Health Stream Literature Summary - Issue 56 - December 2009

Prenatal exposure to tetrachloroethylene-contaminated drinking water and the risk of congenital anomalies: a retrospective cohort study.
Aschengrau, A., Weinberg, J.M., Janulewicz, P.A., Gallagher, L.E., Winter, M.R., Vieira, V.M., Webster, T.F. and Ozonoff, D.M. (2009) Environmental Health 8:44.

In 1980 in New England it was discovered that PCE (perchloroethylene, tetrachloroethylene) was leaching into the public drinking water supplies from the inner vinyl lining (VL) of asbestos cement(AC) water distribution pipes. The pipe lining had been used since the late 1960s to combat taste and odour problems in the distribution system, and it was assumed that the volatile PCE solvent used to apply the vinyl resin would have evaporated from the pipes before they were installed. More than a decade later however, it was discovered that high levels of PCE remained in the liner and this substance was being released into public drinking water supplies. There had been about 660 miles of VL/AC pipes installed in Massachusetts with a large portion in the Cape Cod region. Levels of PCE in residential areas in the Cape Cod town of Falmouth were found to range from undetectable to 80 micro g/L in water pipes along main streets with high water flow and from 1,600 to 7,750 micro g/L in water pipes along dead end streets with low water flow. The current U.S. E.P.A. drinking water regulations set the PCE maximum contaminant level at 5 micro g/L. A flushing and bleeding program in the most problematic areas was introduced to reduce levels below 40 micro g/L, the suggested action guide in 1980. Health concern in relation of PCE have mainly been based on its carcinogenicity however several epidemiological studies have also found associations between prenatal exposure to organic solvents and risk of congenital anomalies. A population-based retrospective cohort study was undertaken to examine the influence of maternal exposure to PCE contaminated drinking water on a variety of pregnancy and developmental outcomes, including low birth weight, prematurity and learning disabilities. This current study focuses on the risk of congenital anomalies among children whose mothers were exposed around the time of conception.

Eligible women were those who gave birth to a child (termed 'index child') during 1969-1983 while they were living in one of 8 Cape Cod towns with some VL/AC water distribution pipes. Two groups of women were selected by reviewing Massachusetts birth certificates: (1) mothers who were 'exposed' to PCE-contaminated drinking water when the 'index' child was born, and (2) mothers who were 'unexposed' when the 'index' child was born. 'Unexposed' mothers were frequency matched to 'exposed' mothers on month and year of birth of their index child. Between 2002 and 2003, follow-up and enrolment of mothers occurred. Self-administered questionnaires were sent to all successfully traced mothers to obtain information on their entire reproductive history, including the presence of congenital anomalies among all index and non-index births. Also information was gathered on maternal demographic characteristics including race and educational level; data on smoking, alcohol intake, caffeine consumption, weight gain and obstetrical complications during each pregnancy; medical conditions such as diabetes and hypertension; occupational exposure to solvents; use of solvent-based spot removers, professional and self-service dry cleaning. Information was also collected on the family's residences from 1969 through 1990 and the proximity of any residences to dry cleaning establishments. Information on mother's water consumption and bathing habits at these residences could not be recalled by a large portion of mothers. All maternal reports of congenital anomalies were reviewed and only diagnoses currently regarded as congenital malformation s were included in this study. Anomalies were categorised into groups including: central nervous, cardiovascular, respiratory, gastrointestinal, genitourinary tract and musculoskeletal systems; eye, ear, face and neck; chromosomal; and other and unspecified anomalies.

All residential addresses in Cape Cod reported on the questionnaires were geocoded to a latitude and longitude. PCE exposure for all index and non-index births was estimated using EPANET water distribution modelling software that used a fate and transport model. There were 61 children with congenital anomalies of the 1,658 children with some prenatal PCE exposure and 95 children with congenital anomalies of the 2,999 children with no prenatal PCE exposure. The prevalence per 1,000 births was 3.7 and 3.2 respectively. Nearly 39% of mothers reported they could not recall their water consumption or bathing patterns during the study pregnancy. Of those who could recall this information, the percentages who drank bottled water (about 22%), consumed more than four glasses of tap water per day (about 51%) and took long showers (about 23%) were similar between the exposed and unexposed groups.

The crude and adjusted generalized estimating equation (GEE) odds ratio for all congenital anomalies combined were 1.2 (95% CI: 0.8, 1.6) and 1.1 (95% CI: 0.8, 1.6), respectively, among children with any prenatal PCE exposure. These odds ratios were virtually unchanged when maternal and paternal age was controlled for simultaneously and when other confounders including calendar year of birth; mother's educational level; cigarette smoking; alcoholic beverage consumption; and prior pregnancy losses; and child's gender were controlled for one at a time. The results were still unchanged when only major malformations were examined. The parental-age adjusted GEE odds ratio for all anomalies was elevated by 40% (95% CI: 0.9-2.2) among those children with average monthly prenatal exposure greater than 1.136 grams, the cut point corresponding to an average drinking water concentration of 40 ug/L, and elevated by 50% among those children whose average monthly prenatal exposure was greater than or equal to the 75th percentile (average monthly prenatal exposure of 2.3 grams) (95% CI: 0.9-2.5). There were no meaningful increases in risk found for lower exposure levels. When organ systems and diagnostic groups were examined, large increases in the odds ratios for neural tube defects (GEE OR 3.5, 95% CI:0.8-14.0) and oral clefts (GEE OR 3.2, 95% CI 0.7-15.0) were found and modest increases were for gastrointestinal (GEE OR 1.8, 95% CI: 0.7-4.4) and genitourinary malformations (GEE OR 1.6, 95% CI: 0.6-3.8), including hypospadias (GEE OR 1.4, 95% CI: 0.4-5.4) and chromosomal malformations (GEE OR 1.4, 95% CI: 0.3-601) among children with any prenatal PCE exposure. Odds ratios for all gastrointestinal defects combined and oral clefts were further increased among children whose average monthly prenatal exposure was greater than 1.136 grams. No dose-response relationship was found for neural tube defects.

The results of this study suggest that prenatal exposure to PCE increases the risk of certain kinds of congenital anomalies. Prenatal exposure was associated with large increases in the risk of gastrointestinal defects (particularly oral clefts) and neural tube defects (particularly anencephaly), however an exposure related dose-response relationship was found for oral clefts but not for neural tube defects. The findings of this study were limited by the small number of children with anomalies also results were based on maternal reports which may have under-reported the number of anomalies, particularly minor ones. It is recommended that a follow-up investigation be conducted with a larger number of affected children who are identified by independent paediatric records. As PCE is still a commonly used solvent and a frequent contaminant of ground and drinking water supplies it is important to understand its relationship to the occurrence of congenital anomalies.

Comment This study relied on reporting of congenital anomalies by mothers and did not verify these reports against official registries. This is a significant weakness as self-reporting might have resulted in incorrect classification of anomalies. The authors also note that the statistical power was low due to the small number of children involved, and none of the reported Odds Ratios were statistically significant.

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