Australian Clinical Guidelines for Radiological Emergencies - September 2012

Prenatal Radiation Exposure

Page last updated: 07 December 2012

Most radiation exposure events are unlikely to expose the foetus to levels causing health effects.

Foetal sensitivity to radiation is dependent on the radiation dose to the foetus. The effect of radiation is reduced with fractionation (division of the dose into units administered at different times) or protraction (lengthening the time to give a dose) of the dose compared with an acute exposure of equivalent magnitude. Consequently, there is a lessening of the incidence or severity of foetal health effects seen as a result of irradiation when the dose is fractionated or protracted.

Additionally, the foetal age determines health consequences for the foetus.

Foetal development

Foetal age may be defined in two different ways. In clinical settings, foetal age is usually referred to in terms of gestational age, the time since the onset of the last menstrual period. However, individual menstrual cycles may be quite variable in length. Foetal age may also be described as the time elapsed post-conception. This is generally two weeks less than gestational age.

Nevertheless, determining exact foetal age is relatively imprecise and the following is meant only as a guide. In this document foetal age is described in relation to time post-conception.

Development of the foetus can be considered in three phases:
  • pre-implantation, from conception to implantation (blastogenesis) (days 0-14)
  • major organogenesis, extending from the third to the eighth week post-conception (days 15-55), and
  • foetal development from the ninth week post-conception until birth. This includes the period of central nervous system development from the 8th to the 25th weeks.
Risks of non-cancer health effects due to radiation are greatest during organogenesis and the early foetal period, less in the second trimester, and least in the third trimester.

Health effects of foetal irradiation

Health effects are due to cell killing or DNA damage. DNA damage may result in leukaemia, cancer or potential hereditary effects. Damage from cell killing may result in a number of effects:
  • failure of embryo implantation
  • increased incidence of miscarriage
  • central nervous system abnormalities
  • cataracts
  • growth retardation
  • malformations
The distribution of these potential health effects is determined by the foetal age at exposure. See table 17.1.

During blastogenesis, when the number of cells in the conceptus is small, the effect of damage to these cells results in failure to implant. At this stage malformations are very rare and surviving embryos appear to be unaffected, essentially an all or nothing effect. From animal studies, the threshold for failure of implantation is 50 mGy. In a human population this would be difficult to detect, as the spontaneous failure rate for implantation is estimated to be as high as 30-50%.

During organogenesis, malformations may be caused in the organ systems under development at the time of exposure. The threshold for malformations is 100-200 mGy or higher. At 100-200 mGy, the risk of malformation is low, but increases with increasing dose.

Central nervous system effects

As the period of foetal neurological development is long and because it is the most radiation-sensitive system, radiation-induced abnormalities are usually accompanied by neuropathology.

From 8 to 25 weeks, the CNS is particularly sensitive to radiation. Foetal doses in excess of 100 mGy are associated with decreased IQ. Below this level, there is no detectable decrease in IQ.

Doses in excess of 1 Gy result in a high probability (40%) of severe intellectual impairment, especially if the dose occurs during the 8th to 15th weeks when the measured effect is a reduction of IQ of 30 points. The effect increases with increasing dose. The decrease in IQ is smaller from the 16th to 25th weeks. The effect of reduced IQ has not been observed for other periods in foetal development.

Heterotopic grey matter and microcephaly are suggestive of radiation as a cause. Similar features are also seen in foetal alcohol syndrome.

Table 17.1 Potential non-cancer health effects of prenatal radiation exposure
Acute radiation dose to foetusTime post-conception

Blastogenesis
Time post-conception

Organogenesis
Time post-conception

Fetogenesis
Time post-conception

Fetogenesis
Time post-conception

Fetogenesis
Acute radiation dose to foetus0-14 days15-55 days8-15 weeks16-25 weeks26-38 weeks
< 50 mGyThreshold for non-cancer health effectsThreshold for non-cancer health effectsThreshold for non-cancer health effectsThreshold for non-cancer health effectsThreshold for non-cancer health effects
50-500 mGySlightly increased incidence of failure to implant.
Surviving embryos have no significant non-cancer health effect.
Increased incidence of major malformations. (Not seen at < 100 mGy)
Growth retardation possible.
Reduction in IQ up to 15 points. Incidence of severe intellectual impairment up to 20%.
(CNS effects not seen at < 100 mGy)
Growth retardation possible.
Non-cancer health effects unlikelyNon-cancer health effects unlikely
> 500 mGy*High incidence of failure to implant. Surviving embryos have no significant non-cancer health effect.Increased incidence of miscarriage.
Substantial risk of major malformations.
Growth retardation likely.
Increasing incidence of miscarriage.
Incidence of severe intellectual impairment > 20%.
Growth retardation likely.
Probable increase in major malformations.
Possible increased incidence of miscarriage.
Growth retardation possible.
Reduction in IQ possible. Severe intellectual impairment possible.
Possible increase in major malformations.
Possible increased incidence of neonatal death
> 1 Gy*50% of embryos killedIncreased incidence of miscarriage.
Substantial risk of major malformations.
Severe permanent growth retardation.
Reduction in IQ up to 30 points. Incidence of severe intellectual impairment up to 40%.
Severe permanent growth retardation.
Possible increased incidence of miscarriage.
Growth retardation possible.
Reduction in IQ possible. Severe intellectual impairment possible.
Possible increase in major malformations.
Possible increased incidence of neonatal death
* The mother may have acute radiation syndrome in this range, depending on her whole body dose.

Adapted from CDC. Prenatal radiation exposure: a fact sheet for physicians. Department of Health and Human Services, Centers for Disease Control and Prevention, 2005.

Childhood cancer

Increased risk of childhood cancer and leukaemia is associated with foetal radiation exposure, based on epidemiological studies of children who were prenatally exposed during diagnostic radiology procedures.

Animal studies have not demonstrated an increase in cancer incidence from prenatal radiation exposures occurring during blastogenesis or early organogenesis. Susceptibility increases gradually up to the neonatal period. Increased incidence of tumours is seen at the following sites: breast, ovary, brain, liver and lung.

In a population exposed only to background radiation, the spontaneous incidence of childhood cancer and leukaemia from ages 0-15 years, is 2-3 per 1000 (0.2-0.3%). At low doses of radiation it is difficult to detect a change in incidence in human populations. The absolute cancer risk in ages 0-15 after foetal irradiation has been estimated as 600 per 10,000 persons each exposed to 1 Gy, or 0.06% per 10 mGy.

Excess cancers as a result of in utero exposure have not been demonstrated among Japanese atomic bomb survivors.

Pre-conception irradiation of either parent’s gonads has not been shown to cause increased cancer or malformations amongst their children. Studies of the descendants of atomic bomb survivors have not demonstrated any hereditary effects, nor have studies on the offspring of survivors of childhood cancer treated with radiation therapy.

Evaluation of risk to the foetus

The foetus may be exposed during external irradiation of the mother, but also by any radionuclide absorbed by the mother, or transferred across the placenta. The estimation of foetal dose requires consideration of all potential sources of exposure.

External irradiation

There are a number of considerations in estimating foetal dose from external radiation sources. The uterus shields the foetus from radiation sources external to the mother. Foetal dose is affected by maternal anatomy, including uterine position and bladder distension. The irradiation of the foetus may not be uniform as the foetus grows larger. And, finally, the mother may have had more than one exposure.

Most diagnostic procedures, performed correctly, do not increase risk of prenatal death, malformation or intellectual impairment. See tables 17.2 and 17.3 for estimated foetal doses from common radiological and nuclear medicine procedures. Dosimetry surveys of medical procedures demonstrate that the delivered dose varies considerably between countries. It may be especially difficult to estimate exposures from fluoroscopy procedures, as the precise duration of the procedure and location of the beam may not be recorded. Therapeutic uses of radiation can result in significant harm to the foetus because of the higher doses delivered to the mother.

Table 17.2 Estimated foetal doses from common diagnostic procedures in the UK.

Conventional x-ray examinations
Examination
Mean (mGy)
Maximum (mGy)
Abdomen
1.4
4.2
Chest
< 0.01
< 0.01
Intravenous pyelogram
1.7
10
Lumbar spine
1.7
10
Pelvis
1.1
4
Skull
< 0.01
< 0.01
Thoracic spine
< 0.01
< 0.01
Fluoroscopic examinations

Examination
Mean (mGy)
Maximum (mGy)
Barium meal
1.1
5.8
Barium enema
6.8
24
Computed tomography

Examination
Mean (mGy)
Maximum (mGy)
Abdomen
8.0
49
Chest
0.06
0.96
Head
< 0.005
< 0.005
Lumbar spine
2.4
8.6
Pelvis
25
79
Doses > 10 mGy are in bold.

Adapted from ICRP. Pregnancy and medical radiation; publication 84. Oxford, United Kingdom: Elsevier Science; 2000.

Table 17.3 Foetal whole body dose from common nuclear medicine procedures in early pregnancy and at term
RadiopharmaceuticalProcedureMaternal administered activity (MBq)Foetal whole body dose

Early (mGy)
Foetal whole body dose

At term (mGy)
99mTcBone scan (phosphate)7504.6-4.71.8
99mTcLung perfusion (MAA)2000.4-0.60.8
99mTcLung ventilation (aerosol)400.1-0.30.1
99mTcThyroid scan (pertechnetate)4003.2-4.43.7
99mTcRed blood cell9303.6-6.02.5
99mTcLiver colloid3000.5-0.61.1
99mTcRenal DTPA7505.9-9.03.5
67GaAbscess / tumour19014-1825
123IThyroid uptake*300.4-0.60.3
131IThyroid uptake*0.550.03-0.040.15
131IMetastases imaging*402.0-2.911.0
*Foetal thyroid doses are much higher than whole body dose, viz. 5-15 mGy/MBq for 123I and 0.5-1.1 Gy/Bq for 131I.
Adapted from ICRP. Pregnancy and medical radiation; publication 84. Oxford, United Kingdom: Elsevier Science; 2000.
The difficulties of dose estimation may be compounded where exposure is accidental or a result of deliberate misuse. A realistic estimate that includes an assessment of the uncertainty regarding the dose should be provided to the patient.

Internal contamination

Maternal biokinetics, the physical, chemical and biological properties of radionuclides and the effect of gestational age on placental structure and function are essential influences on placental transfer of maternally absorbed radionuclides.

For radionuclides that do not cross the placenta, foetal dose is derived from the energetic beta, gamma and x-ray radiation from radionuclides in maternal tissues. However, the risk from maternally absorbed radionuclides may be increased if the substance accumulates within the maternal bladder. Adequate maternal hydration and frequent voiding will reduce the risk to the foetus from renally excreted radionuclides.

Radionuclides that cross the placenta are generally in ionic form and may localise within specific tissues or organs or disseminate throughout the foeto-placental unit. Some radionuclides are selectively concentrated in specific foetal tissues, resulting in higher tissue concentrations relative to the mother. See Table 17. 4.

Many of the radionuclides capable of crossing the placenta are alpha and beta emitters. The concentrated emissions from these radionuclides may not be confined to the organ or tissue of localisation because of the extremely small size of the tissue or its transient nature in foetal development. This further complicates dose estimation and the prediction of potential health effects.

Studies of animals that were exposed to radionuclides as foetuses, have demonstrated dose-related increases in the incidence of tumours. Only a few radionuclides have been studied in this way (iodine, phosphorus, plutonium, tritium & strontium). However, a decrease in breast tumours was also found after chronic exposures to tritiated water caused ovarian dysfunction.

Many radionuclides also transfer to breast milk. Breast-feeding may have to be suspended for a period from several hours to several weeks dependent on the specific radionuclide.

Table 17.4 Selected radionuclides and the foeto-maternal circulation*
Element (& form)Crosses the placentaTissue distributionFoetal tissue concentration > maternal tissue concentrationConsequence
241AmYesVillus yolk sac, mostly, then placenta. Some distributed to skeleton, liver, soft tissuesPotential effects on haemopoietic stem cell lines (which migrate from the yolk sac)
No effect on the maternal blood supply to the placenta (unlike Pu)
Cobalt radioisotopesYesEndocrine organs, renal cortex, gastric mucosa, liver, skeletonYesNot stated
137CsYesUniform distribution throughout the body. Some concentration in muscle & boneNot stated
3H as tritiated waterYesUniform distribution throughout total body waterYes, because of the a relatively greater total body waterGrowth retardation, microcephaly, vascular pathology, sterility.
Embryotoxic & teratogenic at high dose
3H, organic formsYesSelective incorporation into tissues & metabolic pathwaysEmbryotoxic & teratogenic at high dose
Iodine radioisotopesYesSelective concentration in thyroid, especially after the thyroid forms at 8 weeks post conception. Maximum concentrations from 20-28 weeks.YesHypothyroidism, thyroid tumours in later life
Iridium radioisotopes#YesPlacenta, liverYesGrowth retardation, altered postnatal development
32PYesInfluenced by development of ossification sitesSkeletal malformations
Embryotoxic & teratogenic at high dose
Plutonium radioisotopesYesVillus yolk sac, mostly, then placenta. Some distributed to skeleton, liver, soft tissuesPotential effects on germ & haemopoietic stem cell lines (which migrate from the yolk sac). Foetal death.
Embryotoxic & teratogenic at high dose. Interruption to the maternal blood supply to the placenta at the highest doses.
210PoMinimalSome deposition in the visceral yolk sac and placentaFoetal dose derived from maternal and placental sources
Radium radioisotopesYesSkeletonNot stated
90SrYesSkeleton, liver & kidney. Influenced by development of ossification sitesYesSkeletal malformations.
Bone & pituitary tumours.
Embryotoxic & teratogenic at high dose.
Uranium radioisotopesSkeleton, liver, kidney, placenta & foetal membranesFoetal death, growth retardation, major malformations
# Data based on gestational studies on Platinum, which has similar chemical properties and biological behaviour to Iridium.
* Further information on other radionuclides which have been studied in relation to the foeto-maternal circulation is obtainable from National Council on Radiation Protection and Measurements. Radionuclide exposure of the embryo/fetus, NCRP Report No. 128. Bethesda: National Council on Radiation Protection and Measurements; 1998.

Counselling

Irradiation of the pregnant patient can lead to apprehension regarding potential foetal effects. Lack of understanding about the risks of prenatal radiation exposure may lead to unnecessary anxiety. Individual foetal dose estimations should be made by a qualified dosimetry expert who should be involved in advising the patient.

The following considerations are useful in preparing advice for exposed pregnant persons.

In a population exposed only to background radiation, the background incidence of
    • miscarriage, post-implantation, is 15%
    • major malformations 2-4%
    • intrauterine growth retardation 4%
    • genetic diseases 8-10%
    • intellectual impairment (IQ < 70) 3%
    • severe intellectual impairment (IQ < 50) 0.5%
    • the lifetime risk of cancer is 1 in 3, with fatal cancer at 1 in 5
    • childhood cancer is 2-3 per 1000 (0.2-0.3%).
For exposures occurring prior to implantation, surviving embryos are unlikely to be affected. However, there is always considerable uncertainty around the precise gestational age.

Up to radiation doses of 100 mGy, major malformations or neurological impairment probably do not occur. At doses above 100 mGy, there is dose-dependent increasing risk of major malformations, growth retardation and miscarriage. The risk of a measurable reduction in IQ is of particular concern if the foetus was between 8 and 15 weeks post-conception age at doses above 100 mGy, or 16 and 25 weeks at doses above 500 mGy.

The lifetime risk for radiogenic induction of childhood cancer or leukaemia is 1 in 170 (or 0.6%) per 100 mGy.

Foetal doses below 100 mGy should not be considered a medical reason for termination. At foetal doses greater than this, the magnitude of foetal damage is a function of the dose and the stage of pregnancy.

References:

1. International Commission on Radiological Protection. Pregnancy and medical radiation; publication 84. Oxford, United Kingdom: Elsevier Science; 2000.
2. Centers for Disease Control and Prevention. Prenatal radiation exposure: a fact sheet for physicians. Department of Health and Human Services, Centers for Disease Control and Prevention, 2005
3. National Council on Radiation Protection and Measurements. Radionuclide exposure of the embryo/fetus, NCRP Report No. 128. Bethesda: National Council on Radiation Protection and Measurements; 1998.
4. Mettler FA. Accidental radiation exposure during pregnancy. In: Gusev IA, Guskova AK, Mettler FA, editors. Medical management of radiation accidents, 2nd ed. CRC Press; 2001: 527-539.