Skip to main content
Occupational and Environmental Medicine logoLink to Occupational and Environmental Medicine
. 2003 Mar;60(3):173–180. doi: 10.1136/oem.60.3.173

Effect of trihalomethane exposure on fetal development

J Wright 1, J Schwartz 1, D Dockery 1
PMCID: PMC1740495  PMID: 12598663

Abstract

Aims: To examine the effect of trimester specific and pregnancy average total trihalomethane (TTHM) exposure on infant birth weight, low birth weight, and intrauterine growth retardation in term births, as well as gestational age and preterm delivery in all births.

Methods: Cross sectional analysis of 56 513 singleton infants born to residents of Massachusetts during 1990. City specific aggregate data were used to estimate maternal exposure to TTHM concentration; individual maternal information was used to adjust for confounding.

Results: Increased pregnancy average and second trimester TTHM exposure were associated with small for gestational age and reductions in birth weight after adjusting for potential confounding variables. Compared to ≤60 µg/l, pregnancy average TTHM exposure over 80 µg/l was associated with a 32 g reduction in birth weight. There was a 23 g reduction in birth weight in infants born to mothers exposed to greater than 80 µg/l TTHM during the second trimester. For each 20 µg/l increase in TTHM, the estimated reduction in birth was 2.8 g for pregnancy average exposure and 2.6 g for second trimester exposure. An increased risk of small for gestational age births was found for pregnancy average (odds ratio (OR) 1.14; 95% CI 1.02 to 1.26) and second trimester (OR 1.13, 95% CI 1.03 to 1.24) TTHM levels greater than 80 µg/l. There was no evidence of an association between preterm delivery and increased TTHM levels, but there were slight increases in gestational duration associated with TTHM concentrations.

Conclusions: Maternal exposure to THMs may be associated with fetal growth retardation. Our findings are consistent with most previous work, although we generally found smaller effects of TTHMs on low birth weight and intrauterine growth retardation.

Full Text

The Full Text of this article is available as a PDF (135.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander G. R., Kotelchuck M. Quantifying the adequacy of prenatal care: a comparison of indices. Public Health Rep. 1996 Sep-Oct;111(5):408–419. [PMC free article] [PubMed] [Google Scholar]
  2. Aschengrau A., Zierler S., Cohen A. Quality of community drinking water and the occurrence of late adverse pregnancy outcomes. Arch Environ Health. 1993 Mar-Apr;48(2):105–113. doi: 10.1080/00039896.1993.9938403. [DOI] [PubMed] [Google Scholar]
  3. Aschengrau A., Zierler S., Cohen A. Quality of community drinking water and the occurrence of spontaneous abortion. Arch Environ Health. 1989 Sep-Oct;44(5):283–290. doi: 10.1080/00039896.1989.9935895. [DOI] [PubMed] [Google Scholar]
  4. Bove F. J., Fulcomer M. C., Klotz J. B., Esmart J., Dufficy E. M., Savrin J. E. Public drinking water contamination and birth outcomes. Am J Epidemiol. 1995 May 1;141(9):850–862. doi: 10.1093/oxfordjournals.aje.a117521. [DOI] [PubMed] [Google Scholar]
  5. Bove F. J. Public drinking water contamination and birthweight, prematurity, fetal deaths, and birth defects. Toxicol Ind Health. 1996 Mar-Apr;12(2):255–266. [PubMed] [Google Scholar]
  6. Bull R. J., Meier J. R., Robinson M., Ringhand H. P., Laurie R. D., Stober J. A. Evaluation of mutagenic and carcinogenic properties of brominated and chlorinated acetonitriles: by-products of chlorination. Fundam Appl Toxicol. 1985 Dec;5(6 Pt 1):1065–1074. doi: 10.1016/0272-0590(85)90142-3. [DOI] [PubMed] [Google Scholar]
  7. Bull R. J., Sanchez I. M., Nelson M. A., Larson J. L., Lansing A. J. Liver tumor induction in B6C3F1 mice by dichloroacetate and trichloroacetate. Toxicology. 1990 Sep;63(3):341–359. doi: 10.1016/0300-483x(90)90195-m. [DOI] [PubMed] [Google Scholar]
  8. Cantor K. P., Lynch C. F., Hildesheim M. E., Dosemeci M., Lubin J., Alavanja M., Craun G. Drinking water source and chlorination byproducts. I. Risk of bladder cancer. Epidemiology. 1998 Jan;9(1):21–28. [PubMed] [Google Scholar]
  9. David R. J. The quality and completeness of birthweight and gestational age data in computerized birth files. Am J Public Health. 1980 Sep;70(9):964–973. doi: 10.2105/ajph.70.9.964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dodds L., King W., Woolcott C., Pole J. Trihalomethanes in public water supplies and adverse birth outcomes. Epidemiology. 1999 May;10(3):233–237. [PubMed] [Google Scholar]
  11. Dowty B. J., Laseter J. L., Storer J. The transplacental migration and accumulation in blood of volatile organic constituents. Pediatr Res. 1976 Jul;10(7):696–701. doi: 10.1203/00006450-197607000-00013. [DOI] [PubMed] [Google Scholar]
  12. Gallagher M. D., Nuckols J. R., Stallones L., Savitz D. A. Exposure to trihalomethanes and adverse pregnancy outcomes. Epidemiology. 1998 Sep;9(5):484–489. [PubMed] [Google Scholar]
  13. Graves C. G., Matanoski G. M., 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 Oct;34(2):103–124. doi: 10.1006/rtph.2001.1494. [DOI] [PubMed] [Google Scholar]
  14. Hildesheim M. E., Cantor K. P., Lynch C. F., Dosemeci M., Lubin J., Alavanja M., Craun G. Drinking water source and chlorination byproducts. II. Risk of colon and rectal cancers. Epidemiology. 1998 Jan;9(1):29–35. [PubMed] [Google Scholar]
  15. King W. D., Marrett L. D. Case-control study of bladder cancer and chlorination by-products in treated water (Ontario, Canada). Cancer Causes Control. 1996 Nov;7(6):596–604. doi: 10.1007/BF00051702. [DOI] [PubMed] [Google Scholar]
  16. Klotz J. B., Pyrch L. A. Neural tube defects and drinking water disinfection by-products. Epidemiology. 1999 Jul;10(4):383–390. doi: 10.1097/00001648-199907000-00005. [DOI] [PubMed] [Google Scholar]
  17. Koivusalo M., Hakulinen T., Vartiainen T., Pukkala E., Jaakkola J. J., Tuomisto J. Drinking water mutagenicity and urinary tract cancers: a population-based case-control study in Finland. Am J Epidemiol. 1998 Oct 1;148(7):704–712. doi: 10.1093/aje/148.7.704. [DOI] [PubMed] [Google Scholar]
  18. Koivusalo M., Jaakkola J. J., Vartiainen T., Hakulinen T., Karjalainen S., Pukkala E., Tuomisto J. Drinking water mutagenicity and gastrointestinal and urinary tract cancers: an ecological study in Finland. Am J Public Health. 1994 Aug;84(8):1223–1228. doi: 10.2105/ajph.84.8.1223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Koivusalo M., Pukkala E., Vartiainen T., Jaakkola J. J., Hakulinen T. Drinking water chlorination and cancer-a historical cohort study in Finland. Cancer Causes Control. 1997 Mar;8(2):192–200. doi: 10.1023/a:1018420229802. [DOI] [PubMed] [Google Scholar]
  20. Koivusalo M., Vartiainen T., Hakulinen T., Pukkala E., Jaakkola J. J. Drinking water mutagenicity and leukemia, lymphomas, and cancers of the liver, pancreas, and soft tissue. Arch Environ Health. 1995 Jul-Aug;50(4):269–276. doi: 10.1080/00039896.1995.9935953. [DOI] [PubMed] [Google Scholar]
  21. Komulainen H., Kosma V. M., Vaittinen S. L., Vartiainen T., Kaliste-Korhonen E., Lötjönen S., Tuominen R. K., Tuomisto J. Carcinogenicity of the drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone in the rat. J Natl Cancer Inst. 1997 Jun 18;89(12):848–856. doi: 10.1093/jnci/89.12.848. [DOI] [PubMed] [Google Scholar]
  22. Kramer M. D., Lynch C. F., Isacson P., Hanson J. W. The association of waterborne chloroform with intrauterine growth retardation. Epidemiology. 1992 Sep;3(5):407–413. doi: 10.1097/00001648-199209000-00005. [DOI] [PubMed] [Google Scholar]
  23. Kramer M. S. Determinants of low birth weight: methodological assessment and meta-analysis. Bull World Health Organ. 1987;65(5):663–737. [PMC free article] [PubMed] [Google Scholar]
  24. Kurokawa Y., Aoki S., Matsushima Y., Takamura N., Imazawa T., Hayashi Y. Dose-response studies on the carcinogenicity of potassium bromate in F344 rats after long-term oral administration. J Natl Cancer Inst. 1986 Oct;77(4):977–982. [PubMed] [Google Scholar]
  25. Künzli N., Tager I. B. The semi-individual study in air pollution epidemiology: a valid design as compared to ecologic studies. Environ Health Perspect. 1997 Oct;105(10):1078–1083. doi: 10.1289/ehp.105-1470382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Matheus M., Sala M. A. A mathematical model for the curves of intrauterine growth. Acta Physiol Lat Am. 1980;30(2):97–99. [PubMed] [Google Scholar]
  27. McGeehin M. A., Reif J. S., Becher J. C., Mangione E. J. Case-control study of bladder cancer and water disinfection methods in Colorado. Am J Epidemiol. 1993 Oct 1;138(7):492–501. doi: 10.1093/oxfordjournals.aje.a116883. [DOI] [PubMed] [Google Scholar]
  28. Morris R. D., Audet A. M., Angelillo I. F., Chalmers T. C., Mosteller F. Chlorination, chlorination by-products, and cancer: a meta-analysis. Am J Public Health. 1992 Jul;82(7):955–963. doi: 10.2105/ajph.82.7.955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Murray F. J., Schwetz B. A., McBride J. G., Staples R. E. Toxicity of inhaled chloroform in pregnant mice and their offspring. Toxicol Appl Pharmacol. 1979 Sep 30;50(3):515–522. doi: 10.1016/0041-008x(79)90406-x. [DOI] [PubMed] [Google Scholar]
  30. Nieuwenhuijsen M. J., Toledano M. B., Eaton N. E., Fawell J., Elliott P. Chlorination disinfection byproducts in water and their association with adverse reproductive outcomes: a review. Occup Environ Med. 2000 Feb;57(2):73–85. doi: 10.1136/oem.57.2.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ruddick J. A., Villeneuve D. C., Chu I., Valli V. E. A teratological assessment of four trihalomethanes in the rat. J Environ Sci Health B. 1983;18(3):333–349. doi: 10.1080/03601238309372373. [DOI] [PubMed] [Google Scholar]
  32. Savitz D. A., Andrews K. W., Pastore L. M. Drinking water and pregnancy outcome in central North Carolina: source, amount, and trihalomethane levels. Environ Health Perspect. 1995 Jun;103(6):592–596. doi: 10.1289/ehp.95103592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schwetz B. A., Leong B. K., Gehring P. J. Embryo- and fetotoxicity of inhaled chloroform in rats. Toxicol Appl Pharmacol. 1974 Jun;28(3):442–451. doi: 10.1016/0041-008x(74)90229-4. [DOI] [PubMed] [Google Scholar]
  34. Thompson D. J., Warner S. D., Robinson V. B. Teratology studies on orally administered chloroform in the rat and rabbit. Toxicol Appl Pharmacol. 1974 Sep;29(3):348–357. doi: 10.1016/0041-008x(74)90107-0. [DOI] [PubMed] [Google Scholar]
  35. Tuthill R. W., Giusti R. A., Moore G. S., Calabrese E. J. Health effects among newborns after prenatal exposure to ClO2-disinfected drinking water. Environ Health Perspect. 1982 Dec;46:39–45. doi: 10.1289/ehp.824639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Vorherr H. Factors influencing fetal growth. Am J Obstet Gynecol. 1982 Mar 1;142(5):577–588. doi: 10.1016/0002-9378(82)90765-7. [DOI] [PubMed] [Google Scholar]
  37. Waller K., Swan S. H., DeLorenze G., Hopkins B. Trihalomethanes in drinking water and spontaneous abortion. Epidemiology. 1998 Mar;9(2):134–140. [PubMed] [Google Scholar]
  38. Weisel C. P., Jo W. K. Ingestion, inhalation, and dermal exposures to chloroform and trichloroethene from tap water. Environ Health Perspect. 1996 Jan;104(1):48–51. doi: 10.1289/ehp.9610448. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Occupational and Environmental Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES