Fetal Behavior, Brain & Stress Response: Ultrasound Markers of Maternal Smoking

胎儿行为，大脑

• 批准号: 8494256
• 负责人: LAURA R STROUD
• 金额: $ 56.93万
• 依托单位: MIRIAM HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8494256
• 关键词: 3-Dimensional; Acoustics; Adrenal Glands; Alcohol or Other Drugs use; Arousal; Attention; Behavior; Behavioral; Birth; Brain; Cardiac; Cerebellum; Child; Childhood; Clinical; Corpus Callosum; Coupling; Development; Discipline of obstetrics; Disruptive Behavior Disorder; Dose; Fetus; Goals; Healthcare Systems; Heart Rate; High-Risk Pregnancy; Hydrocortisone; Image; Infant; Intervention; Investigation; Lead; Link; Measures; Medical; Methods; Morbidity - disease rate; Mothers; Neurosecretory Systems; Nicotine; Outcome; Perinatal; Pharmaceutical Preparations; Pregnancy; Public Health; Research; Resolution; Risk; Risk Marker; Safety; Seminal; Severities; Smoke; Smoker; Smoking; Stimulus; Stress; Structure; Testing; Third Pregnancy Trimester; Time; Tobacco; Ultrasonography; Work; behavior observation; biobehavior; biological adaptation to stress; clinical care; cost; fetal; fetal tobacco exposure; frontal lobe; high risk; high risk infant; improved; innovation; maternal cigarette smoking; medical complication; mortality; neurobehavior; neurobehavioral; neurobehavioral disorder; new therapeutic target; novel; novel marker; novel strategies; offspring; postnatal; pregnant; prenatal; prenatal stress; prospective; public health relevance; relating to nervous system; response; social

DESCRIPTION (provided by applicant): Maternal smoking during pregnancy is associated with morbidity and mortality in infants and behavioral deficits in infants and older children. Despite pervasive sanctions against smoking during pregnancy, 13-30% of infants are born exposed. Given continued high exposure rates and links to costly offspring outcomes, novel approaches are needed to identify and protect high risk offspring and help pregnant smokers quit. The proposed study offers a paradigm shift in identifying real-time, pre-birth neurobehavioral and neural markers of risk from maternal smoking using 2 and 3-dimensional fetal ultrasound. Specifically, we test the proposal that: a) maternal smoking will influence trajectories of fetal neurobehavior, stress response, and neural and neuroendocrine structures over pregnancy, and b) richly characterized trajectories of fetal neurobehavior, stress response, and neural structures will predict infant neurobehavioral deficits. Using an approach pioneered by our group (2D ultrasound combined with fetal actocardiography), our preliminary work revealed effects of maternal smoking on fetal neurobehavioral deficits and altered stress response during third trimester. However, fetal developmental trajectories leading to third trimester deficits are not known. Further, although structural brain deficits have been proposed as a key candidate mechanism underlying links between maternal smoking and offspring neurobehavioral deficits, no studies have integrated neural and behavioral markers of risk from maternal smoking. The advent of 3D ultrasonography offers higher resolution fetal images, allowing volumetric characterization of specific fetal brain and neuroendocrine structures. Seminal preliminary work from our group demonstrated feasibility of 3D assessment and revealed volume decrements in fronto-cerebellar brain structures in fetuses exposed to maternal smoking. The proposed study is an intensive investigation of ultrasound markers of risk from maternal smoking. Our study involves prospective investigation of smokers and controls over pregnancy. Three fetal ultrasound assessments will be completed using highest safety standards to observe fetal behavior, response to mild stress (vibro-acoustic stimulus), and 3D volumetric assessment of fetal neural (fronto-cerebellar regions) and neuroendocrine (adrenal gland) structures, followed by two infant neurobehavior and cortisol reactivity assessments. Our goals are to determine effects of maternal smoking on: 1) trajectories of fetal neurobehavioral deficits, 2) alterations in fetal stress response, and 3) volume decrements in neural and neuroendocrine structures over pregnancy. We will then test the proposal that trajectories of fetal neuro-behavioral and neural markers of risk predict infant neurobehavioral deficits and stress response. Results offer potential for: a) promoting discovery of mechanisms of maternal smoking in real- time during pregnancy, b) identifying new pre-birth markers of risk that could improve clinical care for pregnant smokers and other high-risk pregnancies, c) identifying novel therapeutic targets to protect exposed fetuses, and d) developing new foci for intervention efforts with pregnant smokers.

描述（由申请人提供）：怀孕期间的孕产妇吸烟与婴儿和大儿童的婴儿和行为缺陷有关。尽管在怀孕期间对吸烟的普遍制裁，但13-30％的婴儿出生。鉴于持续的高暴露率和与昂贵的后代结果的联系，需要采取新颖的方法来识别和保护高风险后代并帮助孕妇戒烟。拟议的研究在识别使用2和3维胎儿超声的孕产妇吸烟中识别实时，出生前神经行为和神经标记的范式转移。具体而言，我们测试了以下建议：a）孕妇吸烟将影响胎儿神经行为的轨迹，压力反应以及神经和神经内分泌结构，以及b）b）胎儿神经行为，压力反应和神经结构的良好特征性轨迹将预测婴儿神经脱落的神经havioral seficits。使用我们的小组开创的方法（2D超声结合胎儿的心态造影），我们的初步工作揭示了孕产妇吸烟对胎儿神经行为缺陷的影响和三个月中三个月的应激反应改变。但是，尚不清楚导致三个月缺陷的胎儿发育轨迹。此外，尽管已经提出了结构性的大脑缺陷作为孕产妇吸烟与后代神经行为缺陷之间联系的关键候选机制，但没有研究综合出孕产妇吸烟风险的神经和行为标志。 3D超声检查的出现提供了更高的分辨率胎儿图像，从而可以对特定的胎儿脑和神经内分泌结构进行体积表征。我们小组的开创性初步工作表明3D评估的可行性，并显示暴露于孕产妇吸烟的胎儿中额脑脑结构的体积减少。拟议的研究是对孕产妇吸烟风险的超声标记的深入研究。我们的研究涉及对吸烟者和对妊娠的控制的前瞻性研究。将使用最高安全标准来完成三项胎儿超声评估，以观察胎儿行为，对轻度压力（颤音声音刺激）以及胎儿神经（额叶脑部区域）和神经内分泌（肾上腺）结构的3D大量评估，然后进行两种婴儿神经脱发和cortistive contiveitive评估。我们的目标是确定孕产妇吸烟对：1）胎儿神经行为缺陷的轨迹，2）胎儿应激反应的改变； 3）体积减少了妊娠期神经和神经内分泌结构的体积。然后，我们将测试以下提议，即风险的胎儿神经行为和神经标志物的轨迹预测婴儿神经行为缺陷和压力反应。结果提供了：a）促进在怀孕期间实时促进孕产妇吸烟机制的发现，b）确定新的风险前标志物，可以改善孕妇吸烟者和其他高风险怀孕的临床护理，c）识别新型的治疗靶标，以保护裸露的胎儿，以及d）为孕妇吸烟者的干预措施而开发新的焦点。