Magnetoencephalography based tracking of fetal neurodevelopment in diabetic pregnancies

基于脑磁图的糖尿病妊娠胎儿神经发育追踪

• 批准号: 10318260
• 负责人: Hari Eswaran
• 金额: $ 38万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-08 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10318260
• 关键词: Attention; Auditory Evoked Potentials; Biological Markers; Birth; Blood; Blood Glucose; Blood specimen; Brain; Brain-Derived Neurotrophic Factor; C-reactive protein; Caring; Characteristics; Child; Clinical; Data; Development; Diabetes Mellitus; Diabetic mother; Environment; Epidemiology; Etiology; Female of child bearing age; Fetal Heart; Fetus; General Population; Gestational Diabetes; Glucose; Goals; Growth; Growth Factor; Health; High-Risk Pregnancy; Human; Hypertension; Impaired cognition; Impairment; Infant; Infant Health; Inflammation; Inflammatory; Insulin-Dependent Diabetes Mellitus; Interleukin-6; Intervention; Investigation; Language Delays; Language Development; Life; Link; MADHIP gene; Magnetoencephalography; Medical; Monitor; Mothers; Neonatal; Neurodevelopmental Deficit; Neurologic; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Observational Study; Outcome; Prediabetes syndrome; Pregnancy; Pregnancy in Diabetics; Prevalence; Process; Protocols documentation; Psychopathology; Reporting; Risk; Risk Factors; Sampling; Schedule; Signal Transduction; Solid; Source; Squid; System; Techniques; Therapeutic; Therapeutic Intervention; Third Pregnancy Trimester; Time; Umbilical Cord Blood; Visit; Visual evoked cortical potential; adverse maternal outcomes; auditory stimulus; base; bioelectricity; comorbidity; cytokine; delivery complications; diabetic; fetal; follow-up; glycemic control; inattention; indexing; infant outcome; inflammatory marker; inflammatory modulation; insight; maternal diabetes; maternal risk; motor deficit; multimodality; neonatal brain; neonate; neural growth; neurobehavioral; neurodevelopment; neurophysiology; non-diabetic; novel; offspring; pregnant; reproductive; response; sensor; signal processing; systemic inflammatory response; targeted treatment; type I and type II diabetes; visual stimulus

Abstract The prevalence of Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D) is on the rise and represents a health concern for women of childbearing age. Over an 8 year period, a major increase in the prevalence of births complicated by pre-gestational diabetes increased by 50% .Pre-gestational diabetes is one of the most common maternal risk factors for maternal, fetal, and infant complications. Preliminary evidence by our group evaluated inflammatory biomarkers in pregnant subjects longitudinally during gestation. Several inflammatory cytokines including C-reactive protein (CRP) were significantly elevated in T2D relative to non-diabetic controls, and this effect was more evident in the third trimester. Thus, maternal inflammation later in pregnancy may represent an important mechanistic link associated with health risks for mother an infant in diabetic pregnancy. Infants and children from diabetic mothers are more likely to suffer neurological impairments compared to offspring of non- diabetic mothers. Thus, we hypothesized that the increase in third trimester inflammation found in diabetic pregnancy could adversely impact fetal brain development, a significant period of brain growth in humans. A majority of the studies to date have linked poor infant outcome with various maternal risk factors. However, these studies were limited in that the assessments did not occur in real time. The world’s first biomagnetic sensing system at UAMS was built specifically to track and understand the process of fetal brain development. The SARA (SQUID Array for Reproductive Assessment) system consists of 151 primary superconducting sensors which detect biomagnetic fields generated in the body including fetal heart, and fetal brain. SARA is based on the non- invasive magnetoencephalography (MEG) technique that permits the investigation of fetal parameters from early gestation until delivery. We developed an optimized combination of recording parameters using auditory and visual stimuli and spontaneous brain activity for a multimodal approach to understand fetal neurological development trajectory. The overall goal is to correlate fetal and infant brain development with inflammatory markers in mothers with pre-gestational T1D and T2D. We will obtain maternal blood samples for cytokine assessment at their regularly scheduled third trimester SARA visit. We will also collect maternal and cord blood samples at delivery. Aim 1: Implement an integrated multimodal approach to investigate fetal and neonatal brain activity along with assessment of blood inflammatory biomarkers in pre-gestational diabetic mothers. Aim 2: Track and quantify brain activity using MEG signals during fetal and neonatal stage of life. Aim 3: Correlate the inflammatory biomarkers to fetal and neonatal brain activity.

摘要 1型糖尿病（T1D）和2型糖尿病（T2D）的患病率正在上升，代表健康 关心育龄的妇女。在8年内，出生率的重大增加 妊娠前糖尿病的复杂性增加了50％。妊娠糖尿病是最常见的糖尿病之一 产妇，胎儿和婴儿并发症的产妇危险因素。我们小组评估的初步证据 妊娠期间，怀孕受试者的炎症生物标志物。几种炎症细胞因子 在T2D中，相对于非糖尿病对照，包括C反应性蛋白（CRP）显着升高，这 效应是三个月中更多的证据。那，孕产妇炎症后来怀孕可能代表 与糖尿病妊娠婴儿健康风险有关的重要机理联系。婴儿和 与非糖尿病母亲的儿童相比，与非 - 的后代相比 糖尿病母亲。这是我们假设糖尿病患者发现的三个月感染的增加 怀孕可能会对胎儿脑发育产生不利影响，这是人类大脑生长的重大生长。一个 迄今为止，大多数研究都将贫困的婴儿结局与各种物质危险因素联系起来。但是，这些 研究受到限制，因为这些评估不是实时进行的。世界上第一个生物磁感觉 UAMS的系统专门用于跟踪和了解胎儿脑发育的过程。萨拉 （用于生殖评估的鱿鱼阵列）系统由151个主要超导传感器组成，这些传感器 检测体内产生的生物磁场，包括胎儿心脏和胎儿大脑。萨拉是基于非 侵入性磁脑电图（MEG）技术，允许早期投资胎儿参数 妊娠直到交货。我们使用听觉和 视觉刺激和赞助大脑活动，用于了解胎儿神经系统的多模式方法 发展轨迹。总体目标是将胎儿和婴儿脑发育与炎症相关联 妊娠前T1D和T2D的母亲的标记。我们将获得细胞因子的材料血液样本 定期安排的三个月访问评估。我们还将收集材料和脐带血 交货时样品。目标1：实施一种集成的多模式方法来研究胎儿和新生儿大脑 活性以及评估妊娠前糖尿病母亲中血液炎症性生物标志物。目标2： 在生命的胎儿和新生儿阶段，使用MEG信号跟踪和量化大脑活动。目标3：关联 对胎儿和新生儿大脑活性的炎症生物标志物。