Magnetoencephalography based tracking of fetal neurodevelopment in diabetic pregnancies

摘要 1型糖尿病（T1 D）和2型糖尿病（T2 D）的患病率正在上升，并代表着健康风险。 关心育龄妇女。在8年的时间里，出生率大幅上升， 妊娠糖尿病是妊娠期糖尿病最常见的并发症之一。 母体、胎儿和婴儿并发症的母体风险因素。我们小组评估的初步证据 妊娠受试者在妊娠期间纵向的炎症生物标志物。几种炎性细胞因子 包括C-反应蛋白（CRP）在T2 D中相对于非糖尿病对照组显著升高， 效果在妊娠晚期更为明显。因此，妊娠后期的母体炎症可能代表了 与糖尿病妊娠中母亲和婴儿健康风险相关重要机制联系。婴儿和 与非糖尿病母亲的后代相比，糖尿病母亲的孩子更容易遭受神经损伤。 糖尿病母亲因此，我们假设糖尿病患者中晚期妊娠炎症的增加 怀孕可能会对胎儿大脑发育产生不利影响，这是人类大脑发育的一个重要时期。一 迄今为止的大多数研究都将婴儿不良结局与各种产妇风险因素联系起来。但这些 研究的局限性在于评估不是真实的进行的。世界上第一个生物磁传感器 UAMS的系统是专门用来跟踪和了解胎儿大脑发育过程的。萨拉 （SQUID阵列生殖评估）系统由151个初级超导传感器组成， 检测包括胎儿心脏和胎儿大脑在内的体内产生的生物磁场。SARA基于非- 侵入性脑磁图（MEG）技术，允许从早期开始研究胎儿参数 怀孕到分娩。我们开发了一个优化的组合记录参数使用听觉和 视觉刺激和自发脑活动的多模式方法，以了解胎儿神经 发展轨迹总的目标是将胎儿和婴儿的大脑发育与炎症反应联系起来。 在患有孕前T1 D和T2 D的母亲中的标记物。我们将采集母亲的血液样本， 在他们定期安排的第三季度SARA访视中进行评估。我们还将收集产妇和脐带血 交货时的样品。目的1：实施一种综合的多模式方法来研究胎儿和新生儿的大脑 活动沿着评估孕前糖尿病母亲的血液炎症生物标志物。目标二： 在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：将 炎症生物标志物对胎儿和新生儿大脑活动的影响。

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.