title: Female survivors of childhood cancer: preterm birth and low birth weight among their children.
abstract: 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.
authors.affiliation: International Epidemiology Institute, 1455 Research Blvd., Ste. 550, Rockville, MD 20850, USA. lisa.signorello@intepi.org
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Signorello
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Cohen
authors.forename: Cristina
authors.initials: C
authors.lastname: Bosetti
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Kasper
authors.forename: Rita E
authors.initials: RE
authors.lastname: Weathers
authors.forename: John A
authors.initials: JA
authors.lastname: Whitton
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Green
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Donaldson
authors.forename: Ann C
authors.initials: AC
authors.lastname: Mertens
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.forename: John D
authors.initials: JD
authors.lastname: Boice
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000970:Antineoplastic Agents / Q000009:adverse effects; D002648:Child; D015986:Confounding Factors, Epidemiologic; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology; D005836:Genitalia, Female / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D007680:Kidney Neoplasms / Q000532:radiotherapy; D016015:Logistic Models; D008297:Male; D008572:Menarche; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D016017:Odds Ratio; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology*; D047928:Premature Birth / Q000209:etiology*; D011878:Radiotherapy / Q000009:adverse effects; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires; D017741:Survivors; D009396:Wilms Tumor / Q000532:radiotherapy
chemical_list: D000970:Antineoplastic Agents