Although studies show that maternal smoking during pregnancy increases the risks of respiratory outcomes in childhood, evidence concerning the effects of household environmental tobacco smoke (ETS) exposure remains inconsistent.
We conducted a population-based study comprised of 5,019 seventh and eighth-grade children in 14 Taiwanese communities. Questionnaire responses by parents were used to ascertain children's exposure and disease status. Logistic regression models were fitted to estimate the effects of ETS exposures on the prevalence of asthma, wheeze, and bronchitic symptoms.
The lifetime prevalence of wheeze was 11.6% and physician-diagnosed asthma was 7.5% in our population. After adjustment for potential confounders, in utero exposure showed the strongest effect on all respiratory outcomes. Current household ETS exposure was significantly associated with increased prevalence of active asthma, ever wheeze, wheeze with nighttime awakening, and bronchitis. Maternal smoking was associated with the increased prevalence of a wide range of wheeze subcategories, serious asthma, and chronic cough, but paternal smoking had no significant effects. Although maternal smoking alone and paternal smoking alone were not independently associated with respiratory outcomes, joint exposure appeared to increase the effects. Furthermore, joint exposure to parental smoking showed a significant effect on early-onset asthma (OR, 2.01; 95% CI, 1.00-4.02), but did not show a significant effect on late-onset asthma (OR, 1.17; 95% CI, 0.36-3.87).
We concluded that prenatal and household ETS exposure had significant adverse effects on respiratory health in Taiwanese children.
Among people with asthma, the clinical impact and relative contribution of maternal smoking during pregnancy (in utero smoking) and current secondhand smoke exposure on asthma control is poorly documented, and there is a paucity of research involving minority populations.
To examine the association between poor asthma control and in utero smoking and current secondhand smoke exposure among Latino and Black children with asthma.
Case-only analysis of 2 multi-center case-control studies conducted from 2008–2010 using similar protocols. We recruited 2,481 Latinos and Blacks with asthma (ages 8–17) from the mainland United States and Puerto Rico. Ordinal logistic regression was used to estimate the effect of in utero smoking and current secondhand smoke exposures on National Heart Lung and Blood Institute-defined asthma control.
Poor asthma control among children 8–17 years of age was independently associated with in utero smoking (odds ratio; 95% confidence interval = 1.5; 1.1–2.0). In utero smoking via the mother was also associated with secondary asthma outcomes, including early onset asthma (1.7; 1.1–2.4), daytime symptoms (1.6; 1.1–2.1), and asthma-related limitation of activities (1.6; 1.2–2.2).
Maternal smoking while in utero is associated with poor asthma control in Black and Latino subjects assessed at 8–17 years of age.
Secondhand smoke; prenatal exposure delayed effects; asthma; health status disparities
Background: Recent findings suggest that maternal smoking during pregnancy may play a role in the development of metabolic alterations in offspring during childhood. However, whether such exposure increases the risk of developing similar metabolic alterations during adulthood is uncertain.
Objective: We evaluated the association of in utero exposure to maternal tobacco smoke with plasma lipids, apolipoprotein B (apoB), and C-reactive protein (CRP) in adulthood.
Methods: The study was based on a subsample of the Norwegian Mother and Child Cohort Study (MoBa) and included 479 pregnant women with plasma lipids, apoB, and CRP measurements. Information on in utero exposure to tobacco smoke, personal smoking, and other factors were obtained from the women by a self-completed questionnaire at enrollment, at approximately 17 weeks of gestation.
Results: Women exposed to tobacco smoke in utero had higher triglycerides [10.7% higher; 95% confidence interval (CI): 3.9, 17.9] and lower high-density lipoprotein cholesterol (HDL) (–1.9 mg/dL; 95% CI: –4.3, 0.5) compared with unexposed women, after adjusting for age, physical activity, education, personal smoking, and current body mass index (BMI). Exposed women were also more likely to have triglycerides ≥ 200 mg/dL [adjusted odds ratio (aOR) = 2.5; 95% CI: 1.3, 5.1] and HDL < 50 mg/dL (aOR = 2.3; 95% CI: 1.1, 5.0). Low-density lipoprotein cholesterol, total cholesterol, and apoB were not associated with the exposure. CRP was increased among exposed women; however, after adjustment for BMI, the association was completely attenuated.
Conclusions: In this population, in utero exposure to tobacco smoke was associated with high triglycerides and low HDL in adulthood, 18–44 years after exposure.
clinical chemistry; C-reactive protein; metabolic syndrome; plasma lipids; prenatal exposure delayed effects; smoking; women
Lung growth in utero and lung function loss during adulthood can be affected by exposure to environmental tobacco smoke (ETS). The underlying mechanisms have not been fully elucidated. Both ETS exposure and single nucleotide polymorphisms (SNPs) in Glutathione S-Transferase (GST) Omega genes have been associated with the level of lung function. This study aimed to assess if GSTO SNPs interact with ETS exposure in utero and during adulthood on the level of lung function during adulthood.
We used cross-sectional data of 8,128 genotyped participants from the LifeLines cohort study. Linear regression models (adjusted for age, sex, height, weight, current smoking, ex-smoking and packyears smoked) were used to analyze the associations between in utero, daily and workplace ETS exposure, GSTO SNPs, the interaction between ETS and GSTOs, and level of lung function (FEV1, FEV1/FVC). Since the interactions between ETS and GSTOs may be modified by active tobacco smoking we additionally assessed associations in never and ever smokers separately. A second sample of 5,308 genotyped LifeLines participants was used to verify our initial findings.
Daily and workplace ETS exposure was associated with significantly lower FEV1 levels. GSTO SNPs (recessive model) interacted with in utero ETS and were associated with higher levels of FEV1, whereas the interactions with daily and workplace ETS exposure were associated with lower levels of FEV1, effects being more pronounced in never smokers. The interaction of GSTO2 SNP rs156697 with in utero ETS associated with a higher level of FEV1 was significantly replicated in the second sample. Overall, the directions of the interactions of in utero and workplace ETS exposure with the SNPs found in the second (verification) sample were in line with the first sample.
GSTO genotypes interact with in utero and adulthood ETS exposure on adult lung function level, but in opposite directions.
Genes; Environmental tobacco smoke; Lung function
The effects of in utero tobacco smoke exposure on childhood respiratory health have been investigated, and outcomes have been inconsistent.
To determine if in utero tobacco smoke exposure is associated with childhood persistent asthma in Mexican, Puerto Rican, and black children.
PATIENTS AND METHODS:
There were 295 Mexican, Puerto Rican, and black asthmatic children, aged 8 to 16 years, who underwent spirometry, and clinical data were collected from the parents during a standardized interview. The effect of in utero tobacco smoke exposure on the development of persistent asthma and related clinical outcomes was evaluated by logistic regression.
Children with persistent asthma had a higher odds of exposure to in utero tobacco smoke, but not current tobacco smoke, than did children with intermittent asthma (odds ratio [OR]: 3.57; P = .029). Tobacco smoke exposure from parents in the first 2 years of life did not alter this association. Furthermore, there were higher odds of in utero tobacco smoke exposure in children experiencing nocturnal symptoms (OR: 2.77; P = .048), daily asthma symptoms (OR: 2.73; P = .046), and emergency department visits (OR: 3.85; P = .015) within the year.
Exposure to tobacco smoke in utero was significantly associated with persistent asthma among Mexican, Puerto Rican, and black children compared with those with intermittent asthma. These results suggest that smoking cessation during pregnancy may lead to a decrease in the incidence of persistent asthma in these populations.
asthma; tobacco; Latino; African American; pregnancy
Rationale: Although involuntary exposure to maternal smoking during the in utero period and to secondhand smoke are associated with occurrence of childhood asthma, few studies have investigated the role of active cigarette smoking on asthma onset during adolescence.
Objectives: To determine whether regular smoking is associated with the new onset of asthma during adolescence.
Methods: We conducted a prospective cohort study among 2,609 children with no lifetime history of asthma or wheezing who were recruited from fourth- and seventh-grade classrooms and followed annually in schools in 12 southern California communities. Regular smoking was defined as smoking at least seven cigarettes per day on average over the week before and 300 cigarettes in the year before each annual interview. Incident asthma was defined using new cases of physician-diagnosed asthma.
Measurements and Main Results: Regular smoking was associated with increased risk of new-onset asthma. Children who reported smoking 300 or more cigarettes per year had a relative risk (RR) of 3.9 (95% confidence interval [95% CI], 1.7–8.5) for new-onset asthma compared with nonsmokers. The increased risk from regular smoking was greater in nonallergic than in allergic children. Regular smokers who were exposed to maternal smoking during gestation had the largest risk from active smoking (RR, 8.8; 95% CI, 3.2–24.0).
Conclusions: Regular smoking increased risk for asthma among adolescents, especially for nonallergic adolescents and those exposed to maternal smoking during the in utero period.
asthma; epidemiology; smoking
Fetal stress has been linked to adult atherosclerosis, obesity, and diabetes. Epidemiology studies have associated fetal exposure to maternal smoking and postnatal exposure to environmental tobacco smoke (ETS) with increased asthma risk.
We tested the hypothesis, in a mouse model of asthma, that in utero ETS exposure alters airway function and respiratory immune responses in adults.
Pregnant Balb/c mice were exposed daily to ETS or HEPA-filtered air (AIR). Offspring inhaled aerosolized ovalbumin (OVA) or saline in weeks 7–8. Regardless of whether they inhaled OVA or saline, mice were sensitized by OVA injections in weeks 11 and 13 followed by OVA aerosol challenge in weeks 14–15. At three time points, we assessed OVA-specific serum immunoglobins, bronchoalveolar lavage cells and cytokines, lung and nasal histopathology, and airway hyperresponsiveness (AHR).
At 6 weeks, we found no significant differences between in utero ETS and AIR mice. At 10 weeks, following OVA aerosol, ETS mice displayed greater AHR than AIR mice (α = 0.05), unaccompanied by changes in histopathology, cytokine profile, or antibody levels. At 15 weeks, mice that had inhaled saline in weeks 7–8 developed airway inflammation: eosinophilia (α = 0.05), interleukin-5 (α = 0.05), and AHR (α = 0.05) were greater in ETS mice than in AIR mice. Mice that had inhaled OVA in weeks 7–8 demonstrated no airway inflammation after sensitization and challenge.
In utero ETS exposure exacerbates subsequent adult responses to initial allergen exposure.
airway hyperresponsiveness; allergens; asthma; environmental tobacco smoke (ETS); in utero; tolerance
Exposure to cigarette smoking during foetal and early postnatal life may have implications for lung health. The aim of this study was to assess the possible effects of such exposure in utero on lower respiratory disease in children up to two years of age.
A birth cohort of 4089 newborn infants was followed for two years using parental questionnaires. When the infant was two months old the parents completed a questionnaire on various lifestyle factors, including maternal smoking during pregnancy and after birth. At one and two years of age information was obtained by questionnaire on symptoms of allergic and respiratory diseases as well as on environmental exposures, particularly exposure to environmental tobacco smoke (ETS). Adjustments were made for potential confounders.
When the mother had smoked during pregnancy but not after that, there was an increased risk of recurrent wheezing up to two years' age, ORadj = 2.2, (95% CI 1.3 – 3.6). The corresponding OR was 1.6, (95% CI 1.2 – 2.3) for reported exposure to ETS with or without maternal smoking in utero. Maternal smoking during pregnancy but no exposure to ETS also increased the risk of doctor's diagnosed asthma up to two years of age, ORadj = 2.1, (95% CI 1.2 – 3.7).
Exposure to maternal cigarette smoking in utero is a risk factor for recurrent wheezing, as well as doctor's diagnosed asthma in children up to two yearsof age.
DNA methylation in AXL, a receptor tyrosine kinase relevant in cancer and immune function, is reportedly highly heritable. We present evidence to suggest that heritability of DNA methylation in AXL is variable, dependent on population characteristics and cell type studied. Moreover, environmental exposures in utero, particularly exposure to maternal smoking, contributes to variation in DNA methylation of select CpG loci that can affect calculations of heritability. Children exposed to maternal smoking in utero had a 2.3% increase (95% CI 0.3, 4.2) in DNA methylation in AXL, which was magnified in girls as compared to boys. These results present compelling evidence that environmental exposure to tobacco smoke during pregnancy may alter DNA methylation levels in subtle but potentially important ways and that these changes are persistent years after birth.
AXL; DNA methylation; heritability; maternal smoking; receptor tyrosine kinase
Low socioeconomic status (SES) and exposure to passive tobacco smoke are associated with increased risk of smoking in adults, but the influences of these factors in earlier life periods on adult smoking behavior are not well understood. We investigated the relationship of SES and passive tobacco exposure over the lifecourse with adult smoking status in a multiethnic cohort of U.S. women (n = 262, average age = 41.8), using prospective data on maternal smoking during pregnancy and childhood SES, and follow-up data on current smoking, adult SES and household tobacco exposure. Low adolescent and adult SES consistently increased the risk of current smoking, but most associations were not statistically significant in multivariable models. Blue collar parental occupation at birth increased the risk of smoking, particularly for current smoking relative to former smoking (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.2–5.9). After adjusting for SES, current and former smokers were more likely than never smokers to have exposures to prenatal tobacco (OR = 4.4, 95% CI = 2.1–9.4 and OR = 2.0, 95% CI = 1.0–4.2, respectively) and adult household tobacco (OR = 2.7, 95% CI = 1.3–5.8 and OR = 2.4, 95% CI = 1.2–4.8, respectively). Our results show that early life conditions have enduring influences on women’s smoking behavior in middle adulthood, even after considering similar types of conditions in later life periods.
Smoking; Life course; Socioeconomic factors; Passive or secondhand smoke; Ethnicity
Associations between single-nucleotide polymorphisms in the β2-adrenergic receptor gene and asthma and wheeze have been inconsistent. Recent studies indicated that tobacco smoke affects β2-adrenergic receptor gene expression and associations of β2-adrenergic receptor gene variants with asthma in adults. We aimed to investigate the joint effects of in utero and childhood secondhand tobacco smoke exposure and 2 well-characterized functional single-nucleotide polymorphisms (Arg16Gly and Glu27Gln) of β2-adrenergic receptor gene on asthma and wheezing in 3128 non-Hispanic and Hispanic white children of the Children's Health Study.
We fitted logistic regression models to estimate odds ratios and 95% confidence intervals for the independent and joint effects of these single-nucleotide polymorphisms and in utero and secondhand tobacco smoke exposure on asthma and wheeze outcomes.
Exposures to in utero maternal smoking and secondhand tobacco smoke were associated with wheezing. Children who were homozygous for the Arg16 allele and were exposed to maternal smoking in utero were at a threefold increased risk for lifetime wheeze compared with children who were unexposed and had at least 1 Gly16 allele. We found similar joint effects of secondhand tobacco smoke and Arg16Gly with wheezing. The risk for lifetime, current, and nocturnal wheeze increased with the number of smokers at home among Arg16 homozygous children. The results were consistent in 2 cohorts of children recruited in 1993 and 1996. Diplotype-based analyses were consistent with the single-nucleotide polymorphism–specific results. No associations were found for Glu27Gln.
Both in utero and childhood exposure to tobacco smoke were associated with an increased risk for wheeze in children, and the risks were greater for children with the Arg16Arg genotype or 2 copies of the Arg16–Gln27 diplotype. Exposures to smoking need to be taken into account when evaluating the effects of β2-adrenergic receptor gene variants on respiratory health outcomes.
β-2 adrenergic receptor; prenatal exposure; secondhand-smoke exposure; asthma; wheeze
Previous studies have reported mixed results regarding the association between age at menarche and environmental tobacco smoke exposure, both prenatally and during early childhood; however, few studies have had data available during both time periods. The present study examined whether exposure to prenatal tobacco smoke (PTS) via maternal smoking during pregnancy or childhood environmental tobacco smoke (ETS) was associated with age at menarche in a multi-ethnic birth cohort. With the uniquely available prospectively collected data on body size and growth at birth and in early life, we further examined whether the association between PTS and ETS exposure and age at menarche was mediated by these variables. From 2001 to 2006, we recruited 262 women born between 1959 and 1963 who were enrolled previously in a New York City site of the National Collaborative Perinatal Project. Mothers who smoked during pregnancy vs. those who did not were more likely to be White, younger, have more education and have lower birthweight babies. Daughters with heavy PTS exposure (≥20 cigarettes per day) had a later age at menarche (>12 years vs. ≤12 years), odds ratio (OR) = 2.1 [95% confidence interval (CI) 0.9, 5.0] compared with daughters with no PTS. Daughters exposed to only childhood ETS had a later age at menarche, OR = 2.1 [95% CI 1.0, 4.3], and those exposed to PTS and ETS combined had a statistically significant later age at menarche, OR = 2.2 [95% CI 1.1, 4.6] compared with daughters with no PTS and no ETS. These results did not change after further adjustment for birthweight and postnatal growth suggesting that exposure to PTS and ETS is associated with later age at menarche even after considering possible relationships with growth.
menarche; puberty; maternal prenatal smoking; childhood environmental tobacco smoke
Whether in utero exposure to tobacco smoke increases a woman's risk of fetal loss later in life is unknown, though data on childhood exposure suggest an association may exist. This study evaluated the association between in utero exposure to tobacco smoke and fetal loss in the Norwegian Mother and Child Cohort Study (MoBa), which enrolled ∼40% of the pregnant women in Norway from 1999 to 2008.
Information on exposure to tobacco smoke in utero, the woman's own smoking behavior during pregnancy and other factors was obtained by a questionnaire completed at ∼17 weeks of gestation. Subsequent late miscarriage (fetal death <20 weeks) and stillbirth (fetal death ≥20 weeks) were ascertained from the Norwegian Medical Birth Registry. This analysis included 76 357 pregnancies (MoBa data set version 4.301) delivered by the end of 2008; 59 late miscarriages and 270 stillbirths occurred. Cox proportional hazards models were fit for each outcome and for all fetal deaths combined.
The adjusted hazard ratio (HR) of late miscarriage was 1.23 [95% confidence interval (CI), 0.72–2.12] in women with exposure to maternal tobacco smoke in utero when compared with non-exposed women. The corresponding adjusted HR for stillbirths was 1.11 (95% CI, 0.85–1.44) and for all fetal deaths combined, it was 1.12 (95% CI, 0.89–1.43).
The relatively wide CI around the HR for miscarriage reflected the limited power to detect an association, due to enrollment around 17 weeks of gestation. However, for in utero exposure to tobacco smoke and risk of stillbirth later in life, where the study power was adequate, our data provided little support for an association.
tobacco smoking; in utero exposure; miscarriage; pregnancy; stillbirth
Early-life experiences and environmental exposures have been associated with childhood asthma. To investigate further whether the timing of such experiences and exposures is associated with the occurrence of asthma by 5 years of age, we conducted a prevalence case-control study nested within the Children's Health Study, a population-based study of > 4,000 school-aged children in 12 southern California communities. Cases were defined as physician-diagnosed asthma by age 5, and controls were asthma-free at study entry, frequency-matched on age, sex, and community of residence and countermatched on in utero exposure to maternal smoking. Telephone interviews were conducted with mothers to collect additional exposure and asthma histories. Conditional logistic regression models were fitted to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Asthma diagnosis before 5 years of age was associated with exposures in the first year of life to wood or oil smoke, soot, or exhaust (OR = 1.74; 95% CI, 1.02-2.96), cockroaches (OR = 2.03; 95% CI, 1.03-4.02), herbicides (OR = 4.58; 95% CI, 1.36-15.43), pesticides (OR = 2.39; 95% CI, 1.17-4.89), and farm crops, farm dust, or farm animals (OR = 1.88; 95% CI, 1.07-3.28). The ORs for herbicide, pesticide, farm animal, and crops were largest among children with early-onset persistent asthma. The risk of asthma decreased with an increasing number of siblings (ptrend = 0.01). Day care attendance within the first 4 months of life was positively associated with early-onset transient wheezing (OR = 2.42; 95% CI, 1.28-4.59). In conclusion, environmental exposures during the first year of life are associated with childhood asthma risk.
In utero and/or childhood environmental tobacco smoke exposure is well known to adversely affect lung function and to depreciate child's health in many ways. Fewer studies have assessed the long-term effects on COPD development and disease severity in later adulthood.
COPD patients were interviewed using a structured questionnaire regarding their personal as well as the smoking habits of their parents. Data were compared with the disease history, e.g. COPD exacerbation rate, and their lung function data.
Between 2003 and 2004 COPD patients were recruited a) in a private practice specialized in pulmonary medicine (n = 133) and b) in a hospital (n = 158). 75% of their fathers and only 15.4 of all mothers smoked regularly. COPD patients from smoking mothers had lower FEV1 predicted than those raised in household without maternal smoking exposure: 39.4 ± 9.5% vs. 51.9 ± 6.0% (P = 0.037). Fathers had no effect on FEV1 regardless if they are smokers or non-smokers. Rate of severe exacerbations requiring hospitalization remained unaffected by parental second hand smoke exposure.
Maternal smoking negatively affects lung function of their offspring even in late adulthood when they develop COPD. It even aggravates the cumulative effect of active cigarette consumption. Clinical course of the COPD remained unaffected.
chronic obstructive pulmonary disease, COPD; second hand smoking
Maternal smoking in utero has been associated with adverse health outcomes including lower respiratory tract infections in infants and children, but the mechanisms underlying these associations continue to be investigated. We hypothesized that nicotine plays a significant role in mediating the effects of maternal tobacco smoke on neonatal alveolar macrophage (AM) function, the resident immune cell in the neonatal lung.
Primary AMs were isolated at postnatal day 7 from a murine model of in utero nicotine exposure. The murine AM cell line MH-S was used for additional in vitro studies.
In utero nicotine increased IL-13 and transforming growth factor beta one (TGFβ1) in the neonatal lung. Nicotine-exposed AMs demonstrated increased TGFβ1 and increased markers of alternative activation with diminished phagocytic function. However, AMs from mice deficient in the α7 nicotinic acetylcholine receptor (α7 nAChR) had less TGFβ1, reduced alternative activation and improved phagocytic functioning despite similar in utero nicotine exposure.
In utero nicotine exposure, mediated in part via the α7 nAChR, may increase the risk of lower respiratory tract infections in neonates by changing the resting state of AM towards alternative activation. These findings have important implications for immune responses in the nicotine-exposed neonatal lung.
In studies of the fetal origins of disease and life course epidemiology, measures of fetal exposure may be based on information reported by the adults who were exposed in utero. In particular, the full spectrum of consequences of in utero exposure to maternal tobacco smoking is now an area of active investigation, and the ability to report such exposure reproducibly is of interest. We evaluated the reproducibility of in utero exposure to tobacco smoke, reported by the adult daughter during consecutive pregnancies.
This study was based on 11,257 women who enrolled for more than one pregnancy in the Norwegian Mother and Child Cohort Study (MoBa). Participants completed a questionnaire around 17 weeks of gestation, which asked about their in utero exposure to tobacco smoke. Kappa statistics were calculated. Determinants of agreement were evaluated using logistic regression.
Weighted Kappa for in utero exposure for the first and second reports was 0.80. Determinants of agreement were higher education (better) and longer time between reports (worse).
Information on in utero exposure to maternal tobacco smoking provided by adult women was highly reproducible in this population.
tobacco smoking; prenatal exposure; reproducibility
The period of in utero development is one of the most critical windows during which adverse intrauterine conditions and exposures may influence the growth and development of the fetus as well as its future postnatal health and behavior. Maternal cigarette smoking during pregnancy remains a relatively common but nonetheless hazardous in utero exposure. Previous studies have associated prenatal smoke exposure with reduced birth weight, poor developmental and psychological outcomes, and increased risk for diseases and behavioral disorders later in life. Researchers are now learning that many of the mechanisms whereby maternal smoke exposure may affect key pathways crucial for proper fetal growth and development are epigenetic in nature. Maternal cigarette smoking during pregnancy has been associated with altered DNA methylation and dysregulated expression of microRNA, but a deeper understanding of the epigenetics of maternal cigarette smoking during pregnancy as well as how these epigenetic changes may affect later offspring health and behavior remain to be elucidated. This review seeks to explore many of the previously described epigenetic alterations associated with maternal cigarette smoking during pregnancy and assesses how such changes may have consequences for both fetal growth and development, as well as later child health, behavior and well-being. We also outline future directions for this new and exciting field of research.
Although tobacco smoke is an established risk factor for adult cancer, studies of the association between parental smoking and childhood cancer have produced inconsistent results. To investigate the transgenerational relationship between pre-natal and post-natal tobacco smoke exposure from the grandmother’s pregnancies until after the post-natal period and childhood cancer.
Exposure to tobacco smoke was recorded for three generations. Data were collected through personal interviews using the paediatric environmental history, and were compared among 128 children with cancer and 128 matched controls. The contingency tables and a logistic multivariable regression model were used to control for possible confounding factors.
Smoke exposure during oogenesis (maternal grandmother smokers) – odds ratio (OR) 2.2 (95% confidence interval (CI) 1.1–4.9) – and during the mother’ pregnancies – OR 1.8 (95% CI 1.1–3.3) – were significantly associated with an increased risk of childhood cancer.
Tobacco smoke exposure during the grandmother’s and mother’s pregnancies increase the risk of cancer in the descendants. The results suggest that the biological plausibility of the association between parental smoking and paediatric cancer can be explained by the large latency period of paediatric carcinogenesis.
case-control studies; childhood cancer; tobacco smoke pollution
Rationale: Transforming growth factor (TGF)-β1 is involved in airway inflammation and remodeling, two key processes in asthma pathogenesis. Tobacco smoke and traffic emissions induce airway inflammation and modulate TGF-β1 gene expression. We hypothesized that the effects of functional TGF-β1 variants on asthma occurrence vary by these exposures.
Objectives: We tested these hypotheses among 3,023 children who participated in the Children's Health Study.
Methods: Tagging single-nucleotide polymorphisms rs4803457 C>T and C-509T (a functional promoter polymorphism) accounted for 94% of the haplotype diversity of the upstream region. Exposure to maternal smoking in utero was based on smoking by biological mother during pregnancy. Residential distance from nearest freeway was calculated based on residential address at study entry.
Measurements and Main Results: Children with the −509TT genotype had a 1.8-fold increased risk of early persistent asthma (95% confidence interval [CI], 1.11–2.95). This association varied marginally significantly by in utero exposure to maternal smoking. Compared with children with the −509CC/CT genotype with no in utero exposure to maternal smoking, those with the −509TT genotype with such exposure had a 3.4-fold increased risk of early persistent asthma (95% CI, 1.46–7.80; interaction, P = 0.11). The association between TGF-β1 C-509T and lifetime asthma varied by residential proximity to freeways (interaction P = 0.02). Children with the −509TT genotype living within 500 m of a freeway had over three-fold increased lifetime asthma risk (95% CI, 1.29–7.44) compared with children with CC/CT genotype living > 1500 m from a freeway.
Conclusions: Children with the TGF-β1 −509TT genotype are at increased risk of asthma when they are exposed to maternal smoking in utero or to traffic-related emissions.
maternal smoking; traffic; asthma; genetics; gene–environment interaction; association study
Background: Abnormal premorbid lung function is a risk factor for subsequent wheezing in children with one or no atopic parent. This study was undertaken to establish whether early lung function in high risk infants (both parents atopic) was a risk factor for respiratory symptoms in infancy and to examine the influence of maternal asthma, smoking, and allergen exposure during pregnancy on any association.
Methods: Infants were recruited from the NAC Manchester Asthma and Allergy Study cohort at birth. Partial forced expiratory flow volume technique under sedation was carried out to determine maximal flow at FRC (V'maxFRC). Children were followed prospectively and parents completed a standard respiratory questionnaire at one year of age.
Results: Sixty nine term infants (34 boys; 88% mothers non-smokers; no household pets) underwent respiratory function testing. Size adjusted V'maxFRC was significantly lower in infants who had recurrent wheeze during the first year of life (mean 1.3 ml/s/cm, 95% CI 0.99 to 1.60) than in those who did not (mean 2.03 ml/s/cm, 95% CI 1.71 to 2.36; p=0.01). V'maxFRC was also significantly lower in infants who had recurrent cough symptoms. In multivariate regression analysis, when adjusted for age at test, sex, maternal asthma, smoking and maternal mattress Der 1 levels, a lower size adjusted V'maxFRC score remained strongly associated with wheezing (OR 0.37, 95% CI 0.18 to 0.77, p=0.007). Maternal smoking also remained an independent risk factor (OR 29.85, 95% CI 2.46 to 362.5, p=0.008).
Conclusion: Significantly diminished lung function was present in high risk infants who subsequently wheezed and coughed. This was independent of maternal exposure to mite allergen, asthma, and smoking during pregnancy.
Maternal smoking during pregnancy is associated with increased risk of childhood overweight body mass index (BMI). Less is known about the association between prenatal secondhand tobacco smoke (SHS) exposure and childhood BMI. We followed 292 mother-child dyads from early pregnancy to 3 years of age. Prenatal tobacco smoke exposure during pregnancy was quantified using self-report and serum cotinine biomarkers. We used linear mixed models to estimate the association between tobacco smoke exposure and BMI at birth, 4 weeks, and 1, 2, and 3 years. During pregnancy, 15% of women reported SHS exposure and 12% reported active smoking, but 51% of women had cotinine levels consistent with SHS exposure and 10% had cotinine concentrations indicative of active smoking. After adjustment for confounders, children born to active smokers had higher BMI at 2 and 3 years of age (self-report or serum cotinine), compared to unexposed children. Children born to women with prenatal serum cotinine concentrations indicative of SHS exposure had higher BMI at 2 (Mean Difference [MD]:0.3; 95% confidence interval [CI]:−0.1, 0.7) and 3 (MD:0.4; [0, 0.8]) years compared to unexposed children. Using self-reported prenatal exposure resulted in non-differential exposure misclassification of SHS exposures that attenuated the association between SHS exposure and BMI compared to serum cotinine concentrations. These findings suggest active and secondhand prenatal tobacco smoke exposure may be related to an important public health problem in childhood and later life. In addition, accurate quantification of prenatal secondhand tobacco smoke exposures is essential to obtaining valid estimates.
Body Mass Index; Children; Cotinine; Growth; Prenatal; Tobacco Smoke
Childhood exposure to environmental tobacco smoke has been extensively associated with childhood respiratory illness; fewer data address adult effects.
We examined childhood environmental tobacco smoke exposure in relation to chronic cough, phlegm and asthma diagnosis among never smokers from a cohort of Singaporeans of Chinese ethnicity, aged 45–74 at enrollment from 1993 to 1998. From 1999 to 2004, subjects were interviewed regarding environmental tobacco smoke exposure before and after age 18 and the presence and duration of current symptoms of chronic cough and phlegm production and asthma diagnosis.
Among 35,000 never smokers, fewer had smoking mothers (19%) than fathers (48%). Although few subjects currently lived (20%) or worked (4%) with smokers, 65% reported living with a daily smoker before age 18 years. Living with a smoker before age 18 increased the odds of chronic dry cough (149 cases, OR = 2.1, 95% CI 1.4–3.3) and, to a lesser extent, phlegm, after adjustment for age, gender, dialect group and current and past exposure to smokers at home and at work after age 18. Associations strengthened with higher numbers of smokers in childhood. There was no association with asthma or chronic bronchitis. We found suggestive evidence of a stronger association among subjects with lower adult intake of fiber, which we previously found to be protective for respiratory symptoms.
In this large study of nonsmokers, living with a smoker in childhood was associated with chronic dry cough and phlegm in adulthood, independently of later exposures to environmental tobacco smoke.
Tobacco smoke pollution; asthma; Signs and Symptoms; Respiratory; Bronchitis; chronic; Dietary Fiber
Background: Childhood exposure to environmental tobacco smoke has been extensively associated with childhood respiratory illness; fewer studies have addressed the effects on adults.
Methods: Childhood environmental tobacco smoke exposure in relation to chronic cough, phlegm, and asthma diagnosis was studied in never smokers from a cohort of Singaporeans of Chinese ethnicity aged 45–74 years at enrolment from 1993 to 1998. From 1999 to 2004 subjects were interviewed regarding environmental tobacco smoke exposure before and after the age of 18 and the presence and duration of current symptoms of chronic cough and phlegm production and asthma diagnosis.
Results: Among 35 000 never smokers, fewer had smoking mothers (19%) than fathers (48%). Although few subjects currently lived (20%) or worked (4%) with smokers, 65% reported living with a daily smoker before the age of 18 years. Living with a smoker before the age of 18 increased the odds of chronic dry cough (149 cases, odds ratio 2.1, 95% CI 1.4 to 3.3) and, to a lesser extent, phlegm, after adjustment for age, sex, dialect group, and current and past exposure to smokers at home and at work after the age of 18. Associations strengthened with higher numbers of smokers in childhood. There was no association with asthma or chronic bronchitis. There was evidence to suggest a stronger association among subjects with a lower adult intake of fibre which has previously been found to be protective for respiratory symptoms.
Conclusions: In this large study of non-smokers, living with a smoker in childhood was associated with chronic dry cough and phlegm in adulthood, independent of later exposures to environmental tobacco smoke.
This study evaluated the relationship between prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAHs) and child intelligence.
Children of nonsmoking black or Dominican-American women residing in New York City were monitored from in utero to 5 years of age, with determination of prenatal PAH exposure through personal air monitoring for the mothers during pregnancy. At 5 years of age, intelligence was assessed for 249 children by using the Wechsler Preschool and Primary Scale of Intelligence-Revised. Multivariate linear regression models were used to estimate and to test the associations between prenatal PAH exposure and IQ.
After adjustment for maternal intelligence, quality of the home caretaking environment, environmental tobacco smoke exposure, and other potentially confounding factors, high PAH levels (above the median of 2.26 ng/m3) were inversely associated with full-scale IQ (P = .007) and verbal IQ (P = .003) scores. Children in the high-exposure group had full-scale and verbal IQ scores that were 4.31 and 4.67 points lower, respectively, than those of less-exposed children (≤2.26 ng/m3). The associations between logarithmically transformed, continuous, PAH levels and these IQ measures also were significant (full-scale IQ: β = −3.00; P = .009; verbal IQ: β = −3.53; P = .002).
These results provide evidence that environmental PAHs at levels encountered in New York City air can affect children’s IQ adversely.
prenatal; fetal; polycyclic aromatic hydrocarbons; air pollution; IQ