Swimming pool water disinfection by-products profiles and association patterns.

The aim of this work was to determine and study the concentration of different groups of disinfection by-products (DBPs): trihalomethanes, haloacetic acids, haloacetonitriles, haloacetones and combined chlorine (as an indicator of chloramine levels), in the water of 175 public swimming pools in Gipuzkoa (Basque Country, Spain). The study included chlorinated and brominated pools, indoor and outdoor, used for recreational and sports purposes, and filled with water from calcareous and siliceous soils. The most abundant were haloacetic acids, followed by trihalomethanes, with chlorinated or brominated forms predominating depending on whether the pools were disinfected by chlorination or bromination, respectively. All the 75th percentiles of DBPs were below the limits established by the European Chemical Agency (ECHA), although the maximum values of trihalomethanes exceeded them. The same was true for dichloroacetonitrile in chlorinated pools and dibromoacetonitrile in brominated pools. All families of DBPs showed positive associations with each other, all being significant except for combined chlorine. Their mean levels were higher in outdoor pools than in indoor pools, significantly so in all except combined chlorine. Recreational pools showed higher levels of haloacetic acids and combined chlorine than sports pools. The concentrations of the different groups of DBPs were higher in the pools than in the mains water that fed them. This increase, especially that of the haloacetonitriles, as well as the high concentrations of brominated forms in the pools disinfected by bromination, make it necessary to focus on their toxicological implication. The differences in the DBP profiles of the filling network water were not transferred to the pool water.

Minimally invasive ultrasound-guided vs open release for carpal tunnel syndrome in working population: A randomized controlled trial.

PURPOSE: To compare the clinical effectiveness of minimally invasive ultrasound (US)-guided vs open release for carpal tunnel syndrome. METHODS: In an open randomized controlled trial, 47 employed patients were allocated to US-guided carpal tunnel release (USCTR) and 42 to an open carpal tunnel release (OCTR) procedure. The main outcome was symptom severity measured by the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ-S). Secondary outcomes were hand functionality (BCTQ-F), nerve conduction, two-point discrimination, handgrip and pinch strength, pain (visual analog scale), work leave and complications. For BCTQ-S and BCTQ-F, minimal clinically important differences (MCID) were also considered. Follow-up duration was 12 months. RESULTS: Mixed model analyses detected no significant differences between the two treatment arms in BCTQ-S (P = .098) while BCTQ-F scores were significantly better in the USCTR group (P = .007). This benefit was, however, not supported by the MCID data. Remaining variables were similar in the two groups except pain which was lower in USCTR at 3 months follow-up. All variables but two-point discrimination showed significant improvement after 3 months. CONCLUSIONS: Our findings reveal similar symptom relief benefits following OCTR or USCTR in these patients. The patients in our USCTR group, however, reported better hand functional status and less pain.

Changes in parental smoking during pregnancy and risks of adverse birth outcomes and childhood overweight in Europe and North America: An individual participant data meta-analysis of 229,000 singleton births.

BACKGROUND: Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. METHODS AND FINDINGS: We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39-3.25] and OR 1.93 [95% CI 1.46-2.57] instead of OR 2.95 [95% CI 2.75-3.15] when reducing from ≥10 to 5-9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16-1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations. CONCLUSIONS: We observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy.

Exposure and health risks perception of extremely low frequency and radiofrequency electromagnetic fields and the effect of providing information.

Given that regardless of actual exposure levels, high-risk perceptions of electromagnetic fields of non-ionizing radiation (EMF-NIR) may cause health effects, it is important to understand the mechanisms behind perceptions in the general population. The aims of this study were to assess perceptions of both exposure and health-risk among mothers of the INMA (Environment and childhood)-Gipuzkoa child cohort; to explore possible determinants that explain such perceptions; and to evaluate whether providing information on exposure levels has any effect on perceptions. Overall, 387 mothers completed a questionnaire composed of four questions on perceived exposure and perceived health-risk of exposure to extremely low frequency (ELF) and radiofrequency (RF) fields answered on a Likert-type scale from 0 to 10. Later, measurements of ELF and RF fields were conducted in the houses of a subsample of 104 participants. All measured levels were far below the levels established by the European Council recommendation. This was explained in the individual reports sent to the families. After reading the results, mothers completed the aforementioned questionnaire a second time, plus two additional questions regarding the role of public health bodies in risk communication. The association between perceived and measured levels as categorical variables was assessed with a chi-square test. Multiple linear regressions were conducted for each of the questions related to perceived exposure and health-risk perceptions. Wilcoxon signed-rank test was conducted to assess the effect of receiving information. Both exposure and health risk were perceived to be very high for both ELF and RF fields, with mean and medians of 7 on a 10-point scale. Reporting higher perception levels was not associated with higher levels of exposure measured at home. Variables that were repeatedly associated with higher perceptions included: manual social class, not having the feeling of living in a good neighborhood, difficulty getting by financially, not having a television antenna within 600 m, being younger and having fewer devices at home. Providing information on EMF-NIR exposure levels at home did not alter health-risk perceptions, but mean perceived RF exposure decreased significantly (by 0.7 points). Most of the participants claimed to have received no or insufficient information regarding exposure and health-risks of EMF-NIR from public bodies and considered it very important that they should.

Maternal cell phone use during pregnancy and child cognition at age 5 years in 3 birth cohorts.

BACKGROUND: There have been few studies of children's cognitive development in relation to mothers' cell phone use, and most were limited to outcomes at age 3 years or younger. We examined the relationship between maternal cell phone use during pregnancy and cognitive performance in 5-year old children. METHODS: This study included data from 3 birth cohorts: the Danish National Birth Cohort (DNBC) (n = 1209), Spanish Environment and Childhood Project (INMA) (n = 1383), and Korean Mothers and Children's Environment Health Study (MOCEH) (n = 497). All cohorts collected information about maternal cell phone use during pregnancy and cognitive performance in children at age 5. We performed linear regression to compute mean differences (MD) and 95% confidence intervals (CI) in children's general, verbal, and non-verbal cognition scores comparing frequency of maternal prenatal cell phone use with adjustments for numerous potential confounding factors. Models were computed separately for each cohort and using pooled data in meta-analysis. RESULTS: No associations were detected between frequency of prenatal cell phone use and children's cognition scores. Scores tended to be lower in the highest frequency of use category; MD (95% CI) in general cognition scores were 0.78 (-0.76, 2.33) for none, 0.11 (-0.81, 1.03) for medium, and -0.41 (-1.54, 0.73) for high compared to low frequency of use. This pattern was seen across all cognitive dimensions, but the results were imprecise overall. CONCLUSION: We observed patterns of lower mean cognition scores among children in relation to high frequency maternal prenatal cell phone use. The causal nature and mechanism of this relationship remain unknown.

FINGER (Forming and Identifying New Groups of Expected Risks): developing and validating a new predictive model to identify patients with high healthcare cost and at risk of admission.

OBJECTIVE: Predictive statistical models used in population stratification programmes are complex and usually difficult to interpret for primary care professionals. We designed FINGER (Forming and Identifying New Groups of Expected Risks), a new model based on clinical criteria, easy to understand and implement by physicians. Our aim was to assess the ability of FINGER to predict costs and correctly identify patients with high resource use in the following year. DESIGN: Cross-sectional study with a 2-year follow-up. SETTING: The Basque National Health System. PARTICIPANTS: All the residents in the Basque Country (Spain) ≥14 years of age covered by the public healthcare service (n=1 946 884). METHODS: We developed an algorithm classifying diagnoses of long-term health problems into 27 chronic disease groups. The database was randomly divided into two data sets. With the calibration sample, we calculated a score for each chronic disease group and other variables (age, sex, inpatient admissions, emergency department visits and chronic dialysis). Each individual obtained a FINGER score for the year by summing their characteristics' scores. With the validation sample, we constructed regression models with the FINGER score for the first 12 months as the only explanatory variable. RESULTS: The annual FINGER scores obtained by patients ranged from 0 to 57 points, with a mean of 2.06. The coefficient of determination for healthcare costs was 0.188 and the area under the receiver operating characteristic curve was 0.838 for identifying patients with high costs (>95th percentile); 0.875 for extremely high costs (>99th percentile); 0.802 for unscheduled admissions; 0.861 for prolonged hospitalisation (>15 days); and 0.896 for death. CONCLUSION: FINGER presents a predictive power for high risks fairly close to other classification systems. Its simple and transparent architecture allows for immediate calculation by clinicians. Being easy to interpret, it might be considered for implementation in regions involved in population stratification programmes.

Children's exposure assessment of radiofrequency fields: Comparison between spot and personal measurements.

INTRODUCTION: Radiofrequency (RF) fields are widely used and, while it is still unknown whether children are more vulnerable to this type of exposure, it is essential to explore their level of exposure in order to conduct adequate epidemiological studies. Personal measurements provide individualized information, but they are costly in terms of time and resources, especially in large epidemiological studies. Other approaches, such as estimation of time-weighted averages (TWAs) based on spot measurements could simplify the work. OBJECTIVES: The aims of this study were to assess RF exposure in the Spanish INMA birth cohort by spot measurements and by personal measurements in the settings where children tend to spend most of their time, i.e., homes, schools and parks; to identify the settings and sources that contribute most to that exposure; and to explore if exposure assessment based on spot measurements is a valid proxy for personal exposure. METHODS: When children were 8 years old, spot measurements were conducted in the principal settings of 104 participants: homes (104), schools and their playgrounds (26) and parks (79). At the same time, personal measurements were taken for a subsample of 50 children during 3 days. Exposure assessment based on personal and on spot measurements were compared both in terms of mean exposures and in exposure-dependent categories by means of Bland-Altman plots, Cohen's kappa and McNemar test. RESULTS: Median exposure levels ranged from 29.73 (in children's bedrooms) to 200.10 µW/m2 (in school playgrounds) for spot measurements and were higher outdoors than indoors. Median personal exposure was 52.13 µW/m2 and median levels of assessments based on spot measurements ranged from 25.46 to 123.21 µW/m2. Based on spot measurements, the sources that contributed most to the exposure were FM radio, mobile phone downlink and Digital Video Broadcasting-Terrestrial, while indoor and personal sources contributed very little (altogether <20%). Similar distribution was observed with personal measurements. There was a bias proportional to power density between personal measurements and estimates based on spot measurements, with the latter providing higher exposure estimates. Nevertheless, there were no systematic differences between those methodologies when classifying subjects into exposure categories. Personal measurements of total RF exposure showed low to moderate agreement with home and bedroom spot measurements and agreed better, though moderately, with TWA based on spot measurements in the main settings where children spend time (homes, schools and parks; Kappa = 0.46). CONCLUSIONS: Exposure assessment based on spot measurements could be a feasible proxy to rank personal RF exposure in children population, providing that all relevant locations are being measured.

Exposure to extremely low and intermediate-frequency magnetic and electric fields among children from the INMA-Gipuzkoa cohort.

Detailed assessment of exposure to extremely low frequency (ELF) and intermediate frequency (IF) fields is essential in order to conduct informative epidemiological studies of the health effects from exposure to these fields. There is limited information available regarding ELF electric fields and on both magnetic and electric field exposures of children in the IF range. The aim of this study was to characterize ELF and IF exposure of children in the Spanish INMA cohort. A combination of spot and fixed measurements was carried out in 104 homes, 26 schools and their playgrounds and 105 parks. Low levels of ELF magnetic fields (ELF-MF) were observed (with the highest 24-h time-weighted average (TWA) exposure being 0.15µT in one home). The interquartile range (IQR) of ELF electric fields (ELF-EF) ranged from 1 to 15V/m indoors and from 0.3 to 1.1V/m outdoors and a maximum value observed was 55.5V/m in one school playground. IQR ranges for IF magnetic and electric fields were between 0.02 and 0.23µT and 0.2 and 0.5V/m respectively and maximum values were 0.03µT and 1.51V/m in homes. Correlations between magnetic and electric fields were weak for ELF (Spearman 0.04-0.36 in different settings) and moderate for IF (between 0.28 and 0.75). Children of INMA-Gipuzkoa cohort were exposed to very low levels of ELF-MF in all settings and to similar levels of ELF-EF compared to the range of previously reported levels, although somewhat higher exposures occurred at home. Children enrolled to our study were similarly exposed to IF in all settings.

Changes in serum dioxin and PCB levels in residents around a municipal waste incinerator in Bilbao, Spain.

There is a great concern in the Basque Country regarding emissions from waste incineration, in particular that of organochlorines (OCs), including dioxins, furans and polychlorinated biphenyls (PCBs), and their potential effect on human health. In 2005, a municipal solid waste plant (MSWP) started to operate in Bilbao, representing an opportunity to assess the exposure to the aforementioned pollutants among people living at various distances from the plant. In 2006 and 2008, we carried out two cross-sectional studies to quantify and assess changes in levels of these pollutants. The objective of this study was to describe the levels of OCs in the blood serum in 2013 of 127 adults of this prospective cohort, in four centres of population, near to and further away from the MSWP, and to study trends over time since it started to operate. This study shows the levels of OCs have decreased significantly, from 37.2% to 80.1%. Further, levels of OCs in areas near to the MSWP were not found to be higher than those in areas further afield.

The association between passive and active tobacco smoke exposure and child weight status among Spanish children.

OBJECTIVE: To assess the impact of passive and active tobacco smoke exposure, both pre- and postnatally, on child body mass index (BMI) and overweight. METHODS: Pregnant women were enrolled into the Spanish INMA prospective birth cohort during 1997 to 2008. Tobacco smoke exposure was assessed by questionnaire and corroborated by pre- and postnatal cotinine measurements. Children were followed up until 4 years in newer subcohorts (N = 1866) and until 14 years in one older subcohort (N = 427). Child age- and sex-specific BMI Z-scores were calculated, and generalized estimating equations were used to model their relationship with repeated measures of tobacco smoke exposure. RESULTS: Associations between prenatal passive exposure to tobacco smoke (adjusted ß = 0.15, 95% CI: 0.05-0.25) and active maternal smoking (adjusted ß = 0.20, 95% CI: 0.08-0.33) and child zBMI up to 4 years were observed. Stronger associations were observed in the older subcohort between both prenatal and child passive smoke exposure and zBMI up to 14 years. CONCLUSIONS: Evidence for an effect of both passive and maternal active smoking on child postnatal growth has been provided. Although residual confounding cannot be completely ruled out, associations were robust to adjustment for a range of lifestyle factors.

Characterisation of exposure to non-ionising electromagnetic fields in the Spanish INMA birth cohort: study protocol.

BACKGROUND: Analysis of the association between exposure to electromagnetic fields of non-ionising radiation (EMF-NIR) and health in children and adolescents is hindered by the limited availability of data, mainly due to the difficulties on the exposure assessment. This study protocol describes the methodologies used for characterising exposure of children to EMF-NIR in the INMA (INfancia y Medio Ambiente- Environment and Childhood) Project, a prospective cohort study. METHODS/DESIGN: Indirect (proximity to emission sources, questionnaires on sources use and geospatial propagation models) and direct methods (spot and fixed longer-term measurements and personal measurements) were conducted in order to assess exposure levels of study participants aged between 7 and 18 years old. The methodology used varies depending on the frequency of the EMF-NIR and the environment (homes, schools and parks). Questionnaires assessed the use of sources contributing both to Extremely Low Frequency (ELF) and Radiofrequency (RF) exposure levels. Geospatial propagation models (NISMap) are implemented and validated for environmental outdoor sources of RFs using spot measurements. Spot and fixed longer-term ELF and RF measurements were done in the environments where children spend most of the time. Moreover, personal measurements were taken in order to assess individual exposure to RF. The exposure data are used to explore their relationships with proximity and/or use of EMF-NIR sources. DISCUSSION: Characterisation of the EMF-NIR exposure by this combination of methods is intended to overcome problems encountered in other research. The assessment of exposure of INMA cohort children and adolescents living in different regions of Spain to the full frequency range of EMF-NIR extends the characterisation of environmental exposures in this cohort. Together with other data obtained in the project, on socioeconomic and family characteristics and development of the children and adolescents, this will enable to evaluate the complex interaction between health outcomes in children and adolescents and the various environmental factors that surround them.

Synergism between exposure to mercury and use of iodine supplements on thyroid hormones in pregnant women.

OBJECTIVE: To evaluate the association between mercury exposure and thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and free thyroxine (FT4) levels during pregnancy as well as to explore if there is any synergic action between mercury and intake of iodine from different sources. METHODS: The study population was 1407 pregnant women participating in the Spanish INMA birth cohort study. Total mercury concentrations were analyzed in cord blood. Thyroid hormones (THs) were measured in serum samples collected at 13.2±1.5 weeks of gestation. The association between mercury and TH levels was evaluated with multivariate linear regression models. Effect modification caused by iodine intake from supplements and diet was also evaluated. RESULTS: The geometric means of TSH, TT3, FT4 and mercury were 1.1µU/L, 2.4nmol/L, 10.5pmol/L and 7.7µg/L, respectively. Mercury levels were marginally significantly associated with TT3 (ß: -0.05; 95%CI: -0.10, 0.01), but were neither associated with TSH nor FT4. The inverse association between mercury and TT3 levels was stronger among the iodine supplement consumers (-0.08; 95%CI: -0.15, -0.02, interaction p-value=0.07). The association with FT4 followed the same pattern, albeit not significant. CONCLUSION: Prenatal mercury exposure was inversely associated with TT3 levels among women who took iodine supplements during pregnancy. These results could be of public health concern, although further research is needed.

Time trends in serum organochlorine pesticides and polychlorinated biphenyls in the general population of Biscay, Spain.

Despite the measures adopted, levels of organochlorine compounds (OCs) are still being detected in the human body. This study aimed to explore factors related to changes in the concentrations of polychlorinated biphenyls (PCBs) and pesticide OCs in blood samples obtained from a general population cohort. Two cross-sectional samples were taken from 162 adults (2-75 years of age), with a gap of 2 years, from four areas in Biscay (Spain). More than 75 % had quantifiable levels of hexachlorobenzene (HCB), beta-hexachlorocyclohexane (ß-HCH), dichlorodiphenyldichloroethylene, and PCBs 138 153 and 180. During this time, significant changes were observed: PCB 180 and HCB levels increased, and PCB 138 and ß-HCH levels decreased. Regarding age, this study shows a decrease suggesting a cohort effect. The period was not related to the decrease of levels in all age intervals, but a statistically significant increase of PCBs in older people was found. High body mass index was associated with lower PCB 180 levels and greater HCH levels. Inversely, greater levels of HCB and ß-HCH were in those who had lost weight before the study. Levels of HCB and ß-HCH were also greater in women who had had children, although they were lower in those who breastfed. Levels of these same OCs were greater in fish consumers, whereas those of PCBs 138 and 153 were greater in those who consumed local produce; all of these trends were close to significance. Efforts should continue to decrease exposure to these pollutants and to assess their influence on general population.

Factors associated with second-hand smoke exposure in non-smoking pregnant women in Spain: self-reported exposure and urinary cotinine levels.

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.

Maternal smoking during pregnancy and fetal biometry: the INMA Mother and Child Cohort Study.

In utero tobacco exposure has been associated with fetal growth restriction, but uncertainty remains about critical windows of exposure and specific effects on body segments. In the present study, we aimed to examine the association of maternal smoking with fetal biometry in different stages of pregnancy. The study population comprised 2,478 fetuses from a Spanish birth cohort study that was established between 2003 and 2008. Biparietal diameter, femur length, abdominal circumference, and estimated fetal weight were evaluated at 12, 20, and 34 weeks of gestation. Fetal size and growth were assessed by standard deviation scores adjusted by maternal and fetal characteristics. Maternal smoking was assessed using questionnaire and a sample of urinary cotinine at week 32 of gestation. Associations were estimated using multiple regression analysis. Smokers at week 12 of gestation showed decreased fetal growth as reflected by all growth parameters at 20-34 weeks, leading to a reduced fetal size at week 34. The reduction was greatest in femur length, at -9.4% (95% confidence interval -13.4, -5.4) and least in abdominal circumference, at -4.4% (95% CI: -8.7, -0.1). Fetuses of smokers who quit smoking before week 12 showed reduced growth only in femur length (-5.5; 95% CI: -10.1, -0.9). Dose-response curves for smoking versus fetal growth parameters (abscissa: log2 cotinine) were linear for biparietal diameter and femur length.

Determinants of self-reported smoking and misclassification during pregnancy, and analysis of optimal cut-off points for urinary cotinine: a cross-sectional study.

OBJECTIVES: To estimate the prevalence and factors associated with smoking and misclassification in pregnant women from INMA (INfancia y Medio Ambiente, Environment and Childhood) project, Spain, and to assess the optimal cut-offs for urinary cotinine (UC) that best distinguish daily and occasional smokers with varying levels of second-hand smoke (SHS) exposure. DESIGN: We used logistic regression models to study the relationship between sociodemographic variables and self-reported smoking and misclassification (self-reported non-smokers with UC >50 ng/ml). Receiver operating characteristic (ROC) curves were used to calculate the optimal cut-off point for discriminating smokers. The cut-offs were also calculated after stratification among non-smokers by the number of sources of SHS exposure. The cut-off points used to discriminate smoking status were the level of UC given by Youden's index and for 50 and 100 ng/ml for daily smokers, or 25 and 50 ng/ml for occasional smokers. PARTICIPANTS: At the third trimester of pregnancy, 2263 pregnant women of the INMA Project were interviewed between 2004 and 2008 and a urine sample was collected. RESULTS: Prevalence of self-reported smokers at the third trimester of pregnancy was 18.5%, and another 3.9% misreported their smoking status. Variables associated with self-reported smoking and misreporting were similar, including born in Europe, educational level and exposure to SHS. The optimal cut-off was 82 ng/ml (95% CI 42 to 133), sensitivity 95.2% and specificity 96.6%. The area under the ROC curve was 0.986 (95% CI 0.982 to 0.990). The cut-offs varied according to the SHS exposure level being 42 (95% CI 27 to 57), 82 (95% CI 46 to 136) and 106 ng/ml (95% CI 58 to 227) for not being SHS exposed, exposed to one, and to two or more sources of SHS, respectively. The optimal cut-off for discriminating occasional smokers from non-smokers was 27 ng/ml (95% CI 11 to 43). CONCLUSIONS: Prevalence of smoking during pregnancy in Spain remains high. UC is a reliable biomarker for classifying pregnant women according to their smoking status. However, cut-offs would differ based on baseline exposure to SHS.

Analysis of population characteristics related to the total effective xenoestrogen burden: a biomarker of xenoestrogen exposure in breast cancer.

To analyse the link between breast cancer and the combined effect of environmental xenoestrogens, we developed, standardised and applied a biomarker of exposure to assess the total effective xenoestrogen burden (TEXB) in human adipose tissue in a case-control study. Environmental oestrogens (TEXB-alpha) are separated from endogenous oestrogens (TEXB-beta), and the combined oestrogenic effect is determined from its proliferative effect (E-Screen assay). The aim of the study was to identify potential confounders, effect modifiers or other covariates associated with higher TEXB levels. In cases, age, family history of breast cancer, lactation experience and smoking were associated with TEXB-alpha. In controls, only age was associated with TEXB-alpha levels. In cases, age, educational level, age at menarche, menopausal status, marital status, lactation experience and smoking were associated with TEXB-beta. In controls, only menopausal status was significantly associated with TEXB-beta levels. In conclusion, TEXB, as a biomarker of exposure, takes account of environmental, dietary, lifestyle, genetic and reproductive factors, which are not usually systematically measured across studies.

Breast cancer risk and the combined effect of environmental estrogens.

OBJECTIVE: The present study aimed to determine whether the combined effects of environmental estrogens measured as the total effective xenoestrogen burden (TEXB-alpha) are a risk factor for breast cancer over and above the risk potentially linked to specific pesticides. METHODS: We measured the levels of 16 organochlorine pesticides as well as TEXB in adipose tissue of 198 women at the time of breast cancer diagnosis. These were compared with findings in 260 age and hospital matched control women without breast cancer. RESULTS: The median levels of p,p'-DDE (1,1-dichloro-2,2-bis( p -chlorophenyl)ethylene), aldrin, endosulfan ether and lindane (the pesticides detected in > 40% of the study population) were higher in cases than controls, although the differences did not reach statistical significance. After adjusting for potential confounders, the odds ratio (OR) for breast cancer in women with detectable levels of aldrin was 1.55 (95% confidence interval (CI) 1.00-2.40). Among the postmenopausal women, the OR for aldrin and lindane was 1.84 (95% CI 1.06-3.18) and 1.76 (95% CI 1.04-2.98), respectively. Among cases with body mass index (BMI) below the median (28.6 kg/m2), the OR was 3.42 (95% CI 1.22-9.58) for women in the highest quartile of TEXB-alpha versus those in the lowest. The subgroup of leaner postmenopausal women showed an increased risk (OR: 5.67; 95% CI 1.59-20.21) for those in the highest tertile versus those in the lowest. CONCLUSIONS: We found an increased risk for breast cancer in the leaner women, especially in the leaner postmenopausal subgroup, related to the TEXB-alpha. The pesticides aldrin and lindane are also individually associated with risk.