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Spontaneous Abortion in a Danish Population-Based Cohort of Childhood Cancer Survivors

Jeanette F. Winther, John D. Boice, Jr, Anne Louise Svendsen, Kirsten Frederiksen, Marilyn Stovall, Jørgen H. Olsen

From the Institute of Cancer Epidemiology, Danish Cancer Society; Department of Biostatistics, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark; International Epidemiology Institute, Rockville, MD; Vanderbilt University, Department of Medicine and Vanderbilt-Ingram Cancer Center, Nashville, TN; and Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX

Corresponding author: Jeanette F. Winther, MD, Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark; e-mail: jeanette{at}cancer.dk

Purpose Radiation induces germ-cell mutations in experimental animals that result in adverse pregnancy outcomes, as does uterine damage caused by high-dose radiotherapy. We assessed the risks for spontaneous abortion and stillbirths among cancer survivors who received radiotherapy and subsequently became pregnant.

Patients and Methods We identified 1,688 female survivors of childhood cancer in the Danish Cancer Registry. Radiation doses to the ovary and uterus were characterized as high to low. The pregnancy outcomes of survivors, 2,737 sisters, and 16,700 comparison women in the population were identified from nationwide registries. The proportions of pregnancies among survivors that resulted in a livebirth, stillbirth, or abortion were compared with the equivalent proportions among the two comparison groups, and proportion ratios (PRs) were computed with sisters as referent.

Results More than 34,000 pregnancies were evaluated, 1,479 of which were among cancer survivors. No significant differences were seen between survivors and comparison women in the proportions of livebirths, stillbirths, or all types of abortions combined. Survivors, however, had a 23% excess risk for spontaneous abortion (PR, 1.23; 95% CI, 1.0 to 1.5), related primarily to prior radiation treatments (PR, 1.58; 95% CI, 1.2 to 2.2) and especially high-dose radiotherapy to the ovaries and uterus (PR, 2.8; 95% CI, 1.7 to 4.7).

Conclusion The pregnancy outcomes of survivors were similar to those of comparison women. A slight excess risk for spontaneous abortion may have resulted from uterine damage after high-dose pelvic radiotherapy, consistent with previous studies, although radiation-induced germinal mutations or decreased hypothalamic-pituitary-ovarian function could not be ruled out.

Supported in part by the Danish Cancer Society, the International Epidemiology Institute (IEI) through a contract with Westlakes Research Institute (agreement 01/12/99 DC), and a grant from the National Cancer Institute (Grant No. CA104666).

Presented in part at the 9th International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer, June 9-10, 2006, Niagara-on-The-Lake, Ontario, Canada.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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