Understanding the Biologic Mechanism for a Relationship between Exposure to Trihalomethanes and Adverse Pregnancy Outcomes

Principal Investigator - Linda Dodds, Professor, Dalhousie University, 2001 - 2004

Understanding the Biologic Mechanism for a Relationship between Exposure to Trihalomethanes and Adverse Pregnancy Outcomes


Most public drinking water systems in North America use chlorine compounds for disinfection. However, chlorine can react with organic material in source water to produce several classes of chemical by-products, such as trihalomethanes (THMs). Exposure to such disinfection by-products during pregnancy has been linked to several adverse birth outcomes, including stillbirths, spontaneous abortions, congenital anomalies and fetal growth restriction. Despite evidence of such a relationship, there is little understanding of potential biologic mechanisms. However, previous studies have revealed that disturbances in maternal and fetal levels of homocysteine, an amino acid involved in several key metabolic processes, have been associated with a suite of adverse outcomes, all of which have also been linked to exposure to THMs in drinking water.

The goal of this project was to improve understanding of the linkages between THMs and adverse pregnancy outcomes by investigating impacts on the homocysteine metabolic pathway.


This project is one of the first studies examining disinfection by-products and adverse birth effects that attempts to identify a biologic mechanism. The researchers hypothesized that exposure to disinfection by-products would interfere with the homocysteine metabolic pathway, resulting in elevated levels of homocysteine. The team investigated whether the presence of specific phenotypes associated with the metabolism of environmental chemicals modified the effect of THMs on homocysteine levels. Critical assumptions around water sampling were also tested, which would provide useful information in terms of individual exposure. The following summations could be made: morning samples were representative of homocysteine levels throughout the day; little variability existed by day of week; by-product levels were elevated in hot tap water samples relative to cold water; and sample levels increased in the absence of pH adjustment at the time of sampling.

Using existing recruitment and blood collection procedures in place from an on-going cohort study, the researchers recruited 170 women at less than 20 weeks’ gestation. The women all provided blood samples and a home water sample, as well as completed a questionnaire on water use behaviours. The blood samples were measured for homocysteine level and genetic susceptibility factors.

Data analysis revealed that there was no relationship between by-product exposure and homocysteine level. There was, however, signification associations with established predictors of homocysteine level, which included age, gestational age, folic acid supplementation and serum folate levels.

Despite null findings in relation to THM exposures, the study provided some useful insights. The study population displayed a high rate of folic acid supplementation, which can reduce elevated homocysteine levels. This suggests that, while a relationship between THM exposure and homocysteine level does not exist in a population with this level of supplementation, it might exist in those without supplementation. The study itself was limited in terms of number of subjects, subject variety, and exposure contrasts, which all lessened the likelihood of observing significant associations with homocysteine level.