Prenatal Risk Factors, Developmental Outcomes, and the Human Brain in utero: Maternal BMI and Fetal Brain Functional Connectivity

Mental illness in the US and worldwide is debilitating, costly, and increasing, yet knowledge and treatment for mental disorders lags far behind what is known and what can be done for physical illness. Recent reckoning with this reality has generated new tools and technology, emphasized developmental and translational work across human and animal models, and inspired calls for radical interdisciplinary training approaches and cultural shifts. With these new directions in mind, the current work leverages methodological advances in functional magnetic resonance imaging (fMRI) and dimensional theoretical frameworks to investigate factors in prenatal development that may relate to risk or resilience for the development of mental illness. This dissertation includes two studies, one assessing the intrauterine influence of elevated maternal weight on fetal brain development, and another, in progress, examining the psychosocial process of maternal-fetal attachment. Prenatal development is a time when the brain is acutely vulnerable to insult and alteration by environmental factors (e.g., toxins, maternal health). It is also a time when prevention and intervention strategies may have the greatest impact in improving developmental outcomes. Recent research indicates that high maternal body mass index (BMI) during pregnancy is associated with increased risk for numerous physical health, cognitive, and mental health problems in offspring across the lifespan. It is possible that heightened maternal prenatal BMI influences the developing brain even before birth. Study 1 of this dissertation examines this possibility at the level of macrocircuitry in the human fetal brain. Using a data-driven strategy for parcellating the brain into subnetworks, I test whether MRI functional connectivity within or between fetal neural subnetworks varies with maternal prenatal BMI in 109 fetuses between the ages of 26 and 39 weeks. I found that strength of connectivity between two subnetworks, left insula/inferior frontal gyrus (aIN/IFG) and bilateral prefrontal cortex (PFC), varied with maternal BMI. Global differences in network topography were not observed. The focal effects were localized in regions that will later support behavioral regulation and integrative processes, regions commonly associated with obesity-related deficits. By establishing onset in neural differences prior to birth, this study supports a model in which maternal BMI-related risk is associated with fetal connectome-level brain organization with implications for offspring long-term cognitive development and mental health. Study 2 of this dissertation examines maternal-fetal attachment (MFA), a psychosocial process involving maternal behaviors and feelings towards the developing fetus. MFA has been shown to relate to maternal mental health, social support, and physical health habits during pregnancy, as well as later maternal-infant attachment. Although MFA has been studied since the 1980s, there is a lack of consensus around what constitutes MFA and how it should be measured. Study 2 evaluates the psychometric properties (factor structure, invariance) of the most commonly used MFA assessments in two large, diverse samples of American women. A follow-up study is planned to assess the validity and prenatal correlates of the modernized MFA measure. This work aims to provide foundational clarity for future investigation of MFA, an area that holds promise for prenatal intervention and improved outcomes in the many domains associated with attachment. Finally, closing remarks address future directions and relevance of the present work in the context of current issues in clinical science and public health.

Advisor: Hinshaw, Stephen P