional recovery had a significant effect on serum leptin (P = 0.001). Age and nutritional recovery had an effect on sOB-R (P < 0.001); all variables included affected the molar excess of sOB-R over leptin (P < 0.001). In conclusion, nucleotide intake and nutritional recovery had a notable effect on IGF-I, IGFBP-3 and other hormonal biomarkers. This outcome could stimulate the catch-up growth of severely malnourished infants and toddlers during the nutritional recovery period.     

The rehabilitation of malnourished rats with different sources of dietary lipids

Effects of different sources of dietary lipids with varying levels of essential fatty acids (EFA) were investigated as the only variables in the rehabilitation of rats previously malnourished by feeding a restricted amount of a low protein, low fat diet for 6 weeks. Five groups of the malnourished weanling rats were rehabilitated for 4 weeks with identical diets containing either soybean, peanut, sesame, palm or coconut oils, respectively. Adequacy of EFA in the diets improved appetite and food intake during rehabilitation. Coconut oil was least effective in growth recovery. Previous malnutrition left permanent growth stunting and deficits in the size of organs. Palm oil produced the highest concentration of plasma cholesterol while coconut oil produced the highest concentration of phospholipids. Total lipid and phospholipid concentrations were adversely affected by malnutrition, but in rehabilitated rats the response varied with the type of tissue and source of dietary lipids. The fatty acid profiles of phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) of the brain and liver were adversely affected by malnutrition, but in the rehabilitated rats, PC and PE fatty acids varied with the level of EFA, type of tissue and source of dietary lipids. Overall, post-malnutrition rehabilitation did not correct all the damage imposed by malnutrition. Recovery, in qualitative and quantitative terms, varied with the type of tissue and dietary lipid fed, and was related positively to the levels of EFA in the diets.