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Brain MRI and cognitive function seven years after surviving an episode of severe acute malnutrition in a cohort of Malawian children.

ABSTRACT: OBJECTIVE:To assess differences in cognition functions and gross brain structure in children seven years after an episode of severe acute malnutrition (SAM), compared with other Malawian children. DESIGN:Prospective longitudinal cohort assessing school grade achieved and results of five computer-based (CANTAB) tests, covering three cognitive domains. A subset underwent brain MRI scans which were reviewed using a standardized checklist of gross abnormalities and compared with a reference population of Malawian children. SETTING:Blantyre, Malawi.ParticipantsChildren discharged from SAM treatment in 2006 and 2007 (n 320; median age 9·3 years) were compared with controls: siblings closest in age to the SAM survivors and age/sex-matched community children. RESULTS:SAM survivors were significantly more likely to be in a lower grade at school than controls (adjusted OR = 0·4; 95 % CI 0·3, 0·6; P < 0·0001) and had consistently poorer scores in all CANTAB cognitive tests. Adjusting for HIV and socio-economic status diminished statistically significant differences. There were no significant differences in odds of brain abnormalities and sinusitis between SAM survivors (n 49) and reference children (OR = 1·11; 95 % CI 0·61, 2·03; P = 0·73). CONCLUSIONS:Despite apparent preservation in gross brain structure, persistent impaired school achievement is likely to be detrimental to individual attainment and economic well-being. Understanding the multifactorial causes of lower school achievement is therefore needed to design interventions for SAM survivors to thrive in adulthood. The cognitive and potential economic implications of SAM need further emphasis to better advocate for SAM prevention and early treatment.

SUBMITTER: Lelijveld N

PROVIDER: S-EPMC6411134 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Brain MRI and cognitive function seven years after surviving an episode of severe acute malnutrition in a cohort of Malawian children.

Lelijveld Natasha N Jalloh Alhaji A AA Kampondeni Samuel D SD Seal Andrew A Wells Jonathan C JC Goyheneix Magdalena M Chimwezi Emmanuel E Mallewa Macpherson M Nyirenda Moffat J MJ Heyderman Robert S RS Kerac Marko M

Public health nutrition 20181203 8

<h4>Objective</h4>To assess differences in cognition functions and gross brain structure in children seven years after an episode of severe acute malnutrition (SAM), compared with other Malawian children.<h4>Design</h4>Prospective longitudinal cohort assessing school grade achieved and results of five computer-based (CANTAB) tests, covering three cognitive domains. A subset underwent brain MRI scans which were reviewed using a standardized checklist of gross abnormalities and compared with a ref ...[more]

PMID: 30501662

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Project description:BackgroundMore children are now surviving severe acute malnutrition (SAM), but evidence suggests that early-life malnutrition is associated with increased risk of long-term cardio-metabolic disorders. To better understand potential mechanisms, we studied the metabolite profiles of children seven years after treatment for SAM.MethodsWe followed-up children (n = 352) treated for SAM in 2006-2007, at Queen Elizabeth Central Hospital, in Malawi. Using nuclear magnetic resonance spectroscopy, tandem mass spectrometry and enzyme-linked immunosorbent assay, we measured circulating metabolites in fasting blood in a subset of SAM survivors (n = 69, 9·6 ± 1·6 years), siblings (n = 44, 10·5 ± 2·7 years), and age and sex-matched community controls (n = 37, 9·4 ± 1·8 years). Data were analysed using univariate and sparse partial least square (sPLS) methods. Differences associated with SAM survival, oedema status, and anthropometry were tested, adjusting for age, sex, HIV, and wealth index.FindingsBased on 194 measured metabolites, the profiles of SAM survivors were similar to those of siblings and community controls. IGF1, creatinine, and FGF21, had loading values >0·3 and ranked stably in the top 10 distinguishing metabolites, but did not differ between SAM survivors and controls with univariate analysis. Current stunting was associated with IGF1 (β = 15·2, SE = 3·5, partial R2 = 12%, p < 0·0001) and this relationship could be influenced by early childhood SAM (β = 17·4, SE = 7·7, partial R2 = 2·8%, p = 0·025). No metabolites were associated with oedema status, duration of hospital stay, anthropometry measured during hospitalization, nor with changes in anthropometry since hospitalization.InterpretationIn this group of survivors, SAM was not associated with longer-term global metabolic changes 7 years after treatment. However, SAM may influence the relationship between current stunting and IGF1. Further risk markers for NCDs in SAM survivors may only be revealed by direct metabolic challenge or later in life.

Project description:BackgroundTackling severe acute malnutrition (SAM) is a global health priority. Heightened risk of non-communicable diseases (NCD) in children exposed to SAM at around 2 years of age is plausible in view of previously described consequences of other early nutritional insults. By applying developmental origins of health and disease (DOHaD) theory to this group, we aimed to explore the long-term effects of SAM.MethodsWe followed up 352 Malawian children (median age 9·3 years) who were still alive following SAM inpatient treatment between July 12, 2006, and March 7, 2007, (median age 24 months) and compared them with 217 sibling controls and 184 age-and-sex matched community controls. Our outcomes of interest were anthropometry, body composition, lung function, physical capacity (hand grip, step test, and physical activity), and blood markers of NCD risk. For comparisons of all outcomes, we used multivariable linear regression, adjusted for age, sex, HIV status, and socioeconomic status. We also adjusted for puberty in the body composition regression model.FindingsCompared with controls, children who had survived SAM had lower height-for-age Z scores (adjusted difference vs community controls 0·4, 95% CI 0·6 to 0·2, p=0·001; adjusted difference vs sibling controls 0·2, 0·0 to 0·4, p=0·04), although they showed evidence of catch-up growth. These children also had shorter leg length (adjusted difference vs community controls 2·0 cm, 1·0 to 3·0, p<0·0001; adjusted difference vs sibling controls 1·4 cm, 0·5 to 2·3, p=0·002), smaller mid-upper arm circumference (adjusted difference vs community controls 5·6 mm, 1·9 to 9·4, p=0·001; adjusted difference vs sibling controls 5·7 mm, 2·3 to 9·1, p=0·02), calf circumference (adjusted difference vs community controls 0·49 cm, 0·1 to 0·9, p=0·01; adjusted difference vs sibling controls 0·62 cm, 0·2 to 1·0, p=0·001), and hip circumference (adjusted difference vs community controls 1·56 cm, 0·5 to 2·7, p=0·01; adjusted difference vs sibling controls 1·83 cm, 0·8 to 2·8, p<0·0001), and less lean mass (adjusted difference vs community controls -24·5, -43 to -5·5, p=0·01; adjusted difference vs sibling controls -11·5, -29 to -6, p=0·19) than did either sibling or community controls. Survivors of SAM had functional deficits consisting of weaker hand grip (adjusted difference vs community controls -1·7 kg, 95% CI -2·4 to -0·9, p<0·0001; adjusted difference vs sibling controls 1·01 kg, 0·3 to 1·7, p=0·005,)) and fewer minutes completed of an exercise test (sibling odds ratio [OR] 1·59, 95% CI 1·0 to 2·5, p=0·04; community OR 1·59, 95% CI 1·0 to 2·5, p=0·05). We did not detect significant differences between cases and controls in terms of lung function, lipid profile, glucose tolerance, glycated haemoglobin A1c, salivary cortisol, sitting height, and head circumference.InterpretationOur results suggest that SAM has long-term adverse effects. Survivors show patterns of so-called thrifty growth, which is associated with future cardiovascular and metabolic disease. The evidence of catch-up growth and largely preserved cardiometabolic and pulmonary functions suggest the potential for near-full rehabilitation. Future follow-up should try to establish the effects of puberty and later dietary or social transitions on these parameters, as well as explore how best to optimise recovery and quality of life for survivors.FundingThe Wellcome Trust.

Project description:BACKGROUND:Computerized cognitive rehabilitation training (CCRT) may be beneficial for alleviating persisting neurocognitive deficits in Ugandan severe malaria survivors. We completed a randomized controlled trial of CCRT for both severe malaria and non-malaria cohorts of children. METHODS:150 school-age severe malaria and 150 non-malaria children were randomized to three treatment arms: 24 sessions of Captain's Log CCRT for attention, working memory and nonverbal reasoning, in which training on each of 9 tasks difficulty increased with proficiency; a limited CCRT arm that did not titrate to proficiency but randomly cycled across the simplest to moderate level of training; and a passive control arm. Before and after 2?months of CCRT intervention and one year following, children were tested with the Kaufman Assessment Battery for Children, 2nd edition (KABC-II), computerized CogState cognitive tests, the Behavior Rating Inventory for Executive Function (BRIEF), and the Achenbach Child Behavior Checklist (CBCL). RESULTS:Malaria children assigned to the limited-CCRT intervention arm were significantly better than passive controls on KABC-II Mental Processing Index (P?=?0.04), Sequential Processing (working memory) (P?=?0.02) and the Conceptual Thinking subtest (planning/reasoning) (P?=?0.02). At one year post-training, the limited CCRT malaria children had more rapid CogState card detection (attention) (P?=?0.02), and improved BRIEF Global Executive Index (P?=?0.01) as compared to passive controls. Non-malaria children receiving CCRT significantly benefited only on KABC-II Conceptual Thinking (both full- and limited-CCRT; P?<?0.01), CogState Groton maze chase and learning (P?<?0.01), and CogState card identification (P?=?0.05, full CCRT only). Improvements in KABC-II Conceptual Thinking planning subtest for the non-malaria children persisted to one-year follow-up only for the full-CCRT intervention arm. CONCLUSION:For severe malaria survivors, limited CCRT improved attention and memory outcomes more than full CCRT, perhaps because of the greater repetition and practice on relevant training tasks in the absence of the performance titration for full CCRT. There were fewer significant cognitive and behavior benefits for the non-malaria children, with the exception of the planning/reasoning subtest of Conceptual Thinking, with stronger full- compared to limited-CCRT improvements persisting to one-year follow-up.

Dataset Information

Brain MRI and cognitive function seven years after surviving an episode of severe acute malnutrition in a cohort of Malawian children.

Publications

Brain MRI and cognitive function seven years after surviving an episode of severe acute malnutrition in a cohort of Malawian children.

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