Maternal smoking during pregnancy is associated with adverse effects on offspring health through impaired placental structure and function. Nicotine and other tobacco-related compounds readily cross the placental barrier, disrupt metabolic pathways, and increase the risk of long-term developmental disorders in newborn. Here, placental metabolic alterations associated with maternal smoking exposure were examined with metabolomics. We used placental samples from the Kuopio Birth Cohort study from 23 nonsmoking controls pregnancies, 19 pregnancies with early smoking exposure (cotinine detected in first-trimester but not in at-term samples), and 13 pregnancies with continuous smoking-exposure (cotinine detected in both first-trimester and at-term samples). Differences in placental metabolomic profiles were seen between controls and both smoking-exposed groups. For example, increased activity of xenobiotic metabolism pathways showed as elevated CYP1A2-related metabolites, e.g., aminoamide local anesthetic metabolite detected in both smoking-exposure groups (p=0.0042 and 0.0019, respectively). Disruptions in amino acid metabolism were observed, e.g., reduced placental tryptophan levels (p=0.0209 and 0.0237). Placentas from women who quit smoking during showed markers of reduced oxidative stress, lower oxidized glutathione (p=0.0119) and higher ergothioneine (p=0.0426) levels. These findings indicate that many smoking-related effects on the placental metabolome persist beyond acute nicotine exposure, showing long-term biological effects of maternal smoking during pregnancy.

Plain language summary Smoking during pregnancy can possibly change how the placenta functions, which also affects the newborn’s long-term health. In this study, we compared placentas from nonsmokers, women who quit during pregnancy, and those who kept smoking. Clear chemical differences were seen in the placentas of smoking exposed pregnant women. The main changes included lowered levels of tryptophan and glutathione, which are important for growth and protection from stress. These results show that smoking-related changes in the placenta can persist beyond active nicotine exposure.

O.K. is a co-founder of Afekta Technologies Ltd., a company providing metabolomics analysis services. W.M, R.H, T.G., M.L, L.K-N, J.R declare no conflicts of interest.

This study was funded by the Finnish Ministry of Social Affairs and Health and the Finnish Cultural Foundation.

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Research Ethics Committee of the Hospital District of Central Finland gave ethical approval for this work.

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