The proposed study utilizes the R21 Exploratory/ Developmental Research Grant Program to explore the effects of restricted prenatal nutrition on cognitive and behavioral/emotional function of juvenile baboons. Significance: Poor nutrition during pregnancy and lactation is correlated with negative outcomes in human offspring, including cognitive deficits and behavioral and emotional problems. The implications of these findings for children's health are highly significant, but it is difficult to determine if inadequate nutrition actually causes the adverse outcomes in humans. A non-human primate model with random assignment to nutritional levels can establish causation, which in turn will lead to testable hypotheses about the mechanisms by which nutritional deficiency during pregnancy affects the fetus. In addition, data are needed on whether the risk conferred to offspring is moderated by factors during pregnancy or by the postnatal care-giving environment. Approach: We will prospectively study offspring of baboons who were randomly assigned to either moderate nutrient restriction (i.e., mothers eating 30% less than ad libitum fed mothers) or ad libitum feeding during pregnancy and lactation. Cognitive and behavioral/emotional function of juveniles will be assessed in the context of a neuropsychological battery, the Cambridge Neuropsychological Test Automated Battery, at 20 months of age (equivalent to 6 years in the human). In addition, we will test whether an association between nutrient restriction during pregnancy and developmental outcomes is moderated by maternal dominance status or postnatal care giving. The proposed study is consistent with the R21 mechanism for two reasons: first, the model, including the dependent measure of cognitive and behavioral/emotional regulation, is new and exploratory;second, the study is a necessary first step to developing a broader research program on mechanisms by which nutrition during pregnancy affects the developing brain. Environment: This project combines the skills of investigators at University of Texas at San Antonio, University of Texas Health Science Center at San Antonio and University of Chicago. The collaboration arises out of an NIMH Translation Science Network. Investigators: Dr. Bartlett has 15 years experience working with captive and wild non-human primates. Dr. Bartlett and Dr. Nijland have worked together for three years collecting data on the social behavior of socially housed baboons. Dr. Keenan's research focuses on pre- and post-natal factors associated with development of psychopathology in early childhood. Innovation: This will be the first test of the causal effects of restricted prenatal nutrition on developmental outcomes of offspring in a non-human primate. The proposed study allows links to humans through the novel use of methods for assessing cognitive and behavioral/emotional function in the baboon that are standard methods for assessing children. Consistent with the NIH mission, the proposed study is designed to maximize translation of the results to the human condition.
We pass more milestones during development in utero than any other time in our lives. Poor nutrition during this period alters the development of key organs including the brain. Our studies are a first step in studying a well controlled nonhuman primate model of fetal nutrient restriction to determine mechanisms by which conditions experienced during development predispose offspring to abnormal behavior, temperament, and cognition in later life.
