Prenatal Tobacco Smoke Exposure Research Articles

Prenatal tobacco smoke exposure and risk for cognitive delays in infants born very premature

Prenatal tobacco smoke exposure (TSE) and prematurity are independent risk factors for abnormal neurodevelopment. The objectives were to compare differences in Bayley-III cognitive, language, and motor scores at 2 years corrected age (CA) in 395 infants born very preterm (≤ 32 weeks gestation) with and without prenatal TSE. We performed multivariable linear regression analyses to examine associations between prenatal TSE and neurodevelopmental outcomes and a mediation analysis to estimate direct effects of prenatal TSE on outcomes and indirect effects through preterm birth. In total, 50 (12.6%) infants had prenatal TSE. Infants with prenatal TSE had lower mean [95% CI] Cognitive score (82.8 [78.6, 87.1]) vs. nonexposed infants (91.7 [90.1, 93.4]). In children with and without prenatal TSE, there were significant differences in mean [95% CI] Language scores (81.7 [76.0, 87.4] vs. 92.4 [90.2, 94.6], respectively) and mean [95% CI] Motor scores (86.5 [82.2, 90.7] vs. 93.4 [91.8, 95.0], respectively); scores remained significant after controlling for confounders. Preterm birth indirectly mediated 9.0% of the total effect of prenatal TSE on Cognitive score (P = NS). However, 91% of the remaining total effect was significant and attributable to TSE’s direct harmful effects on cognitive development (β = − 5.17 [95% CI − 9.97, − 0.38]). The significant association is largely due to TSE’s direct effect on cognitive development and not primarily due to TSE’s indirect effect on preterm birth.

Effect of prenatal passive tobacco smoke exposure on full-term birth weight of born neonates:SR

Abstract Prenatal smoking increases the risks of pre-term birth, stillbirth, neonatal death, and perinatal death as well as neurodevelopmental disorders in children. However, there is a lack of consistency in research published about association/impacts of passive smoking and low birth weight (LBW). Hence, we carried out this systematic review to determine whether or not there is a relation between prenatal tobacco smoke exposure and full-term LBW infants. Following PRISMA guidelines, we carried out systematic searches with PubMed, CINAHL, PsycInfo, and Embase for cohort case-control studies the 31-year period from 1991 - 2022. Of the 2,877 articles identified, 835 duplicates were removed. Title screening was done for 2,126 articles. 25 articles met the inclusion criteria that were Peer reviewed full-text articles in the English language and related to LBW due to passive smoking only. We found 20/25 articles showed a significant relationship with an OR ranging between 2.14 and 54.9 respectively between exposure to environmental tobacco smoke (ETS) and LBW infants at term and 5 articles showed no association with an OR ranging between 0.48 and 1.51. A significant difference found between the sample size among the studies included influencing the outcome of the study (ranging from smallest (n = 208) and largest (n = 17412). Mean age of mother was 29.6±3.8 and mean birth weight was 3,212±467.1. Nicotine level > 4.1 ng/mL or duration of exposure 24.4 hours/week gives strong evidence of prevalence of LBW among SHS exposed mothers. Compiled evidence suggests that, there is a significant association between prenatal passive smoke exposure and neonatal birth-weight at full term. There is a need for health researchers and public health experts to design and implement targeted programmes to reduce LBW due to passive smoke in our societies. Key messages • Exposure to ETS from domestic sources has a substantial influence on birth weight. • Combining educational programmes and legislative interventions is required to eliminate infants’ contact with tobacco smoke in utero and throughout childhood.

AHRR Hypomethylation mediates the association between maternal smoking and metabolic profiles in children.

Tobacco smoking during pregnancy is associated with metabolic dysfunction in children, but mechanistic insights remain limited. Hypomethylation of cg05575921 in the aryl hydrocarbon receptor repressor (AHRR) gene is associated with in utero tobacco smoke exposure. In this study, we evaluated whether AHRR hypomethylation mediates the association between maternal smoking and metabolic dysfunction in children. We assessed metabolic dysfunction using liver fat content (LFC), serum, and clinical data in children aged 7-12 years (n=78) followed since birth. Maternal smoking was self-reported at 12 weeks gestation. Methylation was measured by means of pyrosequencing at 3 sequential CpG sites, including cg05575921, at birth and at ages 7-12. Regression models were used to evaluate whether AHRR methylation mediated the association between maternal smoking and child metabolic dysfunction. Average AHRR methylation at birth was significantly higher among children of nonsmoking mothers compared with children of mothers who smoked (69.8% ± 4.4% vs. 63.5% ± 5.5, p=0.0006). AHRR hypomethylation at birth was associated with higher liver fat content (p=0.01), triglycerides (p=0.01), and alanine aminotransferase levels (p=0.03), and lower HDL cholesterol (p=0.01) in childhood. AHRR hypomethylation significantly mediated associations between maternal smoking and liver fat content (indirect effect=0.213, p=0.018), triglycerides (indirect effect=0.297, p=0.044), and HDL cholesterol (indirect effect = -0.413, p=0.007). AHRR methylation in childhood (n=78) was no longer significantly associated with prenatal smoke exposure or child metabolic parameters (p>0.05). AHRR hypomethylation significantly mediates the association between prenatal tobacco smoke exposure and features of childhood metabolic dysfunction, despite the lack of persistent hypomethylation of AHRR into childhood. Further studies are needed to replicate these findings and to explore their causal and long-term significance.

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.

Prenatal tobacco smoke exposure and risk of brain abnormalities on magnetic resonance imaging at term in infants born very preterm

Prenatal tobacco smoke exposure and preterm birth are associated with abnormal brain and neurodevelopmental outcomes in infants. Studies that can disentangle indirect mediating effects from direct effects of prenatal tobacco smoke exposure on sensitive early brain magnetic resonance imaging biomarkers in very preterm infants are needed. This study aimed to determine whether prenatal tobacco smoke exposure in preterm infants posed any direct effects on magnetic resonance imaging-determined global brain abnormality score and secondary measures of brain abnormalities after removing any indirect mediating effects of preterm birth on neurostructural outcomes. We examined brain magnetic resonance imaging findings collected at 39 to 44 weeks postmenstrual age from a prospective cohort of 395 infants born very preterm (gestational age of ≤32 weeks). The primary outcome was global brain abnormality score, and the secondary outcomes were global efficiency of structural connectome, diffuse white matter abnormality volume, total brain tissue volume, total gray and white matter volumes, and cerebellar volume. Maternal reports of smoking during pregnancy were obtained. We performed multivariable linear regression analyses to examine the association between prenatal tobacco smoke exposure and our magnetic resonance imaging outcomes, controlling for prospectively collected confounders. Moreover, we performed a mediation analysis to estimate the direct effects of prenatal tobacco smoke exposure on brain abnormalities and any indirect effects through preterm birth. Overall, 12.6% of infants had prenatal tobacco smoke exposure. Infants with prenatal tobacco smoke exposure had a higher median global brain abnormality score than nonexposed infants (7 [interquartile range, 0-41] vs 5 [interquartile range, 0-34]; P≤.001); the findings remained significant (P<.001) after controlling for antenatal confounders. Global efficiency (P<.001), diffuse white matter volume (P=.037), and total brain tissue volume (P=.047) were significantly different between TSE groups in multivariable analyses. On mediation analysis, preterm birth mediated between 0% and 29% of the indirect effect of prenatal tobacco smoke exposure on several measures of brain abnormality outcomes. Thus, prenatal tobacco smoke exposure had a direct adverse effect between 71% and 100% on brain injury or abnormal development. Our study has identified multiple adverse effects of prenatal tobacco smoke exposure on sensitive and objective measures of neonatal brain injury and abnormal development; most cases seemed to be a direct effect of prenatal tobacco smoke exposure on fetal brain development. The results underscored the significant adverse neurostructural effects of prenatal tobacco smoke exposure to tobacco smoke pollutants.

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 &amp;#xb1; SD: 0.67 &amp;#xb1; 0.35) and increased in childhood (1.24 &amp;#xb1; 0.50) then slightly declined in adolescence (1.13 &amp;#xb1; 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

Prenatal and early childhood critical windows for the association of nephrotoxic metal and metalloid mixtures with kidney function.

As renal development and maturation processes begin in utero and continue through early childhood, sensitive developmental periods arise during which metal exposures can program subclinical nephrotoxicity that manifests later in life. We used novel dentine biomarkers of established nephrotoxicants including arsenic (As), cadmium (Cd), lead (Pb), chromium (Cr), and lithium (Li), and their mixtures, to identify critical windows of exposure-associated kidney function alterations in preadolescents. Participants included 353 children in the Programming Research in Obesity Growth, Environment and Social Stressors (PROGRESS) longitudinal birth cohort study based in Mexico City. Estimated glomerular filtration rate (eGFR) was assessed in 8-12 year old children using serum cystatin C measures. Pre- and postnatal metal(loid) concentrations were assessed in weekly increments by analyzing deciduous teeth with laser ablation-inductively coupled plasma-mass spectrometry. We used reverse distributed lag models (rDLMs) and lagged Weighted Quantile Sum (L-WQS) regression to examine time-varying associations between weekly perinatal metal(loid) exposure or metal(loid) mixtures and preadolescent eGFR while adjusting for age, sex, BMI z-score, SES and prenatal tobacco smoke exposure. We identified a critical window of susceptibility to Pb exposure, in the late 3rd trimester (5 weeks prior to birth) during which higher Pb exposure was associated with children's increased eGFR. When all elements were assessed as a mixture, we identified late 2nd/early 3rd trimester (weeks 8-17 of gestation) as a window of vulnerability associated with decreased eGFR, with Li and Cr contributing the greatest weights to the association. When stratified by sex, we observed stronger effects among boys than girls. Using tooth-matrix biomarkers, we identified discrete developmental exposure windows wherein Pb and metal(loid) mixtures were associated with altered preadolescent kidney function.

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

High-resolution metabolomics of exposure to tobacco smoke during pregnancy and adverse birth outcomes in the Atlanta African American maternal-child cohort

Exposure to tobacco smoke during pregnancy has been associated with a series of adverse reproductive outcomes; however, the underlying molecular mechanisms are not well-established. We conducted an untargeted metabolome-wide association study to identify the metabolic perturbations and molecular mechanisms underlying the association between cotinine, a widely used biomarker of tobacco exposure, and adverse birth outcomes. We collected early and late pregnancy urine samples for cotinine measurement and serum samples for high-resolution metabolomics (HRM) profiling from 105 pregnant women from the Atlanta African American Maternal-Child cohort (2014–2016). Maternal metabolome perturbations mediating prenatal tobacco smoke exposure and adverse birth outcomes were assessed by an untargeted HRM workflow using generalized linear models, followed by pathway enrichment analysis and chemical annotation, with a meet-in-the-middle approach. The median maternal urinary cotinine concentrations were 5.93 μg/g creatinine and 3.69 μg/g creatinine in early and late pregnancy, respectively. In total, 16,481 and 13,043 metabolic features were identified in serum samples at each visit from positive and negative electrospray ionization modes, respectively. Twelve metabolic pathways were found to be associated with both cotinine concentrations and adverse birth outcomes during early and late pregnancy, including tryptophan, histidine, urea cycle, arginine, and proline metabolism. We confirmed 47 metabolites associated with cotinine levels, preterm birth, and shorter gestational age, including glutamate, serine, choline, and taurine, which are closely involved in endogenous inflammation, vascular reactivity, and lipid peroxidation processes. The metabolic perturbations associated with cotinine levels were related to inflammation, oxidative stress, placental vascularization, and insulin action, which could contribute to shorter gestations. The findings will support the further understanding of potential internal responses in association with tobacco smoke exposures, especially among African American women who are disproportionately exposed to high tobacco smoke and experience higher rates of adverse birth outcomes.

The First 1000 Days: Impact of Prenatal Tobacco Smoke Exposure on Hospitalization Due to Preschool Wheezing.

Preschool wheezing and related hospitalization rates are increasing. Prenatal tobacco smoke exposure (PTSE) increases the risk of wheezing, yet >20% of French women smoke during pregnancy. In this observational retrospective monocentric study, we assessed the link between PTSE and hospital admissions. We included infants <2 years of age admitted for acute wheezing. A phone interview with mothers was completed by electronic records. The primary endpoint was the ratio of cumulative duration of the hospitalization stays (days)/age (months). 129 children were included (36.4% exposed to PTSE vs. 63.6% unexposed). There was a significant difference in the duration of hospitalization/age: 0.9 days/month (exposed) vs. 0.58 days/month (unexposed) (p = 0.008). Smoking one cigarette/day during pregnancy was associated with an increase in hospitalization duration of 0.055 days/month (r = 0.238, p = 0.006). In the multi-variable analysis, this positive association persisted (β = 0.04, p = 0.04; standardized β = 0.27, p = 0.03). There was a trend towards a dose-effect relationship between PTSE and other important parameters associated with hospital admissions. We have demonstrated a dose-effect relationship, without a threshold effect, between PTSE and duration of hospitalization for wheezing in non-premature infants during the first 2 years of life. Prevention campaigns for future mothers should be enforced.

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

Selected Articles from This Issue

The pesticide DDT is still used despite being an endocrine disruptor causing multi-generational harm in animals. Cirillo, La Merrill and colleagues used data from 3-generations of humans in the Child Health and Development Studies cohort. They report that grandmothers' perinatal serum DDT levels were linked directly to obesity (N=258 triads) and earlier first menstrual periods (N=235 triads) in young adult granddaughters. These associations remained significant independent of body mass index in the second generation. Given obesity and early first menstrual period are risk factors for various cancers, ancestral DDT disruption may lead to higher risk of cancers in the current generation of young adults.A data source sufficient to examine lung cancer incidence and risk factors by smoking status among Asian American, Native Hawaiian, and Pacific Islander (AANHPI) females has not been available. DeRouen and colleagues describe development of a large, multilevel resource linking electronic health record data from healthcare systems with high AANHp. representation to cancer registry and geospatial data. The resource comprises 2.2 million adults, including 250,053 AANHPI females across eleven AANHPI single and multi-racial/ethnic groups. Prevalence of never-smoking among AANHPI females with lung cancer varied widely across ethnic groups. Integrative data approaches are valuable for prospective cancer research among small populations.The causes of acute lymphoblastic leukemia (ALL), the most common childhood cancer, remain largely unknown. In this study of 482 B-cell ALL patients in California, Xu and colleagues used epigenetic biomarkers of prenatal tobacco smoke exposure to examine the association with gene deletions in diagnostic leukemia samples. Increased prenatal smoking exposure, as measured by DNA methylation at AHRR CpG cg05575921 and by a polyepigenetic score, was associated with a higher frequency of gene deletions. These findings support that tobacco smoke exposure in early life may have leukemogenic effects on developing B-cells, and warrant further studies into the molecular mechanisms involved.Treatments for childhood cancer can cause neuromuscular dysfunction including impaired strength, sensation, and balance. Rodwin and colleagues estimated the prevalence and cumulative incidence of neuromuscular dysfunction in 25,583 survivors and 5,044 siblings from the Childhood Cancer Survivor Study. Neuromuscular dysfunction was 9.9 times more prevalent in survivors than siblings, had affected 24.3% of survivors by 20 years post-diagnosis, and was associated with adverse health and socioeconomic outcomes. Associated adverse outcomes included obesity, lower educational attainment, and emotional distress. Continued surveillance and better interventions to prevent and treat neuromuscular dysfunction are needed in survivors of childhood cancer.

Epigenetic Biomarkers of Prenatal Tobacco Smoke Exposure Are Associated with Gene Deletions in Childhood Acute Lymphoblastic Leukemia.

Parental smoking is implicated in the etiology of acute lymphoblastic leukemia (ALL), the most common childhood cancer. We recently reported an association between an epigenetic biomarker of early-life tobacco smoke exposure at the AHRR gene and increased frequency of somatic gene deletions among ALL cases. Here, we further assess this association using two epigenetic biomarkers for maternal smoking during pregnancy-DNA methylation at AHRR CpG cg05575921 and a recently established polyepigenetic smoking score-in an expanded set of 482 B-cell ALL (B-ALL) cases in the California Childhood Leukemia Study with available Illumina 450K or MethylationEPIC array data. Multivariable Poisson regression models were used to test the associations between the epigenetic biomarkers and gene deletion numbers. We found an association between DNA methylation at AHRR CpG cg05575921 and deletion number among 284 childhood B-ALL cases with MethylationEPIC array data, with a ratio of means (RM) of 1.31 [95% confidence interval (CI), 1.02-1.69] for each 0.1 β value reduction in DNA methylation, an effect size similar to our previous report in an independent set of 198 B-ALL cases with 450K array data [meta-analysis summary RM (sRM) = 1.32; 95% CI, 1.10-1.57]. The polyepigenetic smoking score was positively associated with gene deletion frequency among all 482 B-ALL cases (sRM = 1.31 for each 4-unit increase in score; 95% CI, 1.09-1.57). We provide further evidence that prenatal tobacco-smoke exposure may influence the generation of somatic copy-number deletions in childhood B-ALL. Analyses of deletion breakpoint sequences are required to further understand the mutagenic effects of tobacco smoke in childhood ALL.

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.

Prenatal tobacco smoke exposure and neurological impairment at 10years of age among children born extremely preterm: a prospective cohort.

To determine the association between prenatal tobacco smoke exposure and neurological impairment at 10years of age among children born extremely preterm (<28weeks of gestation). The Extremely Low Gestational Age Newborn (ELGAN) Study, a prospective cohort. Ten-year follow-up of extremely preterm infants born at 14 US hospitals between 2002 and 2004. Prenatal tobacco smoke exposure was defined as a mother's report at enrolment of active (i.e. maternal) and passive smoking during pregnancy. Poisson regression with generalized estimating equations was used. Models adjusted for mother's age, race/ethnicity, education, insurance, pre-pregnancy body mass index, US region, multiple gestation and infant's sex; and in sensitivity analysis, gestational age at delivery and clinical subtype of preterm birth, given their classification as intermediate and non-confounding variables. Neurological impairment at 10years, epilepsy, cerebral palsy and cognitive impairment. Of 1200 ELGAN study survivors, 856 were assessed at 10years of age with neurological outcomes, of whom 14% (118/856) had active tobacco exposure during pregnancy and 24% (207/852) had passive tobacco exposure. Compared with children who were not exposed prenatally to tobacco, children exposed to active tobacco use during pregnancy had a higher risk of epilepsy (14% versus 5%; adjusted relative risk: 1.68, 95% CI 1.45-1.92). This risk remained after adjustment for gestational age at delivery and clinical subtype of preterm birth. Prenatal tobacco smoke exposure was not associated with other assessed neurological outcomes, including cerebral palsy and multiple measures of cognitive impairment. Among children born extremely preterm, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10years of life. Among infants born before 28weeks of gestation, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10years of life.

360 Prenatal tobacco smoke and risk of neurological impairment at age 10 among extremely preterm infants

To determine the association between prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm (<28 weeks gestation). The multicenter, prospective Extremely Low Gestational Age Newborn (ELGAN) Study enrolled newborns at birth between 2002-2004. Prenatal tobacco smoke included self-reported maternal (i.e., active) and passive smoking during pregnancy at study enrollment. Neurological impairment at 10 years of age included: epilepsy, cerebral palsy, and cognitive impairment. Poisson regression with generalized estimating equations was used to estimate adjusted risk ratios (aRRs), adjusted for mother’s age, race/ethnicity, education, insurance, multiple gestation, and infant’s sex; and separately, we adjusted for gestational age at delivery in sensitivity analysis, given its classification as an intermediate and not confounding variable. Secondarily, we assessed whether 1) the primary association varied by infant sex (male vs. female) given sexual epigenetic dimorphism in the placenta; and 2) postnatal inflammation in the child within 2 weeks after birth. Of 1,200 ELGAN study survivors, 886 were assessed at 10 years of age, of whom 14% (120/867) had been exposed to maternal tobacco use during pregnancy and 24% (210/863) to passive tobacco smoke. Compared to children who were not exposed prenatally to tobacco, children exposed to maternal tobacco use during pregnancy had a higher risk of epilepsy at 10 years of age (14% vs. 5%; aRR: 1.6, 95% CI: 1.6 to 1.7). This risk remained after adjustment for gestational age at delivery. Prenatal tobacco smoke exposure was not associated with cerebral palsy and cognitive impairment. Secondarily, the primary association held for female but not male infants; and tobacco smoke exposure did not influence the contribution of postnatal inflammation to impaired neurodevelopment. Among extremely preterm infants born <28 weeks, active maternal tobacco smoke during pregnancy increases the risk of epilepsy in the offspring at 10 years of life.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Prenatal and Childhood Tobacco Smoke Exposure Are Associated With Sleep-Disordered Breathing Throughout Early Childhood.

To determine whether prenatal and childhood tobacco smoke exposure (TSE) are each independently associated with mild sleep-disordered breathing (SDB) symptoms throughout early childhood, and whether the association between childhood TSE and SDB differs according to the level of prenatal exposure. Longitudinal cohort study, using data from the Avon Longitudinal Study of Parents and Children, a population-based birth cohort from the United Kingdom. Primary exposures were repeated measures of mother-reported prenatal and childhood TSE through age 7 years. Outcomes were mother-reported measures of mild SDB symptoms, including snoring, mouth breathing, and witnessed apnea, repeated annually through age 7 years. A total of 12,030 children were followed for a median duration of 7 years. About 24.2% were exposed to prenatal tobacco smoke, 46.2% were exposed at least once in childhood, and 20.6% were exposed during both periods. Both prenatal and childhood TSE were associated with SDB symptoms throughout early childhood (adjusted OR [aOR] for any prenatal TSE 1.23; 95% confidence interval [CI] 1.08, 1.40; aOR for any childhood TSE 1.17; 95% CI 1.06, 1.29). We observed a dose-response effect between TSE and SBD symptoms, and found evidence of effect modification for those exposed during both time periods (combined high level exposure both prenatally and during childhood: aOR snoring 2.43 [95% CI 1.50, 3.93], aOR apnea 2.65 [95% CI 1.46, 4.82]). Prenatal and childhood TSE were both independently associated with mild SDB symptoms throughout early childhood in a dose-dependent manner, further supporting the critical importance of maintaining a tobacco-free environment throughout gestation and childhood.

Upregulation of placental genes in the Aryl Hydrocarbon Receptor Pathway with Prenatal Tobacco Smoke Exposure

Background: Smoking during pregnancy increases the risk for growth restriction and children’s health outcomes. Epigenomic studies have identified multiple genes within the aryl hydrocarbon receptor (Ahr) pathway as being differentially methylated in response to prenatal tobacco exposure, but it is unclear whether this exposure affects the functional activity of the Ahr pathway. This pathway has also been associated with multiple health outcomes, making it a strong candidate pathway for targeted studies of prenatal tobacco smoke exposure. We aimed to study whether placental expression of genes in the Ahr pathway are responsive to maternal cigarette use during pregnancy and whether this response correlates with dose.Methods: This study included 68 mothers (34 that smoked throughout pregnancy), from which placental gene expression was quantified via RNA-seq. Of the 46 genes that comprise the Ahr Pathway, 34 were detectable and passed QC metrics. We regressed normalized gene-expression on smoking status while adjusting for covariates and surrogate variables. We performed secondary analyses to test whether expression was associated with total cigarettes throughout pregnancy and cotinine concentrations.Results: Four genes within the Ahr pathway, TGFB1, CYP1A1, CYP1A2, and CYP1B1, exhibited increased expression in association with smoking during pregnancy (FDR &lt; 0.05). Among smokers, cumulative dose of cigarettes throughout pregnancy, and average cotinine across three timepoints, was associated with increased expression, particularly for TGFB1 and CYP1A2 (p-value &lt; 0.05).Conclusions: Placental Ahr-pathway genes, particularly TGFB1 and CYP1A1, are up-regulated in response to maternal smoking during pregnancy. TGFB1 is a multifunctional cytokine with critical roles in developmental processes, while CYP1A1 is the primary xenobiotic metabolizing enzyme in the placenta, and others have shown that elevated placental CYP1A1 is associated with adverse pregnancy outcomes. These may represent some of the functional responses of the placenta to prenatal tobacco exposure and potential intermediates on the path to pregnancy outcomes.

Low birthweight of children is positively associated with mother\u2019s prenatal tobacco smoke exposure in Shanghai: a cross-sectional study

IntroductionLow birthweight (LBW) is a significant public health issue, and maternal smoking is the most prevalent preventable cause of LBW. But there is limited evidence on association of LBW among children and cigarette smoke exposure in mothers in China. In this cross-sectional study, we try to explore if the LBW in children is positively associated with mothers’ prenatal cigarette smoke exposure.MethodsWe selected 8, 586 mothers and their singleton children in 2018 in Songjiang district, Shanghai. Birthweight of children and gestational weeks of mother was identified by birth records in the hospital, we classified mothers’ prenatal cigarette smoke status into the first-hand smoke (FHS) exposure and the second-hand smoke (SHS) exposure. We use SAS 9.1.3 software to calculate the prevalence of children’s LBW and the prevalence of mothers’ prenatal cigarette smoke exposure including FHS and SHS. Chi-square test and logistic regression were used to analyze the difference.ResultsIn 8, 586 women, The prenatal FHS and SHS exposure prevalence was 0.9 and 20.8%, respectively. The mean birthweight of children was 3315.5 g with a standard deviation of 497.2 g, the mean birthweight was 167.7 g and 66.1 g lower in children born to mothers with prenatally FHS and SHS exposure compared with those children whose mother were not exposed, respectively. The children’s LBW prevalence was 4.7% in this study. By comparing with children whose mother were not exposed, the LBW prevalence was higher among children whose mother were prenatally exposed to FHS [OR (Odds Ratios) = 2.91, 95% confidence interval (CI) (1.49, 5.68)], and SHS [OR = 2.35, 95% CI (1.90, 2.89)].ConclusionsChildren’s LBW is positively associated with mothers’ prenatal tobacco smoke exposure both for FHS and SHS. So implementing tobacco control measures is crucial to lower smoking prevalence among women, and decrease smoking prevalence of their family members as well as work fellows.