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BACKGROUND
Environmental exposure to hazardous substances and the adverse health
effects that can result are increasing in public health importance. In
1981, the U.S. Environmental Protection Agency (EPA) estimated that 264
million metric tons of hazardous wastes were produced. By 1988, this estimate
had risen to 5.5 billion ( (1)) .
In 1990, an estimated 4 million people in the United States lived within
1 mile of one or more of the 1,135 hazardous waste sites then on the National
Priorities List (NPL) (1) . By 1994, there were more than 1,400 sites
on the NPL ( (2)) .
These sites represented a small fraction of the estimated 439,000 hazardous
waste sites that might be present in the United States (1) . The
number of people actually exposed to toxic substances either at NPL sites
or at hazardous waste sites in general cannot be estimated accurately.
ATSDR is required by law to conduct
a public health assessment at each NPL site. The aim of each assessment
is to determine whether the population residing around a particular site
might have been exposed to any toxic substances and to assess whether adverse
health effects possibly resulted from this exposure. Known health effects
are documented in these assessments, and public health recommendations
are made accordingly. Potential health effects are also identified and
referred to ATSDR scientists for additional investigation. As part of this
health assessment process, Camp Lejeune personnel provided ATSDR with drinking
water monitoring records indicating that two drinking water supplies at
Camp Lejeune were contaminated over a period of 34 months. Included in
the population supplied with this water were slightly more than half of
all residents in family base housing. Because this population consisted
of a large proportion of young married women, concern was raised about
potential health effects on fetuses exposed to toxic substances in utero.
Site Description and Exposure
History
Camp Lejeune is a military base that
comprises approximately 233 square miles in Onslow County on the coast
of North Carolina. It is one of 123 federal facilities on the NPL, and
it is included because of the presence of contaminants in the environment
originating at the facility. The military base consists of six Marine Corps
commands and two Navy commands. Almost 130,000 people have access to the
base. The population includes active military personnel (43,000) and their
dependents (52,000). Base housing for enlisted personnel, officers, and
their families are located in 15 different areas on the base. An average
of 8.3 million gallons of water is distributed daily at Camp Lejeune. More
than 100 wells have been drilled to supply this water. Almost all of these
wells use a sand aquifer that is permeable to contamination (3) .
Personnel at Camp Lejeune first detected
VOC contamination in drinking water in April 1982. This coincided with
a change in the laboratory that conducted routine water-quality testing
and was unlikely to have been related to the onset of first exposure. Because
test results of water samples obtained in April were anomalous, samples
were collected in May and July and analyzed for a limited number of VOCs.
PCE and TCE were found in two drinking water systems, the Tarawa Terrace
system and the Hadnot Point system. However, the source of the contamination
was not identified. Although officials at the base contacted the state
for advice, no further action was taken because water quality standards
had not been established for these VOCs in 1982.
In July 1984, Camp Lejeune began
sampling wells in the Hadnot Point area as part of the base's environmental
restoration program. As a result of this sampling, seven contaminated wells
were closed in November and December 1984. Tap water sampling conducted
in December after the closure of these seven wells showed no additional
evidence of contamination. However, on January 27, 1985, a fuel pump broke
at the Holcomb Boulevard water system. Water from Hadnot Point was supplied
to the Holcomb Boulevard service area while repairs were conducted. Tap
water samples taken from buildings temporarily supplied by Hadnot Point
contained high levels of TCE, which prompted additional tap and finished
water sampling for VOCs at Hadnot Point and Tarawa Terrace. Contaminated
wells in both water systems were closed soon after they were identified
in January and February 1985, and routine sampling was implemented at all
distribution systems on the base. Notable contamination has not been detected
in Camp Lejeune's drinking water systems since February 1985.
The Hadnot Point system has been used primarily for industrial purposes, but the Hospital Point housing area also receives water from the Hadnot Point system. This small housing area was populated by hospital personnel and their families until 1983, when the area became housing for a more diverse group of officers' families. It is not known when the Hadnot Point supply wells first became contaminated, but VOCs were present for at least 2½ years. Industrial activity on the base began in the 1940s. No records indicate when the VOC plumes that contaminated supply wells in the Hadnot Point system originated. A chronology of these events is included in
Table 1.
At Tarawa Terrace, the highest concentrations
of contaminants measured in tap water samples were 215 parts per billion
(ppb) PCE, 8 ppb TCE, and 12 ppb 1,2-DCE. This distribution system continued
to serve base family housing until 1986. The highest contaminant levels
measured in tap water samples from Hadnot Point were 1,400 ppb TCE and
407 ppb 1,2-DCE.
Contamination at Tarawa Terrace probably
occurred many years before it was first documented in 1982. The source
of the PCE at Tarawa Terrace was the ABC One-Hour Cleaners, a dry-cleaning
establishment near Tarawa Terrace ( (3)) .
PCE leaked into the groundwater from the company's septic system. According
to EPA records, the septic system was in operation from 1954 through 1985.
In 1958, military personnel dug a supply well for the Tarawa Terrace system
approximately 900 feet from the dry cleaners. Because this supply well
was near the contaminated septic system, because few changes were made
in the dry-cleaning operation after 1960 ( (4)) ,
and because of the very permeable aquifer at Camp Lejeune, the Tarawa Terrace
well probably was contaminated soon after it was built. Human exposure
to PCE and other contaminants through this well could have occurred for
as long as 30 years (3) .
The housing areas that received contaminated
water in each exposure group, the contaminants, and the estimated contaminant
levels are summarized in Table 2. Each of the affected housing areas received
water containing a mixture of many contaminants, a phenomenon noted with
almost every population exposed to contaminants released from hazardous
waste sites. For simplicity, each group of exposed housing areas is referred
to by the predominant contaminant in the mixture. Residents of Tarawa Terrace
are referred to as the PCE-exposed group, and residents of Hospital Point
are referred to as the long-term TCE-exposed group. The short-term TCE-exposed
group comprises residents of Berkeley Manor, Midway Park, Paradise Point,
and Watkins Village during the 12-day period from January 27 through February
7, 1985, when these residents received water from the same supply as Hospital
Point residents.
The exposure data, summarized in
Tables 3 and 4, are limited. Water samples were collected on three different
dates; the May 1982 samples, however, were preserved for several months
before they were analyzed, which might have decreased the observed concentration
of VOCs. Moreover, the 1985 sampling at Hadnot Point was conducted after
seven of eight contaminated wells were closed. Hence, the expected contamination
levels in the Hadnot Point distribution system before 1985 would have been
higher than the concentrations measured in 1985. In addition, one supply
well for the Hadnot Point distribution system contained concentrations
of benzene as high as 700 ppb. Because the 1982 analyses were limited to
TCE and PCE, and because the well containing benzene was shut off before
the distribution system was sampled again, benzene was never detected in
Hadnot Point tap water. Nonetheless, low-level exposure (an estimated 35
ppb) would have been expected among women receiving Hadnot Point water
before December 1984.
An important feature of the exposure
at Camp Lejeune was its intermittent nature. Each of the contaminated systems
had more wells than were necessary to supply water on any one day. Contaminant
levels have been noted to differ with the supply wells in service. The
process by which a particular well was selected for use was essentially
random, but all wells presumably were used in a given month unless they
were out of service for mechanical failure or contamination. Daily or monthly
well-usage logs were not available for evaluation. Despite these variations,
on any specified day, VOC concentrations were probably distributed uniformly
to all residential units because the water from all wells was mixed before
treatment and distribution. For example, on January 31, 1985, VOC concentrations
were similar in tap water samples obtained from several different buildings
(Table 4).
Human Health Effects of Concern
Human gestation is a time of great
vulnerability to environmental and pharmacologic agents. Environmental
exposure to mercury has been shown to cause adverse effects in utero even
though the pregnant woman is unaffected ( (5)) .
The outcomes evaluated (i.e., decreased MBW, SGA, and preterm delivery)
are several of the many possible adverse pregnancy outcomes that might
be associated with exposure to environmental toxins (
(6)) . These outcomes
are important because of their contribution to infant mortality and morbidity;
moreover, they are among the most practical outcomes to study near hazardous
waste sites because they are common, well-ascertained, and reported in
a standardized fashion on birth records ( (7)) .
Birth records also include information on maternal residence. These practical
aspects of the study outcomes are important in situations, such as that
at Camp Lejeune, in which exposure ceased almost 10 years before the study
and most of the exposed population had moved in the intervening period.
Intrauterine growth retardation (measured as decreased MBW and SGA) and preterm delivery are two conditions with distinct pathogeneses that are usually grouped together and measured as low birth weight. In 1989, 7.0% of infants had low birth weight, weighing <2,500 grams (g) at birth ( (8)) . Low birth weight is the third most important predictor of infant mortality in the United States and the most important predictor of infant mortality among blacks in the United States ( (9)) . In 1980, the risk for infant mortality for singleton infants with very low birth weight (i.e., <1,500 g at birth) was 94 times higher than for infants of normal birth weight (>2,500 g at birth) ( (10)
). Low birth weight and very low
birth weight infants are also at greater risk for neurodevelopmental handicaps
(e.g., cerebral palsy and seizure disorder), lower respiratory tract conditions,
and complications from neonatal care ( (11)).
Distinguishing
between effects on fetal growth and effects on gestational age at delivery
is often difficult because growth and maturity of an infant are both highly
dependent on gestational age. Infants who are born small because they are
born at <37 weeks of gestation are considered to be preterm. Approximately
10% of all infants born during 1988 in the United States were preterm (
(12)). Approximately 40% of these preterm infants weighed <2,500
g (12). Such infants are clearly at higher risk for morbidity and mortality.
The risk for fetal death is three times higher for infants surviving to
26 weeks than for infants surviving to 40 weeks (
(13)). Factors predictive
of preterm delivery include maternal socioeconomic status, race-ethnicity,
cigarette smoking, stress, nutrition, past pregnancy history, access to
prenatal care, and medical complications such as sexually transmitted diseases,
infection, hypertension, and preeclampsia ( (14)).
Infants who have sufficient time
to grow and mature but have low birth weight often are less viable because
of intrauterine processes that delayed their growth. In general, whether
preterm or full-term, growth-retarded infants are at greater risk for antenatal
and neonatal mortality than full-term infants who are at the appropriate
weight for their gestational age (14, (15)).
SGA infants are those within the bottom tenth percentile of the birth weight
distribution at any given gestational age. As with other population-based
measures, some SGA infants will be healthy and simply smaller than average,
but many will be growth retarded. At present, SGA is the only marker for
intrauterine growth retardation that is readily available for population-based
studies.
Biologic factors reducing growth
include young maternal age, low maternal prepregnant weight, short maternal
height, insufficient maternal weight gain during pregnancy, maternal alcohol
consumption, and anoxia resulting from cigarette smoking and altitude (14,
(16)). Maternal medical
complications, such as hypertension, can also produce anoxic conditions
resulting in SGA infants ( (17)).
Plurality, the sex of the infant, and maternal parity also influence birth
weight. Important social determinants of SGA infants in the United States
are maternal race, education, socioeconomic status, and utilization of
prenatal care (14).
Late fetal deaths (i.e., stillbirths) occur more rarely than preterm
birth and SGA but account for a greater proportion of perinatal mortality.
Late fetal deaths, defined as fetal deaths occurring after 20 weeks of
gestation, account for approximately 80% of all perinatal deaths. In 1989,
the fetal death rate after 20 weeks of gestation was 7.5 deaths per 1,000
births, with a rate of 6.4 per 1,000 births in whites and 13.1 per 1,000
births in nonwhites ( (18)).
These rates probably underestimate the actual numbers of fetal deaths because
of underreporting (7, (19)). Despite the
importance of late fetal death, the causes of fetal death have not been
widely studied. Important maternal risk factors for fetal death are maternal
age, race, education, parity, body mass, cigarette smoking, hypertension
and hypertensive disorders, diabetes, and previous adverse pregnancy outcome.
Risk factors inherent to the specific infant or pregnancy include sex,
congenital anomalies, plurality, and cord and placental complications (15,
(20), (21)).
Routes of TCE and PCE Exposure
and Metabolism
PCE and TCE, the predominant
contaminants in the chemical mixtures studied, are structurally similar
chemicals with many common toxicologic properties. Both compounds are lipophilic
( (22), (23))
and readily cross the placenta ( (24),
(25), (26)). Compared with other
solvents, both TCE and PCE have relatively long half-lives in the human
body ( (27)). PCE is retained in the body
three to four times longer than TCE, and females retain both compounds
longer than males (27). A number of models have been developed to estimate
the distribution of PCE and TCE within the human body after exposure to
contaminated air or groundwater ( (28),
(29), (30)). In general, ingesting
contaminated drinking water is not an efficient way to deliver these toxic
chemicals to the fetus (26). Activities that cause VOCs in household water
supplies to evaporate include bathing; showering; cooking; and operating
toilets, washing machines, and dishwashers (29, (31)).
Inhalation of TCE and PCE that have evaporated from household water is
likely to result in higher exposures than ingesting water from the same
water supply (29). Larger fractions of PCE and TCE are metabolised after
ingestion than after inhalation (26). Moreover, trichloroacetic acid (TCA),
a biologically active metabolite of PCE and TCE, has been observed to persist
in the rat fetus after exposure to either PCE or TCE has stopped; TCA can
cycle from the fetus into the amniotic fluid and back into the fetus (25).
Therefore, the relative contributions of inhalation and ingestion of PCE
and TCE depend on whether the primary toxicants are the chemical(s) or
the chemical metabolites.
One potential mechanism for reproductive toxicity of PCE is a generalized
central nervous system depression that suppresses the hypothalmus and pituitary
in the mother, the fetus, or both ( (32)).
A similar mechanism might operate for TCE because it has similar chemical
properties. Although this hypothesis remains untested, central nervous
system depression after PCE and TCE exposure is well-established (22,23),
fatty acid composition changes in the brains of fetal guinea pigs have
been observed after in utero exposure to PCE ( (33)),
and suppression of the fetal hypothalmus would affect fetal growth (
(34), (35)). Suppression of the
maternal hypothalmus probably does not affect fetal growth (34), but the
interactions between the maternal hormonal environment, the placental hormonal
environment, and the fetal hormonal environment are complex.
Metabolites of TCE are possibly responsible for the developmental
defects observed in laboratory animals exposed to TCE in drinking water
( (36), (37),
(38)). Infants with birth defects are often SGA. An association
between SGA or reduced MBW and exposure to PCE or TCE might also be a marker
for birth defects. However, SGA is only a weak surrogate for birth defects
( (39)).
Therefore, an association between exposure and birth defects would have
to be very strong to be detected in this study of SGA. It is not known
whether metabolites of TCE or PCE might affect fetal growth through a mechanism
independent of birth defects.
Toxicologic Literature
The association between low level
environmental exposure to PCE or TCE and adverse pregnancy outcomes has
not been determined. In one controlled clinical trial (
(40)), pregnant mice
exposed to 300 parts per million (ppm) PCE delivered litters that had an
average birth weight that was 9% lower than the normal average; these litters
also were twice as likely to have subcutaneous edema than unexposed mice,
and the increase in the number of litters with delayed ossification of
skull bones was statistically significant. There was a 60% increase in
the number of mice that were runts (defined as weighing less than three
standard deviations below average) among the exposed litters, but this
difference was not statistically significant. Fetal rats exposed to the
same regimen did not have lower birth weight or excessive delays in ossification.
However, there were a greater proportion of fetal resorptions among exposed
rats than among unexposed rats. This effect was not observed among mice.
Maternal toxicity resulting from PCE exposure was manifested by decreased
maternal weight gain and increased maternal liver weight in rats and mice,
respectively. However, it seems unlikely that the developmental effects
of PCE were the result of maternal toxicity because pregnant rodents exposed
to other solvents in this investigation experienced similar toxicity but
their litters were unaffected.
TCE exposure has not been associated
with measured adverse pregnancy outcomes in the late stages of gestation
except with severe maternal toxicity (40). However, both developmental
and behavioral effects in laboratory animals after exposure to TCE have
been noted (38, (41),
(42)).
The timing of the development of human and rat brains is different. Neonatal
development of the rat brain corresponds to development of the human brain
during the third trimester of pregnancy
( (43));
therefore, behavioral effects observed in neonatal rats might be of significance
to the developing human fetus.
Although useful in generating
hypotheses regarding the developmental hazards of specific contaminants,
toxicologic studies are complicated by the need to extrapolate from animal
species and high doses. In addition, laboratory studies do not adequately
capture the complex personal and environmental contexts in which human
exposures to VOCs occur ( (44)).
Epidemiologic Literature
Several studies have examined
the issue of late pregnancy outcomes and occupations in which women might
have been exposed to VOCs ( (45),
(46),
(47),
(48),
(49),
(50),
(51), (52),
(53), (54),
(55),
(56), (57)).
However, fewer of these studies have examined exposure to specific chemicals
or chemical classes. Two studies of maternal occupational exposure to solvents
(47) and degreasing agents (52)
noted small decreases in birth weight (-41
g ±124 g and -16 g ±75 g, respectively), but these decreases
were not statistically significant. A small case-control study (26 cases)
of birth outcomes among female workers in Sweden, Finland, and Norway found
no association between very low birth weight, congenital malformations,
or stillbirths and working in the dry-cleaning or laundry industry (
(58)). However, in
addition to the limited number of cases, all three outcomes were combined
into a single case definition; this categorization did not account for
the different times at which developing organisms are vulnerable to stillbirth
or very low birth weight and when they are vulnerable to congenital malformations.
Only two studies have evaluated
the possible association between halogenated hydrocarbons and late pregnancy
outcomes. Savitz et al. (54) noted no association between exposure to halogenated
hydrocarbons and SGA (OR: 0.6 [95% CL: 0.2, 1.4]), preterm delivery (OR:
1.1 [95% CL: 0.5, 2.4]), and stillbirth (OR: 1.0 [95% CL: 0.7, 1.5]). Windham
et al. (55) noted no association between SGA and maternal exposure to halogenated
solvents during the first 20 weeks of pregnancy (OR: 1.1 [95% CL: 0.4,
2.9]); however, fetal growth is considered most vulnerable to environmental
insults during the third trimester of pregnancy. Therefore, this latter
study might have focused on exposures that occurred at a time when the
fetus was relatively invulnerable to effects on birth weight.
Limitations common to many of
these occupational studies included: indirect estimates of exposure derived
from job titles rather than measured exposure in the work place, the small
numbers of women in specific exposure categories, and differential participation
and recall by underlying maternal risk. In addition, because exposure to
many different substances occurs in the same work place (
(59)), the relevant
hazards could be difficult to identify. Many of these factors are more
likely to introduce bias toward the null hypotheses than they are to introduce
associations where none exist, although an upward bias could be introduced
by differential participation or recall.
Environmental exposures to toxic
substances occur at lower concentrations relative to the occupational setting.
However, environmental exposures often occur through contaminated drinking
water, while occupational exposures usually occur through inhalation or
skin contact. As discussed previously (see "Routes of TCE and PCE Exposure
and Metabolism"), PCE and TCE metabolism differ depending on whether these
compounds are inhaled or ingested. Environmental exposures are not limited
to the 40-hour work week and can occur in populations that are not represented
in the work force. Women who are less likely to work include those who
cannot find work, those who already have children, and those without economic
incentive to work ( (60)). In addition,
women who are at high risk for adverse pregnancy outcomes might be instructed
by their physicians to cease work during pregnancy (60). These factors
all limit the generalizations that can be made from studies of occupational
populations to residential populations exposed to environmental contaminants.
The earliest report of a relationship
between environmental exposure to toxic substances at hazardous waste sites
and late pregnancy outcomes was based on an investigation at Love Canal
in Niagara Falls, New York, a former dump site where 248 different chemicals
were identified. The prevalence of low birth weight was elevated in two
different studies of area residents ( (61),
(62)). Home ownership
among whites in the area of Love Canal where contaminants had seeped into
the basements of several homes was associated with a 60% increase in low
birth weight compared with all white residents of upstate New York (OR:
1.6 [95% CL: 1.0, 2.3]). Both the rate of low birth weight and the rate
of prematurity were higher among Love Canal homeowners compared with rates
among homeowners in neighboring areas of Niagara Falls (low birth weight
OR: 3.1 [95% CL: 1.3, 7.1], prematurity OR: 1.4 [95% CL: 0.8, 3.5]). However,
no increases in low birth weight (OR: 1.1 [95% CL: 0.5, 2.3]) or preterm
delivery (OR: 1.1 [95% CL: 0.6, 2.2]) were observed among renters at Love
Canal when compared with rates among renters in neighboring areas.
More recently, an increased prevalence
of term low birth weight (another index of intrauterine growth retardation)
was found among residents near Lipari landfill in Gloucester County, New
Jersey. During the years when odors were greatest at the site, the OR was
5.1 (90% CL: 2.5, 10.6) ( (63)).
Moreover, a strong correlation was observed between 3-year weighted averages
of excess term low birth weight around the landfill and the timing of dumping
and odors throughout the 25-year study period. A cohort study conducted
near the Stringfellow hazardous waste site in Riverside County, California
( (64)),
and an ecologic study conducted of hazardous waste sites in five counties
in the San Francisco Bay area of California ( (65))
reported no associations between proximity to site and low birth weight
(OR: 0.9 [95% CL: 0.3, 2.7]) or MBW (0.6 g ±12.3).
Each of the studies of birth weight
around hazardous waste sites, summarized in Table 5, had methodologic problems.
One problem faced at Love Canal was that the families living closest to
Love Canal were relocated before the study was conducted (61), and the
remaining families were evacuated selectively, beginning with those families
with pregnant women and young children (61, (66)).
Hence, selective migration could have introduced bias in the association
between exposure and outcome. Selective migration also is likely to be
a problem at other hazardous waste sites, especially when strong odors
reduce the quality of life in a neighborhood. In such a situation, residents
with the highest incomes (who would be at the lowest risk (10)) and residents
who were most sensitive to the exposures would be most likely to leave
the vicinity. Although the effects that selective migration had on the
results cannot be predicted, it seems reasonable that the results of the
Love Canal evaluation might have been biased toward the null hypothesis.
The women who were most likely to have been exposed had already been evacuated
and were not included in the study.
The conflation of preterm delivery
and SGA births in all but two of the studies probably reduced the observed
effect measures. Failure to account for such etiologic heterogeneity has
been discussed in detail elsewhere ( (67)).
The study conducted at Lipari landfill demonstrates this problem: the association
found between residence near the landfill and low birth weight in full-term
infants was stronger than the association found between residence near
the landfill and low birth weight in all infants (63).
Small numbers were also a problem,
especially at the Stringfellow site (64), limiting the precision of the
observed effect estimates. In most cases however, it would not have been
appropriate to increase the sample size because this would have created
a more heterogeneous exposure and, therefore, would have diluted the observed
association between exposure and outcome. Control for most major risk factors
was addressed in the studies summarized in Table 5, except for smoking,
which was not measured in the studies in San Francisco, California (65),
or Gloucester County, New Jersey (63). However, both the San Francisco
and Gloucester County studies controlled for demographic variables that
would have minimized bias from smoking.
The most important limitation
to the studies summarized in Table 5 was misclassification of exposure.
In all these studies, proximity to the hazardous waste site was the primary
classification of exposure.
Although there was some evidence of population exposure to VOCs based on
reports of odors, and at both Love Canal and Lipari minimal air measurements
were taken, it was difficult to determine if the persons included in the
studies had been exposed and, if so, to which substances and at what concentrations.
Because both the probability of exposure and the chemical mixture at each
site differ, it was difficult to evaluate, on the basis of consistency
across these studies, whether exposure to hazardous waste reduces birth
weight. However, in general, it seems reasonable to infer that environmental
exposure to some compounds or combinations of compounds found at hazardous
waste sites might decrease birth weight at least at some sites.
Studies of populations consuming
contaminated drinking water, although still imprecise, are a substantial
improvement over studies based on proximity to site. Even when exposure
data are limited and multiple contaminants are detected in the same water
distribution system, studies that focus on drinking water provide
a well-defined route of exposure, leaving less uncertainty as to whether
there is an exposed population, how many persons might be exposed, which
chemicals are present, and at what concentrations exposures are occurring
or have occurred in the past. Moreover, exposure is defined in a manner
that can be directly compared with exposure in other studies. Only three
analytic studies have investigated the relationship between TCE, PCE, or
DCE in drinking water and late pregnancy outcomes (
(68),
(69), (70)).
As summarized in Table 6, contaminant levels measured in these studies
were comparable to, or lower than, those observed at Camp Lejeune (68,69,70).
Two studies were conducted in
Woburn, Massachusetts, where two wells that supplied the town were found
to be contaminated with TCE, PCE, and chloroform. In the first of the Woburn
studies (68), self-reported outcomes were examined for 4,396 pregnancies
from 1960 through 1982. An important feature of the study was that the
investigators used information about the municipal use of supply wells
in different areas of Woburn to characterize exposure. Based on a logistic
regression model that examined exposure as a continuous variable, women
who received 100% of their water from contaminated wells had a tenfold
increase in risk for perinatal mortality relative to women who received
no water from contaminated wells. Although this risk estimate is impressive,
it was based on small numbers (four exposed cases). Furthermore, only two
women whose infants died could have received 100% of their water supply
from contaminated wells. This effect was noted only among pregnancies occuring
after 1970, with no increase in perinatal mortality noted among women exposed
during the first 10 years of the study. Because exposure was not measured
before 1979 (i.e., when tests first became available) it is possible that
there was less or no contamination during the earlier study period. Despite
the magnitude of the observed association, the small number of exposed
cases and inconsistency across time periods raises the possibility that
this finding was artifactual (i.e., arising through chance or confounding).
No association was noted between exposure to contaminated well water and
low birth weight, but birth weight was not adjusted for gestational age.
Moreover, low birth weight was reported by each mother, and a nonstandard
definition of low birth weight was used. Other limitations included the
sample selection process, which was based on residence in Woburn at the
time the study began, and the convenient selection process which could
have resulted in selection bias.
The second study conducted at
Woburn addressed a number of the methodologic limitations of the first
study by examining birth weight as recorded on birth certificates of infants
born to residents of Woburn during the time of exposure (69). The most
relevant comparisons in this study of SGA were those between birth weights
of live-born infants of East Woburn residents who were exposed to high
or moderate levels of contaminants during 1975 through 1979 and live-born
infants of East Woburn residents who were not exposed to contaminants.
For the approximately 3,000 live births, the prevalence of SGA was not
elevated among live-born infants of women who were highly exposed (OR:
1.1; 95% CL: 0.5, 2.4) or moderately exposed (OR: 0.7; 95% CL: 0.4, 1.4)
when exposure was classified on the basis of the entire pregnancy. However,
when the exposure classification was restricted to the third trimester,
the ORs were 1.6 (95% CL: 0.9, 2.8) and 1.3 (95% CL: 0.8, 2.1) for highly
and moderately exposed births, respectively. Despite the authors' conclusions
that the study "was unable to detect an adverse effect of exposure to Wells
G and H on the reproductive health of exposed subgroups of Woburn residents,"
(69) the specificity of these findings--that is, increasing ORs with more
refined classification of exposure and outcome--provides some evidence
for an association between TCE exposure and SGA.
The relationship between exposure
to TCE, PCE, and DCE (71)>
and late pregnancy outcomes in drinking water was also examined for the
entire state of New Jersey (70). Information was obtained from birth certificates
and fetal death certificates; exposure levels were based on semiannual,
quarterly, or monthly monitoring of drinking water. Maternal residence
on the birth certificate was used to assign exposure and was assumed to
be the residence throughout pregnancy. Although no associations were found
between TCE, PCE, or DCE exposure and SGA, preterm birth, or fetal death,
the median exposures evaluated were 200-1,000 times lower than the exposures
evaluated in this study.
Overall, knowledge about the potential
relationship between PCE, TCE, and 1,2-DCE exposure and late pregnancy
outcome is limited; although the results of several studies indicate that
environmental exposure to these VOCs might affect late pregnancy outcomes,
literature on this topic is limited and equivocal. Maternal occupational
exposure to solvents and other VOCs has been associated with increases
in stillbirths (51,53,54) and decreases in birth weight (53). However,
two occupational studies that focused specifically on halogenated hydrocarbons
reported no associations between these exposures and stillbirths, preterm
deliveries, or birth weight
(54,55). Low birth weight has also been associated
with residence near two different hazardous waste sites containing large
quantities of VOCs and other chemicals (61,62,63), but the exposures were
too poorly defined and too complex to permit generalizations from these
hazardous waste sites to others. Only the investigations (69,70) conducted
in Woburn, Massachusetts, examined the relationship between perinatal mortality
and SGA and a chemical exposure at concentrations similar to those at Camp
Lejeune. These investigations found increased rates of perinatal mortality
and moderate excesses in SGA, but both associations were based on small
numbers.
In addition to this direct, albeit
limited, evidence that one or more of the solvents studied are associated
with adverse late pregnancy outcomes, two studies have noted associations
between term low birth weight and SGA and exposure to carbon tetrachloride
(70) and trihalomethanes, including chlorinated compounds of similar chemical
structure (70, (72)).
Other reports suggest that occupational or environmental exposures to solvents
in general, and to TCE or PCE in particular, can cause other adverse pregnancy
outcomes, such as spontaneous abortion, cardiac anomalies, oral clefts,
and neural tube defects (42,55,70, (73),
(74)).
Finally, there may be an association
between solvent exposure and maternal complications of pregnancy. In a
small prospective study of women occupationally exposed to solvents, Eskenazi
et al. found increased rates of preeclampsia (OR: 3.9; 95% CL: 2.4, 5.4)
and hypertension (OR: 3.0; 95% CL: 0.9, 9.9) (47). Moreover, these complications
were restricted to women who worked during their second trimester of pregnancy.
In a small case-control study of 130 pregnant residents of an industrial
area of Bulgaria, Tabacova et al. ( (75))
found substantially increased odds of exposure to styrene among pregnant
women with anemia (OR: 2.4; 95% CL: 0.5, 13.8), proteinuria (OR: 7.4; 95%
CL: 1.7, 37.2), hyperemesis (OR: 13.1; 95% CL: 1.4, 165.9), arterial hypertension
(OR: 26.4; 95% CL: 2.2, 1266.8), and nephropathy (OR: 30.8; 95% CL: 2.6,
1448.0). However, as one might gather from the wide confidence intervals
(76), that study was extremely
small. Although the literature relating VOC exposure to medical complications
of pregnancy is only suggestive, it provides a biologically plausible mechanism
by which exposure to VOCs might affect fetal growth.
In summary, information is sparse
regarding the relationship between exposure to organic solvents, such as
PCE and TCE in drinking water, and late pregnancy outcomes; and PCE and
TCE frequently occur in the environment. Only three studies have examined
directly the relationship between PCE or TCE in drinking water and late
adverse pregnancy outcomes. Only two of those studies, both analyzing data
from the same city, observed exposures of similar concentration to the
exposures experienced at Camp Lejeune. This study at Camp Lejeune should
add to the existing body of knowledge, providing more information on a
topic of great public health concern.
This page last updated on November 22, 2000
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