Magnetoencephalography based tracking of fetal neurodevelopment in diabetic pregnancies

摘要 1型糖尿病(T1D)和2型糖尿病(T2D)的患病率正在上升，代表着一种健康 关心育龄妇女。在8年的时间里，出生流行率大幅上升 合并孕前糖尿病增加50%。妊娠期糖尿病是最常见的之一 孕产妇、胎儿和婴儿并发症的危险因素。由我们小组评估的初步证据 妊娠期纵向炎症生物标志物的研究。几种炎性细胞因子 包括C-反应蛋白(CRP)在内的T2D组与非糖尿病对照组相比显著升高，而这 这一作用在妊娠晚期更为明显。因此，妊娠后期的母体炎症可能代表着一种 糖尿病妊娠期间与母婴健康风险相关的重要机制联系。婴儿和 与非糖尿病母亲的孩子相比，糖尿病母亲的孩子更有可能遭受神经损伤 糖尿病母亲。因此，我们假设糖尿病患者晚期妊娠炎症的增加 怀孕可能会对胎儿的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。一个 到目前为止，大多数研究都将不良的婴儿结局与各种母亲风险因素联系起来。然而，这些 研究受到限制，因为评估不是实时进行的。世界上第一个生物磁感应 UAMS的系统是专门为跟踪和了解胎儿大脑发育过程而建立的。《莎拉》 (用于生殖评估的SQUID阵列)系统由151个初级超导传感器组成， 检测体内产生的生物磁场，包括胎儿心脏和胎儿大脑。Sara是基于非 侵入性脑磁图(MEG)技术，可从早期开始调查胎儿参数 孕期到分娩。我们开发了一种优化的录音参数组合，使用听觉和 视觉刺激和自发脑活动对了解胎儿神经学的多模式方法 发展轨迹。总体目标是将胎儿和婴儿的大脑发育与炎症联系起来。 孕前T1D和T2D母亲的标志物。我们将获取母体血液样本以检测细胞因子 在他们定期安排的晚孕期Sara探视中进行评估。我们还将收集孕妇和脐带血。 送货时的样品。目标1：实施综合多模式方法来研究胎儿和新生儿的大脑 妊娠期糖尿病母亲的活动性以及血液炎症生物标志物的评估。目标2： 在胎儿和新生儿阶段使用脑磁图信号跟踪和量化大脑活动。目标3：将 炎性生物标志物对胎儿和新生儿脑活动的影响。

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.