A systems immunology investigation of pregnancy immune phenotypic differences between racial groups

In the United States the non-Hispanic black (NHB) infant mortality rate is more than twice the non-Hispanic white (NHW) rate. Further, NHB infants of US-born mothers have statistically worse birth outcomes than infants born to first-generation US immigrants from Africa, indicating trans-generational influences beyond genetics (epigenetics) that impact neonatal health. A successful pregnancy requires a series of well-timed immunological events to support fetal growth and maintain fetal tolerance, including the balance of pro- and anti-inflammatory signals. Growing evidence suggests a relationship between maternal stress, epigenetics, and inflammation, which influences the development of the fetal immune system. We took a systems immunology approach to understand how disrupted immune adaptations during pregnancy affect neonatal immunity and contribute to the racial disparity in neonatal outcomes. Using longitudinal matched maternal and cord blood samples from the Obstetrics and Neonatal Outcomes Study (ONOS) cohort at UVA, we performed multiplexed bead-based assays to measure peripheral maternal inflammatory markers throughout gestation. We discovered pro-inflammatory cytokines and chemokines that are differentially regulated between NHB and NHW women throughout pregnancy as well as cytokines that differ in the cord blood of NHB and NHW neonates. To reveal local, epigenetically regulated immune differences at the maternal-fetal interface of the placenta, we analyzed matched placental mRNA and miRNA data from a separate cohort. This study is the first systems level analysis of racial immune differences in pregnancy and provides a foundation to identify opportunities for therapeutic interventions that will mitigate persistent racial disparities in pregnancy outcomes in Virginia and the US.

2022 UVA Health Disparities Conference - Breakout Session 1: Health Outcomes in Disadvantaged Populations