Spontaneous abortions among women working in the pharmaceutical industry

A register based study was conducted on the pregnancy outcome of female workers in eight Finnish pharmaceutical factories to determine whether they had a higher risk of spontaneous abortion than the general population or matched controls. Information about all female workers who had been employed in the factories during the years 1973 or 1975 (four factories) to 1980 was obtained from the employers. The workers' pregnancy data were collected from the nation wide hospital discharge register and polyclinic data of hospitals from 1973 to 1981. The total number of 1795 pregnancies included 1179 deliveries, 142 spontaneous abortions, and 474 induced abortions. The spontaneous abortion rate (the number of spontaneous abortions X 100, divided by the number of spontaneous abortions plus the number of births) during employment was 10.9% and before/after employment 10.6%. The rate for all the women in the corresponding central hospital districts was 11.3% [corrected] during the study period. A case-control study was also carried out in which the cases were 44 women who had a spontaneous abortion during employment in the pharmaceutical factory. Three age matched female pharmaceutical factory workers who had given birth to a child were chosen as controls for every case. The information about occupational exposures was collected from questionnaires completed by the occupational physician or nurse at the factory. The response rate was 93%. Exposure to chemicals was more common among the cases than among the controls. For methylene chloride, a solvent commonly used in the pharmaceutical industry, the increase in odds ratio of borderline significance (odds ratio 2.3, p = 0.06). In a logistic regression model (which included oestrogen exposure, solvent exposure frequency of the usage, and heavy lifting) the odds ratio was increased for oestrogens (odds ratio 4.2, p = 0.05) and for continuous heavy lifting (odds ratio 5.7, p = 0.02). The odds ratio for spontaneous abortions was greater among those exposed to four or more solvents (odds ratio 3.5, p=0.05) than among those exposed to one to three solvents (odds ration 0.8, p=0.74).     

Spontaneous abortions in an industrialized community in Finland

Spontaneous abortions were analyzed in an industrialized Finnish community according to the occupation and workplace of both the women and their husbands. Information about spontaneous abortions and births was obtained from the hospital discharge register, and data about the women and their families were collected from census files. When compared with all women employed outside the home, women who worked at a textile plant (factory A, a clothing manufacturer) had an increased rate of spontaneous abortion (16.7 per cent vs 11.4 per cent). The rate of spontaneous abortions among women employed at factory A differed according to the husband's workplace. The odds ratio for women employed at factor A whose husbands worked at a large metallurgical factory was 3.8, whereas the odds ratio for women whose husbands worked elsewhere was 1.2. Between 1973 and 1976, the rate of spontaneous abortions in this town was consistently lower for the summer period. (May-August) than for the other periods of the year.     

Spontaneous abortions among women employed in the plastics industry

A matched case-control study was done to analyze whether certain occupational exposures in the plastics industry were related to the risk of spontaneous abortions. Information on spontaneous abortions (cases) and births (controls) was obtained from the hospital discharge register; data on occupational exposures were obtained from the occupational health services of the workplaces. No increased risk of spontaneous abortions was observed among workers processing polymerized plastics or heated plastics made of vinyl chloride or of styrene. Owing to the low statistical power of the study, only strong effects can be ruled out. The odds ratio for workers actually processing polyurethane was increased (1.9, not statistically significant), and that for all workers in polyurethane-processing factories was significantly increased (3.0, p = 0.02). The finding needs to be investigated further in future studies.     

Evidence for adverse reproductive outcomes among women microelectronic assembly workers.

Microelectronics assembly entails complex processes where several potentially fetotoxic chemical compounds are used extensively. This study was undertaken to assess the potential adverse reproductive outcomes among former women workers in a microelectronics assembly plant in New Mexico with respect to a comparable population from the same geographical region and to examine the relation between these outcomes and employment history in this plant. After matching a pool of 143 former microelectronic female workers and 105 referents, 90 former microelectronic female worker-referent pairs were constituted (representing 302 and 324 pregnancies in former workers and referents respectively). The odds ratio (for pair matching design) of spontaneous abortion among women workers, before beginning to assemble microelectronic components, was 0.9 (chi 2 = 0.04; NS). After the beginning of employment this odds ratio became 5.6 (chi 2 = 9.8; p less than 1%). This estimated odds ratio decreased to 4.0, taking into account the increased risk for spontaneous abortion in previous pregnancies before employment (chi 2 = 5.4; p less than 5%). It was not possible to determine if this effect was reversible owing to the small number of pairs available after employment. The findings of this study corroborate the results of former studies that suggest a potential association between electronic manufacturing activity and risk of spontaneous abortion. Although the organic solvents were suspected of being the potential risk factor, this study was inconclusive from this point of view. Nevertheless, these investigations may provide some insight into reproductive outcomes among female workers exposed to solvents.     

Evidence for adverse reproductive outcomes among women microelectronic assembly workers

Microelectronics assembly entails complex processes where several potentially fetotoxic chemical compounds are used extensively. This study was undertaken to assess the potential adverse reproductive outcomes among former women workers in a microelectronics assembly plant in New Mexico with respect to a comparable population from the same geographical region and to examine the relation between these outcomes and employment history in this plant. After matching a pool of 143 former microelectronic female workers and 105 referents, 90 former microelectronic female worker-referent pairs were constituted (representing 302 and 324 pregnancies in former workers and referents respectively). The odds ratio (for pair matching design) of spontaneous abortion among women workers, before beginning to assemble microelectronic components, was 0.9 (chi 2 = 0.04; NS). After the beginning of employment this odds ratio became 5.6 (chi 2 = 9.8; p less than 1%). This estimated odds ratio decreased to 4.0, taking into account the increased risk for spontaneous abortion in previous pregnancies before employment (chi 2 = 5.4; p less than 5%). It was not possible to determine if this effect was reversible owing to the small number of pairs available after employment. The findings of this study corroborate the results of former studies that suggest a potential association between electronic manufacturing activity and risk of spontaneous abortion. Although the organic solvents were suspected of being the potential risk factor, this study was inconclusive from this point of view. Nevertheless, these investigations may provide some insight into reproductive outcomes among female workers exposed to solvents.     

Spontaneous abortions among dental assistants, factory workers, painters, and gardening workers: a follow up study.

This investigation was conducted to test the hypothesis that exposure of pregnant women to chemicals increases the risk of spontaneous abortion. The chemical risk factors under study to which dental assistants, factory workers, painters, and gardening workers were exposed were nitrous oxide, inorganic mercury, organic solvents, and pesticides. The study was carried out within the Danish county of Funen. It included all dental assistants employed in private or public dentistry. A comparable reference group was made up by employees less exposed to chemicals. Further study groups included all women painters within the county, women factory workers from selected factories, and about 50% of the women gardening workers within the county. Shop assistants and packers formed their control group. Information was obtained through a postal questionnaire study in May 1980 and from hospital records. Only among factory workers and painters was the odds ratio of spontaneous abortion found to be significantly increased. Neither among these women nor among dental assistants and gardening workers, however, was the reported exposure to any single chemical during pregnancy associated with a significantly increased odds ratio of spontaneous abortion.     

Spontaneous abortions among factory workers. The importance of gravidity control

The purpose of this study were twofold. First to demonstrate the impact of gravidity control on the crude odds ratio (OR), the risk estimate of the total number of spontaneous abortions among all chemically exposed women in comparison with non-exposed women. Second, to discuss whether the increased proportion of higher gravidities among the exposed subjects did compensate for an increased risk of spontaneous abortion provoked by the chemical exposure. The study included 262 factory workers occupationally exposed predominantly to organic solvents and 241 reference women who were socially comparable and relatively free from chemical exposure of their work. The subjects are included in a historical prospective survey of 6 730 women representing 12 selected occupations in the Danish county of Funen. The data were collected by postal questionnaires in May 1980. The crude OR of spontaneous abortions among factory workers was significantly increased, but when controlled for gravidity, it was no longer statistically significant. The childbearing behaviour of the two groups of women was compared in a logistic regression analysis which suggested that the increased proportion of higher gravidities among the factory workers was not only due to a compensatory behaviour. A desire for more children among the factory workers, or a less careful use of contraception compared to the reference group might explain the findings. Consequently, gravidity should probably be controlled.     

Occupational paternal exposure to benzene and risk of spontaneous abortion.

OBJECTIVE--The purpose of this study was to evaluate the risk of spontaneous abortion among the wives of male workers occupationally exposed to benzene. METHODS--The wives of 823 men working in two chemical plants at the time of the study were asked to complete a questionnaire describing their pregnancies. The analysis of the 1739 pregnancies that ended in a spontaneous abortion or a birth is presented. The firms' payroll records provided all workers' employment history, including dates. Benzene exposure, graded at two levels (< 5, > or = 5 ppm), was determined for every job, so that benzene exposure for each worker's entire professional life (at these companies) could be assessed. This information was linked to the dates of the pregnancies reported in the questionnaires to enable the exposure status of each pregnancy to be defined (1270 non-exposed and 274 exposed). The frequency of spontaneous abortion, defined as the number of spontaneous abortions divided by the total of spontaneous abortions and births was evaluated. RESULTS--When adjusted for tobacco consumption, mother's age and pregnancy order, the odds ratio of the association between paternal exposure to approximately 5 ppm of benzene and the risk of spontaneous abortion was close to and statistically not different from unity (OR = 1.1; 95% CI (0.7-1.8). CONCLUSION--In this study paternal exposure to benzene did not increase the risk of spontaneous abortion.     

Spontaneous abortions and malformations in the offspring of nurses exposed to anaesthetic gases, cytostatic drugs, and other potential hazards in hospitals, based on registered information of outcome.

Nurses working in selected departments of general hospitals in Finland were collected from a central register on health personnel in Finland. Using the Hospital Discharge Register and the Register of Congenital Malformations, case nurses were selected who had had a spontaneous abortion (N = 217) or a malformed child (N = 46) between the years 1973 and 1979. Controls consisted of three nurses who had had a normal birth; the control nurses were matched for age and hospital of employment. Information on exposure in the first trimester of pregnancy was sought through the head nurses of the hospitals. No significant increase in risk of spontaneous abortion or of malformation was observed after exposure to anaesthetic gases (odds ratio for spontaneous abortion 1.2), sterilising gases and soaps, or x-rays. Handling of cytostatic drugs did not affect the frequency of spontaneous abortion but was associated with malformations in the offspring. The odds ratio, based on eight cases, was 4.7 (p = 0.02) when the logistic model was adopted. The results suggest that the exposures investigated, other than cytostatic drugs, do not cause a strong reproductive risk. Further studies are needed, particularly on cytostatic drugs.     

Adverse reproductive effects in female workers of lead battery plants

Fifty seven female workers at mean age 32 years (range, 23-45 years), employed in a storage battery plant and a capacitor factory were investigated. The lead exposure period was 7.4 years (range, 1-17 years). The retrospective method was used to analyse reproductive functions of women: menses, libido, abortion and delivery. The results were compared with the control group (62 female workers, mean age 32 years; range, 24-45 years). The incidence of polymenorrhea, prolonged and abnormal menstruations, hypermenorrhea was significantly higher in the lead exposed group than in controls. The incidence of spontaneous abortions was reported by 6 exposed female workers whereas it was not observed in the control group (p = 0.01). The authors conclude that occupational lead exposure of female workers could lead to the impairment of the functions of reproductive system, however poor working conditions and workload may prove to be additional factors responsible for functional disorders in the subjects under study.     

Induced abortion and the chromosomal characteristics of subsequent miscarriages (spontaneous abortions)

Data from a case-control study of miscarriages (spontaneous abortions) were used to test whether single and multiple induced abortions are associated with miscarriage in subsequent euploid (chromosomally normal) pregnancies. Cases and controls were identified in three New York City hospitals between April 1974 and November 1982. It was hypothesized that, if induced abortion increased the risk of subsequent miscarriage, an association would be observed with euploid but not aneuploid (chromosomally abnormal) miscarriage. The frequencies of single and multiple induced abortions among euploid cases and aneuploid cases were compared with those among controls. Among both private and public patients, the proportion of women reporting a single induced abortion was similar in euploid cases and in aneuploid cases compared to controls. Among public patients only, the proportions reporting multiple induced abortions were also similar in euploid cases and in aneuploid cases compared to controls (odds ratios = 0.9 and 1.0, respectively). In contrast, among private patients, the proportion reporting multiple induced abortions was raised among euploid cases (odds ratio = 2.2, 95% confidence interval = 1.3-3.7), although not among aneuploid cases. This association was strongest when the first induced abortion was carried out before 1973, at a young age, or with a procedure other than suction curettage. In public patients, the associations with miscarriage did not vary with characteristics of the first induced abortion, but multiple induced abortion histories when the first two induced abortions occurred before 1973 were in excess among euploid cases compared to controls. These results suggest that, for both private and public patients, neither single nor multiple induced abortions as now performed are likely to increase the risk of miscarriage in subsequent pregnancies. They also suggest a mechanical origin for some miscarriages.     

Spontaneous abortions among female chemical workers in Finland

Summary Spontaneous abortions were analyzed among Finnish chemical workers in 1973–1976. The information on the workers (9000 women) was obtained from the files of the Union of Chemical Workers; information on the abortions was obtained from the Hospital Discharge Registry of the National Board of Health. Fifty-two spontaneous abortions were recorded among chemical workers. The proportion of spontaneous abortions was 8.54% (spontaneous abortions/pregnancies) and 15.57% (spontaneous abortions/ births), which were significantly higher than the respective proportions among all Finnish women. Risk branches included plastics, particularly styrene, viscose rayon, and pharmaceutical industry and laundries.     

Spontaneous abortions among laboratory workers; a follow up study.

An investigation was conducted among all female laboratory workers in the county of Funen to test the hypothesis that work in laboratories during pregnancy increases the risk of spontaneous abortion. Laboratory workers from hospital, university, and other public laboratories and from laboratories in industry were investigated. A socially comparable reference group less exposed to chemicals at work included office workers, technical assistants and designers, physiotherapists, and occupational therapists. Information was obtained through a postal questionnaire study in May 1980 and from hospital records. Neither the occupation in any single category of laboratory nor the alleged exposure to any single chemical during pregnancy showed a significant increase in the odds ratio for spontaneous abortion. A selection bias was found among the non-respondents with respect to both occupation and outcome of pregnancy, but the influence on the results was slight, owing to the small number of non-respondents. The higher rates of hospital admission for spontaneous abortion among the cases compared with the controls indicates that register data are not more valid than self reported data. This leads to several methodological problems that ought to be studied in further detail.     

Paternal exposure to mercury and spontaneous abortions.

The potential reproductive toxicity of mercury vapour was investigated by comparing the rate of spontaneous abortions among the wives of 152 workers occupationally exposed to mercury vapour with the rate among the wives of 374 controls in the same plant. The results indicate an increase in the rate of spontaneous abortions with an increasing concentration of mercury in the fathers' urine before pregnancy. At concentrations above 50 micrograms/l the risk of spontaneous abortion doubles (odds ratio (OR) = 2.26; 95% confidence interval (95% CI) = 0.99-5.23). Special care was taken to avoid bias in reporting abortions and known risk factors of spontaneous abortions do not seem to explain the results. Several biological mechanisms might account for them including, in particular, direct action of mercury on the paternal reproductive system and indirect toxicity to the mother or embryo through transport of mercury from the father. These indications could be of practical importance and should therefore be further documented.     

Paternal exposure to mercury and spontaneous abortions

The potential reproductive toxicity of mercury vapour was investigated by comparing the rate of spontaneous abortions among the wives of 152 workers occupationally exposed to mercury vapour with the rate among the wives of 374 controls in the same plant. The results indicate an increase in the rate of spontaneous abortions with an increasing concentration of mercury in the fathers' urine before pregnancy. At concentrations above 50 micrograms/l the risk of spontaneous abortion doubles (odds ratio (OR) = 2.26; 95% confidence interval (95% CI) = 0.99-5.23). Special care was taken to avoid bias in reporting abortions and known risk factors of spontaneous abortions do not seem to explain the results. Several biological mechanisms might account for them including, in particular, direct action of mercury on the paternal reproductive system and indirect toxicity to the mother or embryo through transport of mercury from the father. These indications could be of practical importance and should therefore be further documented.     

Fever during pregnancy and spontaneous abortion

The hypothesis that maternal fever during pregnancy is a risk factor for spontaneous abortion was tested in a case-control study by comparing the frequencies and timing of fevers of 100 F (37.78 C) or more among three groups of women: women having euploid abortions, women having aneuploid abortions, and women delivering at 28 weeks gestation or later (controls). Cases and controls were identified in three New York City hospitals between August 1979 and June 1982. It was hypothesized that if fever was an antecedent, rather than a symptom of spontaneous abortion, an association would be detected with euploid but not with aneuploid abortions. Among public patients, reported fevers were significantly more frequent among euploid abortions than among controls (18% vs. 7.1%, odds ratio = 2.96), whereas reported fevers were not more frequent among aneuploid abortions (3.9% vs. 7.1%, odds ratio = 0.52). It was also postulated that variation in the strength of the association of fever with euploid abortion with the duration of the interval between the fever and the abortion might yield insight about mechanisms underlying an association. The odds ratios for fever occurring at three intervals--in the same calendar month as a euploid abortion, one month before, and two or more months before--were 6.04, 3.28, and 1.41, respectively. The findings for private patients--for whom a control group was not recruited--are compatible with those for public patients although not statistically significant: the odds of fever with euploid abortion were 2.18 times those with aneuploid abortion.     

Risk factors for ectopic pregnancy: a comprehensive analysis based on a large case-control,population-based study in France

This case-control study was associated with a regional register of ectopic pregnancy between 1993 and 2000 in France. It included 803 cases of ectopic pregnancy and 1,683 deliveries and was powerful enough to investigate all ectopic pregnancy risk factors. The main risk factors were infectious history (adjusted attributable risk = 0.33; adjusted odds ratio for previous pelvic infectious disease = 3.4, 95% percent confidence interval (CI): 2.4, 5.0) and smoking (adjusted attributable risk = 0.35; adjusted odds ratio = 3.9, 95% CI: 2.6, 5.9 for >20 cigarettes/day vs. women who had never smoked). The other risk factors were age (associated per se with a risk of ectopic pregnancy), prior spontaneous abortions, history of infertility, and previous use of an intrauterine device. Prior medical induced abortion was associated with a risk of ectopic pregnancy (adjusted odds ratio = 2.8, 95% CI: 1.1, 7.2); no such association was observed for surgical abortion (adjusted odds ratio = 1.1, 95% CI: 0.8, 1.6). The total attributable risk of all the factors investigated was 0.76. As close associations were found between ectopic pregnancy and infertility and between ectopic pregnancy and spontaneous abortion, further research into ectopic pregnancy should focus on risk factors common to these conditions. In terms of public health, increasing awareness of the effects of smoking may be useful for ectopic pregnancy prevention.     

Risk of spontaneous abortion in Italy, 1978-1995, and the effect of maternal age, gravidity, marital status, and education

This paper describes the trend in the risk of spontaneous abortion in Italy from 1974 to 1995. There was a dramatic decline in the risk after the law that legalized induced abortion was passed in 1978, which implies that probably many induced abortions performed before 1978 were registered as spontaneous abortions. Data for 1991 have been extracted from the Italian national registers of births and abortions and analyzed to investigate the effects of maternal age, gravidity, marital status, and education on the risk of spontaneous abortion. In comparison with women under age 20 years, the risk is found to be increased for women aged 35-39 (odds ratio = 1.45) and women over age 40 (odds ratio = 3.10). The odds ratio is almost 2 for women who have been pregnant two or more times previously. Unmarried women have an increased risk (odds ratio = 1.33), but no important effect of education was observed. There is an important interaction between maternal age and gravidity. The risk of spontaneous abortion is excessively high for young women with high gravidity. It is hypothesized that this could be due to the effect of short intervals between pregnancies.     

Magnetic fields of video display terminals and spontaneous abortion.

The aim of this study was to examine whether work with a video display terminal and exposure to the magnetic fields of video display terminals are related to spontaneous abortion. The study was conducted among women employed as bank clerks and clerical workers in three companies in Finland. The cases (191 spontaneous abortions) and controls (394 births) were identified from Finnish medical registers for the years 1975-1985. Use of video display terminals was defined using the workers' own reports and information provided by the companies. The assessment of exposure to the magnetic fields was based on measurements of the fields of video display terminals. The odds ratio for spontaneous abortion for working with video display terminals was not increased (odds ratio = 1.1, 95% confidence interval 0.7-1.6). However, the odds ratio for workers who had used a video display terminal with a high level of extremely low frequency magnetic fields (> 0.9 microT) was 3.4 (95% confidence interval 1.4-8.6) compared with workers using a terminal with a low level of these magnetic fields (< 0.4 microT). Adjustment for ergonomic factors and mental work load factors changed the odds ratio for magnetic field exposure only very slightly. The findings suggest the need for future studies with assessment of exposure to the magnetic fields in the actual working environment to confirm the possible risk.