Prenatal Glucocorticoids Influence Brain and Behavior

描述（由申请人提供）：本提案的主要目的是确定产前糖皮质激素（GCs）治疗对早产儿和足月儿童HPA轴的影响，影响调节，认知和大脑。动物模型表明，产前暴露于高水平的GCs对健康和发育具有持续的影响。GC暴露对人类儿童发育的持久影响尚不清楚。每年有数十万有早产风险的妇女接受GCs治疗，以促进胎儿肺部发育。在接受产前GC治疗的儿童中，有多达20%的儿童随后足月出生。这个群体之所以重要，有两个原因。首先，他们面临着暴露于GC的后果的风险，而没有得到早产儿明显的医疗益处。其次，纳入这一关键组可以独立评估GC治疗对早产儿大脑和行为的已知有害长期影响。尽管接触GCs对健康和发育很重要，但现有的研究并没有将其影响与早产的影响分开。参与者将包括300名种族多样化的6至8岁儿童样本（100名对照，100名GC治疗，100名多重治疗）。具体目的是：(i)评估GCs产前治疗对下丘脑-垂体-肾上腺皮质轴（HPA）功能的影响及其调控作用。唾液皮质醇水平将在基线和响应挑战评估HPA轴的完整性进行测量。父母报告的恐惧/焦虑测量将被用作影响调节的测量，（ii）评估产前治疗对认知的影响。认知将使用标准化智力测量和评估记忆和执行功能的神经心理学任务进行评估。（iii）确定产前GCs治疗对大脑结构的影响，特别是对海马体、杏仁核和前额皮质（PFC）体积的影响。磁共振成像（MRI）将用于80名儿童（40名GC暴露）的体内脑结构表征。这个项目将提供第一个机会来检查胎儿暴露于GC对一组足月出生的儿童的独立影响。

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.