Impaired Cardiovascular Structure and Function in Adult Survivors of Severe Acute Malnutrition

Tennant, I; Barnett, Alan T; Thompson, Debbie; Kips, Jan; Boyne, Michael S.; Chung, Edward; Chung, Andrene P; Osmond, Clive; Hanson, Mark A.; Gluckman, Peter D.; Segers, Patrick; Cruickshank, J.; Forrester, Terrence

doi:10.1161/hypertensionaha.114.03230

Cited by 52 publications

(36 citation statements)

References 40 publications

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“…Previously, in a larger group of adult survivors of SAM in this population, we described differences between marasmic and kwashiorkor survivors with marasmic survivors having worse glucose tolerance and beta cell function (Francis-Emmanuel et al, 2014). Also, both kwashiorkor and marasmus adult survivors had differences in cardiac structure and function, and blood pressure when compared with controls (Tennant et al, 2014). Others have documented substantial behavioral and cognitive impairment in all SAM survivors throughout childhood, adolescence and young adulthood, but the syndromic association is not clear.…”

Section: Discussionmentioning

confidence: 99%

Molecular Evidence for Differential Long-term Outcomes of Early Life Severe Acute Malnutrition

Sheppard

Ngo

et al. 2017

EBioMedicine

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BackgroundSevere acute malnutrition (SAM) in infants may present as one of two distinct syndromic forms: non-edematous (marasmus), with severe wasting and no nutritional edema; or edematous (kwashiorkor) with moderately severe wasting. These differences may be related to developmental changes prior to the exposure to SAM and phenotypic changes appear to persist into adulthood with differences between the two groups. We examined whether the different response to SAM and subsequent trajectories may be explained by developmentally-induced epigenetic differences.MethodsWe extracted genomic DNA from muscle biopsies obtained from adult survivors of kwashiorkor (n = 21) or marasmus (n = 23) and compared epigenetic profiles (CpG methylation) between the two groups using the Infinium® 450 K BeadChip array.FindingsWe found significant differences in methylation of CpG sites from 63 genes in skeletal muscle DNA. Gene ontology studies showed significant differential methylation of genes in immune, body composition, metabolic, musculoskeletal growth, neuronal function and cardiovascular pathways, pathways compatible with the differences in the pathophysiology of adult survivors of SAM.InterpretationThese findings suggest persistent developmental influences on adult physiology in survivors of SAM. Since children who develop marasmus have lower birth weights and after rehabilitation have different intermediary metabolism, these studies provide further support for persistent developmentally-induced phenomena mediated by epigenetic processes affecting both the infant response to acute malnutrition and later life consequences.FundingSupported by a Grant from the , Grand Challenge “Discover New Ways to Achieve Healthy Growth.”Evidence Before This StudyPrevious research has shown that infants who develop either kwashiorkor or marasmus in response to SAM differ in birth weight and subsequently have different metabolic patterns in both infancy and adulthood.Added Value of This StudyThis study demonstrates epigenetic differences in the skeletal muscle of adult survivors of marasmus versus kwashiorkor and these differences are in genes that may underlie the longer-term consequences.Implications of All the Available EvidenceThese data are compatible with the different clinical responses to SAM arising from developmentally-induced epigenetic changes laid down largely before birth and provide evidence for the predictive adaptive response model operating in human development.

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Section: Discussionmentioning

confidence: 99%

Molecular Evidence for Differential Long-term Outcomes of Early Life Severe Acute Malnutrition

Sheppard

Ngo

et al. 2017

EBioMedicine

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“…18 A study of survivors of kwashiorkor and marasmus (both severe disorders that occur as a result of protein-energy malnutrition) at a mean of age 29 years showed significantly higher blood pressure as compared with normally nourished controls, possibly mediated through an increase in peripheral vascular resistance. 142 Renal parameters, however, were not studied in this analysis. HBW, exposure to GDM, and childhood obesity are associated with an increased risk of obesity in later life, although the effect on hypertension seems variable (Box 2).…”

Section: Obstruction Of the Developing Kidneymentioning

confidence: 99%

Birth weight, malnutrition and kidney-associated outcomes—a global concern

2015

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An adverse intrauterine environment is associated with an increased risk of elevated blood pressure and kidney disease in later life. Many studies have focused on low birth weight, prematurity and growth restriction as surrogate markers of an adverse intrauterine environment; however, high birth weight, exposure to maternal diabetes and rapid growth during early childhood are also emerging as developmental risk factors for chronic diseases. Altered programming of nephron number is an important link between exposure to developmental stressors and subsequent risk of hypertension and kidney disease. Maternal, fetal, and childhood nutrition are crucial contributors to these programming effects. Resource-poor countries experience the sequential burdens of fetal and childhood undernutrition and subsequent overnutrition, which synergistically act to augment the effects of developmental programming; this observation might explain in part the disproportionate burden of chronic disease in these regions. Numerous nutritional interventions have been effective in reducing the short-term risk of low birth weight and prematurity. Understanding the potential long-term benefits of such interventions is crucial to inform policy decisions to interrupt the developmental programming cycle and stem the growing epidemics of hypertension and kidney disease worldwide.

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“…The long-term consequences of infant malnutrition on blood pressure and renal function have been scarcely studied. Among African-Caribbeans aged 28 years who survived Kwashiorkor or Marasumus, exposure to infant malnutrition was associated with alterations in cardiac function, higher systemic vascular resistance, and increased diastolic blood pressure [219]. These data emphasize the importance of early childhood nutrition in modulating CVD risk and highlight the need for further studies to understand the pathophysiology and determine how best to intervene.…”

Section: Introduction To a Health Problemmentioning

confidence: 99%

The Impact of Kidney Development on the Life Course: A Consensus Document for Action

Brenner

Charlton

Luyckx

et al. 2017

Nephron

123

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Hypertension and chronic kidney disease (CKD) have a significant impact on global morbidity and mortality. The Low Birth Weight and Nephron Number Working Group has prepared a consensus document aimed to address the relatively neglected issue for the developmental programming of hypertension and CKD. It emerged from a workshop held on April 2, 2016, including eminent internationally recognized experts in the field of obstetrics, neonatology, and nephrology. Through multidisciplinary engagement, the goal of the workshop was to highlight the association between fetal and childhood development and an increased risk of adult diseases, focusing on hypertension and CKD, and to suggest possible practical solutions for the future. The recommendations for action of the consensus workshop are the results of combined clinical experience, shared research expertise, and a review of the literature. They highlight the need to act early to prevent CKD and other related noncommunicable diseases later in life by reducing low birth weight, small for gestational age, prematurity, and low nephron numbers at birth through coordinated interventions. Meeting the current unmet needs would help to define the most cost-effective strategies and to optimize interventions to limit or interrupt the developmental programming cycle of CKD later in life, especially in the poorest part of the world.

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Impaired Cardiovascular Structure and Function in Adult Survivors of Severe Acute Malnutrition

Abstract: Abstract-Malnutrition

Cited by 52 publications

References 40 publications

Molecular Evidence for Differential Long-term Outcomes of Early Life Severe Acute Malnutrition

Molecular Evidence for Differential Long-term Outcomes of Early Life Severe Acute Malnutrition

Birth weight, malnutrition and kidney-associated outcomes—a global concern

The Impact of Kidney Development on the Life Course: A Consensus Document for Action

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