Epigenome-wide DNA methylation and spontaneous preterm birth among pregnant black women

Preterm birth (PTB, < 37 weeks of gestation) is a major public health concern in the United States, with Black women experiencing a higher incidence compared to White women. Although some studies have identified social, medical, and obstetric risk factors for PTB, the biological mechanisms underlying spontaneous PTB (sPTB) risk remain unclear. We conducted a secondary analysis using data from Black participants enrolled in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b), (n = 1073) from 2010 to 2013. Peripheral whole blood samples were collected from all participants between 6 + 0/7 and 13 + 6/7 weeks of gestation. Demographic, behavioral and clinical data were gathered through surveys, and pregnancy outcomes were obtained through chart abstraction. We used the Infinium Methylation EPIC v2.0 BeadChip for epigenome-wide association (EWAS) of DNA methylation and sPTB.

We identified 19 differentially methylated CpGs associated with sPTB, 17 CpGs were mapped to 27 annotated genes including CASR (cg19108881), KLF2/ KLF2-DT (cg18473733), SNX14/SYNCRIP (cg25689730), FBXO2 (cg04872402), HPAT5/LOC102725048 (cg12798411), RTN4RL1/LOC105371486 (cg03098704), SETD4 (cg25826287), SLC25A16 (cg15165108), CLYBL/CLYBL-AS3 (cg12328625), HES7 (cg09601704), SLC67A1/ SLC67A1-AS (cg05919744), ATP2A3 (cg12120292), PSMB8/PSMB8-AS1/ PSMB9, TAP2 (cg24031377), SLCO3A1 (cg05111081), KIAA1671 (cg26144263), ALDH4A1 (cg 12,092,708), and GUCD1 and SNRPD3 (cg11895717). Functional enrichment analysis revealed molecular functions related to enzymatic protein degradation (threonine peptidases) and energy-dependent transport of substances across membranes and biological processes including cellular transport and vascular regulation, which may influence early embryonic development and contribute to sPTB risk.

Our study identified potential epigenetic alterations associated with sPTB risk and highlighted candidate genes, molecular functions, and biological processes that may serve as predictors in pregnant Black women. Future research should examine larger samples of Black women and include social determinants of health (SDOH) such as individual- and structural- racism to explain racial disparities in methylation patterns. There is a need for larger studies that examine the interactions between SDOH and epigenomic mechanisms underlying adverse birth outcomes.