Variations in cotinine levels in smokers during and after pregnancy

doi:10.1016/S0002-9378(98)70440-5

American Journal of Obstetrics and Gynecology

Volume 178, Issue 3, March 1998, Pages 568-571

https://doi.org/10.1016/S0002-9378(98)70440-5 Get rights and content

Abstract

Objective: To compare the antenatal and postnatal cotinine levels in smoking women after controlling for the differences in smoking practices. Study Design: A paired comparison of two measurements of cotinine concentration was conducted in 40 smoking women voluntarily recruited in a prenatal education program held in La Fe Hospital, Valencia, Spain, during 1990 and 1991. Cotinine concentration was assayed by gas chromatography in samples of saliva obtained during and after pregnancy. The Wilcoxon matched-pairs test and multiple linear regression analysis were used. Results: The cotinine per cigarette ratio during pregnancy (median 3.53 ng/ml per cigarette) was significantly lower than the ratio in the postnatal testing (median 9.87 ng/ml per cigarette). This difference persisted after allowing for differences in reported cigarette consumption. Conclusion: These findings suggest that the available equivalencies between cotinine level and nicotine intake obtained from adult nonpregnant populations cannot be directly applied during pregnancy. (Am J Obstet Gynecol 1998;178:568-71.)

Section snippets

Material and methods

A comparative study of pairs of salivary cotinine concentrations from female smokers was conducted, the first obtained in the third trimester of pregnancy (range 24 to 38 weeks of gestation) and the second from 1 month after delivery (range 34 to 138 days). The women were voluntarily recruited in the prenatal education program held in La Fe Maternity Hospital, Valencia, Spain, between February 1990 and November 1991. The criterion for inclusion was a self-report of being currently a smoker of

Results

Of the 45 paired observations obtained, two were withdrawn because of incomplete data on exposure assessment and three because women were <24 weeks' gestation at the time of the first interview. Antenatal cotinine values were significantly lower than postnatal values (mean difference = –158.7 ng/ml; Wilcoxon test p < 0.001). The number of cigarettes smoked also varied because women reported smoking less in the days preceding the antenatal than the postnatal test (mean difference = –7.2

Comment

We found marked differences between antenatal and postnatal cotinine levels in smoking mothers that persisted after allowing for differences in tobacco consumption. These differences could in principle reflect measurement error or might be due to other factors than those included in the analysis. Although it is plausible that women might have underreported their cigarette consumption during pregnancy, because of perceptions of social disapproval, this would result in a higher cotinine

Acknowledgements

We thank Dr. Gordon A. Ellard for his enlightening comments on this manuscript.

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Smokers are exposed to the harmful and potentially harmful constituents generated by cigarette combustion. Discriminating the independent effects of nicotine from those of other chemicals present in cigarette smoke is difficult. Nevertheless, investigating circumstances in which individuals are exposed to nicotine without combustion—as with the use of smokeless tobacco products, nicotine replacement therapies, and, to some extent, e-vapor products—provides evidence on the possible health effects of nicotine. Where epidemiological data are lacking, nonclinical studies may provide mechanistic insights into nicotine's ability to modulate molecular and cellular processes. This chapter summarizes the current knowledge about the effects of nicotine exposure on the circulatory system, lungs, female and male reproductive organs, and developing fetus and critically reviews nicotine's potential involvement in cardiovascular diseases, lung cancer, and developmental defects. This chapter also highlights key gaps in our current understanding of the biological effects of nicotine.
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Citation Excerpt :
Nonsmokers exposed to typical levels of SHS had less serum cotinine levels than pointed cutoff. However, it has been found that the ratio of cotinine per cigarette smoked during pregnancy was much lower than the ratio after pregnancy (3.53 ng/mL vs. 9.87 ng/mL of salivary per cigarette) (Rebagliato et al., 1998). This suggest, that the available cutoff value for adult pregnant populations may be not applicable to the general population.
Many women who smoke tobacco continue to do so during lactation, and many non-smoking women are exposed to second-hand tobacco smoke (SHS) during the period that she wishes to breastfeed. There are reports documenting the adverse effects of maternal smoking during lactation on their infant's health; however, the pathophysiological mechanisms underlying these effects are incompletely understood.
Our study purpose was to examine the influence of tobacco smoke on biochemical markers reflecting the intensity of oxidative stress using concentration of total protein (TP), trolox equivalent antioxidant capacity (TEAC), S-nitrosothiols (RSNO), nitric oxide (NO), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), glutathione S-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) in the plasma, colostrum, and mature milk of women who smoke, those only exposed to SHS, and non-smokers.
Questionnaire data on the tobacco smoking status were verified based on the determination of cotinine by high performance liquid chromatography with diode array detector (HPLC-DAD). Relevant markers of oxidative stress and biochemical parameters were determined using spectrophotometric methods.
We found that tobacco smoking during lactation increases oxidative stress in the mother's plasma, colostrum, and mature milk, and lesser so in those exposed to SHS. Tobacco smoke significantly increase TBARS and decrease TEAC in colostrum and mature milk. In response to ROS generated by tobacco smoke increase the activity of antioxidant enzymes (SOD, GST, GPx and CAT), p < 0.05.
Such exposure to tobacco smoke influences the antioxidant barrier of human colostrum and mature milk that can adversely affect their infant's health. Greater public health awareness of the adverse effects of tobacco smoking during lactation on breast milk quality and its protective effects is urgently needed.
Overview of cotinine cutoff values for smoking status classification
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Differential correlations between maternal hair levels of tobacco and alcohol with fetal growth restriction clinical subtypes
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Citation Excerpt :
Rebagliato et al. found marked differences between antenatal and postnatal cotinine concentrations in smokers after controlling for tobacco consumption. The salivary cotinine levels during pregnancy were significantly decreased compared with postnatal levels, which suggest an altered metabolism and distribution of nicotine and cotinine during pregnancy, with higher clearance rates of cotinine compared with non-pregnant women (Rebagliato et al., 1998). Therefore, we have reason to believe that during pregnancy, cotinine may not be the optimal marker used for smoking.
Maternal exposure to tobacco and alcohol is a known cause, among others, for fetal growth restriction (FGR). Clinically, FGR can be subclassified into two forms: intrauterine growth restriction (IUGR) and small for gestational age (SGA), based on the severity of the growth retardation, and abnormal uterine artery Doppler or cerebro-placental ratio. This study aimed at investigating any differential correlation between maternal exposures to these toxins with the two clinical forms of FGR. Therefore, a case-control study was conducted in Barcelona, Spain. Sixty-four FGR subjects, who were further subclassified into IUGR (n = 36) and SGA (n = 28), and 89 subjects matched appropriate-for-gestational age (AGA), were included. The levels of nicotine (NIC) and ethyl glucuronide (EtG), biomarkers of tobacco and alcohol exposure, respectively, were assessed in the maternal hair in the third trimester. Our analysis showed 65% of the pregnant women consumed alcohol, 25% smoked, and 19% did both. The odds ratios (ORs) of IUGR were 21 times versus 14 times for being SGA with maternal heavy smoking, while with alcohol consumption the ORs for IUGR were 22 times versus 37 times for the SGA group. The differential correlations between these toxins with the two subtypes of FGR suggest different mechanisms influencing fetal weight. Our alarming data of alcohol consumption during pregnancy should be considered for further confirmation among Spanish women.
Factors associated with second-hand smoke exposure in non-smoking pregnant women in Spain: Self-reported exposure and urinary cotinine levels
2014, Science of the Total Environment
Citation Excerpt :
UC levels were higher on Monday than other days of the week, reflecting exposure during the previous day, namely Sunday. Given the short half-life of UC in pregnancy (Dempsey et al., 2002; Rebagliato et al., 1998) and that most of the samples were collected in the morning, it is reasonable to conclude that the concentration of UC reflects the SHS exposure during the previous day. One limitation of this study is that no samples were taken on Saturday or Sunday mornings, readings that would provide us with information regarding exposure on Friday and Saturday, which is likely to be higher than on other days.
The aim of this study was to evaluate the main sources of and sociodemographic factors associated with second-hand smoke (SHS) exposure, assessed both by questionnaire and by urinary cotinine (UC) levels, in non-smoking pregnant women. We conducted a cross-sectional study in pregnant women from 4 different regions in Spain. A total of 1783 non-smoking pregnant women completed a questionnaire about their previous smoking habit and SHS exposure in their 3rd trimester of pregnancy and provided a urine sample for measuring UC levels. We used logistic regression models to assess the relationship between several sociodemographic variables and some potential sources of SHS exposure. In addition, we analysed the association of several sociodemographic variables and the SHS exposure according to UC levels, using Tobit regression analysis. More than half of women (55.5%) were exposed to SHS in their 3rd trimester of pregnancy. The following variables were associated with SHS exposure: having smoked previously, low educational level, and being primiparous. Data collection after the first law banning smoking in public places was associated with lower risk of SHS exposure in restaurants and at work. UC levels were higher among women exposed to more than one source. Having a partner who smoked at home was the source of SHS with the greatest impact on UC levels, followed by having a partner who smoked but not at home, other people smoking in the household, being exposed during leisure time, at work and at restaurants. The most important source of SHS exposure was exposure at home. Prevention of SHS exposure should be addressed not only with pregnant women but also with their families.
Using expired air carbon monoxide to determine smoking status during pregnancy: Preliminary identification of an appropriately sensitive and specific cut-point
2013, Addictive Behaviors
Citation Excerpt :
In addition to the factors of cost and inconvenience, and possible influence of environmental tobacco smoke (ETS), establishment of appropriately sensitive and specific cut-off points is far from universal (Benowitz, 1999), especially for pregnant women due to differences in metabolism. This has led to conclusions that established cotinine cut-off levels used to determine smoking status do not apply during pregnancy (Dempsey, Jacob, & Benowitz, 2002; Rebagliato et al., 1998). Carboxyhaemoglobin (COHb), a byproduct of inhaled cigarette smoke, is another biomarker of smoking.
Measurement of carbon monoxide in expired air samples (ECO) is a non-invasive, cost-effective biochemical marker for smoking. Cut points of 6 ppm–10 ppm have been established, though appropriate cut-points for pregnant woman have been debated due to metabolic changes. This study assessed whether an ECO cut-point identifying at least 90% of pregnant smokers, and misidentifying fewer than 10% of non-smokers, could be established.
Pregnant women (N = 167) completed a validated self-report smoking assessment, a urine drug screen for cotinine (UDS), and provided an expired air sample twice during pregnancy.
Half of women reported non-smoking status early (51%) and late (53%) in pregnancy, confirmed by UDS. Using a traditional 8 ppm + cut-point for the early pregnancy reading, only 1% of non-smokers were incorrectly identified as smokers, but only 56% of all smokers, and 67% who smoked 5 + cigarettes in the previous 24 h, were identified. However, at 4 ppm +, only 8% of non-smokers were misclassified as smokers, and 90% of all smokers and 96% who smoked 5 + cigarettes in the previous 24 h were identified. False positives were explained by heavy second hand smoke exposure and marijuana use. Results were similar for late pregnancy ECO, with ROC analysis revealing an area under the curve of .95 for early pregnancy, and .94 for late pregnancy readings.
A lower 4 ppm ECO cut-point may be necessary to identify pregnant smokers using expired air samples, and this cut-point appears valid throughout pregnancy. Work is ongoing to validate findings in larger samples, but it appears if an appropriate cut-point is used, ECO is a valid method for determining smoking status in pregnancy.

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^☆: From the Departamento de Salud Pública, Facultad de Medicina, Universidad de Alicante,^a the Department of Epidemiology and Public Health, Ninewells Hospital and Medical School,^b the Imperial Cancer Research Fund, Health Behaviour Unit,^c and the Instituto Valenciano de Estudios en Salud Pública (IVESP).^d

^☆☆: Supported by grant 89/2342 of the Fondo de Investigaciones Sanitarias (FIS) of the Spanish Ministry of Health.

^★: Reprint requests: Marisa Rebagliato, PhD, Departamento de Salud Pública, Facultad de Medicina, Campus San Juan, Ap. Correo 374, 03080-Alicante, Spain.

^★★: 6/1/85908

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Variations in cotinine levels in smokers during and after pregnancy☆,☆☆,★,★★

Abstract

Section snippets

Material and methods

Results

Comment

Acknowledgements

The use of biologic fluid samples in assessing tobacco smoke consumption

Application of biochemical intake markers to passive smoking measurement and risk estimation

Mutat Res

Steady-state concentration of cotinine as a measure of nicotine-intake by smokers

Eur J Clin Pharmacol

Tobacco sidestream smoke: uptake by nonsmokers

Prev Med

Absorption of nicotine and carbon monoxide from passive smoking under natural conditions of exposure

Thorax

Intravenous nicotine simulation of passive smoking to estimate dosage to exposed non-smokers

Br J Addict

Assessment of exposure to environmental tobacco smoke in nonsmoking pregnant women in different environments of daily living

Am J Epidemiol

Cigarette consumption and serum cotinine in relation to birth weight

Br J Obstet Gynecol

Second-trimester serum cotinine levels in nonsmokers in relation to birth weight

Am J Obstet Gynecol

Effects of short-term use of nicotine gum in pregnant smokers

Clin Pharmacol Ther

Use of serum cotinine to assess the accuracy of self-reported nonsmoking

BMJ