Measuring the effects of pesticides on occupationally exposed humans with the comet assay.

In this study we examine the effects of a mixture of pesticides on occupationally exposed agricultural workers. The study was performed on 149 people, 84 agricultural workers and 65 healthy men from the same area, who served as the control group. The exposed group was divided into a subgroup with 65 individuals moderately exposed (39 men and 26 women) and a highly exposed subgroup consisted of 19 men. The statistical analysis of the comet assay results showed that there were no significant differences in basal DNA damage between pesticide-exposed workers and the control group nor between moderately and highly exposed ones. In addition, exposure of peripheral blood lymphocytes to hydrogen peroxide or gamma-irradiation led to a similar degree of DNA damage and subsequent repair for all the studied populations.

Description and mission evaluation of the Hungarian case-control surveillance of congenital abnormalities, 1980-1996.

BACKGROUND: The Hungarian Case-Control Surveillance of Congenital Abnormalities was established in 1980. This article describes how the Hungarian Case-Control Surveillance of Congenital Abnormalities was first organized and is currently maintained. The baseline statistics are provided and potential venues of postmarketing surveillance of drug teratogenicity and other public health tasks and research are proposed. METHODS: Cases with congenital abnormalities and patient controls with Down syndrome were selected from the Hungarian Congenital Abnormality Registry. Population controls without congenital abnormalities were selected from the National Birth Registry on the basis of three matching criteria: sex, week of birth, and district of parent's residence. Three sources of information concerning drug exposures, maternal disorders, and pregnancy complications, among others, were used: (1) prospective and medically recorded data from antenatal care logbooks and discharge summaries; (2) retrospective maternal self-reported data obtained with a structured questionnaire in all the three study groups; and (3) data collected by regional nurse in house visits to nonrespondent cases and patient controls. Twenty-five congenital abnormality groups were evaluated. During the 17-year period of data collection, 22,843 cases, 38,151 population controls, and 834 patient controls were incorporated into the data set, constituting the largest population-based case-control data set of congenital abnormalities to date. RESULTS: Demographic features of pregnant women and informative offspring are presented along with the distribution of 25 main groups of congenital abnormalities. CONCLUSIONS: This system is appropriate for postmarketing the surveillance of drug teratogenicity, for the improvement of congenital abnormality diagnosis, to get informed consent, to have a communication with parents and to provide material for research.

Spina bifida and parental occupation: results from three malformation monitoring programs in Europe.

As the evidence for an association between spina bifida and parental agricultural occupations is inconclusive, we evaluated this association and the potential associations between spina bifida and other parental occupations. Three register-based case-referent studies were conducted in Sweden, Spain, and Hungary. From the registries of congenital malformations in each country, 482, 478, and 1119 cases with spina bifida were identified, respectively. Identified as referents were 964, 434, and 1489 children without abnormalities. Information on parental occupation was available in the registries from questionnaires or interviews conducted among the parents. Occupations with a potential for physical or chemical exposure were compared to non-exposed occupations. Increased odds ratios (ORs) were observed for women in agricultural occupations in Sweden (OR: 1.8, 95% CI: 0.8-4.2) and in Spain (OR: 2.2, 95% CI: 0.8-5.9), but not in Hungary (OR: 1.1, 95% CI: 0.7-1.7). Several other parental occupations were analysed, but the associations with spina bifida were inconsistent. Concluding, the results are not totally consistent but point to an increased risk of spina bifida among women in agricultural occupations.

Time trends in neural tube defects prevalence in relation to preventive strategies: an international study.

OBJECTIVE: To examine time trends in neural tube defects (NTD) prevalence from 1987 to 1996 in relation to the primary prevention policies for folic acid supplementation strategies in different countries. DESIGN: Retrospective time trends analysis of NTD prevalence. SETTING: 11 birth defect registries of congenital malformations participating in the International Clearinghouse for Birth Defects Monitoring System, in the period from 1 July 1987 to 30 June 1996. SUBJECTS: 8207 live births, stillbirths and terminated pregnancies affected by anencephaly or spina bifida registered by the 11 participating centres 1987-1996. OUTCOME MEASURES: Prevalence rate ratios based on the annual rates, using the Poisson regression model. RESULTS: During the study period a significant fall in prevalence rates for all NTD is present in Atlanta (USA), England and Wales, Hungary and Japan, and a significant rise in Norway and South America. After adjusting for the secular trends observed in the earlier years of the study, no significant trend can be attributed to preventive strategies. Data on NTD prevalence are supplemented with information on folate awareness among some of the populations studied. CONCLUSION: There is no evidence that, up to the middle of 1996, any change in time trend was attributable to the introduction of national folate supplementation policies. The possible effectiveness of folate supplementation policies for the reduction of NTD clearly needs to be tried and studied for several more years. Considering that in the Western world about 50% of pregnancies are unplanned, a policy that rests on action taken before conception can only have limited success. Strategies based on food enrichment, such as was introduced in the USA from the beginning of 1998, may prove to be more successful.

Using the Hungarian Birth Defects Registry for surveillance, research and intervention.

The Hungarian Congenital Abnormality Registry (HCAR) was established in 1962 due to the growing public health importance of congenital abnormalities (CAs). The HCAR is a population-based registry; it collects and keeps permanent records of medical and personal information about malformed newborns and infants (notification of CAs Is mandatory for physicians) in order to develop baseline data for different types of CAs, to search for increases in the incidence of specific CAs, to provide rates, and identify geographic areas of concern for cluster investigation. In the last 25 years numerous studies have been carried out. In the 1970s two significant increases were noticed: i) in the rate of terminal transverse type of limb reduction defects and ii) in the rate of hypospadias. As a result of our epidemiological investigations and case-control studies we were able to identify the possible factors which caused these increases. In the first case, for example, the Ministry of Health changed the policy of using high oestrogens dosage (which increased the risk of this defect 6.1 times) for artificial abortions in 1978 and after this time the increase was stopped. In 1989-1990 a geographical cluster was found. An extremely high rate of cases with Down's syndrome (27%) was identified in a small village and the case-control study and environmental investigations pointed suspicion on the excessive use of a chemical, trichlorfon at local fish farms. All mothers of babies with Down's syndrome had consumed contaminated fish during critical period. The use of this chemical was prohibited and no CAs were recorded after this time at this place. A special case-control surveillance system has been operating since 1980 in Hungary based on the HCAR. The objective of this system is to obtain information on pregnancy exposures and other risk factors for the study and identification of causes of CAs. The teratogenicity of several drugs taken during pregnancy has been examined so far, most of them ended up with negative results. Our system is suitable for surveillance, research and intervention.

Congenital abnormalities and indicators of germinal mutations in the vicinity of the Paks nuclear plant, Hungary.

The objective of the study was to check the occurrence of phenotypic manifestations of germinal mutations in children born within a 30 km radius of the Paks nuclear power plant, Hungary. The study took the form of a comparative analysis between observed and expected rates based on the Hungarian baseline rates, as well as between children born before and after the operation of the nuclear plant. Data were taken from the database of the Hungarian Congenital Abnormality Registry completed by active search in the study region, and comprised 26 893 children born between 1980 and 1992 in the 55 settlements of the study region. The results were presented as overall figures as well as being grouped by different congenital abnormalities, in addition to the so-called indicators of germinal mutations: sentinel anomalies, Down syndrome and unidentified multiple congenital abnormalities. The observed occurrence of all but one group of congenital abnormalities corresponded to the expected rate, as did the three groups of indicator conditions. Of the 55 settlements, eight had spatial clusters; however, these could be explained by overdiagnosis or chance. There was no significant increase in the variables studied after the operation of the nuclear plant. We conclude that the slightly elevated radiation background (0.2-0.4 microSv/year) due to the operation of the nuclear plant studied does not affect germinal and somatic mutations in children.

Study of developmental abnormalities and deaths after human zygote exposure.

Experimental studies indicated that the mouse zygote is susceptible to experimental induction of developmental anomalies including defects (mainly hydrops), growth retardation and mid- and late-gestational death with certain mutagenic agents. The material of the Hungarian Optimal Family Planning Program is appropriate to check this finding in a human material because participants were asked to visit the coworkers of the Program immediately after the first missed menstrual period and data concerning potentially hazardous environmental factors were obtained. At that time participants were immediately after the pre- and implantation period and they had no knowledge about their pregnancy outcomes. In 1994 the data of their pregnancy outcomes are available. Of 5453 evaluated pregnancies, 1167 were selected for this study because they visited the coworkers of the Program within 28 days post conception. Of 1167 pregnancies, 316 (27%) were exposed to some environmental factors, mainly drugs. A mild intrauterine growth retardation was found in the exposed group. The rate of congenital abnormalities and infant death did not differ between the exposed and unexposed groups. The detailed analysis of different congenital abnormality groups also did not show any significant difference between the exposed and unexposed groups. These negative results are explained by the fact that the observed environmental factors are not mutagenic, at least not in the dosage which was used, or the human zygote is not sensitive to mutagenic agents in the post-conceptional days.