Radiotherapy and birth risks

Women who receive radiotherapy for childhood cancers have increased risk of their pregnancies resulting in stillbirth, BBC News has reported.

The news is based on well-conducted research that followed 2,805 childhood cancer survivors during adulthood. Males exposed to radiation had no increased risk of fathering a child who was stillborn or died in the first weeks of life, but females given high doses of radiation to the pelvis had a greater risk of these adverse pregnancy outcomes. The scientists believe that female reproductive organs may be damaged by direct radiation exposure.

Importantly, the risk of stillbirth or newborn death was low, with 93 stillbirths or newborn deaths compared with 4,853 live births across the whole study. The results highlight the importance of careful management and monitoring of pregnancies in women who have previously received radiation to the pelvis.

Where did the story come from?

The study was carried out by researchers from Vanderbilt University Medical Center, the Vanderbilt-Ingram Cancer Center, the International Epidemiology Institute and other US institutions. It was funded by the Westlakes Research Institute, the US National Cancer Institute and the Children’s Cancer Research Fund (University of Minnesota). The study was published in the peer-reviewed medical journal The Lancet.

News reports have represented the findings of this research in a balanced way.

What kind of research was this?

This was a cohort study that periodically assessed childhood cancer survivors some years after their cancer experiences. The questionnaires issued assessed reports of pregnancies and their outcomes, which the researchers used to determine whether cancer treatments in childhood had later effects on reproductive outcomes (in both male and female survivors).

What did the research involve?

The Childhood Cancer Survivor Study (CCSS) was made up of people diagnosed with cancer between 1970 and 1986 when they were less than 21 years of age. The study was conducted in 25 US centres and one in Canada. All participants had to have survived for at least five years after their diagnosis.

The participants were followed up by questionnaire from 1994 onwards. Data gathered included the outcomes of any pregnancies in women, or for any children fathered by male cancer survivors. The study specifically identified all live births, stillbirths (defined in this study as stillbirth after 20 weeks of pregnancy; prior to 20 weeks was considered miscarriage and not included) and newborn deaths (death before 28 days of life) reported by the participants between 1971 and 2002. Children conceived by IVF were excluded, as were multiple pregnancies and pregnancies occurring at or around the time the cancer had been diagnosed.

The researchers used medical records to determine the chemotherapy (drug therapy) given to treat the cancer and doses of radiotherapy given to different sites of the body. They specifically estimated the likely level of exposure to the testes, ovaries, uterus and pituitary gland (which regulates the sex hormones). They then related these treatments and exposures to the risk of stillbirth or newborn death.

What were the basic results?

The study included 2,805 childhood cancer survivors (1,148 men and 1,657 women), 57% of whom had had lymphoma. Most people in the sample had received some radiotherapy, either alone or in combination with chemotherapy (61% of women and 62% of men).

Across all survivors there was a total of 4,946 pregnancies, with 93 of these resulting in stillbirth or newborn death (1.9% of the pregnancies). A total of 1,774 survivors had been given radiotherapy to treat their cancer, and in this group there were 3,077 live births and 60 stillbirths or newborn deaths (1.9% of the pregnancies to those given radiotherapy).

Clinical doses of radiation are measured in units called ‘Grays’ (Gy), which denotes the amount of radiation a person’s physical mass will typically absorb. One Gray is the amount of radiation typically absorbed from around 50,000 chest X-rays, and normal environmental exposure in the UK is approximately 0.0022Gy per year. The researchers found no increase in risk of stillbirth or newborn death with:

radiation exposure to the testes (average dose 0.53Gy)
radiation exposure to the pituitary gland in women (doses up to and exceeding 20Gy; average dose was 10.20Gy)
chemotherapy (both men and women)

However, the researchers found that radiation exposure to the uterus or ovaries (at a dose above 10Gy) significantly increased the woman’s risk of experiencing stillbirth or newborn death (five occurrences among 28 who received this radiation; relative risk 9.1, 95% CI 3.4 to 24.6).

They also found that girls whose ovaries or uterus had been exposed to radiation before their periods had started had increased risk of stillbirth or newborn death in later pregnancy, even at doses of radiotherapy as low as 1.00 to 2.49Gy (three occurrences among 69 women who received this exposure; relative risk 4.7, 95% CI 1.2 to 19.0).

How did the researchers interpret the results?

The researchers conclude that their study findings do not suggest an increased risk of stillbirth or newborn death from pregnancies fathered by a man who had received radiotherapy exposure to his testes as a child. However, for a woman who received radiation exposure to her uterus or ovaries as a girl, there is an increased risk of stillbirth or newborn death during later pregnancy. This, the researchers say, is probably as a result of uterine damage.

Conclusion

This is a well-conducted study of 2,805 childhood cancer survivors that reaches two main conclusions. Firstly, that the risk of experiencing stillbirth or newborn death in a later pregnancy was increased after certain doses of radiation were given to the ovaries and uterus in a girl, which may be the result of radiation causing some damage to the developing organs. Secondly, radiotherapy to the sex organs of boys did not increase the risk of them later fathering a child who was stillborn or died in the first weeks of life, which may suggest that radiotherapy did not induce DNA damage.

The study’s analyses have some strengths, in that the researchers adjusted their calculations for a number of health and lifestyle confounders that could potentially affect the risk of stillbirth or newborn death. They also validated self-reports of pregnancy outcomes against medical records.

However, importantly:

Overall, the risk of a childhood cancer survivor experiencing stillbirth or newborn death in their own or their partner’s later pregnancy was still relatively low, with 93 stillbirths or newborn deaths from 4,946 pregnancies – a rate of 1.9%. This proportion of stillbirths or newborn deaths was equal in both radiotherapy and non-radiotherapy groups. It is not possible to say from this study how these rates compare to people who did not have cancer or treatment for cancer in their childhood.
The small number of stillbirths and newborn deaths means a small sample size for some of the analyses. For example, while those receiving more than 10Gy radiation to their uterus or ovaries had an increased risk of stillbirth or death, this risk estimate was based on just five adverse outcomes in only 28 women receiving this level of exposure. These subgroup analyses may increase the possibility of chance findings when the risks were calculated according to radiation site.
The study has not looked at other pregnancy complications such as miscarriage or congenital diseases or malformations in the offspring, which may or may not be associated with radiation.
Although radiation damage to the uterus was suspected by the researchers, this was not clinically assessed, and therefore remains a theory.
The research also could not analyse 15% of the potential total cohort as they did not sign medical release forms.
It is possible that those who experienced an adverse pregnancy outcome were more likely to participate in the study.
The participants had their cancers diagnosed from 1970 to 1986, and the treatments available at that time may have been slightly different from those given today.

As the researchers say, their findings highlight the need for women who received radiation exposure to their pelvis as a child to receive careful management and monitoring during pregnancy.