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Fact Sheets

Spontaneous Abortion

Issue: Environmental chemicals in our environment may be causing spontaneous abortions in exposed women and men.

Background: Spontaneous abortion is defined as the loss of a fetus weighing less than 500 grams before 20 weeks gestation counted from the first day of the last menstrual period. The known causes of spontaneous abortion in the first trimester are primarily chromosomal abnormalities. In the second trimester, spontaneous abortions are often attributed to uterine abnormalities. Risk factors for spontaneous abortion include advanced maternal age, increasing parity, and increasing paternal age preconception solvent exposure of fathers and maternal heavy lifting. Other factors that are known to cause spontaneous abortion are therapeutic agents such as chemotherapy, radiation and anesthetic agent exposures. Tobacco and ethanol exposure also have an impact, alone and in combination. Substance abuse related to cocaine and other drugs is also associated with fetotoxic responses. Paternal exposures to toxicants may also play a role in the etiology of spontaneous abortion through two proposed mechanisms: (1) direct effects on the germ cells; or (2) indirect effects by the transmission of the toxicant to the mother and fetus through the seminal fluid or maternal and fetal exposures brought home by the father.

Disease Trends: The incidence of spontaneous abortion is estimated to be 50% of all pregnancies, based on the assumption that many pregnancies abort spontaneously with no clinical recognition. The frequency of spontaneous abortions in Ontario between 1979 and 1984 were calculated from data on hospital admissions for all Ontario hospitals. In this study the frequency of clinically recorded spontaneous abortions were found to be steady over the time period 1979 to 1984 ranging between 6.8 and 7.2%. Several Ontario counties consistently experienced high rates of spontaneous abortions although the reasons remain undetermined. These data suggest that overall there appears to be no increase in spontaneous abortion, at least for Ontario, but there is evidence that there may be regional effects where investigation of the cause is warranted. However as these data are based on hospital admissions and the majority of women who experience a spontaneous abortion are not admitted to hospital, these data are an underestimate of the true rate of clinically recognized pregnancy loss. The self-reported rates of spontaneous abortion range from 10 to 20 percent and the early abortions in particular are likely influenced by how aware the woman is of her menstrual cycle.

Consistency of the data: There is evidence that organochlorine and carbamate pesticides cross the placenta and possibly cause fetal death. Another Indian study reported that wives of worker's exposed to organochlorine pesticides had elevated risk of spontaneous abortion and stillbirth. In a study of couples living and working on Ontario farms, increased miscarriage rates were observed when certain pesticides (atrazine, glyphosate, 2,4-D, 2,4-DB, MCPA, carbaryl, thiocarbamates, and insecticides), were applied in the 3-month window of time before conception. Pesticides associated with increased risk of miscarriage when exposure occurred during the first trimester of pregnancy were atrazine, dicamba, and 2,4-D. Several studies have also reported increased risk of miscarriage in occupations associated with agriculture (e.g., gardeners, greenhouse workers, veterinarians). Women exposed to hexachlorobenzene (HCB) as children, who developed severe porphyria cutanea tarda, have been followed for approximately 40 years. The residues are still present in many of the survivors. During a review of the reproductive outcomes of these women, an unexpected finding was the association of high serum concentrations of HCB with high rates of spontaneous abortion. No effect of polybrominated biphenyl contamination of the food supply in Michigan in the mid-1970s on spontaneous abortion could be found in another study. Low to moderate blood lead levels have been associated with increased risks of spontaneous abortion. Other heavy metals such as mercury may also be fetotoxic. There is suggestive evidence that women exposed to substances produced by molds, some of which are highly estrogenic, in grain have a 2-fold increase in risk of spontaneous abortion in addition to estrogen-related cancer. Paternal exposure to oil and oil products was not associated with an increase in the risk for spontaneous abortion in one study. Both maternal and paternal occupational exposure to organic solvents have been linked with increased rates of miscarriage. Taken together these data suggest that spontaneous abortion is affected by occupation, contaminant, and level of exposure. There is also evidence that the risk factors for early spontaneous abortions (< 12 weeks) differ from later abortions (12 - 19 weeks).

Experimental evidence: A number of reports have shown that chemical contaminants are detectable in human serum and ovarian follicular fluid of both pregnant and non-pregnant women, respectively. Contaminants such as herbicides, lead, mercury, dioxins, drugs, and tobacco smoke by-products have also been measured in seminal fluid. These data suggest that potential toxic agents are present in the body and in some cases may achieve concentrations in target tissues sufficient to induce an adverse effect. In one study, HCB treatment induced decreased levels of serum progesterone in the luteal phase of the menstrual cycle in cynolmogus monkeys. The mechanism is not understood, although it may involve a reduction in steroid metabolizing function in the ovary. The persistence of this chemical in fat could explain an effect observed over many years. Several in vitro studies have demonstrated that environmental contaminants such as HCB, PCBs, dioxins, and DDE alter steroid hormone enzymes that are both involved in the production of gonadal steroids and their metabolism.

Biological plausibility: While in none of the above cases has a causal link between pesticide exposure and an environmental contaminant or the relevant mechanism involved been established, a number of pesticides have been shown to have estrogenic or anti-progestagenic activity. Elevated estrogen may be toxic to the conceptus prior to implantation and thus induce early fetal loss. It is well known that high doses of estrogen, the so-called "morning after pill" can be used to prevent implantation following unprotected intercourse. Progesterone is critical for implantation and the maintenance of human pregnancy. Therefore, compounds that impair progesterone production increase its metabolism or block its action that is of most interest. Interference with either progesterone production by removing the corpus luteum, or alternatively inhibiting progesterone function by administration of an antiprogestin such as mifepristone (RU-486), can result in a spontaneous abortion. These observations suggest theoretical mechanisms by which environmental chemicals might induce abortions but dose considerations cast some doubt on the probability that low-level environmental chemical exposures would have an effect, unless the chemicals were persistent in the body.

Conclusions: It is clear that there is an increased risk of spontaneous abortion with high level exposure as shown for some occupational groups. However, there are substantial gaps in our knowledge about whether exposure to environmental chemicals has an impact on spontaneous abortion for the general population.



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