Alterations in the Plasma Metabolome Associated With Maternal Smoking During the First Trimester and Foetal Growth

Tobacco smoking during pregnancy has been associated with an increased risk of adverse outcomes like low birth weight. This study determined changes in the circulating metabolome linked to maternal smoking in the first trimester and correlated these changes to the growth of the foetus. The circulating metabolome was examined from first trimester plasma samples by non-targeted (global) liquid chromatography mass spectrometry-based metabolite profiling of 227 pregnant women (99 smokers and 117 non-smokers) from the Kuopio Birth Cohort Study. Tobacco smoking was self-reported through a questionnaire and verified with cotinine measurements from plasma samples. In summary, 64 significant differences were observed between the groups after correction for multiple testing e.g. in metabolites indicating endocrine disruption (e.g. dehydroepiandrosterone sulphate [DHEA-S], VIP = 2.70, d = 0.68, p < 0.0001), metabolites associated with oxidative stress (e.g. bilirubin, VIP = 2.00, d = 0.50, p < 0.0001) and lipid metabolism (e.g. LysoPC 16:1, VIP = 2.07, d = 0.51, p < 0.0001). Some of these metabolites, e.g. DHEA-S and bilirubin, correlated with low birth weight, and some, e.g. LysoPC 16:1, correlated with small head circumference at birth. In conclusion, maternal smoking during the first trimester of pregnancy was associated with an altered metabolite profile linked to endocrine disruption and increased oxidative stress.