Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality, with long-term sequelae for both mother and infant. Despite many known risk factors for PTB, prevention and treatment options are limited. Non-Hispanic (NH) Black women are 2-3 times more likely to experience PTB compared to NH White women, and some subgroups of Hispanic women also have increased risk. Racism has been hypothesized as a root cause of perinatal health inequities in the United States (U.S.), yet its mechanisms remain understudied. Epigenetics is a field with great promise for understanding how racism affects gene expression and identifying risk for adverse birth outcomes among women of color. Most studies of epigenomics in pregnancy have had low representation of NH Black and Hispanic women, and few have included structural racism exposures. Further, prospective analyses from early pregnancy to birth outcomes are lacking, limiting identification of high- risk women for improved prenatal surveillance. We propose to address these crucial knowledge gaps by leveraging one of the largest and best-phenotyped cohorts to date, the nuMoM2b Study (2010-2015), a multicenter, longitudinal cohort study of nulliparous pregnant women across the U.S. Existing data from this study include: extracted maternal DNA from blood, Krieger’s individual experiences of discrimination, geocoded participant addresses, pregnancy complications, and birth outcomes. We have assembled a multidisciplinary team with expertise in maternal stress, epigenomics, and perinatal health inequities to complete three aims. Aim 1: Determine the interactive effects of individual- and structural- level racism on PTB among NH Black, Hispanic, and NH White participants (n=8,681). We will use the experiences of discrimination scale score for individual level racism, and derive six measures of structural racism: residential segregation, income, immigrant political climate, political participation, judicial treatment, and homeownership. We will study within-racial and ethnic group differences in PTB; and then examine multilevel (the interaction of individual and structural) racism in the whole group to determine if racism explains the excess PTB observed in NH Black and Hispanic women. Aim 2: Characterize the methylome of all NH Black women in the cohort (n=1,306). We will conduct an epigenome-wide association study of early pregnancy and study candidate genes on stress pathways leading to PTB. Aim 3: Identify whether DNA methylation mediates the association between multilevel racism and PTB among NH Black women (n=1,306). Aims 2 and 3 focus on NH Black women as they bear the highest burden of PTB. This study will be the largest to examine multilevel racism factors and epigenomics in pregnancy among NH Black women. Findings will address knowledge gaps by 1) contributing epigenomic data towards discovery of mechanisms underlying PTB and other adverse birth outcomes in Black women; and 2) informing health policy development related to racism and perinatal health inequities across diverse geographic locations in the U.S.

PROJECT NARRATIVE Though anti-Black racism has been identified as a main driver of perinatal health inequities, no studies have examined how racism experienced at both the individual and structural levels interact to produce preterm birth. In addition, examination of how stressors such as racism affect the epigenome of Non-Hispanic Black women is similarly understudied and essential for guiding interventions to reduce health inequities. The proposed study addresses a key theme of the National Institute of Health’s strategic plan (understanding biological, behavioral, and social determinants of population health) by examining how epigenomic changes may mediate the association between racism and preterm birth.