Drinking Water Contaminants, Gene Polymorphisms, and Fetal Growth

There are still many uncertainties regarding the risk of adverse pregnancy outcomes associated with exposure to drinking water disinfection by-products. In Montréal, Québec, Canada, we carried out a hospital-based case–control study including 493 cases of intrauterine growth restriction defined as birth weight below the 10th percentile for gestational age and sex, according to Canadian standards. Controls were babies (n = 472) delivered at the same hospital whose birth weight was at or above the 10th percentile, matched for gestational age, race, and sex. Exposure to total and specific trihalomethanes was measured using regulatory data collected by municipalities and the provincial Ministry of Environment. Residential history, water drinking, and shower habits during pregnancy, as well as known risk factors for intrauterine growth restriction, were measured with a face-to-face interview with all mothers. Mothers and newborns were characterized for two genetic polymorphisms, one in the CYP2E1 gene (G1259C), and another in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T). Exposure to specific and total trihalomethanes from drinking water, determined for 458 cases and 426 controls, did not result in an increased risk of intrauterine growth restriction. However, significant effect modification was observed between newborns with and without the CYP2E1 variant; among newborns with the variant, the adjusted odds ratio for intrauterine growth restriction associated with exposure to average total trihalomethanes above the 90th percentile (corresponding to 29.4 μg/L) was 13.20 (95% confidence interval, 1.19–146.72). These findings suggest that exposure to trihalomethanes at the highest levels can affect fetal growth but only in genetically susceptible newborns

Analysis of Case-Parent Trios Using a Loglinear Model with Adjustment for Transmission Ratio Distortion

Transmission of the two parental alleles to offspring deviating from the Mendelian ratio is termed Transmission Ratio Distortion (TRD), occurs throughout gametic and embryonic development. TRD has been well-studied in animals, but remains largely unknown in humans. The Transmission Disequilibrium Test (TDT) was first proposed to test for association and linkage in case-trios (affected offspring and parents); adjusting for TRD using control-trios was recommended. However, the TDT does not provide risk parameter estimates for different genetic models. A loglinear model was later proposed to provide child and maternal relative risk (RR) estimates of disease, assuming Mendelian transmission. Results from our simulation study showed that case-trios RR estimates using this model are biased in the presence of TRD; power and Type 1 error are compromised. We propose an extended loglinear model adjusting for TRD. Under this extended model, RR estimates, power and Type 1 error are correctly restored. We applied this model to an intrauterine growth restriction dataset, and showed consistent results with a previous approach that adjusted for TRD using control-trios. Our findings suggested the need to adjust for TRD in avoiding spurious results. Documenting TRD in the population is therefore essential for the correct interpretation of genetic association studies

Markers of infection, breast-feeding and childhood acute lymphoblastic leukaemia

Infections are suspected to play a role in the aetiology of childhood leukaemia. In 1989–95, we evaluated the relation between childhood acute lymphoblastic leukaemia and pre- and postnatal markers of exposure to infection, as well as breast-feeding. A population-based case-control study was carried out in certain regions of Québec, Canada, in 1989–95 including 491 incident cases diagnosed between 1980 and 1993 and aged between 0 and 9 years. An identical number of healthy controls matched for age, sex and region of residence at the date of diagnosis was included. Having older siblings, mother's use of antibiotics during pregnancy, and being born second or later were all associated with increased risk of leukaemia while early day-care attendance (odds ratio (OR) = 0.49; 95% CI 0.31–0.77), and breast-feeding (OR = 0.68; 95% CI 0.49–0.95) were significantly protective. A marker of population mixing was not a risk factor. When including all variables defining family structure in a model, having older siblings at time of diagnosis was a risk factor among children diagnosed before 4 years of age (OR = 4.54; 95% CI 2.27–9.07) whereas having older siblings in the first year of life was protective among children diagnosed at 4 years of age or later (OR = 0.46; 95% CI 0.22–0.97). © 2000 Cancer Research Campaign http://www.bjcancer.co

Exploration and comparison of methods for combining population- and family-based genetic association using the Genetic Analysis Workshop 17 mini-exome

We examine the performance of various methods for combining family- and population-based genetic association data. Several approaches have been proposed for situations in which information is collected from both a subset of unrelated subjects and a subset of family members. Analyzing these samples separately is known to be inefficient, and it is important to determine the scenarios for which differing methods perform well. Others have investigated this question; however, no extensive simulations have been conducted, nor have these methods been applied to mini-exome-style data such as that provided by Genetic Analysis Workshop 17. We quantify the empirical power and false-positive rates for three existing methods applied to the Genetic Analysis Workshop 17 mini-exome data and compare relative performance. We use knowledge of the underlying data simulation model to make these assessments

La relation chômage-santé : une étude prospective. Présentation sommaire et premiers résultats d’une recherche

Les auteurs ont entrepris en 1984 une importante étude sur les multiples interrelations entre le chômage et la santé. La méthodologie retenue est prospective, longitudinale, avec groupe contrôle. Ils présentent d'abord une synthèse des travaux effectués puis exposent les résultats obtenus jusqu'à maintenant. Ces résultats vont dans le sens des quatre hypothèses posées a priori. Cependant, ces résultats ne sont pas définitifs. L'analyse se poursuit.In 1984, the authors undertook a major study on the multiple interrelations between unemployment and health. Tlie methodology in use is prospective, longitudinal, with a control group. Their presentation consists of a synthesis of work carried out so far followed by corresponding results. These results are in compliance with the four hypotheses developed through a priori reasoning. However, these results are not definitive. The analysis continues

Maternal Exposure to Occupational Solvents and Childhood Leukemia

Many organic solvents are considered probable carcinogens. We carried out a population-based case–control study including 790 incident cases of childhood acute lymphoblastic leukemia and as many healthy controls, matched on age and sex. Maternal occupational exposure to solvents before and during pregnancy was estimated using the expert method, which involves chemists coding each individual’s job for specific contaminants. Home exposure to solvents was also evaluated. The frequency of exposure to specific agents or mixtures was generally low. Results were generally similar for the period ranging from 2 years before pregnancy up to birth and for the pregnancy period alone. For the former period, the odds ratio (OR), adjusted for maternal age and sex, for any exposure to all solvents together was 1.11 [95% confidence interval (CI), 0.88–1.40]. Increased risks were observed for specific exposures, such as to 1,1,1-trichloroethane (OR = 7.55; 95% CI, 0.92–61.97), toluene (OR = 1.88; 95% CI, 1.01–3.47), and mineral spirits (OR = 1.82; 95% CI, 1.05–3.14). There were stronger indications of moderately increased risks associated with exposure to alkanes (C5–C17; OR = 1.78; 95% CI, 1.11–2.86) and mononuclear aromatic hydrocarbons (OR = 1.64; 95% CI, 1.12–2.41). Risk did not increase with increasing exposure, except for alkanes, where a significant trend (p = 0.04) was observed. Home exposure was not associated with increased risk. Using an elaborate exposure coding method, this study shows that maternal exposure to solvents in the workplace does not seem to play a major role in childhood leukemia

Pesticide Flow Analysis to Assess Human Exposure in Greenhouse Flower Production in Colombia

Human exposure assessment tools represent a means for understanding human exposure to pesticides in agricultural activities and managing possible health risks. This paper presents a pesticide flow analysis modeling approach developed to assess human exposure to pesticide use in greenhouse flower crops in Colombia, focusing on dermal and inhalation exposure. This approach is based on the material flow analysis methodology. The transfer coefficients were obtained using the whole body dosimetry method for dermal exposure and the button personal inhalable aerosol sampler for inhalation exposure, using the tracer uranine as a pesticide surrogate. The case study was a greenhouse rose farm in the Bogota Plateau in Colombia. The approach was applied to estimate the exposure to pesticides such as mancozeb, carbendazim, propamocarb hydrochloride, fosetyl, carboxin, thiram, dimethomorph and mandipropamide. We found dermal absorption estimations close to the AOEL reference values for the pesticides carbendazim, mancozeb, thiram and mandipropamide during the study period. In addition, high values of dermal exposure were found on the forearms, hands, chest and legs of study participants, indicating weaknesses in the overlapping areas of the personal protective equipment parts. These results show how the material flow analysis methodology can be applied in the field of human exposure for early recognition of the dispersion of pesticides and support the development of measures to improve operational safety during pesticide management. Furthermore, the model makes it possible to identify the status quo of the health risk faced by workers in the study area

Reference values for an index of fetal aortic isthmus blood flow during the second half of pregnancy

ABSTRACT Objective During fetal life, the parallel position of the two cardiac ventricles confers a special status to the aortic isthmus. Flow through the isthmus reflects the balance between the performances of the two ventricles and their respective peripheral impedances. This study proposes a fetal aortic isthmus flow velocity index and its reference values defined on the basis of gestational age (GA). Methods Video recordings of 111 normal fetuses from 18 to 39 weeks of gestation were retrospectively reviewed. An isthmus flow velocity index (IFI) was calculated as follows: IFI = (systoli