Malnutrition and Childhood Disability in Turkana, Kenya: Results from a Case-Control Study.

BACKGROUND: Children with disabilities may be particularly vulnerable to malnutrition, as a result of exclusions and feeding difficulties. However, there is limited evidence currently available on this subject. METHODS: A population-based case-control study was conducted in Turkana County, Kenya, between July and August 2013. Key informants in the community identified children aged 6 months to 10 years who they believed may have a disability. These children were screened by a questionnaire (UNICEF-Washington Group) and assessed by a paediatrician to confirm whether they had a disability and the type. Two controls without disabilities were selected per case: A sibling control (sibling nearest in age) and a neighbourhood control (nearest neighbour within one year of age). The caregiver completed a questionnaire on behalf of the child (e.g. information on feeding, poverty, illness, education), and anthropometric measures were taken. We undertook multivariable logistic and linear regression analyses to estimate the relationship between disability and malnutrition. RESULTS: The study included 311 cases with disabilities, 196 sibling controls and 300 neighbour controls. Children with disabilities were more likely to report a range of feeding difficulties. They were 1.6-2.9 times more likely to have malnutrition in comparison to neighbour controls or family controls, including general malnutrition (low weight for age), stunting (low height for age), low body mass index (BMI) or low mid upper arm circumference (MUAC) for age. Children with disabilities were almost twice as likely to have wasting (low weight for height) in comparison to neighbour controls (OR = 1.9, 95% CI 1.1-3.2), but this difference was not apparent compared with siblings (OR = 1.5, 95% CI 0.8-2.7). Children with disabilities also faced other exclusions. For instance those aged 5+ were much more likely not to attend school than neighbour controls (OR = 8.5, 95% CI 4.3-16.9). CONCLUSIONS: Children with disabilities were particularly vulnerable to malnutrition, even within this area of food insecurity and widespread malnutrition. Efforts need to be made to include children with disabilities within food supplementation programmes, and school based programmes alone may be inadequate to meet this need. Exclusion of children with disabilities from education is also a priority area to be addressed.

Assessing chaperone for Zn, Cu-superoxide dismutase as an indicator of copper deficiency in malnourished children.

UNLABELLED: It is not clear how frequent is copper deficiency in humans. Current copper markers are not sensitive enough to detect early copper deficiency and new markers are needed. CCS is a candidate to become a copper biomarker. OBJECTIVE: Measuring CCS mRNA relative expression in malnourished children and compare results (a) with those of the same children after nutritional recovery and (b) with well-nourished children. METHOD: On admission to the protocol and after 15 day nutritional treatment, severely (G1=18) and moderately (G2=10) malnourished children were compared with well-nourished healthy controls (G3=15), measuring anthropometric indicators, blood biochemistry, Cu, Fe and Zn serum concentrations, ceruloplasmin, C Reactive protein and mRNA abundance of CCS, SOD and MT2 in peripheral mononuclear cells. RESULT: In malnourished groups, mean serum copper concentration was below the cut-off on admission to hospital and increased after 15 days (t-test, p<0.01). On admission to protocol, CCS mRNA abundance in G1 and G2 was higher than in G3 (one way ANOVA, p<0.001). After 15 days, CCS expression decreased as expected (t-test, p<0.001). Initial SOD mRNA relative abundance was higher in study groups than controls and also between G1 and G2 (One way ANOVA, both p<0.01); after 15 days, G1 and G2 were not different (t-test, NS). MT2A abundance of transcripts did not follow a clear change pattern. CONCLUSION: CCS mRNA abundance responded as expected, being higher in malnourished children than in controls; nutritional recovery in these latter resulted in decreasing expression of the chaperone, supporting the hypothesis that CCS may be a copper biomarker.

A preliminary examination of the effects of genetic variants of redox enzymes on susceptibility to oedematous malnutrition and on percentage cytotoxicity in response to oxidative stress in vitro.

BACKGROUND: The causes of oedematous vs non-oedematous childhood malnutrition (OM vs NOM) remain elusive. It is possible that inherited differences in handling oxidant stressors are a contributing factor. AIMS: To test for associations between polymorphisms in five genes and (i) risk of OM, a case-control study, and (ii) percentage cytotoxicity in peripheral blood mononuclear cells (PBMCs) exposed to hydrogen peroxide (H(2)O(2)), an in vitro cell challenge study. METHODS: Participants had been admitted previously for treatment of OM (cases, n = 74) or NOM (controls, n = 50), or were an independent set of healthy pregnant women (n = 47) who donated peripheral blood mononuclear cells. We tested for associations between genetic variation and outcome using single markers or a bivariate score constructed by counting numbers of deleterious alleles for each of 15 possible pairs of markers. RESULTS: In the case-control study there were no significant single-marker associations with OM. We did find that higher bivariate scores were associated with OM for the pair of NAD(P)H:quinone oxidoreductase 1 and catalase (odds ratio 2·00, 95% CI 1·05-3·82). In the cell challenge experiments, there were no significant associations with percentage cytotoxicity. CONCLUSIONS: Variation in this small set of genes seems unlikely to have a large impact on either risk of OM or cytotoxicity after H(2)O(2) exposure. The use of larger sample sizes to test the effects of a much larger set of genetic variants will be required in order to determine whether genetic variation contributes to the risk of OM. Such studies have potential for improving our understanding of causal pathways in OM.

Jejunal disaccharidases in protein energy malnutrition and recovery.

The jejunal disaccharidases, sucrase, maltase and lactase, were determined in jejunal biopsies obtained from 43 malnourished children and 10 controls. In the study group, 63% were girls and 93% had severe malnutrition. Lactase activity was significantly reduced in third and fourth degree malnutrition (p < 0.05 and p < 0.005, respectively), but maltase activity was significantly reduced only in the fourth degree malnutrition (p < 0.01). After recovery, maltase and sucrase activities showed a marginally significant increase (p = 0.06), where lactase showed no significant increase (p > 0.05). We conclude that jejunal disaccharidase activity decreases significantly with increasing severity of malnutrition, lactase being the most severely affected and the last to recover.

Elevated glutathione S-transferase activity in erythrocytes from malnourished children.

Glutathione S-transferases (GSTs) are principally involved in detoxification. These enzymes can be induced by an increased flux of substrate, such as occurs during pro-oxidative stress or antioxidant deficiency. We tested the hypothesis that the postulated oxidative stress in severe malnutrition would result in induction of GSTs in erythrocytes. Erythrocyte GST activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was measured in 271 malnourished children (22 undernourished; 92 marasmic; 82 kwashiorkor; 75 marasmic-kwashiorkor) and 48 healthy children. GST activity in the malnourished children was significantly higher than the control group (P < 0.01). The GST activity in the four classes of malnutrition did not differ. There was a weak relationship between GST activity and the height deficit, but not with the weight deficit, or the clinical features displayed by the children. The 11 children that died had a higher value than the survivors. There was no change in GST with anthropometric recovery. We conclude that erythrocyte GST has been induced in children with malnutrition. Induction of erythrocyte GST may be the result of exposure of the children to oxidative stress during the months prior to their presentation with severe malnutrition.

Elevated glutathione S-transferase activity in erythrocytes from malnourished children

Glutathione S-transferases (GSTs) are principally involved in detoxication. These enzymes can be induced by an increased flux of substrate, such as occurs during pro-oxidative stress or antioxidant deficiency. We tested the hypothesis that the postulated oxidative stress in severe malnutrition would result in induction of GSTs in erythocytes. Erythrocyte GST activity towards 1-chloro-2, 4-dinitrobenzene (CDNB) was measured in 271 malnourished children (22 undernourished; 92 marasmic; 82 kwashiorkor; 75 marasmic-kwashiorkor) and 48 healthy children. GST activity in the malnourished children was significnatly higher than the control group (p < 0.01). The GST activity in the four classes of malnutrition did not differ. There was a weak relationship between GST activity and the height deficit, but not with the weight deficit, or the clinical features displayed by the children. The 11 children that died had a higher value than the survivors. There was no change in GST with anthropometric recovery. We conclude that erythrocyte GST has been induced in children with malnutrition. Induction of erythrocyte GST may be the result of exposure of the children to oxidative stress during the months prior to their presentation with severe malnutrition (AU)