Imaging the Developing Fetal Brain: Novel Markers of Risk for Maternal Smoking

胎儿大脑发育成像：母亲吸烟风险的新标志

• 批准号: 8570379
• 负责人: LAURA R STROUD
• 金额: $ 22.84万
• 依托单位: MIRIAM HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8570379
• 关键词: 3-Dimensional; Adherence; Adrenal Glands; Alcohol or Other Drugs use; Attention; Award; Behavior; Behavioral; Birth; Brain; Cerebellum; Child; Clinical Research; Corpus Callosum; Data; Development; Diagnosis; Discipline of obstetrics; Disruptive Behavior Disorder; Dose; Early Intervention; Fetal Structures; Fetus; Future; Goals; Healthcare Systems; Image; Infant; Infant Behavior; Investigation; Lead; Link; Measures; Medical; Methodology; Methods; Morbidity - disease rate; Mothers; Neurobiology; Neurosecretory Systems; Nicotine; Outcome; Participant; Pharmaceutical Preparations; Pilot Projects; Pregnancy; Preparation; Protocols documentation; Public Health; Research; Research Infrastructure; Resolution; Risk; Risk Marker; Safety; Science; Smoke; Smoker; Smoking; Smoking Behavior; Structure; Technology; Testing; Time; Tobacco; Ultrasonography; adverse outcome; c new; clinical care; cost; cost effective; drug of abuse; fetal; fetal drug exposure; fetal tobacco exposure; frontal lobe; high risk; improved; infant outcome; innovation; maternal cigarette smoking; medical complication; mortality; neurobehavior; neurobehavioral; neuromechanism; new technology; new therapeutic target; novel; novel marker; offspring; pregnant; prenatal; programs; public health relevance; relating to nervous system; response

DESCRIPTION (provided by applicant): This application is responsive to PAR-12-066; Imaging-Science Track Award for Research Transition; I/START). The proposed study will facilitate the addition of neural mechanisms to the PI's program of maternal smoking/offspring behavior research. Maternal smoking during pregnancy is associated with morbidity and mortality in infants and behavioral deficits (attention deficits, substance use, disruptive behaviors) in 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, innovative approaches are needed to identify and protect high risk offspring and help pregnant smokers quit. Identification of pre-birth markers of offspring risk offers potential for developing novel therapeutic targets and early intervention efforts to mitigate adverse outcomes. Our group previously utilized 2D ultrasound to reveal effects of maternal smoking on fetal behavioral deficits. However, although structural brain deficits have been proposed as a key candidate mechanism underlying links between maternal smoking and offspring neurobehavioral deficits, no studies have included neural markers of fetal risk from maternal smoking. The proposed I/START will allow the PI to expand and increase the impact of her program of maternal smoking research by including novel neural markers of fetal risk. The advent of 3D ultrasound offers higher resolution fetal images and allows volumetric characterization of specific fetal structures in clinical studies. The proposed I/START study will determine, for the first time, the feasibility of applying 3D ultrasound technology to identify neural markers of risk from maternal smoking in the developing fetus. The I/START study will capitalize on infrastructure and participants from the PI's ongoing study of maternal smoking and infant behavior (R01 DA031188). Pregnant smokers and controls from the ongoing study will complete three fetal ultrasound assessments involving 3D volumetric assessment of fetal neural (fronto-cerebellar regions) and neuroendocrine (adrenal gland) structures. Acceptability and adherence to ultrasound protocols and reliability of volumetric assessments will be assessed. Our goals are: 1) to demonstrate feasibility of our novel ultrasound methodology for volumetric assessment of fetal neural and neuroendocrine structures, and 2) to conduct a preliminary characterization of effects of maternal smoking on fetal neural and neuroendocrine structures over pregnancy in preparation for a larger R01 study. If successful, results from this pilot study offer future potential for: a) promoting discovery of mechanisms of maternal smoking in real-time during pregnancy, b) improving clinical care for pregnant smokers, c) identifying novel therapeutic targets to protect exposed fetuses, and d) developing new foci for cessation efforts with pregnant smokers.

描述（由申请人提供）：此申请对PAR-12-066响应；成像科学轨道研究过渡奖；我/开始）。拟议的研究将促进在PI的孕产妇吸烟/后代行为研究计划中添加神经机制。怀孕期间的孕产妇吸烟与婴儿的发病率和死亡率有关（注意力缺陷，药物使用，破坏性行为）。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成果的联系，需要创新的方法来识别和保护高风险后代，并帮助孕妇的吸烟者辞职。鉴定后代风险的生殖前标记为开发新的治疗靶标和早期干预工作以减轻不良后果的可能性提供了潜力。我们的小组以前利用2D超声来揭示孕产妇吸烟对胎儿行为缺陷的影响。但是，尽管已经提出了结构性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，但尚无研究包括孕产妇吸烟的胎儿风险的神经标记。拟议的I/开始将使PI通过包括胎儿风险的新神经标志物来扩展和增加其孕产妇研究计划的影响。 3D超声的出现提供了更高的分辨率胎儿图像，并在临床研究中允许对特定胎儿结构进行体积表征。拟议的I/开始研究将首次确定应用3D超声技术以确定发育中胎儿孕产妇吸烟的风险神经标记的可行性。 I/开始研究将利用PI正在进行的孕产妇和婴儿行为研究的基础设施和参与者（R01 DA031188）。正在进行的研究中的孕妇吸烟者和对照将完成三项胎儿超声评估，涉及胎儿神经（额叶脑部区域）和神经内分泌（肾上腺）结构的3D体积评估。将评估对超声协议的可接受性和依从性和体积评估的可靠性。我们的目标是：1）证明我们新颖的超声方法学对胎儿神经和神经内分泌结构进行体积评估的可行性，以及2）对孕产妇吸烟对胎儿神经和神经内分泌结构的影响进行初步表征，以制备较大的R01研究。如果成功的话，这项试验研究的结果为未来的潜力提供：a）促进在怀孕期间实时实时吸烟机制，b）改善孕妇吸烟者的临床护理，c）识别新型的治疗靶标，以保护裸露的胎儿，d）d）为孕妇提供新的焦点，以与怀孕的吸烟者开发新的治疗剂。