Cyralene P. Bryce

Infant malnutrition is associated with persisting attention deficits in middle adulthood.

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.

Early Childhood Malnutrition Predicts Depressive Symptoms at Ages 11–17

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. METHODS Depressive symptoms were assessed using a 20-item scale administered to youths (11-17 years of age) who had experienced an episode of protein-energy malnutrition (marasmus or kwashiorkor) during the first year of life and in a comparison group of healthy youths without a history of malnutrition. Their mothers completed the same questionnaire on the same test on three occasions when their children were 5-17 years of age at 2-5-year intervals. RESULTS The prevalence of depressive symptoms was elevated among previously malnourished youth relative to healthy comparison children (p < .001). When youth depression scores were subjected to a longitudinal multiple regression analysis, adjusting for the effect of maternal depressive symptoms, significant effects due to the history of early childhood malnutrition remained and were not discernibly attenuated from an unadjusted analysis. We also found significant independent effects of maternal depressive symptoms on youth depressive symptoms. CONCLUSION Early childhood malnutrition contributed independently to depressive symptoms in youths who experienced a significant episode of malnutrition in the first year of life. This relationship was not mediated or moderated by the effects of maternal depression. Whether the later vulnerability to depression is a direct effect of the episode of malnutrition and related conditions early in life or whether it is mediated by the more proximal neurobehavioral effects of the malnutrition remains to be determined.

Socioeconomic Outcomes in Adults Malnourished in the First Year of Life: A 40-Year Study

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 site-specific 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.

DNA Methylation Signatures of Early Childhood Malnutrition Associated With Impairments in Attention and Cognition

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, including 50 generation 1 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 the Connors Adult Attention Rating Scale and Wechsler Abbreviated Scale of Intelligence. Expression of nutrition-sensitive genes was explored by quantitative reverse transcriptase polymerase chain reaction in rat prefrontal cortex. RESULTS We identified 134 nutrition-sensitive, differentially methylated genomic regions, with most (87%) specific for generation 1. Multiple neuropsychiatric risk genes, including COMT, IFNG, MIR200B, SYNGAP1, and VIPR2 showed associations of specific methyl-CpGs with attention and IQ. 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.

Cognitive Impairment as a Mediator in the Developmental Pathway From Infant Malnutrition to Adolescent Depressive Symptoms in Barbadian Youth

Objective: Depressive symptoms are elevated in adolescents who experienced significant malnutrition early in life. Early malnutrition can also have a significant impact on cognitive functioning, presumably because of the adverse impact of the malnutrition on the very young brain. In the context of a developmental cascade model, we tested the hypothesis that the association between early malnutrition and adolescent depressive symptoms is mediated by the cognitive impairment that ensues from the malnutrition. Methods: We evaluated Barbadian youth (N = 57) hospitalized for moderate to severe protein-energy malnutrition in the first year of life and healthy controls (N = 60) longitudinally. The primary hypothesis was tested by multiple regression models. Results: After adjusting for covariates, early malnutrition predicted both cognitive functioning in childhood (IQ, p < .001; attention problems, p < .01; Common Entrance Examination, p < .01; and adolescent depressive symptoms, p < .05). Childhood cognitive functioning mediated the association between early malnutrition and depressive symptoms in adolescence (p < .001). Maternal depressive symptoms were a significant but independent predictor of adolescent depressive symptoms (p < .05). Conclusions: Cognitive compromise in childhood accounts indirectly for elevated depressive symptoms in previously malnourished adolescents, consistent with a developmental cascade model. The direct link between malnutrition and depressive symptoms in adolescence is small.

Malnutrition in the first year of life and personality at age 40

BACKGROUND Early childhood malnutrition is associated with cognitive and behavioral impairment during childhood and adolescence, but studies in adulthood are limited. METHODS Using the NEO-PI-R personality inventory, we compared personality profiles at 37-43 years of age (M 40.3 years, SD 1.9) of Barbadian adults who had experienced moderate-to-severe protein-energy malnutrition (PEM) in the first year of life (n = 77) with healthy controls, who were former classmates of the index cases and were matched for age, gender, and handedness in childhood (n = 57). The previously malnourished participants had been rehabilitated, with good health and nutrition documented up to 12 years of age, and study participants were followed longitudinally from childhood to 40 years. Group comparisons were adjusted for childhood and adolescent standard of living, with and without correcting for IQ. RESULTS At the broad domain or factor level, previously malnourished participants had higher scores on Neuroticism and lower scores on Extraversion, Openness, Agreeableness, and Conscientiousness than did the healthy controls. At the subdomain or facet level, previously malnourished participants reported more anxiety, vulnerability, shyness and lowered sociability, less intellectual curiosity, greater suspiciousness of others, a more egocentric than altruistic orientation, and a lowered sense of efficacy or competence. CONCLUSIONS Malnutrition limited to the first year of life with good health and nutrition documented up to 12 years of age is associated with a significant overrepresentation of adult personality trait scores outside of the average range. This outcome has important implications for a variety of important life and mental health outcomes.

Impaired IQ and academic skills in adults who experienced moderate to severe infantile malnutrition: A 40-year study

Abstract 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 nine times more prevalent in the previously malnourished group (odds ratio = 9.18; 95% confidence interval = 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.

Neuropsychological outcomes at midlife following moderate to severe malnutrition in infancy.

OBJECTIVE To compare neuropsychological profiles of adults who had experienced an episode of moderate to severe protein-energy malnutrition confined to the first year of life with that of a healthy community comparison group. METHOD We assessed neuropsychological functioning in a cohort of Barbadian adults, all of whom had birth weight >2268 g. The previously malnourished group (N = 77, mean age = 38 years, 53% male) had been hospitalized during the first year of life for moderate to severe protein energy malnutrition and subsequently enrolled in a program providing nutrition education, home visits and subsidized foods to 12 years of age. They also had documented, adequate nutrition throughout childhood and complete catch-up in growth by the end of adolescence. The healthy comparison group (N = 59, mean age = 38 years, 54% male) were recruited as children from the same classrooms and neighborhoods. RESULTS Adjusted for effects of standard of living during childhood and adolescence and current intellectual ability level, there were nutrition group differences on measures of cognitive flexibility and concept formation, as well as initiation, verbal fluency, working memory, processing speed, and visuospatial integration. Behavioral and cognitive regulation were not affected. CONCLUSIONS Postnatal malnutrition confined to the first year of life is associated with neurocognitive compromise persisting into midlife. Early malnutrition may have a specific neuropsychological signature, affecting response initiation to a somewhat greater extent than response inhibition.

Infant malnutrition predicts conduct problems in adolescents

Abstract Objectives The purpose of this study was to compare the prevalence of conduct problems in a well-documented sample of Barbadian adolescents malnourished as infants and a demographic comparison group and to determine the extent to which cognitive impairment and environmental factors account for this association. Methods Behavioral symptoms were assessed using a 76-item self-report scale in 56 Barbadian youth (11–17 years of age) with histories of protein–energy malnutrition (PEM) limited to the first year of life and 60 healthy classmates. Group comparisons were carried out by longitudinal and cross-sectional multiple regression analyses at 3 time points in childhood and adolescence. Results Self-reported conduct problems were more prevalent among previously malnourished youth (P < 0.01). Childhood IQ and home environmental circumstances partially mediated the association with malnutrition. Teacher-reported classroom behaviors at earlier ages were significantly correlated with youth conduct problems, confirming the continuity of conduct problems through childhood and adolescence. Discussion Self-reported conduct problems are elevated in children and adolescents with histories of early childhood malnutrition. Later vulnerability to increased conduct problems appears to be mediated by the more proximal neurobehavioral effects of the malnutrition on cognitive function and by adverse conditions in the early home environment.

Early malnutrition predicts parent reports of externalizing behaviors at ages 9–17

Abstract Objective To determine whether externalizing behaviors are more prevalent in youth who have experienced an episode of malnutrition in the first year of life than in healthy comparison youth. Method Parents of previously malnourished youth and a matched healthy comparison group completed a behavior rating scale when the youth were 9–15 years of age and again, 2 years later, when they were 11–17 years of age. Longitudinal multiple regression analysis was applied to evaluate group differences adjusted for baseline age, sex, household standard of living, and maternal depressive symptoms. Results Early childhood malnutrition was associated with problems in executive functioning at both occasions. Malnutrition also predicted discernibly higher parent-reported levels of aggression toward peers at 9–15 years than at 11–17 years. These findings were independent of baseline age, sex, household standard of living, and maternal depressive symptoms. Problem behaviors in general decreased during follow-up. Conclusion Parents report persisting problems with executive functioning through adolescence in youth who suffered an episode of moderate-to-severe protein-energy malnutrition in the first year of life, while reports of aggression, although more common when this cohort were younger, did not persist at follow-up.