Effects Of Early-life Exposure Research Articles

Traffic-Related Air Pollution and Childhood Asthma

We congratulate Clark et al. (2010) for their interesting article concerning traffic-related air pollution and asthma in children. They examined early-life (in utero and during the first year of life) exposure to traffic-related air pollution in a large population-based study (a nested case–control study including nearly 3,500 children). The authors found an association between elevated early-life exposure to traffic-related air pollution and a higher risk of asthma in preschool-aged children. However, Clark et al. (2010) address aspects, raise questions, and give results that deserve further comment—both concerning specific items and general “structural” criteria used in epidemiological studies on adverse health effects from air pollution. Recent reports have suggested that individual susceptibility could play a previously unsuspected role in the occurrence of diseases (Cetta et al. 2009a), perhaps a role greater than that of the intrinsic toxicity of pollutants (Cetta et al. 2009b). This could explain, at least in part, why it is so difficult to determine a precise threshold concentration that is harmful or safe for each individual (Cetta et al. 2007). But this is just one side of the question. The main question is that, in the absence of adequate and specific markers of exposure, effect and susceptibility, the linear dose and effect model, and the concomitant pollutant concentration and disease occurrence relationship cannot explain the complexity of the phenomenon of host–particle interactions. In particular, initial cell alterations (e.g., oxidative stress, DNA adduct formation) rarely turn into permanent tissue damage and evident disease because of host repair and defence mechanisms. In their article Clark et al. (2010) noted another important aspect that should be considered when comparing pollutant concentrations with the burden of deleterious effects, both at the individual and population levels: acute effects of peak concentrations of pollutants that lead to acute admission to hospital and the chronic damage that causes long-term effects. In fact, we should consider both of these as separate entities. However, we also should consider the effect of air pollution on newborns, which greatly depends on individual susceptibility—either congenital or acquired. This could play a major role in future outcomes and shed new light on the peculiar pathophysiological mechanisms of most pollution-related diseases. Clark et al. (2010) correctly outlined the asynchronism and the delay (0–4 years) between the initial pathogenetic exposure to pollutants (in utero or during the first year of life) and the occurrence and detectability of clinically relevant asthma. This further adds to the complexity of host-particle interactions. There are three issues that should be taken into account in developmental epidemiology studies such as that by Clark et al. (2010). First, epidemiological studies that concomitantly evaluate pollutant concentration and detectable diseases or hospital admissions usually neglect the perinatal damage in fetuses and newborns, which is not immediately detectable but is a delayed manifestation. Second, perinatal damage from air pollution deserves further attention and detailed analysis because it includes fetal malformations, birth defects, and developmental alterations of newborns. Injury from perinatal air pollution exposure could also be responsible for the increased proportion of unsusceptible individuals who, because of their exposure to pollutants during the susceptibility window and because of epigenetic alterations due to environmental factors, will become susceptible. Epigenetic alterations could also transfer this susceptibility to future generations, leading to individuals developing not only asthma at 4 years of age but also respiratory, cardiovascular or systemic diseases ≥ 20 years later. Third, clinical and pathophysiological details are not “details” but basic issues and questions—still unsolved— that should be primary goals for future research. They are critical to improving design of epidemiologic studies and to selecting appropriate models, which should also include biological and pathophysiological parameters and variables because they significantly affect clinical outcomes.

Unraveling Environmental Effects on Mitochondria

Look into any cell today, and you’ll see remnants of ancient bacteria by the thousands. These mitochondria—tiny organelles in the cell that each possess their own DNA—have come under a growing scientific spotlight; scientists increasingly believe they play a central role in many, if not most, human illnesses. Exquisitely sensitive to environmental threats, mitochondria convert dietary sugars into a high-energy molecule—adenosine triphosphate (ATP)—that cells use as fuel. And when mitochondria falter, cells lose power, just as a flashlight dims when its batteries weaken. Now scientists are linking environmental interactions with the mitochondria to an array of metabolic and age-related maladies, including cancer, autism, type 2 diabetes, Alzheimer disease, Parkinson disease, and cardiovascular illness.

No consistent effects of prenatal or neonatal exposure to Spanish flu on late-life mortality in 24 developed countries

We test the effects of early life exposure to disease on later health by looking for differences in late-life mortality in cohorts born around the 1918-1919 flu pandemic using data from the Human Mortality Database for 24 countries. After controlling for age, period, and sex effects, residual mortality rates did not differ systematically for flu cohorts relative to surrounding cohorts. We calculate at most a 20-day reduction in life expectancy for flu cohorts; likely values are much smaller. Estimates of influenza incidence during the pandemic suggest that exposure was high enough for this to be a robust negative result.

The effects of early life exposure to citalopram on glomerular morphology and aquaporin 2 distribution in rat kidneys

Thirty percent of infants exposed in utero to SSRIs display behavioral and physiological abnormalities in the first few weeks after birth including increased incidence of pulmonary hypertension. Rats exposed from postnatal day (PN) 1–21 to SSRIs display persistent neurobehavioral abnormalities which include severe deficits in social interactions and expression of serotonergic neurons. Disturbances in serotonin levels result in alterations in mood, sleep, sexuality, and depression. SSRIs have been developed to restore serotonin homeostasis. Adult treatment with SSRIs cause increased water resorption by increasing ADH secretion or increased aquaporin‐2 (AQ‐2) channels in the collecting ducts. The goal of this study was to investigate the lasting effects of early life SSRI exposure on AQ‐2 distribution in the kidneys. Long Evans rats ( 30 male, 30 female) were treated from PN 1–21 with 0.1 mL s.c. of either saline or citalopram (5mg/Kg, 10 mg/Kg, or 20mg/Kg). Animals were sacrificed at PN‐180. Distribution of AQ‐2 and glomeruli size was evaluated. The results show a dose dependent increase in AQ‐2 distribution within the kidney tubules without alterations in glomerular size (p<0.05). No gender differences were observed, which is in contrast to the neurobehavioral effects of early life citalopram exposure. Additional research is needed to determine if ADH secretion or an increase in corticosteroids leads to increased aquaporin‐2 distribution. Supported by RR‐017701 to IAP and KLS and MH‐084194 to RCSL.

Effect of Early Life Exposure to Air Pollution on Development of Childhood Asthma

BackgroundThere is increasing recognition of the importance of early environmental exposures in the development of childhood asthma. Outdoor air pollution is a recognized asthma trigger, but it is unclear whether exposure influences incident disease. We investigated the effect of exposure to ambient air pollution in utero and during the first year of life on risk of subsequent asthma diagnosis in a population-based nested case–control study.MethodsWe assessed all children born in southwestern British Columbia in 1999 and 2000 (n = 37,401) for incidence of asthma diagnosis up to 3–4 years of age using outpatient and hospitalization records. Asthma cases were age- and sex-matched to five randomly chosen controls from the eligible cohort. We estimated each individual’s exposure to ambient air pollution for the gestational period and first year of life using high-resolution pollution surfaces derived from regulatory monitoring data as well as land use regression models adjusted for temporal variation. We used logistic regression analyses to estimate effects of carbon monoxide, nitric oxide, nitrogen dioxide, particulate matter ≤ 10 μm and ≤ 2.5 μm in aerodynamic diameter (PM10 and PM2.5), ozone, sulfur dioxide, black carbon, woodsmoke, and proximity to roads and point sources on asthma diagnosis.ResultsA total of 3,482 children (9%) were classified as asthma cases. We observed a statistically significantly increased risk of asthma diagnosis with increased early life exposure to CO, NO, NO2, PM10, SO2, and black carbon and proximity to point sources. Traffic-related pollutants were associated with the highest risks: adjusted odds ratio = 1.08 (95% confidence interval, 1.04–1.12) for a 10-μg/m3 increase of NO, 1.12 (1.07–1.17) for a 10-μg/m3 increase in NO2, and 1.10 (1.06–1.13) for a 100-μg/m3 increase in CO. These data support the hypothesis that early childhood exposure to air pollutants plays a role in development of asthma.

Early life exposure to poor nutrition and infectious diseases and its effects on the health of older Puerto Rican adults.

We examined the effects of early life exposure to poor nutrition and infectious diseases on adult heart disease and diabetes using season of birth as an indicator to help disentangle the effects on health of early life exposure from effects associated with other childhood conditions. Using data from 60- to 74-year-old Puerto Ricans who lived in rural areas during childhood (n = 1,457), we estimated the effects of seasonal exposure during late gestation on the probability of diabetes and heart disease, controlling for adult obesity and other childhood conditions (health, socioeconomic status, knee height). We found (a) strong associations between exposure and heart disease; (b) weaker associations between exposure and diabetes, although significant negative interaction effects between exposure and having a family member with diabetes suggest the possibility of either strong gene-environment or early adult-environment interactions; (c) virtually no attenuation of effects of self-reported childhood health with controls for exposure. Timing of birth may reveal conditions experienced perinatally that affect adult heart disease and diabetes. The results suggest that examination of the effects of season of birth on these chronic conditions among older Puerto Rican adults and among older adults from similar populations deserves deeper scrutiny.

Health Effects of Early Life Exposure to Arsenic

Inorganic arsenic is a potent human carcinogen and general toxicant. More than one hundred million people are exposed to elevated concentrations, mainly via drinking water, but also via industrial emissions. Arsenic is metabolized via methylation and reduction reactions, methylarsonic acid and dimethylarsinic acid being the main metabolites excreted in urine. Both inorganic arsenic and its methylated metabolites easily pass the placenta and both experimental and human studies have shown increased risk of impaired foetal growth and increased foetal loss. Recent studies indicate that prenatal arsenic exposure also increases the risk of adverse effects during early childhood. There is a growing body of evidence that the intrauterine or early childhood exposure to arsenic also induces changes that will become apparent much later in life. One epidemiological study indicated that exposure to arsenic in drinking water during early childhood or in utero was associated with an increased mortality in young adults from both malignant and non-malignant lung disease. Furthermore, a series of experimental animal studies provide strong support for late effects of arsenic, including various forms of cancer, following intrauterine arsenic exposure. The involved modes of action include epigenetic effects, mainly via DNA hypomethylation, endocrine effects (most classes of steroid hormones), immune suppression, neurotoxicity, and interaction with enzymes critical for foetal development and programming.

Children's Response to Air Pollutants

It is important to focus on children with respect to air pollution because (1) their lungs are not completely developed, (2) they can have greater exposures than adults, and (3) those exposures can deliver higher doses of different composition that may remain in the lung for greater duration. The undeveloped lung is more vulnerable to assault and less able to fully repair itself when injury disrupts morphogenesis. Children spend more time outside, where concentrations of combustion-generated air pollution are generally higher. Children have higher baseline ventilation rates and are more physically active than adults, thus exposing their lungs to more air pollution. Nasal breathing in adults reduces some pollution concentrations, but children are more typically mouth-breathers—suggesting that the composition of the exposure mixture at the alveolar level may be different. Finally, higher ventilation rates and mouth-breathing may pull air pollutants deeper into children's lungs, thereby making clearance slower and more difficult. Children also have immature immune systems, which plays a significant role in asthma. The observed consequences of early life exposure to adverse levels of air pollutants include diminished lung function and increased susceptibility to acute respiratory illness and asthma. Exposure to diesel exhaust, in particular, is an area of concern for multiple endpoints, and deserves further research.

Changes of immunoresponse in BALB/c mice neonatally treated with periodontopathic bacterial endotoxin

The aim of this investigation was to analyze the effects of early life exposure to periodontopathic bacterial lipopolysaccharides on immunoresponse. Newborn BALB/c mice were subcutaneously injected with 20 ng lipopolysaccharide of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans or Escherichia coli daily for 2 days, starting within 24 h after birth. The treated mice were given intraperitoneal injections of bovine serum albumin at 180 and 187 days of age. Seventeen hours after each injection, the mice were bled and sera were separated. Their sera were tested in an enzyme-linked immunosorbent assay system. The mean interleukin-4, interleukin-5, interleukin-6 and immunoglobulin E levels in the sera of mice treated neonatally with P. gingivalis lipopolysaccharide were significantly higher than those of the controls. However, in all cases, no significant difference was noted between mice treated neonatally with A. actinomycetemcomitans- or E. coli lipopolysaccharide and control mice. These data suggest that neonatal exposure to P. gingivalis lipopolysaccharide induces changes in immunological responses when the mice reach maturity.

Editorial???Behavioural Pharmacology of Cannabinoids

Editorial???Behavioural Pharmacology of Cannabinoids

Prenatal Dichlorodiphenyldichloroethylene (DDE) and Asthma in Children

Prevalence of asthma increases with increasing dichlorodiphenyldichloroethylene (DDE) levels. However, the effect of early-life exposure, the fundamental window of exposure, is unknown. We assessed the association between prenatal DDE and other organochlorine compounds, and atopy and asthma during infancy. All women presenting for antenatal care in Menorca (Spain) over 12 months starting in mid-1997 were invited to take part in a longitudinal study; 482 children were subsequently enrolled, and 468 (97.1%) provided complete outcome data up to the fourth year of study. Prenatal exposure of organochlorine compounds was measured in cord serum in 405 (83%) children. Asthma was defined on the basis of wheezing at 4 years of age, persistent wheezing, or doctor-diagnosed asthma. We measured specific immunoglobulin-E (IgE) against house dust mite, cat, and grass in sera extracted at 4 years of age. DDE (median = 1.03 ng/mL) was detected in all children, as well as hexachlorobenzene (0.68 ng/mL) and polychlorobiphenyls (0.69 ng/mL). Wheezing at 4 years of age increased with DDE concentration, particularly at the highest quartile [9% in the lowest quartile (< 0.57 ng/mL) vs. 19% in the highest quartile (1.90 ng/mL); relative risk = 2.63 (95% confidence interval 1.19–4.69), adjusting for maternal asthma, breast-feeding, education, social class, or other organochlorines]. The association was not modified by IgE sensitization and occurred with the same strength among nonatopic subjects and among those with persistent wheezing or diagnosed asthma. DDE was not associated with atopy alone. Prenatal exposure to DDE residues may contribute to development of asthma.

Are Adolescents Who Were Breast-fed Less Likely to Be Overweight?

Cohort analyses suggesting that breast-feeding protects against being overweight have been criticized for inadequately controlling for confounding associated with the self-selection of feeding practices. Using nationally representative U.S. data from the National Longitudinal Study of Adolescent Health (1994-1996), we performed traditional cohort analyses (n = 11,998) using logistic regression to estimate the relation between breast-feeding and adolescent overweight (body mass index > or =85 percentile, based on year 2000 CDC growth charts), controlling for known potential confounders. Breast-feeding also was assessed in a subsample of 850 sibling pairs to account for unmeasured genetic and environmental factors. Among girls in the full cohort, the odds of being overweight declined among those who had been breast-fed at least 9 months; odds ratios ranged from 0.90 (95% confidence interval = 0.74-1.09) for <3 months of breast-feeding to 0.78 (0.64-0.96) for > or =9 months. A similar effect was seen in boys, although these trends were less consistent. In contrast, an analysis of sibling pairs provided no evidence of breast-feeding effects on weight within discordant trends. Cohort data indicate that odds of being overweight decrease as breast-feeding duration increases, at least among girls. However, sibling analyses suggest that this relationship may not be causal but rather attributable to unmeasured confounding related to mothers' choice to breast-feed, or to other childhood risk factors for overweight. Our results illustrate the utility of sibling analyses in understanding the true effect of early life exposures (such as breast-feeding) on health outcomes over time, independent of confounding factors that may not be satisfactorily controlled using traditional prospective cohort methods.

Endotoxin in inner-city homes and atopy and wheeze in the first two years of life

Rationale Studies have reported a protective effect of early life exposure to endotoxin against the development of allergic diseases, but few have examined an inner-city population. Due to temporal differences between increased hygienic living in NYC (early 20th century) and the asthma increase (later 20th century), we hypothesized that endotoxin's protective effect would not be observed in this inner-city community. Methods As part of an ongoing prospective birth cohort study sponsored by CCCEH, children of Dominican and African-American mothers living in NYC underwent detailed questionnaires quarterly, home dust collection, and IgE measurement. The 176 dust samples collected thus far from bedroom floors at age 12 months were extracted in pyrogen-free water with tween and assayed for endotoxin by LAL assay. Results The geometric mean of endotoxin in the dust was 78 EU/mg [95% CI 65-93]. Endotoxin concentrations were slightly higher in homes of mothers reporting weekly cockroach sightings (88 EU/mg vs. 72 EU/mg, p=0.3) or pet ownership (93 EU/mg vs. 75 EU/mg, p=0.4), and significantly higher with weekly mouse sightings (108 EU/mg vs. 69 EU/mg, p=0.043). There was no association between those children living in homes with endotoxin concentrations in the highest quartile (>163 EU/mg) and wheeze at 12 (RR 0.92 [0.8-1.1]) or 24 months (RR 0.96 [0.8-1.1]); doctor diagnosed eczema at 12 (RR 0.94 [0.8-1.1]) or 24 months (RR 1.0 [0.8-1.3]); or total IgE in the highest quartile at 24 months (RR 1.1 [0.8-1.5]). Conclusions At this age in this inner-city community we observed no association between high endotoxin and a lower prevalence of early markers of allergic disease, while endotoxin concentrations were comparable to those reported elsewhere.

A longitudinal analysis of wheezing in young children: The independent effects of early life exposure to house dust endotoxin, allergens, and pets

Background: It has been postulated that exposure to bacterial endotoxins and animals early in life might confer protection against the development of asthma and allergies. Objective: We investigated the longitudinal effects of exposure to house dust endotoxin (HDE), allergen levels, and the presence of a dog in the home on wheezing in young children over a 4-year period. Methods: Two hundred twenty-six children younger than 5 years were followed for 4 years. Endotoxin and allergen levels were measured from house dust collected at baseline. Longitudinal associations were investigated by using a proportional hazards technique that allowed for multiple outcomes per subject. Results: Exposure to high concentrations of HDE of greater than the median level was associated with an increased risk for wheezing over the period of observation (multivariate relative risk, 1.52; 95 % CI, 1.07-2.14), but this risk rapidly decreased over time (P for trend = .005). Exposure to cockroach allergen was associated with increased risk for wheezing, whereas exposure to cat allergen and the presence of a dog in the home were both associated with decreased risk for wheezing. The risks associated with cockroach allergen, cat allergen, and dog did not change over the period of observation. Conclusion: The negative associations between exposures to dogs and cat allergen and wheeze appear to be independent of the effects of endotoxin and suggest that separate mechanisms might mediate the effects of HDE exposure and pet exposure on the developing immune system. (J Allergy Clin Immunol 2002;110:736-42.)

Environmental and dietary endocrine disruptors and women's health

Endocrine disruptors are substances which can potentially modify the normal hormonal functions of the body, and include both naturally occurring compounds (such as plant phytoestogens) and anthropogenically derived environmental contaminants. This article reviews the evidence for possible links between exposure to anthropogenic chemicals and a number of common conditions in women, including breast cancer, cardiovascular disease and atherosclerosis, osteoporosis, endometrial disease, autoimmunity and menopausal symptoms. The question whether phytoestrogens might exert some beneficial effects during the postmenopausal period is also addressed. In addition, the possible consequences of early life exposure to potential endocrine disruptors or phytoestrogens are discussed.

Prenatal and perinatal risk factors for breast cancer in young women.

There is increasing interest in the role of early life exposures in breast carcinogenesis, especially estrogen exposure in utero. Estrogen levels during pregnancy may be higher in twin pregnancies and among older women and slightly lower among smokers. We analyzed early life risk factors in a population-based case-control study in the United States of 2,202 breast cancer cases and 2,009 controls under age 55 years. Twins were at an increased risk of breast cancer compared with singletons (relative risk = 1.62; 95% confidence interval = 1.0-2.7), particularly women with a twin brother (relative risk = 2.06), a finding consistent with the observation of high estrogen levels in dizygotic twin pregnancies. Little association was seen between maternal age at birth and breast cancer risk. We carried out further analyses for 534 cases and 497 controls under age 45 years, using data from a questionnaire completed by their mothers relating to the daughters' early life exposures. There was no evidence of an effect of smoking or diethylstilbestrol exposure during pregnancy on daughters' breast cancer risk. A reduced breast cancer risk was seen among women who had been breastfed (relative risk = 0.74; 95% confidence interval = 0.6-1.0). These findings indicate some effect of early life exposures on breast cancer risk, although the role of estrogen exposure may be less central than previously suggested.