Prenatal Environmental Tobacco Smoke Exposure Research Articles

Prenatal and early life exposure to fine particulate matter and telomere length in early childhood

BackgroundTelomere length is a biomarker of molecular aging that may be impacted by air pollution exposure starting in utero. We aimed to examine the association between prenatal and early life exposure to fine particulate matter (PM2.5) and leukocyte telomere length (LTL) in children and explore sex differences. MethodsAnalyses included 384 mother–child pairs enrolled in the Programming Research in Obesity, Growth, and Environmental Stressors (PROGRESS) birth cohort in Mexico City. Exposure to PM2.5 was estimated at the residential level using a satellite based spatio-temporally resolved prediction model. Average relative LTL was measured in DNA isolated from blood collected at age 4–6 years using quantitative real-time polymerase chain reaction. Linear regression models were used to examine the association between average PM2.5 across pregnancy, individual trimesters, first postnatal year, and LTL. Models were adjusted for maternal age and education at enrollment, prenatal environmental tobacco smoke exposure, child sex, age, and body mass index z-score at LTL measurement. Effect modification by sex was investigated with interaction terms and stratification. ResultsIn trimester specific models, we found an association between 2nd trimester PM2.5 and elongated LTL (β: 4.34, 95%CI [0.42, 8.42], per 5 μg/m3 increase). There was suggestive effect modification by sex on average 2nd trimester PM2.5 with stronger associations seen in females compared to males (β: 7.12, [95%CI: 0.98, 13.6] and β: 1.43 [95%CI: −3.46, 6.57]) per 5 μg/m3 increase respectively. ConclusionSecond trimester PM2.5 levels were associated with changes in LTL in early childhood. Understanding temporal and sex differences in PM2.5 exposure may provide insights into telomere dynamics over early life.

Mitochondrial DNA copy number dynamics and associations with the prenatal environment from birth through adolescence in a population of Dominican and African American children

Mitochondrial DNA copy number (mtDNAcn) dynamics throughout childhood are poorly understood. We profiled mtDNAcn from birth through adolescence and evaluated how the prenatal environment influences mtDNAcn across childhood. Data were collected from children from New York City followed through 18 years. Using duplexed qRT-PCR, we quantified mtDNAcn relative to nuclear DNA in blood collected from the umbilical cord (n = 450), children aged 5–7 (n = 510), and adolescents aged 15–18 (n = 278). We examined mtDNAcn across childhood with linear mixed-effects models (LMM). Relative mtDNAcn was lowest at birth (mean ± SD: 0.67 ± 0.35) and increased in childhood (1.24 ± 0.50) then slightly declined in adolescence (1.13 ± 0.44). We observed no differences in mtDNAcn by sex or race/ethnicity. mtDNAcn was positively associated with prenatal environmental tobacco smoke exposure (0.077 [ 0.01, 0.14] change in relative mtDNAcn) but negatively associated with maternal completion of high school (-0.066 [-0.13, 0.00]), with the receipt of public assistance at birth (-0.074 [-0.14, -0.01]), and when mother born outside the U.S (-0.061 [-0.13, 0.003]). Infant birth outcomes were not associated with mtDNAcn. MtDNAcn levels were dynamic through childhood and associated with some prenatal factors, underscoring the need for the investigation of longitudinal mtDNAcn for human health research.

Mitochondrial DNA Copy Number Dynamics from Birth through Adolescence in a Population of Dominican and African American Children

Background: Mitochondria are vital for cellular energy production, metabolism, and signaling; however, they are uniquely susceptible to damage from environmental toxicants. Mitochondrial DNA copy number (mtDNAcn) is a widely used biomarker in human population studies and is associated with several exposures, including air pollution and metals. Yet, little is known about the dynamics of mtDNAcn throughout childhood and its longitudinal associations with key population characteristics. Our objective was to profile mtDNAcn from birth through adolescence to better inform future environmental health research. Methods: Data were collected from a cohort of mother-child pairs from New York City recruited 1998-2006 and followed through 18 years. Using duplexed qRT-PCR we quantified mtDNAcn relative to nuclear DNA from 662 participants using blood collected from the umbilical cord (n=450), children aged 5-7 (n=510), and adolescents aged 15-18 (n=278). We examined mtDNAcn across childhood with linear mixed-effects models (LMM) and latent class growth models (LGCM). We then examined associations with key population characteristics (maternal lifestyle during pregnancy and birth outcomes). Results: Relative mtDNAcn was lowest at birth (mean ± SD: 0.67 ± 0.35) and increased in childhood (1.24 ± 0.50) then slightly declined in adolescence (1.13 ± 0.44). MtDNAcn values across visits were moderately correlated (r=0.32-0.44). LGCM identified two trajectories of mtDNAcn: a high group (n=615) and a smaller low group (n=47). We observed no differences in mtDNAcn by sex or by race/ethnicity. In LMMs, longitudinal mtDNAcn was positively associated with prenatal environmental tobacco smoke exposure but negatively associated with maternal education and maternal receipt of public assistance at birth. No associations were observed with child birth outcomes. Conclusions: MtDNAcn levels were dynamic through childhood and are associated with prenatal factors. These results underscore the need for the investigation of mtDNAcn dynamics and predictors for environmental health research. Keywords: Biomarkers, mitochondria, mtDNA, children’s environmental health

Tobacco Use and Exposure to Environmental Tobacco Smoke amongst Pregnant Women in the United Arab Emirates: The Mutaba'ah Study.

Self-reported tobacco use is high in the male adult Emirati population (males ~36% vs. females ~3%); however, there are minimal data on tobacco use or exposure to environmental tobacco smoke (ETS) during pregnancy in the United Arab Emirates (UAE). This study investigated the prevalence of, and factors associated with, tobacco use and exposure to environmental tobacco smoke (ETS) amongst pregnant women in the UAE. Baseline cross-sectional data were analysed from the Mutaba’ah Study. Expectant mothers completed a self-administered questionnaire collecting sociodemographic information, maternal tobacco use, and ETS exposure during antenatal visits at three hospitals in Al Ain (UAE; May 2017–February 2021). Amongst 8586 women included in the study, self-reported tobacco use during pregnancy was low (0.7%), paternal tobacco use was high (37.9%), and a third (34.8%) of expectant mothers were exposed to ETS (28.0% at home only). Pregnant women who were employed (adjusted odds ratio (aOR): 1.35, 95% confidence interval (CI): 1.19–1.52), with childbirth anxiety (aOR 1.21, 95% CI 1.08–1.36), and with an increased number of adults living in the same household (aOR 1.02 95% CI 1.01–1.03) were independently more likely to be exposed to ETS. Pregnant women with higher education levels (aOR 0.84, 95% CI 0.75–0.94) and higher gravidity (aOR 0.95, 95% CI 0.92–0.99) were less likely to be exposed to ETS. Public health efforts targeting smoking cessation amongst husbands and promoting smoke-free homes are warranted to help reduce prenatal ETS exposure in the UAE.

Critical window for the association between prenatal environmental tobacco smoke exposure and preterm birth

Although environmental tobacco smoke (ETS) exposure is considered to be a severe public health problem and a modifiable risk factor for preterm birth (PTB), we still lack a comprehensive understanding of the PTB risk associated with trimester-specific prenatal ETS exposure. This study aimed to examine the accumulation of risk across trimester ETS exposure and the critical window of the association between maternal ETS exposure during pregnancy and PTB. A total of 63,038 mother-child pairs were involved in the analysis of the 2017 survey of Longhua Child Cohort Study. Information about socio-demographic characteristics, prenatal ETS exposure, and birth outcomes were collected using a self-report questionnaire. A series of logistic regression models were employed to assess the associations between prenatal ETS exposure and PTB. We found that maternal ETS exposure during pregnancy significantly increased the risk of PTB and this association increased with both the average level of daily ETS exposure and the number of trimesters of ETS exposure. Moreover, mothers who were initially exposed to ETS in the 1st trimester of pregnancy had significant higher risk of PTB (OR = 1.34, 95% CI: 1.25–1.44). Furthermore, mothers exposed to ETS in the 1st trimester only (OR = 1.26, 95%CI: 1.04–1.50), in both 1st and 2nd trimester (OR = 1.35, 95%CI: 1.08–1.67) and throughout pregnancy (OR = 1.35, 95%CI: 1.24–1.46) experienced a significantly high risk of PTB. Prenatal maternal ETS exposure during only the 2nd trimester also resulted in a high risk of PTB with marginal significance (OR = 1.33, 95% CI:0.78–2.13). To conclude, the 1st and early 2nd trimester might be the critical window for prenatal ETS exposure causing PTB.

Early Life Stress, Prenatal Environmental Tobacco Smoke Exposure, and the Development of Internalizing Symptoms Across Childhood

Early Life Stress, Prenatal Environmental Tobacco Smoke Exposure, and the Development of Internalizing Symptoms Across Childhood

Maternal Smoking During Pregnancy Affects Adult Onset of Asthma in Offspring: A Follow Up From Birth to Age 46 Years

Previous evidence has revealed an effect of environmental tobacco smoke (ETS) exposure on the development of childhood asthma. However, few studies have investigated the link between prenatal ETS exposure and adult-onset asthma. Therefore, in this study, we aim to determine if an association exists between adult-onset asthma and prenatal ETS exposure. Genetic predisposition to the development of asthma was also examined in conjunction with prenatal ETS exposure.This study was comprised of mothers and their offspring who were included in the Northern Finland Birth Cohort in 1966, a total of 12053 births. Data were collected from 7148 subjects, and 5491 met the inclusion criteria. The final study population consisted of 5200 subjects.Analysis was conducted on maternal smoking status in the last 3 months of pregnancy, and asthma status was conducted at 31 and 46 years of age (n = 5200). Questionnaire data were collected from subjects at 31 and 46 years of age regarding history of asthma or wheeze to determine incident asthma between 31 and 46 years. Information regarding maternal smoking status was gathered at clinical visits via questionnaire at 6- and 7-months’ gestation. Association between the development of asthma and maternal smoking (1 or more cigarette/pipe per day) was analyzed via Pearson’s χ2 test. Maternal smoking and associated changes in forced expiratory volume in 1 second (FEV1) and the FEV1 to forced vital capacity ratio were examined by using linear regression. Binary logistic regression was used to evaluate the relationship between maternal smoking status, adult-onset asthma, and single-nucleotide polymorphisms (SNPs). Linear regression controlled for covariates including maternal education and parental asthma as well as offspring smoking status, education, ponderal index, parity, and Apgar score at first minute.Maternal smoking during the last 3 months of pregnancy was associated with an increased risk for the development of asthma in offspring between 31 and 46 years of age, and reduced offspring FEV1 to forced vital capacity ratio at 31 years of age. This association was more prominent in individuals with haplotype rs11702779-AA and with the subgroup that reported previous wheeze. No association was found between maternal smoking during the last 3 months of pregnancy and offspring FEV1 at 31 years.Gestational smoke exposure is associated with increased incidence of adult-onset asthma and reduced pulmonary function in adult offspring.The results of this study are consistent with previous research revealing an association between gestational maternal smoke exposure and the subsequent development of asthma in offspring. This reveals susceptibility of the developing airway to maternal ETS exposure and the importance of smoking cessation during pregnancy. A limitation of this study is the inability to distinguish the role of prenatal maternal smoke exposure from maternal smoking in the home during the postnatal period.

Association between prenatal metal exposure and respiratory symptoms in childhood

BACKGROUND AND AIM: Arsenic, manganese, and lead have been cross-sectionally associated with adverse respiratory outcomes in childhood but there is limited data on their combined effects starting in utero. Our aim was to examine associations between prenatal lead, arsenic, and manganese exposure and respiratory symptoms in childhood. METHODS: We assessed 637 mother-child dyads enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) birth cohort in Mexico City. Blood manganese (BMn), arsenic (BAs), and lead (BPb) were measured in mothers at 2nd trimester. Ever wheeze, current wheeze and asthma diagnosis was based on the caregiver’s answers (yes/no) from the International Study of Asthma and Allergies in Childhood (ISAAC) survey applied at 4-5 and 6-7 years old. Covariates included maternal education, maternal asthma status, maternal age at enrollment, child’s sex, and prenatal environmental tobacco smoke exposure. A logistic mixed model regression was generated to simultaneously assess the association between prenatal metals and ever wheeze, current wheeze, and asthma diagnosis longitudinally across both the 4-5 and 6-7 year study visits. RESULTS:The mean ± standard deviation for log-transformed BMn, BPb, and BAs at 2nd trimester were 0.14 µg/dL ± 0.15, 0.48 µg/dL ± 0.27, and -1.11 µg/dL ± 0.19, respectively. In the adjusted model, BPb (Odds Ratio (OR): 1.95, 95% CI: 1.04-3.66) and BAs (OR: 3.44, 95% CI: 1.05-11.34) at 2nd trimester were associated with increased odds of ever wheeze and current wheeze, respectively. BMn at 2nd trimester (OR: 0.05, 95% CI: 0.01-0.27) was negatively associated with current wheeze. CONCLUSIONS:Prenatal exposure to arsenic and lead was associated with higher odds of ever and current wheeze while manganese was negatively associated with odds of current wheeze in childhood. These findings underscore the need to consider prenatal metal exposure, including low levels of exposure, in the study of respiratory diseases. KEYWORDS: Respiratory outcomes, Heavy metals, Allergies, Asthma, Children's environmental health

Prenatal environmental tobacco smoke exposure alters children’s cognitive control circuitry: A preliminary study

Background and ObjectivesPrenatal exposure to environmental tobacco smoke (ETS) is associated with increased attention problems in children, however, the effects of such exposure on children’s brain structure and function have not been studied. Herein, we probed effects of prenatal ETS on children’s cognitive control circuitry and behavior. MethodsForty-one children (7–9 years) recruited from a prospective longitudinal birth cohort of non-smoking mothers completed structural and task-functional magnetic resonance imaging to evaluate effects of maternal ETS exposure, measured by maternal prenatal urinary cotinine. Attention problems and externalizing behaviors were measured by parent report on the Child Behavior Checklist. ResultsCompared to non-exposed children, exposed children had smaller left and right thalamic and inferior frontal gyrus (IFG) volumes, with large effect sizes (p-FDR < .05, Cohen’s D range from 0.79 to 1.07), and increased activation in IFG during the resolution of cognitive conflict measured with the Simon Spatial Incompatibility Task (38 voxels; peak t(25) = 5.25, p-FWE = .005). Reduced thalamic volume was associated with increased IFG activation and attention problems, reflecting poor cognitive control. Mediation analyses showed a trend toward left thalamic volume mediating the association between exposure and attention problems (p = .05). ConclusionsOur findings suggest that maternal ETS exposure during pregnancy has deleterious effects on the structure and function of cognitive control circuitry which in turn affects attentional capacity in school-age children. These findings are consistent with prior findings documenting the effects of active maternal smoking on chidlren’s neurodevleoment, pointing to the neurotixicity of nicotine regardless of exposure pathway.

Perinatal exposure to particulate matter, environmental tobacco smoke and respiratory symptoms in Mexican children

Background: Particulate matter &lt;2.5 microns in diameter (PM2.5) and environmental tobacco smoke (ETS) are associated with respiratory morbidity starting in utero. However, their potential synergistic effects have not been completely elucidated. Here, we examined the joint effects of perinatal PM2.5 and prenatal ETS exposure on respiratory outcomes in children. Methods: We studied 514 mother-child dyads in the Programming Research in Obesity, Growth, Environment and Social Stressors study in Mexico City. Exposure to PM2.5 was estimated using residence in pregnancy and child’s first year of life and a satellite-based spatio-temporal model. ETS exposure was assessed by caregiver’s report of any smoker in household during second or third trimester. Outcomes included report of ever wheeze, wheeze in the past 12 months (current wheeze) and ever diagnosis of asthma assessed at 6-7 year visit in separate models. Associations were modeled using distributed lag models with daily PM2.5 averages for pregnancy and the first year of life, adjusting for child’s sex, birth weight z-score, mother’s age and education at enrollment, maternal asthma, season and stratified by prenatal ETS exposure (yes/no). Results: Exposure to ETS was reported in 178/514 participants (34.6%). We found significant associations between higher perinatal PM2.5 exposure and higher cumulative odds of ever wheeze(OR:3.72, 95%CI [1.37, 10.10] per 5 µg/m3) and wheezing in the past year at age 6 (OR:6.98, 95%CI [1.30, 37.50] per 5 µg/m3) only in children with ETS exposure. We did not find any evidence of an association between perinatal PM2.5 exposure and report of ever diagnosis of asthma or effect modification of the association by ETS exposure. Conclusions: Exposure to prenatal ETS modified the association between perinatal PM2.5 exposure and respiratory outcomes at age 6-7 years. It is important to consider concurrent chemical exposures to more comprehensively characterize children's environmental risk.

Prenatal and early life exposure to particulate matter, environmental tobacco smoke and respiratory symptoms in Mexican children

BackgroundExposure to particulate matter <2.5 μm in diameter (PM2.5) and environmental tobacco smoke (ETS) are associated with respiratory morbidity starting in utero. However, their potential synergistic effects have not been completely elucidated. Here, we examined the joint effects of prenatal and early life PM2.5 and prenatal ETS exposure on respiratory outcomes in children. Material and methodsWe studied 536 mother-child dyads in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study in Mexico City. Exposure to PM2.5 was estimated using residence in pregnancy and child's first year of life with a satellite-based spatio-temporal model. ETS exposure was assessed by caregiver's report of any smoker in the household during the second or third trimester. Outcomes included report of ever wheeze and wheeze in the past 12 months (current wheeze) assessed when children were 6–8 years old considered in separate models. Associations were modeled using distributed lag models (DLM) with daily PM2.5 averages for pregnancy and the first year of life, adjusting for child's sex, birth weight z-score, mother's age and education at enrollment, maternal asthma, season of conception and stratified by prenatal ETS exposure (yes/no). ResultsWe identified a sensitive window from gestational week 14 through postnatal week 18 during which PM2.5 was associated with higher risk of ever wheeze at age 6–8 years. We also observed a critical window of PM2.5 exposure between postnatal weeks 6–39 and higher risk of current wheeze. We found significant associations between higher prenatal and early life PM2.5 exposure and higher cumulative risk ratios of ever wheeze (RR:3.76, 95%CI [1.41, 10.0] per 5 μg/m3) and current wheeze in the past year (RR:7.91, 95%CI [1.5, 41.6] per 5 μg/m3) only among children born to mothers exposed to ETS in pregnancy when compared to mothers who were not exposed. ConclusionsExposure to prenatal ETS modified the association between prenatal and early life PM2.5 exposure and respiratory outcomes at age 6–8 years. It is important to consider concurrent chemical exposures to more comprehensively characterize children's environmental risk. Interventions aimed at decreasing passive smoking might mitigate the effects of ambient air pollution.

Maternal blood arsenic levels and associations with birth weight-for-gestational age

BackgroundAmong highly exposed populations, arsenic exposure in utero may be associated with decreased birth weight, however less is known about potential effects of arsenic exposure in urban communities without contaminated sources such as drinking water. ObjectiveInvestigate the association of blood arsenic levels with birth weight-for-gestational age categories within a prospective birth cohort study. Design/methodsWe analyzed 730 mother-infant dyads within the Programming Research in Obesity, GRowth, Environment and Social Stressors (PROGRESS) cohort in Mexico City. Total arsenic was measured in maternal blood samples from the 2nd and 3rd trimesters, at delivery, as well as from infant umbilical cord blood samples. Multivariable, multinomial logistic regression models adjusting for maternal age at enrollment, pre-pregnancy body mass index, parity, infant sex, socioeconomic position, and prenatal environmental tobacco smoke exposure were used to calculate odds ratios of small-for-gestational age (<10th percentile, SGA) and large-for-gestational age (>90th percentile, LGA) compared to appropriate-for-gestational age (AGA) per unit increase of log-transformed arsenic. ResultsMedian (IQR) blood arsenic levels for maternal second trimester were 0.72 (0.33) μg/L, maternal third trimester 0.75 (0.41) μg/L, maternal at delivery 0.85 (0.70) μg/L, and infant cord 0.78 (0.65) μg/L. Maternal delivery and infant cord blood samples were most strongly correlated (spearman r = 0.65, p < 0.0001). Maternal arsenic levels at delivery were associated with significantly higher odds of both SGA (adj. OR = 1.44, 95% CI: 1.08–1.93) and LGA (adj. OR = 2.03, 95% CI: 1.12–3.67) compared to AGA. Results were similar for cord blood. There were 130 SGA infants and 22 LGA infants. Earlier in pregnancy, there were no significant associations of arsenic and birth weight-for-gestational age. However, we observed non-significantly higher odds of LGA among women with higher arsenic levels in the 3rd trimester (adj. OR = 1.46, 95% CI: 0.67–3.12). ConclusionWe found that in a Mexico City birth cohort, higher maternal blood arsenic levels at delivery were associated with higher odds of both SGA and LGA. However, sources and species of arsenic were not known and the number of LGA infants was small, limiting the interpretation of this finding and highlighting the importance of future large studies to incorporate arsenic speciation. If our findings were confirmed in studies that addressed these limitations, determining modifiable factors that could be mitigated, such as sources of arsenic exposure, may be important for optimizing fetal growth to improve long-term health of children.

Association between prenatal particulate air pollution exposure and telomere length in cord blood: Effect modification by fetal sex

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.

Appetite during the second and third trimesters mediates the impact of prenatal environmental tobacco smoke exposure on symmetric full-term low birth weight

Objective: To examine the relationship of prenatal environmental tobacco smoke (ETS) exposure and full-term low birth weight (FT-LBW) when taking anthropometric proportionality into consideration, and explore whether appetite mediates their association.Study design: We conducted a case-control study among pregnant women at two Women and Children’s Hospitals in Guangdong, China. Information was collected through interview and medical records review. A series of logistic and linear regressions were used to examine the relationships of prenatal ETS exposure, appetite, and FT-LBW.Results: After adjusting for the potential confounders, prenatal ETS exposure was significantly negatively associated with FT-LBW (OR: 1.83, 95%CI: 1.35–2.48) and negatively correlated with maternal appetite in second and third trimester during pregnancy (β: −0.11, standard error: 0.03). Moreover, mediation analysis illustrated that maternal appetite partially mediated 12.00% of their relationship. However, subgroup analysis showed that prenatal ETS exposure was linked to higher risk of symmetric FT-LBW (OR: 2.26, 95%CI: 1.56–3.26) but not asymmetric FT-LBW. And maternal appetite explained only 6.45% of their relationship.Conclusions: Maternal prenatal ETS exposure increased risk of having symmetric FT-LBW infant, and appetite might mediate their relationship partially. This study emphasizes the importance of sample homogeneity and stresses the needs to improve the public awareness of the harmful effects of ETS.

High Maternal Circulating Cotinine During Pregnancy is Associated With Persistently Shorter Stature From Birth to Five Years in an Asian Cohort.

Self-reported maternal active smoking has been associated with reduced offspring birth length and shorter stature in early and late childhood. To use circulating cotinine as an objective biomarker to investigate the association between smoking and environmental tobacco smoke (ETS) exposure in pregnancy and longitudinal measures of offspring length/height from birth to 60 months. In 969 maternal-offspring dyads from the GUSTO cohort, maternal plasma cotinine at 26-28 weeks' gestation was measured by LC/MS/MS and categorized into four groups: Group 1: cotinine <0.17 ng/mL (the assay's detection limit) and no ETS exposure; Group 2: cotinine <0.17 ng/mL but self-reported ETS; Group 3: cotinine 0.17-13.99 ng/mL (ETS or light smoking); Group 4: cotinine ≥14 ng/mL (active smoking). Adjusting for infant sex, gestational age at birth, ethnicity, maternal age, education, parity, BMI, and height, Group 4 offspring were shorter at birth [z-score β = -0.42 SD units (SDs) (95% CI = -0.77 to -0.06)] than Group 1 offspring. Group 4 offspring continued to be shorter at older ages, with similar effect sizes at 3 months [-0.57 SDs (-0.95 to -0.20)], 36 months [-0.53 SDs (-0.92 to -0.15)], 48 months [-0.43 SDs (-0.81 to -0.04)], and 60 months [-0.57 SDs (-0.96 to -0.17)]. Associations were particularly marked in boys. No significant differences in stature were observed in Groups 2 or 3 compared with Group 1. This Asian longitudinal study associated high prenatal cotinine with persistently shorter stature in offspring from birth and into early childhood, whilst low prenatal cotinine levels and ETS exposure showed no such association. Little is known about the long-term effects of prenatal tobacco exposure on offspring stature in Asia where passive smoking is common. This study has used an objective biomarker to reveal that the association of prenatal tobacco exposure with offspring length/height mainly occurs at a high maternal cotinine level of greater than 14 ng/mL in pregnancy, consistent with active smoking, but no significant associations were found with lower cotinine levels, consistent with passive smoking. Encouraging women to quit smoking prior to or during pregnancy may avert the long-term negative impact on their child's height despite appreciable prenatal ETS exposure.

Prenatal Exposure to Environmental Tobacco Smoke and Hyperactivity Behavior in Chinese Young Children.

This study aimed to examine the association between prenatal environmental tobacco smoke (ETS) exposure and hyperactivity behaviors in young children. A cross-sectional study was undertaken among 21,243 participants from all of the kindergartens in Longhua District of Shenzhen, China. Multivariate logistic regression models and hierarchical linear models were employed to assess the associations. After adjusting for potential confounders of gender, preterm birth, birth asphyxiation, etc., prenatal ETS exposure was significantly associated with an increased risk of hyperactivity behaviors in young children (OR (95% CI) = 1.51 (1.28–1.77); β (95% CI) = 0.017 (0.013–0.020)). Along with increases in children’s prenatal ETS exposure dose (measured by daily ETS exposure duration, daily cigarette consumption by household members, and overall score of prenatal ETS exposure), the children were also increasingly more likely to exhibit hyperactivity behaviors. Furthermore, children whose mothers had prenatal ETS exposure in any one or more of the pregnancy trimesters were more likely to exhibit hyperactivity behaviors as compared with those born to non-exposure mothers (all p < 0.05). Overall, prenatal ETS exposure could be associated with a detrimental impact on offspring’s hyperactivity behaviors, and public health efforts are needed to reduce prenatal ETS exposure.

Prenatal environmental tobacco smoke exposure increases allergic asthma risk with methylation changes in mice.

Allergic asthma remains an inadequately understood disease. In utero exposure to environmental tobacco smoke (ETS) has been identified as an environmental exposure that can increase an individual's asthma risk. To improve our understanding of asthma onset and development, we examined the effect of in utero ETS exposure on allergic disease susceptibility in an asthmatic phenotype using a house dust mite (HDM) allergen-induced murine model. Pregnant C57BL/6 mice were exposed to either filtered air or ETS during gestation, and their offspring were further exposed to HDM at 6-7 weeks old to induce allergic inflammation. Methylation in the promoter regions of allergic inflammation-related genes and genomic DNA was quantified. Exposure to HDM resulted in the onset of allergic lung inflammation, with an increased presence of inflammatory cells, Th2 cytokines (IL-4, IL-5, and IL-13), and airway remodeling. These asthmatic phenotypes were significantly enhanced when the mice had been exposed to in utero ETS. Furthermore, prenatal ETS exposure and subsequent HDM (ETS/HDM)-induced asthmatic phenotypes agree with methylation changes in the selected asthma-related genes, including IL-4, IL-5, IL-13, INF-γ, and FOXP3. Global DNA methylation was significantly lower in ETS/HDM-exposed mice than that of controls, which coincides with the results observed in lung, spleen, and blood DNAs. Prenatal ETS exposure resulted in a severe increase in allergic inflammatory responses after an HDM challenge, with corresponding methylation changes. Prenatal ETS exposure may influence developmental plasticity and result in altered epigenetic programming, leading to an increased susceptibility to asthma. Environ. Mol. Mutagen. 58:423-433, 2017. © 2017 Wiley Periodicals, Inc.

Identifying sensitive windows for prenatal particulate air pollution exposure and mitochondrial DNA content in cord blood

IntroductionChanges in mitochondrial DNA (mtDNA) can serve as a marker of cumulative oxidative stress (OS) due to the mitochondria's unique genome and relative lack of repair systems. In utero particulate matter ≤2.5μm (PM2.5) exposure can enhance oxidative stress. Our objective was to identify sensitive windows to predict mtDNA damage experienced in the prenatal period due to PM2.5 exposure using mtDNA content measured in cord blood. Material and methodsWomen affiliated with the Mexican social security system were recruited during pregnancy in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study. Mothers with cord blood collected at delivery and complete covariate data were included (n=456). Mothers' prenatal daily exposure to PM2.5 was estimated using a satellite-based spatio-temporally resolved prediction model and place of residence during pregnancy. DNA was extracted from umbilical cord leukocytes. Quantitative real-time polymerase chain reaction (qPCR) was used to determine mtDNA content. A distributive lag regression model (DLM) incorporating weekly averages of daily PM2.5 predictions was constructed to plot the association between exposure and OS over the length of pregnancy. ResultsIn models that included child's sex, mother's age at delivery, prenatal environmental tobacco smoke exposure, birth year, maternal education, and assay batch, we found significant associations between higher PM2.5 exposure during late pregnancy (35–40weeks) and lower mtDNA content in cord blood. ConclusionsIncreased PM2.5 during a specific prenatal window in the third trimester was associated with decreased mtDNA content suggesting heightened sensitivity to PM-induced OS during this life stage.

Bisphenol A exposure and behavioral problems among inner city children at 7–9 years of age

BackgroundBisphenol A (BPA) is a ubiquitous endocrine disrupting compound. Several experimental and epidemiological studies suggest that gestational BPA exposure can lead to neurodevelopmental and behavioral problems in early-life, but results have been inconsistent. We previously reported that prenatal BPA exposure may affect child behavior and differently among boys and girls at ages 3–5 years. ObjectivesWe investigated the association of prenatal and early childhood BPA exposure with behavioral outcomes in 7–9 year old minority children and hypothesized that we would observe the same sex-specific pattern observed at earlier ages. MethodsAfrican-American and Dominican women enrolled in an inner-city prospective cohort study and their children were followed from mother’s pregnancy through children’s age 7–9 years. Women during the third trimester of pregnancy and children at ages 3 and 5 years provided spot urine samples. BPA exposure was categorized by tertiles of BPA urinary concentrations. The Child Behavioral Checklist (CBCL) was administered at ages 7 and 9 to assess multiple child behavior domains. Associations between behavior and prenatal (maternal) BPA concentrations and behavior and postnatal (child) BPA concentration were assessed via Poisson regression in models stratified by sex. These models accounted for potential confounders including prenatal or postnatal urinary BPA concentrations, child age at CBCL assessment, ethnicity, gestational age, maternal intelligence, maternal education and demoralization, quality of child’s home environment, prenatal environmental tobacco smoke exposure, and prenatal mono-n-butyl phthalate concentration. ResultsThe direction of the associations differed between boys and girls. Among boys (n=115), high prenatal BPA concentration (upper tertile vs. lower two tertiles) was associated with increased internalizing (β=0.41, p<0.0001) and externalizing composite scores (β=0.40, p<0.0001) and with their corresponding individual syndrome scales. There was a general decrease in scores among girls that was significant for the internalizing composite score (β=−0.17, p=0.04) (n=135). After accounting for possible selection bias, the results remained consistent for boys. Conversely, high postnatal BPA concentration was associated with increased behaviors on both the internalizing composite (β=0.30, p=0.0002) and externalizing composite scores (β=0.33, p<0.0001) and individual subscores in girls but fewer symptoms in boys. These results remained significant in girls after accounting for selection bias. ConclusionThese results suggest BPA exposure may affect childhood behavioral outcomes in a sex-specific manner and differently depending on timing of exposure.

Prenatal exposure to environmental tobacco smoke and language development in toddlers

Background: Maternal exposure to environmental tobacco smoke (ETS) associated with children’s neurobehavioral development has been reported. There is also a study indicating that maternal smoking during pregnancy can affect newborns’ speech processing ability. Language is a result of cognitive development; however, there is no study focus on the effects of maternal ETS exposure during pregnancy to toddlers’ language and communication development. Aims: The aim of this study is to examine the effect of prenatal exposure to ETS on the language development in toddlers. Methods: A total of 103 children from the Taiwan Birth Panel Study (TBPS) were followed up in northern Taiwan. We enrolled their mothers before delivery, interviewed them using a structured questionnaire, and collected umbilical cord blood. Umbilical cord cotinine, a blood indicator of prenatal ETS exposure, was analyzed by using HPLC-MS/MS. The Mandarin-Chinese Communicative Developmental Inventory (MCDI) for toddlers was used to assess these children’s language and communication development at 2 years of age. We examined the children’s language development between exposed and control groups by multiple linear and logistic regression models to control for potential confounders. Results: Maternal ETS exposure during pregnancy was negatively associated with language and communication development. The adverse effects to the exposed group was significantly showed on the total MCDI score (?=-71.04; p=0.0396), word produced part (?=-65.81; p=0.0433) and syntax complexity part (?=-4.91; p=0.146) in multiple linear regression models. Conclusions: Our results indicate that maternal ETS exposure was related to the adverse effects on early children’s language development. Further studies are needed to clarify the causal relationship between cord blood cotinine and children’s language development.