Prenatal Factors Contribute to the Emergence of Kwashiorkor or Marasmus in Severe Undernutrition: Evidence for the Predictive Adaptation Model

Abstract

BackgroundSevere acute malnutrition in childhood manifests as oedematous (kwashiorkor, marasmic kwashiorkor) and non-oedematous (marasmus) syndromes with very different prognoses. Kwashiorkor differs from marasmus in the patterns of protein, amino acid and lipid metabolism when patients are acutely ill as well as after rehabilitation to ideal weight for height. Metabolic patterns among marasmic patients define them as metabolically thrifty, while kwashiorkor patients function as metabolically profligate. Such differences might underlie syndromic presentation and prognosis. However, no fundamental explanation exists for these differences in metabolism, nor clinical pictures, given similar exposures to undernutrition. We hypothesized that different developmental trajectories underlie these clinical-metabolic phenotypes: if so this would be strong evidence in support of predictive adaptation model of developmental plasticity.Methodology/Principal FindingsWe reviewed the records of all children admitted with severe acute malnutrition to the Tropical Metabolism Research Unit Ward of the University Hospital of the West Indies, Kingston, Jamaica during 1962–1992. We used Wellcome criteria to establish the diagnoses of kwashiorkor (n = 391), marasmus (n = 383), and marasmic-kwashiorkor (n = 375). We recorded participants' birth weights, as determined from maternal recall at the time of admission. Those who developed kwashiorkor had 333 g (95% confidence interval 217 to 449, p<0.001) higher mean birthweight than those who developed marasmus.Conclusions/SignificanceThese data are consistent with a model suggesting that plastic mechanisms operative in utero induce potential marasmics to develop with a metabolic physiology more able to adapt to postnatal undernutrition than those of higher birthweight. Given the different mortality risks of these different syndromes, this observation is supportive of the predictive adaptive response hypothesis and is the first empirical demonstration of the advantageous effects of such a response in humans. The study has implications for understanding pathways to obesity and its cardio-metabolic co-morbidities in poor countries and for famine intervention programs.

Influence of early-life nutrition on mortality and reproductive success during a subsequent famine in a preindustrial population

“…Results consistent with plasticity providing an early-life survival advantage were reported by a study of infants (mean age 12 mo) admitted to Jamaican hospitals with kwashiorkor, a symptom of malnutrition associated with edema but retention of some fat and protein reserves, and marasmus, a symptom characterized by a lack of edema and wasting. Individuals who responded to malnutrition with kwashiorkor experienced higher mortality and were significantly heavier at birth than those displaying marasmus, suggesting that lighterborn individuals used their energy reserves more efficiently to survive a period of malnutrition (34). These results were interpreted as evidence consistent with a short-term PAR.…”

QQSorphan gene regulates carbon and nitrogen partitioning across species via NF-YC interactions

“…In addition to the enigma surrounding how metabolic partitioning is controlled, the regulation of seed composition has major practical implications. Low protein intake contributes to mental retardation, stunting, susceptibility to disease, wasting diseases, and sometimes death in hundreds of millions of children each year (34,35). Because plants provide over 60% of human dietary protein and are the major source of protein for many of the world's at-risk populations (36), increasing protein content in staple crop plants could greatly impact human health.…”

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

“…Average age at original admission was 11.6 months (marasmic group) and 12.4 months (kwashiorkor). 10 Tropical Metabolism Research Unit has treated SAM since 1956, using standardized feeding protocols, and mortality rates approximate 4%. 10,13 A total of 629 subjects were traced as adults by community health aides and nurses.…”

“…10 Tropical Metabolism Research Unit has treated SAM since 1956, using standardized feeding protocols, and mortality rates approximate 4%. 10,13 A total of 629 subjects were traced as adults by community health aides and nurses. Of these, 28 had died (cause of death unknown), 140 were not found at their last known address, and 94 did not participate because of migration (n=53), mental incompetence (n=16), pregnancy (n=3), missing hospital records (n=6), or were unavailable (n=16).…”

“…We have used a retrospective cohort of adult survivors of SAM previously treated in the Tropical Metabolism Research Unit, Kingston, Jamaica, to explore the effects of malnutrition on adult cardiovascular structure and function and shown that birth weight is 333 g lower in infants presenting with marasmus when compared with those with kwashiorkor. 10 Lower birth weight suggests more severe intrauterine undernutrition, and marasmus survivors would, therefore, be expected to have greater later cardiovascular dysfunction than after kwashiorkor. However, because children with kwashiorkor are less able to sustain amino acid and lipid supply than children with marasmus, 11,12 kwashiorkor children may also have poorer cardiovascular development, with later consequences for risk.…”