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Fetal exposure to tobacco smoke is an adverse risk factor for newborns. A plausible mechanism of how this exposure may negatively impact long term health is differential methylation of deoxyribonucleic acid (DNAm) and its relation to birth weight. We examined whether self-reported gestational smoking status and maternal exhaled carbon monoxide (eCO) during early pregnancy were associated with methylation of cytosine by guanines (CpG) sites that themselves predicted birth weight. We focused first on CpGs associated with maternal smoking, and secondly, among these, on CpGs related to birth weight found in another cohort. Then in 94 newborns from the Breathing for Life Trial (BLT) DNAm levels in cord blood were determined using Infinium Methylation EPIC BeadChip measuring &gt;850K CpGs. We regressed CpGs on eCO and tested via mediation analysis whether CpGs link eCO to birth weight. Nine smoking related CpG sites were significantly associated with birth weight. Among these nine CpGs the methylation of cg02264407 on the LMO7 gene was statistically significant and linked with eCO measurements. eCO greater than six ppm showed a 2.3% decrease in infant DNAm ( p = 0.035) on the LMO7 gene. A 1% decrease in methylation at this site resulted in decreased birth weight by 44.8 g ( p = 0.003). None of the nine CpGs tested was associated with self-reported smoking. This is the first study to report potential mediation of DNA methylation, linking eCO measurements during early pregnancy with birth weight.

Variation of DNA Methylation in Newborns Associated with Exhaled Carbon Monoxide during Pregnancy