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.
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.
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).
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.
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.
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.