Critical Windows Of Exposure Research Articles

Term birthweight and critical windows of prenatal exposure to average meteorological conditions and meteorological variability

BackgroundHeat stress during pregnancy may limit fetal growth, with ramifications throughout the life course. However, critical exposure windows are unknown, and effects of meteorological variability have not been investigated. ObjectivesWe aimed to identify sensitive windows for the associations of mean and variability of temperature and humidity with term birthweight. MethodsWe analyzed data from two French mother–child cohorts, EDEN and PELAGIE (n = 4771), recruited in 2002–2006. Temperature exposure was assessed using a satellite-based model with daily 1-km2 resolution, and relative humidity exposure data were obtained from Météo France monitors. Distributed lag models were constructed using weekly means and standard deviation (SD, to quantify variability) from the first 37 gestational weeks. Analyses were then stratified by sex. Results for each exposure were adjusted for the other exposures, gestational age at birth, season and year of conception, cohort and recruitment center, and individual confounders. ResultsThere was no evidence of association between term birthweight and mean temperature. We identified a critical window in weeks 6–20 for temperature variability (cumulative change in term birthweight of −54.2 g [95% CI: −102, −6] for a 1 °C increase in SD of temperature for each week in that window). Upon stratification by sex of the infant, the relationship remained for boys (weeks 1–21, cumulative change: −125 g [95% CI: −228, −21]). For mean humidity, there was a critical window in weeks 26–37, with a cumulative change of −28 g (95% CI: −49, −7) associated with a 5% increase in humidity for each week. The critical window was longer and had a stronger association in boys (weeks 29–37; −37 g, 95% CI: −63, −11) than girls (week 14; −1.8 g, 95% CI: −3.6, −0.1). DiscussionWeekly temperature variability and mean humidity during critical exposure windows were associated with decreased term birthweight, especially in boys.

Lagged WQS regression for mixtures with many components

The developmental timing of exposures to toxic chemicals or combinations of chemicals may be as important as the dosage itself. This concept is called “critical windows of exposure.” The time boundaries of such windows can be detected if exposure data are collected repeatedly in short time intervals. The development of tooth-matrix biomarkers which provide prenatal and postnatal exposure measures in repeated intervals can provide such data. Using teeth, we use reverse distributed lagged models (DLMs) to incorporate weekly prenatal and postnatal measures of exposures to estimate time-varying associations with developmental effects. The analysis of such data using lagged weighted quantile sum (WQS) regression as an extension to reverse DLMs for complex mixtures was first proposed by Bello et al. This prior algorithm was not operationally generalizable to large numbers of components (say, more than five or six). We propose a revised algorithm that may be useful for larger mixtures by combining time-specific WQS(t) indices in a reverse DLM. We demonstrate the new algorithm using tooth data in association with a neurodevelopmental score and in simulated data from 3 cases wherein different components of a mixture have time varying associations and in the case where none have associations. The new algorithm correctly detects the simulated associations when the number of samples within the time-specific analyses is moderate to large.

Identifying a critical window of maternal metal exposure for maternal and neonatal thyroid function in China: A cohort study

BackgroundChina, a developing country, has a particularly serious problem with metal pollution. We evaluated the association of metal exposure during pregnancy with maternal and neonatal thyroid function, and identified the critical window for maternal metal exposure effects on maternal and neonatal thyroid functions. MethodsThe maternal urinary concentrations of mercury (Hg), cadmium (Cd), arsenic (As) and cesium (Cs) were determined in pregnant women during their first (n = 389) or third (n = 257) trimesters in a prospective cohort from 2014 to 2015 in Nanjing, China, using an inductively coupled plasma mass spectrometry (ICP-MS) instrument. Maternal serum-free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were measured by electrochemiluminescent microparticle immunoassays in the second and third trimesters. Neonatal TSH levels were detected 72 h after birth. ResultsHg (>0.162 µg/L), Cd (>0.084 µg/L), As (>0.348 µg/L) and Cs (>0.093 µg/L) were detectable in 76.9%, 90.1%, 100% and 100% of maternal urine samples from women in the first trimester of pregnancy. In the multiple adjusted linear regression models, maternal exposures to Hg and Cd in the first trimester were positively associated with maternal TSH levels in the second trimester (P < 0.01, P = 0.02). Moreover, maternal exposures to Cd and Cs in the first trimester were positively associated with neonatal TSH levels (P = 0.04, P = 0.02). In the Bayesian kernel machine regression (BKMR) model, the results were stable and consistent with the linear regression model. ConclusionsMaternal exposure to Hg, Cd and Cs in the first trimester was related to TSH levels in mothers and newborns. Efforts to identify maternal and neonatal thyroid disruptors should carefully consider the effects of exposure to these metals.

Infant Mortality Related to NO2 and PM Exposure: Systematic Review and Meta-Analysis.

Background: We conducted this systematic review and meta-analysis to address the crucial public health issue of the suspected association between air pollution exposure during pregnancy and the risk of infant mortality. Methods: We searched on MEDLINE ® databases among articles published until February, 2019 for case-control, cohort, and ecological studies assessing the association between maternal exposure to Nitrogen Dioxide (NO2) or Particular matter (PM) and the risk of infant mortality including infant, neonatal, and post-neonatal mortality for all-and specific-causes as well. Study-specific risk estimates were pooled according to random-effect and fixed-effect models. Results: Twenty-four articles were included in the systematic review and 14 of the studies were taken into account in the meta-analysis. We conducted the meta-analysis for six combinations of air pollutants and infant death when at least four studies were available for the same combination. Our systematic review has revealed that the majority of studies concluded that death risk increased with increased exposure to air pollution including PM10, PM2.5, and NO2. Our meta-analysis confirms that the risk of post-neonatal mortality all-causes for short-term exposure to PM10 increased significantly (pooled-OR = 1.013, 95% CI (1.002, 1.025). When focusing on respiratory-causes, the risk of post-neonatal death related to long-term exposure to PM10 reached a pooled-OR = 1.134, 95% CI (1.011, 1.271). Regarding Sudden Infant Death Syndrome (SIDS), the risk also increased significantly: pooled-OR = 1.045, 95% CI (1.01, 1.08) per 10 µg/m3), but no specific gestational windows of exposure were identified. Conclusion: In spite of a few number of epidemiological studies selected in the present literature review, our finding is in favor of a significant increase of infant death with the increase of air pollution exposure during either the pregnancy period or the first year of a newborn’s life. Our findings have to be interpreted with caution due to weaknesses that could affect the strength of the associations and then the formulation of accurate conclusions. Future studies are called to overcome these limitations; in particular, (i) the definition of infant adverse outcome, (ii) exposure assessment, and (iii) critical windows of exposure, which could affect the strength of association.

Environmental mixtures and children's health: identifying appropriate statistical approaches.

Biomonitoring studies have shown that children are constantly exposed to complex patterns of chemical and nonchemical exposures. Here, we briefly summarize the rationale for studying multiple exposures, also called mixture, in relation to child health and key statistical approaches that can be used. We discuss advantages over traditional methods, limitations and appropriateness of the context. New approaches allow pediatric researchers to answer increasingly complex questions related to environmental mixtures. We present methods to identify the most relevant exposures among a high-multitude of variables, via shrinkage and variable selection techniques, and identify the overall mixture effect, via Weighted Quantile Sum and Bayesian Kernel Machine regressions. We then describe novel extensions that handle high-dimensional exposure data and allow identification of critical exposure windows. Recent advances in statistics and machine learning enable researchers to identify important mixture components, estimate joint mixture effects and pinpoint critical windows of exposure. Despite many advantages over single chemical approaches, measurement error and biases may be amplified in mixtures research, requiring careful study planning and design. Future research requires increased collaboration between epidemiologists, statisticians and data scientists, and further integration with causal inference methods.

A spatially varying distributed lag model with application to an air pollution and term low birth weight study.

Distributed lag models have been used to identify critical pregnancy periods of exposure (i.e. critical exposure windows) to air pollution in studies of pregnancy outcomes. However, much of the previous work in this area has ignored the possibility of spatial variability in the lagged health effect parameters that may result from exposure characteristics and/or residual confounding. We develop a spatially varying Gaussian process model for critical windows called 'SpGPCW' and use it to investigate geographic variability in the association between term low birth weight and average weekly concentrations of ozone and PM2:5 during pregnancy by using birth records from North Carolina. SpGPCW is designed to accommodate areal level spatial correlation between lagged health effect parameters and temporal smoothness in risk estimation across pregnancy. Through simulation and a real data application, we show that the consequences of ignoring spatial variability in the lagged health effect parameters include less reliable inference for the parameters and diminished ability to identify true critical window sets, and we investigate the use of existing Bayesian model comparison techniques as tools for determining the presence of spatial variability. We find that exposure to PM2:5 is associated with elevated term low birth weight risk in selected weeks and counties and that ignoring spatial variability results in null associations during these periods. An R package (SpGPCW) has been developed to implement the new method.

Associations of maternal ozone exposures during pregnancy with maternal blood pressure and risk of hypertensive disorders of pregnancy: A birth cohort study in Guangzhou, China

Although studies have assessed the associations of maternal exposure to ozone (O3) during pregnancy with blood pressure and the risk of hypertensive disorders of pregnancy (HDP), the results were inconsistent. Furthermore, no studies have been conducted in China where the ambient O3 concentration continuedly increased. The present study aimed to estimate the effects of maternal exposure to O3 during pregnancy on the HDP risk, systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP). All participants of pregnant women were selected from the prospective birth cohort study on Prenatal Environments and Offspring Health conducted in Guangzhou, China. A spatiotemporal land-use-regression model was used to estimate individual monthly air pollution exposure from three months before pregnancy to childbirth date. Information on HDP, SBP, DBP and PP was obtained from maternal medical records. A Logistic regression model and a mixed linear model were used to estimate the associations of maternal exposure to O3 with the risk of HDP and blood pressure (SBP, DBP and PP), respectively. We found significant associations of maternal exposure to O3 during the third (OR = 1.31, 95%CI: 1.07, 1.60) and the second month (OR = 1.25, 95%CI: 1.02, 1.51) before pregnancy with the risk of HDP. Observed significantly positive associations of O3 exposures with SBP, DBP and PP during the two months before pregnancy and during the early pregnancy. The peak effects of O3 exposure on SBP, DBP and PP were respectively observed during the second month of pregnancy (β = 1.07 mmHg, 95%CI: 0.84, 1.31 mmHg), the first month before pregnancy (β = 0.40 mmHg, 95%CI: 0.21, 0.50 mmHg) and the second month of pregnancy (β = 0.78 mmHg, 95%CI: 0.59, 0.97 mmHg). Our results suggest that maternal exposure to O3 were positively associated with blood pressure and the risk of HDP, and the period from three months before pregnancy to the first trimester might be the critical exposure window.

Early Life Exposure to Air Pollution and Autism Spectrum Disorder: Findings from a Multisite Case-Control Study.

Epidemiologic studies have reported associations between prenatal and early postnatal air pollution exposure and autism spectrum disorder (ASD); however, findings differ by pollutant and developmental window. We examined associations between early life exposure to particulate matter ≤2.5 µm in diameter (PM2.5) and ozone in association with ASD across multiple US regions. Our study participants included 674 children with confirmed ASD and 855 population controls from the Study to Explore Early Development, a multi-site case-control study of children born from 2003 to 2006 in the United States. We used a satellite-based model to assign air pollutant exposure averages during several critical periods of neurodevelopment: 3 months before pregnancy; each trimester of pregnancy; the entire pregnancy; and the first year of life. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for study site, maternal age, maternal education, maternal race/ethnicity, maternal smoking, and month and year of birth. The air pollution-ASD associations appeared to vary by exposure time period. Ozone exposure during the third trimester was associated with ASD, with an OR of 1.2 (95% CI: 1.1, 1.4) per 6.6 ppb increase in ozone. We additionally observed a positive association with PM2.5 exposure during the first year of life (OR = 1.3 [95% CI: 1.0, 1.6] per 1.6 µg/m increase in PM2.5). Our study corroborates previous findings of a positive association between early life air pollution exposure and ASD, and identifies a potential critical window of exposure during the late prenatal and early postnatal periods.

Associations of maternal quitting, reducing, and continuing smoking during pregnancy with longitudinal fetal growth: Findings from Mendelian randomization and parental negative control studies.

Maternal smoking during pregnancy is an established risk factor for low infant birth weight, but evidence on critical exposure windows and timing of fetal growth restriction is limited. Here we investigate the associations of maternal quitting, reducing, and continuing smoking during pregnancy with longitudinal fetal growth by triangulating evidence from 3 analytical approaches to strengthen causal inference. We analysed data from 8,621 European liveborn singletons in 2 population-based pregnancy cohorts (the Generation R Study, the Netherlands 2002-2006 [n = 4,682]) and the Born in Bradford study, United Kingdom 2007-2010 [n = 3,939]) with fetal ultrasound and birth anthropometric measures, parental smoking during pregnancy, and maternal genetic data. Associations with trajectories of estimated fetal weight (EFW) and individual fetal parameters (head circumference, femur length [FL], and abdominal circumference [AC]) from 12-16 to 40 weeks' gestation were analysed using multilevel fractional polynomial models. We compared results from (1) confounder-adjusted multivariable analyses, (2) a Mendelian randomization (MR) analysis using maternal rs1051730 genotype as an instrument for smoking quantity and ease of quitting, and (3) a negative control analysis comparing maternal and mother's partner's smoking associations. In multivariable analyses, women who continued smoking during pregnancy had a smaller fetal size than non-smokers from early gestation (16-20 weeks) through to birth (p-value for each parameter < 0.001). Fetal size reductions in continuing smokers followed a dose-dependent pattern (compared to non-smokers, difference in mean EFW [95% CI] at 40 weeks' gestation was -144 g [-182 to -106], -215 g [-248 to -182], and -290 g [-334 to -247] for light, moderate, and heavy smoking, respectively). Overall, fetal size reductions were most pronounced for FL. The fetal growth trajectory in women who quit smoking in early pregnancy was similar to that of non-smokers, except for a shorter FL and greater AC around 36-40 weeks' gestation. In MR analyses, each genetically determined 1-cigarette-per-day increase was associated with a smaller EFW from 20 weeks' gestation to birth in smokers (p = 0.01, difference in mean EFW at 40 weeks = -45 g [95% CI -81 to -10]) and a greater EFW from 32 weeks' gestation onwards in non-smokers (p = 0.03, difference in mean EFW at 40 weeks = 26 g [95% CI 5 to 47]). There was no evidence that partner smoking was associated with fetal growth. Study limitations include measurement error due to maternal self-report of smoking and the modest sample size for MR analyses resulting in unconfounded estimates being less precise. The apparent positive association of the genetic instrument with fetal growth in non-smokers suggests that genetic pleiotropy may have masked a stronger association in smokers. A consistent linear dose-dependent association of maternal smoking with fetal growth was observed from the early second trimester onwards, while no major growth deficit was found in women who quit smoking early in pregnancy except for a shorter FL during late gestation. These findings reinforce the importance of smoking cessation advice in preconception and antenatal care and show that smoking reduction can lower the risk of impaired fetal growth in women who struggle to quit.

Time-varying associations between prenatal metal mixtures and rapid visual processing in children

BackgroundHumans are exposed to mixtures of chemicals across their lifetimes, a concept sometimes called the “exposome.” Mixtures likely have temporal “critical windows” of susceptibility like single agents and measuring them repeatedly might help to define such windows. Common approaches to evaluate the effects of chemical mixtures have focused on their effects at a single time point. Our goal is to expand upon these previous techniques and examine the time-varying critical windows for metal mixtures on subsequent neurobehavior in children.MethodsWe propose two methods, joint weighted quantile sum regression (JWQS) and meta-weighted quantile sum regression (MWQS), to estimate the effects of chemical mixtures measured across multiple time points, while providing data on their critical windows of exposure. We compare the performance of both methods using simulations. We also applied both techniques to assess second and third trimester metal mixture effects in predicting performance in the Rapid Visual Processing (RVP) task from the Cambridge Neuropsychological Test Automated Battery (CANTAB) assessed at 6–9 years in children who are part of the PROGRESS (Programming Research in Obesity, GRowth, Environment and Social Stressors) longitudinal cohort study. The metals, arsenic, cadmium (Cd), cesium, chromium, lead (Pb) and antimony (Sb) were selected based on their toxicological profile.ResultsIn simulations, JWQS and MWQS had over 80% accuracy in classifying exposures as either strongly or weakly contributing to an association. In real data, both JWQS and MWQS consistently found that Pb and Cd exposure jointly predicted longer latency in the RVP and that second trimester exposure better predicted the results than the third trimester. Additionally, both JWQS and MWQS highlighted the strong association Cd and Sb had with lower accuracy in the RVP and that third trimester exposure was a better predictor than second trimester exposure.ConclusionsOur results indicate that metal mixtures effects vary across time, have distinct critical windows and that both JWQS and MWQS can determine longitudinal mixture effects including the cumulative contribution of each exposure and critical windows of effect.

Identifying critical windows of prenatal particulate air pollution exposure and children’s blood pressure at age 4-6

TPS 671: Cardiometabolic effects of long-term air pollution exposure, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Background: Exposure to air pollution is associated with increased blood pressure (BP) in adults and children. Limited evidence suggests that air pollution exposure during the prenatal period may contribute to adverse cardiorenal health later in life. Here we apply a distributed lag model (DLM) approach to identify critical windows that may underlie the association between prenatal particulate matter ≤ 2.5 μm in diameter (PM2.5) and children’s BP at 4-6 years. Methods: Participants included 537 mother-child dyads enrolled in the longitudinal cohort study Programming Research in Obesity, GRowth, Environment, and Social Stress (PROGRESS) based in Mexico City. Prenatal daily PM2.5 exposure was estimated using a validated satellite-based spatio-temporal model and BP was measured using the automated Spacelabs system with a sized cuff. We used DLMs to examine associations between daily PM2.5 exposure and systolic BP (SBP), adjusting for child’s age, sex and BMI, as well as maternal education and indoor smoking report during the second and third trimester. Results: We found that PM2.5 exposure between weeks 17 to 35 of gestation (days 115 to 244) was significantly associated with children’s increased SBP. To place this into context, a constant 10 µg/m3 increase in PM2.5 sustained throughout this critical window would predict a cumulative increase of 1.4 mmHg (CI: 0.3, 2.5) in SBP at age 4-6. In a stratified analysis by sex, this association persisted in boys but not in girls. Conclusions: Second and third trimester PM2.5 exposure may increase children’s BP. Further work investigating PM2.5 exposure with BP and kidney function changes later in childhood will be important to understanding cardiorenal trajectories that may predict adult disease. Our results underscore the importance of reducing air pollution exposure among susceptible populations.

Pre- and Postnatal Air Pollution Exposure and Autism Spectrum Disorder

TPS 731: Neurological effects in children, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Background: Epidemiologic studies have reported associations between prenatal and early postnatal air pollution exposure and autism spectrum disorder (ASD); however, few studies to date have assessed associations between air pollution and ASD across different geographic locations using uniform exposure and outcome assessment methods. Methods: We examined associations between early life exposure to PM2.5 and ozone in association with ASD across multiple U.S. regions. Our study participants included 674 children with clinically confirmed ASD and 855 population controls from the Study to Explore Early Development, a multi-site case-control study of children born from 2003 to 2006 in the United States. We used a satellite-based model to assign air pollutant exposure averages during several critical periods of neurodevelopment: three months before pregnancy, each trimester of pregnancy, the entire pregnancy, and the first year of life. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs), adjusting for study site, maternal age, maternal education, maternal race/ethnicity, maternal smoking, and month and year of birth. Results: The association between air pollution and ASD appeared to vary by exposure time period. PM2.5 exposure during the first year of life was associated with ASD, with an OR of 1.26 (95% CI: 1.02, 1.57) per 1.6 µg/m3 increase in PM2.5. We additionally observed an association with ozone exposure during the third trimester [OR = 1.22 (95% CI: 1.05, 1.42) per 6.6 ppb increase in ozone]. Conclusions: Our study provides evidence for a positive association between early life air pollution exposure and ASD, and identifies a potential critical window of exposure during the late prenatal and early postnatal periods. This abstract does not necessarily represent the official positions of the Centers for Disease Control and Prevention or the Environmental Protection Agency.

Using Bayesian distributed lag models to identify the susceptible window for maternal air pollution exposure and low birth weight at term in Guangzhou, China

TPS 691: Methods of measurement, design and data analysis, Exhibition Hall, Ground floor, August 28, 2019, 3:00 PM - 4:30 PM Background: Maternal exposure to ambient air pollution during pregnancy has been associated with low birth weight (LBW, birthweight < 2500 grams), however, the critical exposure windows remain unclear. This study aimed to identify potential susceptible air pollution exposure windows for LBW at term in Guangzhou, China at weekly levels. Methods: Based on birth certificate data, 444,082 singleton live births between January 2015 and July 2017 were included. Weekly district-specific exposures (PM2.5, PM10, NO2, SO2, and O3) for each participant were estimated based on their district of residence during pregnancy. Logistic regression models fitted in the Bayesian setting, with smoothed Gaussian process prior distribution, were applied to estimate the risk parameters. Post mean odds ratios (ORs) and 95% credible intervals (CIs) were calculated for an interquartile range (IQR) increase in each pollutant during the study period. Results: Of the 444,082 term births included in the study, 8,638 (1.9 %) were LBW. During the study period, the mean concentrations of PM2.5, PM10, NO2, SO2, and O3 were 39.1 µg/m3, 60.2 µg/m3, 46.1 µg/m3, 13.2 µg/m3, and 84.5 µg/m3, respectively. Increased O3 exposure during pregnancy weeks 15-16 was associated with increased odds of LBW at term. Post mean odds ratios (ORs) and 95% credible intervals (CIs) were 1.020 (1.001-1.041) and 1.024 (1.004-1.047), respectively. We didn’t observe any association between exposure to PM2.5, PM10, NO2, SO2 and LBW at term. Conclusion: Our results suggest that maternal exposure to O3 increases risk of LBW at term and weeks 15-16 of gestation are potential susceptible exposure windows among women living in Guangzhou.

Dairy consumption during adolescence and endometriosis risk

Modifiable risk factors such as diet may be important in both the etiology and progression of endometriosis as well as the prevalence of pain symptoms and infertility associated with this condition. In adults, higher intake of dairy has been associated with a lower risk of endometriosis diagnosis. There is currently no literature on whether dairy intake during adolescence, a potentially critical window of exposure, influences endometriosis risk. The objectige of the study was to evaluate the association between consumption of dairy foods in adolescence and the risk of laparoscopically confirmed endometriosis. This was a prospective cohort study, the Nurses' Health Study II, which has prospectively collected data since 1989. In 1998, when participants were aged 34-51 years, they completed a 124 item food frequency questionnaire about their high school diet. Cases were defined as those who self-reported laparoscopically confirmed endometriosis. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for the association between dairy foods and laparoscopically confirmed endometriosis. Among women who completed the questionnaire abouttheir high school diet in 1998, 581 cases of laparoscopically confirmed endometriosis were diagnosed among 32,868 premenopausal women from 1998 to 2013. Women who consumed more than 4 servings per day of dairy foods during adolescence had a 32% lower risk of laparoscopically confirmed endometriosis during adulthood (95% confidence interval, 0.47-0.96; Ptrend= .04) compared with women consuming 1 or fewer servings per day. The association was similar for low-fat and high-fat dairy foods. Yogurt and ice cream consumption, specifically, were associated with a lower risk of endometriosis. Those who consumed 2 or more servings of yogurt per week as an adolescent had a 29% lower risk of endometriosis diagnosis (95% confidence interval, 0.52-0.97; Ptrend= .02) compared with those consuming less than 1 serving per week. In addition, women who consumed 1 or more servings per day of ice cream per day during adolescence had a 38% lower risk of endometriosis diagnosis (95% confidence interval, 0.40-0.94; Ptrend= .20) compared with those consuming less than 1 serving per week. Our findings suggest that dairy consumption, specifically yogurt and ice cream intake, in adolescence may reduce the risk of subsequent endometriosis diagnosis. Future studies in adolescent populations are needed to confirm these results.

Developmental immunotoxicology: What underlies the critical windows of exposure?

Trabajo presentado en 3rd International Conference on Fish and Shellfish Immunology (ISFSI), celebrado en Gran Canaria (Espana), del 16 al 20 de junio de 2019

Ambient Fine Particulate Matter and Preterm Birth in California: Identification of Critical Exposure Windows.

Exposure to ambient fine particulate matter (particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5)) during pregnancy is associated with preterm birth (PTB), a leading cause of infant morbidity and mortality. Results from studies attempting to identify etiologically relevant exposure periods of vulnerability have been inconsistent, possibly because of failure to consider the time-to-event nature of the outcome and lagged exposure effects of PM2.5. In this study, we aimed to identify critical exposure windows for weekly PM2.5 exposure and PTB in California using California birth cohort data from 2005-2010. Associations were assessed using distributed-lag Cox proportional hazards models. We assessed effect-measure modification by race/ethnicity by calculating the weekly relative excess risk due to interaction. For a 10-μg/m3 increase in PM2.5 exposure over the entire period of gestation, PTB risk increased by 11% (hazard ratio = 1.11, 95% confidence interval: 1.09, 1.14). Gestational weeks 17-24 and 36 were associated with increased vulnerability to PM2.5 exposure. We find that non-Hispanic black mothers may be more susceptible to effects of PM2.5 exposure than non-Hispanic white mothers, particularly at the end of pregnancy. These findings extend our knowledge about the existence of specific exposure periods during pregnancy that have the greatest impact on preterm birth.

Early life exposure of a biocide, CMIT/MIT causes metabolic toxicity via the O-GlcNAc transferase pathway in the nematode C. elegans

Unusual cases of fatal lung injury, later determined to be a result of exposure to chemicals used as humidifier disinfectants, were reported among Korean children from 2006 to 2011. This resulted in considerable study of the pulmonary toxicity of humidifier disinfectant chemicals to establish the causal relationship between exposure and lung disease. However, the systemic toxicity of the former and health effects other than lung disease are not fully understood. Here, we investigated the effect of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), among the humidifier disinfectants used in the accidents, on the development of metabolic toxicity in the model organism, Caenorhabditis elegans using an exposure scenario comparison. We screened the potential of CMIT/MIT to induce metabolic toxicity using C. elegans oga-1(ok1207) and ogt-1(ok1474) mutants. We also performed a pathway analysis based on C. elegans transcription factor RNAi library screening to identify the underlying toxicity mechanisms. Finally, to understand the critical window of exposure for metabolic toxicity, responses to exposure during different periods in the life cycles of the worms were compared. We determined that CMIT/MIT could induce metabolic toxicity through O-linked N-acetylglucosamine transferase and early life seems to be the critical window for exposure for metabolic toxicity for this substance. The O-linked N-acetylglucosamine transferase pathway is conserved from worms to humans; our results thus insinuate that early-life exposure to CMIT/MIT could cause metabolic health problems during adult life in humans. We therefore suggest that a systemic toxicity approach should be considered to comprehensively understand the adverse health effects of humidifier disinfectant misuse.

Maternal urinary benzophenones and infant birth size: Identifying critical windows of exposure

Benzophenones (BPs) are widely used as ultraviolet absorbers and fragrance retention agents. Evidences from animal studies have suggested that exposure to BPs may affect fetal growth, but human data is limited and no study is concerning critical windows of BPs exposure throughout pregnancy in relation to fetal growth. We aimed to investigate the associations of prenatal exposure to BPs with birth size and examine the critical exposure windows of fetus development. We measured BPs (including 2,4-dihydroxybenzophenone (BP-1), 2-hydroxy-4-methoxybenzophenone (BP-3) and 4-hydroxybenzophenone (4-OH-BP)) in maternal urine samples collected in the first, second, and third trimester from 847 mothers recruited in Wuhan, China. The general estimation equations were used to analyze the relationships between maternal exposure to BPs levels and birth size. In all newborns, we found each log unit increase in maternal urinary concentrations of BP-1 and 4-OH-BP in the 1st trimester were associated with decreases in birth length by 0.06 cm (95% confidence interval (CI): −0.11, −0.01) and 0.08 cm (95% CI: −0.15, −0.01), respectively, but only the association with BP-1 in the boys remained significant in the stratified analysis by infant sex. In girls, urinary concentrations of BP-1 and BP-3 in the 3rd trimester were associated with decreased birth weight (adjusted β = −27.99 g, 95% CI: −50.66, −5.31 and −19.75 g, 95% CI: −37.31, −2.19, respectively) and length (adjusted β = −0.08 cm, 95% CI: −0.17, 0.00 and −0.08 cm, 95% CI: −0.15, −0.02) (p for interaction = 0.04). Our findings indicate that maternal urinary levels of BPs in the early and late periods during pregnancy may have impacts on delayed fetal growth, and the effects were more pronounced in girls.

Associations of adult-attained height and early life energy restriction with postmenopausal breast cancer risk according to estrogen and progesterone receptor status.

Adult-attained height is a marker for underlying mechanisms, such as cell growth, that may also influence postmenopausal breast cancer (BC) risk, perhaps specifically hormone-sensitive BC subtypes. Early life energy restriction may inhibit these mechanisms, resulting in shorter height and a reduced postmenopausal BC risk. Women (62,573) from the Netherlands Cohort Study completed a self-administered questionnaire in 1986 when 55-69 years old, and were followed-up for 20.3 years (case-cohort: Nsubcohort = 2,438; Ncases = 3,354). Cox multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated for BC risk overall and by estrogen and progesterone receptor subtypes in relation to height and early life energy restriction during the Hunger Winter, War Years, and Economic Depression. Although energy restriction can only influence longitudinal growth in women exposed before and/or during the growth spurt, it may also influence BC risk when occurring after the growth spurt, possibly through different growth processes. Therefore, Cox analyses were additionally conducted according to timing of energy restriction in relation to the growth spurt. Height was associated with an increased BC risk (HRper 5cm = 1.07, 95%CI:1.01-1.13), particularly hormone receptor-positive BC. Energy restriction before and/or during the growth spurt was associated with a decreased hormone receptor-positive BC risk. Energy restriction during the Hunger Winter increased the estrogen receptor-negative BC risk regardless of the timing of energy restriction. In conclusion, height and energy restriction before and/or during the growth spurt were both associated with hormone receptor-positive BC risk, in the direction as expected, indicating critical exposure windows for hormonal growth-related mechanisms.

Drilling into Critical Windows of Exposure: Trimester-Specific Associations between Gas Development and Preterm Birth.

Vol. 126, No. 10 Science SelectionOpen AccessDrilling into Critical Windows of Exposure: Trimester-Specific Associations between Gas Development and Preterm Birthis accompanied byDrilling and Production Activity Related to Unconventional Gas Development and Severity of Preterm Birth Lindsey Konkel Lindsey Konkel Search for more papers by this author Published:1 October 2018CID: 104002https://doi.org/10.1289/EHP3762View Article in:中文版AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Several studies suggest that living near unconventional gas development during pregnancy may contribute to poor birth outcomes, including low birth weight,1,2 prematurity,3,4 and some birth defects.5 The emissions and activities related to unconventional gas wells (i.e., those that use hydraulic fracturing to release gas from shale rock) vary at each phase of the site’s life. A new proximity study reported in Environmental Health Perspectives takes a first look at phase- and trimester-specific associations between unconventional gas activity and preterm birth.6“[Unconventional gas] activity is a proxy for a multitude of exposures,” says lead study author Kristina Whitworth, an epidemiologist at UTHealth School of Public Health in San Antonio, Texas. These exposures could include chemical stressors, such as potential endocrine disrupters used in fracking fluid7 and air emissions from vehicle exhaust,8 or nonchemical stressors such as noise and light pollution.9 Anxiety and fear are additional nonchemical stressors for people who are worried about fracking’s potential impacts on health or the environment.10“A primary challenge in this research area is moving beyond proximity-based metrics to individual measurements of exposure,” Whitworth says. That type of data is costly and time-consuming to collect, she adds, but it will be key to understanding and preventing any health risks posed by unconventional gas development.Different phases of well development involve the potential for different exposures among the people living, working, or attending school near a rig. Image: © Topher Donohue/Getty Images.Whitworth and colleagues obtained birth records from the Texas Department of State Health Services on all singleton births in the 24-county Barnett Shale region between 2010 and 2012. The study included 13,332 preterm birth cases—defined as birth before 37 weeks’ gestation—and 66,933 term births.The researchers estimated unconventional gas development activity within a half-mile radius of each mother’s residence at the time she gave birth. They differentiated between wells that were still being drilled and those that were already producing gas. Then, they identified when those activities took place during pregnancy. If a well was in either phase in any trimester, it was classified as active.Activities and emissions vary by the phase of well development. During the drilling phase, for instance, heavy diesel-powered equipment is used to drill the well, and large volumes of fracking fluids are injected underground at high pressure. The drilling phase is a relatively short period of intense activity that may involve exposures not only to spilled hydraulic fracturing chemicals but also air pollutants, including benzene and polycyclic aromatic hydrocarbons.11After drilling, the production phase begins. During this phase, which can last for years, natural gas and wastewater flows from the well. Production-related exposures may involve leaks of wastewater that is stored on the site.11In the current study,6 women living near the most drilling and production activity had an estimated 20% and 15% (respectively) higher risk of preterm birth, compared with women with no drilling activity near their homes. In their statistical analysis, the researchers controlled for other factors that could affect preterm birth, including the mother’s education level and prepregnancy weight, whether she smoked during pregnancy, and the number and timing of her prenatal health-care visits.6The researchers observed the greatest proximity-related risk for extremely premature births, meaning those before 28 weeks’ gestation. Women who lived near the densest drilling and production activity were 100% and 53% (respectively) more likely to have extremely premature babies, compared with women who did not live near a well. The authors found only limited evidence of trimester-specific differences in estimated risks.6Preterm babies are at risk of developmental delays and disabilities, asthma, and vision and hearing problems.12 Future studies could focus on interpreting the clinical relevance of the current findings for later-life health outcomes, suggests Bruce Pitt, a professor of environmental and occupational health at the University of Pittsburgh. Pitt was not involved in the research.The new study adds to the evidence that fracking may present some risk to fetal health. However, fracking is just one part of well development. The specific exposure or combination of exposures that could be driving the association between unconventional gas development and prematurity remains unclear; fracking itself may pose less risk than other elements of well activity.Lindsey Konkel is a New Jersey–based journalist who reports on science, health, and the environment.