Adverse pregnancy outcomes in relation to water consumption: a re-analysis of data from the original Santa Clara County Study, California, 1980-1981.

Residents of a census tract that received drinking water from a well contaminated with solvents were previously shown to experience a spontaneous abortion rate over twice that occurring in an unexposed census tract. In addition, the rate of birth defects in the exposed tract was three times that in the unexposed tract. Surprisingly, increased tapwater consumption was associated with higher rates of spontaneous abortions in both the exposed and the unexposed tracts. Subsequent studies in this area have investigated the relation between spontaneous abortions and consumption of tapwater in more detail. In this report, data from the original study have been re-analyzed using methods comparable with those used in more recent studies. These results confirm the association between spontaneous abortions and reported cold tapwater consumption that was seen in the original study. The observed effect was not due to maternal risk factors, nor was it a function of consumption of bottled water. After controlling for bottled water, the odds ratio for consumption of tapwater was 3.4 (95% confidence interval = 0.6-19.4).     

Nationwide data base on medically diagnosed spontaneous abortions in Finland

The content and technical quality of the Finnish data base on medically diagnosed spontaneous abortions, retrieved from hospital discharges and polyclinic records, are described. The validity and suitability of the data for epidemiological studies is also evaluated. The rate was 8.9 in 1973-83 and it increased from 7.8 to 10.2 during the study period. The rates are at the same level as the ones obtained in other register-based studies, and slightly lower than those of the interview studies. A comparison of self-reported spontaneous abortions to those in our data base showed that 20% of all the abortions reported by the nurses, and 17% of those by the solvent-exposed women, were not found in the hospital register. About half of these are likely to be due to erroneous personal identification codes in the records of the patients. The absence of a spontaneous abortion was related to the length of gestation, with early abortions more often missing. Women in different occupational groups confirmed spontaneous abortions retrieved from our data base to a different degree: nurses in 91% of the cases, whereas industrial workers in only about 79% of the cases. Confirmation was also related to time elapsed since abortion. As the nationwide data base on medically diagnosed spontaneous abortions provides data, independent of an individual's own definition, recognition and reporting, it is a powerful tool in retrospective reproductive studies. Its limitations regarding early abortions need to be recognized, however.     

The negative effect of the IUCD on the occurrence of heteroploidy--correlated abnormalities in spontaneous abortions: an update

Two prior studies done in the seventies had shown that spontaneous abortions in current IUCD-wearers were never associated with morphologic abnormalities, previously demonstrated to correlate significantly with cytogenetically proven heteroploidy. This study, carried out in the early eighties and based on 45 IUCD-associated and 882 IUCD-unrelated non-molar spontaneous abortions, confirmed this negative effect of the IUCD with a difference. Structural abnormalities, suggestive of heteroploidy, were seen for the first time in IUCD-associated spontaneous abortions but their prevalence (9.8%) was significantly lower than that observed in the IUCD-unrelated abortions (54.1%). The clinical relevance of this finding is briefly discussed.     

复发性流产的遗传因素与同种免疫因素分析

目的:探讨复发性流产的遗传因素和同种免疫因素的关系。方法:根据流产胚胎的绒毛染色体畸形与否对复发性流产的患者进行分组,采用单向混合淋巴细胞培养方法比较孕前、孕早期、流产后不同时段的淋巴细胞转化率。结果:胚胎染色体异常组流产后绒毛细胞诱导的淋巴细胞转化率(11.37±6.65%)较孕前、孕早期(7.94±4.17%、8.78±4.74%)显著升高(P<0.05);较胚胎染色体正常组绒毛细胞诱导的淋巴细胞转化率(7.84±3.97%),也显著升高(P<0.05)。结论:遗传和同种免疫因素是复发性流产的两大重要因素,可以同时存在;胚胎染色体异常有可能诱发母体产生更多的封闭抗体。     

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.     

Spontaneous abortions in female populations occupationally exposed to ionizing radiation

Objective Exposure to radioisotopes of metals and halogen elements occurring in medical practice may cause spontaneous abortions. The potential role of occupational exposure to X-rays and internal radioisotopes on pregnancy outcome in childbearing age women employed in hospital departments were analyzed in order to estimate miscarriage risk. Methods Over a period of 16 years, the occurrence of miscarriages in 61 women exposed to radioisotopes was compared to that reported in 170 X-ray exposed women. Chromosomal aberrations (CA) were measured in both radiation-exposed groups and in 53 non-exposed women. Results Women exposed to radioisotopes experienced at least a threefold higher rate of spontaneous abortions than those exposed to X-ray (OR = 3.68, 95% CI = 1.39–9.74, P < 0.01). Although X-ray and radioisotopes exposed women had significantly higher levels of chromosome type frequency (0.51 ± 0.82, and 0.63 ± 0.99, respectively) than referents (0.17 ± 0.34), there was no clear difference between radiation-exposed women. Conclusions For exposure levels within standard recommended guidelines, radioisotopes are far more likely to play a role in the occurrence of spontaneous abortions than X-rays. Such biological effect is not detectable by deviations in CA frequency. The corresponding author has the right to grant on behalf of all authors and does grant on behalf of all authors, a non-exclusive license on a worldwide basis to the BMJ Publishing Group Ltd. and its Licensees to permit this article (if accepted) to be published in Occupational and Environmental Medicine editions.     

Occupational and environmental risks of spontaneous abortions around a smelter

BACKGROUND: This study represents part of a follow-up study on reproductive outcome around a smelter in Sweden. METHODS: Employees at the smelter, a random sample including neighbors of the smelter and referents were analyzed by a register study, covering 1982-1990, a questionnaire study performed in 1992 and a case-referent study with cases of spontaneous abortions and live borns as referents. Risk factors were studied by logistic regression. A validity-study between register and questionnaire data on spontaneous abortions and legal abortions was completed. RESULTS: The studies showed no risk increase for the exposed groups of smelter workers and neighbors compared to the reference group, 10, 11, and 12%, respectively. A validation of the data on abortions between register and questionnaire data showed good agreement. CONCLUSIONS: We found no increase of spontaneous abortion associated to smelter work or to living close to the smelter which could be a result of radically reduced emissions.     

Safety of MenACWY-CRM vaccine exposure during pregnancy

BackgroundAlthough the meningococcal conjugate MenACWY-CRM vaccine is not approved for use in pregnant women, unintentional exposure during pregnancy can occur, especially during early pregnancy among women of child-bearing age. This study provides safety information about inadvertent MenACWY-CRM vaccination during pregnancy.MethodsThe evaluated population consisted of pregnant female members of Kaiser Permanente Southern California who inadvertently received MenACWY-CRM at 11–21 years of age during 09/30/2011-06/30/2013 within 28 days prior to conception or during pregnancy. Chart abstraction was conducted to identify pregnancy and birth outcomes, including spontaneous and induced abortions, preterm births, low weight births, and major congenital malformations (MCMs).ResultsThere were 92 women who received MenACWY-CRM during the pregnancy exposure period, mainly during the first trimester (76.1%). Hispanics represented the largest race/ethnicity category (68.5%). Among the known pregnancy outcomes (n = 66; excluding induced abortions and unknown pregnancy outcomes), the prevalence of spontaneous abortions was 18.2% (n = 12). Among live born infants (n = 55; from 54 pregnancies), 14.5% (n = 8) were born preterm (<37 weeks gestation) and 9.1% (n = 5) had a low birthweight (<2500 g). The prevalence rate of MCMs among live born infants (n = 55) was 1.8% (n = 1).ConclusionsThis study provides baseline prevalence estimates of spontaneous abortions, preterm births, low weight births, and MCMs among women inadvertently exposed to MenACWY-CRM during the pregnancy period. These estimates appear to be comparable with U.S. background prevalence estimates.     

Risk of spontaneous abortion in workers exposed to toluene.

Rates of spontaneous abortions were determined using a reproductive questionnaire administered by personal interview to 55 married women with 105 pregnancies. They were employed in an audio speaker factory and were exposed to high concentrations of toluene (mean 88, range 50-150 ppm). These rates of spontaneous abortion were compared with those among 31 women (68 pregnancies) who worked in other departments in the same factory and had little or no exposure to toluene (0-25 ppm), as well as with a community control group of women who underwent routine antenatal and postnatal care at public maternal health clinics (190 women with 444 pregnancies). Significantly higher rates for spontaneous abortions were noted in the group with high exposure to toluene (12.4 per 100 pregnancies) compared with those in the internal control group (2.9 per 100 pregnancies) and in the external control group (4.5 per 100 pregnancies). Among the exposed women, significant differences were also noted in the rates of spontaneous abortion before employment (2.9 per 100 pregnancies) and after employment in the factory (12.6 per 100 pregnancies). Almost all the women were nonsmokers and did not drink; other known risk factors such as maternal age at pregnancy, order of gravidity, and race were not likely to explain the results. Thus, specific exposure to toluene seems to be associated with a risk of foetal loss.     

Risk of spontaneous abortion in workers exposed to toluene.

Rates of spontaneous abortions were determined using a reproductive questionnaire administered by personal interview to 55 married women with 105 pregnancies. They were employed in an audio speaker factory and were exposed to high concentrations of toluene (mean 88, range 50-150 ppm). These rates of spontaneous abortion were compared with those among 31 women (68 pregnancies) who worked in other departments in the same factory and had little or no exposure to toluene (0-25 ppm), as well as with a community control group of women who underwent routine antenatal and postnatal care at public maternal health clinics (190 women with 444 pregnancies). Significantly higher rates for spontaneous abortions were noted in the group with high exposure to toluene (12.4 per 100 pregnancies) compared with those in the internal control group (2.9 per 100 pregnancies) and in the external control group (4.5 per 100 pregnancies). Among the exposed women, significant differences were also noted in the rates of spontaneous abortion before employment (2.9 per 100 pregnancies) and after employment in the factory (12.6 per 100 pregnancies). Almost all the women were nonsmokers and did not drink; other known risk factors such as maternal age at pregnancy, order of gravidity, and race were not likely to explain the results. Thus, specific exposure to toluene seems to be associated with a risk of foetal loss.     

Environmental tobacco smoke and risk of spontaneous abortion

BACKGROUND: Studies of exposure to environmental tobacco smoke (ETS) and risk of spontaneous abortion are limited to a few studies of self-reported exposure, and the results have been inconsistent. The aim of this study was to investigate risk of early spontaneous abortion related to ETS and active smoking as defined by plasma cotinine levels. METHODS: We conducted a population-based case-control study in Uppsala County, Sweden, between January 1996 and December 1998. Cases were 463 women with spontaneous abortion at 6 to 12 completed weeks of gestation, and controls were 864 pregnant women matched to cases according to the week of gestation. Exposure status was defined by plasma cotinine concentrations: nonexposed, <0.1 ng/mL; ETS-exposed, 0.1-15 ng/mL; and exposed to active smoking, >15 ng/mL. Multivariable analysis was used to estimate the relative risk of spontaneous abortion associated with exposure to ETS and active smoking. RESULTS: Nineteen percent of controls and 24% of cases were classified as having been exposed to ETS. Compared with nonexposed women, risk of spontaneous abortion was increased among both ETS-exposed women (adjusted odds ratio = 1.67; 95% confidence interval = 1.17-2.38) and active smokers (2.11; 1.36-3.27). We could not show a differential effect of exposure to ETS or active smoking between normal and abnormal fetal karyotype abortions. CONCLUSIONS: Nonsmoking pregnant women exposed to ETS may be at increased risk of spontaneous abortion. Given the high prevalence of ETS exposure, the public health consequences of passive smoking regarding early fetal loss may be substantial.     

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.     

Self-reported data on spontaneous abortions compared with data obtained by computer linkage with the hospital registry

In a study of occupational causes of spontaneous abortions, based upon self-reported data and data from the hospital registry, evidence of differential misclassification was noted. Among those exposed a larger proportion of the self-reported spontaneous abortions were identified in the hospital registry, compared with what was found in the control group. This could be due to recall bias of the questionnaire data masking an effect of exposure, or a lower threshold for hospitalization among those exposed vis-à-vis controls, which would exaggerate the effect of exposure, if any. The analysis tended to support the idea of a less accurate recall of spontaneous abortions among controls, especially for abortion that occurred more than 3 years before the questionnaires were sent out. A second questionnaire was sent out to a subset of the participants 3 1/2 years after the first questionnaire. 17% reported fewer spontaneous abortions in this second questionnaire compared with the situation in the first questionnaire, for the period 1973 to 1980.     

Spontaneous abortion among women using video display terminals

This case-base study with a source population of 214 108 commercial and clerical workers investigated the risk of adverse pregnancy outcome among women working with a video display terminal (VDT) in Denmark. A subpopulation was obtained by register linkage between a trade union membership file, the Medical Birth Register, and the National Register of In-Patients. In two years 24,352 pregnancy outcomes were registered, 2248 spontaneous abortions were recorded, and a base sample of 2252 pregnancies was randomly selected. Data on VDT use, job stress, ergonomic factors, and life-style factors were collected with questionnaires sent to 6212 women and 426 employers. There was no increased risk of medically verified spontaneous abortion among women with VDT use. The relative risk for women exposed to any degree of use was 0.94 (95% confidence interval 0.77-1.14). Ergonomic work load and job stress were not confounders.     

Cytogenetic studies of couples with repeated spontaneous abortions of known karyotype

Several cytogenetic studies have reported an increased frequency of aneuploidy in peripheral blood cultures of couples with multiple spontaneous abortions. However, in none of the studies have the chromosome constitutions of the fetuses been known, making it difficult to interpret these observations. In the present study, we summarize our cytogenetic observations on 23 couples with multiple miscarriages, 12 of whom had repeated chromosomally normal spontaneous abortions, and 11 repeated trisomic spontaneous abortions. We were unable to demonstrate a significant difference in the level of aneuploidy between the two groups. Therefore, it seems unlikely that aneuploidy detectable in peripheral blood preparations is an important indicator of fetal aneuploidy.     

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.     

An exploratory analysis of the effect of pesticide exposure on the risk of spontaneous abortion in an Ontario farm population

The toxicity of pesticides on human reproduction is largely unknown--particularly how mixtures of pesticide products might affect fetal toxicity. The Ontario Farm Family Health Study collected data by questionnaire on the identity and timing of pesticide use on the farm, lifestyle factors, and a complete reproductive history from the farm operator and eligible couples living on the farm. A total of 2,110 women provided information on 3,936 pregnancies, including 395 spontaneous abortions. To explore critical windows of exposure and target sites for toxicity, we examined exposures separately for preconception (3 months before and up to month of conception) and postconception (first trimester) windows and for early (< 12 weeks) and late (12-19 weeks) spontaneous abortions. We observed moderate increases in risk of early abortions for preconception exposures to phenoxy acetic acid herbicides [odds ratio (OR) = 1.5; 95% confidence interval (CI), 1.1-2.1], triazines (OR = 1.4; 95% CI, 1.0-2.0), and any herbicide (OR = 1.4; 95% CI, 1.1-1.9). For late abortions, preconception exposure to glyphosate (OR = 1.7; 95% CI, 1.0-2.9), thiocarbamates (OR = 1.8; 95% CI, 1.1-3.0), and the miscellaneous class of pesticides (OR = 1.5; 95% CI, 1.0-2.4) was associated with elevated risks. Postconception exposures were generally associated with late spontaneous abortions. Older maternal age (> 34 years of age) was the strongest risk factor for spontaneous abortions, and we observed several interactions between pesticides in the older age group using Classification and Regression Tree analysis. This study shows that timing of exposure and restricting analyses to more homogeneous endpoints are important in characterizing the reproductive toxicity of pesticides.     

Maternal fertility, reproductive loss, and defective human embryos.

It is possible that many abnormal conceptuses are lost at an early stage without the mother's knowledge. To investigate this further the reproductive history of the mothers of defective embryos (neural tube defects, holoprosencephaly, cleft lip, polydactyly, and early embryonic resorption) was compared with that of the mothers of normal embryos. The frequency of prior miscarriages was higher in the case mothers than in normal controls matched for maternal age and gravidity, the difference being significant for all the anomalies except for polydactyly. The case mothers had fewer prior recognised pregnancies than control mothers matched for maternal age. There were more primigravid mothers in abnormal groups, and the difference from controls was significant for neural tube defects. It was assumed that the gravidity of the case mothers may be underestimated, possibly due to increased early abortions which are not recognised clinically. Thus, it seems that both recognised and unrecognised abortions occur more often in the mothers of defective embryos. Since many spontaneous abortuses are morphologically and/or cytogenetically abnormal, some women appear to conceive abnormal embryos repeatedly. Most of these embryos, however, may be screened out prenatally and escape clinical detection. Information on prior reproductive history of the woman should be examined carefully in genetic counselling.     

Estimating the probability of spontaneous abortion in the presence of induced abortion and vice versa.

An integrated approach to estimate the total number of pregnancies that begin in a population during one calendar year and the probability of spontaneous abortion is described. This includes an indirect estimate of the number of pregnancies that result in spontaneous abortions. The method simultaneously takes into account the proportion of induced abortions that are censored by spontaneous abortions and vice versa in order to estimate the true annual number of spontaneous and induced abortions for a population. It also estimates the proportion of pregnancies that women intended to allow to continue to a live birth. The proposed indirect approach derives adjustment factors to make indirect estimates by combining vital statistics information on gestational age at induced abortion (from the 12 States that report to the National Center for Health Statistics) with a life table of spontaneous abortion probabilities. The adjustment factors are applied to data on induced abortions from the Alan Guttmacher Institute Abortion Provider Survey and data on births from U.S. vital statistics. For the United States in 1980 the probability of a spontaneous abortion is 19 percent, given the presence of induced abortion. Once the effects of spontaneous abortion are discounted, women in 1980 intended to allow 73 percent of their pregnancies to proceed to a live birth. One medical benefit to a population practicing induced abortion is that induced abortions avert some spontaneous abortions, leading to a lower mean gestational duration at the time of spontaneous abortion.