When epidemiological databases inform injury mechanisms: biomechanical analysis of injury associations.

BACKGROUND: Vehicle accidents are still a heavy social burden despite improvements due the latest technologies and policies. To pursue the trend of decrease, having a more detailed view and understanding of the injury patterns would contribute to inform both the rescue team to optimize victim's management and policymakers in order for them to tackle at best this issue. METHODS: Two complementary analyses of injury associations were performed, one using a biomechanical classification and the other an anatomic one, computed on data stratified by car accident type (lateral or frontal). Our objective is to understand whether these two categories of crash lead to similar or heterogeneous injury association patterns, and analyze these findings from an impact mechanics point of view. Indeed, having an improved understanding of the injury mechanisms would facilitate their diagnosis and prevention. RESULTS: While each type of accident possesses its own injury profile, most injury associations are found for both types. Injuries such as clavicle and rib fractures were identified as involved in a high number of associations. Several associations between fractures and blood vessel injuries were found. CONCLUSIONS: The results suggests three main conclusions: (i) Injury associations are rather independent from crash characteristics, (ii) Clavicle and rib fractures are typical of poly-traumatized victims, (iii) Certain fractures can be used to early detect victims at higher risk of hemorrhage. Overall, this study provide paramedics and doctors with data to orientate them toward a faster and more appropriate decision. Moreover, this exploratory work revealed the potential that injury association analyses have to inform policy-making and issue recommendations to decrease road accident mortality and morbidity.

Organophosphate pesticide exposure during pregnancy and childhood and onset of juvenile delinquency by age 16 years: The CHAMACOS cohort.

BACKGROUND: Though prenatal organophosphate pesticide (OP) exposure has been associated with lower intellectual quotient and behavioral disorders in childhood, factors related to later delinquency, no research has directly evaluated the impact of OPs on delinquency. OBJECTIVE: To evaluate the association between prenatal and childhood OP exposure and juvenile delinquency in Mexican-American youth in the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS). METHODS: We measured dialkyl phosphate (DAPs) urinary metabolites of OPs in two prenatal maternal samples and in five child samples collected between six months and five years of age. Youth completed delinquency questionnaires at 16 years. We examined associations of prenatal and childhood DAPs with several delinquency outcomes (n = 313) using survival and generalized linear models. RESULTS: Almost 60% of youth reported delinquent acts (mostly minor), and 8% reported a police arrest. We observed largely null results of prenatal or childhood DAP concentrations and delinquency outcomes, with some isolated associations. A ten-fold increase in maternal dimethylphosphate (DM) concentrations measured after 20 weeks gestation was associated with an earlier age of first delinquent act (Hazard Ratio = 1.38, 95% CI: 1.01, 1.88) and an increased Odds Ratio (OR) of having committed 1-3 or ≥4 delinquent acts, compared to the no delinquency reference group (OR = 1.77, 95% CI: 1.01-3.08 and 2.17, 95% CI: 1.13-4.17, respectively). Higher childhood diethylphosphate (DE) concentrations were associated with a later age of first delinquent act (HR: 0.67; 95% CI: 0.46-0.97). DISCUSSION: We did not find strong evidence of association between prenatal or childhood OP exposure and juvenile delinquency in the present cohort. There is an increasing literature that relates OP exposure to neurobehavioral impairments in childhood, and there is a need to understand long-term potential neurodevelopmental effects of early-life OP exposure.

An Empirical Validation of the Within-subject Biospecimens Pooling Approach to Minimize Exposure Misclassification in Biomarker-based Studies.

BACKGROUND: Within-subject biospecimens pooling can theoretically reduce bias in dose-response functions from biomarker-based studies when exposure assessment suffers from classical-type error. However, collecting many urine voids each day is cumbersome. We evaluated the empirical validity of a within-subject pooling approach and compared several options to avoid sampling each void. METHODS: In 16 pregnant women who collected a spot of each urine void over several nonconsecutive weeks, we compared concentrations of 10 phenols in daily, weekly, and pregnancy within-subject pools. We pooled either three or all daily samples. In a simulation study using these data, we quantified bias in dose-response functions when using one to 20 urine samples per subject to assess methylparaben (a compound with moderate within-subject variability) and bisphenol A (high variability) exposures. RESULTS: Correlations between exposure estimates from pools of all and of only three voids per day were above 0.80 for all time windows and compounds, except for benzophenone-3 and triclosan in the daily time window (correlations, 0.57-0.68). With one spot sample to assess pregnancy exposure, correlations were all below 0.74. Using only one biospecimen led to attenuation bias in the dose-response functions of 29% (methylparaben) and 69% (bisphenol A); four samples for methylparaben and 18 for bisphenol A decreased bias to 10%. CONCLUSIONS: For nonpersistent chemicals, collecting and pooling three samples per day instead of all daily samples efficiently estimates exposures over a week or more. Collecting around 20 biospecimens can strongly limit attenuation bias for nonpersistent chemicals such as bisphenol A.

Use of personal care products during pregnancy in relation to urinary concentrations of select phenols: A longitudinal analysis from the SEPAGES feasibility study.

BACKGROUND: Exposure to certain synthetic phenols is of growing concern, in particular among pregnant women, because of their endocrine disrupting nature. Many phenols are still authorized in personal care products (PCP). We aimed to assess if use of PCPs, by pregnant women could influence their urinary concentrations of synthetic phenols. METHODS: We used a panel design with intense urine sample collection. Eight women completed a diary with exact time and use of PCPs in three weeks. We measured the concentrations of phenols (four parabens, bisphenol A and S, two dichlorophenols, triclosan, and benzophenone-3) in 178 urine samples, collected during 7 consecutive days at 3 time points during pregnancy. We characterized PCP use as the total number of PCP applications or as a single PCP use (yes/no) in three time windows (0-6, 6 to 12 and 12 to 24h before each urine sample collection). We used adjusted linear and Tobit regressions to assess associations between PCP use and phenol urinary concentrations. RESULTS: The total number of PCP applications was positively associated with ethylparaben, propylparaben and butylparaben concentrations. We observed a peak in urinary concentration of ethylparaben, butylparaben and propylparaben at 2.86, 2.55 and 2.67 h since last PCP use, respectively and twelve different types of PCPs were positively associated with at least one of these parabens. The bisphenol S concentration increased by 12.4% (95%CI: confidence interval: 5.9; 19.3) for each additional PCP application in the 12 to 24 time window and use of specific PCPs such as anti-stretchmarks cream, facial cleanser and shower gel. Associations varied by time window. CONCLUSION: Our study showed that PCP use was associated with a short-term increase in the urinary concentration of ethylparaben, butylparaben and propylparaben, but not methylparaben. This study also reported a positive association between the use of PCPs and the bisphenol S concentration, a finding that warrants further investigation in cohorts with repeated collection of urine samples and detailed information on PCP use.

Within-Day, Between-Day, and Between-Week Variability of Urinary Concentrations of Phenol Biomarkers in Pregnant Women.

BACKGROUND: Toxicology studies have shown adverse effects of developmental exposure to industrial phenols. Evaluation in humans is challenged by potentially marked within-subject variability of phenol biomarkers in pregnant women, which is poorly characterized. OBJECTIVES: We aimed to characterize within-day, between-day, and between-week variability of phenol urinary biomarker concentrations during pregnancy. METHODS: In eight French pregnant women, we collected all urine voids over a 1-wk period (average, 60 samples per week per woman) at three occasions (15±2, 24±2, and 32±1 gestational weeks) in 2012-2013. Aliquots of each day and of the whole week were pooled within-subject. We assayed concentrations of 10 phenols in these pools, and, for two women, in all spot (unpooled) samples collected during a 1-wk period. We characterized variability using intraclass correlation coefficients (ICCs) with spot samples (within-day variability), daily pools (between-day variability), and weekly pools (between-week variability). RESULTS: For most biomarkers, the within-day variability was high (ICCs between 0.03 and 0.50). The between-day variability, based on samples pooled within each day, was much lower, with ICCs >0.60 except for bisphenol S (0.14, 95% confidence interval [CI]: 0.00, 0.39). The between-week variability differed between compounds, with triclosan and bisphenol S having the lowest ICCs (<0.3) and 2,5-dichlorophenol the highest (ICC >0.9). CONCLUSION: During pregnancy, phenol biomarkers showed a strong within-day variability, while the variability between days of a given week was more limited. One biospecimen is not enough to efficiently characterize exposure; collecting biospecimens during a single week may be enough to represent well the whole pregnancy exposure for some but not all phenols. https://doi.org/10.1289/EHP1994.

Prenatal Exposure to Phthalates and the Development of Eczema Phenotypes in Male Children: Results from the EDEN Mother-Child Cohort Study.

BACKGROUND: Contradictory results exist regarding the importance of early-life exposure to phthalates for development of childhood eczema. OBJECTIVES: We evaluated the association between maternal urinary concentrations of phthalate metabolites between the 24th and 28th week of gestation and occurrence of eczema in their sons up to 5 y of age, according to allergic sensitization as assessed by total immunoglobulin E (IgE) in a subsample of individuals. METHODS: Data on health outcomes and background factors were collected using five standardized annual questionnaires completed by parents at the children's ages of 1-5 y, and their associations with phthalate metabolite urinary concentrations were assessed in 604 mother-son pairs with adjusted multiple logistic regression and Cox's survival model. Several eczema phenotypes were considered. Atopic status was assessed at 5 y of age in 293 boys through total IgE assessment. RESULTS: At 5 y of age, the prevalence of ever eczema was 30.4%. Metabolites of di-isobutyl phthalate (DiBP) and di-isononyl phthalate (DiNP) were positively associated with early-onset (0-24 mo of age) eczema (15.7%) and late-onset (24-60 mo of age) eczema (14.7%). Applying the Cox's model showed a significant association of occurrence of eczema in the first 5 y of life with DiBP and DiNP metabolites. Among IgE-sensitized boys, metabolites of di-n-butyl phthalate (DBP) and DiBP were significantly associated with ever eczema {hazard ratio (HR)=1.67 [95% confidence interval (CI): 1.10, 2.54], p=0.01 and HR=1.87 (95% CI: 1.01, 3.48), p=0.04, respectively}. CONCLUSIONS: Occurrence of eczema in early childhood may be influenced by prenatal exposure to certain phthalates in boys. Further investigations are needed to confirm this observation. https://doi.org/10.1289/EHP1829.

Variability of urinary concentrations of non-persistent chemicals in pregnant women and school-aged children.

BACKGROUND: Exposome studies are challenged by exposure misclassification for non-persistent chemicals, whose temporal variability contributes to bias in dose-response functions. OBJECTIVES: We evaluated the variability of urinary concentrations of 24 non-persistent chemicals: 10 phthalate metabolites, 7 phenols, 6 organophosphate (OP) pesticide metabolites, and cotinine, between weeks from different pregnancy trimesters in pregnant women, and between days and between seasons in children. METHODS: 154 pregnant women and 152 children from six European countries were enrolled in 2014-2015. Pregnant women provided three urine samples over a day (morning, midday, and night), for one week in the 2nd and 3rd pregnancy trimesters. Children provided two urines a day (morning and night), over two one-week periods, six months apart. We pooled all samples for a given subject that were collected within a week. In children, we also made four daily pools (combining morning and night voids) during the last four days of the first follow-up week. Pools were analyzed for all 24 metabolites of interest. We calculated intraclass-correlation coefficients (ICC) and estimated the number of pools needed to obtain an ICC above 0.80. RESULTS: All phthalate metabolites and phenols were detected in >90% of pools whereas certain OP pesticide metabolites and cotinine were detected in <43% of pools. We observed fair (ICC = 0.40-0.59) to good (0.60-0.74) between-day reliability of the pools of two samples in children for all chemicals. Reliability was poor (<0.40) to fair between trimesters in pregnant women and between seasons in children. For most chemicals, three daily pools of two urines each (for weekly exposure windows) and four weekly pools of 15-20 urines each would be necessary to obtain an ICC above 0.80. CONCLUSIONS: This quantification of the variability of biomarker measurements of many non-persistent chemicals during several time windows shows that for many of these compounds a few dozen samples are required to accurately assess exposure over periods encompassing several trimesters or months.

Characterizing the effect of endocrine disruptors on human health: The role of epidemiological cohorts.

Research on endocrine disruptors (EDs) developed from numerous disciplines. In this concert of disciplines, epidemiology is central to inform on the relevance for humans of mechanisms and dose-response functions identified in animals, to characterize the health impact (number of attributable disease cases), the cost associated with ED exposure, and the efficiency of the measures taken to limit exposure. Here, we present epidemiological tools to draw valid inference regarding effects of potential EDs. Epidemiology is generally observational, requiring care to control confounding bias. Many potential EDs have a short biological half-life; approaches relying on repeated biospecimens sampling allow limiting exposure misclassification and the resulting bias. For non-persistent compounds, couple-child cohorts are a central study design. Cohorts can now rely on molecular biology approaches to characterize exposures and intermediate pathways, which corresponds to the advent of molecular epidemiology and allows stronger interactions between epidemiology, toxicology, and molecular epidemiology to characterize the health effects of EDs.

In Utero Exposure to Select Phenols and Phthalates and Respiratory Health in Five-Year-Old Boys: A Prospective Study.

BACKGROUND: Phenols and phthalates may have immunomodulatory and proinflammatory effects and thereby adversely affect respiratory health. OBJECTIVE: We estimated the associations between gestational exposure to select phthalates and phenols and respiratory health in boys. METHODS: Among 587 pregnant women from the EDEN (Etude des Déterminants pré et post natals du développement et de la santé de l'Enfant) cohort who delivered a boy, 9 phenols and 11 phthalates metabolites were quantified in spot pregnancy urine samples. Respiratory outcomes were followed up by questionnaires until age 5, when forced expiratory volume in 1 s (FEV1) was measured by spirometry. Adjusted associations of urinary metabolites log-transformed concentrations with respiratory outcomes and FEV1 in percent predicted (FEV1%) were estimated by survival and linear regression models, respectively. RESULTS: No phenol or phthalate metabolite exhibited clear deleterious associations simultaneously with several respiratory outcomes. Ethyl-paraben was associated with increased asthma rate [hazard rate (HR)=1.10; 95% confidence interval (CI): 1.00, 1.21] and tended to be negatively associated with FEV1% (beta=-0.59; 95% CI: -1.24, 0.05); bisphenol A tended to be associated with increased rates of asthma diagnosis (HR=1.23; 95% CI: 0.97, 1.55) and bronchiolitis/bronchitis (HR=1.13; 95% CI: 0.99, 1.30). Isolated trends for deleterious associations were also observed between 2,5-dichlorophenol and wheezing, and between monocarboxynonyl phthalate, a metabolite of di-isodecyl phthalate (DIDP), and wheezing. CONCLUSION: Ethyl-paraben, bisphenol A, 2,5-dichlorophenol, and DIDP tended to be associated with altered respiratory health, with ethyl-paraben and bisphenol A exhibiting some consistency across respiratory outcomes. The trends between bisphenol A pregnancy level and increased asthma and bronchiolitis/bronchitis rates in childhood were consistent with a previous cohort study. https://doi.org/10.1289/EHP1015.