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A sensitivity analysis of bias in relative risk estimates due to disinfection by-product exposure misclassification

Abstract

We conducted a sensitivity analysis of relative risk estimates using local area mean disinfection by-product exposures. We used Monte Carlo simulations to generate data representing 100 towns, each with 100 births (n=10,000). Each town was assigned a mean total trihalomethane (TTHM) exposure value (mean=45, SD=28) based on a variable number of sampling locations (range 2–10). True maternal TTHM exposure was randomly assigned from a lognormal distribution using that town's true mean value. We compared the effect of a 20 μg/l increase in TTHM exposure on the risk of small-for-gestational age infancy using the true maternal exposure compared to various weighting measures of the town mean exposures. The exposure metrics included: (1) unweighted town mean, (2) town mean weighted by the inverse variance of the town mean, (3) town mean weighted by the inverse standard deviation of the town mean, (4) town mean weighted by 1−(standard deviation of sites per town/mean across all towns), and (5) a randomly selected value from one of the sites within the town of residence. To estimate the magnitude of misclassification bias from using the town mean concentrations, we compared the true exposure odds ratios (1.00, 1.20, 1.50, and 2.00) to the mean exposure odds ratios from the five exposure scenarios. Misclassification bias from the use of unweighted town mean exposures ranged from 19 to 39%, increasing in proportion to the size of the true effect estimates. Weighted town mean TTHM exposures were less biased than the unweighted estimates of maternal exposure, with bias ranging from 0 to 23%. The weighted town mean analyses showed that attenuation of the true effect of DBP exposure was diminished when town mean concentrations with large variability were downweighted. We observed a trade-off between bias and precision in the weighted exposure analyses, with the least biased effects estimates having the widest confidence intervals. Effect attenuation due to intrasystem variability was most evident in absolute and relative terms for larger odds ratios.

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References

  • Bove F.J., Fulcomer M.C., and Klotz J.B., et al. Public drinking water contamination and outcomes. Am J Epidemiol 1995: 141: 850–862.

    Article  CAS  Google Scholar 

  • Bove F., Shim Y., and Zeitz P. Drinking water contaminants and adverse pregnancy outcomes: a review. Environ Health Perspect 2002: 110(Suppl 1): 61–74.

    Article  Google Scholar 

  • Chen W.J., and Weisel C.P. Halogenated DBP concentrations in a distribution system. J Am Water Works Assoc 1998: 90(4): 151–163.

    Article  CAS  Google Scholar 

  • Dodds L., King W., and Woolcott C., et al. Trihalomethanes in public water supplies and adverse birth outcomes. Epidemiology 1999: 10(3): 233–237.

    Article  CAS  Google Scholar 

  • Gallagher M.D., Nuckols J.R., and Stallones L., et al. Exposure to trihalomethanes and adverse pregnancy outcomes. Epidemiology 1998: 9(5): 484–489.

    Article  CAS  Google Scholar 

  • Graves C.G., Matanoski G.M., and Tardiff R.G. Weight of evidence for an association between adverse reproductive and developmental effects and exposure to disinfection by products: a critical review. Regul Toxicol Pharmacol 2001: 34: 103–124.

    Article  CAS  Google Scholar 

  • Hozalski R.M., Zhang L., and Arnold W.A. Reduction of haloacetic acids by FeO: implications for treatment and fate. Environ Sci Technol 2001: 35(11): 2258–2263.

    Article  CAS  Google Scholar 

  • King W.D., Dodds L., Armson B.A., Allen A.C., Fell D.B., and Nimrod C Exposure assessment in epidemiologic studies of adverse pregnancy outcomes and disinfection byproducts. J Expos Anal Environ Epidemiol 2004, doi: 10.1038/sj.jea 7500345.

  • Klotz J.B., and Pyrch L.A. Neural tube defects and drinking water disinfection by-products. Epidemiology 1999: 10(4): 383–390.

    Article  CAS  Google Scholar 

  • Kramer M., Lynch C., Isacson P., and Hanson J.W. The association of waterborne chloroform with intrauterine growth retardation. Epidemiology 1992: 3(5): 407–413.

    Article  CAS  Google Scholar 

  • Krasner S.W., McGuire M.J., Jacangelo J.G., Patania N.L., Reagan K.M., and Aieta E.M. The occurrence of disinfection by-products in US drinking water. J Am Water Works Assoc 1989: 81: 41–53.

    Article  CAS  Google Scholar 

  • Nieuwenhuijsen M.J., Toledano M.R., and Eaton N.E., et al. Chlorination disinfection by-products in water and their association with adverse reproductive outcomes: a review. Occup Environ Med 2000: 57: 73–85.

    Article  CAS  Google Scholar 

  • Rodriquez M.J., and Serodes J.-B. Spatial and temporal evolution of trihalomethanes in three water distribution systems. Water Res 2001: 35(6): 1572–1586.

    Article  Google Scholar 

  • SAS. Version 8.2. SAS Institute, Inc., Cary, NC, 2000.

  • Savitz D., Andrews K., and Pastore L. Drinking water and pregnancy outcomes in central North Carolina: source, amount, and trihalomethane levels. Environ Health Perspect 1995: 103(6): 592–596.

    Article  CAS  Google Scholar 

  • Singer P. Control of disinfection by-products in drinking water. J Environ Eng 1994: 120(4): 727–744.

    Article  CAS  Google Scholar 

  • Sohn J., Gatel D., and Amy G. Monitoring and modeling of disinfection by-products (DBPs). Environ Monit Assess 2001: 70(1–2): 211–222.

    Article  CAS  Google Scholar 

  • Stevens A.A., Moore L.A., and Miltner R.J. Formation and control of non-trihalomethane disinfection by-products. J Am Water Works Assoc 1989: 81(8): 54–60.

    Article  CAS  Google Scholar 

  • Waller K., Swan S.H., and DeLorenze G., et al. Trihalomethanes in drinking water and spontaneous abortion. Epidemiology 1998: 9(2): 134–140.

    Article  CAS  Google Scholar 

  • Waller K., Swan S.H., Windham G.C., and Fenster L. Influence of exposure assessment methods on risk estimates in an epidemiologic study of total trihalomethane exposure and spontaneous abortion. J Expos Anal Environ Epidemiol 2001: 11(6): 522–531.

    Article  CAS  Google Scholar 

  • Whitaker H., Nieuwenhuijsen M.J., Best N., Fawell J., Gowers A., and Elliott P. Description of trihalomethane levels in three UK water suppliers. J Expos Anal Environ Epidemiol 2003a: 13: 17–23.

    Article  CAS  Google Scholar 

  • Whitaker H.J., Nieuwenhuijsen M.J., and Best N.G. The relationship between water concentrations and individual uptake of chloroform: a simulation study. Environ Health Perspect 2003b: 111(5): 688–694.

    Article  CAS  Google Scholar 

  • Wright J.M., Schwartz J., and Dockery D.W. Effect of trihalomethane exposure on fetal development. Occup Environ Med 2003: 60(3): 173–180.

    Article  CAS  Google Scholar 

  • Wright J.M., Schwartz J., and Dockery D.W. The effect of disinfection by-products and mutagenic activity on birth weight and gestation duration. Environ Health Perspect 2004: 112: 920–925.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr. Kevin Brand for his review of the manuscript and providing constructive comments and suggestions.

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Correspondence to J Michael Wright.

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Wright, J., Bateson, T. A sensitivity analysis of bias in relative risk estimates due to disinfection by-product exposure misclassification. J Expo Sci Environ Epidemiol 15, 212–216 (2005). https://doi.org/10.1038/sj.jea.7500389

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