Infantile malnutrition is known to be associated with cognitive and behavioral impairment during childhood and adolescence. Data pertaining to longer-term effects on behavioral outcomes in adulthood are limited. In this study, we report associations between infantile malnutrition and attention problems in adults at midlife. Attention problems were assessed by the Conners Adult ADHD Rating Scales (CAARS) and the Conners Continuous Performance Test (CPT) in 145 Barbadian adults (aged 37-43 y) who had been followed longitudinally since childhood. Previously malnourished participants (n = 80) had experienced moderate to severe protein-energy malnutrition in the first year of life and were successfully rehabilitated thereafter. They were compared with healthy adults (n = 65) who were former classmates of the index cases and who had been matched for age, sex, and handedness in childhood. Multiple regression analyses showed persisting effects of childhood malnutrition on both the CAARS and the CPT, independent of effects of household standard of living assessed in childhood. The malnutrition effect on the CAARS ratings was independent of IQ, whereas this effect was attenuated for the CPT after adjustment for IQ. Teacher-reported attention problems in childhood predicted attention problems in adulthood, indicating continuity over the life span. Infantile malnutrition may have long-term effects on attentional processes nearly 40 y after the episode, even with excellent long-term nutritional rehabilitation and independent of socioeconomic conditions in childhood and adolescence. This finding has major public health implications for populations exposed to early childhood malnutrition.

Background Early childhood malnutrition affects 113 million children worldwide, impacting health and increasing vulnerability for cognitive and behavioral disorders later in life. Molecular signatures after childhood malnutrition, including the potential for intergenerational transmission, remain unexplored. Methods We surveyed blood DNA methylomes (~483,000 individual CpG sites) in 168 subjects across two generations (G1,G2), including 50 G1 individuals hospitalized during the first year of life for moderate to severe protein energy malnutrition, then followed up to 48 years in the Barbados Nutrition Study. Attention deficits and cognitive performance were evaluated with Connors Adult Attention Rating Scale (CAARS) and Wechsler Abbreviated Scale of Intelligence (WASI). Expression of nutrition-sensitive genes was explored by qRT-PCR in rat prefrontal cortex. Results We identified altogether 134 nutrition-sensitive differentially methylated genomic regions (DMR), with the overwhelming majority (87%) specific for G1. Multiple neuropsychiatric risk genes, including COMT, IFNG, MIR200B, SYNGAP1 and VIP2R showed associations of specific methyl-CpGs with attention and IQ. Interferon Gamma (IFNG) expression was decreased in prefrontal cortex of rats showing attention deficits after developmental malnutrition. Conclusions Early childhood malnutrition entails long lasting epigenetic signatures associated with liability for attention and cognition, and limited potential for intergenerational transmission.

WHAT'S KNOWN ON THIS SUBJECT: Infant malnutrition is known to be associated with behavioral and cognitive impairment throughout childhood, adolescence, and young adulthood. However, controlled studies addressing adult outcomes in middle life, including earning potential, educational attainment, and standard of living, are limited. WHAT THIS STUDY ADDS:A discrete episode of moderate to severe malnutrition in infancy, with good rehabilitation thereafter, is associated with lower adult social status and a widening income gap relative to healthy controls, partially attributable to cognitive impairment in the previously malnourished. abstract OBJECTIVE: Lifelong functional, adaptive, and economic outcomes of moderate to severe infantile malnutrition are not well known. We assessed social status and income at midlife in a cohort of Barbadian adults, hospitalized for protein-energy malnutrition (PEM) during the first year of life, with good nutrition and health thereafter, in the context of a 40-year longitudinal case-control study. We also examined to what extent childhood IQ mediated any group differences.METHODS: Educational achievement, occupational status, and standard of living were assessed by the Hollingshead scales and a sitespecific Ecology Questionnaire in Barbadian adults (aged 37-43 years) with a history of malnutrition (n = 80) and a matched healthy control group (n = 63), classmates of the index cases. Malnutrition effects, adjusted for childhood standard of living, were estimated by longitudinal multiple regression analyses, with and without childhood IQ, in the models.RESULTS: PEM predicted poorer socioeconomic outcomes with medium to large effect sizes (0.50-0.94), but childhood IQ substantially attenuated the magnitude of these effects (adjusted effect sizes: 0.17-0.34). The gap in weekly household income between the PEM and control groups increased substantially over the life span (P , .001).CONCLUSIONS: Moderate to severe PEM during the first year of life with adequate nutrition and health care thereafter is associated with significant depression of socioeconomic outcomes in adulthood, mediated in part by cognitive compromise in affected individuals. This finding underscores the potential long-term economic burden of infant malnutrition, which is of major concern given the continued high prevalence of malnutrition worldwide. Pediatrics 2012;130:e1-e7 AUTHORS:

Background-We examined the prevalence of depressive symptoms in Barbadian youth with histories of infantile malnutrition and in a healthy comparison group and the extent to which the effect of malnutrition was mediated/moderated by maternal depression.

Objectives To evaluate IQ and academic skills in adults who experienced an episode of moderate to severe infantile malnutrition and a healthy control group, all followed since childhood in the Barbados Nutrition Study. Methods IQ and academic skills were assessed in 77 previously malnourished adults (mean age=38.4 years; 53% male) and 59 controls (mean age=38.1 years; 54% male). Group comparisons were carried out by multiple regression and logistic regression, adjusted for childhood socioeconomic factors. Results The previously malnourished group showed substantial deficits on all outcomes relative to healthy controls (p<0.0001). IQ scores in the Intellectual Disability range (< 70) were 9 times more prevalent in the previously malnourished group (OR=9.18; 95% CI=3.50-24.13). Group differences in IQ of approximately one standard deviation were stable from adolescence through mid-life. Discussion Moderate to severe malnutrition during infancy is associated with a significantly elevated incidence of impaired IQ in adulthood, even when physical growth is completely rehabilitated. An episode of malnutrition during the first year of life carries risk for significant lifelong functional morbidity.