Magnetoencephalography based tracking of fetal neurodevelopment in diabetic pregnancies

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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.