The Maternal Obesity-Placenta-Brain Axis: Longitudinal MRI Assessment from Gestation to Infancy

Pre-pregnancy obesity (PPO) affects 29% of U.S. pregnant women, posing a significant public health challenge by impacting perinatal neurodevelopment and increasing risk for psychiatric disorders in offspring. While alterations in placental function are likely involved, current studies examine PPO, placenta, and brain parameters in isolation, leading to fragmented understanding. Moreover, there is a critical lack of longitudinal studies spanning different trimesters through the postnatal period, limiting prospects for timely intervention. To address these gaps, we propose recruiting 400 pregnant participants (200 BMI ≥30, 200 BMI 18.5-30) from Emory's obstetric network in Atlanta—a region with among the highest maternal obesity rates nationally. Participants will undergo three MRI assessments: second trimester (24-28 weeks, n=300), third trimester (32-36 weeks, n=240), and neonatal (1-2 months, n=210 expected to complete all three scans). Each <30-minute prenatal scan captures: (1) multimodal placental MRI (multi-echo T2* for oxygenation; IVIM for perfusion/diffusion); (2) multimodal fetal brain MRI (T2-weighted, resting-state, and diffusion-weighted imaging); and (3) maternal abdominal MRI for visceral adipose tissue quantification. The neonatal scan focuses solely on infant brain MRI. Maternal metabolic profiling includes pre-pregnancy BMI, gestational weight gain, first-trimester waist-hip ratio, and MRI-derived VAT. Neurobehavioral phenotyping will use the NIH Baby Toolbox at 6 and 12 months and ASQ:SE-2 at 6, 9, and 12 months. Our pilot data demonstrate that PPO associates with reduced maternal-side placental T2* (third trimester, sex-specific), reduced placental perfusion fraction f (second trimester), and altered fetal brain connectivity and white matter integrity. Building on these findings, we hypothesize that PPO compromises placental oxygenation and perfusion, which disrupts fetal brain development, leading to measurable neurobehavioral liabilities through 12 months. Aim 1 will determine whether PPO and central adiposity reduce placental oxygenation and microcirculation using T2* and IVIM metrics. Aim 2 will investigate how PPO shapes brain structure, function, and behavior from fetal period through 12 months, assessing attention, self-regulation, and social communication. Aim 3 will examine whether placental dysfunction mediates the PPO effect on brain and behavior through longitudinal mediation models. This comprehensive approach will elucidate the PPO-placenta-brain axis, informing targeted interventions to mitigate neurodevelopmental risks associated with maternal obesity. Project Number: 1R01HD121683-01 | Fiscal Year: 2026 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: YUN WANG (+1 co-PI) | Institution: EMORY UNIVERSITY, ATLANTA, GA | Award Amount: $639,857 | Activity Code: R01 | Study Section: Developmental Brain Disorders Study Section[DBD] View on NIH RePORTER: https://reporter.nih.gov/project-details/11342946