Cord Blood Adductomic Profiling Provides Preliminary Insights on Perinatal Smoking Exposure: A Pilot Analysis

Maternal smoking during pregnancy (MSDP) remains a significant public health concern. The molecular mechanisms underlying smoking-induced maternal-fetal impact remain incompletely understood. Newer omics platforms, such as cord blood adductomics, can provide preliminary insight into the "perinatal exposome" leading up to birth. The objective of this study is to explore the adductomic signatures of oxidant stress in cord blood associated with MSDP. In a cohort of mother-infant dyads enrolled at a single birth center in Chicago, IL (2008-2021), we conducted a secondary analysis of self-reported maternal smoking exposure data that was linked to an existent adductomics database of 105 addition products (adducts) measured in cord blood plasma. Principal component analysis (PCA), volcano plots and PERMANOVA were used to visualize the variability in adductomic profiles and to compare significantly increased and decreased adduct concentrations according to self-reported current-smokers, former-smokers, and never-smokers. N = 158 participants (N = 6 current-smokers, 26 former-smokers, and 126 never-smokers) had documented self-reported smoking status and were included in the analysis. PCA demonstrated separation between current-smokers and the other groups (R² = 0.026 for current vs. never-smokers, R² = 0.115 for current vs. former-smokers; Padj = 0.0075 for both) and no difference between former vs. never-smokers. Among 56 annotated adducts, 27 were increased in current vs. never-smokers, and 32 in current vs. former-smokers. Mode of delivery (p = 0.02) and maternal hypertension (p = 0.001) were significantly different among the three groups. Matched analysis by chronic hypertension (yes/no) supported the main finding that current-smoker adductomic profiles were distinct from both former (p = 0.015) and never-smoker (p = 0.0225) profiles. Self-reported MSDP appears to be associated with cord blood adductomic signatures of oxidant stress. Further studies are needed to determine how the duration, extent and timing of exposure correlate with exposomic changes at birth.