Comparison of urinary and plasma cotinine levels during the three trimesters of pregnancy

Assays of metabolised cotinine are considered to be an accurate measure of exposure to cigarette smoke among pregnant women. We investigated the association and differences between the cotinine levels in maternal urine and blood, and the umbilical cord blood of three tobacco exposure groups at different stages of pregnancy. A prospective study was conducted among 398 pregnant women undergoing prenatal care in different trimesters at two medical centres and one regional hospital in central Taiwan. All 398 subjects (including 25 smokers, 191 passive smokers and 182 non-smokers) remained in the study up to the time of delivery; 384 of them delivered singleton live births. Cotinine levels were assayed in the maternal plasma and urine of the mothers at each trimester and in the cord blood of the newborns. All specimens were measured using a sensitive high-performance liquid chromatography. Cotinine concentrations in plasma and urine showed a significant dose-dependent difference among the three groups (non-smoker, passive and active smoker) and a trend that increased with gestation among the pregnant women. Significant correlations between cotinine concentrations in plasma and urine among the pregnant women in each trimester were found. In addition, the level of cotinine in umbilical cord blood was significantly correlated with that in maternal blood at term (r = 0.89, P < 0.001). A pattern of elevated cotinine concentrations in the plasma and urine of pregnant women from the beginning to the end of pregnancy was found, and this correlated significantly with the cotinine levels in the umbilical cord blood.     

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.     

被动吸烟的孕妇体内生物标志物的检测与分析

目的通过检测被动吸烟的孕妇体内生物标志物,研究被动吸烟对孕妇及胎儿健康的影响。方法采用自制问卷,由236个孕妇自填问卷的形式,进行被动吸烟相关信息的问卷调查,调查同时收集孕妇唾液、静脉血、尿和脐带血,将所调查的236名孕妇按被动吸烟量分为无被动吸烟、被动吸烟量<10支/d、10支/d≤被动吸烟量<20支/d和被动吸烟量≥20支/d共4个组,用吡啶-巴比妥酸法测定唾液硫氰酸盐含量,用巴比妥酸比色法测定孕妇静脉血、尿及脐带血可铁宁含量。结果不同被动吸烟量各组孕妇唾液硫氰酸盐含量差异有统计学意义,随着被动吸烟量的增加,唾液中硫氰酸盐含量升高;各组间静脉血、尿、脐带血可铁宁含量差异分别亦有统计学意义,随着被动吸烟量的增加,静脉血、尿、脐带血可铁宁含量升高。结论静脉血、尿、脐带血可铁宁含量是孕妇被动吸烟的体内生物标志物,孕妇被动吸烟可对自身及胎儿的健康产生影响。     

The influence of active and passive smoking during pregnancy on umbilical cord blood levels of vitamins A and E and neonatal anthropometric indices

Smoking during pregnancy has been shown to be detrimental for the developing fetus. The effects of active and passive maternal smoking on umbilical cord serum levels of vitamin A and vitamin E were examined. Secondary measures included anthropometric parameters in the newborn. Maternal and umbilical cord serum levels of vitamins A and E were measured at delivery. The mothers were assigned to three groups: non-smoking (n 12); passive smoking (n 13); active smoking (n 18). Based on multivariate linear regressions, active smoking during pregnancy was associated with increased umbilical cord serum levels of vitamin A and vitamin E. While enhanced circulating levels of vitamin A in cord blood were also found in non-smoking mothers exposed to tobacco smoke during pregnancy, those of vitamin E were not influenced. Further, an inverse association between smoking behaviour during pregnancy and birth length was observed, with shortest length in active smokers followed by passive smoking mothers. Active and passive maternal smoking behaviour during pregnancy increases the fetal demand for antioxidant compounds in order to counteract the oxidative burden by cigarette smoke. Against this background, the observed increase in umbilical cord serum levels of vitamins A and E may subserve antioxidative processes in response to tobacco smoke-induced oxidative stress. This would reduce the availability of vitamins A and E for fetal maturation, which is critical inasmuch as both compounds are indispensable for the developing fetus. However, due to the cross-sectional nature of our observation, this line of reasoning definitely requires validation in cause-effect experiments in the future.     

胎儿脐带缠绕与环境暴露因素的关联

  目的  了解中国胎儿脐带缠绕现状及其与环境暴露因素的相关性,为预防和干预脐带缠绕提供科学的指导。  方法  以中国孕产妇队列研究·协和项目的孕妇为研究对象,在孕早期收集孕妇的一般人口学信息和环境暴露信息,随访获取脐带缠绕相关结局,应用多因素非条件Logistic回归分析模型分析胎儿脐带缠绕的影响因素。  结果  胎儿脐带缠绕的发生率为9.00%。Logistic回归分析模型分析结果显示:调整混杂因素后,与孕期没有暴露于被动吸烟或噪声的孕妇相比,暴露于被动吸烟(OR=1.199, 95% CI: 1.010~1.423, P=0.038)或噪声(OR=1.242, 95% CI: 1.002~1.541, P=0.048)的孕妇发生脐带缠绕的风险较高。  结论  孕妇孕期被动吸烟和接触噪声对胎儿脐带缠绕有影响,应加强孕期教育,减少孕妇孕期被动吸烟和噪声环境暴露。     

孕妇被动吸烟对自身健康及胎儿生长发育的影响

目的 :研究被动吸烟对孕妇健康及胎儿生长发育的影响。方法 :以整群抽样的方法对兰州市 3所医院在 2 0 0 3年3月 15日～ 8月 2 0生产的 2 3 6名孕妇被动吸烟情况采用自制问卷进行调查。于入院时采集孕妇唾液 ,分娩时采取脐带血 ,用吡啶-巴比妥酸法定量分析唾液硫氰酸盐含量 ;用巴比妥酸比色法测定脐带血可铁宁含量 ;同时在孕妇生产时测量新生儿体重。结果 :孕妇被动吸烟量不同 ,其唾液中硫氰酸盐含量不同 ,二者呈正相关关系 ;不同被动吸烟量的孕妇脐带血可铁宁含量均有显著性差异 ;不同被动吸烟量的孕妇所生产新生儿体重差异有显著性。结论 :被动吸烟对孕妇自身健康及胎儿生长发育均有影响     

Maternal tobacco smoke exposure and persistent pulmonary hypertension of the newborn.

We propose that in utero exposure to tobacco smoke products places a newborn at risk for persistent pulmonary hypertension of the newborn (PPHN). To test this hypothesis, infants with PPHN were identified. Healthy newborns of similar ethnicity were identified as a comparison group. Cord blood cotinine concentrations and maternal questionnaires were obtained. The number of women exposed to tobacco smoke in each group ascertained by questionnaire was borderline significantly different (38.7% vs. 20.5%; p = 0.080). However, more PPHN infants had detectable cotinine in their cord blood (64.5% vs. 28.2%; p = 0.002), and the median cotinine concentrations were significantly higher (5.2 ng/ml vs. 2 ng/ml; p = 0.051) than the comparison infants. Among infants delivered to nonsmoking women, more PPHN infants had detectable cotinine (50% vs. 19%; p = 0.015), and the cotinine concentrations were higher (3.5 ng/ml vs. 1.65 ng/ml; p = 0.022) than the comparison group. We conclude that active and passive smoking during pregnancy is a risk factor for PPHN. Therefore, we recommend that pregnant women cease smoking and avoid environmental tobacco smoke. Key words. cotinine, newborns, passive, persistent pulmonary hypertension, smoking, tobacco smoke pollution.     

Prevalence of cigarette smoking in pregnant women participating in the special supplemental nutrition programme for Women,Infants and Children (WIC) in Minneapolis and Saint Paul,Minnesota, USA

Several adverse birth outcomes are associated with cigarette smoking. It is important to determine the prevalence of cigarette smoking among pregnant low-income women and to evaluate their smoking cessation patterns in order to target appropriate interventions. Ethnically diverse pregnant women aged 15-45 years were recruited from Minneapolis or Saint Paul Women, Infants, and Children (WIC) clinics before their third trimester. Serum cotinine levels were assayed for 98 women and compared with self-report. The women were unaware that their smoking status would be validated. Twenty-one (21%) women had a positive serum cotinine value (> or =3 ng/mL); 16 (76%) admitted smoking within the previous 24 h before interview and five denied smoking. Of the five, four had cotinine levels that could suggest passive smoke exposure. Thirty-seven women (38%) admitted cigarette smoking during the pregnancy but before knowing that they were pregnant; 18 (49%) of these denied current smoking at the interview and also presented with negative cotinine levels. These data suggest that some participants in WIC make a concerted effort to quit smoking when they find out they are pregnant, and are generally truthful when reporting their smoking habits during pregnancy.     

Active and passive maternal smoking during pregnancy and the risks of low birthweight and preterm birth: the Generation R Study

The objective of this study was to examine the associations between active and passive smoking in different periods of pregnancy and changing smoking habits during pregnancy, with low birthweight and preterm birth. The study was embedded in the Generation R Study, a population-based prospective cohort study from early fetal life onwards in Rotterdam, The Netherlands. Active and passive smoking were assessed by questionnaires in early, mid- and late pregnancy. Analyses were based on 7098 pregnant women and their children. Active smoking until pregnancy was ascertained and was not associated with low birthweight and preterm birth. Continued active smoking after pregnancy was also recorded and was associated with low birthweight (adjusted odds ratio 1.75 [95% CI 1.20, 2.56]) and preterm birth (adjusted odds ratio 1.36 [95% CI 1.04, 1.78]). The strongest associations were found for active maternal smoking in late pregnancy. Passive maternal smoking in late pregnancy was associated with continuously measured birthweight (P for trend <0.001). For all active smoking categories in early pregnancy, quitting smoking was associated with a higher birthweight than continuing to smoke. Tendencies towards smaller non-significant beneficial effects on mean birthweight were found for reducing the number of cigarettes without quitting completely. This study shows that active and passive smoking in late pregnancy are associated with adverse effects on weight and gestational age at birth. Smoking in early pregnancy only, seems not to affect fetal growth adversely. Health care strategies for pregnant women should be aimed at quitting smoking completely rather than reducing the number of cigarettes.     

Aryl hydrocarbon hydroxylase activity in human placenta of passive smokers

The levels of smoke components and metabolites in maternal blood and urine are useful in assessing direct exposure but they do not appear to be sufficiently sensitive as a long-term indicator of passive smoke exposure. Induction of aryl hydrocarbon hydroxylase (AHH) activity in the placenta as a result of maternal smoking has been well documented. This enzyme oxidizes various polycyclic aromatic hydrocarbons abundantly present in cigarette smoke. We hypothesized that passively inhaled tobacco smoke may induce placental AHH activity. Placental AHH levels were determined in 207 pregnancies at birth. As has been found in previous studies, we demonstrated that smoking during pregnancy is associated with a marked increase in placental AHH activity. A relationship was found between the recorded number of cigarettes smoked per day and the placental AHH activity. Moreover, AHH activity was significantly higher in pregnant women passively exposed to tobacco smoke relative to controls. The usefulness of analysis of placental AHH activity as a biological marker of in utero smoke exposure in epidemiological studies is considered.     

Low-Level Prenatal Toxin Exposures and Breastfeeding Duration: A Prospective Cohort Study

Introduction Maternal exposure to tobacco smoke is associated with shortened breastfeeding duration, but few studies have examined the effects on breastfeeding outcomes of low level exposures to other toxic chemicals. Moreover, it is unclear if passive smoking is associated with duration of breastfeeding. Our objective was therefore to examine the effect of low-level prenatal exposures to common environmental toxins (tobacco smoke, lead, and phthalates) on breastfeeding exclusivity and duration. Methods We conducted an analysis of data from the Health Outcomes and Measures of the Environment (HOME) Study. Serum and urine samples were collected at approximately 16 and 26 weeks gestation and at delivery from 373 women; 302 breastfed their infants. Maternal infant feeding interviews were conducted a maximum of eight times through 30 months postpartum. The main predictor variables for this study were gestational exposures to tobacco smoke (measured by serum cotinine), lead, and phthalates. Passive smoke exposure was defined as cotinine levels of 0.015–3.0 μg/mL. Primary outcomes were duration of any and exclusive breastfeeding. Results Serum cotinine concentrations were negatively associated with the duration of any breastfeeding (29.9 weeks unexposed vs. 24.9 weeks with passive exposure, p?=?0.04; and 22.4 weeks with active exposure, p?=?0.12; p?=?0.03 for linear trend), but not duration of exclusive breastfeeding. Prenatal levels of blood lead and urinary phthalate metabolites were not significantly associated with duration of any or exclusive breastfeeding. Conclusions Passive exposure to tobacco smoke during pregnancy was associated with shortened duration of any breastfeeding.     

被动吸烟与母婴CYP450、GST基因多态性对低出生体重的交互作用

目的:探讨被动吸烟与细胞色素P4501A1(CYP1A1)、谷胱甘肽S-转移酶M1(GSTM1)、谷胱甘肽S-转移酶T1(GSTT1)基因多态性对新生儿低出生体重的影响。方法:采用病例对照研究方法,调查2009～2011年在该院产科入院分娩孕妇及其单胎、活产的低出生体重儿,同期正常出生体重新生儿作为对照;液相色谱法(HPLC)检测母血、脐带血可替宁水平;PCR-RFLP技术确定其CYP1A1、GSTM1、GSTT1基因型。结果:期间共得到328个母亲-新生儿对,其中低出生体重组128对,正常出生体重对照组200对。低出生体重组母血、脐带血可替宁水平分别为(536.12±15.56)ng/ml、(255.36±16.08)ng/ml,正常出生体重对照组母血、脐带血可替宁水平分别为(110.25±10.65)ng/ml、(20.35±5.45)ng/ml。低出生体重组的CYP1A1基因MSP1多态C型(纯合子突变型)的频率与正常出生体重对照组差异有统计学意义(P<0.05),携带C型的个体为低出生体重的危险度比B型(杂合子突变型)与A型(野生型)个体的高(OR=1.98,95%CI:1.08～3.62);低出生体重组中单一的GSTM1或GSTT1基因缺失型分布频率与正常出生体重对照组相比无统计学差异(P>0.05);同时携带CYP-lAl C型和GSTM1、GSTT1缺失型的联合基因型个体为低出生体重儿的风险明显增加(OR=2.24,95%CI:1.18～4.26)。结论:被动吸烟对低出生体重有明显影响;CYP1A1基因MSP1多态纯合子突变型(C型)与低出生体重的易感性可能有关;单一的GSTM1或GSTT1基因缺失型与低出生体重易感性可能无关;同时携带CYP1A1 C型和GSTM1、GSTT1基因缺失型可能是低出生体重的易感因素之一。     

A review of the use of saliva cotinine as a marker of tobacco smoke exposure

Cotinine, the major metabolite of nicotine, is a useful marker of exposure to tobacco smoke. It can be measured in plasma, urine, or saliva. However, distinguishing between active and passive smoking on the basis of a cotinine measurement may be difficult. In order to evaluate the relationship between saliva cotinine concentration and self-reported tobacco smoke exposure in both active and passive smokers, an English-language literature search using MEDLINE was conducted (1973-1989), and the bibliographies of identified articles were reviewed. Of 43 originally identified articles, only 22 met the criteria for inclusion. Specific information regarding population studied, reported tobacco smoke exposure, method of measurement, and cotinine concentrations was assessed. Passive smokers usually have cotinine concentrations in saliva below 5 ng/ml, but heavy passive exposure can result in levels greater than or equal to 10 ng/ml. Levels between 10 and 100 ng/ml may result from infrequent active smoking or regular active smoking with low nicotine intake. Levels greater than 100 ng/ml are probably the result of regular active smoking. Four categorizations of tobacco smoke exposure are suggested on the basis of saliva cotinine concentrations.     

Association of passive smoking with increased coronary heart disease risk is not explained by elevation of leucocyte count

The increased risk of coronary heart disease in cigarette smokersmay be due at least partly to an elevation of the leucocytecount Chronic passive smoking has also been found to be associatedwith an increased risk of coronary heart disease, but its effecton the leucocyte count has not been reported. In this study250 male factory employees aged 20–64 years were interviewedon smoking behaviour and exposure to environmental tobacco smoke,and blood counts were determined. Urinary cotinine was measureby radio-immunoassay and corrected for urinary creatinine concentrations.Mean leucocyte count was significantly higher among smokerscompared with non-smokers (8,666 compared to 6, 900; p<0.001).On the basis of smoking history, passive smokers had leucocytecounts similar to non-smokers. These findings were confirmedwhen leucocyte counts were compared with urine cotinine to creatinineratios. The association of haematocrlt and haemoglobin withsmoking was similar to that of leucocyte count These findingssuggest that any association of passive smoking with coronaryheart disease is not through an elevation of leucocyte count.     

妊娠期被动吸烟与母亲血清和脐带血清炎性因子的关系

目的探讨母亲孕期被动吸烟（passive smoking）与母亲外周血清及脐带血清中炎性因子水平的关系。方法调查79名孕产妇的一般人口学、妇产科学特征及在孕期的被动吸烟情况,采集孕产妇外周静脉血及脐带静脉血,检测血清单核细胞趋化因子-1（monocyteche motactic protein-1,MCP-1）、白介素-6（interleukin-6,IL-6）、肿瘤坏死因子-α（tumor necrosis factor—α,TNF-α）、白介素1β（interleukin-1β,IL-1β）、C反应蛋白（C—reactive protein,CRP）和血管细胞粘附因子-1（soluble vascular cell adhesion molecule-1,VCAM-1）。在控制年龄、孕周、婚姻状态、教育水平、家庭收入、孕产妇孕前体质指数（body mass index,BMI）、产次、胎儿性别等？昆杂因素后,采用有序Logistic回归模型分析母亲孕期被动吸烟暴露与母亲血清及脐血清中炎性因子水平的关系。结果79名调查对象中46人（58．2％）报告其在孕期有被动吸烟暴露,28人（35．4％）报告被动吸烟暴露平均每天为1～15min,18人（22．8％）报告被动吸烟暴露平均每天超过15min。在控制混杂因素后,与非暴露者相比,每天平均暴露1～15min者母血清中IL－1β（OR=3．00,95％C／：1．10—8．14）和CRP（OR=4．10,95％C／：1．47～11．47）水平升高,平均每天暴露超过15min者母血清IL-6（OR=5．19,95％C／：1．56—17．29）和TNF-α（OR：6．87,95％C／：1．97～23．96）水平升高。与非暴露者相比,平均每天暴露超过15min者脐带血清IL－1β（OR=0．21,95％CI：0．07～0．59）水平降低。结论母亲孕期被动吸烟暴露对母亲和胎儿的炎性反应有所不同,对母亲的炎性反应影响较大,对胎儿的炎性反应影响较小。     

香烟烟雾对大鼠血压和可替宁含量影响的实验研究

目的 研究香烟烟雾暴露对大鼠血压水平变化和血清、尿液中可替宁含量的影响，并探讨两者之间的相关性。 方法 健康雄性SD大鼠60只,按随机数字表随机分为实验组（即香烟烟雾暴露组）和对照组,每组30只。实验组大鼠给予香烟烟雾暴露干预12周，对照组大鼠正常饲养。在香烟烟雾暴露干预开始及以后的1周、2周、3周、4周、6周、8周、12周分别从实验组和对照组中随机抓取3只大鼠测量血压，采用两独立样本 t 检验法分析比较两组大鼠在不同时间点血压的差异；用酶联免疫吸附试验测定不同时间点大鼠血清和尿液中可替宁的水平，并采用Pearson相关分析法进行血压和可替宁含量的相关性检验。 结果 大鼠在接受香烟烟雾暴露干预2周后血压开始上升，和对照组相比血压升高，差异有统计学意义（ P <0.05）；实验组大鼠血清及尿液中可替宁水平随烟雾暴露时间的延长而增高；实验组大鼠收缩压和舒张压均与血清中可替宁水平呈正相关（ r =0.883， P <0.05； r =0.814， P <0.05），与尿液中可替宁水平呈正相关（ r =0.873， P <0.05； r =0.798， P <0.05），差异均有统计学意义。 结论 香烟烟雾暴露可引起大鼠血压增高，并随暴露时间的延长，血压水平和大鼠体内可替宁含量也逐渐上升，且大鼠血压和体内可替宁水平变化正相关。     

Estimating Cotinine Associations and a Saliva Cotinine Level to Identify Active Cigarette Smoking in Alaska Native Pregnant Women

Studies indicate nicotine metabolism varies by race and can change during pregnancy. Given high rates of tobacco use and limited studies among Alaska Native (AN) women, we estimated associations of saliva cotinine levels with cigarette use and second-hand smoke (SHS) exposure and estimated a saliva cotinine cutoff to distinguish smoking from non-smoking pregnant AN women. Using questionnaire data and saliva cotinine, we utilized multi-variable linear regression (n = 370) to estimate cotinine associations with tobacco use, SHS exposure, demographic, and pregnancy-related factors. Additionally, we estimated an optimal saliva cotinine cutoff for indication of active cigarette use in AN pregnant women using receiver operating characteristic (ROC) curve analysis (n = 377). Saliva cotinine significantly decreased with maternal age and significantly increased with cigarettes smoked per day, SHS exposure, and number of previous full term pregnancies. Using self-reported cigarette use in the past 7 days as indication of active smoking, the area under the ROC curve was 0.975 (95 % CI: 0.960–0.990). The point closest to 100 % specificity and sensitivity occurred with a cotinine concentration of 1.07 ng/mL, which corresponded to sensitivity of 94 % and specificity of 94 %. We recommend using a saliva cotinine cutoff of 1 ng/mL to distinguish active smoking in pregnant AN women. This cutoff is lower than used in other studies with pregnant women, most likely due to high prevalence of light or intermittent smoking in the AN population. Continued study of cotinine levels in diverse populations is needed.     

Fetal Exposure to Secondhand Tobacco Smoke Assessed by Maternal Self-reports and Cord Blood Cotinine: Prospective Cohort Study in Krakow

Objectives While the validity of self-reported smoking habits is generally judged as satisfactory, objective markers of secondhand smoke (SHS) exposure may be more useful in validating the causal links between prenatal SHS and health effects. The cohort study in Krakow provided an opportunity for comparative assessment of fetal exposure to SHS based upon questionnaires and cord blood cotinine measurements. Methods The study sample included 467 newborns born to women recruited in the first and second trimester of pregnancy. To compare the validity of self-reported SHS and cord blood cotinine levels in assessing the association between fetal passive smoking and health effects of newborns, we separately examined the regression coefficients of birthweight on self-reported number of cigarettes smoked by other household members during the entire pregnancy and cord blood cotinine levels. Results In the non-exposed newborns the geometric mean of cord blood cotinine was 0.077 ng/ml and was significantly lower than in newborns with a maternal report of SHS. Cord cotinine levels were more highly correlated with a self-reported number of cigarettes smoked daily at home in the third trimester of pregnancy. The two measures of SHS (number of cigarettes and number of hours of daily exposure) were equally well correlated with cord blood cotinine levels. Using cotinine as the exposure variable, overall the association was not significant; but among the subgroup with cord cotinine levels above the median (≥0.083 ng/ml), the association with birthweight was significant (beta coefficient = −113.65, P = 0.041). Conclusion The study provides evidence that the assessment of fetal SHS exposure based on cord blood cotinine produced better estimates of the association between exposure and birth outcomes. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.     

Environmental tobacco smoke exposure among pregnant women: impact on fetal biometry at 20–24 weeks of gestation and newborn child’s birth weight

Aim While there are sufficient data regarding the negative effect of exposure to the constituents of tobacco smoke on newborn infants birth weights, it is still unclear whether this effect may originate in early pregnancy. The aim of the present study was to evaluate the impact of exposure to tobacco smoke components in early pregnancy (20–24 weeks) on fetal biometry.Methods The study population comprised 183 women consecutively enrolled at 20–24 weeks of pregnancy at the two antenatal care units. Ultrasound biometric measurements of fetal bi-parietal diameter (BPD), abdominal circumference (AC) and femur length (FL) were performed at the time of enrolment. Serum cotinine concentration was determined at 20–24 weeks of gestation by gas chromatography with mass spectrometry detector (GC/MS) to assess environmental tobacco smoke (ETS) exposure during the previous evening and the morning of the same day (blood collection at 1200–1300 h). ETS exposure (passive smoking) was assumed to occur when the level of serum cotinine ranged from 2–10 ng/ml.Results In a multiple regression model for bi-parietal diameter (BPD), after adjustment for pregnancy duration at the time of ultrasound examination, fetal gender, and maternal pre-pregnancy weight, a statistically significant negative association was found between the BPD and serum cotinine concentration. A similar association was identified for subjects with serum cotinine concentrations below 10 ng/ml (corresponding to passive smoking) (P=0.06). After controlling for pregnancy duration, maternal pre-pregnancy weight and infants gender, we found that serum cotinine levels at 20–24 weeks of gestation was inversely associated with infant birth weight (P=0.004). For the subjects with serum cotinine levels below 10 ng/ml, a borderline association (P=0.09) with infant birth weight was found.Conclusions Maternal exposure to tobacco smoke in early pregnancy, as measured by serum cotinine concentrations at 20–24 weeks of gestation, adversely affects fetal BPD. Preventive measures need to be undertaken to encourage pregnant women to stop smoking and avoid passive exposure to tobacco smoke from the very beginning of pregnancy.     

Self-reported smoking, cotinine levels, and patterns of smoking in pregnancy

Non-pregnant adult smokers generally exhibit fairly stable smoking behaviour over time. In studies of this population, cotinine assays are considered a 'gold standard' measure of exposure to cigarette smoke; current smoking status can be validated with high sensitivity and specificity. In contrast, there is substantial within-person fluctuation in pregnancy smoking, as women try repeatedly to quit or cut down. As a result, cotinine measures may be of limited use for validation of amount smoked, as they are informative only about recent exposure, vary with individual smoking topography and are dependent on time lapsed since the last cigarette smoked. Thus, in reproductive epidemiology, where timing, intensity and duration of exposure are critical, self-reported history of cigarette consumption may be a more relevant fetal exposure than current smoking status. If there were substantial within-person variation over the course of pregnancy, numerous measures of cotinine would be needed to characterise patterns of fetal exposure and would not be feasible in many studies. We examined self-reported smoking patterns and compared them to patterns of urinary cotinine levels in a prospective study of 998 pregnant women, recruited 1988-92. Fluctuations in smoking were considerable and, while cotinine measures and self-reported number of cigarettes were highly correlated at any given time point across women (r=0.70), the within-person correlation between the patterns of self-reported number of cigarettes and cotinine levels was weaker (r=0.33). For researchers interested in fetal outcomes in which intensity and timing of exposure are critical, we conclude that self-reported variations in smoking during pregnancy may be a valid way to characterise detailed patterns of fetal exposure in epidemiological studies.