Critical Windows Of Exposure Research Articles

Identifying critical windows of air pollution exposure during preconception and gestational period on birthweight: a prospective cohort study

BackgroundFew studies have assessed air pollution exposure association with birthweight during both preconception and gestational periods.MethodsLeveraging a preconception cohort consisting of 14220 pregnant women and newborn children in Shanghai, China during 2016–2018, we aim to assess associations of NO2 and PM2.5 exposure, derived from high-resolution spatial-temporal models, during preconception and gestational periods with outcomes including term birthweight, birthweight Z-score, small-for-gestational age (SGA) and large-for-gestational age (LGA). Linear and logistic regressions were used to estimate 3-month preconception and trimester-averaged air pollution exposure associations; and distributed lag models (DLM) were used to identify critical exposure windows at the weekly resolution from preconception to delivery. Two-pollutant models and children’s sex-specific associations were explored.ResultsAfter controlling for covariates, one standard deviation (SD) (11.5 μg/m3, equivalent to 6.1 ppb) increase in NO2 exposure during the second and the third trimester was associated with 13% (95% confidence interval: 2 – 26%) and 14% (95% CI: 1 – 29%) increase in SGA, respectively; and one SD (9.6 μg/m3) increase in PM2.5 exposure during the third trimester was associated with 15% (95% CI: 1 – 31%) increase in SGA. No association have been found for outcomes of birthweight, birthweight Z-score and LGA. DLM found that gestational weeks 22–32 were a critical window, when NO2 exposure had strongest associations with SGA. The associations of air pollution exposure tended to be stronger in female newborns than in male newborns. However, no significant associations of air pollution exposure during preconception period on birthweight outcomes were found.ConclusionConsistent with previous studies, we found that air pollution exposure during mid-to-late pregnancy was associated with adverse birthweight outcomes.

Association of PM2.5 mass and its components with ovarian reserve in a northern peninsular province, China: The critical exposure period and components

BackgroundA possible role of PM2.5 components on ovarian reserve has not been adequately unexplored. ObjectiveTo evaluate the association between PM2.5 components and women’ ovarian reserve over critical exposure periods in northern China, where the level of air pollution is among the nation’s highest. MethodsWe included 15,102 women with serum anti-Müllerian hormone (AMH) measurements from the Center for Reproductive Medicine of Shandong University during 2015–2019. Concentrations of PM2.5 and its five major components (0.1° × 0.1°), including sulfate, nitrate, ammonium, organic matter, and black carbon, were assigned to each residential address. Multivariable linear mixed effect models combined with constituent-residual models were performed to estimate the effect sizes of essential components over six short- to long-term exposure periods. ResultsThe strength of association was stronger during the process from primary to small antral follicle compared with other longer windows. For every interquartile range increase in PM2.5 mass was associated with − 8.7% (95%CI: −12.3%, −4.9%) change in AMH and the effect size was greatest for sulfate. Women with the lower level of attained education and those living inland were more susceptible compared with other population subgroups. ConclusionExposure to specific components of air pollution during critical exposure windows is associated with a decline in ovarian reserve. These data add to the growing body of evidence that environmental factors have adverse effects on reproductive health, particularly for vulnerable population subgroups.

Association of Prenatal Exposure to Organophosphate, Pyrethroid, and Neonicotinoid Insecticides with Child Neurodevelopment at 2 Years of Age: A Prospective Cohort Study.

Widespread insecticide exposure might be a risk factor for neurodevelopment of our children, but few studies examined the mixture effect of maternal coexposure to organophosphate insecticides (OPPs), pyrethroids (PYRs), and neonicotinoid insecticides (NNIs) during pregnancy on child neurodevelopment, and critical windows of exposure are unknown. We aimed to evaluate the association of prenatal exposure to multiple insecticides with children's neurodevelopment and to identify critical windows of the exposure. Pregnant women were recruited into a prospective birth cohort study in Wuhan, China, from 2014-2017. Eight metabolites of OPPs (mOPPs), three metabolites of PYRs (mPYRs), and nine metabolites of NNIs (mNNIs) were measured in 3,123 urine samples collected at their first, second, and third trimesters. Children's neurodevelopment [mental development index (MDI) and psychomotor development index (PDI)] was assessed using the Bayley Scales of Infant Development at 2 years of age (). Multivariate linear regression models, generalized estimating equation models, and weighted quantile sum (WQS) regression were used to estimate the association between the insecticide metabolites and Bayley scores. Potential sex-specific associations were also examined. Single chemical analysis suggested higher urinary concentrations of some insecticide metabolites at the first trimester were significantly associated with lower MDI and PDI scores, and the associations were more prominent among boys. Each 1-unit increase in ln-transformed urinary concentrations of two mOPPs, 3,5,6-trichloro-2-pyridinol and 4-nitrophenol, was associated with a decrease of 3.16 points [95% confidence interval (CI): , ] and 3.06 points (95% CI: , ) respectively in boys' MDI scores. Each 1-unit increase in that of trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid (trans-DCCA; an mPYR) was significantly associated with a decrease of 2.24 points (95% CI: , ) in boys' MDI scores and 1.90 points (95% CI: , ) in boys' PDI scores, respectively. Significantly positive associations of maternal urinary biomarker concentrations [e.g., dimethyl phosphate (a nonspecific mOPP) and desmethyl-clothianidin (a relatively specific mNNI)] with child neurodevelopment were also observed. Using repeated holdout validation, a 1-quartile increase in the WQS index of the insecticide mixture (in the negative direction) at the first trimester was significantly associated with a decrease of 3.02 points (95% CI: , ) in MDI scores among the boys, and trans-DCCA contributed the most to the association (18%). Prenatal exposure to higher levels of certain insecticides and their mixture were associated with lower Bayley scores in children, particularly in boys. Early pregnancy may be a sensitive window for such an effect. Future studies are needed to confirm our findings. https://doi.org/10.1289/EHP12097.

The association between newborn cord blood steroids and ambient prenatal exposure to air pollution: findings from the ENVIRONAGE birth cohort

Knowledge of whether prenatal exposure to ambient air pollution disrupts steroidogenesis is currently lacking. We investigated the association between prenatal ambient air pollution and highly accurate measurements of cord blood steroid hormones from the androgenic pathway.This study included 397 newborns born between the years 2010 and 2015 from the ENVIRONAGE cohort in Belgium of whom six cord blood steroid levels were measured: 17α-hydroxypregnenolone, 17α-hydroxyprogesterone, dehydroepiandrosterone, pregnenolone, androstenedione, and testosterone. Maternal ambient exposure to PM2.5 (particles with aerodynamic diameter ≤ 2.5 μm), NO2, and black carbon (BC) were estimated daily during the entire pregnancy using a high-resolution spatiotemporal model. The associations between the cord blood steroids and the air pollutants were tested and estimated by first fitting linear regression models and followed by fitting weekly prenatal exposures to distributed lag models (DLM). These analyses accounted for possible confounders, coexposures, and an interaction effect between sex and the exposure. We examined mixture effects and critical exposure windows of PM2.5, NO2 and BC on cord blood steroids via the Bayesian kernel machine regression distributed lag model (BKMR-DLM).An interquartile range (IQR) increment of 7.96 µg/m3 in PM2.5 exposure during pregnancy trimester 3 was associated with an increase of 23.01% (99% confidence interval: 3.26–46.54%) in cord blood levels of 17α-hydroxypregnenolone, and an IQR increment of 0.58 µg/m³ in BC exposure during trimester 1 was associated with a decrease of 11.00% (99% CI: -19.86 to -0.012%) in cord blood levels of androstenedione. For these two models, the DLM statistics identified sensitive gestational time windows for cord blood steroids and ambient air pollution exposures, in particular for 17α-hydroxypregnenolone and PM2.5 exposure during trimester 3 (weeks 28–36) and for androsterone and BC exposure during early pregnancy (weeks 2–13) as well as during mid-pregnancy (weeks 18–26). We identified interaction effects between pollutants, which has been suggested especially for NO2.Our results suggest that prenatal exposure to ambient air pollutants during pregnancy interferes with steroid levels in cord blood. Further studies should investigate potential early-life action mechanisms and possible later-in-life adverse effects of hormonal disturbances due to air pollution exposure.

Ambient climatic factors and term birthweight: A study of critical windows of exposure in the Republic of Cyprus

BackgroundReduced birthweight is associated with adverse perinatal and long-term outcomes. A few studies examined the association between climatic factors and birthweight with inconsistent results probably due to differences in exposure assessment, statistical models, climatic parameters, and study populations. MethodsWe obtained data from the Republic of Cyprus birth registry from 2007 to 2020, and matched climatic exposures (i.e., temperature, relative humidity, temperature variability, humidity variability) by the hospital district at birth. We used distributed lag models to examine the association between term birthweight, temperature, humidity, and their variability to identify critical windows. Our models were adjusted for coarse particulate matter level (≤10 μm [PM10), and individual-level covariates. Subgroup analysis was conducted to examine effect modification by maternal age and education. ResultsWe identified two critical windows of exposure to ambient temperature at early and late pregnancy. The cumulative change of birthweight per 5 °C increases in mean weekly temperature was −57.27 (2%) (95% Confidence Interval [CI]: 99.62 (3.1%), −14.92 (0.5%)) and −79.2 (2.5%) (95%CI: 117.03 (3.5%), −41.52 (1.3%)) grams during weeks 1–8 and weeks 28–37, respectively. There was no significant effect of humidity, temperature variability, or humidity variability on birthweight. Based on subgroup analysis, mothers with post-secondary education were more sensitive to temperature, but the marginal significance of differences in effect estimates may be linked with differences in sample size. ConclusionOur study suggests that higher ambient temperature exposure during early and late pregnancy is associated with lower birthweight in main and subgroup analysis. The findings demonstrate in a country highly impacted by climate change like Cyprus that rising temperatures may be associated with perinatal outcomes in susceptible populations during sensitive windows of exposure.

Association between exposure to air pollution during preconception and risk of gestational diabetes mellitus: The role of anti-inflammatory diet

BackgroundRegarding the association between the sensitive time-windows of air pollution (AP) exposure and gestational diabetes mellitus (GDM), epidemiological findings are inconsistent. The dietary inflammatory potential has been implicated in the development of GDM, but it is unclear whether an anti-inflammatory diet during pregnancy reduces the association between AP and GDM. ObjectiveWe aimed to characterize the sensitive time-windows of AP to GDM risk. Further, to verify whether a maternal anti-inflammatory diet can reduce the risk of AP-induced GDM, by inhibiting inflammation. MethodsA total of 8495 pregnant women were included between 2015 and 2021 in the Maternal & Infants Health in Hefei study. Weekly mean AP exposure to fine particles (PM2.5 and PM10), SO2, and NO2 was estimated from the data of Hefei City Ecology and Environment Bureau. High-sensitivity C-reactive protein (hs-CRP) concentrations were measured to evaluate systemic inflammation. The empirical dietary inflammatory pattern (EDIP) score based on a validated food frequency questionnaire was used to assess the dietary inflammatory potential of pregnant women.Logistic regression models with distributed lags were used to identify the sensitive time-window for the effect of AP on GDM. Mediation analysis estimated the mediated effect of hs-CRP, linking AP with GDM. Stratified analysis was used to investigate the potential effect of anti-inflammatory diet on GDM risk. ResultsThe increased risks of GDM were found to be positively associated with exposure to PM2.5 (OR = 1.11, 95% CI:1.07–1.15), PM10 (OR = 1.12, 95% CI:1.09–1.16), and SO2 (OR = 1.42, 95% CI:1.25–1.60) by distributed lag models, and the critical exposure windows were 21st to 28th weeks of preconception. The proportion of association between PM2.5, PM10, and SO2 with GDM mediated by hs-CRP was 25.9%, 21.1%, and 19.4%, respectively, according to mediation analysis. In the stratified analyses by EDIP, the association between AP and GDM was not statistically significant among women those with anti-inflammatory diets. ConclusionsExposure to AP, especially in 21st to 28th week of preconception, is associated with risk of GDM, which is partly mediated by hs-CRP. Adherence to the anti-inflammatory dietary pattern may reduce the risk of AP-induced GDM.

Ambient cold exposure amplifies the effect of ambient PM1 on blood pressure and hypertensive disorders of pregnancy among Chinese pregnant women: A nationwide cohort study

BackgroundLittle evidence exists regarding the combined effect between ambient temperature and air pollution exposure on maternal blood pressure (BP) and hypertensive disorders of pregnancy (HDP). ObjectivesTo assess effect modification by temperature exposure on the PM1-BP/HDP associations among Chinese pregnant women based on a nationwide study. MethodsWe conducted a cross-sectional country-based population study in China, enrolling 86,005 participants from November 2017 to December 2021. BP was measured with standardized sphygmomanometers. HDP was defined according to the American College of Obstetricians and Gynecologists' recommendations. Daily temperature data were obtained from the European Centre for Medium-Range Weather Forecasts. PM1 concentrations were evaluated using generalized additive model. Generalized linear mixed models were used to examine the health effects, controlling for multiple covariates. We also performed a series of stratified and sensitivity analyses. ResultsThe pro-hypertensive effect of PM1 was observed in the first trimester. Cold exposure amplifies the first-trimester PM1-BP/HDP associations, with adjusted estimate (aβ) for systolic blood pressure (SBP) of 3.038 (95 % CI: 2.320–3.755), aβ for diastolic blood pressure (DBP) of 2.189 (95 % CI: 1.503–2.875), and aOR for HDP of 1.392 (95 % CI: 1.160–1.670). Pregnant women who were educated longer than 17 years or living in urban areas appeared to be more vulnerable to the modification in the first trimester. These findings remained robust after sensitivity analyses. ConclusionsFirst trimester maybe the critical exposure window for the PM1-BP/HDP associations among Chinese pregnant women. Cold exposure amplifies the associations, and those with higher education level or living in urban areas appeared to be more vulnerable.

Intrauterine and early postnatal exposure to air pollution associated with childhood allergic rhinitis

BackgroundDespite mounting evidence linking allergic rhinitis (AR) to air pollution, it remains unclear which major air pollutant(s) and critical window(s) of exposure play important roles in children's AR. ObjectiveTo examine the effects of intrauterine and early postnatal exposure to outdoor air pollution on children with doctor-diagnosed allergic rhinitis (DDAR). MethodsA retrospective cohort study involving 8689 kindergarten children was conducted in Changsha, China, from 2019 to 2020. A questionnaire survey was conducted to collect information on the health status of children and their family members, as well as their living habits and home environment. Personal exposure to daily outdoor air pollutants (PM2.5, PM2.5-10, PM10, SO2, NO2, and CO) was estimated during 40 gestational weeks, three trimesters, the entire pregnancy, and the first year after birth. Multiple logistic regression models were used to assess the associations between air pollution and children's DDAR. ResultsChildren's DDAR was associated with intrauterine CO exposure, with adjusted ORs (95% CI) of 1.18 (1.03–1.34) for each IQR increase in CO exposure. The second and third trimesters were critical windows for PM2.5 and CO exposure in relation to DDAR. Furthermore, early postnatal exposure to PM2.5-10 and PM10 in first year of life was associated with DDAR development, with adjusted ORs (95% CI) of 1.11 (1.01–1.22) and 1.27 (1.09, 1.47). The entire pregnancy and the first year of life were critical windows for CO and PM10 exposure. Some children were predisposed to DDAR risk due to exposure to traffic-related air pollution (TRAP). ConclusionOur findings support the hypothesis of “fetal origin of allergic rhinitis” by demonstrating that intrauterine and early postnatal exposure to air pollution plays an important role in children's DDAR.

Prenatal exposure to polycyclic aromatic hydrocarbons and cognition in early childhood

BackgroundEpidemiological evidence for gestational polycyclic aromatic hydrocarbon (PAH) exposure and adverse child cognitive outcomes is mixed; little is known about critical windows of exposure. ObjectiveWe investigated associations between prenatal PAH exposure and child cognition in a large, multi-site study. MethodsWe included mother–child dyads from two pooled prospective pregnancy cohorts (CANDLE and TIDES, N = 1,223) in the ECHO-PATHWAYS Consortium. Seven urinary mono-hydroxylated PAH metabolites were measured in mid-pregnancy in both cohorts as well as early and late pregnancy in TIDES. Child intelligence quotient (IQ) was assessed between ages 4–6. Associations between individual PAH metabolites and IQ were estimated with multivariable linear regression. Interaction terms were used to examine effect modification by child sex and maternal obesity. We explored associations of PAH metabolite mixtures with IQ using weighted quantile sum regression. In TIDES, we averaged PAH metabolites over three periods of pregnancy and by pregnancy period to investigate associations between PAH metabolites and IQ. ResultsIn the combined sample, PAH metabolites were not associated with IQ after full adjustment, nor did we observe associations with PAH mixtures. Tests of effect modification were null except for the association between 2-hydroxynaphthalene and IQ, which was negative in males (βmales = −0.67 [95%CI:−1.47,0.13]) and positive in females (βfemales = 0.31 [95%CI:−0.52,1.13])(pinteraction = 0.04). In analyses across pregnancy (TIDES-only), inverse associations with IQ were observed for 2-hydroxyphenanthrene averaged across pregnancy (β = −1.28 [95%CI:−2.53,−0.03]) and in early pregnancy (β = −1.14 [95%CI:−2.00,−0.28]). SignificanceIn this multi-cohort analysis, we observed limited evidence of adverse associations of early pregnancy PAHs with child IQ. Analyses in the pooled cohorts were null. However, results also indicated that utilizing more than one exposure measures across pregnancy could improve the ability to detect associations by identifying sensitive windows and improving the reliability of exposure measurement. More research with multiple timepoints of PAH assessment is warranted.

The exposome in respiratory diseases: multiple preventable risk factors from early life to adulthood.

The increasing global burden of respiratory diseases over the last decades raises questions about the impact of environmental factors during industrialisation and urbanisation. Although the knowledge of environmental epidemiology is growing, it is still unclear what the most critical exposure windows are for respiratory health. In addition, the relationships between different environmental exposures can be complex. The exposome approach investigating all non-genetic factors on health has been developed in recent years but has been little applied in respiratory health to date. This journal club article reviews three recent publications investigating the effects of environmental exposures, considered separately or in an exposome approach with different exposure windows, on respiratory health outcomes. These three studies highlight targets for action in primary and secondary prevention. Two studies, using data from the INMA and RHINESSA cohorts, support the regulation and reduction of phthalates and air pollution, respectively. Moreover, the exposome approach conducted in the NutriNet-Santé cohort emphasises that risk reduction must involve a multi-interventional approach targeting both specific early-life risk factors and promotion of a healthy lifestyle in adulthood. These three articles also present research perspectives in environmental epidemiology.

Multigenerational impacts of EE2 on reproductive fitness and immune competence of marine medaka

Estrogenic endocrine disrupting chemicals (EEDC) have been suspected to impact offspring in a transgenerational manner via modifications of the germline epigenome in the directly exposed generations. A holistic assessment of the concentration/ exposure duration-response, threshold level, and critical exposure windows (parental gametogenesis and embryogenesis) for the transgenerational evaluation of reproduction and immune compromise concomitantly will inform the overall EEDC exposure risk. We conducted a multigenerational study using the environmental estrogen, 17α-ethinylestradiol (EE2), and the marine laboratory model fish Oryzias melastigma (adult, F0) and their offspring (F1-F4) to identify transgenerationally altered offspring generations and phenotype persistence. Three exposure scenarios were used: short parental exposure, long parental exposure, and a combined parental and embryonic exposure using two concentrations of EE2 (33ng/L, 113ng/L). The reproductive fitness of fish was evaluated by assessing fecundity, fertilization rate, hatching success, and sex ratio. Immune competence was assessed in adults via a host-resistance assay. EE2 exposure during both parental gametogenesis and embryogenesis was found to induce concentration/ exposure duration-dependent transgenerational reproductive effects in the unexposed F4 offspring. Furthermore, embryonic exposure to 113 ng/L EE2 induced feminization of the directly exposed F1 generation, followed by subsequent masculinization of the F2 and F3 generations. A sex difference was found in the transgenerationally impaired reproductive output with F4 females being sensitive to the lowest concentration of EE2 (33 ng/L) upon long-term ancestral parent exposure (21 days). Conversely, F4 males were affected by ancestral embryonic EE2 exposure. No definitive transgenerational impacts on immune competence were identified in male or female offspring. In combination, these results indicate that EEDCs can be transgenerational toxicants that may negatively impact the reproductive success and population sustainability of fish populations.

Exploring Relevant Time Windows in the Association Between PM2.5 Exposure and Amyotrophic Lateral Sclerosis: A Case-Control Study in Denmark.

Studies suggest a link between particulate matter less than or equal to 2.5 μm in diameter (PM2.5) and amyotrophic lateral sclerosis (ALS), but to our knowledge critical exposure windows have not been examined. We performed a case-control study in the Danish population spanning the years 1989-2013. Cases were selected from the Danish National Patient Registry based on International Classification of Diseases codes. Five controls were randomly selected from the Danish Civil Registry and matched to a case on vital status, age, and sex. PM2.5 concentration at residential addresses was assigned using monthly predictions from a dispersion model. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for confounding. We evaluated exposure to averaged PM2.5 concentrations 12-24 months, 2-6 years, and 2-11 years pre-ALS diagnosis; annual lagged exposures up to 11 years prediagnosis; and cumulative associationsfor exposure in lags 1-5 years and 1-10 yearsprediagnosis, allowing for varying association estimates by year. We identified 3,983 cases and 19,915 controls. Cumulative exposure to PM2.5 in the period 2-6 years prediagnosis was associated with ALS (OR=1.06, 95% CI: 0.99, 1.13). Exposures in the second, third, and fourth years prediagnosis were individually associated with higher odds of ALS (e.g., for lag 1, OR=1.04, 95% CI: 1.00, 1.08). Exposure to PM2.5 within 6 years before diagnosis may represent a critical exposure window for ALS.

Association between ambient PM1 and semen quality: A cross-sectional study of 27,854 men in China

BackgroundExposure to ambient fine and respirable particulate matter is associated with poor sperm quality, but evidence for particulate matter with an aerodynamic diameter ≤ 1 μm (PM1) is scarce. We aimed to estimate the association between PM1 exposure and sperm concentration, sperm count, sperm total motility, and sperm progressive motility in Chinese men. MethodsWe conducted a cross-sectional study of 33,221 men attending an infertility clinic in Hubei, China, between 2014 and 2020. Daily concentrations of PM1 data were estimated from a validated spatiotemporal artificial intelligence model. We used multivariate linear regression to estimate the association between PM1 exposure and sperm parameters during the spermatogenesis period after adjusting for age, body mass index (BMI), education, ever having fathered a child, and season of semen collection. In addition, we performed stratified analysis to assess whether the association was varied by age, BMI, and educational attainment. ResultsA total of 27,854 participants were included in the final analysis. An interquartile range (17.2 μg/m3) increase in PM1 during the entire period of semen development was associated with declined semen concentration [-4.39% (95% CI: −7.67%, −1.12%)] and sperm count [–23.56% (95% CI: −28.95%, −18.18%)], reduced total motility [-0.86% (95% CI: −1.66%, −0.06%)] and progressive motility [-2.22% (95% CI: −3.00%, −1.43%)]. The associations were homogeneous across subgroups defined by age and education, but were more pronounced among men with underweight for sperm concentration and sperm count. We identified a critical exposure window of 0–9 lag days, 10–14 lag days, and 70–90 lag days before semen collection for sperm count and progressive motility. ConclusionsAmong men attending an infertility clinic in China, exposure to PM1 was associated with poor semen quality, especially during the 70–90 days before ejaculation. These results suggest that exposure to PM1 might be a novel risk factor for impaired semen quality.

Prenatal arsenic exposure, arsenic metabolism and neurocognitive development of 2-year-old children in low-arsenic areas

BackgroundThere is limited evidence on the effects of arsenic species and metabolic capacity on child neurodevelopment, particularly at low levels. Further, little is known about the critical window of exposure. ObjectiveTo estimate the associations of arsenic exposure and arsenic metabolism in different pregnancy periods with neurodevelopment of two-year-old children. MethodsConcentrations of arsenobetaine (AsB), arsenite, arsenate, monomethyl arsenic acid (MMA), and dimethyl arsenic acid (DMA) in urine samples collected in three trimesters from 1006 mothers were measured using HPLC − ICPMS. Inorganic arsenic (iAs) was calculated as the sum of arsenite and arsenate. Total arsenic (tAs) was calculated as the sum of iAs, MMA and DMA. Child neurodevelopment was assessed with the Bayley Scales of Infant Development. ResultsThe geometric mean (GM) of SG-adjusted tAs in the first, second, third trimester was 16.37, 12.94, 13.04 μg/L, respectively. The mental development index (MDI) score was inversely associated with iAs and tAs. Compared to the 1st quartile, the MDI score decreased 0.43 (95%CI: −4.22, 3.36) for the 2nd, 6.50 (95%CI: −11.73, −1.27) for the 3rd, 5.42 (95%CI: −10.74, −0.10) for the 4th quartiles of iAs, and decreased 4.03 (95%CI: −7.90, −0.15) in the 4th quartile of tAs. In trimester-specific models, negative associations of DMA [−1.94 (95%CI: −3.18, −0.71)] and tAs [−1.61 (95%CI: −3.02, −0.20)] with the psychomotor development index (PDI) were only observed in 1st trimester. ConclusionsOur study found inverse associations between prenatal arsenic exposure, especially in early pregnancy, and neurodevelopment of children at two years old, even at low exposure levels.

Prenatal Exposure to Air Pollution and Pre-Labor Rupture of Membranes in a Prospective Cohort Study: The Role of Maternal Hemoglobin and Iron Supplementation.

Exposure to air pollution in prenatal period is associated with prelabor rupture of membranes (PROM). However, the sensitive exposure time windows and the possible biological mechanisms underlying this association remain unclear. We aimed to identify the sensitive time windows of exposure to air pollution for PROM risk. Further, we examined whether maternal hemoglobin levels mediate the association between exposure to air pollution and PROM, as well as investigated the potential effect of iron supplementation on this association. From 2015 to 2021, 6,824 mother-newborn pairs were enrolled in the study from three hospitals in Hefei, China. We obtained air pollutant data [particulate matter (PM) with aerodynamic diameter (), PM with aerodynamic diameter (), sulfur dioxide (), and carbon monoxide (CO)] from the Hefei City Ecology and Environment Bureau. Information on maternal hemoglobin levels, gestational anemia, iron supplementation, and PROM was obtained from medical records. Logistic regression models with distributed lags were used to identify the sensitive time window for the effect of prenatal exposure to air pollutant on PROM. Mediation analysis estimated the mediated effect of maternal hemoglobin in the third trimester, linking prenatal air pollution with PROM. Stratified analysis was used to investigate the potential effect of iron supplementation on PROM risk. We found significant association between prenatal exposure to air pollution and increased PROM risk after adjusting for confounders, and the critical exposure windows of , , and CO were the 21th to 24th weeks of pregnancy. Every increase in and , increase in , and increase in CO was associated with low maternal hemoglobin levels [ (95% confidence interval (CI): , ), (95% CI: , ), (95% CI: , ), and (95% CI: , ), respectively] in the third trimester. The proportion of the association between air pollution and PROM risk mediated by hemoglobin levels was 20.61% [average mediation effect (95% CI): 0.02 (0.01, 0.05); average direct effect (95%): 0.08 (0.02, 0.14)]. The PROM risk associated with exposure to low-medium air pollution could be attenuated by maternal iron supplementation in women with gestational anemia. Prenatal exposure to air pollution, especially in the 21st to 24th weeks of pregnancy, is associated with PROM risk, which is partly mediated by maternal hemoglobin levels. Iron supplementation in anemia pregnancies may have protective effects against PROM risk associated with exposure to low-medium air pollution. https://doi.org/10.1289/EHP11134.

Traffic-Related Air Pollution and Ultrasound Parameters of Fetal Growth in Eastern Massachusetts.

Previous studies have examined the association between prenatal nitrogen dioxide (NO2)-a traffic emissions tracer-and fetal growth based on ultrasound measures. Yet, most have used exposure assessment methods with low temporal resolution, which limits the identification of critical exposure windows given that pregnancy is relatively short. Here, we used NO2 data from an ensemble model linked to residential addresses at birth to fit distributed lag models that estimated the association between NO2 exposure (resolved weekly) and ultrasound biometric parameters in a Massachusetts-based cohort of 9,446 singleton births from 2011-2016. Ultrasound biometric parameters examined included biparietal diameter (BPD), head circumference, femur length, and abdominal circumference. All models adjusted for sociodemographic characteristics, time trends, and temperature. We found that higher NO2 was negatively associated with all ultrasound parameters. The critical window differed depending on the parameter and when it was assessed. For example, for BPD measured after week 31, the critical exposure window appeared to be weeks 15-25; 10-parts-per-billion higher NO2 sustained from conception to the time of measurement was associated with a lower mean z score of -0.11 (95% CI: -0.17, -0.05). Our findings indicate that reducing traffic emissions is one potential avenue to improving fetal and offspring health.

Potential impact of ambient temperature on maternal blood pressure and hypertensive disorders of pregnancy: A nationwide multicenter study based on the China birth cohort

Limited evidence exists regarding the association between ambient temperature and blood pressure (BP) level of pregnant women. To investigate the associations of ambient temperature with maternal BP and hypertensive disorders of pregnancy (HDP), we studied 105,063 participants in 38 centers of 17 provinces from November 2017 to December 2021. BP was measured with standardized automated digital sphygmomanometers. Ambient temperature was classified into five classes as very hot, moderate hot, mild, moderate cold, and very cold. Generalized linear mixed models were used to investigate the ambient temperature-BP/HDP associations, controlling for multiple covariates. No significant associations of first-trimester ambient temperature with maternal BP and HDP prevalence were observed. Compared with mild temperature, second-trimester very cold and second-trimester moderate cold were statistically associated with the increase of 1.239 mmHg (95% CI: 0.908, 1.569) and 0.428 mmHg (95% CI: 0.099, 0.757) for second-trimester systolic blood pressure (SBP), respectively. Similar trends were also observed in the association between second-trimester cold exposure and second-trimester diastolic blood pressure (DBP), in the association between second-trimester cold exposure and third-trimester SBP/DBP as well as in the association between third-trimester cold exposure and third-trimester SBP/DBP although some estimates were not statistically significant. Furthermore, in the second and third trimester, very cold [second trimester: adjusted odds ratio (aOR) = 1.298; third trimester: aOR = 1.236) and moderate cold (second trimester: aOR = 1.208; third trimester: aOR = 1.146) exposures also increased the odds of HDP, and these associations were stronger among participants aged ≥35 years or from North China. The second and third trimesters are the critical exposure windows for ambient temperature exposure-BP/HDP associations. During this period, exposure to cold ambient temperature was associated with elevated BP as well as increased HDP prevalence among most Chinese pregnant women, those aged ≥35 years or from North China being more vulnerable.

Critical windows of exposure to air pollution and gestational diabetes: assessing effect modification by maternal pre-existing conditions and environmental factors

BackgroundAmbient air pollution has been associated with gestational diabetes (GD), but critical windows of exposure and whether maternal pre-existing conditions and other environmental factors modify the associations remains inconclusive.MethodsWe conducted a retrospective cohort study of all singleton live birth that occurred between April 1st 2006 and March 31st 2018 in Ontario, Canada. Ambient air pollution data (i.e., fine particulate matter with a diameter ≤ 2.5 μm (PM2.5), nitrogen dioxide (NO2) and ozone (O3)) were assigned to the study population in spatial resolution of approximately 1 km × 1 km. The Normalized Difference Vegetation Index (NDVI) and the Green View Index (GVI) were also used to characterize residential exposure to green space as well as the Active Living Environments (ALE) index to represent the active living friendliness. Multivariable Cox proportional hazards regression models were used to evaluate the associations.ResultsAmong 1,310,807 pregnant individuals, 68,860 incident cases of GD were identified. We found the strongest associations between PM2.5 and GD in gestational weeks 7 to 18 (HR = 1.07 per IQR (2.7 µg/m3); 95% CI: 1.02 – 1.11)). For O3, we found two sensitive windows of exposure, with increased risk in the preconception period (HR = 1.03 per IQR increase (7.0 ppb) (95% CI: 1.01 – 1.06)) as well as gestational weeks 9 to 28 (HR 1.08 per IQR (95% CI: 1.04 –1.12)). We found that women with asthma were more at risk of GD when exposed to increasing levels of O3 (p- value for effect modification = 0.04). Exposure to air pollutants explained 20.1%, 1.4% and 4.6% of the associations between GVI, NDVI and ALE, respectively.ConclusionAn increase of PM2.5 exposure in early pregnancy and of O3 exposure during late first trimester and over the second trimester of pregnancy were associated with gestational diabetes whereas exposure to green space may confer a protective effect.

Association between ambient temperature and semen quality among sperm donation volunteers in South China

BackgroundPotential adverse effects of non-optimum temperatures on human semen quality have drawn much concern worldwide; however, the exposure–response relationship remains less understood. ObjectivesTo quantitatively assess the association between exposure to ambient temperature and semen quality in South China, and to identify potential critical exposure windows. MethodsWe conducted a longitudinal study to investigate 11,050 volunteers who lived in Guangdong province, China and intended to donate sperm in the Guangdong provincial human sperm bank during 2016–2021. Exposure to ambient temperature during 0–90 days before semen collection was assessed by extracting daily temperatures from a validated grid dataset at each subject’s residential address. Linear mixed models and linear regression models were used to perform exposure–response analyses. ResultsDuring the study period, the 11,050 subjects underwent 44,564 semen analyses. Each 5 °C increase of lag 0–90 day exposure to ambient temperature was approximately linearly associated with a 3.11 (95 % confidence interval [CI]: 2.08, 4.14) × 106/ml, 9.31 (4.83, 13.80) × 106, 1.27 % (0.91 %, 1.62 %), 8.20 (5.33, 11.08) × 106, 1.37 % (1.01 %, 1.74 %), 8.29 (5.52, 11.06) × 106, 0.67 % (0.28 %, 1.05 %), and 4.50 (2.20, 6.80) × 106 reduction in sperm concentration, total sperm number, total motility, total motile sperm number, progressive motility, total progressive sperm number, normal forms, and total normal form sperm number, respectively (all p < 0.001), which was not significantly modified by age (all p for effect modification > 0.05). We identified a critical exposure period of 10–14 days before semen collection for sperm motility, and 70–90 days before semen collection for sperm count and morphology. ConclusionsOur study provides consistent evidence that higher ambient temperature was significantly associated with a reduction in semen quality in South China. The findings highlight the needs to reduce high temperature exposures during 3 months before ejaculation to maintain better semen quality.

The impact of correlated exposures and missing data on multiple informant models used to identify critical exposure windows.

There has been heightened interest in identifying critical windows of exposure for adverse health outcomes; that is, time points during which exposures have the greatest impact on a person's health. Multiple informant models implemented using generalized estimating equations (MIM GEEs) have been applied to address this research question because they enable statistical comparisons of differences in associations across exposure windows. As interest rises in using MIMs, the feasibility and appropriateness of their application under settings of correlated exposures and partially missing exposure measurements requires further examination. We evaluated the impact of correlation between exposure measurements and missing exposure data on the power and differences in association estimated by the MIM GEE and an inverse probability weighted extension to account for informatively missing exposures. We assessed these operating characteristics under a variety of correlation structures, sample sizes, and missing data mechanisms considering various exposure-outcome scenarios. We showed that applying MIM GEEs maintains higher power when there is a single critical window of exposure and exposure measures are not highly correlated, but may result in low power and bias under other settings. We applied these methods to a study of pregnant women living with HIV to explore differences in association between trimester-specific viral load and infant neurodevelopment.