Epigenetic biomarkers and preterm birth

Preterm birth (PTB) is a major public health challenge, and novel, sensitive approaches to predict PTB are still evolving. Epigenomic markers are being explored as biomarkers of PTB because of their molecular stability compared to gene expression. This approach is also relatively new compared to gene-based diagnostics, which relies on mutations or single nucleotide polymorphisms. The fundamental principle of epigenome diagnostics is that epigenetic reprogramming in the target tissue (e.g. placental tissue) might be captured by more accessible surrogate tissue (e.g. blood) using biochemical epigenome assays on circulating DNA that incorporate methylation, histone modifications, nucleosome positioning, and/or chromatin accessibility. Epigenomic-based biomarkers may hold great potential for early identification of the majority of PTBs that are not associated with genetic variants or mutations. In this review, we discuss recent advances made in the development of epigenome assays focusing on its potential exploration for association and prediction of PTB. We also summarize population-level cohort studies conducted in the USA and globally that provide opportunities for genetic and epigenetic marker development for PTB. In addition, we summarize publicly available epigenome resources and published PTB studies. We particularly focus on ongoing genome-wide DNA methylation and epigenome-wide association studies. Finally, we review the limitations of current research, the importance of establishing a comprehensive biobank, and possible directions for future studies in identifying effective epigenome biomarkers to enhance health outcomes for pregnant women at risk of PTB and their infants.