Diagnostic agents

X-ray examinations

Effects of radiation

With X-rays – as with other ionizing rays – two categories of biological radiation effects are distinguished: deterministic and stochastic effects. Deterministic effects only appear above a certain threshold dose and lead to a reduction or a complete loss of organ or tissue function due to cellular death ( ). Teratogenic effects belong to these deterministic effects. Depending on the dose and the embryonic developmental stage, this may result in the death of the embryo, or malformation of various organ systems, specifically the eyes, general growth retardation, microcephaly and mental retardation. This has been documented both in animal experiments as well as empirically in humans ( ). During the first 5 days after conception (i.e., during the “all-or-nothing phase”) the lowest lethal dose is calculated at 100 mGy. During actual embryogenesis, this value is estimated at 250–500 mGy, then later at >1 Gy ( ). Severe CNS malformations during the early embryogenesis period (18–36 days after conception) are only to be expected beginning at 200 mGy. Permanent growth retardation can be expected at 250–500 mGy. Microcephaly and mental retardation is observed, above all, after doses >200 mGy between gestational weeks 10 and 17.

With a radiation dose of <50 mGy most studies conclude that no substantially increased malformation risk in humans is expected ( ). One study observed a lower birth weight after dental X-rays during pregnancy. The authors speculated that impairment of maternal thyroid function by X-rays was responsible for these findings ( ). Other authors discuss the underlying dental illness as causal ( ).

Much more difficult than estimating the teratogenic X-ray risk is assessing the stochastic mutagenic and carcinogenic effects, because there is no threshold dose under which no effect would be expected. Damage of a single cell can lead to an illness which, with higher exposure may result in a greater incidence of, for example, leukemia following prenatal X-ray exposure ( ). Point mutations might also occur spontaneously. The radiation dose leading to a doubling of the point mutation rate is given as 1.2 Gy ( ). A doubling of the mutation rate of a certain gene does not necessarily mean a doubling of the associated frequency of the disease. On the other hand, the completely inadequate knowledge of the effects on later generations must lead to greater caution in the definition of safe exposure values for the population at large ( ).

Empirical evidence on the risk for stochastic X-ray effects in the literature is still inconsistent. Among the parents of some 500 children with neuroblastomas, the use of X-ray examinations before pregnancy was no more frequent than that in a healthy control group ( ). In a case control study no significant association between a history of radiography in pregnancy and a risk of childhood leukemia was found ( ). A study of twin pregnancies reported a 2.4 factor increase in the risk of leukemia with a fetal dose of 0.01 Sv or more ( ). already considers an increased leukemia risk when additional prenatal X-ray exposure of the embryo lies in the range of the natural background radiation of about 0.001 Sv/year. By contrast, other authors assume there is no risk for the embryo with exposure of 0.02–0.05 Sv ( ). In a case control study from the USA, an increased risk for rhabdomyosarcoma was found in the children of mothers who had had an X-ray examination during pregnancy ( ). However, due to methodological irregularities, these results should be interpreted with necessary caution.

calculated the relative and absolute risk for children under the age of 15 years to become affected by a cancer after intrauterine X-ray exposure. They gave the absolute risk as 8% per Gray. Their detailed calculation was based on the largest world-wide data collection on the risk of cancer through intrauterine X-ray exposure, primarily pelvimetry, in the Oxford Survey of Childhood Cancers ( ). The authors derive comparable risk coefficients from the Japanese data on the atomic bomb victims and conclude that there is also an increased risk from a comparatively low fetal dose of 10 mSv, which, in the 1950s, was reached during a pelvic X-ray. Other authors consider such an assumption of risk to be too high and suggest that the risk of an exposure lower than 100 mSv is negligible compared to the background risk for cancer ( ). They also point to the group of intrauterine-exposed Hiroshima victims comprising not even 1,000 survivors, and to the data of the experience of exposed children in Hiroshima. However, these studies, frequently cited as proof for a rather low risk of cancer after radioactive exposure, should be critically evaluated in the light of the methodological shortcomings and the political interests of the American researchers at that time.

Ultrasound

For about 30 years, ultrasound has been used during all phases of pregnancy. Numerous animal experiments (overview in ) and epidemiological studies (overview in ) have analyzed the effects on the fetus. Negative effects could be caused mainly by local hyperthermia. Although anomalies such as an increase in fetal activity, reduced birth weight, delayed speech development and increased left-handedness, have been mentioned by individual researchers ( ) as consequences of ultrasound examinations, these effects cannot be confirmed ( ). Follow-up studies on considerably more than 1,000 children between the ages of 1–8 years, whose mothers had received ultrasound examinations between the eighteenth and thirty-eighth week, showed no differences related to weight gain and other developmental parameters between children whose mothers were examined by ultrasound five times and those whose mothers had only one ultrasound examination ( ). Pulsed doppler studies, flow measurements, and studies in the first trimester require a higher dose of energy and, theoretically, can damage embryonic tissue by warming. Thermal or non-thermal damage of the fetus cannot be ruled out, especially with the modern high output devices, and is theoretically conceivable ( ). The sees the available data as insufficient for proving a causal relationship between medically indicated ultrasound examinations and damaging effects on the fetus. Using ultrasound only when medically indicated, as well as adhering to the ALARA principle (as low as reasonably achievable), is recommended for obstetrical ultrasound.