Since Dr. Fogh-Andersen's legendary 1942 thesis, the Danish facial cleft population has been one of the most extensively studied in terms of epidemiology and genetic-epidemiology. The etiology of cleft lip and/or palate (CLP) is still largely an enigma, and different results concerning environmental and genetic risk factors are obtained in different countries and regions. This may be due to etiological heterogeneity between settings. Therefore, an in-depth studied area with an ethnically homogeneous population, such as Denmark, has provided one of the best opportunities for progress in CLP etiological research. The present review summarizes epidemiological and genetic-epidemiological studies conducted in the 20th century Danish facial cleft population. Furthermore, analyses of sex differences, time trends and seasonality for more than 7000 CLP cases born in Denmark in the period 1936 to 1987 are presented. The review also points toward the excellent opportunities for continued etiological CLP research in Denmark in the 21st century using already established resources and an on-going prospective cohort study of 100,000 pregnant women.
Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA.
Epigenetic modifications, such as DNA methylation, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear.
We investigated epigenome-wide methylation in cord blood of newborns in relation to maternal smoking during pregnancy.
We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethylation450 BeadChip (450K).
We found differential DNA methylation at epigenome-wide statistical significance (p-value
BACKGROUND. The rate of recurrence of a broad range of birth defects may decrease among women who change residence after the birth of their first infant. The aim of the present study was to determine the effect of changing residence on the recurrence of congenital facial-cleft defects. METHODS. We identified 4189 women who had infants with facial-cleft defects by linking a data base comprising the records of children with facial clefts born between 1952 and 1987 with the Central Person Registry in Denmark. Among the 4189 mothers, 1902 each had additional children after the first child with a facial-cleft defect. A total of 2692 younger siblings were identified. We compared the proportion of infants with facial-cleft defects among the younger siblings between mothers who had changed municipalities or sexual partners and those who had not. RESULTS. Changing the municipality of residence did not decrease the frequency with which facial-cleft defects recurred in younger siblings. Among the 907 infants of mothers who changed municipalities but not partners, 29 (3.2 percent) had facial-cleft defects, as compared with 48 (3.4 percent) of 1425 infants of mothers who changed neither municipality nor partner (relative risk, 0.9; 95 percent confidence interval, 0.6 to 1.5). However, a change of partner reduced the recurrence risk significantly. Among 236 infants of mothers who changed partners, 1 (0.4 percent) had a facial-cleft defect, as compared with 77 (3.3 percent) of 2350 infants of mothers who did not change partners (relative risk, 0.1; 95 percent confidence interval, 0.02 to 0.9). CONCLUSIONS. Recurrence of facial-cleft defects is not linked to the residence of the mother, but having a different partner reduced a woman's risk of having a second child with this defect.
A statistical and epidemiological review of British Columbia native Indian and non-Indian mortality revealed that accidents were the leading cause of death among Indians but ranked only fourth among non-Indians. Comparison of accidental death rates by age and sex showed that, without exception, the rates among Indians were considerably higher than the corressponding rates for non-Indians. While the Indians represented some 2% of the total population of British Columbia, they accounted for over 10% of the total accident fatalities, 29% of drownings, and 21% of fatal burns.Socioeconomic, environmental and psychosocial factors and excessive drinking are considered the chief causes responsible for this rather unusual epidemiological phenomenon.This study revealed certain hazardous conditions which are specific to the Indian's present way of life. In the authors' opinion the recognition of these specific hazards is imperative for the planning of effective preventive campaigns.
Cites: Can J Public Health. 1962 Oct;53:409-1213992080
The APHEA 2 project investigated short-term health effects of particles in eight European cities. In each city associations between particles with an aerodynamic diameter of less than 10 microm (PM(10)) and black smoke and daily counts of emergency hospital admissions for asthma (0-14 and 15-64 yr), chronic obstructive pulmonary disease (COPD), and all-respiratory disease (65+ yr) controlling for environmental factors and temporal patterns were investigated. Summary PM(10) effect estimates (percentage change in mean number of daily admissions per 10 microg/m(3) increase) were asthma (0-14 yr) 1.2% (95% CI: 0.2, 2.3), asthma (15-64 yr) 1.1% (0.3, 1.8), and COPD plus asthma and all-respiratory (65+ yr) 1.0% (0.4, 1.5) and 0.9% (0.6, 1.3). The combined estimates for Black Smoke tended to be smaller and less precisely estimated than for PM(10). Variability in the sizes of the PM(10) effect estimates between cities was also investigated. In the 65+ groups PM(10) estimates were positively associated with annual mean concentrations of ozone in the cities. For asthma admissions (0-14 yr) a number of city-specific factors, including smoking prevalence, explained some of their variability. This study confirms that particle concentrations in European cities are positively associated with increased numbers of admissions for respiratory diseases and that some of the variation in PM(10) effect estimates between cities can be explained by city characteristics.
The Inuit population of Nunavik (Canada) is exposed to immunotoxic organochlorines (OCs) mainly through the consumption of fish and marine mammal fat. We investigated the effect of perinatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) on the incidence of acute infections in Inuit infants. We reviewed the medical charts of a cohort of 199 Inuit infants during the first 12 months of life and evaluated the incidence rates of upper and lower respiratory tract infections (URTI and LRTIs, respectively), otitis media, and gastrointestinal (GI) infections. Maternal plasma during delivery and infant plasma at 7 months of age were sampled and assayed for PCBs and DDE. Compared to rates for infants in the first quartile of exposure to PCBs (least exposed), adjusted rate ratios for infants in higher quartiles ranged between 1.09 and 1.32 for URTIs, 0.99 and 1.39 for otitis, 1.52 and 1.89 for GI infections, and 1.16 and 1.68 for LRTIs during the first 6 months of follow-up. For all infections combined, the rate ratios ranged from 1.17 to 1.27. The effect size was similar for DDE exposure but was lower for the full 12-month follow-up. Globally, most rate ratios were > 1.0, but few were statistically significant (p
Beginning approximately 4 years after the Chernobyl nuclear accident a steady increase in the incidence of thyroid cancer was observed in children and adolescents of the Bryansk Oblast, which received the highest level of radionuclide contaminants in Russia. We examined the spatial relationship between the residence location of patients with identified thyroid cancer (0-18 years old at the time of the accident) and a number of geographic parameters to better account for the etiology of thyroid cancer spatial distribution. Geographic parameters analyzed included spatial distribution of 137Cs and 131I in soil, population demographics, measurements and reconstructions. of absorbed thyroid 131I doses in the population, and maps of major transportation arteries. An interesting finding is the lack of a consistent correlation between the spatial distribution of radionuclides in the soil and thyroid cancer incidence. Instead, most of the thyroid cancer cases were diagnosed in settlements situated on major railways and roads. Correlating population with thyroid cancer cases and transportation arteries reveals a much higher cancer rate on or near major roads and railways than at a distance from them, again independent of radionuclide soil concentration. There are other important factors, of course, that must be considered in future evaluations of this phenomenon. These include the influence of iodine endemic zones, genetic predisposition to thyroid cancer, and duration of residence time in contaminated areas. The feasibility of radionuclide transport on railways and roads is discussed, together with the vectors for transfer of the contaminants to the human population. Developing a model to reconstruct the radiation dose to the thyroid over time in this geographic region is proposed in light of the impact of transportation arteries. Specific studies are outlined to provide the data necessary to develop this model as well as to better characterize the feasibility and scientific validity of the contribution to human health effects of this transport factor. Transport factor refers to the transport of radionuclides on transportation arteries and the transfer of these agents to the human population residing in the vicinity of these arteries. If the impact on thyroid cancer of the transport of radionuclides on major railways and roads is indeed significant, a major reappraisal of the risk of large-scale radioactive release into the environment is necessary.
This retrospective cohort study evaluated adverse birth outcomes in infants whose birth records indicated maternal residence in villages containing dumpsites potentially hazardous to health and environment. Birth records from 1997 to 2001 identified 10,073 eligible infants born to mothers in 197 Alaska Native villages. Outcomes included low or very low birth weight, preterm birth, and intrauterine growth retardation. Infants from mothers in villages with intermediate (odds ratio (OR) = 1.73, 95% confidence interval (CI): 1.06, 2.84) and high (OR = 2.06, 95% CI: 1.28, 3.32) hazard dumpsites had a higher proportion of low birth weight infants than did infants from mothers in the referent category. More infants born to mothers from intermediate (OR = 4.38, 95% CI: 2.20, 8.77) and high (OR = 3.98, 95% CI: 1.93, 8.21) hazard villages suffered from intrauterine growth retardation. On average, infants weighed 36 g less (95% CI: -71.2, -0.8) and 55.4 g less (95% CI: -95.3, -15.6) when born to highly exposed mothers than did infants in the intermediate and low exposure groups, respectively, an effect even larger in births to Alaska Native mothers only. No differences in incidence were detected across exposure levels for other outcomes. This is the first study to evaluate adverse pregnancy outcomes associated with open dumpsites in Alaska Native villages.
Human teeth have been considered as dosimeters for decades. Methods include the in vivo measurement of 90Sr/90Y in teeth with a tooth-beta counter, the radiochemical determination of 90Sr in whole teeth, and the measurement of dose in teeth by use of electron paramagnetic resonance. Presented in this paper are results of 2,514 tooth-beta counter measurements, 334 radiochemical measurements, and 218 electron paramagnetic resonance measurements for residents living in settlements along the Techa River. All three kinds of measurements indicate a sharp peak that corresponds to the uptake of 90Sr by tooth tissue. The results can be interpreted in terms of an intake function for 90Sr only if the period of calcification of each individual tooth is considered--such detail on a tooth-by-tooth basis is presented in this paper. The conclusion is reached that the tooth-beta counter data are the most reliable in terms of reconstruction of 90Sr intake; this is due in part to the fact that the tooth-beta counter measures four teeth (all at position 1) with essentially the same time periods of mineralization and because there are a large number of tooth-beta counter measurements. The main utility of electron paramagnetic resonance measurements is considered to be the validation of estimates of external dose; but for this purpose teeth with 90Sr taken up into enamel must be avoided.
To determine the influence of endotoxin on the incidence of acute respiratory illness during the first 2 years of life, we carried out a longitudinal follow-up study, beginning at birth, of 332 children born in Prince Edward Island, Canada. We measured 5-day averaged air endotoxin in the homes of children, whose parents provided information by daily symptom diaries and twice-monthly telephone contact for up to 2 years. Endotoxin concentration was 0.49 +/- 3.49 EU/m3 (geometric mean +/- geometric SD), and number of annualized illness episodes was 6.83 +/- 2.80 (mean +/- SD). A doubling of the air endotoxin concentration was associated with an increase of 0.32 illness episodes per year (p = 0.0003), adjusted for age, year of study, breast-feeding, environmental tobacco smoke, child care attendance, indoor temperature, and income. Indoor mold surface area and fungal ergosterol were not significantly associated with endotoxin. Airborne endotoxin appears to be a risk factor for clinically symptomatic respiratory illnesses during the first 2 years of life independent of indoor fungus.
Airborne particulate matter from primarily geologic, non-industrial sources at levels below National Ambient Air Quality Standards is associated with outpatient visits for asthma and quick-relief medication prescriptions among children less than 20 years old enrolled in Medicaid in Anchorage, Alaska.
In Anchorage, Alaska, particulates with aerodynamic diameter or = 34 micro g/m(3). A significant 18.1% increase (RR: 1.181, 95% CI: 1.010-1.381) in the rate of quick-relief medication prescriptions occurred during days with PM(10) of 34-60 micro g/m(3), and a 28.8% increase (RR: 1.288, 95% CI: 1.026-1.619) occurred during days with PM(10) > or = 61 micro g/m(3). Similar results for outpatient asthma visits and quick-relief medication occurred in weekly models. There were no significant associations with PM(2.5) in either daily or weekly models. These subtle but statistically significant associations suggest that non-industrial, geologic sources of PM(10) may have measurable health effects at levels below current national standards.
Cancer incidence and its possible relation to environmental contaminants, including radiation, continues to be a perceived health threat for the arctic-dwelling Alaska Native (Inupiat Eskimo) people despite the lack of a direct link to high-dose exposure. To better understand this concern, all known malignancies diagnosed in this population (n = 177) in three consecutive eight-year periods (1971-1994) were evaluated. The most recent average incidence rate (age-adjusted to world standard population) of 315 per 100,000 (95% confidence interval, CI = 248-382) represents a 33% surge (albeit non-significant) in Alaska Native cancer incidence over the initial period studied. The male rate 366 (95% CI = 266-466) for the same period exceeds the female rate 258 (95% CI = 169-347) by 42%. Two patterns of cancer incidence are seen at the village level. One, a 24 y upward trend found in the villages of Barrow, Point Hope and Kaktovik (combined rate of increase significant [P = 0.047]) associated with lung cancer; and the other, a stable trend over the past 16 y, associated with colon and rectal cancer. Lung cancer is the predominant cancer by site and is primarily a male disease. The recent male lung cancer incidence rate of 137 (95% CI = 73-201) exceeds the female rate by greater than five times. Total lung cancer cases are primarily confined to four villages where the incidence significantly (P = 0.0043) exceeds the remaining population. The major female cancers are colon/rectal and breast with cancer of the cervix virtually eliminated. Breast cancer is found primarily in two villages where its excess is significant (P = 0.025). Inupiat Eskimo cancer epidemiology is unique, differing from both the Alaska Native and other Circumpolar populations. At present, this uniqueness cannot be explained by an overt environmental contaminant exposure. Although tobacco very likely plays a central role, it by itself cannot fully explain the extremely high male lung cancer rate and why only specific villages are affected. Genetic predisposition and environmental factors may play a synergistic role as cofactors. A cooperative investigative effort with the Inupiat population is indicated and may go a long way in reducing cancer concern in the region.
As demonstrated by many studies, emergency department (ED) visits for asthma can be associated with air pollution exposures. The aim of this study was to examine and assess the potential relations between ED visits for asthma and the concentrations of ambient air pollutants.
Generalized linear mixed model was applied to study 62,563 ED visits for asthma (ICD-9: 493) in Edmonton, Canada. Two age groups, with 10 years of age as a separator, were considered by gender and season of the year: all (I-XII), warm (IV-IX) and cold (X-III).
The percentage increase in daily ED visits for asthma was 17.8% (95% CI: 7.1-29.5) and 13.8% (95% CI: 3.3-25.3) for females below 10 years of age, in the period of IV-IX, for current day and 1-day lagged exposure to ozone (O(3)), respectively. The percentage increase was 19.2% (95% CI: 11.4-27.6) for males below 10 years of age, in the period of IV-IX, for 2-day lagged exposure to nitrogen dioxide (NO(2)).
The findings provide support for the hypothesis that ED visits for asthma are associated with exposure to O(3). This study underlines the significant role of air pollutants as triggering asthma attacks.
The aim of this study was to assess the influence of social environmental factors on school performance and behavioural problems among 14-year-old children who had been exposed to amphetamine during foetal life. The study group comprised a cohort of 65 children who had suffered intrauterine exposure to amphetamine due to maternal drug abuse. This group has been followed since birth and examined at regular intervals. Information regarding the academic performance of the children was gathered from the school authorities. The psychosocial environment of the children was determined through interviews and through information obtained from the social authorities. Of the 64 children who attended a school within the state school system, 10 (15%) were a year behind for their age. The mean grades were significantly lower than those of their classmates. Behavioural problems were mentioned in the social authority documentation of one-third of the children, regardless of whether the child was placed in a foster home or was residing with the biological mother. A positive significant correlation was found between maternal age and the outcome of the children, as well as between therapy during pregnancy and outcome, whilst several environmental factors, particularly during the child's first four years, correlate negatively to outcome. Psychosocial factors early in life influence the outcome at 14 years. The positive effect of intervention during pregnancy illustrates the importance of early identification preferable during pregnancy.
The epidemiologic triad of causation states that all illness results from a disequilibrium between host, agent and environmental factors. The "illness" investigated in this report--increased LOS--resulted from a combination of: patient factors--the increased prevalence of chronic diseases in childhood, a revolution in neonatal survival and an increase in survivorship in general for severe diseases, such as congenital anomalies and genetic diseases; agent factors--the transition from agents of infectious disease to agents of chronic disease as well as iatrogenesis; and health care environmental factors--equity issues involving the ethics of treatment, changes in medical technology and patterns of medical practice. The use of preadmission testing, increased participation by parents in the care of their children, an investigation of the appropriate venue for care of chronically ill children and the back transfer of recovering children to their home hospitals were recommended and considered by the hospital's administration and board of governors.
Pneumonia and influenza represent a significant public health burden in Canada and abroad. Knowledge of how this burden varies geographically provides clues to understanding the determinants of these illnesses, and insight into the effective management of health-care resources. We conducted a retrospective, population-based, ecological-level study to assess age- and gender-specific spatial patterns of pneumonia and influenza hospitalizations in the province of Ontario, Canada from 1992 to 2001. Results revealed marked variability in hospitalization rates by age, as well as clear and statistically significant patterns of high rates in northern rural counties and low rates in southern urban counties. A moderate yet significant level of positive spatial autocorrelation (Moran's I=0.21, P