Gaining a deeper understanding of social determinants of preterm birth by integrating multi-omics data.

In the US, high rates of preterm birth (PTB) and profound Black-White disparities in PTB have persisted for decades. This review focuses on the role of social determinants of health (SDH), with an emphasis on maternal stress, in PTB disparity and biological embedding. It covers: (1) PTB disparity in US Black women and possible contributors; (2) the role of SDH, highlighting maternal stress, in the persistent racial disparity of PTB; (3) epigenetics at the interface between genes and environment; (4) the role of the genome in modifying maternal stress-PTB associations; (5) recent advances in multi-omics studies of PTB; and (6) future perspectives on integrating multi-omics with SDH to elucidate the Black-White disparity in PTB. Available studies have indicated that neither environmental exposures nor genetics alone can adequately explain the Black-White PTB disparity. Preliminary yet promising findings of epigenetic and gene-environment interaction studies underscore the value of integrating SDH with multi-omics in prospective birth cohort studies, especially among high-risk Black women. In an era of rapid advancements in biomedical sciences and technologies and a growing number of prospective birth cohort studies, we have unprecedented opportunities to advance this field and finally address the long history of health disparities in PTB. IMPACT: This review provides an overview of social determinants of health (SDH) with a focus on maternal stress and its role on Black-White disparity in preterm birth (PTB). It summarizes the available literature on the interplay of maternal stress with key biological layers (e.g., individual genome and epigenome in response to environmental stressors) and significant knowledge gaps. It offers perspectives that such knowledge may provide deeper insight into how SDH affects PTB and why some women are more vulnerable than others and underscores the critical need for integrating SDH with multi-omics in prospective birth cohort studies, especially among high-risk Black women.