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Serious psychiatric outcome of subjects prenatally exposed to diethylstilboestrol in the E3N cohort study

  • HELENE VERDOUX (a1), JACQUES ROPERS (a2), DOMINIQUE COSTAGLIOLA (a3), FRANÇOISE CLAVEL-CHAPELON (a4) and XAVIER PAOLETTI (a5)...

Abstract

Background

Prenatal exposure to diethylstilboestrol (DES) may induce neurodevelopmental disturbances potentially mediating an increased risk of psychiatric disorders in exposed subjects. Most findings of an increased prevalence of psychiatric disorders in men and women prenatally exposed to DES are not easy to interpret because of selection biases.

Method

Information on hormonal treatment during pregnancy and on offspring's medical outcome was collected from women participating in the Etude Epidemiologique de femmes de la Mutuelle Générale de l'Education Nationale (E3N) prospective cohort who completed consecutive postal questionnaires on a range of medical events since 1990. Information on hormonal treatment during pregnancy was collected in 1992 and on offspring's medical outcome in 2004. The psychiatric outcome of subjects prenatally exposed to DES was compared to that of their unexposed siblings.

Results

A total of 1352 mothers with DES treatment for at least one pregnancy provided information on 1680 exposed children and 1447 unexposed siblings. After adjustment for duration of follow-up, educational level, history of obstetric complication, prenatal exposure to progestagen drugs or other hormones and parental history of psychiatric hospitalization, no association was found between prenatal exposure to DES and occurrence of strictly defined serious psychiatric outcome (suicide or psychiatric hospitalization) [adjusted odds ratio (OR) 0·8, 95% confidence interval (CI) 0·5–1·2], or of broadly defined serious psychiatric outcome (same events plus psychiatric or psychological consultation) (adjusted OR 1·0, 95% CI 0·8–1·2).

Conclusions

These findings suggest that the impact of prenatal DES exposure on foetal brain development, if any, is unlikely to increase the risk of serious psychiatric disorders.

Copyright

Corresponding author

*Address for correspondence: Xavier Paoletti, Institut National du Cancer, Department of Clinical Research and Biostatistics, 52 avenue Morizet, 92513 Boulogne cedex, France. (Email: xpaoletti@institutcancer.fr)

References

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Cannon, M., Kendell, R., Susser, E. & Jones, P. (2003). Prenatal and perinatal risk factors for schizophrenia. In The Epidemiology of Schizophrenia (ed. Murray, R., Jones, P., Susser, E., Van Os, J. and Cannon, M.), pp. 7499. Cambridge University Press: Cambridge.
Clavel-Chapelon, F. (2002). Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women. British Journal of Cancer 86, 723727.
Crow, T. J., Done, D. J. & Sacker, A. (1996). Cerebral lateralization is delayed in children who later develop schizophrenia. Schizophrenia Research 22, 181185.
Ehrhardt, A. A., Feldman, J. F., Rosen, L. R., Meyer-Bahlburg, H. F., Gruen, R., Veridiano, N. P., Endicott, J. & Cohen, P. (1987). Psychopathology in prenatally DES-exposed females: current and lifetime adjustment. Psychosomatic Medicine 49, 183196.
Fournier, A., Berrino, F., Riboli, E., Avenel, V. & Clavel-Chapelon, F. (2005). Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. International Journal of Cancer 114, 448454.
Fried-Cassorla, M., Scholl, T., Borow, L., Strassman, H. & Bowers, E. (1987). Depression and diethylstilbestrol exposure in women. Journal of Reproductive Medicine 32, 847850.
Geschwind, N. & Galaburda, A. (1985). Cerebral lateralization. Biological mechanisms, associations, and pathology: II. A hypothesis and program for research. Archives of Neurology 42, 521552.
Gustavson, C. R., Gustavson, J. C., Noller, K. L., O'Brien, P. C., Melton, L. J., Pumariega, A. J., Kaufman, R. H. & Colton, T. (1991). Increased risk of profound weight loss among women exposed to diethylstilbestrol in utero. Behavioral and Neural Biology 55, 307312.
Kaufman, R. H., Adam, E., Hatch, E. E., Noller, K., Herbst, A. L., Palmer, J. R. & Hoover, R. N. (2000). Continued follow-up of pregnancy outcomes in diethylstilbestrol-exposed offspring. Obstetrics and Gynecology 96, 483489.
Lewis, S. & Murray, R. (1987). Obstetric complications, neurodevelopmental deviance, and risk of schizophrenia. Journal of Psychiatry Research 21, 413421.
Meyer-Bahlburg, H. F., Ehrhardt, A. A., Feldman, J. F., Rosen, L. R., Veridiano, N. P. & Zimmerman, I. (1985). Sexual activity level and sexual functioning in women prenatally exposed to diethylstilbestrol. Psychosomatic Medicine 47, 497511.
Murray, R. & Lewis, S. W. (1987). Is schizophrenia a neurodevelopmental disorder? British Medical Journal 295, 681682.
Newbold, R. R. (2004). Lessons learned from perinatal exposure to diethylstilbestrol. Toxicology and Applied Pharmacology 199, 142150.
Orr, K. G., Cannon, M., Gilvarry, C. M., Jones, P. B. & Murray, R. M. (1999). Schizophrenic patients and their first-degree relatives show an excess of mixed-handedness. Schizophrenia Research 39, 167176.
Palmlund, I., Apfel, R., Buitendijk, S., Cabau, A. & Forsberg, J. G. (1993). Effects of diethylstilbestrol (DES) medication during pregnancy: report from a symposium at the 10th International Congress of ISPOG. Journal of Psychosomatic Obstetrics and Gynecology 14, 7189.
Pillard, R. C., Rosen, L. R., Meyer-Bahlburg, H., Weinrich, J. D., Feldman, J. F., Gruen, R. & Ehrhardt, A. A. (1993). Psychopathology and social functioning in men prenatally exposed to diethylstilbestrol (DES). Psychosomatic Medicine 55, 485491.
Porrini, S., Belloni, V., Della Seta, D., Farabollini, F., Giannelli, G. & Dessi-Fulgheri, F. (2005). Early exposure to a low dose of bisphenol A affects socio-sexual behavior of juvenile female rats. Brain Research Bulletin 65, 261266.
Reinisch, J. M. & Sanders, S. A. (1992). Effects of prenatal exposure to diethylstilbestrol (DES) on hemispheric laterality and spatial ability in human males. Hormones and Behavior 26, 6275.
Romieu, I., Avenel, V., Leynaert, B., Kauffmann, F. & Clavel-Chapelon, F. (2003). Body mass index, change in body silhouette, and risk of asthma in the E3N cohort study. American Journal of Epidemiology 158, 165174.
Schachter, S. (1994). Handedness in women with intrauterine exposure to diethystilbestrol. Neuropsychologia 32, 619623.
Scheirs, J. G. & Vingerhoets, A. J. (1995). Handedness and other laterality indices in women prenatally exposed to DES. Journal of Clinical and Experimental Neurophysiology 17, 725730.
Slikker, W. Jr., Bailey, J. R., Newport, D., Lipe, G. W. & Hill, D. E. (1982). Placental transfer and metabolism of 17 alpha-ethynylestradiol-17 beta and estradiol-17 beta in the rhesus monkey. Journal of Pharmacology and Experimental Therapeutics 223, 483489.
Smith, L. L. & Hines, M. (2000). Language lateralization and handedness in women prenatally exposed to diethylstilbestrol (DES). Psychoneuroendocrinology 25, 497512.
Tehard, B., Kaaks, R. & Clavel-Chapelon, F. (2005). Body silhouette, menstrual function at adolescence and breast cancer risk in the E3N cohort study. British Journal of Cancer 92, 20422048.
Titus-Ernstoff, L., Perez, K., Hatch, E. E., Troisi, R., Palmer, J. R., Hartge, P., Hyer, M., Kaufman, R., Adam, E., Strohsnitter, W., Noller, K., Pickett, K. E. & Hoover, R. (2003). Psychosexual characteristics of men and women exposed prenatally to diethylstilbestrol. Epidemiology 14, 155160.
Verdoux, H. (2002). Long-term psychiatric and behavioural consequences of prenatal exposure to psychoactive drugs [in French]. Therapie 57, 181185.
Verdoux, H. (2004). Perinatal risk factors for schizophrenia: how specific are they? Current Psychiatry Reports 6, 162167.
Verdoux, H., Geddes, J., Takei, N., Lawrie, S., Bovet, P., Eagles, J., Heun, R., McCreadie, R., McNeil, T., O'Callaghan, E., Stöber, G., Willinger, U., Wright, P. & Murray, R. (1997). Obstetric complications and age at onset in schizophrenia. An international collaborative meta-analysis of individual patient data. American Journal of Psychiatry 154, 12201227.
Vessey, M. P., Fairweather, D. V., Norman-Smith, B. & Buckley, J. (1983). A randomized double-blind controlled trial of the value of stilboestrol therapy in pregnancy: long-term follow-up of mothers and their offspring. British Journal of Obstetrics and Gynaecology 90, 10071017.
Watier, L., Richardson, S. & Hemon, D. (1997). Accounting for pregnancy dependence in epidemiologic studies of reproductive outcomes. Epidemiology 8, 629636.

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