Prenatal Glucocorticoids Influence Brain and Behavior

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DESCRIPTION (provided by applicant): The primary aim of this proposal is to determine the effects of prenatal treatment with glucocorticoids (GCs) on the HPA axis, affect regulation, cognition and the brain in children born preterm and term. Animal models have demonstrated that prenatal exposure to elevated levels of GCs has persisting consequences for health and development. The lasting influences of GC exposure on development of the human child are not known. Every year hundreds of thousands of women at risk of premature labor are treated with GCs to facilitate lung development in the fetus. As many as 20% of children who were exposed to prenatal GC treatment subsequently were born at term. This group is important for two reasons. First, they are at risk for the consequences of GC exposure without receiving the medical benefits evident for preterm infants. Second, inclusion of this critical group allows the impact of GC treatment to be evaluated independently from the known and deleterious long-term effects on the brain and behavior of premature delivery. Despite the importance to health and development of exposure to GCs, existing research has not separated their effects from the impact of preterm delivery. Participants will include a racially diverse sample of 300 six to eight year old children (100 controls, 100 GC treatment, 100 multiple treatments). The specific aims are to: (i) Assess the influence of prenatal treatment with GCs on hypothalamic pituitary adrenocortical axis (HPA) function and affect regulation. Salivary cortisol levels will be measured at baseline and in response to challenge to assess the integrity of the HPA axis. Parent report measures of fear/anxiety will be employed as a measure of affect regulation, (ii) Evaluate the impact of prenatal treatment with GCs on cognition. Cognition will be assessed using both standardized intelligence measures and neuropsychological tasks that evaluate memory and executive functions, (iii) Determine the effect prenatal treatment with GCs on brain structure, specifically on the volume of the hippocampus, amygdala, and prefrontal cortex (PFC). Magnetic Resonance Imaging (MRI) will be employed, in a subset of 80 children (40 GC exposed), for the in vivo characterization of brain structure. This project will provide the first opportunity to examine the independent influence of fetal exposure to GC's in a group of children born at term.