Approximately 10% US infants are born small for gestational age (SGA), a condition linked to increased morbidity and mortality. Infants born to Black women are twice as likely to be SGA compared with those born to White women. Although maternal factors, including epigenetic modifications, likely contribute to SGA, the underlying biological mechanisms remain poorly understood. We evaluated whether epigenetic modifications in early pregnancy were associated with SGA among pregnant Black women. We analyzed data from 931 pregnant non-Hispanic Black women (6-13 weeks of gestation) enrolled in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) cohort across eight academic medical centers. We conducted an epigenome-wide association study using the Infinium MethylationEPIC assay on blood samples from women who delivered SGA infants (n = 133) and appropriate for gestational age infants (n = 798). We adjusted for maternal age, prenatal smoking, education, body mass index, and infant sex, and corrected with multiple testing. We identified 14 differentially methylated 5'-C-phosphate-G-3' (CpG) sites mapping to genes involved in placental development, vascular remodeling, and fetal growth regulation. Functional enrichment analysis highlighted the pathways involved in early embryonic development and placental function, implicating early-pregnancy maternal epigenetic alterations in SGA delivery among Black women and supporting DNA methylation profiling as a potential SGA biomarker.
