Date Published: September 7, 2010
Publisher: Public Library of Science
Author(s): Eduardo L. Franco, Guy-Anne Turgeon
Abstract: Eduardo Franco and Guy-Anne Turgeon discuss new findings from Joel Ray and colleagues on the cancer risk following prenatal exposure to radiodiagnostic imaging, and where new research needs to be focused.
Partial Text: Determining carcinogenic risk following imaging radiation exposure is based mostly on predictive mathematical models developed from empirical data provided by large observational studies, such as the large cohort study of Japanese atomic bomb survivors . The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) model developed by the United Nations  and the Biological Effects of Ionizing Radiation (BEIR) VII model developed by the US National Research Council  have been validated for risk assessment using smaller exposed cohorts, for example, those of nuclear plant workers, the Chernobyl population, workers exposed occupationally, and patients undergoing medical procedures involving radiation exposure. In general, these models have been used to establish maximum acceptable levels of exposure and protection guidelines in occupational environments and for setting limits and safety standards in radiodiagnostic and therapeutic exposures . In this issue of PLoS Medicine, Joel Ray and colleagues report a large study from Ontario, Canada that adds to our growing understanding of cancer risk following prenatal exposure to radiodiagnostic imaging .
The possibility that pre- or postnatal exposure to radiation from diagnostic imaging procedures increases cancer risk is among the most controversial topics in medicine –. The association of in utero irradiation and increased risk of childhood malignancies has been studied since the 1950s. Ionizing radiation has been shown to cause leukaemia and solid tumours in both exposed adults and children ,,. However, for in utero exposure the magnitude of the risk from low-dose radiation and whether risk varies throughout pregnancy have been open to debate. Some supporting empirical data exist for the increased risk of leukaemia , but the issue is far from resolved despite numerous case-control and cohort studies, and in spite of meta-analyses that have attempted to provide average risk effects ,.
It is against the above backdrop of findings spanning multiple eras of exposure dose that the innovative study by Joel Ray and colleagues  in this issue of PLoS Medicine tries to advance our understanding of this important public health concern. The authors used a meticulous record linkage of administrative and health care utilization databases to identify all 1.8 million mother–child pairs from 1991 to 2008 in Ontario, Canada. They identified all term obstetrical deliveries and newborn records, and inpatient and outpatient major radiodiagnostic services, and linked these data to the Ontario tumour registry records to identify children who developed a malignant tumour after birth. There were four cancer cases among the children of 5,590 mothers having received any form of radiodiagnostic imaging procedure during pregnancy, versus 2,539 cases documented among the offspring of 1,829,927 mothers with no exposure. This translates into a RR (with pregnancies as denominators for rates) of 0.52. Most importantly, however, the authors analyzed the risk effect on the basis of the accrued person–time denominators for all children. This resulted in a crude hazard ratio [HR] of 0.69 (95% CI 0.26–1.82). Adjustment for a priori confounders, such as maternal age, income, urban status, maternal cancer, infant sex, history of chromosomal or congenital anomalies, and radiodiagnostic exposure after birth, did not materially change the association (HR = 0.68, 95% CI 0.25–1.80). Because their study was population-based and enrolled all eligible pregnancy–child pairs in the province during the accrual period, the incidence of childhood cancers observed among those with radiodiagnostic exposures represents a reduced burden of disease. For external validity purposes, however, the authors prudently concluded that, although the point estimate of the association was consistent with reduced risk, the statistical boundaries gauging the precision of the measure prevented them from ruling out a harmful effect from prenatal irradiation from medical sources. As an additional finding, the authors showed that radiodiagnostic testing increased about 6-fold, from 1.1 to 6.3 per 1,000 pregnancies during the nearly two decades covered by the study, with nearly three-fourths of these procedures being CT scans.
The ongoing controversy about cancer risk following prenatal exposure to radiodiagnostic imaging has not been solved, but there seems to be a general consensus that diagnostic imaging poses a high risk of inducing childhood malignancies and that the null results must be interpreted carefully. Diagnostic CT imaging radiation involving the pelvis and the abdomen yields a high dose to the foetus , and may thus, at least theoretically, increase the risk of childhood and even adult malignancies  relative to imaging procedures taken with the foetus outside of the field of view, which provides negligible scattered radiation exposure. Future studies should focus on accurately stratifying risk on the basis of this premise. We also believe that an international consortium that attempts to pool the data from the available investigations with the primary aim of categorizing exposure-risk associations on the basis of the magnitude of the dose delivered to the foetus could shed much light into this issue and assist policymakers in the future.