Reduced global DNA methylation in maternal peripheral blood is associated with preterm birth: an exploratory study in women with diabetes in pregnancy

Pregnancies complicated by diabetes pose a significant risk to maternal and neonatal health. Epigenetic mechanisms, particularly DNA methylation, have emerged as potential biomarkers for both pregnancy and birth outcomes. The aim of this exploratory study was to investigate the association between global DNA methylation and birth outcomes in South African women with different types of diabetes in pregnancy. Global DNA methylation levels were measured at less than 28 weeks of gestation, in peripheral blood samples of women with type 1 diabetes (T1DM, n = 26), type 2 diabetes (T2DM, n = 77), gestational diabetes mellitus (GDM, n = 58), and normoglycemia (n = 69), using the Imprint DNA quantification kit. Associations between DNA methylation and diabetes type, maternal characteristics, and birth outcomes were analysed. Women who delivered prematurely had 1.6-fold lower (<i>p</i> = 0.019) global DNA methylation levels compared to those who delivered at full term. This association remained significant after adjusting for confounders, age, body mass index, and gestational age (<i>p</i> = 0.031). A decreased trend towards significance was observed with 5 min Apgar score &lt; 7 (<i>p</i> = 0.09), an indicator of overall neonatal health issues. No association between global DNA methylation and fetal growth, birth weight, and offspring sex were observed. These findings suggest that maternal global DNA methylation may serve as an early indicator of preterm birth in high risk women. Future studies focused on gene-specific DNA methylation are needed to elucidate the mechanisms involved in preterm birth.