High-dose irradiation to the uterus, ovaries at young age increased risk for still births, neonatal deaths

Signorello LB. Lancet. 2010;doi:10.1016/S0140-6736(10)60752-0.

Female childhood cancer survivors who were exposed to high-dose irradiation to the uterus or ovaries are at increased risk for still births and neonatal deaths.

Therefore, researchers recommended careful management in pregnant women treated with high-dose pelvic irradiation before puberty, according to a retrospective cohort analysis of the Childhood Cancer Survivor Study published in The Lancet.

“For men exposed to gonadal irradiation, there does not seem to be an increased risk of stillbirth or neonatal death among their offspring, which is reassuring not only for male survivors of childhood cancer but also for men exposed to ionizing radiation in occupational or other settings,” wrote the researchers, led by Lisa B. Signorello, MD,of the International Epidemiology Institute, Rockville, Md. “For women, however, high-dose uterine or ovarian radiation does seem to have important adverse effects, which are most likely to be attributable to uterine damage.”

As the reproductive implications of radiation and chemotherapy treatments administered to children with cancer are not clear, Signorello and colleagues assessed the risk for still birth and neonatal death in 1,148 men and 1,657 women included in the Childhood Cancer Survivor Study.

Poisson regression analysis was used to measure the amount of preconception chemotherapy and irradiation to the testes, ovaries, uterus or pituitary gland. There were 4,946 documented pregnancies and 93 still births and neonatal deaths. There were 1,744 survivors who had been treated with radiotherapy. Of those, there were 60 reported stillbirths or neonatal deaths.

Irradiation to the testes in men (adjusted RR=0.8; 95% CI, 0.4-1.6), pituitary gland (adjusted RR=1.1 for more than 20 Gy; 95% CI, 0.5-2.4), and use of alkylating chemotherapy agents in both men (adjusted RR=1.2; 95% CI, 0.5-2.5) and women (adjusted RR=0.9; 95% CI, 0.5-1.5) were not associated with an increased risk for still birth.

However, irradiation to the uterus or ovaries at doses greater than 10 Gy were associated with a ninefold increased risk for still birth and neonatal death for all age groups (adjusted RR=9.1; 95% CI, 3.4-24.6).

Moreover, irradiation to the uterus or ovaries at doses as low as 1 Gy to 2.49 Gy were associated with an almost fivefold increased risk for still birth or neonatal death — the risk increased 12-fold with irradiation greater than 2.5 Gy.

“High-dose pelvic irradiation can permanently impair growth and blood flow to the uterus and results in a reduced uterine volume, and these effects of radiation are likely to be dependent on age,” the researchers wrote. “Whether these types of effects on the uterus increase the risk of placental or umbilical-cord anomalies or other factors already linked to still birth, or whether they operate through different mechanisms needs clarification.”

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