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糖皮质激素（GC）产前治疗对HPA轴的影响，影响早产儿和足月儿的调节、认知和大脑。动物模型表明，产前暴露于高水平的GC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GC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%的儿童在足月时出生。这个群体之所以重要，有两个原因。首先，他们有风险的GC暴露的后果，没有收到的医疗福利明显的早产儿。其次，纳入这一关键组允许GC治疗的影响独立于对大脑和早产行为的已知和有害的长期影响进行评估。尽管暴露于GC对健康和发育的重要性，但现有的研究尚未将其影响与早产的影响分开。参与者将包括300名6至8岁儿童的种族多样性样本（100名对照，100名GC治疗，100名多重治疗）。具体目标是：（i）评估产前GC治疗对下丘脑垂体肾上腺皮质轴（HPA）功能和影响调节的影响。将在基线和激发后测量唾液皮质醇水平，以评估HPA轴的完整性。父母报告措施的恐惧/焦虑将作为一种措施的影响调节。（ii）评价产前治疗与GC认知的影响。认知将使用标准化的智力测量和神经心理学任务来评估记忆和执行功能。（iii）确定用GC进行产前治疗对大脑结构的影响，特别是对海马体、杏仁核和前额叶皮质（PFC）的体积的影响。将在80名儿童（40名暴露于GC）的亚组中使用磁共振成像（MRI），以进行脑结构的体内表征。这个项目将提供第一次机会来检查胎儿暴露于GC的独立影响，在一组足月出生的儿童。

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.