Although more children are surviving a cancer diagnosis, there may be unintended long-term effects from treatment on reproduction, a study published Thursday found.
Female survivors who had irradiation of the uterus and ovaries at a high dose when they were children had a significantly elevated risk of stillbirth or neonatal death during a subsequent pregnancy, according to Lisa Signorello of the International Epidemiology Institute in Rockville, Md., and colleagues.
The link appeared only in those who received radiation treatment before puberty, the researchers reported online in The Lancet.
The absolute risk of stillbirth or neonatal death was 3 percent overall.
If the radiation is indeed the underlying cause of the birth problems, the increased risk is "probably related to uterine damage," they wrote.
"Careful management is warranted for pregnant women treated with high doses of pelvic irradiation before they have reached puberty," they concluded.
There was no increased risk of an adverse outcome among the offspring of men who had had their testes irradiated after a childhood cancer diagnosis, "which is reassuring not only for male survivors of childhood cancer but also for men exposed to ionizing radiation in occupational or other settings," the researchers wrote.
Looking at the risk of stillbirth and neonatal death is a way of assessing the potential for the damage caused by radiation or chemotherapy to affect DNA across generations.
To explore the issue, Signorello and her colleagues evaluated data from the Childhood Cancer Survivor Study. All participants were younger than 21 when they were initially diagnosed with cancer from 1970 to 1986. They were followed through 2002 with periodic questionnaires.
The researchers included 1,148 men and 1,657 women who had survived at least five years after their diagnosis.
There were 4,946 singleton pregnancies among these participants, of which 93 ended in stillbirth or neonatal death; 3 percent of women and 2 percent of men reported a pregnancy ending in one of those two outcomes.
Irradiation of the testes and pituitary gland in childhood was not associated with stillbirth or neonatal death. Neither was chemotherapy with alkylating drugs.
The overall increased risk of stillbirth or neonatal death associated with uterine and ovarian irradiation was found only in women who had received radiation before the onset of puberty at both low doses and high doses.
"We could not directly assess whether uterine damage (e.g., to the musculature, vasculature, or endometrium) or oocyte damage was the cause of the association with stillbirth or neonatal death, although we believe a uterine effect was most likely," Signorello and her colleagues wrote.
They acknowledged some limitations of the study, including the possibility that participants who had an adverse pregancy outcome were more likely to report their pregnancies on the questionnaires and the exclusion of 15 percent of the potential study group because of missing information.