Dataset Information

Prenatal particulate air pollution and newborn telomere length: Effect modification by maternal antioxidant intakes and infant sex.

ABSTRACT:

Background

Evidence links gestational exposure to particulate matter with an aerodynamic diameter of less than 2.5 μm (PM_2.5) with changes in leukocyte telomere length in cord blood with some studies showing sex-specific effects. PM_2.5 exposure in utero increases oxidative stress, which can impact telomere biology. Thus, maternal antioxidant intakes may also modify the particulate air pollution effects.

Methods

We examined associations among prenatal PM_2.5 exposure and newborn relative leukocyte telomere length (rLTL), and the modifying effects of maternal antioxidant intake and infant sex. We estimated daily PM_2.5 exposures over gestation using a validated spatiotemporally resolved satellite-based model. Maternal dietary and supplemental antioxidant intakes over the prior three months were ascertained during the second trimester using the modified Block98 food frequency questionnaire; high and low antioxidant intakes were categorized based on a median split. We employed Bayesian distributed lag interaction models (BDLIMs) to identify both sensitive windows of exposure and cumulative effect estimates for prenatal PM_2.5 exposure on newborn rLTL, and to examine effect modification by maternal antioxidant intakes. A 3-way interaction between PM_2.5, maternal antioxidant intake and infant sex was also explored.

Results

For the main effect of PM_2.5, BDLIMs identified a sensitive window at 12-20 weeks gestation for the association between increased prenatal PM_2.5 exposure and shorter newborn rLTL and a cumulative effect of PM_2.5 over gestation on newborn telomere length [cumulative effect estimate (CEE) = -0.29 (95% CI -0.49 to -0.10) per 1μg/m³ increase in PM_2.5]. In models examining maternal antioxidant intake effects, BDLIMs found that children born to mothers reporting low antioxidant intakes were most vulnerable [CEE of low maternal antioxidant intake = -0.31 (95% CI -0.55 to -0.06) vs high maternal antioxidant intake = -0.07 (95% CI -0.34 to 0.17) per 1μg/m³ increase in PM_2.5]. In exploratory models examining effect modification by both maternal antioxidant intakes and infant sex, the cumulative effect remained significant only in boys whose mothers reported low antioxidant intakes [CEE = -0.38 (95% CI -0.80 to -0.004)]; no sensitive windows were identified in any group.

Conclusions

Prenatal PM_2.5 exposure in mid-gestation was associated with reduced infant telomere length. Higher maternal antioxidant intakes mitigated these effects.

SUBMITTER: Lee AG

PROVIDER: S-EPMC7844769 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionIn utero particulate matter exposure produces oxidative stress that impacts cellular processes that include telomere biology. Newborn telomere length is likely critical to an individual's telomere biology; reduction in this initial telomere setting may signal increased susceptibility to adverse outcomes later in life. We examined associations between prenatal particulate matter with diameter ≤2.5 µm (PM2.5) and relative leukocyte telomere length (LTL) measured in cord blood using a data-driven approach to characterize sensitive windows of prenatal PM2.5 effects and explore sex differences.MethodsWomen who were residents of Mexico City and affiliated with the Mexican Social Security System were recruited during pregnancy (n = 423 for analyses). Mothers' prenatal exposure to PM2.5 was estimated based on residence during pregnancy using a validated satellite-based spatio-temporally resolved prediction model. Leukocyte DNA was extracted from cord blood obtained at delivery. Duplex quantitative polymerase chain reaction was used to compare the relative amplification of the telomere repeat copy number to single gene (albumin) copy number. A distributed lag model incorporating weekly averages for PM2.5 over gestation was used in order to explore sensitive windows. Sex-specific associations were examined using Bayesian distributed lag interaction models.ResultsIn models that included child's sex, mother's age at delivery, prenatal environmental tobacco smoke exposure, pre-pregnancy BMI, gestational age, birth season and assay batch, we found significant associations between higher PM2.5 exposure during early pregnancy (4-9 weeks) and shorter LTL in cord blood. We also identified two more windows at 14-19 and 34-36 weeks in which increased PM2.5 exposure was associated with longer LTL. In stratified analyses, the mean and cumulative associations between PM2.5 and shortened LTL were stronger in girls when compared to boys.ConclusionsIncreased PM2.5 during specific prenatal windows was associated with shorter LTL and longer LTL. PM2.5 was more strongly associated with shortened LTL in girls when compared to boys. Understanding sex and temporal differences in response to air pollution may provide unique insight into mechanisms.

Project description:BackgroundTelomere length (TL) predicts the onset of cellular senescence and correlates with longevity and age-related disease risk. While telomeres erode throughout life, adults display fixed ranking and tracking of TL, supporting the importance of the early environment in determining inter-individual variability across the life course. Given their guanine-rich structure, telomeres are highly susceptible to oxidative stress (OS). We examined maternal metal exposure, which can induce OS, in relation to newborn TL. We also considered the modifying role of maternal antioxidant intake.MethodsAnalyses included 100 mother-newborn pairs enrolled in the Boston and New York City-based PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy cohort. We measured As, Ba, Cd, Ni, and Pb in maternal late-pregnancy urine by ICP-MS and quantified relative leukocyte TL (rLTL) in cord blood using qPCR. We used Weighted Quantile Sum (WQS) regression to estimate the metal mixture - rLTL association and conducted repeated holdout validation to improve the stability of estimates across data partitions. We examined models stratified by high (>median) versus low (≤median) maternal antioxidant intake, estimated from Block98 Food Frequency Questionnaires. We considered urinary creatinine, week of urine collection, maternal age, and race/ethnicity as covariates.ResultsIn adjusted models, urinary metals were inversely associated with newborn rLTL (βWQS = -0.50, 95% CI: -0.78, -0.21). The top metals contributing to the negative association included Ba (weight: 35.4%), Cd (24.5%) and Pb (26.9%). In models stratified by antioxidant intake, the significant inverse association between metals and rLTL remained only among mothers with low antioxidant intake (low: βWQS = -0.92, 95% CI: -1.53, -0.30; high: βWQS = -0.03, 95% CI: -0.58, 0.52). Results were similar in unadjusted models.ConclusionsRelative LTL was shorter among newborns of mothers with higher exposure to metals during pregnancy. Higher maternal antioxidant intake may mitigate the negative influence of metals on newborn rLTL.

Project description:BackgroundTelomere length is a molecular marker of biological aging.ObjectiveHere we investigated whether early-life exposure to residential air pollution was associated with leukocyte telomere length (LTL) at 8 y of age.MethodsIn a multicenter European birth cohort study, HELIX (Human Early Life Exposome) ([Formula: see text]), we estimated prenatal and 1-y childhood exposure to nitrogen dioxide ([Formula: see text]), particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text]), and proximity to major roads. Average relative LTL was measured using quantitative real-time polymerase chain reaction (qPCR). Effect estimates of the association between LTL and prenatal, 1-y childhood air pollution, and proximity to major roads were calculated using multiple linear mixed models with a random cohort effect and adjusted for relevant covariates.ResultsLTL was inversely associated with prenatal and 1-y childhood [Formula: see text] and [Formula: see text] exposures levels. Each standard deviation (SD) increase in prenatal [Formula: see text] was associated with a [Formula: see text] (95% CI: [Formula: see text], [Formula: see text]) change in LTL. Prenatal [Formula: see text] was nonsignificantly associated with LTL ([Formula: see text] per SD increase; 95% CI: [Formula: see text], 0.6). For each SD increment in 1-y childhood [Formula: see text] and [Formula: see text] exposure, LTL shortened by [Formula: see text] (95% CI: [Formula: see text], [Formula: see text]) and [Formula: see text] (95% CI: [Formula: see text], 0.1), respectively. Each doubling in residential distance to nearest major road during childhood was associated with a 1.6% (95% CI: 0.02, 3.1) lengthening in LTL.ConclusionLower exposures to air pollution during pregnancy and childhood were associated with longer telomeres in European children at 8 y of age. These results suggest that reductions in traffic-related air pollution may promote molecular longevity, as exemplified by telomere length, from early life onward. https://doi.org/10.1289/EHP4148.

Project description:Low birth weight is an important risk factor for many co-morbidities both in early life as well as in adulthood. Numerous studies report associations between prenatal exposure to particulate matter (PM) air pollution and low birth weight. Previous systematic reviews and meta-analyses report varying effect sizes and significant heterogeneity between studies, but did not systematically evaluate the quality of individual studies or the overall body of evidence. We conducted a new systematic review to determine how prenatal exposure to PM2.5, PM10, and coarse PM (PM2.5-10) by trimester and across pregnancy affects infant birth weight. Using the Navigation Guide methodology, we developed and applied a systematic review protocol [CRD42017058805] that included a comprehensive search of the epidemiological literature, risk of bias (ROB) determination, meta-analysis, and evidence evaluation, all using pre-established criteria. In total, 53 studies met our inclusion criteria, which included evaluation of birth weight as a continuous variable. For PM2.5 and PM10, we restricted meta-analyses to studies determined overall as "low" or "probably low" ROB; none of the studies evaluating coarse PM were rated as "low" or "probably low" risk of bias, so all studies were used. For PM2.5, we observed that for every 10 µg/m3 increase in exposure to PM2.5 in the 2nd or 3rd trimester, respectively, there was an associated 5.69 g decrease (I2: 68%, 95% CI: -10.58, -0.79) or 10.67 g decrease in birth weight (I2: 84%, 95% CI: -20.91, -0.43). Over the entire pregnancy, for every 10 µg/m3 increase in PM2.5 exposure, there was an associated 27.55 g decrease in birth weight (I2: 94%, 95% CI: -48.45, -6.65). However, the quality of evidence for PM2.5 was rated as "low" due to imprecision and/or unexplained heterogeneity among different studies. For PM10, we observed that for every 10 µg/m3 increase in exposure in the 3rd trimester or the entire pregnancy, there was a 6.57 g decrease (I2: 0%, 95% CI: -10.66, -2.48) or 8.65 g decrease in birth weight (I2: 84%, 95% CI: -16.83, -0.48), respectively. The quality of evidence for PM10 was rated as "moderate," as heterogeneity was either absent or could be explained. The quality of evidence for coarse PM was rated as very low/low (for risk of bias and imprecision). Overall, while evidence for PM2.5 and course PM was inadequate primarily due to heterogeneity and risk of bias, respectively, our results support the existence of an inverse association between prenatal PM10 exposure and low birth weight.

Project description:BackgroundPrenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes.ObjectivesWe aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter [Formula: see text] ([Formula: see text]) or [Formula: see text] ([Formula: see text]) and DNA methylation in newborns and children.MethodsWe meta-analyzed associations between exposure to [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. We used two approaches, one focusing on single cytosine-phosphate-guanine (CpG) sites and another on differentially methylated regions (DMRs). We also related PM exposures to blood mRNA expression.ResultsSix CpGs were significantly associated [false discovery rate (FDR) [Formula: see text]] with prenatal [Formula: see text] and 14 with [Formula: see text] exposure. Two of the [Formula: see text] CpGs mapped to FAM13A (cg00905156) and NOTCH4 (cg06849931) previously associated with lung function and asthma. Although these associations did not replicate in the smaller newborn sample, both CpGs were significant ([Formula: see text]) in 7- to 9-y-olds. For cg06849931, however, the direction of the association was inconsistent. Concurrent [Formula: see text] exposure was associated with a significantly higher NOTCH4 expression at age 16 y. We also identified several DMRs associated with either prenatal [Formula: see text] and or [Formula: see text] exposure, of which two [Formula: see text] DMRs, including H19 and MARCH11, replicated in newborns.ConclusionsSeveral differentially methylated CpGs and DMRs associated with prenatal PM exposure were identified in newborns, with annotation to genes previously implicated in lung-related outcomes. https://doi.org/10.1289/EHP4522.

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