Blood Cotinine Research Articles

Determining nicotine-related behavior changes in juvenile female rats through long-term maternal nicotine exposure.

Nicotine replacement therapy (NRT) has been developed as a drug therapy for smoking cessation and has been considered a safe alternative to smoking during pregnancy. However, the effects of long-term nicotine exposure via NRT on the fetus are still being debated. Here, we determined the effects of long-term maternal nicotine exposure in gestation and lactation on nicotine-related behavior and drug vulnerability in dams and offspring rats. To expose long-term nicotine, on gestation day 14, pregnant rats were implanted with osmotic minipumps releasing nicotine tartrate (6 mg/kg/day, subcutaneously, equivalent to 2 mg nicotine-freebase) for 28 days. The concentration of cotinine in blood was 373.0 ± 109.0 ng/ml in dams and 12.50 ± 1.19 ng/ml in offspring rats. In dams, we found no significant differences in anxiety-like behaviors and various maternal behaviors such as touching, sniffing, pup licking, laying on pups, and retrieval between saline- and nicotine-exposed groups. Adolescent offspring female rats showed no significant differences in anxiety-like behavior and forced alcohol consumption between saline- and nicotine-exposed groups. Nicotine-exposed offspring rats showed more increased nicotine aversion than saline-exposed groups, but the effect was disturbed in the forced alcohol consumption condition on the first day of the nicotine consumption test. Taken together, these results suggest that, in the last gestation and lactation period corresponding to the second and third trimester of human pregnancy, long-term maternal nicotine exposure has a minor effect on dam and female offspring health and does not involve serious pathological changes in rat offspring, despite the presence of nicotine in their blood.

The Authors Respond

To the Editor: We thank Finn Diderichsen, Ingelise Andersen, Theis Lange, and Naja Hulvej Rod for their comments on our article.1 To the extent that we understand all the points raised, we attempt to address them here. The authors indicate that they would expect the relative effect of smoking on chronic disease not to vary across levels of socioeconomic position. This runs counter to our thinking and the results from selected extant studies. As we outlined in the original article,2 in analyses of large, population-based surveys, where self-reported cigarette smoking is held constant, cotinine, a biomarker of tobacco smoke exposure, has markedly higher levels in the most disadvantaged folk relative to the affluent.3 This could be because people from lower social groups smoke their cigarettes differently, including inhaling more deeply and more frequently, and/or by choosing higher tar-containing brands. We, as others have before us, therefore hypothesized that the risk to health of smoking in disadvantaged individuals may be elevated in comparison to the more affluent – that is, smoking is most deleterious in lower social groups. While there is some support for this hypothesis – as we describe in our article – and more recently, for health behaviors in aggregate,4 this is not a universal observation; hence, our interest in further testing it is in a well-powered study. Although Diderichsen et al. claim that by computing hazard ratios in this context our work is less comparable to other findings, our reckoning is that the majority of articles in fact report this measure of risk. In the interests of being as comprehensive as possible, we also computed absolute measures of risk in our article – age-standardized mortality rates. Diderichsen and others also raise the issue of biased reporting of cigarette smoking habits, which may be most acute in disadvantaged populations and which may provide a further explanation for any effect modification of the health consequences of smoking across social groups. This is precisely why we used blood and salivary cotinine to corroborate self-reported smoking – to the best of our knowledge, the first study to do so in the context of the present research question. The use of this biomarker also has the value of capturing cigarette dose in smokers, as would the analyses we computed by self-reported numbers of cigarettes that can be found in the appendix of the article. G. David Battya and Carlos de MestralbFrom the aDepartment of Epidemiology and Public Health, University College London, London, United Kingdom andbInstitute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.

Histopathologic and Immunohistochemical Investigation of the Effects of Vitamin C on Bone Healing in Rats Exposed to Nicotine

The aim of the present study was to perform a histopathologic and immunohistochemical investigation of the effects of vitamin C on bone healing in rats exposed to nicotine. A total of 52 male Sprague-Dawley rats were assigned to 4 main groups: control, vitamin C, nicotine, and nicotine plus vitamin C. The rats in the nicotine groups were injected with nicotine at 12-hour intervals for 4weeks. At the end of 4weeks, a tibial defect was created in all the rats. Subcutaneous injections were administered at the same intervals postoperatively, and the vitamin C groups received intraperitoneal vitamin C injections every day for the first 3days and then every other day postoperatively. The rats were sacrificed on postoperative days 7 and 21. The blood samples collected during sacrifice were tested to determine the blood cotinine levels, and histopathological and immunohistochemical analyses were performed on tibia samples. The histopathologic evaluation revealed that nicotine significantly increased the amount of necrosis and significantly decreased new bone formation and the bone healing score. The presence of necrosis in the nicotine plus vitamin C group was significantly lower on day 21 (P=.005). A statistically significant difference was observed among the new bone formation of the control, nicotine, vitamin C, and nicotine plus vitamin C groups on day 21 (P=.001). The new bone healing score of the nicotine group was significantly lower than that of the control, vitamin C, and nicotine plus vitamin C groups (P=.003, P = .001, and P=.001). The immunohistochemical evaluation showed that nicotine increased the hypoxia-inducible factor-1α and vascular endothelial growth factor levels and decreased the bone morphogenetic protein-2 levels, especially in the groups sacrificed on day21. Vitamin C did not have a significant effect on bone healing. However, vitamin C administered with nicotine decreased the metabolism of nicotine and, thus, increased nicotine excretion.

Association between self-reported length of time in the USA and blood lead levels: National Health and Nutrition Examination Survey 2013–2016

ObjectivesThe aim of this study is to determine the association between length of time in the USA with blood lead (BPb).DesignPopulation-based cross-sectional study using data from the 2013–2016 National Health...

Abstract 599: Smoking-associated AHRR demethylation in cord blood DNA: Impact of CD235a+ nucleated red blood cells

Abstract Prenatal tobacco smoke exposure is associated with numerous adverse health outcomes at birth and in later life. Numerous studies have demonstrated that Aryl Hydrocarbon Receptor Repressor gene (AHRR) hypomethylation in umbilical cord blood is significantly associated with prenatal tobacco smoke exposure and is suitable as a fetal exposure biomarker. The mechanism driving this demethylation and whether all cord blood cell types are impacted is unclear. Nucleated red blood cells (nucleated CD235a+ cells, nRBCs) are developmentally immature RBCs that display genome-wide demethylation and are observed at increased frequency in the cord blood of smoking mothers. We assessed if nRBC counts or methylation level affected smoking-associated DNA methylation in the AHRR gene as measured in whole cord blood. We analyzed methylation in DNA from whole cord blood, CD14+ monocytes, and nRBCs across four AHRR CpGs using pyrosequencing and also with Illumina 850K arrays (cg05575921) from smoking (n=34) and nonsmoking (n=19) mothers. nRBCs present in cord blood were determined by conventional CBCs and also estimated with a Houseman deconvolution model. AHRR methylation levels were significantly lower in nRBCs relative to whole blood and CD14+ monocytes. Methylation values at each AHRR CpG averaged 14.6% lower in nRBCs (range 0.4% to 24%, p=3.9E-13) relative to CD14+ monocytes with nonsmokers displaying significantly greater hypomethylation in nRBCs than smokers. Methylation levels at each CpG across the AHRR DMR were strongly associated with either self-reported smoking or cord blood cotinine levels in both CD14+ monocytes (r2=0.45, p=4.6E-08) and nRBCs (r2=0.26, p=1.2E-04). The most significant prenatal smoking effect on methylation occurred in CD14+ monocytes at the CpG located at chr5:373490 (-16.7%, p=6.7E-09), 112nt downstream of cg05575921. For subjects with 850K data, adjusting a regression analysis model with estimated cell-type composition, including nRBC counts or estimates, marginally increased the magnitude and significance of the prenatal smoke exposure effect on AHRR cg05575921 methylation. Prenatal tobacco smoke exposure strongly affects DNA methylation in the AHRR gene and this prenatal smoke exposure biomarker is largely unaffected by cord blood cell type composition. Citation Format: Matthew A. Bergens, Gary S. Pittman, Isabel J. Thompson, Michelle R. Campbell, Xuting Wang, Ma Wan, Cathrine Hoyo, Douglas A. Bell. Smoking-associated AHRR demethylation in cord blood DNA: Impact of CD235a+ nucleated red blood cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 599.

The effects of amniotic fluid and foetal cord blood cotinine concentrations on pregnancy complications and the anthropometric measurements of newborns

Our objective was determining the effects of amniotic fluid (AF) and fetal cord blood (FCB) cotinine concentrations on pregnancy complications and the anthropometric measurements in the newborns whose mothers underwent amniocentesis. This study was conducted as a case-control study, in Turkey. A total of 250 pregnant women with amniocentesis indication were recruited into the study and the cotinine levels in the AF and FCB were determined. A smoking habit did not statistically affect the incidence of pregnancy complications (p>.05). The birth weights of the newborns were negatively correlated with the AF cotinine levels. The incidences of low birth weight, low Apgar scores and RDS were positively correlated with higher levels of cotinine in AF and FCB. It is important for healthcare staff to provide training and consultancy services for the health improvement of pregnant women and the prevention of smoking during pregnancy.Impact statementWhat is already known on this subject? The pre-pregnancy smoking habit usually continues during the pregnancy. A significant negative correlation was present between the foetal cord blood cotinine levels and the birth weight.What do the results of this study add? The anthropometric measurements of the newborns born from mothers with high AF cotinine levels were lower than newborns born from mothers with low amniotic fluid cotinine levels. Respiratory Distress syndrome is more often determined in newborns born from mothers with high AF cotinine levels.What are the implications of these findings for clinical practice and/or further research? Future studies should be performed to investigate the effects of cigarette smoking on the health problems, the growth characteristics and the neurological development of newborns and infants within the first year of life.

Smoking in pregnancy, cord blood cotinine and risk of celiac disease diagnosis in offspring

Ecological observations suggest an inverse relationship between smoking in pregnancy and celiac disease (CD) in offspring. While individual-level analyses have been inconsistent, they have mostly lacked statistical power or refined assessments of exposure. To examine the association between pregnancy-related smoking and CD in the offspring, as well as its consistency across data sets, we analyzed: (1) The Norwegian Mother and Child Cohort (MoBa) of 94,019 children, followed from birth (2000–2009) through 2016, with 1035 developing CD; (2) a subsample from MoBa (381 with CD and 529 controls) with biomarkers; and (3) a register-based cohort of 536,861 Norwegian children, followed from birth (2004–2012) through 2014, with 1919 developing CD. Smoking behaviors were obtained from pregnancy questionnaires and antenatal visits, or, in the MoBa-subsample, defined by measurement of cord blood cotinine. CD and potential confounders were identified through nationwide registers and comprehensive parental questionnaires. Sustained smoking during pregnancy, both self-reported and cotinine-determined, was inversely associated with CD in MoBa (multivariable-adjusted [a] OR = 0.61 [95%CI, 0.46–0.82] and aOR = 0.55 [95%CI, 0.31–0.98], respectively); an inverse association was also found with the intensity of smoking. These findings differed from those of our register-based cohort, which revealed no association with sustained smoking during pregnancy (aOR = 0.97 [95%CI, 0.80–1.18]). In MoBa, neither maternal smoking before or after pregnancy, nor maternal or paternal smoking in only early pregnancy predicted CD. In a carefully followed pregnancy cohort, a more-detailed smoking assessment than oft-used register-based data, revealed that sustained smoking during pregnancy, rather than any smoking exposure, predicts decreased likelihood of childhood-diagnosed CD.

Kronik obstrüktif akciğer hastalığında pulmoner fonksiyonel parametreler ve kan kotinin düzeyi

Smoking is the leading cause of chronic obstructive pulmonary disease (COPD) and cotinine is reliable marker of tobacco exposure. We aimed to investigate the relationship between pulmonary function tests (FVC%, FEV1, FEV1/FVC and FEF25-75%), smoking history and blood cotinine levels in healthy volunteers as a control and patients who have COPD in our study. One hundred and two COPD patients and 106 healthy volunteers who admitted to our institution were included. Spirometric investigations of the patients and volunteers were performed. A simple, rapid and reliable gas chromatography-mass spectrometry (GC-MS) method was used for determination of cotinine levels in blood samples. The cut-off value of cotinine was determined as 41.12 ng/mL (97.2% sensitivity and 100% specificity). A significant relationship was observed between average pack-year and cotinine level in current smoker group (p< 0.05). The mean cotinine levels were 6.1, 8.8, and 467.0 ng mL-1 in never smokers, ex-smokers and current smokers, respectively. No relationship was observed between cotinine level and FVC%, FEV1% and FEV1/FVC (p> 0.05). In patient group, there was also no relationship between FEF25-75% and cotinine level however, in control group-smokers a negative correlation was found (p< 0.05; r= -0.372). We observed once again with our study that cotinine is a reliable marker of tobacco exposure. The most obvious result is the negative correlation between FEF25-75% value and cotinine level and this result may be caused by the effect of smoking in the peripheral airways at early stages of COPD.

Parental Smoking and Risk of Childhood-onset Type 1 Diabetes.

A few prospective studies suggest an association between maternal smoking during pregnancy and lower risk of type 1 diabetes. However, the role of unmeasured confounding and misclassification remains unclear. We comprehensively evaluated whether maternal smoking in pregnancy predicts lower risk of childhood-onset type 1 diabetes in two Scandinavian pregnancy cohorts (185,076 children; 689 cases) and a Norwegian register-based cohort (434,627 children; 692 cases). We measured cord blood cotinine as an objective marker of nicotine exposure during late pregnancy in 154 cases and 476 controls. We also examined paternal smoking during pregnancy, in addition to environmental tobacco smoke exposure the first 6 months of life, to clarify the role of characteristics of smokers in general. In the pregnancy cohorts, maternal smoking beyond gestational week 12 was inversely associated with type 1 diabetes, pooled adjusted hazard ratio (aHR) 0.66 (95% CI = 0.51, 0.85). Similarly, in the Norwegian register-based cohort, children of mothers who still smoked at the end of pregnancy had lower risk of type 1 diabetes, aHR 0.65 (95% CI = 0.47, 0.89). Cord blood cotinine ≥30 nmol/L was also associated with reduced risk of type 1 diabetes, adjusted odds ratio 0.42 (95% CI = 0.17, 1.0). We observed no associations of paternal smoking during pregnancy, or environmental tobacco smoke exposure, with childhood-onset type 1 diabetes. Maternal sustained smoking during pregnancy is associated with lower risk of type 1 diabetes in children. This sheds new light on the potential intrauterine environmental origins of the disease.

Characteristics of Adult Cigarette Smokers Who "Relight" and the Effects of Exposure to Tobacco Smoke Constituents.

About half of smokers relight their cigarette, a habit that is a risk factor for chronic bronchitis and possibly lung cancer. Little is known about the characteristics of smokers who relight and their dependence on nicotine. It is unknown whether relighting affects exposure to tobacco smoke constituents. This study examined the characteristics of relighters of usual brand cigarettes and whether relighting affects exposure to selected tobacco smoke constituents. We explored relighting status and frequency, using baseline data from 248 adult smokers participating in studies of reduced nicotine cigarettes in relation to demographic and cigarette characteristics, smoking behaviors, nicotine dependence, biomarkers of exposure (exhaled carbon monoxide, blood cotinine), and biomarkers of oxidative stress (ratio of oxidized/reduced glutathione). 69.4% (n = 172) of subjects reported relighting, and they relit an average of five cigarettes out of 20. Both relighters and non-relighters smoked a mean of 20 cigarettes per day (p = .6). Relighting was significantly associated with higher nicotine dependence, use of longer rod cigarettes, older age, lower income, and unemployment. There were no significant associations between relighting and blood cotinine, exhaled carbon monoxide or measures of oxidized/reduced blood glutathione. The majority of subjects were relighters, who had higher levels of nicotine dependence than non-relighters. Relighters had similar levels of plasma cotinine and exhaled carbon monoxide to non-relighters. No study has compared the cigarette characteristics and biomarkers of exposure of adult cigarette smokers who relight with those who do not. Relighting behavior was common in our sample and was associated with low income, not currently working, higher nicotine dependence, cigarette rod length, daily cigarette use years, and a lifetime history of depressed mood.

The Effects of Firsthand and Secondhand Cigarette Smoking on Immune System Cells and Antibodies in Saudi Arabian Males.

Firsthand and, to a lesser degree, secondhand tobacco smoking are considered the greatest causes of preventable illnesses and premature death worldwide. Firsthand and secondhand smoking have adverse consequences on the immune system, although these effects are not fully understood. A few serological studies have been done on firsthand and secondhand smokers in Saudi Arabia. The present study investigates the effects of firsthand and secondhand smoking on the immune system of randomly chosen male firsthand (50 subjects) and secondhand (50 subjects) cigarette smokers, residing in Jeddah, Saudi Arabia, with an age range of 20-40years. Firsthand smokers were categorized according to the number of cigarettes smoked daily (frequency of smoking). Blood samples were collected and differential complete blood counts, cotinine concentrations, and antibodies (IgG, IgM, and IgA) concentrations were determined. Additionally, T, B, NK, CD4+ and CD8+ cells counts and percentages were determined. Compared to secondhand smokers, firsthand smokers showed a highly significantly highermean cotinine concentration and a highly significantly lower mean IgA concentration. Additionally,Secondhand smokers had significantly highermean lymphocyte count and CD4+/CD8+ ratio, and significantly lower mean basophil and NK cells counts. All other parameters showed no significant differences between firsthand and secondhand smokers and there were no differences between the frequency of smoking categories for the firsthand smokers. Therefore,The resultsshow suggest that passive and active smoking havedifferent immunological effects since IgAlevels and some white blood cells counts weredifferentinfirsthand and secondhand smokers.

Long-term cardiovascular reprogramming by short-term perinatal exposure to nicotine's main metabolite cotinine.

Gather 'proof-of-concept' evidence of the adverse developmental potential of cotinine (a seemingly benign biomarker of recent nicotine/tobacco smoke exposure). Pregnant C57 mice drank nicotine- or cotinine-laced water for 6 wks from conception (NPRE = 2% saccharin + 100 μg nicotine/mL; CPRE = 2% saccharin + 10 μg cotinine/mL) or 3 wks after birth (CPOST = 2% saccharin + 30 μg cotinine/mL). Controls drank 2% saccharin (CTRL). At 17 ± 1 weeks (male pups; CTRL n = 6; CPOST n = 6; CPRE n = 8; NPRE n = 9), we assessed (i) cardiovascular control during sleep; (ii) arterial reactivity ex vivo; and (iii) expression of genes involved in arterial constriction/dilation. Blood cotinine levels recapitulated those of passive smoker mothers' infants. Pups exposed to cotinine exhibited (i) mild bradycardia - hypotension at rest (p < 0.001); (ii) attenuated (CPRE , p < 0.0001) or reverse (CPOST ; p < 0.0001) BP stress reactivity; (iii) adrenergic hypocontractility (p < 0.0003), low protein kinase C (p < 0.001) and elevated adrenergic receptor mRNA (p < 0.05; all drug-treated arteries); and (iv) endothelial dysfunction (NPRE only). Cotinine has subtle, enduring developmental consequences. Some cardiovascular effects of nicotine can plausibly arise via conversion into cotinine. Low-level exposure to this metabolite may pose unrecognised perinatal risks. Adults must avoid inadvertently exposing a foetus or infant to cotinine as well as nicotine.

Cigarette Smoke and Oxidative Stress Indices in Male Active Smokers

Increased generation of reactive oxygen species and peroxidation of biomolecules associated with cigarette smoking have been implicated in multiple organ dysfunctions among smokers. This study assessed the oxidative stress indices, including nitric oxide (NO), reduced glutathione (GSH), ferritin, malondialdehyde (MDA), total antioxidant capacity (TAC), and total plasma peroxide (TPP), and oxidative stress index (OSI), as well as cotinine levels in relation to duration of smoking in male active smokers in Calabar, Nigeria. Ninety consenting male subjects aged 18‒60 years comprising 50 smokers and 40 nonsmokers were studied. Anthropometric indices, blood pressure, and socio-demographic information were obtained using standard methods. Oxidative stress indices; GSH, ferritin, NO, MDA, TAC, and TPP were estimated by colorimetric methods and cotinine by ELISA method. Data were analyzed using ANOVA, LSD post-hoc and Pearson’s correlation at p < 0.05. The results showed that the systolic blood pressure, TPP, OSI, NO, MDA, ferritin, and cotinine levels were significantly higher in smokers compared to nonsmokers. Increasing duration of smoking was associated with increased MDA and decreased GSH and NO levels, while increasing number of cigarette sticks smoked per day was associated with decreased MDA levels. Cotinine correlated positively with ferritin (r = 0.387, p = 0.005) and TPP (r = 0.377, p = 0.007) only in smokers. In conclusion, cigarette smoking results in enhanced NO, ferritin, and lipid peroxidation, with concomitant depletion of GSH which may lead to oxidative stress and smoking-related illness in cigarette smokers studied.

Menthol disrupts nicotine’s psychostimulant properties in an age and sex-dependent manner in C57BL/6J mice

Menthol is a commonly used flavorant in tobacco and e-cigarettes, and could contribute to nicotine sensitivity. To understand how menthol could contribute to nicotine intake and addiction, it is important to determine whether specific mechanisms related to sex and age could underlie behavioral changes induced by menthol-laced nicotinic products. Using a validated paradigm of nicotine-dependent locomotor stimulation, adolescent and adult C57BL/6J mice of both sexes were exposed to nicotine, or nicotine laced with menthol, as their sole source of fluid, and psychostimulant effects were evaluated by recording home cage locomotor activity for ten days. Nicotine and cotinine blood levels were measured following exposure. Results show an interaction between treatment, age, and sex on liquid consumption, indicating that mice responded differently to menthol and nicotine based on their age and sex. Adult male mice greatly increased their nicotine intake when given menthol. In female mice of both age groups, menthol did not have this effect. Despite an increase in nicotine intake promoted by menthol, adult male mice showed a significant decrease in locomotion, suggesting that menthol blunted nicotine-induced psychostimulation. This behavioral response to menthol was not detected in adolescent mice of either sex. These data confirm that menthol is more than a flavorant, and can influence both nicotine intake and its psychostimulant effects. These results suggest that age- and sex-dependent mechanisms could underlie menthol’s influence on nicotine intake and that studies including adolescent and adult menthol smokers of both sexes are warranted.

Blood cadmium and depressive symptoms: Confounded by cigarette smoking

Our aim was to explore the association between blood cadmium (BCd) and depressive symptoms, adjusting for pack years and blood cotinine, and also stratifying by smoking status. Using data from the US National Health and Nutrition Examination Survey (NHANES) 2005–2012, we categorized depressive symptoms using the PHQ-9 (Patient Health Questionnaire-9) survey and modeled depressive symptoms in relation to BCd adjusted for blood cotinine, pack years of smoking, and other covariates. We also stratified by self-reported smoking status (current, former, never). There were 11,209 subjects from 2005 to 2012, age ≥ 18 with PHQ-9, smoking, and blood cadmium data available. 876 (7.8%) met criteria for depressive symptoms. Depressive symptoms were associated with BCd levels in a crude model and with adjustment for pack years and cotinine. The association disappeared when analyzed among current, former, or never smokers. Consistent with the literature, we found an association between BCd and depressive symptoms; however, that association disappears in analyses stratified by smoking status. This suggests residual confounding may be present. It is important to stratify by smoking status when investigating health outcomes associated with BCd.

Pregnancy outcome and cord blood cotinine level: A cross-sectional comparative study between secondhand smokers and non-secondhand smokers

ObjectiveTo compare the pregnancy outcome and cord blood cotinine levels between secondhand smokers and non-secondhand smokers. Study designThis was a cross-sectional comparative study in a Malaysian tertiary obstetric hospital involving 200 non-smoking pregnant women at term, of whom 100 were secondhand smokers and 100 were non-secondhand smokers. Those with multiple pregnancies, with a body mass index (BMI) of more than 30kg/m2 or who delivered by Caesarean section were excluded. The participants’ basic demographic details, delivery details, neonatal outcome and placental weight were recorded. Umbilical cord blood samples were obtained, and cord blood cotinine levels were measured with a Cotinine ELISA kit. The primary outcomes were baby’s birth weight, length, and head circumference, Apgar score at 5min and placental weight. The secondary outcome was difference in cord blood cotinine levels between the two groups and the correlation of these differences with the neonatal outcome. ResultsThe secondhand smoker group had significantly lower baby weight (2.94±0.31kg vs 3.05±0.40kg), head circumference (30.87±2.35cm vs 37.13±2.36cm), length (46.58±1.95cm vs 51.53±2.05cm) and placental weight (520±73.5g vs 596±61.3g) and significantly higher cord blood cotinine levels (16.35±12.84ng/mL vs 0.56±0.22ng/mL). Cord blood cotinine levels had significant negative correlations with placental weight (r=−0.461), baby’s weight (r=−0.297), baby’s head circumference (r=−0.501) and baby’s length (r=−0.374). ConclusionSecondhand smoke increases the incidence of adverse pregnancy outcomes (newborns’anthropometric measurements and placental weight) and causes higher cord blood cotinine levels.

A two-site, two-arm, 34-week, double-blind, parallel-group, randomized controlled trial of reduced nicotine cigarettes in smokers with mood and/or anxiety disorders: trial design and protocol

BackgroundThe U.S. Food and Drug Administration can set standards for cigarettes that could include reducing their nicotine content. Such a standard should improve public health without causing unintended serious consequences for sub-populations. This study evaluates the effect of progressive nicotine reduction in cigarettes on smoking behavior, toxicant exposure, and psychiatric symptoms in smokers with comorbid mood and/or anxiety disorders using a two-site, two-arm, double-blind, parallel group, randomized controlled trial (RCT) in four phases over 34 weeks.MethodsAdult smokers (N = 200) of 5 or more cigarettes per day will be randomized across two sites (Penn State and Massachusetts General). Participants must have not had a quit attempt in the prior month, nor be planning to quit in the next 6 months, meet criteria for a current or lifetime unipolar mood and/or anxiety disorder based on the structured Mini-International Neuropsychiatric Interview, and must not have an unstable medical or psychiatric condition. After a week of smoking their own cigarettes, participants receive two weeks of Spectrum research cigarettes with usual nicotine content (11.6 mg). After this baseline period, participants will be randomly assigned to continue smoking Spectrum research cigarettes that contain either (a) Usual Nicotine Content (11.6 mg); or (b) Reduced Nicotine Content: the nicotine content per cigarette is progressively reduced from approximately 11.6 mg to 0.2 mg in five steps over 18 weeks. At the end of the randomization phase, participants will be offered the choice to either (a) quit smoking with assistance, (b) continue smoking free research cigarettes, or (c) return to purchasing their own cigarettes, for the final 12 weeks of the study. The primary outcome measure is blood cotinine; key secondary outcomes are: exhaled carbon monoxide, urinary total NNAL- 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and 1-hydroxypyrene, oxidative stress biomarkers including 8-isoprostanes, measures of psychiatric symptoms (e.g., depression, anxiety), smoking behavior and dependence (e.g., cigarette consumption, quit attempts), and health effects (e.g., blood pressure, respiratory symptoms).DiscussionResults from this study will inform FDA on the potential effects of regulating the nicotine content of cigarettes and help determine whether smokers with mood and/or anxiety disorders can safely transition to significantly reduced nicotine content cigarettes.Trial registrationTRN: NCT01928758, registered August 21, 2013.

The Impacts of Cord Blood Cotinine and Glutathione-S-Transferase Gene Polymorphisms on Birth Outcome

This study aimed to investigate the association between cord blood cotinine levels and birth outcome, and to determine whether fetal metabolic gene polymorphisms of glutathione-S-transferase (GST) modulate the effect of environmental tobacco smoke exposure during pregnancy. This study included 328 maternal and neonatal pairs. Maternal and cord blood cotinine levels were measured using high performance liquid chromatography. The GST T1 (GSTT1) and GST M1 (GSTM1) polymorphisms were examined using the polymerase chain reaction method. The birth outcomes included birth weight, length, and head circumference, and the risks of having low birth weight and being small for gestational age (SGA). Cord cotinine level had a dose-dependent impact on the reduction of birth weight, length, and head circumference in newborns. Elevation of cord blood cotinine concentration increased the rate of SGA and low birth weight. The neonates who had GSTT1 or GSTM1 polymorphism were associated with an increased risk of being SGA. A combination of the GSTT1 and GSTM1 null genotype exacerbated the effect of maternal environmental tobacco smoke exposure on SGA more than the presence of either genotype alone (odds ratio=8.90, 95% confidence interval=1.00-79.5). Cord blood cotinine adversely affects birth outcomes. GSTT1 and GSTM1 null genotype may modify the effect of cord blood cotinine on birth outcomes.

Self-Reported Tobacco Use and Correlation with Umbilical Cord Blood Cotinine levels at Delivery among Appalachian Gravidas

The detrimental effects of cigarette use during pregnancy are well documented. Studies have shown that cigarette smoking while pregnant is associated with multiple adverse outcomes including: pre-term birth, placental abruption, placenta previa, fetal growth restriction, stillbirth, increased rate of birth defects, and increased risk of sudden infant death syndrome. Cotinine is the primary metabolite of nicotine and allows for measurement of active as well as passive exposure. Cotinine freely cross the placental barrier and maternal concentrations are closely correlated with newborn plasma levels. The aim of this study was to compare maternally reported rates of tobacco use to fetal umbilical cord blood cotinine levels at the time of delivery. A cross-sectional study was conducted on 172 patients. Patients were asked a single yes or no question in regards to their cigarette use during pregnancy. Cord blood was collected at the time of delivery and analyzed for serum concentrations of cotinine. Cotinine levels greater than 3.0 ng/mL were considered consistent with the use of tobacco or tobacco cessation products. Maternal self-reporting of tobacco use indicates a reported tobacco use rate of 27.3% and an actual use rate of 30.2%. The reported tobacco non-use rate was 72.7% and the actual non-use rate was 66.3%. The prevalence of tobacco use during pregnancy in our study was 30.2%, while the overall rate in the United States is reported to be 12.3%. Our findings indicate that self-reported smoking prevalence and verified umbilical cord blood cotinine levels at the time of delivery have excellent correlation (kappa=0.76). Compared to the national average our study group also had nearly double the rate of tobacco use. Due to the deleterious effects of cigarette use during pregnancy continued efforts to educate patients regarding cigarette cessation is of utmost importance as cessation of tobacco products will improve and promote maternal and fetal well-being.

Determination of Nicotine and Cotinine in Human Blood by Dried Blood Spot-LC-Orbitrap MS Technique

Background Dried blood spot DBS have been applied in many application as alternate analytical solution for limitations and challenges in conventional methods and validated methods demand by DBS technique are still required in nicotine Nic research area Aim The development and validation of a new bioanalytical method for simultaneous determination of Nic and cotinine Cot in human blood using DBS and LC Orbitrap MS technique Methods The DBS was punched at mm diameter and extracted by w v of trichloroacetic acid solution containing Nic d as an internal standard IS The extracted samples were then injected into a Kinetex C column and eluted by mobile phase of methanol water formic acid v v v Chromatographic effect for DBS was investigated by decentralized disk punching peripheral area The developed method was validated according to European and American guidelines for bioanalytical method validation Results Nic Cot and IS were detected accurately by Orbitrap MS using heated ESI source at positive ions m z of and respectively The established calibration ranges for Nic and Cot were linear between ng mL and ng mL respectively Within and between run measurements accuracy for Nic and Cot were all higher than for LLOQ and for QC levels and the measurements precision for Nic and Cot were all within Conclusion The developed method for Nic and Cot determination in human blood was successfully validated using DBS LC Orbitrap MS technique Nic and Cot investigation was not affected by DBS rsquo s chromatographic influence