PROJECT SUMMARY The prenatal period is regarded as one of the most sensitive phases in human development. Events that occur during gestation can alter the course of development with lasting impact. Presently, the COVID-19 pandemic is exerting wide-spread impact on the lives of expectant mothers around the world. Particularly salient pandemic- related stressors that are being experienced by pregnant women are social isolation and uncertainty stress. There is ample physiological and behavioral literature showing that social isolation and uncertainty stress affect typical human and animal psychobiological functioning, but there is an absence of knowledge about how these conditions might impact the physical and psychological health of a pregnant woman, and what the consequences of those changes might be for her developing child. The central objective of this proposal is to build foundational knowledge about the effects of prenatal social isolation and uncertainty stress on maternal psychobiology and infant neurobehavior. We will explore several candidate physiological systems in the mother to elucidate mechanisms that underlie associations between maternal stressors and child outcomes. To achieve these goals, we will recruit 200 women from a large New York City cohort established at the height of the pandemic into a prospective, longitudinal study that will include pre- and postnatal biospecimen collection and child neurobehavioral assessments at 6-, 12- and 24 months. Multi-modal neuroimaging strategies, including infant EEG and quantitative MRI, and innovative remote biophysical data collection strategies will be employed. The primary aims of this project are to (i) examine the impact of prenatal social isolation and uncertainty stress on maternal biology and postnatal mental health; (ii) evaluate the influence of maternal prenatal social isolation and uncertainty stress on infant neurobehavioral development; and (iii) examine the role of prenatal social isolation and uncertainty stress on mother-infant bi-directional interactions. We will thus be able to meaningfully evaluate whether, and how, prenatal social isolation and uncertainty stress modify maternal biology and affect, and the neurobehavioral consequences of those impacts on infants. Such work would constitute a substantial advance in our understanding of the longitudinal effects of prenatal psychosocial stress exposures, the underlying mechanistic pathways, and the origins of child neurobehavioral disorders.

PUBLIC HEALTH RELEVANCE Isolation, insecurity and uncertainty can impact the psychiatric health of pregnant mothers, with substantial lasting morbidity for mother and child. The goal of this project is to lay critical foundations for understanding the biological consequences of social isolation and uncertainty stress, and the roles they play in both maternal and child outcomes.