JEP  Vol.2 No.6 , August 2011
Persistent Organochlorine Exposure and Pregnancy Loss: A Prospective Cohort Study
Polychlorinated biphenyls (PCBs) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) are suspected re-productive toxicants. We assessed serum concentration of 76 PCB congeners, DDE, and risk of human chorionic gonadotropin confirmed pregnancy loss among 79 women followed for up to 12 menstrual cycles or until pregnancy. 55 women had live births, 14 experienced pregnancy losses, and 10 did not achieve pregnancy. PCBs and DDE were quantified using gas chromatography with electron capture. PCBs were grouped a priori by biologic activity. Cox proportional hazard regression adjusting for age (categorized 24 - 29, 30 - 34) and average standardized alcohol and cigarette intake (continuous) was used to estimate hazard ratios (HR) of pregnancy loss. Estrogenic PCBs (HR = 1.66, 95% CI: 0.68, 4.02), anti-estrogenic PCBs (HR = 0.10, 95% CI: <0.01, 67.07) and DDE (HR = 1.43, 95% CI: 0.45, 4.52) were not statistically significantly associated with pregnancy loss. Our results provide some signal that estrogenic and antiestrogenic PCBs may be differentially associated with pregnancy loss. Further research is needed to elucidate these associations.

Cite this paper
nullA. Pollack, G. Louis, C. Lynch and P. Kostyniak, "Persistent Organochlorine Exposure and Pregnancy Loss: A Prospective Cohort Study," Journal of Environmental Protection, Vol. 2 No. 6, 2011, pp. 683-691. doi: 10.4236/jep.2011.26079.
[1]   J. M. Wood, “Dynamics of Human Reproduction: Biology, Biometry, Demography.” Aldine de Gruyter, New York, 1994.

[2]   C. Gini, “Premieres Recheres Sur la Fecondabilite de la Femme,” Proceedings of the International Mathematical Conference, Vol. 2, 1924, pp. 889-892.

[3]   A. J. Wilcox, C. R. Weinberg, J. F. O’Connor, D. D. Baird, J. P. Schlatterer, R. E. Canfield, et al., “Incidence of Early Loss of Pregnancy,” New England Journal of Medicine, Vol. 319, No. 4, 1988, pp. 189-194. doi:10.1056/NEJM198807283190401

[4]   G. P. Daston, J. W. Gooch, W. J. Breslin, et al., “Environmental Estrogens and Reproductive Health: A Discussion of the Human and Environmental Data,” Reproductive Toxicology, Vol. 11, No. 4, 1997, pp. 465-481. doi:10.1016/S0890-6238(97)00014-2

[5]   E. Diamanti-Kandarakis, J. P. Bourguignon, L. C. Giudice, R. Hauser, G. S. Prins, A. M. Soto, et al., “Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement,” Endocrine Reviews, Vol. 30, No. 4, 2009, pp. 293-342. doi:10.1210/er.2009-0002

[6]   G. Toft, L. Hagmar, A. Giwercman and J. P. Bonde, “Epidemiological Evidence on Reproductive Effects of Persistent Organochlorines in Humans,” Reproductive Toxicology, Vol. 19, No. 1, 2004, pp. 5-26. doi:10.1016/j.reprotox.2004.05.006

[7]   T. M. Crisp, E. D. Clegg, R. L. Cooper, W. P. Wood, D. G. Anderson, K. P. Baetcke, et al., “Environmental Endocrine Disruption: An Effects Assessment and Analysis,” Environ Health Perspect, Vol. 106, Supplement 1, 1998, pp. 11-56.

[8]   L. G. M. Buck, C. D. Lynch and M. A. Cooney, “Environmental Influences on Female Fecundity and Fertility,” Seminars in Reproductive Medicine, Vol. 24, No. 3, 2006, pp. 147-155. doi:10.1055/s-2006-944421

[9]   P. Mendola, G. M. Buck, J. E. Vena, M. Zielezny and L. E. Sever, “Consumption of PCB-Contaminated Sport Fish and Risk of Spontaneous Fetal Death,” Environ Health Perspect, Vol. 103, No. 5, 1995, pp. 498-502. doi:10.1289/ehp.95103498

[10]   A. Axmon, L. Rylander, U. Stromberg and L. Hagmar, “Miscarriages and Stillbirths in Women with a High Intake of Fish Contaminated with Persistent Organochlorine Compounds,” International Archives of Occupational and Environmental Health, Vol. 73, No. 3, 2000, pp. 204-208. doi:10.1007/s004200050028

[11]   K. Hemminki, M. L. Niemi, I. Saloniemi, H. Vainio and E. Hemminki, “Spontaneous Abortions by Occupation and Social Class in Finland,” International Journal of Epidemiology, Vol. 9, No. 2, 1980, pp. 149-153. doi:10.1093/ije/9.2.149

[12]   D. O. Carpenter, Y. Shen, T. Nguyen, L. Le and L. L. Lininger, “Incidence of Endocrine Disease among Residents of New York Areas of Concern,” Environmental Health Perspectives, Vol. 109, Supplement 6, 2001, pp. 845-851. doi:10.2307/3454646

[13]   S. A. Korrick, C. Chen, A. I. Damokosh, J. Ni, X. Liu, S. I. Cho, et al., “Association of DDT with Spontaneous Abortion: A Case-Control Study,” Annals of Epidemiology, Vol. 11, No. 7, 2001, pp. 491-496. doi:10.1016/S1047-2797(01)00239-3

[14]   M. P. Longnecker, M. A. Klebanoff, D. B. Dunson, X. Guo, Z. Chen, H. Zhou, et al., “Maternal Serum Level of the DDT Metabolite DDE in Relation to Fetal Loss in Previous Pregnancies,” Environmental Research, Vol. 97, No. 2, 2005, pp. 127-133. doi:10.1016/S0013-9351(03)00108-7

[15]   A. M. Sweeney, M. R. Meyer, J. H. Aarons, J. L. Mills and R. E. LaPorte, “Evaluation of Methods for the Prospective Identification of Early Fetal Losses in Environmental Epidemiology Studies,” American Journal of Epidemiology, Vol. 127, No. 4, 1988, pp. 843-850.

[16]   R. E. Chapin, W. A. Robbins, L. A. Schieve, A. M. Sweeney, S. A. Tabacova and K. M. Tomashek, “Off to a Good Start: The Influence of Pre- and Periconceptional Exposures, Parental Fertility, and Nutrition on Children’s Health,” Environmental Health Perspectives, Vol. 112, No. 1, 2004, pp. 69-78. doi:10.1289/ehp.6261

[17]   G. M. Buck, C. D. Lynch, J. B. Stanford, A. M. Sweeny, L. A. Schieve, J. C. Rockett, et al., “Prospective Pregnancy Study Designs for Assessing Reproductive and Developmental Toxicants,” Environmental Health Perspectives, Vol. 112, No. 1, 2004, pp. 79-86. doi:10.1289/ehp.6262

[18]   S. A. Venners, S. Korrick, X. Xu, C. Chen, W. Guang, A. Huang, et al., “Preconception Serum DDT And Pregnancy Loss: A Prospective Study Using A Biomarker Of Pregnancy,” American Journal of Epidemiology, Vol. 162, No. 8, 2005, pp. 709-716. doi:10.1093/aje/kwi275

[19]   M. Sugiura-Ogasawara, Y. Ozaki, S. Sonta, T. Makino and K. Suzumori, “PCBs, Hexachlorobenzene and DDE Are Not Associated with Recurrent Miscarriage,” American Journal of Epidemiology, Vol. 50, No. 6, 2003, pp. 485-489.

[20]   I. Gerhard, V. Daniel, S. Link, B. Monga and B. Runnebaum, “Chlorinated Hydrocarbons in Women with Repeated Miscarriages,” Environmental Health Perspectives, Vol. 106, No. 10, 1998, pp. 675-681. doi:10.1289/ehp.98106675

[21]   L. A. Cole, S. A. Khanlian, J. M. Sutton, S. Davies and W. F. Rayburn, “Accuracy of Home Pregnancy Tests at the Time of Missed Menses,” American Journal of Obstetrics and Gynecology, Vol. 190, No. 1, 2004, pp. 100-105. doi:10.1016/j.ajog.2003.08.043

[22]   M. S. Bloom, L. G. M. Buck, E. F. Schisterman, A. Liu and P. J. Kostyniak, “Maternal Serum Polychlorinated Biphenyl Concentrations Across Critical Windows of Human Development,” Environmental Health Perspectives, Vol. 115, No. 9, 2007, pp. 1320-1324. doi:10.1289/ehp.10086

[23]   H. B. Greizerstein, P. Gigliotti, J. Vena, J. Freudenheim and P. J. Kostyniak, “Standardization of a Method for the Routine Analysis of Polychlorinated Biphenyl Congeners and Selected Pesticides in Human Serum and Milk,” Journal of Analytical Toxicology, Vol. 21, No. 7, 1997, pp. 558-566.

[24]   P. S. Cooke, T. Sato and D. L. Buchanan, “Disruption of Steroid Hormone Signaling by PCBs,” In: L. W. Robertson and L. G. Hansen, Eds., PCBs: Recent Advances in Environmental Toxicology and Health Effects, The University Press of Kentucky, Lexington, 2001, pp. 257-263.

[25]   L. G. M. Buck, J. Dmochowski, C. Lynch, P. Kostyniak, B. M. McGuinness and J. E. Vena, “Polychlorinated Biphenyl Serum Concentrations, Lifestyle and Time-to- Pregnancy,” Human Reproduction, Vol. 24, No. 2, 2009, pp. 451-458. doi:10.1093/humrep/den373

[26]   E. F. Schisterman, A. Vexler, B. W. Whitcomb and A. Liu, “The Limitations Due to Exposure Detection Limits for Regression Models,” American Journal of Epidemiology, Vol. 163, No. 4, 2006, pp. 374-383. doi:10.1093/aje/kwj039

[27]   D. B. Richardson and A. Ciampi, “Effects of Exposure Measurement Error When an Exposure Variable Is Constrained by a Lower Limit,” American Journal of Epidemiology, Vol. 157, No. 4, 2003, pp. 355-363. doi:10.1093/aje/kwf217

[28]   E. F. Schisterman, B. W. Whitcomb, G. M. Louis and T. A. Louis, “Lipid Adjustment in the Analysis of Environmental Contaminants and Human Health Risks,” Environ Health Perspect, Vol. 113, No. 7, 2005, pp. 853-857. doi:10.1289/ehp.7640

[29]   D. L. Phillips, J. L. Pirkle, V. W. Burse, J. T. Bernert, L. O. Henderson and L. L. Needham, “Chlorinated Hydrocarbon Levels in Human Serum: Effects of Fasting and Feeding,” Archives of Environmental Contamination and Toxicology, Vol. 18, No. 4, 1989, pp. 495-500. doi:10.1007/BF01055015

[30]   S. D. Holladay and R. J. Smialowicz, “Development of the Murine and Human Immune System: Differential Effects of Immunotoxicants Depend on Time of Exposure,” Environmental Health Perspectives, Vol. 108, No. S3, 2000, pp. 463-473. doi:10.2307/3454538

[31]   G. J. van der Heijden, A. R. Donders, T. Stijnen and K. G. Moons, “Imputation of Missing Values Is Superior to Complete Case Analysis and the Missing-Indicator Method in Multivariable Diagnostic Research: A Clinical Example,” Journal of Clinical Epidemiology, Vol. 59, No. 10, 2006, pp. 1102-1109. doi:10.1016/j.jclinepi.2006.01.015

[32]   K. G. Moons, R. A. Donders, T. Stijnen and F. E. Harrell, “Using the Outcome for Imputation of Missing Predictor Values Was Preferred,” Journal of Clinical Epidemiology, Vol. 59, No. 10, 2006, pp. 1092-1101. doi:10.1016/j.jclinepi.2006.01.009

[33]   W. Vach and M. Blettner, “Biased Estimation of the Odds Ratio in Case-Control Studies Due to the Use of Ad Hoc Methods of Correcting for Missing Values for Confounding Variables,” American Journal of Epidemiology, Vol. 134, No. 8, 1991, pp. 895-907.

[34]   P. P. Howards, E. F. Schisterman and P. J. Heagerty, “Potential Confounding by Exposure History and Prior Outcomes: An Example from Perinatal Epidemiology,” Epidemiology, Vol. 18, No. 5, 2007, pp. 544-551. doi:10.1097/EDE.0b013e31812001e6

[35]   C. R. Weinberg, “Toward a Clearer Definition of Confounding,” American Journal of Epidemiology, Vol. 137, No. 1, 1993, pp. 1-8.

[36]   C. Gnoth, D. Godehardt, E. Godehardt, P. Frank-Herr- mann and G. Freundl, “Time to Pregnancy: Results of the German Prospective Study and Impact on the Management of Infertility,” Human Reproduction, Vol. 18, No. 9, 2003, pp. 1959-1966. doi:10.1093/humrep/deg366

[37]   X. Wang, C. Chen, L. Wang, D. Chen, W. Guang and J. French, “Conception, Early Pregnancy Loss, and Time to Clinical Pregnancy: A Population-Based Prospective Study,” Fertility and Sterility, Vol. 79, No. 3, 2003, pp. 577-584. doi:10.1016/S0015-0282(02)04694-0

[38]   W. J. Rogan and A. Chen, “Health Risks and Benefits of Bis(4-Chlorophenyl)-1,1,1-Trichloroethane (DDT),” Lancet, Vol. 366, No. 9487, 2005, pp. 763-773. doi:10.1016/S0140-6736(05)67182-6

[39]   A. Chen, M. L. Pennell, M. A. Klebanoff, W. J. Rogan and M. P. Longnecker, “Maternal Smoking during Pregnancy in Relation to Child Overweight: Follow-up to Age 8 Years,” International Journal of Epidemiology, Vol. 35, No. 1, 2006, pp. 121-130. doi:10.1093/ije/dyi218

[40]   L. E. Redding, M. D. Sohn, T. E. McKone, J. W. Chen, S. L. Wang, D. P. Hsieh, et al., “Population Physiologically Based Pharmacokinetic Modeling for the Human Lactational Transfer of PCB-153 with Consideration of Worldwide Human Biomonitoring Results,” Environmental Health Perspectives, Vol. 116, No. 12, 2008, pp. 1629- 1635. Perspectives, Vol. 116, No. 12, 2008, pp. 1629- 1635. doi:10.1289/ehp.11519

[41]   H. R. Chao, S. L. Wang, C. C. Lee, H. Y. Yu, Y. K. Lu and O. Papke, “Level of Polychlorinated Dibenzo-P-Dioxins, Dibenzofurans and Biphenyls (PCDD/Fs, Pcbs) in Human Milk and the Input to Infant Body Burden,” Food and Chemical Toxicology, Vol. 42, No. 8, 2004, pp. 1299-1308. doi:10.1016/j.fct.2004.03.008

[42]   L. A. Gallenberg and M. J. Vodicnik, “Potential Mechanisms for Redistribution of Polychlorinated Biphenyls during Pregnancy and Lactation,” Xenobiotica, Vol. 17, No. 3, 1987, pp. 299-310. doi:10.3109/00498258709043940

[43]   A. Axmon, A. M. Thulstrup, A. Rignell-Hydbom, H. S. Pedersen, V. Zvyezday, J. K. Ludwicki, et al., “Time to Pregnancy as a Function of Male and Female Serum Concentrations of 2,2'4,4'5,5'-Hexachlorobiphenyl (CB-153) and 1,1-Dichloro-2,2-Bis (P-Chlorophenyl)-Ethylene (p,p'- DDE),” Human Reproduction, Vol. 21, No. 3, 2006, pp. 657-665. doi:10.1093/humrep/dei397

[44]   J. S. Ireland, V. R. Mukku, A. K. Robison and G. M. Stancel, “Stimulation of Uterine Deoxyribonucleic Acid Synthesis by 1,1,1-Trichloro-2-(p-Chlorophenyl)-2-(o- Chlorophenyl)ethane (o,p'-DDT),” Biochemical Pharmacology, Vol. 29, No. 11, 1980, pp. 1469-1474. doi:10.1016/0006-2952(80)90596-1

[45]   G. M. Stancel, J. S. Ireland, V. R. Mukku and A. K. Robison, “The Estrogenic Activity of DDT: In Vivo and in Vitro Induction of a Specific Estrogen Inducible Uterine Protein by o,p’-DDT,” Life Science, Vol. 27, No. 12, 1980, pp. 1111-1117. doi:10.1016/0024-3205(80)90037-5

[46]   R. W. Nims, R. A. Lubet, S. D. Fox, P. E. Thomas, A. B. Reddy, T. A. Kocarek, et al., “Comparative Pharmacodynamics of CYP2B Induction by DDT, DDE, and DDD in Male Rat Liver and Cultured Rat Hepatocytes,” Journal of Toxicology and Environmental Health, Part A, Vol. 53, No. 6, 1998, pp. 455-477. doi:10.1080/009841098159187

[47]   R. W. Nims and R. A. Lubet, “Induction of Cytochrome P-450 in the Norway Rat, Rattus Norvegicus, Following Exposure to Potential Environmental Contaminants,” Journal of Toxicology and Environmental Health, Vol. 46, No. 3, 1995, pp. 271-292. doi:10.1080/15287399509532035

[48]   M. S. Petersen, J. Halling, P. Damkier, N. Flemming, P. Grandjean, P. Weihe, et al., “Polychlorinated Biphenyl (PCB) Induction of CYP3A4 Enzyme Activity in Healthy Faroese Adults,” Toxicology and Applied Pharmacology, Vol. 224, No. 2, 2007, pp. 202-206. doi:10.1016/j.taap.2007.07.002

[49]   F. P. Guengerich, D. H. Kim and M. Iwasaki, “Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects,” Chemical Research in Toxicology, Vol. 4, No. 2, 1991, pp. 168-179. doi:10.1021/tx00020a008