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. 2003 Jun;111(7):947–953. doi: 10.1289/ehp.6080

Maternal serum dioxin levels and birth outcomes in women of Seveso, Italy.

Brenda Eskenazi 1, Paolo Mocarelli 1, Marcella Warner 1, Wan-Ying Chee 1, Pier Mario Gerthoux 1, Steven Samuels 1, Larry L Needham 1, Donald G Patterson Jr 1
PMCID: PMC1241530  PMID: 12782497

Abstract

2,3,7,8-Tetrachlorodibenzo-(italic)para(/italic)-dioxin (TCDD), a ubiquitous environmental contaminant, is associated with increased fetal loss and reduced birth weight in animal studies. In 1976, an explosion at a trichlorophenol plant near Seveso, Italy, resulted in the highest TCDD exposure known in human residential populations. In 1996, we initiated the Seveso Women's Health Study, a retrospective cohort study of women who resided in the most contaminated areas, zones A and B. We examined the relation of pregnancy outcome in 510 women (888 total pregnancies) to maternal TCDD levels measured in serum collected shortly after the explosion. Ninety-seven pregnancies (10.9%) ended as spontaneous abortions (SABs). There was no association of log(subscript)10(/subscript) TCDD with SAB [adjusted odds ratio (OR) = 0.8; 95% confidence interval (CI), 0.6-1.2], with birth weight (adjusted beta = -4 g; 95% CI, -68 to 60), or with births that were small for gestational age (SGA) (adjusted OR = 1.2; 95% CI, 0.8-1.8). However, associations with birth weight (adjusted beta = -92 g; 95% CI, -204 to 19) and with SGA (adjusted OR = 1.4; 95% CI, 0.6-2.9) were stronger for pregnancies within the first 8 years after exposure. TCDD was associated with a 1.0-1.3 day nonsignificant adjusted decrease in gestational age and a 20-50% nonsignificant increase in the odds of preterm delivery. It remains possible that the effects of TCDD on birth outcomes are yet to be observed, because the most heavily exposed women in Seveso were the youngest and the least likely to have yet had a pregnancy.

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Selected References

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  1. Abraham K., Knoll A., Ende M., Päpke O., Helge H. Intake, fecal excretion, and body burden of polychlorinated dibenzo-p-dioxins and dibenzofurans in breast-fed and formula-fed infants. Pediatr Res. 1996 Nov;40(5):671–679. doi: 10.1203/00006450-199611000-00005. [DOI] [PubMed] [Google Scholar]
  2. Abraham K., Päpke O., Gross A., Kordonouri O., Wiegand S., Wahn U., Helge H. Time course of PCDD/PCDF/PCB concentrations in breast-feeding mothers and their infants. Chemosphere. 1998 Oct-Nov;37(9-12):1731–1741. doi: 10.1016/s0045-6535(98)00238-0. [DOI] [PubMed] [Google Scholar]
  3. Akins J. R., Waldrep K., Bernert J. T., Jr The estimation of total serum lipids by a completely enzymatic 'summation' method. Clin Chim Acta. 1989 Oct 16;184(3):219–226. doi: 10.1016/0009-8981(89)90054-5. [DOI] [PubMed] [Google Scholar]
  4. Allen J. R., Barsotti D. A., Lambrecht L. K., Van Miller J. P. Reproductive effects of halogenated aromatic hydrocarbons on nonhuman primates. Ann N Y Acad Sci. 1979 May 31;320:419–425. doi: 10.1111/j.1749-6632.1979.tb56623.x. [DOI] [PubMed] [Google Scholar]
  5. Axelsson G., Rylander R. Validation of questionnaire reported miscarriage, malformation and birth weight. Int J Epidemiol. 1984 Mar;13(1):94–98. doi: 10.1093/ije/13.1.94. [DOI] [PubMed] [Google Scholar]
  6. Birnbaum L. S. The mechanism of dioxin toxicity: relationship to risk assessment. Environ Health Perspect. 1994 Nov;102 (Suppl 9):157–167. doi: 10.1289/ehp.94102s9157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Birnbaum L. S., Tuomisto J. Non-carcinogenic effects of TCDD in animals. Food Addit Contam. 2000 Apr;17(4):275–288. doi: 10.1080/026520300283351. [DOI] [PubMed] [Google Scholar]
  8. Bjerke D. L., Sommer R. J., Moore R. W., Peterson R. E. Effects of in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on responsiveness of the male rat reproductive system to testosterone stimulation in adulthood. Toxicol Appl Pharmacol. 1994 Aug;127(2):250–257. doi: 10.1006/taap.1994.1159. [DOI] [PubMed] [Google Scholar]
  9. Burns T. L., Moll P. P., Rost C. A., Lauer R. M. Mothers remember birthweights of adolescent children: the Muscatine Ponderosity Family Study. Int J Epidemiol. 1987 Dec;16(4):550–555. doi: 10.1093/ije/16.4.550. [DOI] [PubMed] [Google Scholar]
  10. Constable J. D., Hatch M. C. Reproductive effects of herbicide exposure in Vietnam: recent studies by the Vietnamese and others. Teratog Carcinog Mutagen. 1985;5(4):231–250. doi: 10.1002/tcm.1770050404. [DOI] [PubMed] [Google Scholar]
  11. Courtney K. D. Mouse teratology studies with chlorodibenzo-p-dioxins. Bull Environ Contam Toxicol. 1976 Dec;16(6):674–681. doi: 10.1007/BF01685572. [DOI] [PubMed] [Google Scholar]
  12. Eskenazi B., Gold E. B., Lasley B. L., Samuels S. J., Hammond S. K., Wight S., O'Neill Rasor M., Hines C. J., Schenker M. B. Prospective monitoring of early fetal loss and clinical spontaneous abortion among female semiconductor workers. Am J Ind Med. 1995 Dec;28(6):833–846. doi: 10.1002/ajim.4700280615. [DOI] [PubMed] [Google Scholar]
  13. Eskenazi B., Mocarelli P., Warner M., Samuels S., Needham L., Patterson D., Brambilla P., Gerthoux P. M., Turner W., Casalini S. Seveso Women's Health Study: does zone of residence predict individual TCDD exposure? Chemosphere. 2001 May-Jun;43(4-7):937–942. doi: 10.1016/s0045-6535(00)00454-9. [DOI] [PubMed] [Google Scholar]
  14. Fara G. M., Del Corno G. Pregnancy outcome in the Seveso area after TCDD contamination. Prog Clin Biol Res. 1985;163B:279–285. [PubMed] [Google Scholar]
  15. Guo Y. L., Lambert G. H., Hsu C. C. Growth abnormalities in the population exposed in utero and early postnatally to polychlorinated biphenyls and dibenzofurans. Environ Health Perspect. 1995 Sep;103 (Suppl 6):117–122. doi: 10.1289/ehp.95103s6117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hassoun E. A., Walter A. C., Alsharif N. Z., Stohs S. J. Modulation of TCDD-induced fetotoxicity and oxidative stress in embryonic and placental tissues of C57BL/6J mice by vitamin E succinate and ellagic acid. Toxicology. 1997 Dec 19;124(1):27–37. doi: 10.1016/s0300-483x(97)00127-3. [DOI] [PubMed] [Google Scholar]
  17. Kreuzer P. E., Csanády G. A., Baur C., Kessler W., Päpke O., Greim H., Filser J. G. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and congeners in infants. A toxicokinetic model of human lifetime body burden by TCDD with special emphasis on its uptake by nutrition. Arch Toxicol. 1997;71(6):383–400. doi: 10.1007/s002040050402. [DOI] [PubMed] [Google Scholar]
  18. Kunita N., Kashimoto T., Miyata H., Fukushima S., Hori S., Obana H. Causal agents of yusho. Am J Ind Med. 1984;5(1-2):45–58. [PubMed] [Google Scholar]
  19. Le T. N., Johansson A. Impact of chemical warfare with agent orange on women's reproductive lives in Vietnam: a pilot study. Reprod Health Matters. 2001 Nov;9(18):156–164. doi: 10.1016/s0968-8080(01)90102-8. [DOI] [PubMed] [Google Scholar]
  20. Lucier G. W., Sunahara G. I., Wong T. K. Placental markers of human exposure to polychlorinated dibenzofurans and polychlorinated biphenyls: implications for risk assessment. IARC Sci Publ. 1990;(104):55–62. [PubMed] [Google Scholar]
  21. Mastroiacovo P., Spagnolo A., Marni E., Meazza L., Bertollini R., Segni G., Borgna-Pignatti C. Birth defects in the Seveso area after TCDD contamination. JAMA. 1988 Mar 18;259(11):1668–1672. [PubMed] [Google Scholar]
  22. Mocarelli P., Brambilla P., Gerthoux P. M., Patterson D. G., Jr, Needham L. L. Change in sex ratio with exposure to dioxin. Lancet. 1996 Aug 10;348(9024):409–409. doi: 10.1016/s0140-6736(05)65030-1. [DOI] [PubMed] [Google Scholar]
  23. Mocarelli P., Gerthoux P. M., Ferrari E., Patterson D. G., Jr, Kieszak S. M., Brambilla P., Vincoli N., Signorini S., Tramacere P., Carreri V. Paternal concentrations of dioxin and sex ratio of offspring. Lancet. 2000 May 27;355(9218):1858–1863. doi: 10.1016/S0140-6736(00)02290-X. [DOI] [PubMed] [Google Scholar]
  24. Murray F. J., Smith F. A., Nitschke K. D., Humiston C. G., Kociba R. J., Schwetz B. A. Three-generation reproduction study of rats given 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the diet. Toxicol Appl Pharmacol. 1979 Sep 15;50(2):241–252. doi: 10.1016/0041-008x(79)90149-2. [DOI] [PubMed] [Google Scholar]
  25. Nau H., Bass R., Neubert D. Transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) via placenta and milk, and postnatal toxicity in the mouse. Arch Toxicol. 1986 May;59(1):36–40. doi: 10.1007/BF00263955. [DOI] [PubMed] [Google Scholar]
  26. Parazzini F., Cortinovis I., Bortolus R., Fedele L., Decarli A. Weight at birth by gestational age in Italy. Hum Reprod. 1995 Jul;10(7):1862–1863. doi: 10.1093/oxfordjournals.humrep.a136192. [DOI] [PubMed] [Google Scholar]
  27. Patandin S., Koopman-Esseboom C., de Ridder M. A., Weisglas-Kuperus N., Sauer P. J. Effects of environmental exposure to polychlorinated biphenyls and dioxins on birth size and growth in Dutch children. Pediatr Res. 1998 Oct;44(4):538–545. doi: 10.1203/00006450-199810000-00012. [DOI] [PubMed] [Google Scholar]
  28. Patterson D. G., Jr, Hampton L., Lapeza C. R., Jr, Belser W. T., Green V., Alexander L., Needham L. L. High-resolution gas chromatographic/high-resolution mass spectrometric analysis of human serum on a whole-weight and lipid basis for 2,3,7,8-tetrachlorodibenzo-p-dioxin. Anal Chem. 1987 Aug 1;59(15):2000–2005. doi: 10.1021/ac00142a023. [DOI] [PubMed] [Google Scholar]
  29. Peterson R. E., Theobald H. M., Kimmel G. L. Developmental and reproductive toxicity of dioxins and related compounds: cross-species comparisons. Crit Rev Toxicol. 1993;23(3):283–335. doi: 10.3109/10408449309105013. [DOI] [PubMed] [Google Scholar]
  30. Pirkle J. L., Wolfe W. H., Patterson D. G., Needham L. L., Michalek J. E., Miner J. C., Peterson M. R., Phillips D. L. Estimates of the half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Vietnam Veterans of Operation Ranch Hand. J Toxicol Environ Health. 1989;27(2):165–171. doi: 10.1080/15287398909531288. [DOI] [PubMed] [Google Scholar]
  31. Pluim H. J., van der Goot M., Olie K., van der Slikke J. W., Koppe J. G. Missing effects of background dioxin exposure on development of breast-fed infants during the first half year of life. Chemosphere. 1996 Oct;33(7):1307–1315. doi: 10.1016/0045-6535(96)00268-8. [DOI] [PubMed] [Google Scholar]
  32. Rasmussen S. A., Mulinare J., Khoury M. J., Maloney E. K. Evaluation of birth defect histories obtained through maternal interviews. Am J Hum Genet. 1990 Mar;46(3):478–485. [PMC free article] [PubMed] [Google Scholar]
  33. Reed P. I., Jazrawi R. P., Northfield T. C., Carr-Locke D., Mountford R. A., Williams J. G., Schiller K. F., English J. R. Enprostil, a prostaglandin E2 analogue, in the treatment of gastric ulcer--a multicentre comparison with pirenzepine. Br J Clin Pract. 1990 Feb;44(2):48–51. [PubMed] [Google Scholar]
  34. Revich B., Aksel E., Ushakova T., Ivanova I., Zhuchenko N., Klyuev N., Brodsky B., Sotskov Y. Dioxin exposure and public health in Chapaevsk, Russia. Chemosphere. 2001 May-Jun;43(4-7):951–966. doi: 10.1016/s0045-6535(00)00456-2. [DOI] [PubMed] [Google Scholar]
  35. Rogan W. J. PCBs and cola-colored babies: Japan, 1968, and Taiwan, 1979. Teratology. 1982 Dec;26(3):259–261. doi: 10.1002/tera.1420260307. [DOI] [PubMed] [Google Scholar]
  36. Rylander L., Strömberg U., Hagmar L. Decreased birthweight among infants born to women with a high dietary intake of fish contaminated with persistent organochlorine compounds. Scand J Work Environ Health. 1995 Oct;21(5):368–375. doi: 10.5271/sjweh.51. [DOI] [PubMed] [Google Scholar]
  37. Schantz S. L. Developmental neurotoxicity of PCBs in humans: what do we know and where do we go from here? Neurotoxicol Teratol. 1996 May-Jun;18(3):217–276. doi: 10.1016/s0892-0362(96)90001-x. [DOI] [PubMed] [Google Scholar]
  38. Schecter A. A selective historical review of congener-specific human tissue measurements as sensitive and specific biomarkers of exposure to dioxins and related compounds. Environ Health Perspect. 1998 Apr;106 (Suppl 2):737–742. doi: 10.1289/ehp.98106737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Schecter A., Startin J., Wright C., Papke O., Ball M., Lis A. Concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans in human placental and fetal tissues from the U.S. and in placentas from Yu-Cheng exposed mothers. Chemosphere. 1996 Feb;32(3):551–557. doi: 10.1016/0045-6535(96)00002-1. [DOI] [PubMed] [Google Scholar]
  40. Stockbauer J. W., Hoffman R. E., Schramm W. F., Edmonds L. D. Reproductive outcomes of mothers with potential exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Am J Epidemiol. 1988 Aug;128(2):410–419. doi: 10.1093/oxfordjournals.aje.a114981. [DOI] [PubMed] [Google Scholar]
  41. Sunahara G. I., Nelson K. G., Wong T. K., Lucier G. W. Decreased human birth weights after in utero exposure to PCBs and PCDFs are associated with decreased placental EGF-stimulated receptor autophosphorylation capacity. Mol Pharmacol. 1987 Nov;32(5):572–578. [PubMed] [Google Scholar]
  42. Susser E. Spontaneous abortion and induced abortion: an adjustment for the presence of induced abortion when estimating the rate of spontaneous abortion from cross-sectional studies. Am J Epidemiol. 1983 Mar;117(3):305–308. doi: 10.1093/oxfordjournals.aje.a113542. [DOI] [PubMed] [Google Scholar]
  43. Svensson B. G., Nilsson A., Hansson M., Rappe C., Akesson B., Skerfving S. Exposure to dioxins and dibenzofurans through the consumption of fish. N Engl J Med. 1991 Jan 3;324(1):8–12. doi: 10.1056/NEJM199101033240102. [DOI] [PubMed] [Google Scholar]
  44. Tsutsumi O., Uechi H., Sone H., Yonemoto J., Takai Y., Momoeda M., Tohyama C., Hashimoto S., Morita M., Taketani Y. Presence of dioxins in human follicular fluid: their possible stage-specific action on the development of preimplantation mouse embryos. Biochem Biophys Res Commun. 1998 Sep 18;250(2):498–501. doi: 10.1006/bbrc.1998.9340. [DOI] [PubMed] [Google Scholar]
  45. Umbreit T. H., Hesse E. J., Gallo M. A. Reproductive toxicity in female mice of dioxin-contaminated soils from a 2,4,5-trichlorophenoxyacetic acid manufacturing site. Arch Environ Contam Toxicol. 1987 Jul;16(4):461–466. doi: 10.1007/BF01055268. [DOI] [PubMed] [Google Scholar]
  46. Vartiainen T., Jaakkola J. J., Saarikoski S., Tuomisto J. Birth weight and sex of children and the correlation to the body burden of PCDDs/PCDFs and PCBs of the mother. Environ Health Perspect. 1998 Feb;106(2):61–66. doi: 10.1289/ehp.9810661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Wilcox A. J., Weinberg C. R., O'Connor J. F., Baird D. D., Schlatterer J. P., Canfield R. E., Armstrong E. G., Nisula B. C. Incidence of early loss of pregnancy. N Engl J Med. 1988 Jul 28;319(4):189–194. doi: 10.1056/NEJM198807283190401. [DOI] [PubMed] [Google Scholar]
  48. Yamashita F., Hayashi M. Fetal PCB syndrome: clinical features, intrauterine growth retardation and possible alteration in calcium metabolism. Environ Health Perspect. 1985 Feb;59:41–45. doi: 10.1289/ehp.59-1568075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. di Domenico A., Silano V., Viviano G., Zapponi G. Accidental release of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at Sèveso, Italy. III. Monitoring of residual TCDD levels in reclaimed buildings. Ecotoxicol Environ Saf. 1980 Sep;4(3):321–326. doi: 10.1016/0147-6513(80)90033-0. [DOI] [PubMed] [Google Scholar]

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