Lancet: Pediatric rad therapy in women raises risk of later stillbirth, neonatal death

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Women exposed to uterine and ovarian radiation therapy during childhood reported a higher incidence of stillbirth and neonatal death, according to a study published in Lancet online on July 23.

The retrospective cohort analysis of pregnancies within the Childhood Cancer Survivor Study (CCSS) population focused on the risk of stillbirth and neonatal death among adults who had survived childhood cancer, explained study authors John Boice, MD, and Lisa B. Signorello, MD, both from  Vanderbilt University in Nashville, Tenn.

The study population was comprised of 1,148 men and 1,657 women younger than 21 years at initial diagnosis of an eligible cancer between Jan. 1, 1970 and Dec. 31, 1986 at 25 U.S. institutions and one Canadian institution, and who had survived for at least five years after diagnosis, wrote the authors. Eligible cancers were leukemia, Hodgkin’s lymphoma, non-Hodgkin lymphoma, bone sarcoma, soft tissue sarcoma, CNS cancer, kidney cancer or Wilms’ tumor and neuroblastoma.

Participants completed a baseline questionnaire in 1994 and periodically thereafter. Researchers identified all live births and stillbirths for 1971-2002 and obtained medical data about cancer treatment including dates and types of treatment and anatomical sites exposed during radiation therapy. They estimated doses absorbed by the testes, ovaries, uterus and pituitary gland and used Poisson regression to estimate relative risk associated with dose to various organs.

“The final study population consisted of 93 cases of stillbirths and neonatal deaths and 4,853 live births among 2,805 cancer survivors. The 1,774 survivors who were given radiotherapy reported 60 stillbirths or neonatal deaths and 3,077 live births,” wrote Boice and Signorello.

Researchers did not confirm a link between testicular radiation and risk of stillbirth or neonatal death, nor did they note an association between pituitary radiation exposure for women before conception and the risk of stillbirth or neonatal death.

However, researchers did find that uterine or ovarian radiation exposure greatly increased the risk of stillbirth or neonatal death. High radiation doses (at least 2.50 Gy) were linked with a greater than 12-fold risk for women treated before menarche; for women treated with 10 Gy or more, the risk was 22 percent, reported the authors. Treatment with alkylating drugs did not increase the risk of stillbirth or neonatal death among men or women.

Boice and Signorello could not directly assess whether uterine or oocyte damage was responsible for the increased risk, but wrote, “high-dose pelvic radiation can permanently impair growth and blood flow to the uterus, resulting in reduced uterine volume,” adding that further studies are needed to clarify the mechanisms that increase risk.

“Careful management is warranted for pregnant women treated with high doses of pelvic irradiation before they have reached puberty,” concluded the authors.