The Impact of Polycyclic Aromatic Hydrocarbons and Fine Particles on Pregnancy Outcome.The relationship between intrauterine growth retardation Intrauterine Growth Retardation Definition
Intrauterine growth retardation (IUGR) occurs when the unborn baby is at or below the 10th weight percentile for his or her age (in weeks). (IUGR IUGR intrauterine growth retardation (or restriction).
intrauterine growth retardation
IUGR Intrauterine growth retardation, see there ) and exposure to particulate matter particulate matter
n. Abbr. PM
Material suspended in the air in the form of minute solid particles or liquid droplets, especially when considered as an atmospheric pollutant.
Noun 1. [is less than or equal to] 10 [micro]m ([PM.sub.10]) and particulate matter [is less than or equal to] 2.5 [micro]m ([PM.sub.2.5]) in early pregnancy early pregnancy Obstetrics First trimester of pregnancy was recently studied in the highly polluted district of Teplice (Northern Bohemia). From this observation rose the question about the possible role of the carcinogenic carcinogenic
having a capacity for carcinogenesis. fraction of polycyclic aromatic hydrocarbons (c-PAHs), which are usually bound to fine particles. The impact of c-PAHs and fine particles on IUGR was analyzed in Teplice and in Prachatice, a region with similarly high c-PAH but low particle levels. All European, single live births occurring in a 4-year period in Teplice (n = 3,378) and Prachatice (n = 1,505) were included. Detailed personal data were obtained via questionnaires and medical records. Mean [PM.sub.10], [PM.sub.2.5], and c-PAHs levels during the 9 gestational months (GM) were estimated for each mother. Adjusted odds ratios (AORs) of IUGR for three levels of c-PAHs (low, medium, and high) and for continuous data were estimated after adjustment for a range of covariates using logistic regression models. In the present 4-year sample from Teplice, previously published results about increasing IUGR risk after exposure to particles in the first GM were fully confirmed, but no such effects were found in Prachatice. The AOR AOR
The ISO 4217 currency code for Angolan Reajustado Kwanza. of IUGR for fetuses from Teplice exposed to medium levels of c-PAHs in the first GM was 1.60 [confidence interval confidence interval,
n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%. (CI), 1.06-2.15], and to high levels 2.15 (CI, 27-3.63). An exposure-response relationship was established by analyzing the continuous data. For each 10 ng increase of c-PAHs in the first GM, the AOR was 1.22 (CI, 1.07-1.39). About the same relationship was observed in Prachatice in spite of the low particle levels. The results prove that exposure to c-PAHs in early gestation may influence fetal growth. The particulate matter--IUGR association observed earlier may be at least partly explained by the presence of c-PAHs on particle surfaces. Key words: air pollution, fetal growth, intrauterine growth retardation, particulate matter, polycyclic aromatic hydrocarbons, reproductive effects. Environ Health Perspect 108:1159-1164 (2000). [Online 7 November 2000]
There is widespread concern over the health effects of ambient air pollution (1,2). There is growing support for the idea that adverse pregnancy outcomes may result from maternal (parental) exposures to airborne pollution (3-8). A consistent relationship between maternal exposure to fine particles in early gestation and intrauterine growth retardation (IUGR) was recently observed in Teplice, a highly polluted district of northern Bohemia (9). One possible explanation for this finding is that rather than particles, some associated copollutant such as polycyclic aromatic hydrocarbons (PAHs) may interfere with fetal development. Most of these compounds are usually adsorbed on the surface of fine particles (10,11).
The genotoxicity Genotoxic substances are a type of carcinogen, specifically those capable of causing genetic mutation and of contributing to the development of tumors. This includes both certain chemical compounds and certain types of radiation. and embryotoxicity of particulate matter in the ambient air of the Teplice district were also investigated (12). Extracts eluted from fine particles were examined by an in vitro in vitro /in vi·tro/ (in ve´tro) [L.] within a glass; observable in a test tube; in an artificial environment.
In an artificial environment outside a living organism. acellular acellular /acel·lu·lar/ (a-sel´u-ler) not cellular in structure.
1. Containing no cells; not made of cells.
2. Devoid of cells; noncellular. assay coupled with [sup.32]P-postlabeling of DNA adducts and a chick embryotoxicity screening test. The extracts were able to preferentially produce DNA-PAH adducts in calf thymus thymus
Pyramid-shaped lymphoid organ (see lymphoid tissue) between the breastbone and the heart. Starting at puberty, it shrinks slowly. It has no lymphatic vessels draining into it and does not filter lymph; instead, stem cells in its outer cortex develop into DNA DNA: see nucleic acid.
or deoxyribonucleic acid
One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. and were also embryotoxic. The highest activity was found for fractions containing mainly PAHs (12). In addition, another study using the same population suggested that IUGR was positively related to the level of DNA-PAH adducts in placentae (13). These results indicate that PAHs are a major source of the genotoxic genotoxic /ge·no·tox·ic/ (je´no-tok?sik) damaging to DNA: pertaining to agents known to damage DNA, thereby causing mutations, which can result in cancer.
adj. and embryotoxic activities of organic mixtures associated with the air pollution in the Teplice district.
This study examined the impact of PAHs on fetal growth in a larger data set from the same population. To enable a valid comparison, the effect of particulate matter on IUGR [examined recently in a 2-year data set (9)] was reanalyzed in this more complete (4-year) data set.
It is important to determine the real contribution (if any) of particulate matter and PAHs to the risk of IUGR; but this may not be an easy task. Dockery (14) discussed the methodologic problems in these types of studies: he suggested that such studies are intrinsically difficult because exposure is common, the expected effects are weak, the random misclassification of exposure is frequent, and the health indicators have multiple etiology. In addition, ambient air frequently represents a complex mixture of pollutants (14). We attempted to overcome or minimize these problems by using a specific study design.
Exposure to ambient air pollution is common for populations living in a particular area. Because the heterogeneity of exposure is low, the distribution of possible health effects is hard to distinguish. In this respect, studies of the reproductive effects of common contaminants have a distinct advantage over studies of respiratory health effects or daily mortality. The probability of inducing some reproductive end points depends on the stage of the reproductive cycle reproductive cycle
The cycle of physiological changes that begins with conception and extends through gestation and parturition. (e.g., germinal Germinal
conflict of capital vs. labor: miners strike en masse. [Fr. Lit.: Germinal]
See : Riot
portrays the sufferings of workers in the French mines. [Fr. Lit. mutations originate only before or during conception, and major birth defects birth defects, abnormalities in physical or mental structure or function that are present at birth. They range from minor to seriously deforming or life-threatening. A major defect of some type occurs in approximately 3% of all births. invariably in·var·i·a·ble
Not changing or subject to change; constant.
in·vari·a·bil arise during the first 8 weeks of gestation). Thus, the induction of such effects is possible only in a relatively narrow sensitivity window. Some other reproductive outcomes may be less stage specific (e.g., spontaneous abortion spon·ta·ne·ous abortion
A naturally occurring termination of a pregnancy. Also called miscarriage.
spontaneous abortion , low birth weight). Air pollution levels vary considerably over the course of a year, whereas conceptions in the human population occur more or less continually. Therefore, it is possible to compare the prevalence of a particular stage-specific outcome in the offspring of parental groups that differ considerably in their exposure to certain pollutants during the same gestational stage.
It has been suggested that IUGR is triggered by the abnormal reaction of the trophoblast trophoblast /tro·pho·blast/ (tro´fo-blast) the peripheral cells of the blastocyst, which attach the blastocyst to the uterine wall and become the placenta and the membranes that nourish and protect the developing organism. with uterine uterine /uter·ine/ (u´ter-in) pertaining to the uterus.
Of, relating to, or in the region of the uterus. tissues during the implantation period (15). If so, IUGR is a typical outcome with a sensitivity window that can be used to assess the effects of ambient air pollution.
Another methodologic difficulty results from the complex nature of air pollution. One possible way to distinguish between the effects of different components of a complex mixture that are closely related is to examine a group from a population with limited exposure to one of the pollutants (14). A population living in a relatively clean region of southern Bohemia was examined for this purpose. This region, the district of Prachatice, is known to have relatively low levels of particulate matter compared to the Teplice district.
The main aim of the present study was to examine the impact of carcinogenic PAHs (c-PAHs) and particulate matter on fetal growth in Teplice, a severely polluted district of northern Bohemia. Data from the Prachatice region were used to evaluate the respective roles of c-PAHs and fine particles in the retardation of fetal growth.
Material and Methods
The background sample included all single births that occurred in the Teplice and Prachatice districts during the 4-year period from April 1994 through March 1998 [the previously mentioned study about PM/IUGR was based on 2-year data from the Teplice district only (9)]. The district of Teplice, with approximately 120,000 inhabitants
The game is based loosely on the concepts from SameGame. and 1,100 births per year, lies in the brown-coal basin of northern Bohemia, along with chemical industry, surface mining, and large coal power plants. Prachatice, with approximately 50,000 inhabitants and about 450 births per year, is a mostly agricultural district in southern Bohemia without heavy industry; there are many forests in this mountainous region and only moderate levels of air pollution.
We restricted the study samples to full-term births of European origin. Preterm preterm /pre·term/ (-term´) before completion of the full term; said of pregnancy or of an infant.
adj. births ([is less than] 37 weeks gestation) were excluded from analysis because of the differences in factors affecting fetal growth (16). Pregnancies of women of non-European origin were excluded to avoid additional variability related to ethnic and cultural differences (9). Detailed health, personal, and lifestyle data were obtained via self-administered maternal questionnaires and medical records. We defined an IUGR birth as birth weight below the 10th percentile, by sex and gestational week, in the general Czech population. We estimated gestational age estimated gestational age
n. Abbr. EGA
The estimated age of a fetus, usually reported in weeks and based on the date of the last menstrual period. using each woman's last menstrual period last menstrual period Gynecology The most recent time that a ♀ notes menstruation, a datum recorded in a chart during a routine gynecologic visit. See Menstruation. date (LMP LMP left mentoposterior (position of fetus); last menstrual period.
last menstrual period
LMP Last menstrual period, see there ), decreasing the gestational age ges·ta·tion·al age
See estimated gestational age.
The estimated age of a fetus expressed in weeks, calculated from the first day of the last normal menstrual period. by 2 weeks [for more details, see Dejmek et al. (9)].
The concentrations of particulate matter [is less than or equal to] 10 [micro]m ([PM.sub.10]) and particulate matter [is less than or equal to] 2.5 [micro]m ([PM.sub.2.5]) were measured continuously using a Versatile Air Pollution Sampler (VAPS VAPS Video Arcade Preservation Society
VAPS Variable Assist Power Steering
VAPS Virtual Avionics Prototyping System
VAPS Virtual Applications Prototyping System
VAPS Virginia Power Shift (student conference on global climate change) ) (17); this modified dichotomous di·chot·o·mous
1. Divided or dividing into two parts or classifications.
2. Characterized by dichotomy.
di·chot sampler collects ambient aerosol in two fine particle samples and one coarse particle sample. We obtained 24-hr values directly from an analysis of the filters. PAHs were obtained by extraction of the polyurethane foam trap and quartz filters of VAPS (17). Twelve PAHs were extracted from the filters and analyzed by HPLC HPLC high-performance liquid chromatography.
high performance liquid chromatography.
HPLC High-performance liquid chromatography Lab instrumentation A highly sensitive analytic method in which analytes are placed with fluorometric detection according to U.S. Environmental Protection Agency Environmental Protection Agency (EPA), independent agency of the U.S. government, with headquarters in Washington, D.C. It was established in 1970 to reduce and control air and water pollution, noise pollution, and radiation and to ensure the safe handling and methods (18); seven of them, potentially carcinogenic to humans according to the International Agency for Research on Cancer The International Agency for Research on Cancer (IARC, or CIRC in its French acronym) is an intergovernmental agency forming part of the World Health Organisation of the United Nations.
Its main offices are in Lyon, France. (19), were evaluated separately as the sum of c-PAHs: chrysene, benz[a]anthracene anthracene (ăn`thrəsēn), C14H10, solid organic compound derived from coal tar. It melts at 218°C; and boils at 354°C;. , benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenz[a,h] anthracene, and indeno [ 1,2,3-c,d] pyrene.
We determined each mother's [PM.sub.10], [PM.sub.2.5], and c-PAHs levels using averages for each of nine consecutive 30-day periods after the estimated date of conception (EDC EDC
See: Export Development Corp. ); these periods correspond roughly to the 9 months of gestation. For each month, the pollutant data were divided into three categories for analysis: low (L), medium (M), and high (H). For [PM.sub.10] these cutoffs were L = [is less than] 40 [micro]g/[m.sup.3], M = 40 to [is less than] 50 [micro]g/[m.sup.3], and H = 50 [micro]g/[m.sup.3] or higher; for [PM.sub.2.5], L = [is less than] 27 [micro]g/[m.sup.3], M = 27-37 [micro]g/[m.sup.3], and H = 37 [micro]g/[m.sup.3] or higher; for c-PAHs, L = [is less than] 15 ng/[m.sup.3],M= 15 to [is less than] 30 ng/[m.sup.3],and H=30 ng/[m.sup.3] or higher. In the analyses, these categories were examined as dummy variables (medium vs. low, high vs. low). Finally, we analyzed continuous data to test for the possibility of a dose-response relationship.
We estimated adjusted odds ratios (AORs) and their 95% confidence intervals (CI) using logistic regression models (20). First, the crude odds ratios were estimated. A continuum of covariates associated with fetal growth or exposure was screened for inclusion into logistic models logistic models,
n.pl statistical models that describe the relationship between a qualitative dependent variable (that is, one that can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. . These were maternal age maternal age,
n the age of the mother at the period of conception. ([is less than] 19, 19-34, [is greater than] 34 years), maternal and paternal education (basic, high school, university), marital status marital status,
n the legal standing of a person in regard to his or her marriage state. (currently married, other), parity (first, second, third, higher), spontaneous abortion ([is less than] 2, [is greater than] 1), induced abortion in·duced abortion
Abortion caused intentionally by the administration of drugs or by mechanical means.
induced abortion ([is less than] 2, [is greater than] 1), alcohol habits of mother and father ([is less than] 1 drinks in a week, other), maternal smoking before conception (0, 1-9, [is greater than]9 cigarettes per day), passive smoking (0, 1-9, [is greater than] 9 cigarettes per day), paternal smoking (0, 1-9, [is greater than] 9 cigarettes per day), and employment of mother and father (employed or not).
Long-term and/or seasonal rhythms of conceptions in the Czech population were estimated on the basis of 10-year data from official statistics; a parameter "rhythm" was introduced weighting each calendar month by its relative contribution in long-term yearly totals. Each month of pregnancy was analyzed separately, allowing some factors to vary over time (e.g., pollutant levels, maternal smoking, alcohol consumption, and season). Although pollution levels were associated with season, season alone might also be a surrogate for other factors such as weather patterns or diet. "Summer" was defined as the months from April through September and "winter" as October through March. Some variables considered for analysis were correlated (e.g., smoking variables, maternal weight and height), and thus we used a stepwise stepwise
incremental; additional information is added at each step.
stepwise multiple regression
used when a large number of possible explanatory variables are available and there is difficulty interpreting the partial regression approach to develop the final models. Finally, we examined other factors for potential confounding confounding
when the effects of two, or more, processes on results cannot be separated, the results are said to be confounded, a cause of bias in disease studies.
confounding factor by comparing the AORs of IUGR for exposure to determine how much change resulted from inclusion versus exclusion of the potential confounder. A change in [Beta] of [is greater than] 15% was used as a reasonable criterion for inclusion (20). We used SAS (1) (SAS Institute Inc., Cary, NC, www.sas.com) A software company that specializes in data warehousing and decision support software based on the SAS System. Founded in 1976, SAS is one of the world's largest privately held software companies. See SAS System. version 6.12 for statistical analysis (21).
The mean monthly concentrations of pollutants fluctuate, with the highest values observed during winter and the lowest during summer (Figures 1 and 2). The mean annual levels of [PM.sub.10] in the Teplice district ([micro]g/[m.sup.3]) also changed during the 4 years of the study (Table 1). The mean annual concentrations of [PM.sub.10] were always much lower in the Prachatice district. In contrast, the mean yearly concentrations of c-PAHs were about the same. The mean monthly levels of c-PAHs were highly correlated with the concentration of particles in Teplice (r = 0.74, p [is greater than or equal to] 0.0001 for [PM.sub.10]; r = 0.78, p [is greater than or equal to] 0.0001 for [PM.sub.2.5]). Yearly correlations remained stable around 0.8 in all 4 years of the study in the Teplice region. A much lower PAH-particles correlation was observed in the Prachatice district. The overall correlation of c-PAHs in Prachatice was r = 0.58 for [PM.sub.10] and r = 0.53 for [PM.sub.2.5] (both p [is less than] 0.0001). In addition, the yearly correlation values of c-PAHs fluctuated for both PM classes between r = 0.35 in the second year and r = 0.85 in the third. The correlations between annual as well as total mean levels of the two overlapping classes of particles were invariably high in both districts (between 0.92 and 0.99).
Table 1. Yearly mean concentrations of pollutants in the two districts during the study period? Pollutant District 1st year [PM.sub.10] Teplice 48.7 [+ or -] 13.1 ([micro]g/ Prachatice 31.9 [+ or -] 11.1 [m.sup.3]) [PM.sub.2.5] Teplice 36.1 [+ or -] 12.9 ([micro]g/ Prachatice 28.7 [+ or -] 11.1 [m.sup.3]) c-PAH Teplice 13.3 [+ or -] 11.0 (ng/[m.sup.3]) Prachatice 8.2 [+ or -] 5.8 2nd year 3rd year [PM.sub.10] 42.7 [+ or -] 10.2 49.4 [+ or -] 12.5 ([micro]g/ 21.8 [+ or -] 7.9 30.9 [+ or -] 14.0 [m.sup.3]) [PM.sub.2.5] 30.8 [+ or -] 10.2 38.6 [+ or -] 11.0 ([micro]g/ 18.4 [+ or -] 6.7 24.9 [+ or -] 12.7 [m.sup.3]) c-PAH 9.5 [+ or -] 7.6 17.4 [+ or -] 13.0 (ng/[m.sup.3]) 9.9 [+ or -] 9.8 19.6 [+ or -] 18.5 4th year Total [PM.sub.10] 37.7 [+ or -] 17.9 44.9 [+ or -] 14.3 ([micro]g/ 25.0 [+ or -] 10.9 27.5 [+ or -] 11.8 [m.sup.3]) [PM.sub.2.5] 29.9 [+ or -] 16.7 33.9 [+ or -] 12.8 ([micro]g/ 19.5 [+ or -] 10.2 23.1 [+ or -] 11.1 [m.sup.3]) c-PAH 16.9 [+ or -] 18.0 14.0 [+ or -] 13.0 (ng/[m.sup.3]) 17.3 [+ or -] 16.7 13.1 [+ or -] 13.8 (a) Values shown are arithmetic means [+ or -] SDs.
A total of 3,349 pregnancies were included in the Teplice study sample; 322 (9.6%) of them exhibited IUGR. In the Prachatice sample 1,505 pregnancies were enrolled, 124 (8.2%) of which were IUGR. Ten covariates were included in the final models for analysis of all three pollutants studied: parity, maternal age and height, prepregnancy weight, education, marital status, month-specific maternal smoking, season, rhythm, and year of the study. We tested season and year for confounding, given their association with exposure and potential association with IUGR. Year, added alone to the final model, did not appreciably affect the results; season, however, did. When both season and year were added, confounding was noted, especially in the high exposure groups. Therefore, all subsequent analyses include season and year.
As a first step, we estimated the relative risk of IUGR for mothers exposed to low, medium, and high (L, M, H) levels of [PM.sub.10] and [PM.sub.2.5]; as in the previous analysis of 2-year data (9), a consistent association was found only in the first month of gestation. In Teplice, sample AORs of IUGR for [PM.sub.10] were M = 1.44 (CI, 1.03-1.2.02) and H = 2.14 (CI, 1.42-3.23). Corresponding values for [PM.sub.2.5] were M = 1.38 (CI, 0.95-1.92, p [is less than] 0.15) and H = 1.96 (CI, 1.02-3.11, p [is less than] 0.002). In the district of Prachatice, the only significant association was also observed in the first gestational month, but the results were not consistent: AORs of IUGR for [PM.sub.10] were M = 2.11 (CI, 1.03-4.33) and H = 1.09 (CI, 0.49-2.46; Table 2). No statistically significant association at any stage of gestation was found for [PM.sub.2.5] in the Prachatice sample. The analysis using dummy variables indicated the exposure-response relationships; this suggestion was tested by analyzing the continuous data. For each 10 tag increase of [PM.sub.10] in the first gestational month, the AORs of IUGR in Teplice increased significantly by 1.19 (CI 1.06-1.33, p [is less than] 0.003); this value was only 1.04 (CI, 0.86-1.27, p [is less than] 0.7) for the Prachatice region (Table 3).
Table 2. AORs of IUGR by c-PAHs and [PM.sub.10] in the first gestational month in Teplice and Prachatice. Medium(a) Pollutant Specification District AOR(b) 95% CI [PM.sub.10] -- Teplice 1.44 (1.03-2.02) -- Prachatice 2.11 (1.03-4.33) c-PAHs -- Teplice 1.59 (1.06-2.39) -- Prachatice 1.49 (0.81-2.73) < 7.5 km Prachatice 1.89 (0.56-6.29) (n = 551)(c) Lower Prachatice 1.63 (0.87-3.06) cut-offs(d) High(a) Pollutant AOR(b) 95% CI [PM.sub.10] 2.14 (1.42-3.23) 1.09 (0.49-2.46) c-PAHs 2.15 (1.27-3.63) 1.26 (0.60-2.63) 2.44 (0.60-9.83) 2.39 (1.01-5.65) (a) See text for cutoffs. (b) Adjusted for parity, maternal age and height, prepregnancy weight, education, marital status, month-specific maternal smoking, season, rhythm, and year of the study. (c) Only mothers living up to 7 km from the monitor station in Prachatice region. (d) c-PAHs: low = < 2 ng/[m.sup.3]; Medium = 2 to < 20 ng/[m.sup.3]; High = [is greater than or equal to] 20 ng/[m.sup.3]. Table 3. AORs of IUGR by c-PAHs and [PM.sub.10] in the first gestational month in Teplice and Prachatice: models with continuous variables. Pollutant/ Crude increase District OR 95% CI PM.sub.10] 10 [micro]g/ Teplice 1.07 (0.99-1.16) [m.sup.3] 10 [micro]g/ Prachatice 1.07 (0.92-1.24) [m.sup.3] c-PAHs 10 ng/[m.sup.3] Teplice 1.08 (1.00-1.18) 10 ng/[m.sup.3] Prachatice 1.08 (0.95-1.22) Pollutant/ increase AOR(a) 95% CI PM.sub.10] 10 [micro]g/ 1.19 (1.06-1.33) [m.sup.3] 10 [micro]g/ 1.04 (0.86-1.27) [m.sup.3] c-PAHs 10 ng/[m.sup.3] 1.22 (1.07-1.39) 10 ng/[m.sup.3] 1.17 (0.92-1.89) (a) Adjusted for parity, maternal age and height, prepregnancy weight, education, marital status, month-specific maternal smoking, season, rhythm, and year of the study.
The crude odds ratios of IUGR increased exclusively for c-PAH levels in the first gestational month in Teplice (M = 1.17, CI, 0.90-1.52, p [is less than] 0.24; H = 1.32, CI, 0.94-1.87, p [is less than] 0.10). AORs of IUGR for c-PAHs in the Teplice district are presented in Figure 3. A consistent and significant association of IUGR was observed again in the first month of pregnancy, when M = 1.59 (CI, 1.06-2.39, p [is less than] 0.025) and H = 2.15, (CI, 1.27-3.63, p [is less than] 0.0043; Table 2 and Figure 3). However, in contrast to our expectation about particulate matter, IUGR risk seemed to be related to exposure during late pregnancy. AORs of IUGR for exposure to medium and high c-PAHs levels during the eighth gestational month were M = 1.52 (CI, 1.02-2.27, p [is less than] 0.05) and H = 1.51 (CI, 0.92-2.47, p [is less than] 0.10; Figure 3).
Using the same cutoffs for Prachatice, IUGR showed no association with c-PAH levels in the first gestational month (AOR for M = 1.49, CI, 0.81-2.73, p [is less than] 0.19; H = 1.26, CI, 0.60-2.63, p [is less than] 0.54; Table 2). However, for mothers living less than 7.5 km from the monitoring station, the values of AOR were M = 1.89 (CI, 0.56-6.29) and H = 2.44 (CI, 0.60-9.83; Table 2). Thus, in this area the AORs were close to those for Teplice, though not significant (mostly due to the smaller sample size; n = 551). It may be expected that the accuracy of the exposure estimates would be higher for mothers living nearer to the monitor (22). When other concentration intervals were checked, the cutoffs L [is less than] 2 ng/[m.sup.3], M 2-[is less than]20, and H [is greater than or equal to] 20 gave a good dose-effect scale. Using these lower cutoffs and the whole Prachatice data set, the results were similar to those for the Teplice district. Again, the only consistent c-PAH/IUGR association was observed in the first gestational month (AOR for M = 1.63, CI, 0.87-3.06, p [is less than] 0.13; H = 2.39, CI, 1.01-5.65, p [is less than] 0.045; Table 2).
The analysis of continuous data revealed an exposure-response relationship between c-PAH levels in the first month of gestation and IUGR even in the crude ORs (Table 3). This relationship was highly significant, especially after adjustment: each 10-ng increase in c-PAH levels in the Teplice district resulted in an increase of AORs by 1.22 (CI, 1.07-1.39, p [is less than] 0.004; Table 3); a similar, but nonsignificant non·sig·nif·i·cant
1. Not significant.
2. Having, producing, or being a value obtained from a statistical test that lies within the limits for being of random occurrence. increase was found for Prachatice (1.17, CI, 0.92-1.89). No significant difference of AORs from 1.0 was observed in any gestational month other than the first. This was also valid for the eighth month of pregnancy in Teplice (AOR = 1.06, CI, 0.93-1.22), for which a weak association was found using the analysis of dummy variables.
Air pollution levels were changing during the study period in Teplice as well as in Prachatice (Figures 1 and 2). The annual averages of particulate matter decreased in the second and fourth years in both districts without any general tendency. In contrast, c-PAH levels were low in the first 2 years (approximately 10 ng/[m.sup.3]) and increased considerably in the last 2 years in both localities (Table 1). The most important phenomena were that levels of particulate matter were always higher by 60-70% in the Teplice region than in Prachatice, and c-PAH levels were rather high and similar in both districts (Table 1). This situation enabled us to evaluate the influence of particles and PAHs more or less independently. Such an evaluation would not be possible using the Teplice data set alone.
Despite the similar annual averages, there were differences between the c-PAH pollution patterns in the two districts. The c-PAH/PM correlations were high in the Teplice region (around 0.8), and the correlation matrix there was relatively stable through all the 4 years studied. The mean total c-PAHs/PM correlation in Prachatice was much lower and fluctuated considerably between 0.34 and 0.87 in individual years. This may be connected with a particular phenomenon discovered in 1998 during Teplice program research activities (23): There is one extremely potent point-source of PAHs in Prachatice town (close to the monitoring station): emissions from the chimney of a small furniture factory. These emissions seem to be a significant source of PAHs throughout the whole district. However, it is unlikely that these emissions are dispersed uniformly in the area's broken, mountainous terrain. It is possible that the differences in the dose--effect association course between the two districts may be connected with emissions from the furniture factory. Confirming this association in Prachatice will require using either a smaller area with more reliable exposure estimates or lower cutoffs. However, the results of the continuous data analysis demonstrated that the IUGR/c-PAHs association is as real a phenomenon in Prachatice as it is in the Teplice region.
A possible relationship between the two pollutants and fetal growth was examined in 9 monthly exposure windows from conception until delivery to evaluate potentially sensitive stages of prenatal development. Initially the association of IUGR with exposure to two overlapping classes of particles, [PM.sub.10] and [PM.sub.2.5], was evaluated. This relationship was previously observed in the same population using a smaller, 2-year Teplice data set (9). The results of the present analysis for the Teplice district are similar to those of our recently published study. IUGR risk was associated with the concentration of particles exclusively in the first month of gestation. The AORs for [PM.sub.10] in the previous and the present study were 1.62 and 1.42 for medium levels and 2.64 and 2.10 for high levels, respectively. The AOR values seem to be slightly lower in the present study, though at the same levels of significance. As in the previous 2-year study, the association of IUGR with [PM.sub.2.5] in early gestation is weaker than the association with [PM.sub.10]: the AORs are lower than for [PM.sub.10] and they are significant for high levels only.
In Prachatice the association of IUGR risk with [PM.sub.10] levels was not significant either in the analysis using concentration categories or in analysis of continuous data (Tables 2 and 3). Thus, the significant elevation of IUGR risk found in Prachatice (9) for those exposed to [PM.sub.10] = 40 [micro]g/[m.sup.3] during preliminary analysis was not confirmed in the present larger data set. The results for the [PM.sub.2.5] fraction in the Prachatice region also provided no significant information.
A sensitive period for retardation of fetal growth in early gestation observed for particulate matter in Teplice was also seen for c-PAHs. The AORs of IUGR we. re consistently rising with the levels of c-PAHs in the first month, and this relationship was highly significant; the same time trend, though not always significant, held true for Prachatice (Tables 2 and 3, Figure 3).
Thus, the first gestational month seems to be the critical period for the effects of pollution on fetal growth. The timing of this association is in agreement with the current hypothesis that IUGR pathogenesis is triggered by an abnormal reaction between the trophoblast and uterine tissues in the first weeks of pregnancy (24). The altered growth may arise from defective trophoblast invasion, resulting in suboptimal Suboptimal
A solution is called suboptimal if a part of the solution has been optimized without regards to the overall objective. placentation and maternal hemodynamic he·mo·dy·nam·ics
n. (used with a sing. verb)
The study of the forces involved in the circulation of blood.
he maladaptation mal·ad·ap·ta·tion
Faulty or inadequate adaptation. (15,25).
The ability of PAHs to reach placental placental
pertaining to or emanating from placenta.
the placental separation of maternal and fetal blood which varies in its structure and permeability between the species. tissue has been suggested in many experimental and human studies of aryl ar·yl
An organic radical derived from an aromatic compound by the removal of one hydrogen atom. hydrocarbon hydroxylase (AHH AHH AllHipHop.com (website)
AHH Aryl Hydrocarbon Hydroxylase
AHH Arizona Heart Hospital
AHH Ace's Happy Homepage
AHH Adaptive Hard Handoff ) activities in placenta placenta (pləsĕn`tə) or afterbirth, organ that develops in the uterus during pregnancy. It is a unique characteristic of the higher (or placental) mammals. In humans it is a thick mass, about 7 in. and cord blood cord blood
Blood present in the umbilical vessels at the time of delivery. (26-29). Hatch at al. (30) suggested that the placenta and the fetus are targets for DNA damage: PAH-DNA adducts were found in the placenta and various fetal organs from spontaneously aborted fetal tissue from nonsmoking non·smok·ing
1. Not engaging in the smoking of tobacco: nonsmoking passengers.
2. Designated or reserved for nonsmokers: the nonsmoking section of a restaurant. women. This idea was confirmed in many later studies observing PAH-DNA adducts in term placentas and cord blood (13,31,32). Using monoclonal antibodies, Zenzes et al. (33) found benzo[a]pyrene diol diol
an organic compound containing two hydroxy groups, a dihydric alcohol. Called also glycol. epoxide epoxide /epox·ide/ (e-pok´sid) an organic compound containing a reactive group resulting from the union of an oxygen atom with two other atoms, usually carbon, that are themselves joined together. DNA adducts even in preimplantation human embryos.
Little is known about a possible mechanism of the observed PAH PAH, PAHA aminohippuric acid.
PAH 1 Polycyclic aromatic hydrocarbon, see there 2. Pulmonary artery HTN influence on fetal growth. A direct effect of PAHs on receptors for epidermal growth factor Epidermal growth factor or EGF is a growth factor that plays an important role in the regulation of cell growth, proliferation and differentiation. Human EGF is a 6045 Da protein with 53 amino acid residues and three intramolecular disulfide bonds. (EGF EGF
epidermal growth factor ) and insulin-like growth factors insulin-like growth factors (IGF),
n a group of polypeptides responsible for the activity of growth hormones, similar in chemical structure to insulin. (IGF (Internet Governance Forum) An international organization of governments and U.N. agencies that was founded to discuss Internet issues such as security and spam. It was created at the United Nations Summit in 2005 after the U.S. ) I and II in placental cells was found by Guyda (34); these changes tended to influence placental growth. Benzo[a]pyrene, one of the carcinogenic PAHs, was the most potent PAH tested. Benzo[a]pyrene inhibited EGF more significantly than IGF or insulin receptor insulin receptor A heterodimeric membrane receptor composed of α and
β chains, which has tyrosine kinase activity after binding insulin; IR deficiency is a rare cause of DM and may be due to a gene rearrangement, causing a deletion in the binding in early gestation placentas (34). This observation was recently confirmed by Zhang et al. (35), who showed that benzo[a]pyrene mediates a loss of EGF receptors and alters trophoblast proliferation as well as its endocrine function. This indicates that PAHs may directly affect early trophoblast proliferation due to their reaction with growth factor receptors. In this way feto-placental exchange and, consequently, fetal nourishment and growth, may be impaired.
The fetotoxicity of PAHs has been demonstrated in several experimental studies. Prenatal exposure to benzo[a]pyrene affected fetal development and viability and lowered litter weights in rats and mice (36,37). However, the experimental daily dose of 10 mg benzo[a]pyrene/kg body weight that was used is about 1 million times the mainstream dose in 100 cigarettes (38). Therefore, the mechanism involved and also the biological end points may be substantially different. In addition, Shum et al. (39) suggested a genetic predisposition genetic predisposition Molecular medicine The tendency to suffer from certain genetic diseases–eg, Huntington's disease, or inherit certain skills–eg, musical talent to AHH induction, hypothesizing that the genotype of both parents may determine the reproductive effects of PAHs on the offspring. This idea was recently confirmed in the polluted regions of Poland (40) and the Czech Republic (13).
The question about the respective role of particles and c-PAHs should be studied further.
Examining the Teplice data, the shape and size of the association between c-PAHs and IUGR were similar to those of particles and IUGR; these results did not provide a sufficient indication of which of these two relationships is the primary one. This striking similarity may be' partly due to the high correlation between PAHs and particle levels. It is also well known that PAHs, especially those with larger molecules, are mostly adsorbed on fine particles (10,11).
Thus, the results based on the Teplice data alone are consistent with the idea that the effects of c-PAHs and particles on IUGR could be combined, probably in an additive rather than in a synergistic manner. However, another hypothesis, that only one of the two factors--either particulate matter or c-PAHs--may be the major etiological etiological
pertaining to etiology.
the name of a disease which includes the identification of the causative agent, e.g. Streptococcus agalactiae mastitis. factor, is also compatible with the results. There are many observations that support the idea of a primary role of c-PAHs and their reactive derivatives in the observed slow-down of fetal growth.
* The observed association of the IUGR risk with particulate matter could be explained due to the close correlation between both noxae, particles and PAHs, irrespective of the real effects of particles.
* Another argument follows from the analysis of the Prachatice data set: the levels of particles in this region were considerably lower during the study period (Table 1, Figure 1). It was shown that the effects of c-PAHs combined with low levels of PM in Prachatice were as strong as in Teplice, where c-PAHs occur simultaneously with much higher levels of particles (Tables 2 and 3). Also, the differences in the prevalence of IUGR between Teplice and Prachatice were relatively small (9.5 vs. 8.3, respectively), in spite of large differences in the levels of particulate matter. This shows that the influence of c-PAHs on fetal growth is more or less independent of the relative PM concentrations.
* At this time almost nothing is known about a possible mechanism of the reproductive effects of particulate matter. There is some information that may contribute to a plausible explanation of the effects of PAHs on fetal development and growth: PAHs may penetrate the human placenta and different fetal tissues (28-30), and c-PAHs may directly interfere with placental growth factors (34,35).
These arguments in favor of c-PAH influence on fetal growth do not rule out a simultaneous influence of particles. Airborne particles always originate in combustion processes together with polynuclear polynuclear /poly·nu·cle·ar/ (-noo?kle-er) having several nuclei; said of cells.
pol·y·nu·cle·ar or pol·y·nu·cle·ate or pol·y·nu·cle·at·ed
Multinuclear. organic compounds. Thus, c-PAHs and airborne particulate matter always operate simultaneously. The critical point seems to be the proportion of organic compounds adsorbed on fine particles. The observed association between particles and IUGR could be at least partly explained by the presence of c-PAHs and their highly biologically active derivatives. Fine particles might influence the transport, penetration, and deposition of organic compounds. Because respiratory tract respiratory tract
The air passages from the nose to the pulmonary alveoli, including the pharynx, larynx, trachea, and bronchi.
Respiratory tract deposition of particles generally increases with size from 2.5 [micro]m to 10 [micro]m (41), [PM.sub.10] may better represent an individual's total exposure, as supported by the results of the present study.
It can be concluded that the risk of delivering a growth-retarded infant increases with the level of fine particles and c-PAHs in early gestation (first month). Our results support the hypothesis that c-PAHs play a primary role in the retardation of fetal growth. According to some experimental results, c-PAHs may directly modulate the proliferation of the trophoblast due to their reaction with receptors for placental growth factors. In this way the feto-placental, exchange of oxygen and nutrients may be reduced and fetal growth can be impaired. The present results show that the effects of c-PAHs on fetal growth can be more or less independent of the concentration of associated particulate matter. In contrast, the impact of airborne particles on fetal growth may depend on the proportion of c-PAHs adsorbed on fine particles. However, the results cannot exclude other explanations, including some interaction between the effects of particles and PAHs on fetal growth. Particulate matter can influence the transport and penetration of c-PAHs from the ambient air into the maternal organism. Further investigation of the simultaneous impact of particles and PAHs on pregnancy outcome is needed. The effects of PAHs on the fetus may be affected by the genotypes of the parents. Elucidating the influence of genetic polymorphisms on pregnancy outcome and specifically on IUGR induction will certainly be a task for future research.
REFERENCES AND NOTES
(1.) Dockery DW, Pope CA, Xu X, Spengler ID, Ware JH, Fay IH, Fay ME, Ferris BG, Speizer FE. An association between air pollution and mortality in six U.S. cities. N Engl J Med 329:1753-1759 (1993).
(2.) Katsouyanni K. Health effects of air pollution in southern Europe: are there interacting factors? Environ Health Perspect 103(suppl)2:23-27 (1995).
(3.) Bobak M, Leon DA. Air pollution and infant mortality (hardware) infant mortality - It is common lore among hackers (and in the electronics industry at large) that the chances of sudden hardware failure drop off exponentially with a machine's time since first use (that is, until the relatively distant time at which enough mechanical in the Czech Republic, 1986-1988. Lancet 340:1010-1014 (1992).
(4.) Bobak M, Leon DA. Pregnancy outcomes and outdoor levels of air pollution: an ecological study in districts of Czech Republic 1986-1988. Occup Environ Med 56:539-543 (1999).
(5.) Sram RJ. Impact of air pollution on reproductive health [Editorial). Environ Health Perspect 107:A542-A 543 (1999).
(6.) Wang X, Ding H, Ryan L, Xu X. Association between air pollution and low birth weight: a community-based study. Environ Health Perspect 105:514-520 (1997).
(7.) Woodruff TI, Grillo J, Schoendorf KC. The relationship between selected causes of post-neonatal infant mortality and particulate air pollution in the United States. Environ Health Perspect 105:606-612 (1997).
(8.) Xu X, Ding H, Wang X. Acute effects of total suspended particles and sulfur dioxides on preterm delivery; a community-based cohort study. Arch Environ Health 50:407-415 (1995).
(9.) Dejmek J, Selevan SG, Benes I, Solansky I, Sram RJ. Fetal growth and parental exposure to particulate matter during gestation. Environ Health Perspect 107:475-480 (1999).
(10.) Schuetzle D, Lee FS, Prater prate
v. prat·ed, prat·ing, prates
To talk idly and at length; chatter.
To utter idly or to little purpose.
n. TJ. The identification of polynuclear aromatic hydrocarbon (PAH) derivatives in mutagenic mutagenic
inducing genetic mutation. fractions of diesel exhaust. Int J Environ Anal Chem 9:93-144 (1981).
(11.) Morozzi G, Conti Conti (kôNtē`), cadet branch of the French royal house of Bourbon. Although the title of prince of Conti was created in the 16th cent. R, Pampanella I, Marchetti, Bucci P, Scardazza F, Manenti R, Sebastiani B. Chemical analysis and biological activity of airborne particulate matter. J Environ Pathol Toxicol Oncol 16:219-225 (1997).
(12.) Binkova B, Vesely D, Vesela D, Jel'nek R, Sram RI. Genotoxicity and embryotoxicity of urban air particulate matter collected during winter and summer period in two different districts of the Czech Republic
The Czech Republic used to be divided into seventy-three districts (okresy, sing. okres); three statutory cities with the status of districts (Statutární města, sing. . Mutat Res 440:45-58 (1999).
(13.) Sram RJ, Binkova B, Rossner P, Rubes Rubes is a syndicated newspaper single panel cartoon created by Leigh Rubin in 1984.
Leigh Rubin began making and distributing his own greeting cards in 1979 through his company Rubes. J, Topinka J, Dejmek J. Adverse reproductive outcomes from exposure to environmental mutagens. Mutat Res 428:203-215 (1999).
(14.) Dockery DW. Epidemiologic study epidemiologic study A study that compares 2 groups of people who are alike except for one factor, such as exposure to a chemical or the presence of a health effect; the investigators try to determine if any factor is associated with the health effect design for investigating respiratory health effects of complex air pollution mixtures. Environ Health Perspect 101(suppl 4):187-191 (1993).
(15.) Duvekot JJ, Cheriex EC, Pieters FAA. Severely impaired growth is preceded by maternal hemodynamic maladaptation in very early pregnancy. Acta Obstet Gynecol Scand 74:693-697 (1995).
(16.) Villar J, Belizan JM. The relative contribution of prematurity and fetal growth retardation to low birth weight in developing and developed societies. Am J Obstet Gynecology 143:793-798 (1982).
(17.) Pinto JP, Stevens RK, Willis RD, Kellogg R, Mamane Y, Novak J, Santroch J, Benes I, Lenicek J, Bures V. Czech air quality monitoring and receptor modeling study Environ Sci Technol 32:843-854 (1998).
(18.) U.S. EPA EPA eicosapentaenoic acid.
n.pr See acid, eicosapentaenoic.
n. . Methods for Determination of Toxic Organic Compounds in Ambient Air. EPA 600/4-84-041. Research Triangle Park Research Triangle Park, research, business, medical, and educational complex situated in central North Carolina. It has an area of 6,900 acres (2,795 hectares) and is 8 × 2 mi (13 × 3 km) in size. Named for the triangle formed by Duke Univ. , NC:U.S. Environmental Protection Agency, 1984.
(19.) IARC. Evaluation of the carcinogenic risk of chemicals to humans: polynuclear aromatic compounds. IARC Monogr Eval Carcinog Risks Hum 34:101-131 (1984).
(20.) Rothman KJ, Greenland S. Modern Epidemiology, 2nd ed. Philadelphia, PA:Lippincot-Raven Publishers, 1998;256-257.
(21.) SAS/STAT Software. Changes and Enhancements for Release 6.12. Cary, NC:SAS Institute Inc., 1997.
(22.) Dejmek J, Jelinek R, Solansky I, Benes, I, Sram Rj. Fecundability fecundability /fe·cun·da·bil·i·ty/ (fe-kun?dah-bil´i-te) the probability that conception will occur in a given population of couples during a specific time period. and parental exposure to ambient sulfur dioxide. Environ Health Perpect 108:647-654 (2000).
(23.) Bures V, Novak J. Evaluation of polyaromatic hydrocarbons from selected sources in Teplice Program [in Czech]. Ochrana Ovzdusi 11:6-10 (1999).
(24.) Khong TY, De Wolf F, Robertson WB, Brosens I. Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-for-gestational age infants. Br J Obstet Gynecol 93:1049-1059 (1986).
(25.) Roberts JM, Taylor RN, Goldfein A. Clinical and biochemical evidence of endothelian cell dysfunction in the pregnancy syndrome preeclampsia preeclampsia /pre·eclamp·sia/ (pre?e-klamp´se-ah) a toxemia of late pregnancy, characterized by hypertension, proteinuria, and edema.
n. . Am J Hypertens 4:700-708 (1991).
(26.) Manchester DK, Parker NB, Bowman CM. Maternal smoking increases xenobiotic xen·o·bi·ot·ic
Foreign to the body or to living organisms. Used of chemical compounds.
A xenobiotic chemical.
any substance, harmful or not, that is foreign to the animal's biological system. metabolism in placenta but not in umbilical vein umbilical vein
The left umbilical vein. endothelium endothelium /en·do·the·li·um/ (-the´le-um) pl. endothe´lia the layer of epithelial cells that lines the cavities of the heart, the serous cavities, and the lumina of the blood and lymph vessels. . Pediatr Res 18:1071-1075 (1984).
(27.) Huel G, Godin J, Girard F, Sahuquillo J, Hellier G, Blot P. Aryl hydrocarbon hydroxylase activity in human placenta of passive smokers. Environ Res 50:173-183 (1989).
(28.) Huel G, Girard F, Nessmann C, Godin J, Blot P, Breart G, Moreau T. Placental aryl hydrocarbon hydroxylase activity and placental calcifications. Toxicology 71:257-266 (1992).
(29.) Huel G, Godin J, Frery N, Girard F, Moreau T, Nessmann C, Blot P. Aryl hydrocarbon hydroxylase activity in human placenta and threatened preterm delivery. J Expo Anal Environ Epidemiol 3(suppl 1) :187-189 (1993).
(30.) Hatch MC, Warburton D, Santella RM. Polycyclic polycyclic
having two or more usually fused chemical ring structures in their molecule.
thyroid initiators, i.e. they increase the incidence of thyroid tumors. aromatic hydrocarbon-DNA adducts in spontaneously aborted fetal tissue. Carcinogenesis car·ci·no·gen·e·sis
The production of cancer.
production of cancer.
viruses and some parasites are capable of initiating neoplasia. 11:1673-1675 (1990).
(31.) Madhavan ND, Naidu K. Polycyclic aromatic hydrocarbons in placenta, maternal blood, umbilical cord blood umbilical cord blood Transplantation A source of primitive and stem cells that can be used to reconstitute BM destroyed by aplastic anemia or by RT or chemotherapy for CA, lymphoproliferative malignancies. See Bone marrow transplantation, Stem cell therapy. and milk of Indian women. Hum Exp Toxicot 14:503-506 (1995).
(32.) Arnould JP, Verhoest P, Bach V, Libert JP, Belegaud J. Detection of benzo[a]pyrene-DNA adducts in human placenta and umbilical cord blood. Hum Exp Toxicol 16:716-721 (1997).
(33.) Zenzes MT, Puy Pu´y
n. 1. See Poy. LA, Bielicki R, Reed TE. Detection of benzo[a]pyrene diol epoxide-DNA adducts in embryos from smoking couples: evidence for transmission by spermatozoa spermatozoa
see spermatozoon. . Mol Hum Reprod 5:125-131 (1999).
(34.) Guyda HI. Metabolic effects of growth factors and poly-cyclic aromatic hydrocarbons on cultured human placental cells of early and late gestation. J Clin Endocrinol Metab 72:718-723 (1991).
(35.) Zhang L, Connor EE, Chegini N, Shiverick KT. Modulation by benzo[a]pyrene of epidermal growth factor receptors, cell proliferation, and secretion of human chorionic gonadotropin human chorionic gonadotropin (HCG): see gonadotropic hormone. in human placental lines. Biochem Pharmacol 50:1171-1180 (1995).
(36.) Ridgon RH, Rennels EG. Effect of feeding benzpyrene on reproduction in the rat. Experientia 4:224-226 (1964).
(37.) MacKenzie KM, Angevine DM. Infertility in mice exposed in utero in utero (in u´ter-o) [L.] within the uterus.
In the uterus.
in utero adv. to benzo[a]pyrene. Biol Reprod 24:83-191 (1981).
(38.) Kristensen P, Eilertsen E, Einarsdottir E, Haugen A, Skaug V, Ovrebo S. Fertility in mice and prenatal exposure to benzo[a]pyrene and inorganic lead. Environ Health Perspect 103:588-590 (1995).
(39.) Shum S, Jensen NM, Nebert DW. The murine murine /mu·rine/ (mur´en) pertaining to, derived from, or characteristic of mice or rats.
adj. Ah locus: in utero toxicity and teratogenesis teratogenesis /ter·a·to·gen·e·sis/ (ter?ah-to-jen´e-sis) the production of birth defects in embryos and fetuses.teratogenet´ic
n. associated with genetic differences in benzo[a]pyrene metabolism. Teratology teratology /ter·a·tol·o·gy/ (ter?ah-tol´ah-je) that division of embryology and pathology dealing with abnormal development and the production of congenital anomalies.teratolog´ic
n. 20:365-376 (1979).
(40.) Perere FP, Whyatt RM, Jendrychowski W, Raugh V, Manchester D, Santella RM, Ottman R. Recent developments in molecular epidemiology molecular epidemiology Molecular medicine An evolving field that combines the tools of standard epidemiology–case studies, questionnaires and monitoring of exposure to external factors with the tools of molecular biology–eg, restriction endonucleases, . A study of the effects of environmental polycyclic aromatic hydrocarbons on birth outcomes in Poland. Am J Epidemiol 47:309-314 (1998).
(41.) Schlesinger RB. Deposition and clearance of inhaled particles. In: Concepts in Inhalation Toxicology (McClellan RO, Henderson RF, ads). New York New York, state, United States
New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of :Hemisphere Publishing Corp, 1989;163-192.
Address correspondence to J. Dejmek, Laboratory of Genetic Ecotoxicology The term ecotoxicology was coined by Truhaut in 1969, who defined it as "the branch of toxicology concerned with the study of toxic effects, caused by natural or synthetic pollutants, to the constituents of ecosystems, animal (including human), vegetable and microbial, in an , Institute of Experimental Medicine, Academy of Sciences of the Czech Republic The Academy of Sciences of the Czech Republic Czech: Akademie věd České republiky, abbr. AV ČR , 142 20 Prague 4, Videnska 1083, Czech Republic. Telephone: +420-2-4724756. Fax: +4202-4752785. E-mail: email@example.com
We are grateful to the many gynecologists and their staffs from the Departments of Obstetrics and Gynecology obstetrics and gynecology
Medical and surgical specialty concerned with the management of pregnancy and childbirth and with the health of the female reproductive system. in the hospitals of Teplice, Duchcov, Prachatice, Vimperk, and Pisek. We thank them for their dedication and participation in this study. We also thank our colleagues from the District Institutes of Hygiene in Teplice and Prachatice for their support and collaboration.
This work was supported by grants from the Czech Ministry of Environment (Teplice Program II), the U.S. Environmental Protection Agency/U.S. Agency for International Development, and the Commission of European Communities (PHARE II, EC/HEA-18/CZ). This work is attributed to the Laboratory of Genetic Ecotoxicology, Regional Institute of Hygiene of Central Bohemia and Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague. Received 8 February 2000; accepted 15 August 2000.
Jan Dejmek,(1) Ivo Solansky,(1) Ivan Benes,(2) Jan Lenicek,(3) Radim J. Sram(1)
(1)Laboratory of Genetic Ecotoxicology, Regional Institute of Hygiene of Central Bohemia and Institute of Experimental Medicine, Academy of Science of the Czech Republic, Prague, Czech Republic; (2)District Institute of Hygiene, Teplice, Czech Republic; (3)Regional Institute of Hygiene, Usti nad Labem Ú·stí nad La·bem
A city of northwest Czech Republic on the Elbe River near the German border. Population: 96,100. , Czech Republic