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JNCI Journal of the National Cancer Institute 2006 98(20):1453-1461; doi:10.1093/jnci/djj394
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© The Author 2006. Published by Oxford University Press.

ARTICLE

Female Survivors of Childhood Cancer: Preterm Birth and Low Birth Weight Among Their Children

Lisa B. Signorello, Sarah S. Cohen, Cristina Bosetti, Marilyn Stovall, Catherine E. Kasper, Rita E. Weathers, John A. Whitton, Daniel M. Green, Sarah S. Donaldson, Ann C. Mertens, Leslie L. Robison, John D. Boice, Jr.

Affiliations of authors: International Epidemiology Institute, Rockville, MD (LBS, SSC, JDB); Department of Medicine, Vanderbilt University, Nashville, TN (LBS, JDB); Instituto di Ricerche Farmacologiche Mario Negri, Milan, Italy (CB); Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX (MS, CEK, REW); Department of Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, WA (JAW); Department of Pediatrics, Roswell Park Cancer Institute, Buffalo, NY (DMG); Department of Pediatrics, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY (DMG); Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA (SSD); Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, Minneapolis, MN (ACM, LLR)

Correspondence to: Lisa B. Signorello, ScD, International Epidemiology Institute, 1455 Research Blvd., Ste. 550, Rockville, MD 20850 (e-mail: lisa.signorello{at}intepi.org).

Background: Improved survival after childhood cancer raises concerns over the possible long-term reproductive health effects of cancer therapies. We investigated whether children of female childhood cancer survivors are at elevated risk of being born preterm or exhibiting restricted fetal growth and evaluated the associations of different cancer treatments on these outcomes. Methods: Using data from the Childhood Cancer Survivor Study, a large multicenter cohort of childhood cancer survivors, we studied the singleton live births of female cohort members from 1968 to 2002. Included were 2201 children of 1264 survivors and 1175 children of a comparison group of 601 female siblings. Data from medical records were used to determine cumulative prepregnancy exposures to chemotherapy and radiotherapy. Logistic regression was used to estimate odds ratios (ORs) for the association between quantitative therapy exposures and preterm (<37 weeks) birth, low birth weight (<2.5 kg), and small-for-gestational-age (SGA) (lowest 10th percentile) births. All statistical tests were two-sided. Results: Survivors' children were more likely to be born preterm than the siblings' children (21.1% versus 12.6%; OR = 1.9, 95% confidence interval [CI] = 1.4 to 2.4; P<.001). Compared with the children of survivors who did not receive any radiotherapy, the children of survivors treated with high-dose radiotherapy to the uterus (>500 cGy) had increased risks of being born preterm (50.0% versus 19.6%; OR = 3.5, 95% CI = 1.5 to 8.0; P = .003), low birth weight (36.2% versus 7.6%; OR = 6.8, 95% CI = 2.1 to 22.2; P = .001), and SGA (18.2% versus 7.8%; OR = 4.0, 95% CI = 1.6 to 9.8; P = .003). Increased risks were also apparent at lower uterine radiotherapy doses (starting at 50 cGy for preterm birth and at 250 cGy for low birth weight). Conclusions: Late effects of treatment for female childhood cancer patients may include restricted fetal growth and early births among their offspring, with risks concentrated among women who receive pelvic irradiation.



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Editorial about this Article

After the Deluge: The Emerging Landscape of Childbearing Potential in Pediatric Cancer Survivors
Leslie R. Schover
J Natl Cancer Inst 2006 98: 1434-1435. [Extract] [Full Text] [PDF]



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