A longitudinal study of prenatal maternal obesity and the fetal origins of impulsivity in Puerto Rican children

项目总结 此K08应用程序旨在检查抑制控制困难的潜在胎儿来源：宫内暴露 到孕期母体肥胖。这项研究通过检查抑制控制缺陷填补了一个关键的空白 在美国的波多黎各人的代际样本。这个社区，和其他拉美裔人口一样， 肥胖和冲动相关疾病的增加，如注意力缺陷/多动障碍 多动症(ADHD)，但研究仍然很少。这份为期五年的K08申请提供了一个研究和 支持申请人成为独立调查员的培训，重点是 用跨学科方法(生命历程)研究抑制控制缺陷的早期起源 流行病学、婴儿神经成像和生物统计学)。培训计划建立在应聘者之前的培训基础上 和经验，并利用优秀的指导团队和研究环境来促进 培养候选人在(1)收集、分析和解释婴儿休息状态方面的专业知识 功能磁共振成像(FMRI)资料；(2)围产期体重与炎症及其关系 对胎儿神经发育的影响；(3)少数民族/少数民族人群的生命周期流行病学研究；(4) 幼儿抑制性控制的现象学和评估；以及(5)科学中负责任的行为 研究。本项目将调查孕妇产前体重指数(BMI)过高对 子代婴儿的额叶纹状体连接(即，与抑制性控制障碍有关的回路)(目标1)和 关于2岁时抑制控制的行为评估(目标2)。据推测，炎症是关键 母体产前BMI导致额纹状体连接中断的介体(即机制) 婴幼儿和幼儿抑制性控制受损。该项目将收集孕产妇的产前评估。 体重指数和炎症，2-4周龄婴儿的静息状态fMRI数据，以及行为和父母 报告2岁时抑制控制能力的测量。目前，拟议的研究参与者已登记在册 在NIH环境对儿童健康结局的影响(ECHO)研究中，该研究将收集 500个婴儿。在此结构的基础上，我们建议选择平均值(BMI=18.5)的子样本(n=76) 24.9 kg m−2(n=38)和肥胖(BMI⩾30 kg m−2；n=38)孕妇及其子女纳入本项目。 拟议的研究产生的数据将导致未来的R01应用程序检查后代的抑制 纵向控制电路。总而言之，研究和培训的经验和专业知识 通过这项K08奖项，将支持申请者向研究独立性的过渡，并确保 申请者成为抑制控制缺陷的产前起源方面的主要权威。

PROJECT SUMMARY This K08 application aims at examining a potential fetal origin of inhibitory control difficulties: in utero exposure to prenatal maternal obesity. This study fills a crucial gap by examining inhibitory control deficits in an intergenerational sample of Puerto Ricans in the US. This community, alongside other Latino populations, has seen an increase in obesity and impulsivity-related disorders such as attention-deficit/hyperactivity disorder (ADHD), yet remains vastly understudied. This five-year K08 application presents a program for research and training that will support the applicant on a path towards becoming an independent investigator, focused on studying the early origins of inhibitory control deficits through an interdisciplinary approach (life course epidemiology, infant neuroimaging, and biostatistics). The training plan builds on the candidate's prior training and experience and capitalizes on an outstanding mentorship team and research environment to foster the development of the candidate's expertise in (1) collection, analysis, and interpretation of infant resting state functional Magnetic Resonance Imaging (fMRI) data; (2) perinatal weight and inflammation and its relationship to fetal neurodevelopment; (3) life course epidemiologic research with ethnic/racial minority populations; (4) phenomenology and assessment of inhibitory control in toddlers; and (5) responsible conduct in scientific research. This project will investigate the influence of high maternal prenatal body mass index (BMI) on frontostrialal connectivity (i.e., circuits implicated in inhibitory control disorders) in offspring infants (Aim #1) and on behavioral assessments of inhibitory control at age 2 (Aim # 2). It is hypothesized that inflammation is a key mediator (i.e. mechanism) by which maternal prenatal BMI leads to disruptions in frontostriatal connectivity in infants and impaired inhibitory control in toddlers. The project will collect prenatal assessments of maternal BMI and inflammation, resting state fMRI data from infants at 2-4 weeks of age, and behavioral and parent report measures of inhibitory control abilities at age 2. Currently, the proposed study participants are enrolled in the NIH Environmental influences on Child Health Outcomes (ECHO) study, which will collect MRI data on 500 infants. Building on this structure, we propose to select a subsample (n=76) of average (BMI=18.5– 24.9 kg m−2; n=38) and obese (BMI⩾30 kg m−2; n=38) pregnant women and offspring to include in this project. Data yielded from the proposed study will lead to a future R01 application examining offspring's inhibitory control circuits longitudinally. Together, the research and training experiences and expertise developed through this K08 award will support the applicant's transition to research independence and ensure the applicant becomes a leading authority in the prenatal origins of inhibitory control deficits.