Low-level maternal exposure to nicotine associates with significant metabolic perturbations in second-trimester amniotic fluid

• Authors: S. Taylor Fischer, Emory University; Loukia N. Lili, Emory University; Shuzhao Li, Emory University; ViLinh Tran, Emory University; Kim B. Stewart, Greenwood Genetic Center; Charles E. Schwartz, Greenwood Genetic Center; Dean Jones, Emory University; Stephanie Sherman, Emory University; Judith Fridovich-Keil, Emory University
• Journal Title: Environment International
• Volume: Volume 107
• Publisher: Elsevier | 2017-10-01, Pages 227-234
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.envint.2017.07.019
• Subjects: Environmental Sciences; Health Sciences, Obstetrics and Gynecology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Environmental Sciences; Environmental Sciences & Ecology; Nicotine; Cotinine; Tobacco smoke; Pregnancy; Prenatal exposure; Metabolomics; Amniotic fluid; ENVIRONMENTAL TOBACCO-SMOKE; PERINATAL OUTCOMES; MASS-SPECTROMETRY; COTININE LEVELS; PREGNANT-WOMEN; BIRTH-WEIGHT; EXPOSOME; IMPACT

Abstract

Decades of public health research have documented that smoking in pregnancy poses significant health risks to both mother and child. More recent studies have shown that even passive maternal exposure to secondhand smoke associates with negative birth outcomes. However, the mechanisms linking exposure to outcomes have remained obscure. As a first step toward defining the metabolic consequence of low-level nicotine exposure on fetal development, we conducted an untargeted metabolomic analysis of 81 paired samples of maternal serum and amniotic fluid collected from karyotypically normal pregnancies in the second trimester. By comparing the m/z and retention times of our mass spectral features with confirmed standards, we identified cotinine, a nicotine derivative, and used the calculated cotinine concentrations to classify our maternal serum samples into exposure groups using previously defined cut-offs. We found that cotinine levels consistent with low-level maternal exposure to nicotine associated with distinct metabolic perturbations, particularly in amniotic fluid. In fact, the metabolic effects in amniotic fluid of ostensibly low-level exposed mothers showed greater overlap with perturbations previously observed in the sera of adult smokers than did the perturbations observed in the corresponding maternal sera. Dysregulated fetal pathways included aspartate and asparagine metabolism, pyrimidine metabolism, and metabolism of other amino acids. We also observed a strong negative association between level of maternal serum cotinine and acetylated polyamines in the amniotic fluid. Combined, these results confirm that low-level maternal nicotine exposure, indicated by a maternal serum cotinine level of 2–10 ng/mL, is associated with striking metabolic consequences in the fetal compartment, and that the affected pathways overlap those perturbed in the sera of adult smokers.