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BACKGROUND: Gestational exposure to toxic environmental chemicals and maternal social hardships are individually associated with impaired fetal growth, but it is unclear whether the effects of environmental chemical exposure on infant birth weight are modified by maternal hardships. METHODS: We used data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canadian cohort of 1982 pregnant females enrolled between 2008 and 2011. We quantified eleven environmental chemical concentrations from two chemical classes - six organochlorine compounds (OCs) and five metals - that were detected in ≥ 70% of blood samples collected during the first trimester. We examined fetal growth using birth weight adjusted for gestational age and assessed nine maternal hardships by questionnaire. Each maternal hardship variable was dichotomized to indicate whether the females experienced the hardship. In our analysis, we used elastic net to select the environmental chemicals, maternal hardships, and 2-way interactions between maternal hardships and environmental chemicals that were most predictive of birth weight. Next, we obtained effect estimates using multiple linear regression, and plotted the relationships by hardship status for visual interpretation. RESULTS: Elastic net selected trans-nonachlor, lead, low educational status, racially minoritized background, and low supplemental folic acid intake. All were inversely associated with birth weight. Elastic net also selected interaction terms. Among those with increasing environmental chemical exposures and reported hardships, we observed stronger negative associations and a few positive associations. For example, every two-fold increase in lead concentrations was more strongly associated with reduced infant birth weight among participants with low educational status (ß = -100 g (g); 95% confidence interval (CI): -215, 16), than those with higher educational status (ß = -34 g; 95% CI: -63, -3). In contrast, every two-fold increase in mercury concentrations was associated with slightly higher birth weight among participants with low educational status (ß = 23 g; 95% CI: -25, 71) compared to those with higher educational status (ß = -9 g; 95% CI: -24, 6). CONCLUSIONS: Our findings suggest that maternal hardships can modify the associations of gestational exposure to some OCs and metals with infant birth weight.
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Peso al Nacer , Contaminantes Ambientales , Hidrocarburos Clorados , Exposición Materna , Humanos , Femenino , Embarazo , Hidrocarburos Clorados/sangre , Peso al Nacer/efectos de los fármacos , Adulto , Contaminantes Ambientales/sangre , Canadá , Recién Nacido , Adulto Joven , Metales/sangre , Factores Socioeconómicos , Estudios de Cohortes , MasculinoRESUMEN
BACKGROUND: Air pollution exposure during pregnancy affects children's brain function. Maternal stress and nutrition, socioeconomic status, and the child's sex may modify this relationship. OBJECTIVE: To identify characteristics of children with the largest increases in full-scale IQ (FSIQ) after their mothers used HEPA filter air cleaners during pregnancy. METHODS: In this randomized controlled trial we randomly assigned women to receive 1-2 air cleaners or no air cleaners during pregnancy. We analyzed maternal hair samples for cortisol and dehydroepiandrosterone (DHEA). When the children were 48 months old, we measured FSIQ with the Wechsler Preschool and Primary Scale of Intelligence. We evaluated ten potential modifiers of the intervention-FSIQ relationship using interaction terms in separate regression models. To account for correlations between modifiers, we also used a single regression model containing main effects and intervention x modifier terms for all potential modifiers. RESULTS: Among 242 mother-child dyads with complete data, the intervention was associated with a 2.3-point increase (95% CI: -1.5, 6.0 points) in mean FSIQ. The intervention improved mean FSIQ among children of mothers in the bottom (5.4 points; 95% CI: -0.8, 11.5) and top (6.1 points; 95% CI: 0.5, 11.8) cortisol tertiles, but not among those whose mothers were in the middle tertile. The largest between-group difference in the intervention's effect was a 7.5-point (95% CI: -0.7, 15.7) larger increase in mean FSIQ among children whose mothers did not take vitamins than among children whose mothers did take vitamins (interaction p-value = 0.07). We also observed larger benefits among children whose mothers did not complete university, and those with lower hair DHEA concentrations, hair cortisol concentrations outside the middle tertile, or more perceived stress. CONCLUSION: The benefits of reducing air pollution during pregnancy on brain development may be greatest for children whose mothers who do not take vitamins, experience more stress, or have less education.
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Contaminación del Aire , Hidrocortisona , Niño , Embarazo , Preescolar , Humanos , Femenino , Cognición , Deshidroepiandrosterona , VitaminasRESUMEN
BACKGROUND: Unsupervised machine learning techniques have become increasingly popular for studying associations between gestational exposure mixtures and human health. Latent profile analysis is one method that has not been fully explored. METHODS: We estimated associations between gestational chemical mixtures and child neurodevelopment using latent profile analysis. Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) research platform, a longitudinal cohort of pregnant Canadian women and their children, we generated latent profiles from 27 gestational exposure biomarkers. We then examined the associations between these profiles and child Verbal IQ, Performance IQ, and Full-Scale IQ, measured with the Wechsler Preschool and Primary Scale of Intelligence, Third Edition (WPPSI-III). We validated our findings using k-means clustering. RESULTS: Latent profile analysis detected five latent profiles of exposure: a reference profile containing 61% of the study participants, a high monoethyl phthalate (MEP) profile with moderately low persistent organic pollutants (POPs) containing 26%, a high POP profile containing 6%, a low POP profile containing 4%, and a smoking chemicals profile containing 3%. We observed negative associations between both the smoking chemicals and high MEP profiles and all IQ scores and between the high POP profile and Full-Scale and Verbal IQ scores. We also found a positive association between the low POP profile and Full-Scale and Performance IQ scores. All associations had wide 95% confidence intervals. CONCLUSIONS: Latent profile analysis is a promising technique for identifying patterns of chemical exposure and is worthy of further study for its use in examining complicated exposure mixtures.
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Ácidos Ftálicos , Niño , Preescolar , Embarazo , Lactante , Humanos , Femenino , Canadá/epidemiología , Pruebas de Inteligencia , Escalas de WechslerRESUMEN
The Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study is a randomized controlled trial of the effects of portable high efficiency particulate air (HEPA) filter air cleaner use during pregnancy on fetal growth and child health outcomes. A challenge with the study is that the outcome variables cannot be measured in the absence of a live birth. Thus pregnancy loss is a competing event for the outcome variables that can obscure the intervention-outcome relationship. This phenomenon is called "live birth bias" in the epidemiological literature, and it is an example of selection bias due to adjustment for variables affected by previous exposure. Methods: In this investigation, we reanalyzed data from the UGAAR study and examined the impacts of the intervention on three health outcomes: preterm birth (PTB), birth weight, and full-scale IQ (FSIQ) measured with the Wechsler Preschool and Primary Scale of Intelligence III when children were four years old, while accounting for live birth bias. Specifically, we used a novel multiple imputation approach to simulate scenarios in which pregnancy losses had instead been born alive and experienced a range of health outcomes. Results: After accounting for live birth bias, the association between the intervention and PTB diminished. Additionally, the magnitude of intervention effect on birth weight and FSIQ increased. FSIQ was less sensitive to live birth bias than birth weight. Conclusion: We introduced a novel analysis approach to examine the role of live birth bias, and the findings will be useful in environmental epidemiology studies of birth cohorts.
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BACKGROUND: Developmental exposure to airborne particulate matter (PM) may increase children's risk of developing autism spectrum disorder. We quantified the impact of reducing PM exposure during pregnancy on the development of autistic traits in children. We also assessed associations between indoor fine PM (PM2.5) concentrations during pregnancy and autistic traits. METHODS: In this parallel-group randomized controlled trial, we randomized 540 non-smoking pregnant women to receive HEPA filter air cleaners or to a control group, which did not receive air cleaners. We administered the Social Responsiveness Scale (SRS-2) to caregivers when children were a median of 48 months (range: 48 to 51 months). Our primary outcome was the SRS-2 total T-score. We imputed missing data using multiple imputation with chained equations and our primary analysis was by intention to treat. In secondary analyses, we estimated associations between full pregnancy and trimester-specific indoor PM2.5 concentrations and T-scores. RESULTS: We enrolled participants at a median of 11 weeks' gestation. Our analysis included 478 children (233 control, 245 intervention). The intervention reduced average indoor PM2.5 concentrations by 29 % (95 % CI: 21, 37 %). The mean SRS-2 total T-score was 0.5 units lower (95 % CI: -2.5, 1.5) among intervention participants, with evidence of larger benefits for children at the high end of the T-score distribution. An interquartile range (9.6 µg/m3) increase in indoor PM2.5 during pregnancy was associated with 1.8-unit (95 % CI: 0.3, 3.2) increase in mean SRS-2 total T-score. Effect estimates for PM2.5 concentrations by trimester were smaller and confidence intervals spanned no effect. CONCLUSION: Reducing indoor PM during pregnancy had little impact on mean autism-related behavior scores in children. However, indoor PM2.5 concentrations during pregnancy were associated with higher scores. Exposure to particulate matter during pregnancy may influence the development of autistic traits in childhood. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01741051.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , Trastorno del Espectro Autista , Trastorno Autístico , Humanos , Niño , Femenino , Embarazo , Contaminación del Aire Interior/prevención & control , Contaminación del Aire Interior/análisis , Trastorno del Espectro Autista/prevención & control , Material Particulado/análisis , Edad Gestacional , Contaminantes Atmosféricos/análisisRESUMEN
BACKGROUND: Developmental exposure to air pollution is associated with diminished cognitive abilities in observational studies, but no randomized controlled trial has examined the effect of reducing air pollution on cognition in children. OBJECTIVES: We sought to quantify the impact of reducing exposure to particulate matter (PM) during pregnancy on children's cognitive performance at 4 y of age. METHODS: In this single-blind, parallel-group, randomized controlled trial in Ulaanbaatar, Mongolia, we randomly assigned 540 nonsmoking pregnant women (268 intervention and 272 control) to receive 1-2 portable high-efficiency particulate air (HEPA) filter air cleaners or no air cleaners. The air cleaners were used from a median of 11 wk gestation until the end of pregnancy. The primary outcome was full-scale intelligence quotient (FSIQ) assessed using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) when children were a median of 48 months old. We imputed missing outcome data using multiple imputation with chained equations, and our primary analysis was by intention to treat. RESULTS: After excluding known miscarriages, stillbirths, neonatal deaths, and medical conditions that impeded cognitive testing and imputation, 475 (233 control and 242 intervention) children were included in our analyses. In an unadjusted analysis, the mean FSIQ of children who were randomly assigned to the intervention group was 2.5 points [95% confidence interval (CI): -0.4, 5.4 points] higher than that of children in the control group. After adjustment to account for an imbalance in preterm birth between groups, the effect estimate increased to 2.8 points (95% CI: -0.1, 5.7). CONCLUSIONS: Reducing PM air pollution during pregnancy may improve cognitive performance in childhood. https://doi.org/10.1289/EHP10302.
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Contaminación del Aire , Nacimiento Prematuro , Niño , Preescolar , Carbón Mineral , Cognición , Polvo , Femenino , Humanos , Recién Nacido , Material Particulado , Embarazo , Método Simple CiegoRESUMEN
IMPORTANCE: Gestational exposure to particulate matter (PM) air pollution may increase the risk of childhood obesity, but the impact of reducing air pollution during pregnancy on obesity-related outcomes in childhood has not been examined. OBJECTIVE: To assess the impact of reducing gestational PM exposure on body mass index (BMI) at two years of age. METHODS: In this single-blind, parallel group randomized controlled trial in Ulaanbaatar Mongolia, we randomly assigned 540 pregnant women to receive 1-2 portable high efficiency particulate air (HEPA) filter air cleaners or no air cleaners. We measured height and weight when children were a mean age of 23.8 months. Our primary outcome was age- and sex-specific BMI z-score based on the World Health Organization 2007 Growth Charts. Secondary outcomes included age- and sex-specific weight z score, overweight/obesity (defined as BMI z-score > 2.00), and catch-up growth (defined using various cut-offs to identify children with relatively low birth weight for sex and gestational age and relatively high age- and sex-specific weight in childhood). We imputed missing outcome data using multiple imputation with chained equations and our primary analysis was by intention to treat (ITT). We estimated intervention effects on continuous and binary outcomes using linear and logistic regression, respectively. RESULTS: After excluding known miscarriages, still births, and neonatal deaths our analysis included 480 children (235 control and 245 intervention). The mean (SD) child BMI z score was 0.79 (1.0); 9.8% of children were overweight or obese. The mean BMI z score of children who were randomly assigned to the intervention group was 0.16-units lower (95% CI: -0.35, 0.04) than children in the control group. The intervention was also associated with reductions in overweight/obesity (odds ratio = 0.59; 95% CI: 0.31, 1.12). Catch-up growth occurred less frequently in the intervention group, but effect estimates varied depending on the specific definition of catch-up growth and confidence intervals consistently spanned no effect. CONCLUSIONS: We found that the use of portable air cleaners during pregnancy was associated with improvements in obesity-related outcomes, although some effect estimates lacked precision. Reducing PM exposure during pregnancy may lead to improvements in cardiometabolic health in childhood.
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Filtros de Aire , Contaminación del Aire , Obesidad Infantil , Índice de Masa Corporal , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Sobrepeso , Obesidad Infantil/epidemiología , Obesidad Infantil/prevención & control , Embarazo , Método Simple CiegoRESUMEN
BACKGROUND: Developmental exposure to particulate matter (PM) air pollution may impair children's behaviors. Our objectives were to quantify the impact of reducing indoor PM using portable HEPA filter air cleaners during pregnancy on behavioral problems in children and to assess associations between indoor fine PM (PM2.5) concentrations during pregnancy and children's behavior. METHODS: This is a secondary analysis of a single-blind parallel-group randomized controlled trial in which we randomly assigned 540 non-smoking pregnant women to receive 1 or 2 HEPA filter air cleaners or no air cleaners. We administered the Behavior Assessment System for Children (BASC-3) to caregivers when children were a mean age of 23 months, and again at a mean age of 48 months. Primary outcomes were the four BASC-3 composite scales: externalizing problems, internalizing problems, adaptive skills, and the behavioral symptoms index. We imputed missing data using multiple imputation with chained equations. The primary analysis was by intention-to-treat. In a secondary analysis, we evaluated associations between BASC-3 composite indices and modeled trimester-specific PM2.5 concentrations inside residences. RESULTS: We enrolled participants at a median of 11 weeks gestation. After excluding miscarriages, still births and neonatal deaths, our analysis included 478 children (233 control and 245 intervention). We observed no differences in the mean BASC-3 scores between treatment groups. An interquartile increase (20.1 µg/m3) in first trimester PM2.5 concentration was associated with higher externalizing problem scores (2.4 units, 95% CI: 0.7, 4.1), higher internalizing problem scores (2.4 units, 95% CI: 0.7, 4.0), lower adaptive skills scores (-1.5 units, 95% CI: -3.0, 0.0), and higher behavior symptoms index scores (2.3 units, 95% CI: 0.7, 3.9). Third trimester PM2.5 concentrations were also associated with some behavioral indices at age 4, but effect estimates were smaller. No significant associations were observed with PM2.5 concentrations during the second trimester or for any of the BASC indices when children were 2 years old. CONCLUSION: We found no benefit of reducing indoor particulate air pollution during pregnancy on parent-reported behaviors in children. Associations between indoor PM2.5 concentrations in the first trimester and behavioral scores among 4-year old children suggest that it may be necessary to intervene early in pregnancy to protect children, but these exploratory findings should be interpreted cautiously. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01741051.
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Contaminación del Aire Interior/prevención & control , Conducta Infantil , Exposición Materna/prevención & control , Efectos Tardíos de la Exposición Prenatal/prevención & control , Problema de Conducta , Filtros de Aire , Contaminantes Atmosféricos/análisis , Preescolar , Femenino , Humanos , Masculino , Material Particulado/análisis , Embarazo , UltrafiltraciónRESUMEN
Studying the effects of gestational exposures to chemical mixtures on infant birth weight is inconclusive due to several challenges. One of the challenges is which statistical methods to rely on. Bayesian factor analysis (BFA), which has not been utilized for chemical mixtures, has advantages in variance reduction and model interpretation. METHODS: We analyzed data from a cohort of 384 pregnant women and their newborns using urinary biomarkers of phthalates, phenols, and organophosphate pesticides (OPs) and serum biomarkers of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), perfluoroalkyl substances (PFAS), and organochlorine pesticides (OCPs). We examined the association between exposure to chemical mixtures and birth weight using BFA and compared with multiple linear regression (MLR) and Bayesian kernel regression models (BKMR). RESULTS: For BFA, a 10-fold increase in the concentrations of PCB and PFAS mixtures was associated with an 81 g (95% confidence intervals [CI] = -132 to -31 g) and 57 g (95% CI = -105 to -10 g) reduction in birth weight, respectively. BKMR results confirmed the direction of effect. However, the 95% credible intervals all contained the null. For single-pollutant MLR, a 10-fold increases in the concentrations of multiple chemicals were associated with reduced birth weight, yet the 95% CI all contained the null. Variance inflation from MLR was apparent for models that adjusted for copollutants, resulting in less precise confidence intervals. CONCLUSION: We demonstrated the merits of BFA on mixture analysis in terms of precision and interpretation compared with MLR and BKMR. We also identified the association between exposure to PCBs and PFAS and lower birth weight.
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Autism spectrum disorder, which is characterized by impaired social communication and stereotypic behaviors, affects 1%-2% of children. Although prenatal exposure to toxicants has been associated with autistic behaviors, most studies have been focused on shifts in mean behavior scores. We used Bayesian quantile regression to assess the associations between log2-transformed toxicant concentrations and autistic behaviors across the distribution of behaviors. We used data from the Maternal-Infant Research on Environmental Chemicals study, a pan-Canadian cohort (2008-2011). We measured metal, pesticide, polychlorinated biphenyl, phthalate, bisphenol-A, and triclosan concentrations in blood or urine samples collected during the first trimester of pregnancy. Using the Social Responsiveness Scale (SRS), in which higher scores denote more autistic-like behaviors, autistic behaviors were assessed in 478 children aged 3-4 years old. Lead, cadmium, and most phthalate metabolites were associated with mild increases in SRS scores at the 90th percentile of the SRS distribution. Manganese and some pesticides were associated with mild decreases in SRS scores at the 90th percentile of the SRS distribution. We identified several monotonic trends in which associations increased in magnitude from the bottom to the top of the SRS distribution. These results suggest that quantile regression can reveal nuanced relationships and, thus, should be more widely used by epidemiologists.
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Trastorno del Espectro Autista/inducido químicamente , Exposición a Riesgos Ambientales/efectos adversos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Adolescente , Adulto , Teorema de Bayes , Compuestos de Bencidrilo/efectos adversos , Preescolar , Estudios de Cohortes , Femenino , Humanos , Metales Pesados/efectos adversos , Plaguicidas/efectos adversos , Fenoles/efectos adversos , Ácidos Ftálicos/efectos adversos , Bifenilos Policlorados/efectos adversos , Embarazo , Triclosán/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Pregnant women are regularly exposed to a multitude of endocrine disrupting chemicals (EDCs). EDC exposures, both individually and as mixtures, may affect fetal growth. The relationship of EDC mixtures with infant birth weight, however, remains poorly understood. We examined the relations between prenatal exposure to EDC mixtures and infant birth weight. METHODS: We used data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canadian cohort of 1857 pregnant women enrolled between 2008 and 2011. We quantified twenty-one chemical concentrations from five EDC classes, including organochlorine compounds (OCs), metals, perfluoroalkyl substances (PFAS), phenols and phthalate metabolites that were detected in >70% of urine or blood samples collected during the first trimester. In our primary analysis, we used Bayesian kernel machine regression (BKMR) models to assess variable importance, explore EDC mixture effects, and identify any interactions among EDCs. Our secondary analysis used traditional linear regression to compare the results with those of BKMR and to quantify the changes in mean birth weight in relation to prenatal EDC exposures. RESULTS: We found evidence that mixtures of OCs and metals were associated with monotonic decreases in mean birth weight across the whole range of exposure. trans-Nonachlor from the OC mixture and lead (Pb) from the metal mixture had the greatest impact on birth weight. Our linear regression analysis corroborated the BKMR results and found that a 2-fold increase in trans-nonachlor and Pb concentrations reduced mean birth weight by -38 g (95% confidence interval (CI): -67, -10) and -39 g (95% CI: -69, -9), respectively. A sex-specific association for OC mixture was observed among female infants. PFAS, phenols and phthalates were not associated with birth weight. No interactions were observed among the EDCs. CONCLUSIONS: Using BKMR, we observed that both OC and metal mixtures were associated with decreased birth weight in the MIREC Study. trans-Nonachlor from the OC mixture and Pb from the metal mixture contributed most to the adverse effects.
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Disruptores Endocrinos , Contaminantes Ambientales , Efectos Tardíos de la Exposición Prenatal , Teorema de Bayes , Peso al Nacer , Canadá , Disruptores Endocrinos/toxicidad , Contaminantes Ambientales/toxicidad , Femenino , Humanos , Lactante , Masculino , Exposición Materna/efectos adversos , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/epidemiologíaRESUMEN
BACKGROUND: To apply a novel method to adjust for HIV knowledge as an unmeasured confounder for the effect of unsafe injection on future HIV testing. METHODS: The data were collected from 601 HIV-negative persons who inject drugs (PWID) from a cohort in San Francisco. The panel-data generalized estimating equations (GEE) technique was used to estimate the adjusted risk ratio (RR) for the effect of unsafe injection on not being tested (NBT) for HIV. Expert opinion quantified the bias parameters to adjust for insufficient knowledge about HIV transmission as an unmeasured confounder using Bayesian bias analysis. RESULTS: Expert opinion estimated that 2.5%-40.0% of PWID with unsafe injection had insufficient HIV knowledge; whereas 1.0%-20.0% who practiced safe injection had insufficient knowledge. Experts also estimated the RR for the association between insufficient knowledge and NBT for HIV as 1.1-5.0. The RR estimate for the association between unsafe injection and NBT for HIV, adjusted for measured confounders, was 0.96 (95% confidence interval: 0.89,1.03). However, the RR estimate decreased to 0.82 (95% credible interval: 0.64, 0.99) after adjusting for insufficient knowledge as an unmeasured confounder. CONCLUSION: Our Bayesian approach that uses expert opinion to adjust for unmeasured confounders revealed that PWID who practice unsafe injection are more likely to be tested for HIV - an association that was not seen by conventional analysis.
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Sesgo , Testimonio de Experto , Infecciones por VIH/transmisión , Seropositividad para VIH/epidemiología , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adulto , Teorema de Bayes , Consumidores de Drogas , Femenino , Prueba de VIH , Humanos , Masculino , Estudios Prospectivos , Análisis de Regresión , Asunción de Riesgos , San Francisco/epidemiología , Adulto JovenRESUMEN
INTRODUCTION: Despite a recent meta-analysis including 31 randomised controlled trials comparing methadone and buprenorphine for the treatment of opioid use disorder, important knowledge gaps remain regarding the long-term effectiveness of different treatment modalities across individuals, including rigorously collected data on retention rates and other treatment outcomes. Evidence from real-world data represents a valuable opportunity to improve personalised treatment and patient-centred guidelines for vulnerable populations and inform strategies to reduce opioid-related mortality. Our objective is to determine the comparative effectiveness of methadone versus buprenorphine/naloxone, both overall and within key populations, in a setting where both medications are simultaneously available in office-based practices and specialised clinics. METHODS AND ANALYSIS: We propose a retrospective cohort study of all adults living in British Columbia receiving opioid agonist treatment (OAT) with methadone or buprenorphine/naloxone between 1 January 2008 and 30 September 2018. The study will draw on seven linked population-level administrative databases. The primary outcomes include retention in OAT and all-cause mortality. We will determine the effectiveness of buprenorphine/naloxone vs methadone using intention-to-treat and per-protocol analyses-the former emulating flexible-dose trials and the latter focusing on the comparison of the two medication regimens offered at the optimal dose. Sensitivity analyses will be used to assess the robustness of results to heterogeneity in the patient population and threats to internal validity. ETHICS AND DISSEMINATION: The protocol, cohort creation and analysis plan have been approved and classified as a quality improvement initiative exempt from ethical review (Providence Health Care Research Institute and the Simon Fraser University Office of Research Ethics). Dissemination is planned via conferences and publications, and through direct engagement and collaboration with entities that issue clinical guidelines, such as professional medical societies and public health organisations.
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Buprenorfina , Trastornos Relacionados con Opioides , Adulto , Analgésicos Opioides/uso terapéutico , Colombia Británica , Buprenorfina/uso terapéutico , Combinación Buprenorfina y Naloxona/uso terapéutico , Humanos , Metadona/uso terapéutico , Estudios Observacionales como Asunto , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
OBJECTIVES: To examine the relation between prenatal urinary phthalate metabolite concentrations and preterm birth (PTB). METHODS: The data were drawn from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canadian cohort of 1857 pregnant women enrolled between 2008 and 2011. We quantified urinary concentrations of 7 phthalate metabolites that were detected in > 70% of urine samples collected during the first trimester. Gestational age was obtained from either the last menstrual period or early ultrasound. We used Cox proportional hazard models to examine the associations of urinary phthalate metabolite concentrations, plus the molar sum of di-2-ethylhexyl phthalate metabolites (∑DEHP), with time to delivery before 37 weeks of gestation. We also examined PTB by clinical presentation. PTBs presented with either spontaneous labour or premature rupture of the membrane were considered spontaneous PTB (sPTB). Additionally, we used multiple linear regression to model changes in mean gestational age in relation to phthalate exposure. RESULTS: We found no evidence of an association between first trimester phthalate metabolite concentrations and PTB among the MIREC study participants. For example, each 2-fold increase in any of the 7 phthalate concentrations or ∑DEHP was associated with hazard ratios (HRs) for PTB ranging from 0.95 to 1.07 with 95% confidence intervals including the null. An assessment of non-linear trends showed some evidence of non-monotonic dose-response relationships between phthalates and PTB. Furthermore, male infants exposed to MCPP showed higher sPTB risk compared with female infants. CONCLUSION: Phthalate exposure during early pregnancy is not clearly associated with the risk of PTB among this Canadian population.
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Ácidos Ftálicos/toxicidad , Ácidos Ftálicos/orina , Nacimiento Prematuro/inducido químicamente , Efectos Tardíos de la Exposición Prenatal , Adulto , Canadá/epidemiología , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Primer Trimestre del Embarazo/orina , Nacimiento Prematuro/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Gestational cadmium exposure may impair fetal growth. Coal smoke has largely been unexplored as a source of cadmium exposure. We investigated the relationship between gestational cadmium exposure and fetal growth, and assessed coal smoke as a potential source of airborne cadmium, among non-smoking pregnant women in Ulaanbaatar, Mongolia, where coal combustion in home heating stoves is a major source of outdoor and indoor air pollution. METHODS: This observational study was nested within the Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study, a randomized controlled trial of portable high efficiency particulate air (HEPA) filter air cleaner use during pregnancy, fetal growth, and early childhood development. We measured third trimester blood cadmium concentrations in 374 out of 465 participants who had a live birth. We used multiple linear and logistic regression to assess the relationships between log2-transformed maternal blood cadmium concentrations and birth weight, length, head circumference, ponderal index, low birth weight, small for gestational age, and preterm birth in crude and adjusted models. We also evaluated the relationships between log2-transformed blood cadmium concentrations and the density of coal-burning stoves within 5000â¯m of each participant's apartment as a proxy of coal smoke emissions from home heating stoves. RESULTS: The median (25th,75th percentile) blood cadmium concentration was 0.20 (0.15, 0.29) µg/L. A doubling of blood cadmium was associated with a 95â¯g (95% CI: 34, 155â¯g) reduction in birth weight in adjusted models. An interquartile range increase in coal stove density (from 3.4 to 4.9 gers/hectare) surrounding participants' apartments was associated with a 12.2% (95% CI: 0.3, 25.6%) increase in blood cadmium concentrations. CONCLUSIONS: Gestational cadmium exposure was associated with reduced birth weight. In settings where coal is a widely used fuel, cadmium may play a role in the putative association between air pollution and impaired fetal growth.
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Contaminantes Atmosféricos/toxicidad , Cadmio/toxicidad , Carbón Mineral/toxicidad , Desarrollo Fetal/efectos de los fármacos , Contaminación del Aire/estadística & datos numéricos , Peso al Nacer , Niño , Preescolar , Femenino , Humanos , Recién Nacido , Exposición Materna/estadística & datos numéricos , Mongolia , Material Particulado , EmbarazoRESUMEN
There is little known about geographic variability in the incidence of glomerular disease and its potential implications for care delivery. To evaluate this, we performed a population-level cohort study using a provincial renal pathology database (2000-2012) to capture all incident cases of glomerulonephritis in British Columbia, Canada. This included 401 patients with membranous nephropathy (MN), 824 patients with IgA nephropathy (IgAN), 385 patients with focal segmental glomerulosclerosis (FSGS), 397 patients with lupus nephritis (LN) and 399 patients with ANCA-related glomerulonephritis (ANCA-GN). Geographic clusters were identified using Bayesian spatial models to estimate the incidence of each disease in 74 regions compared to the mean incidence in the entire province (incidence rate ratio, [IRR]), adjusted for region-level age, sex and race. The proportion of overall variability in incidence attributed to inter-regional differences varied by disease: 18% in MN, 81% in IgAN, 18% in FSGS, 59% in ANCA-GN, and 89% in LN. Except for LN, clustering was not explained by demographics. All IgAN and LN clusters were in urban regions close to nephrology centers, whereas ANCA-GN, MN and FSGS clustered mainly in rural regions. All ANCA-GN clusters were rural with median population density 1.2 persons/km2 and driving distances of 10-676 km to the nearest nephrology center. Thus, we found significant geographic clustering in the incidence of different glomerular diseases. MN, FSGS and ANCA-GN clustered in sparsely populated regions with limited access to care, underscoring the importance of regional variability in glomerular diseases to inform health services delivery.
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Glomerulonefritis/epidemiología , Accesibilidad a los Servicios de Salud/organización & administración , Necesidades y Demandas de Servicios de Salud , Área sin Atención Médica , Población Rural/estadística & datos numéricos , Adulto , Anciano , Teorema de Bayes , Colombia Británica/epidemiología , Análisis por Conglomerados , Femenino , Geografía , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Población Urbana/estadística & datos numéricos , Adulto JovenRESUMEN
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and repetitive or stereotypic behaviours. In utero exposure to environmental chemicals, such as polychlorinated biphenyls (PCBs), may play a role in the etiology of ASD. We examined the relation between plasma PCB concentrations measured during pregnancy and autistic behaviours in a subset of children aged 3â»4 years old in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pregnancy and birth cohort of 546 mother-infant pairs from Canada (enrolled: 2008â»2011). We quantified the concentrations of 6 PCB congeners that were detected in >40% of plasma samples collected during the 1st trimester. At age 3â»4 years, caregivers completed the Social Responsiveness Scale-2 (SRS), a valid and reliable measure of children's reciprocal social and repetitive behaviours and restricted interests. We examined SRS scores as both a continuous and binary outcome, and we calculated Bayesian predictive odds ratios for more autistic behaviours based on a latent variable model for SRS scores >60. We found no evidence of an association between plasma PCB concentrations and autistic behaviour. However, we found small and imprecise increases in the mean SRS score and odds of more autistic behaviour for the highest category of plasma PCB concentrations compared with the lowest category; for instance, an average increase of 1.4 (95%PCI: -0.4, 3.2) in the mean SRS (exposure contrast highest versus lowest PCB category) for PCB138 translated to an odds ratio of 1.8 (95%PCI: 1.0, 2.9). Our findings illustrate the importance of measuring associations between PCBs and autistic behaviour on both continuous and binary scales.
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Trastorno del Espectro Autista/inducido químicamente , Contaminantes Ambientales/sangre , Exposición Materna/efectos adversos , Bifenilos Policlorados/sangre , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Trastorno del Espectro Autista/sangre , Teorema de Bayes , Canadá , Estudios de Casos y Controles , Preescolar , Monitoreo del Ambiente , Femenino , Humanos , Masculino , Oportunidad Relativa , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Factores de RiesgoRESUMEN
BACKGROUND: Mercury is toxic to the developing brain, but the lowest concentration associated with the development of behavior problems is unclear. The purpose of this study was to examine the association between very low-level mercury exposure during fetal development and behavior problems in children. METHODS: We used data from 389 mothers and children in a prospective pregnancy and birth cohort study. We defined mean prenatal mercury concentration as the mean of total whole blood mercury concentrations in maternal samples collected at 16- and 26-weeks of gestation, delivery, and neonatal cord blood samples. We assessed parent-reported child behavior up to five times from two to 8 years of age using the Behavioral Assessment System for Children (BASC-2). At 8 years of age, we assessed self-reported child anxiety using the Spence Children's Anxiety Scale (SCAS). We used multiple linear mixed models and linear regression models to estimate the association between mean prenatal mercury concentrations and child behavior and anxiety, respectively. RESULTS: The median prenatal total blood mercury concentrations was 0.67 µg/L. Overall, we did not find statistically significant associations between mean prenatal mercury concentrations and behavior problems scores, but a 2-fold increase in mercury concentrations at 16-weeks gestation was associated with 0.83 point (95% CI: 0.05, 1.62) higher BASC-2 anxiety scores. Maternal and cord blood mercury concentrations at delivery were associated with parent-reported anxiety at 8 years. CONCLUSION: We found limited evidence of an association between very-low level prenatal mercury exposure and behaviors in children, with an exception of anxiety.
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Conducta Infantil/efectos de los fármacos , Contaminantes Ambientales/efectos adversos , Sangre Fetal/química , Exposición Materna/efectos adversos , Mercurio/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Adulto , Ansiedad/epidemiología , Niño , Preescolar , Estudios de Cohortes , Contaminantes Ambientales/sangre , Femenino , Humanos , Masculino , Intercambio Materno-Fetal , Mercurio/sangre , EmbarazoRESUMEN
BACKGROUND: Indoor and outdoor fine particulate matter (PM2.5) are both leading risk factors for death and disease, but making indoor measurements is often infeasible for large study populations. METHODS: We developed models to predict indoor PM2.5 concentrations for pregnant women who were part of a randomized controlled trial of portable air cleaners in Ulaanbaatar, Mongolia. We used multiple linear regression (MLR) and random forest regression (RFR) to model indoor PM2.5 concentrations with 447 independent 7-day PM2.5 measurements and 87 potential predictor variables obtained from outdoor monitoring data, questionnaires, home assessments, and geographic data sets. We also developed blended models that combined the MLR and RFR approaches. All models were evaluated in a 10-fold cross-validation. RESULTS: The predictors in the MLR model were season, outdoor PM2.5 concentration, the number of air cleaners deployed, and the density of gers (traditional felt-lined yurts) surrounding the apartments. MLR and RFR had similar performance in cross-validation (R2â¯=â¯50.2%, R2â¯=â¯48.9% respectively). The blended MLR model that included RFR predictions had the best performance (cross validation R2â¯=â¯81.5%). Intervention status alone explained only 6.0% of the variation in indoor PM2.5 concentrations. CONCLUSIONS: We predicted a moderate amount of variation in indoor PM2.5 concentrations using easily obtained predictor variables and the models explained substantially more variation than intervention status alone. While RFR shows promise for modelling indoor concentrations, our results highlight the importance of out-of-sample validation when evaluating model performance. We also demonstrate the improved performance of blended MLR/RFR models in predicting indoor air pollution.
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Contaminación del Aire Interior/análisis , Exposición Materna , Modelos Teóricos , Material Particulado/análisis , Filtros de Aire , Monitoreo del Ambiente/métodos , Femenino , Humanos , Modelos Lineales , Mongolia , Tamaño de la Partícula , Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Estaciones del AñoRESUMEN
Causal mediation analysis techniques enable investigators to examine whether the effect of the exposure on an outcome is mediated by some intermediate variable. Motivated by a data example from epidemiology, we consider estimation of natural direct and indirect effects on a survival outcome. An important concern is bias from confounders that may be unmeasured. Estimating natural direct and indirect effects requires an elaborate series of assumptions in order to identify the target quantities. The analyst must carefully measure and adjust for important predictors of the exposure, mediator and outcome. Omitting important confounders may bias the results in a way that is difficult to predict. In recent years, several methods have been proposed to explore sensitivity to unmeasured confounding in mediation analysis. However, many of these methods limit complexity by relying on a handful of sensitivity parameters that are difficult to interpret, or alternatively, by assuming that specific patterns of unmeasured confounding are absent. Instead, we propose a simple Bayesian sensitivity analysis technique that is indexed by four bias parameters. Our method has the unique advantage that it is able to simultaneously assess unmeasured confounding in the mediator-outcome, exposure-outcome and exposure-mediator relationships. It is a natural Bayesian extension of the sensitivity analysis methodologies of VanderWeele, which have been widely used in the epidemiology literature. We present simulation findings, and additionally, we illustrate the method in an epidemiological study of mortality rates in criminal offenders from British Columbia.