Document Detail

Cotinine in human placenta predicts induction of gene expression in fetal tissues.
MedLine Citation:
PMID:  23209192     Owner:  NLM     Status:  MEDLINE    
Maternal cigarette smoking during pregnancy is associated with increased risk of perinatal morbidity and mortality. However, the mechanisms underlying adverse birth outcomes following prenatal exposure to cigarette smoke remain unknown due, in part, to the absence or unreliability of information regarding maternal cigarette smoke exposure during pregnancy. Our goal was to determine if placental cotinine could be a reliable biomarker of fetal cigarette smoke exposure during pregnancy. Cotinine levels were determined in placentas from 47 women who reported smoking during pregnancy and from 10 women who denied cigarette smoke exposure. Cotinine levels were significantly higher in placentas from women reporting cigarette smoking (median = 27.2 ng/g) versus women who reported no smoke exposure (2.3 ng/g, P < 0.001). Receiver operating characteristic curve analysis identified an optimal cut point of 7.5 ng/g (sensitivity = 78.7%, specificity = 100%) to classify placenta samples from mothers who smoked versus those from mothers who did not. Among 415 placentas for which maternal cigarette smoking status was unavailable, 167 had cotinine levels > 7.5 ng/g and would be considered positive for cigarette smoke exposure. Data from quantitative reverse-transcription polymerase chain reaction analyses demonstrated that in utero cigarette smoke exposure predicted by cotinine in placenta is associated with changes in the expression of xenobiotic-metabolizing enzymes in fetal tissues. CYP1A1 mRNA in fetal lung and liver tissue and CYP1B1 mRNA in fetal lung tissue were significantly induced when cotinine was detected in placenta. These findings indicate that cotinine in placenta is a reliable biomarker for fetal exposure and response to maternal cigarette smoking during pregnancy.
Carrie A Vyhlidal; Amanda K Riffel; Kathleen J Haley; Sunita Sharma; Hongying Dai; Kelan G Tantisira; Scott T Weiss; J Steven Leeder
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-12-03
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  41     ISSN:  1521-009X     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-18     Completed Date:  2013-07-12     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  United States    
Other Details:
Languages:  eng     Pagination:  305-11     Citation Subset:  IM    
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MeSH Terms
Aryl Hydrocarbon Hydroxylases / biosynthesis,  genetics
Biological Markers / metabolism
Case-Control Studies
Cotinine / blood,  metabolism*
Cytochrome P-450 CYP1A1 / biosynthesis,  genetics
Enzyme Induction
Fetus / drug effects*,  metabolism
Gene Expression Regulation, Developmental / drug effects*
Gestational Age
Liver / drug effects,  embryology,  enzymology
Lung / drug effects,  embryology,  enzymology
Maternal Behavior*
Mice, Inbred C57BL
Models, Animal
Placenta / drug effects*,  metabolism
Predictive Value of Tests
RNA, Messenger / biosynthesis
ROC Curve
Reverse Transcriptase Polymerase Chain Reaction
Sensitivity and Specificity
Smoking / adverse effects*,  metabolism
Grant Support
Reg. No./Substance:
0/Biological Markers; 0/RNA, Messenger; EC Hydrocarbon Hydroxylases; EC protein, human; EC P-450 CYP1A1; EC P-450 CYP1B1; K5161X06LL/Cotinine
Comment In:
Drug Metab Dispos. 2013 Feb;41(2):256-62   [PMID:  23328895 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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