A team from Washington University, St. Louis that includes two BBRF Scientific Council members has reported results from two studies involving mother-child pairs that is part of a larger project to trace the fetal origins of health and disease. The two studies focused on whether a mother’s exposure to adversity in the prenatal period had any detectable effects on infant brain development as measured immediately following birth.

One study, appearing in JAMA Network Open, focused on the potential impact of poverty. Analysis was performed on 280 women who had been recruited in the second or third trimester of pregnancy, average age 29, 61% of whom were “Black/African-American”, 35% “White” and 4% “Other.” All in this cohort gave birth to healthy, full-term infants between 2017 and 2020.

Within a few days or weeks of birth, each infant was given a functional MRI scan. Mothers, meanwhile, provided data which enabled the team to assess “disadvantage” in those who experienced it. The sample included women from across the socioeconomic spectrum. Disadvantage was reflected in income data for the subject’s home neighborhood, and measures of their diet, how much education they had received, and their insurance status. Indices of psychosocial stress were also collected, including measures of stress, anxiety, depression, and discrimination.

The research was led by Christopher Smyser, M.D. and Regina Triplett, M.D. The team included four-time BBRF grantee and Scientific Council member Deanna Barch, Ph.D.; two-time BBRF grantee, past BBRF Klerman and Ruane Prize winner and BBRF Scientific Council member Joan Luby, M.D.; as well as 2019 BBRF Young Investigator Rachel Lean, Ph.D.

The prenatal period is a particularly vulnerable stage of brain development, the team noted, encompassing the birth of most neurons and their migration to places throughout the brain, as well as the process of synapse formation, the pruning of excess synapses, and myelination—when the axons connecting neurons acquire a fatty protective insulation to protect signal transmission.

Most existing research has focused on ways in which psychosocial stress impacts brain areas central in the processing of emotions, notably the hippocampus and amygdala. But possible impacts related to economic disadvantage have not been well explored. The U.S. rate of childhood poverty is about 16%, and “pregnant women with low incomes are at disproportionately greater risk of psychiatric disorders and stress during pregnancy,” the team noted.

Analysis of the fMRI scans of infants born to mothers who were exposed to poverty during pregnancy showed reduced grey matter in the cerebral cortex and in subcortical areas, as well as reduced white matter and reduced folding of the cortex. Cortical folding increases the brain’s surface area and is essential for optimal functioning.

“The associations between poverty and reduced brain volumes begin in utero and are evident in the first weeks of life,” the team wrote. At the same time, the study did not show a “preferential association” between maternal poverty or psychosocial stress in pregnancy and the structure of the hippocampus or amygdala. What was seen was “a more widespread alteration of brain growth and development.”

Future studies will seek to determine the role of specific contributing factors, including macro- and micronutrient deficiencies, impacts of environmental toxins including lead and water or air pollution, as well as the potential contributions of racial discrimination and socioeconomic inequities.

Many of the same team members contributed a separate paper to Biological Psychiatry, involving over 300 members of the same cohort of women and their newborns. This study focused on the potential impact of maternal exposure to neighborhood crime upon infant brain development in the fetal period, as measured immediately following birth. This study was led by Dr. Symser and Rebecca Brady, Ph.D. In addition to Drs. Barch, Luby and Lean, 2015 BBRF Young Investigator George Slavich, Ph.D. contributed to this second study.

The study found that mothers who, during pregnancy, lived in a neighborhood with high levels of property crime were more likely to give birth to infants with weaker limbic and frontal brain connections. The limbic system regulates mood and emotions.

In this respect the second study differed from the first. Unlike the effects of poverty, the effects of exposure to crime were seen in specific areas of the infant brain. “We found that this weakening of the functional connections between emotion-processing structures in the babies’ brains was very robust when we controlled for other types of adversity, such as poverty. It appears stresses linked to crime had more specific effects,” said Dr. Brady.

But the two studies had something important in common: environmental stressors (poverty and local crime) experienced by pregnant women were found to impact the way the brain developed in their infants, prior to birth. Future research based on members of the same cohort of mothers and children will now be able to track how departures from developmental norms seen in these two studies change over time. They may prove transitory—or, they could worsen with the passage of years. The two studies thus establish a baseline for these two specific environmental exposures in the gestational period.