Questionnaire and hair measurement of exposure to tobacco smoke

To assess the relation between nicotine and cotinine levels in hair and reported exposure to environmental tobacco smoke (ETS), hair samples from 112 children (aged 3 months to 10 years) and 76 of their mothers were analyzed and information on the smoking habits of household adults in the preceding 6 months recorded. It was found that the levels of nicotine in children's hair were related to the number of smokers in the house, and increased with the total number of cigarettes smoked by all household adults (P<0.0001). In a multiple regression analysis, mother's smoking was much more a contributor to children's nicotine levels than smoking by the father or other household adults. Cotinine levels were less strongly associated with reported ETS exposure than nicotine. There was a strong correlation between nicotine hair levels in children and mothers (r(s)=0.7, P<0.0001). However, nicotine levels in the hair of active smokers were not correlated with the reported number of cigarettes they smoked per day. In this population, there was a consistent relation between exposure to ETS (assessed by questionnaire) and dose (as measured by nicotine in hair). We conclude that hair nicotine levels rather than hair cotinine levels provide an informative and objective measure of ETS exposure. The number of cigarettes smoked by active smokers may not be an accurate measure of the total nicotine levels in their bodies.     

Is the hair nicotine level a more accurate biomarker of environmental tobacco smoke exposure than urine cotinine?

STUDY OBJECTIVE: The aim of this study was to compare the two biomarkers of exposure to environmental tobacco smoke (ETS); urine cotinine and hair nicotine, using questionnaires as the standard. DESIGN: A cross sectional study of children consecutively admitted to hospital for lower respiratory illnesses during the period of the study. SETTINGS: Three regional hospitals in the larger Wellington area, New Zealand. PARTICIPANTS: Children aged 3-27 months and admitted to the above hospitals during August 1997 to October 1998. A total of 322 children provided 297 hair samples and 158 urine samples. MAIN RESULTS: Hair nicotine levels were better able to discriminate the groups of children according to their household's smoking habits at home (no smokers, smoke only outside the home, smoke inside the house) than urine cotinine (Kruskall-Wallis; chi(2)=142.14, and chi(2)=49.5, respectively (p<0.0001)). Furthermore, hair nicotine levels were more strongly correlated with number of smokers in the house, and the number of cigarettes smoked by parents and other members of the child's households. Hair nicotine was better related to the questionnaire variables of smoking in a multivariate regression model (r(2)=0.55) than urine cotinine (r(2)=0.31). CONCLUSIONS: In this group of young children, hair nicotine was a more precise biomarker of exposure to ETS than urine cotinine levels, using questionnaire reports as the reference. Both biomarkers indicate that smoking outside the house limits ETS exposure of children but does not eliminate it.     

Neonatal hair nicotine levels and fetal exposure to paternal smoking at home

Exposure to environmental tobacco smoke (ETS) is a major risk to human health, and the home is the greatest single source of ETS for children. The authors investigated fetal exposure to paternal smoking at home during pregnancy. Korean families were included as trios of fathers, mothers, and neonates identified in 2005-2007. Sixty-three trios were finally enrolled in this study after exclusion of those in which the mother was a smoker or was regularly exposed to ETS at places other than the home. Nicotine and cotinine concentrations in hair were measured by using liquid chromatography-tandem mass spectrometry to determine long-term exposure to ETS. The difference between neonatal nicotine concentrations in the smoker and nonsmoker groups was not statistically significant. However, in the indoor-smoker group, neonatal nicotine concentrations were significantly higher than in the outdoor and nonsmoker groups (P < 0.05). Furthermore, neonatal nicotine concentrations in the outdoor-smoker group were not different from those in the nonsmoker group. These findings indicate that paternal smoking inside the home leads to significant fetal and maternal exposure to ETS and may subsequently affect fetal health. Conversely, findings show that paternal smoking outside the home prevents the mother and her fetus from being exposed to ETS.     

Racial differences in exposure to environmental tobacco smoke among children

Exposure to environmental tobacco smoke (ETS) is a major cause of morbidity and mortality among U.S. children. Despite African-American children's having a lower reported exposure to tobacco compared to whites, they suffer disproportionately from tobacco-related illnesses and have higher levels of serum cotinine than white children. The goal of this study was to test whether African-American children have higher levels of serum and hair cotinine, after accounting for ETS exposure and various housing characteristics. We investigated the level of cotinine in both hair and serum in a sample of 222 children with asthma. Using a previously validated survey for adult smokers, we assessed each child's exposure to ETS. We collected detailed information on the primary residence, including home volume, ventilation, and overall home configuration. Despite a lower reported ETS exposure, African-American children had higher mean levels of serum cotinine (1.41 ng/mL vs. 0.97 ng/mL; p = 0.03) and hair cotinine (0.25 ng/mg vs. 0.07 ng/mg; p < 0.001) compared with white children. After adjusting for ETS exposure, housing size, and other demographic characteristics, serum and hair cotinine levels remained significantly higher in African-American children (ss = 0.34, p = 0.03) than in white children (ss = 1.06, p < 0.001). Housing volume was significantly associated with both serum and hair cotinine but did not fully explain the race difference. Our results demonstrate that, despite a lower reported exposure to ETS, African-American children with asthma had significantly higher levels of both serum and hair cotinine than did white children. Identifying causes and consequences of increased cotinine may help explain the striking differences in tobacco-related illnesses.     

Importance of exposure to gaseous and particulate phase components of tobacco smoke in active and passive smokers

Summary The uptake of tobacco smoke constituents from gaseous and particulate phases of mainstream smoke (MS), inhaled by smokers, and of environmental tobacco smoke (ETS), breathed in by non-smokers, was investigated in two experimental studies. Tobacco smoke uptake was quantified by measuring carboxyhemoglobin (COHb), nicotine and cotinine in plasma and urine and the data obtained were correlated with urinary excretion of thioethers and of mutagenic activity. An increase in all biochemical parameters was observed in smokers inhaling the complete MS of 24 cigarettes during 8 h, whereas only an increase in COHb and, to a minor degree, in urinary thioethers was found after smoking the gas phase of MS under similar conditions. Exposure of non-smokers to the gaseous phase of ETS or to whole ETS at similar high concentrations for 8 h led to identical increases in COM, plasma nicotine and cotinine as well as urinary excretion of nicotine and thioethers which were much lower than in smokers. Urinary mutagenicity was not found to be elevated under either ETS exposure condition. As shown by our results, the biomarkers most frequently used for uptake of tobacco smoke (nicotine and cotinine) indicate on the one hand the exposure to particulate phase constituents in smoking but on the other hand the exposure to gaseous phase constituents in passive smoking. Particle exposure during passive smoking seems to be low and a biomarker which indicates ETS particle exposure is as yet not available. These findings emphasize that risk extrapolations from active smoking to passive smoking which are based on cigarette equivalents or the use of one biomarker (e.g. cotinine) might be misleading.     

Restrictive workplace smoking policies: impact on nonsmokers' tobacco exposure.

The health consequences of exposure to environmental tobacco smoke (ETS) are well documented. Although nonsmokers are generally aware of the health risks of ETS exposure, the majority of nonsmokers are regularly exposed. The most common source of exposure is the workplace. Restrictive workplace smoking policies are being used as a primary means of reducing ETS exposure. However, few studies have focused on the relation between workplace policy and ETS exposure. We performed two studies which examined the relationship between smoking policy, self-reported ETS exposure, and salivary cotinine concentrations. Study I, a pilot study, focused on a workplace-based sample of 106 volunteers; Study 2 examined exposure among 881 nonsmokers in workplace settings. In both studies, more restrictive workplace smoking policies were associated with a lower proportion of nonsmoking volunteers with detectable salivary cotinine. In Study 2, the larger study, the only other variable found to be significantly related to cotinine detection was the presence of smokers in the home. These results suggest that restrictive workplace smoking policies may reduce employees' overall ETS exposure.     

Comparison of parental reports of smoking and residential air nicotine concentrations in children

Background

Using questionnaires to assess children''s residential exposure to environmental tobacco smoke (ETS) may result in misclassification from recall and response bias. Questionnaire data have frequently been validated against urinary cotinine measurements, but rarely against actual measurements of residential air nicotine.

Objective

To compare questionnaire reported smoking with air nicotine concentrations in a large population of children and with urinary cotinine levels in a subpopulation; and to assess the potential impact of the symptom status of the children on the agreement between different measures of exposure.

Methods

The authors assessed residential exposure to ETS in 347 German, 335 Dutch, and 354 Swedish preschool and schoolchildren by questionnaire and air nicotine measurements, and in a subset of 307 German children by urinary cotinine measurements. They then compared the different measures of ETS exposure.

Results

In all countries, air nicotine concentrations increased with increasing questionnaire reported smoking in a dose‐response fashion. Specificity and negative predictive values of questionnaire reports for nicotine concentrations were excellent. Sensitivity and positive predictive values were moderate to good. Excluding occasional smokers, the overall percentage of homes misclassified was 6.9%, 6.7%, and 5.1% in Germany, the Netherlands, and Sweden, respectively. Similar results were found for the agreement of urinary cotinine concentrations with questionnaire reports and air nicotine levels. There was no indication of underreporting by parents of symptomatic children.

Conclusion

Despite some misclassification, questionnaire reports are an inexpensive and valid estimate of residential ETS exposure among preschool and school children.     

Assessment of environmental tobacco smoke exposure in children with asthmatic symptoms by questionnaire and cotinine concentrations in plasma, saliva, and urine

To validate a detailed questionnaire for assessment of environmental tobacco smoke (ETS) exposure by the biomarker cotinine in various media, a population-based study in the urban area of Malm?, Sweden was performed in children aged 8-13 years with and without asthmatic symptoms. There were strong correlations between urinary and saliva cotinine concentrations and also, though to a lesser extent, between these media and plasma. Even a detailed questionnaire gave only a rough picture of the ETS exposure, as indicated by the biomarkers. In a multivariate model, the most significant questionnaire-derived predictor of the cotinine levels was the maternal smoking habits; other questionnaire variables gave only a minimal explained variance. Children with a history of asthmatic symptoms had statistically significantly lower median cotinine levels in urine and saliva compared to referent children, most likely because of the antismoking information to their parents. This should be considered in epidemiological studies of ETS risks.     

Relationship between environmental tobacco smoke and urinary cotinine levels in passive smokers at their residence

Studies of the health effects of environmental tobacco smoke (ETS) using measured air concentrations are subject to bias. Cotinine, a nicotine metabolite detected in urine, has been recommended as a quantitative measure of nicotine intake and thus as a marker for ETS exposure in humans. The aim of this study was to correlate home indoor ETS levels with passive smokers' urinary cotinine levels. The urinary cotinine concentrations of 57 non-smoking women who spend >19 h a day at home and the nicotine levels in their living room air were measured over a period of 24 h. Nicotine and urinary cotinine levels were analyzed using GC/MS and HPLC/UV, respectively. In addition, information was collected regarding the smoking habits of the subjects' families. A significant correlation was found between the nicotine levels in indoor air and the urinary cotinine to creatinine ratio of the passive smokers. The smoking habits of the subjects' family members were also correlated to the urinary cotinine levels of the passive smokers.     

Validation of a five-question survey to assess a child's exposure to environmental tobacco smoke

PURPOSE: To study the potentially adverse health effects of environmental tobacco smoke (ETS) exposure in young children, a short five-question survey was developed to identify routine exposure to ETS in a large epidemiological study. METHODS: The survey is administered to parents of a healthy cohort of children starting at age 3 months. To validate the survey, urinary cotinine levels were measured on 50 children from this cohort who were selected based on ETS exposure as reported in the survey: 24 with no exposure and 26 with exposure. Cotinine was adjusted for creatinine. RESULTS: Overall, children with some form of reported ETS exposure had urinary cotinine levels 7.5 times higher than those who were not exposed. Analysis of variance shows that mean levels of log transformed cotinine in children whose parent(s) smoke in the home, parent(s) who smoke but not in the home, and non-smoking parents are 137.13, 75.60, and 43.28 respectively (p = 0.0009), indicating decreasing levels of cotinine as reported exposure decreases. Using a cut-point of 30 ng/mg of cotinine to differentiate unexposed and exposed to ETS, we found 80% agreement with our survey. A Spearman's ranked correlation coefficient of 0.62 indicates a direct relationship between cotinine and an ETS exposure intensity score (p < 0.0001).CONCLUSIONS: These results suggest that the 5-question survey reflects the child's exposure to passive smoke and that the survey is sensitive to varying levels of exposure.     

Personal exposure to environmental tobacco smoke: salivary cotinine, airborne nicotine, and nonsmoker misclassification.

A large study was conducted to assess exposure to environmental tobacco smoke (ETS) in a geographically dispersed study population using personal breathing zone air sampling and salivary cotinine levels. Approximately 100 self-reported nonsmoking subjects in each of 16 metropolitan areas were recruited for this investigation. Cumulative distributions of salivary cotinine levels for subjects in smoking and nonsmoking homes and workplaces exhibited a general trend of decreasing salivary cotinine levels with decreasing time spent in smoking environments. Median salivary cotinine levels for the four experimental cells in the study (product of smoking and nonsmoking home and workplaces) were comparable to those reported for a large national study of serum levels of cotinine (Third National Health and Nutrition Examination Survey, NHANES III), when the latter was corrected for expected differences between serum and saliva concentrations. However, the most highly exposed group in this study had a median salivary cotinine concentration approximately a factor of 2 greater than that of the comparable group in the NHANES III study. Misclassification rates, both simple (for self-reported nonsmokers) and complex (self-reported lifetime never smokers), were near the median of those reported for other studies. Estimated misclassification rates for self-reported lifetime never-smoking females are sufficiently high (2.95% using a discrimination level of 106 ng/ml) that, if used in the Environmental Protection Agency (EPA) risk assessment related to ETS and lung cancer, would place the lower 90% confidence interval (CI) for relative risk at nearly 1.00, i.e., no statistically significant increased risk. For the 263 most highly exposed subjects in the study whose self-reported nonsmoking status was accurate, the correlation between airborne exposure to nicotine and average salivary cotinine is so small, on an individual basis, that it makes the relationship useless for estimating exposure on a quantitative basis. When subjects are grouped according to likely categories of nicotine exposure, correlation between group median airborne nicotine exposure and salivary cotinine level increases dramatically. The comparison improves for the most highly exposed subjects, suggesting that such quantitative comparisons are useful for only those subjects who are exposed to the higher levels of ETS. However, airborne nicotine exposure for most of the subjects does not account for estimated systemic levels of nicotine, based on salivary cotinine levels.     

Studies on a simultaneous analytical method of urinary nicotine and its metabolites, and their half-lives in urine

The objectives of this research were to improve and standardize a relatively easy, highly sensitive and highly accurate method of measuring nicotine, cotinine and trans-3'-hydroxycotinine in the urine of non-smokers exposed to environmental tobacco smoke (ETS) and to clarify the reliability of this method. Blinded studies using this analytical method were conducted in two universities. Standard solutions of nicotine, cotinine and trans-3'-hydroxycotinine were prepared at one university, divided in two parts and sent to another two universities for analyses by gas chromatography-mass spectrometry (GC/MS) without revealing the concentrations. It was found that the assay lower limit was at a level that could be used in passive smoking surveys and good results were obtained in crosschecks of samples of unknown concentration between the two universities. Since this method was considered to be useful for analyzing these urinary substances, ETS exposure experiments were performed in three universities using urinary nicotine, cotinine and trans-3'-hydroxycotinine as specific biomarkers of the urine. Non-smokers were exposed to ETS in an exposure room in each university. It was found that the nicotine concentrations in the urine of the subjects exposed to ETS reached a peak at about 2 hours after the end of exposure, which was somewhat later than that in active smokers. Because cotinine and trans-3'-hydroxycotinine in the urine are metabolites of nicotine, it was evident that the quantities were lower and the increasing rates were also less than that of nicotine. When the deceases in nicotine/ creatinine, cotinine/creatinine and trans-3'-hydroxycotinine/creatinine ratios in the urine were calculated using theoretical curves, the half-life times were calculated to be 13.9, 20.0 and 63.0 hours, respectively.     

Children's exposure to environmental tobacco smoke: using diverse exposure metrics to document ethnic/racial differences

Four metrics were used to assess exposure to environmental tobacco smoke (ETS) for a probability sample (n = 152) of elementary school-age children in two economically disadvantaged neighborhoods: a) caregiver responses to a baseline questionnaire (BQ) about smoking status and behavior; b) 48-hr time-activity (T-A) data on location and time spent by children in the presence of tobacco smoke; c) total urinary cotinine as a marker for nicotine uptake; and d) urinary NNAL [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol] + NNAL-Gluc [4-(methylnitrosamino)-1- (3-pyridyl)-1-(O-beta-D-glucopyranuronosyl)butane] as a marker for uptake of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Consistent differences in ETS exposure by ethnicity and race were observed. Although data were insufficient to determine differences for NNAL + NNAL-Gluc, BQ responses, T-A data, and cotinine levels all indicated that average ETS exposure was highest for African-American children, moderately high for those designated "other" (white, Southeast Asian, Native American), moderately low for Hispanic children, and lowest for Somali immigrant children. For example, in February 2000, mean cotinine levels were 14.1 ng/mL for African Americans, 12.2 ng/mL for other, 4.8 ng/mL for Hispanics, and 4.4 ng/mL for Somalis. The BQ and T-A data together were reasonably good predictors of total cotinine levels (adjusted r2 = 0.69), and based on limited data, measured total cotinine values were a relatively good predictor of NNAL + NNAL-Gluc (adjusted r2 = 0.73). The results suggest that when children are exposed to ETS primarily in their homes, questionnaires and T-A logs might be effective screening tools for identifying those likely to experience higher uptake of nicotine.     

A personal monitoring study to assess workplace exposure to environmental tobacco smoke.

We enrolled 15 nonsmoking volunteers to evaluate the feasibility of measuring personal exposure to environmental tobacco smoke (ETS) at work and to characterize workplace exposures. During one workshift, we obtained questionnaires on exposure, saliva and urine for cotinine, and personal air samples for respirable particles and nicotine. The levels of cotinine, respirable particles, and nicotine varied widely with self-reports of exposure to ETS, but on average increased with increasing exposure.     

Serum cotinine as a marker of environmental tobacco smoke exposure in epidemiological studies: the experience of the MATISS project

To describe serum cotinine levels in a rural Italian population and to examine its usefulness as an epidemiologic biomarker of nicotine exposure, cross-sectional data collected in 1993 for the MATISS Project (2098 men and 1352 women, aged 20–79 years) were used. The study population consisted of 977 current smokers, 882 nonsmokers reporting exposure to environmental tobacco smoke (ETS) and 1520 nonsmokers reporting no ETS exposure. Mean values of serum cotinine measured by radioimmunoassay for never smokers, ex-smokers and current smokers (including four categories of cigarette consumption), and for categories of ETS exposure in all nonsmokers were calculated. In univariate analysis, there was a positive association between self-reported nicotine exposure and serum cotinine levels in all groups. Using self-reported status as truth, sensitivity and specificity for various cotinine cutoff points were estimated to distinguish nonsmokers from smokers. The value of 15 ng/mL represented the best combined levels of sensitivity (95%) and specificity (96%). Using this cutoff point, the overall misclassification rate for self-reported nonsmokers was 2.1% and about two times greater for the more vs. the less educated. In multivariate analysis, reported ETS exposure among nonsmokers was significantly associated with serum cotinine even after adjusting for age, socio-demographic and behavioural factors, though the strength of the association was not strong. In conclusion, serum cotinine represents a reliable epidemiological marker of nicotine intake and may be helpful when studying ETS exposure. Improved information collection is needed to reduce misclassification among nonsmokers and enhance our understanding of the relationship between ETS and cotinine measures.     

Exposure to environmental tobacco smoke in pregnant women: the association between self-report and serum cotinine

The risk of delivering a low-birth-weight infant as the result of exposing a nonsmoking pregnant woman to environmental tobacco smoke (ETS) is not well defined. The method of ascertaining ETS exposure during pregnancy may explain the lack of consistent study findings. In a large sample of pregnant women, we compared distributions between two methods of ETS exposure: self-report and cotinine, a nicotine metabolite, from serum. At livery, subjects were asked about duration and location of exposure to ETS during their second trimester. A single cotinine measurement was assayed from serum collected at 15-19 weeks gestation (limit of detection=0.05 ng/mL). Self-reported (hours per day) ETS exposure was correlated (r=0.38) with cotinine concentration. Regression analysis revealed that while self-reported ETS was significantly associated with (log) cotinine, it did not explain a large amount of total variation. While 72% of subjects reported no exposure to ETS, almost all had measurable levels of cotinine. Studies of pregnant women based upon an hours per day ETS question have likely misclassified a sizable portion of ETS-exposed women as "unexposed." Since there is recent evidence that low levels of ETS exposure result in unfavorable pregnancy outcomes, these studies have underestimated the effect of ETS.     

Correlating atmospheric and biological markers in studies of secondhand tobacco smoke exposure and dose in children and adults

OBJECTIVE: We sought to directly compare secondhand smoke (SHS) atmospheric markers to each other and to SHS dosimetric biomarkers, permitting intercomparison of clinical and atmospheric studies. METHODS: We used atmospheric and pharmacokinetic (PK) models for the quantitative estimation of SHS exposure and dose for infants, children, and adults, based on building smoker density and air exchange rate, and from exposure duration, default PK parameters, and respiration rates. RESULTS: We estimate the SHS serum cotinine doses for the typical and most-exposed individuals in the U.S. population; predictions compare well to measurements on a national probability sample. Using default respiration rates, we estimate serum cotinine dose from SHS nicotine exposure for 40 adults exposed to SHS in an environmental chamber; predictions agreed with observations. We correlate urine cotinine and hair nicotine levels for 127 infants exposed to parental smoking, and estimate corresponding atmospheric nicotine exposure via PK modeling. CONCLUSIONS: Our "Rosetta Stone" Equations allow the SHS atmospheric markers, respirable particles, nicotine, and carbon monoxide, to be related to the SHS biomarkers, cotinine in blood, urine, and saliva and nicotine in hair, permitting intercomparison of clinical and atmospheric studies of SHS for the first time.     

Urinary nicotine and its metabolites as a biomarker of exposure to environmental tobacco smoke

The validity of urinary nicotine and its metabolites as a biomarker of exposure to environmental tobacco smoke (ETS) has been investigated. After exposure to ETS, urine samples were collected from 10 subjects for the analyses of nicotine, cotinine and 3'-hydroxycotinine. The former two chemicals were detected in the urine of all subjects, and 3'-hydroxycotinine was detected in the urine of 9 subjects out of 10, indicating these three chemicals can be used as a biomarker of ETS exposure. 3'-Hydroxycotinine was not detected in the urine of one subject, suggesting that this subject may be a poor metabolizer of nicotine. In 9 subjects with 3'-hydroxycotinine excreted, the amounts of nicotine and cotinine started to increase after exposure, reached the peak at the end of the second exposure and decreased gradually. 3'-Hydroxycotinine started to be excreted into urine from 3 hours after exposure and kept the same level until 72 hours after exposure. In the urine of 72 hours after exposure, the amount of 3'-hydroxycotinine was the highest among these three chemicals.     

Cotinine and N-(2-hydroxyethyl)valine as markers of passive exposure to tobacco smoke in children

Large segments of populations, including children, are exposed to environmental tobacco smoke (ETS), a risk factor for lung cancer and heart, circulatory and respiratory diseases. Recently, ETS was classified as a class A carcinogen by USEPA, as carcinogenic to humans by IARC (group 1) and by the National Toxicology Program of the US National Institutes of Health. Cotinine, a product of the metabolism of nicotine, is measurable in urine and, correlates strictly and directly to ETS exposure, therefore representing a well-known internal dose marker. Another marker of active tobacco smoking is the N-(2-hydroxyethyl) valine (HOEtVal) which results from the reaction between ethylene oxide (EtO) and the N-terminal valine of hemoglobin. The aim of this study was the evaluations of ETS markers, namely urinary cotinine and HOEtVal measured in blood in 100 children with ages ranging between 3 and 13 years. Experimental findings show that cotinine, as a specific internal dose marker, and HOEtVal, as a nonspecific biological effective dose marker, both depend on the passive exposure to ETS as well as on the active habit of smoking.     

Cord serum cotinine as a biomarker of fetal exposure to cigarette smoke at the end of pregnancy

This study investigated the association between biomarkers of fetal exposure to cigarette smoke at the end of pregnancy, cotinine in cord serum and in maternal and newborn urine samples, and quantitative measurement of smoking intake and exposure evaluated by maternal self-reported questionnaire. Study subjects were 429 mothers and their newborns from a hospital in Barcelona, Spain. A questionnaire including smoking habits was completed in the third trimester of pregnancy and on the day of delivery. Cotinine concentration in cord serum was associated with daily exposure to nicotine in nonsmokers and with daily nicotine intake in smokers. The geometric mean of cotinine concentration in cord serum statistically discriminated between newborns from nonexposed and exposed nonsmoking mothers, and between these two classes and smokers, and furthermore was able to differentiate levels of exposure to tobacco smoke and levels of intake stratified in tertiles. Urinary cotinine levels in newborns from nonsmoking mothers exposed to more than 4 mg nicotine daily were statistically different from levels in two other categories of exposure. Cotinine concentration in urine from newborns and from mothers did not differentiate between exposure and nonexposure to environmental tobacco smoke (ETS) in nonsmoking mothers. Cord serum cotinine appeared to be the most adequate biomarker of fetal exposure to smoking at the end of pregnancy, distinguishing not only active smoking from passive smoking, but also exposure to ETS from nonexposure.