Chloroform contamination at 50 ppb or more has been associated with SGA in some studies 9 — 11 but not others 12 , One study found that trichloroethylene exposure 6— ppb during the third trimester of pregnancy was associated with SGA 14 ; a study of lower-level exposure to trichloroethylene 10 ppb or more revealed no association with SGA 9.
Both receive water from the same water distribution system. As shown in table 1 , drinking water supplied to TT contained PCE and lower levels of other volatile organic compounds 15 , PCE was released to the ABC septic system via a floor drain during routine storage, use, and recycling. The septic system discharged wastewater directly into subsurface soil. Supply well 26 TT26 is located approximately feet m from this septic field. Information regarding levels of volatile organic compounds in TT26 was not available prior to , but we assumed that the supply well was contaminated soon after it was dug in ABC opened in ; according to the owners, business practices were essentially unchanged between and , although volume decreased temporarily in TT26 and two other contaminated wells were permanently disconnected from the TT water system on February 8, After that date, TT26 samples were not indicative of previous contamination levels, because the pumping operation itself was responsible for drawing con-taminants into the well.
TT26 was the only one of six routinely used wells with detectable contamination. On any given day, use of five of the wells was essentially random. Therefore, exposure over time was intermittent and fluctuated depending on the proportion of water pumped from the contaminated well each day. PCE concentrations in finished water samples were consistent with what might be expected if water from TT26 had been diluted with a similar volume of water from four other wells.
A notable characteristic of the water distribution systems at Camp Lejeune is that all supply wells for a given system were mixed before distribution. Therefore, PCE concentrations were not related to the distance between particular housing units and TT Because the water was mixed prior to distribution, we expected that PCE concentrations in water delivered to each TT housing unit would have been similar on any given day The study population consisted of singleton liveborn infants of 20 or more completed weeks of gestation born to Camp Lejeune residents in — We selected as the first year of study because it was the first year that that part of the North Carolina birth certificate was computerized.
Birth certificates were matched to base family housing records on mother's address and, in most cases, father's name. Housing records contained dates of occupancy and military pay grade for the family member assigned to the unit. Births to mothers who were living in base family housing when they delivered and who had lived there for at least 1 week prior to giving birth were included.
TT residents were considered PCE exposed. Two groups of residents were exposed to trichloroethylene through a different water system and were excluded. Residents of base trailer parks were excluded because housing records were incomplete.
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The remaining base family housing residents were classified as unexposed based on water samples drawn from supply wells and finished distribution systems in and We excluded less than 5 percent of the exposed and unexposed groups because of poor data quality. Premature births were defined as livebirths occurring at less than 37 completed weeks of gestation. Gestational age was calculated from the mother's last menstrual period.
Approximately 1 percent of observations were deleted from the mean birth weight and SGA analysis, but not from the preterm birth analyses, because of extremely unlikely combinations of gestational age and birth weight 17 ; all of these observations were for preterm births.
Years later, Marine families bear scars of poisoning at Camp Lejeune
SGA is normally measured by comparing birth weight at specific gestational ages with a gestational-age-specific birth-weight distribution. Livebirths of infants weighing less than the 10th percentile are classified as SGA. Given the military's somewhat unique social and health care environment, we would ideally have used a standard birth-weight distribution for a military population during the years of study. Because such a standard was not available, we evaluated three different standards 9 , 17 , 18 and selected the one published by Williams et al.
Of the three standards evaluated, this was the only one derived specifically from White births, but, when all races were included, it fit best. Mean differences or odds ratios and 90 percent confidence intervals were computed.
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The covariates included in simple stratified analyses were infant's sex and year of birth; mother's race, age, educational level, parity, adequacy of prenatal care 19 , marital status, and history of fetal death; and father's age, educational level, and military pay grade. Variable selection in regression models proceeded by backward elimination. Initial models considered main effects only, treating covariates as potential confounders. Subsequently, effect modification was also considered. For the analyses of SGA and preterm birth, covariates were retained as effect modifiers in regression models only if they were biologically plausible, described heterogeneous groups in which the odds ratios differed by more than 25 percent, and had p values of less than 0.
For mean birth weight, covariates for which at least one stratum-specific estimate showed a mean difference between PCE-exposed and unexposed births of at least 50 g were examined for effect modification. We adjusted for gestational age in mean birth-weight analyses to distinguish between associations with reduced fetal weight gain and those with early time of birth; failure to make this distinction can obscure associations between exposure to hazardous waste and delayed fetal growth 10 , The influence of duration of exposure was also explored. For each household, the dates of occupancy were used to determine whether and when each family moved during the mother's pregnancy.
Length of residence at TT prior to giving birth served as a surrogate for length of exposure. Following analysis of a sample of housing records, we assumed that length of exposure indicated the number of consecutive weeks prior to delivery that a mother lived at TT.
For example, a mother residing at TT for 10 weeks lived at TT during the last 10 weeks of the pregnancy. Cutpoints for duration of exposure analyses were developed following a literature review to identify periods during gestation when a toxic agent might most interfere with fetal growth or timing of birth. In the absence of more refined historical information, we assumed that PCE exposures were essentially constant throughout the years of study.
However, we also conducted separate analyses of births occurring during the period of documented exposure—May 27, , through February 7, The distribution of demographic characteristics in the unexposed and PCE-exposed groups is presented in table 2. PCE-exposed mothers were less likely to be White, less likely to live in officer's housing, less likely to be college educated, and less likely to have a college-educated partner.
The odds ratio for PCE exposure and preterm birth was 1. Adjustment for potential confounders did not tangibly affect these estimates. Table 3 examines birth outcomes by length of exposure to PCE. Associations between PCE exposure and mean birth weight, SGA, and preterm birth followed no obvious pattern with duration of exposure. Maternal age and maternal history of fetal loss seemed to interact with PCE for both birth-weight outcomes table 4.
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These groups appear to be distinct; 17 percent of PCE-exposed older mothers had had two or more fetal losses, and 3 percent of PCE-exposed mothers with prior fetal losses were older. Compared with their unexposed counterparts, older PCE-exposed mothers were more likely to be non-White The model also adjusted for gestational age, mother's race, living in an officer's or warrant officer's household, year of birth, and sex of the infant.
The model also adjusted for primiparity, living in an officer's or warrant officer's household, year of birth, and mother's education no. When analyses were restricted to births in the period of documented exposure, the results did not change meaningfully.
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Our study sample was too small to examine interaction during the period of documented exposure. The odds ratio for preterm delivery was 1. Analyses for this time period were adjusted for mother's race and educational level and for pay grade. Mean birth-weight analyses were also adjusted for gestational age. Stronger associations were observed between PCE exposure and both birth-weight outcomes for infants of mothers who were 35 years of age or older and for infants of mothers with a history of fetal death, especially those who had experienced two or more fetal deaths.
For preterm birth, no biologically relevant interactions were found between PCE and covariates. These results indicate nothing about the potential effects of PCE on other pregnancy outcomes including spontaneous abortions and birth defects, which were more plausible given findings from previous literature 4 — 9 but could not be studied by using our records-based approach at Camp Lejeune. The observation of at most a very weak effect for most infants must be tempered by an assessment of potential biases. Some potentially important confounders, such as maternal smoking habits and height, were not controlled.
It seems unlikely that these factors could have totally obscured a strong effect, especially in a population as homogeneous as the one studied.
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Misclassification of exposure is a chronic problem in environmental epidemiology. In this study, water quality data were available for less than a 3-year period, although the study examined 28 years of birth-outcome data. However, the circumstances that led to the contamination were present throughout the study period.
Moreover, to the limited extent that we could assess them, the results of analyses conducted during the period of known exposure were consistent with those for the entire study period. Other sources of misclassification were likely to have been more relevant. Even during the known exposure period, exposure was intermittent. Nonetheless, given the practice of rotating use of wells, exposure probably occurred during a majority of the days in every month of the study period.
The amount of exposure to PCE varied across the different persons studied, because women would have drunk different quantities of water and would have spent variable amounts of time showering. Unfortunately, we lacked information on variations in the personal habits of individual women. It is expected that these sources of misclassification would have reduced our ability to detect exposure-related effects.