Fetal Risk in Diagnostic Radiology

Article Outline

• Abstract
• Radiobiology and Radiation Basics
• Biological Effects of Radiation
• Effects of In Utero Radiation Exposure on the Developing Embryo or Fetus
  • Noncancer Risks From In Utero Irradiation
  • Cancer Risks from In Utero Irradiation
• General Guidelines Regarding Diagnostic Imaging During Pregnancy and Different Fetal-Dose Reduction Techniques
• Conclusions
• References
• Copyright

It is not uncommon to encounter situations in which radiologic examinations are necessary for accurate diagnosis and effective treatment of an expectant mother. The potential deleterious health consequences to the developing embryo and fetus from in utero irradiation include fetal death, congenital malformations, growth retardation, and carcinogenic and mutagenic effects. The likelihood of each effect is greatly dependent on the radiation dose and the gestational age of the conceptus at the time of exposure. In general, the average fetal doses from diagnostic imaging are <50 mGy (5 rad) and have not been associated with any significant adverse fetal effects. However, each case should be evaluated on an individual basis, and the risks should be explained to the patient before the examination. In addition, every effort should be made to reduce the fetal dose to as low as reasonably achievable. The biological effects of in utero radiation exposure, estimated fetal doses from various radiologic examinations, and general guidelines regarding diagnostic imaging during pregnancy will be discussed in this article.

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Radiobiology and Radiation Basics 

Radiobiology is an interdisciplinary branch of biophysics that studies the biological effects of ionizing radiation in living organisms at the cellular level. A mammalian cell cycle is divided into 4 phases: mitosis (M), G1, DNA synthesis (S), and G2. In general, actively dividing cells are more sensitive to the effects of radiation than cells that have already completed cell division or are differentiated. Therefore, cells are most radiosensitive during the M and G1 phases and most radioresistant during the late S phase. Ionizing radiations with sufficient energy can result in significant damage to the genetic infrastructure of a cell by causing DNA breaks. Single-strand DNA breaks are likely to be repaired. However, double-strand DNA breaks are detrimental and can result in chromosomal aberrations, potential cell death, mutations, and carcinogenesis. The time lag between a DNA insult and the appearance of biological effects can be hours to years, depending on the extent of the cellular damage.¹

To fully comprehend the biological effects of ionizing radiation, one needs to be familiar with the radiation nomenclature and dosimetry. The absorbed dose is the amount of radiation energy absorbed per unit mass of a medium (eg, biological tissue) measured in gray. Biological effects of radiation depend on both the total energy absorbed (ie, the absorbed dose) and the type of radiation. For instance, radiation emitted from alpha particles produces ionizing events that are close to one another and thus have a greater ability to cause biological damage in living tissue than sparsely ionizing radiation from x-rays and gamma rays, which produce well-dispersed ionizing events. Therefore, biological effect is best approximated by the equivalent dose, which takes into account the effectiveness of the different types of radiation in causing biological damage. The equivalent dose (expressed in sievert) is the product of the absorbed dose and the radiation weighting factor. A radiation weighting factor is a measure of the quality of the radiation. For example, alpha particles have a radiation weighting factor of 20, whereas x-rays, gamma rays, and beta particles, which are the primary types of radiation used in diagnostic radiology, have radiation weighting factors of 1. In diagnostic radiology, the absorbed dose equals the equivalent dose. The following conversions are commonly used to quantify biological effects in diagnostic radiology¹:

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Biological Effects of Radiation 

Biological effects of radiation can be categorized into stochastic or deterministic. A stochastic effect is one in which the probability of the effect increases with dose. Moreover, a stochastic effect does not require a dose threshold because injury to either a single cell or a group of cells can potentially result in the same disease. The severity of the stochastic effect is independent of the radiation dose. Radiation-induced cancer is an example of stochastic effects. Conversely, a deterministic effect is one in which the severity of the injury increases with the radiation dose. Moreover, a deterministic effect requires a dose threshold below which the effect is not clinically appreciable. Skin erythema and cataracts are examples of deterministic effects. Deterministic effects are rarely seen at the absorbed doses encountered in diagnostic radiology; however, stochastic effects and potential biological harms to the developing embryo or fetus remain a concern for expectant mothers and physicians.² Different recommended dose limits and biological effects from radiation are summarized in Fig 1.

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• Figure 1. 

  Summary of recommended annual doses and different kinds of potential biological effects. Dose limit for members of the public recommended by ICRP is 1 mSv/y, excluding natural background radiation and medical doses. In the United States, annual exposure to natural background radiation is approximately 3 mSv/y, including 2 mSv attributed to indoor radon. ICRP recommends an annual occupational dose limit of 20 mSv/y when averaged over 5 years. For pregnant workers, ICRP recommends a limit of 1 mSv from declaration of pregnancy to birth of a child. Recommendation from National Council on Radiation Protection for a declared pregnant worker is maximum of 0.5 mSv/month, which equals a total dose of 5 mSv. Radiation sickness is due to an extremely high, albeit brief, whole-body lethal dose. Severity of symptoms associated with radiation sickness increases as dose increases, ranging from nausea, vomiting, anorexia, diarrhea, hypotension, and death. LD 50/60 is the single, uniform whole-body lethal dose that would kill 50% of the irradiated human population within 60 days and is estimated to be 3-5 Sv.¹, ³

(Reprinted with permission from Wolbarst AB.³)

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Effects of In Utero Radiation Exposure on the Developing Embryo or Fetus 

Noncancer Risks From In Utero Irradiation 

A human embryo is a rapidly proliferating organism and therefore is particularly sensitive to the effects of radiation. The first reported cases of suspected radiogenic harms from prenatal exposure to radiation were described in 1929 by Goldstein and Murphy, who published 38 case reports of children with mental retardation and microcephaly who were born to mothers who received pelvic radiotherapy during pregnancy. Since then, the potential effects of ionizing radiation to a developing embryo or fetus have been extensively studied by using animal models (Fig. 2) and data extrapolation from investigations involving atomic bomb survivors in Hiroshima and Nagasaki.⁴ On the basis of the data collected from these studies, the potential adverse health consequences from prenatal radiation exposure can be classified into 4 categories: (1) pregnancy complications (eg, spontaneous abortion, stillbirth), (2) congenital malformations, (3) growth retardation, and (4) mutagenic and carcinogenic effects.⁵, ⁶

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• Figure 2. 

  Litter of a female mouse irradiated with x-rays during organogenesis and killed at 19 days. Multiple anomalies are evident. Among the 5 embryos in the top row, only the middle third is normal. Remainder of embryos demonstrate exencephaly, exencephaly and evisceration, and anencephaly (from left to right). The 4 embryos on the bottom row are resorbed.

(Reprinted with permission from Hall and Giaccia.⁴ Photograph by Dr. Roberts Rugh.)

The 2 most important determinants of radiation-induced harm to the unborn child are radiation dose and the developmental stage of the conceptus at the time of exposure. The human embryo or fetus is most sensitive to the deleterious effects of radiation during the first trimester and less so during the second and third trimesters. The central nervous system, in particular, is most sensitive to in utero radiation exposure. Radiation exposure in excess of 100 mGy to a pregnant woman during the first 2 weeks after conception demonstrates an “all-or-none” phenomenon and could potentially result in either spontaneous abortion or a completely unaffected embryo.¹ During the 3rd-8th weeks after conception, the period of organogenesis, the human embryo or fetus is most vulnerable to radiation-induced congenital malformations (Figure 3, Figure 4). From the 8th-15th weeks after conception, the fetus has the highest risk of radiation-induced mental retardation. According to several epidemiologic studies of the prenatally exposed population of atomic bomb survivors in Japan, 86% of individuals with microcephaly were exposed in the first (55%) or second trimester (31%).⁷, ⁸ In addition, a majority of cases (83%) of both severe mental retardation and microcephaly were due to irradiation at 8-15 weeks after ovulation. Time of ovulation was defined in these studies as 2 weeks after the onset of the last menstrual period. Data analysis from these studies also demonstrated that during this particular gestational age, the average intelligence quotient (IQ) reduction is approximately 25-31 points per Gy above 0.1 Gy, and the risk for severe mental retardation is estimated to be about 40% per Gy above 0.1 Gy. The risk of mental retardation is less during weeks 16-25 after conception by a factor of 4.⁴, ⁷, ⁸ Atomic bomb survivor data also showed that ionizing radiation-induced permanent growth retardation is possible with increasing dose, particularly at a level >1 Gy. Moreover, growth restriction can occur at any time after the first 14 days after conception; however, it is most pronounced when the radiation exposure occurs during the first trimester.⁹ At >26 weeks after conception, the risk of noncancer biological effects from radiation is miniscule at exposure levels seen in diagnostic radiology. However, at doses above 1 Gy, the risk of neonatal death or miscarriage increases and might still occur during this late stage of fetal development.⁹, ¹⁰, ¹¹ The potential radiation-induced noncancer health effects from in utero exposure at different developmental stages are shown in Table 1. According to the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) 2010 Report, although there is currently no epidemiologic evidence of hereditary effects in exposed human embryos, the Committee considers that there is a potential threshold of approximately 100 mGy, on the basis of data collected from multiple studies involving animal models and from some observations of high-dose exposures in pregnant women. It is further stated in the UNSCEAR 2010 Report that a fetal dose >100 mGy can result in some IQ loss, and doses in the range of 1000 mGy can cause severe mental retardation and microcephaly.¹² The whole-body fetal dose from diagnostic imaging procedures rarely exceeds 100 mGy (Table 2).⁹, ¹³, ¹⁴

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• Figure 3. 

  MR image of 41-year-old man who was exposed to in utero radiation at 8-9 weeks after conception from the atomic bomb in Hiroshima. Coronal MR image demonstrates thinning of the cortical gray matter of both cerebral hemispheres as well as subependymal heterotopic gray matter nodules lining both lateral ventricles, characteristic of congenital central nervous system malformation.

(Reprinted with permission from Wolbarst AB.³)

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• Figure 4. 

  Photograph of teenage survivor of the atomic bomb in Nagaski with microcephaly and growth retardation. On the right of the photograph is 15-year-old boy who was exposed to in utero radiation at approximately 7 weeks of gestation and at 1.2 km from the hypocenter. A normal 12-year-old boy is seen on the left of the photograph.

(Courtesy of the Atomic Bomb Disease Institute of Nagasaki University.)

Table 1. Potential Radiation-Induced Noncancer Health Effects From In Utero Exposure⁹, ¹⁰, ¹¹

Developmental Stage	Gestational Age	Time After Conception	<50 mGy	50-100 mGy	>100 mGy
Blastogenesis	0-2wk	Before conception	None	None	None
	3-4wk	1-2 wk	None	Likely none	Spontaneous abortion might occur.⁎
Organogenesis	5-10wk	3-8 wk	None	Potential biological effects are not clinically detectable	Congenital malformations might occur, and the risk increases with increasing dose.
Fetogenesis	11-17wk	9-15 wk	None	Potential biological effects are not clinically detectable	Increased risk of IQ reduction or mental retardation with increasing severity as the dose increases.
	18-27wk	16-25 wk	None	None	IQ loss is not detectable at the average dose range in diagnostic radiology.
	>27wk	>25 wk	None	None	None at the average dose range in diagnostic radiology.

Table 2. Estimated Fetal Doses From Various Radiologic Examinations in Diagnostic Radiology⁹, ¹³, ¹⁴

Type of Examination	Average Dose (mGy)⁎	Maximum⁎ Dose (mGy)
Skull radiograph	<0.01	<0.01
Chest radiograph	<0.01	<0.01
Abdominal radiograph	1.4	4.2
Pelvis radiograph	1.1	4
Cervical spine radiograph	<0.01
Thoracic spine radiograph	<0.01	<0.01
Lumbar spine radiograph	1.7	10
Intravenous urogram	1.7	10
Mammogram (2 views)	Negligible
CT (head)	<0.005	<0.005
CT (chest)	<0.06	1
CT (abdomen)	8	49
CT (pelvis)	25	80
CT renal stone protocol	8-12(at 0-month gestation)†
	4-7(at 3-month gestation)
CT appendix: protocol	15.2-16.8 (at 0-month gestation)†
	20-40 (at 3-month gestation)
CT pulmonary embolus protocol	2.4-4.7 (at 0-month gestation)†
	6.1-6.6 (at 3-month gestation)
Perfusion lung scan with Tc 99m MAA	0.06-0.12
Ventilation lung scan with xenon 133	0.01-0.19
Barium meal (UGI)	1.1	5.8
Barium enema	6.8	24
Cerebral angiography	<0.1
Pulmonary angiogram via femoral route	2.21-3.74
Pulmonary angiogram via brachial route	<0.5

MAA, macroaggregated albumin; UGI, upper gastrointestinal.

Cancer Risks from In Utero Irradiation 

In 1956, Stewart and Kneale reported an increase in incidence of leukemia and childhood cancer in children born to mothers who received pelvic x-irradiation for medical purposes.², ⁴ It is now well-acknowledged that there is an association between the risk of childhood cancer and prenatal radiation exposure. However, whether prenatal radiation exposure is the causative agent of childhood cancer remains a controversial debate. Data analysis from animal studies indicates that carcinogenic risk is greatest in late fetal development; however, whether the carcinogenic risks vary at different stages of the human fetal development has not been revealed to date. Presently, the carcinogenic risk in the irradiated human embryo or fetus is assumed to be constant throughout the pregnancy.¹¹ According to the International Commission on Radiological Protection (ICRP) publication 84, an embryo or fetus that has been exposed to a fetal dose of 10 mGy has a relative risk of up to 1.4 of developing radiation-induced cancer as compared with the nonexposed counterpart. This risk is approximately the same as that of lifetime cancer risk from childhood radiation exposure.⁹ Therefore, although the lifetime cancer risk from in utero radiation exposure has not been elucidated, the lifetime cancer risk from childhood radiation exposure provides a good approximation of the prenatal risk. The estimated childhood cancer risk from prenatal irradiation is provided in Table 3, and comparison of the risk of childhood leukemia from in utero irradiation to other risk groups is shown in Table 4.

Table 3. Estimated Cancer Risk From In Utero Radiation Exposure⁹, ¹⁰, ¹¹

Table 4. Comparison of Risk of Childhood Leukemia Among Different Patient Populations¹⁵

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General Guidelines Regarding Diagnostic Imaging During Pregnancy and Different Fetal-Dose Reduction Techniques 

According to the 2008 American College of Radiology practice guidelines for imaging pregnant or potentially pregnant patients, all women of reproductive age should be screened for the possibility of pregnancy at the time of the radiologic examination. If necessary, a pregnancy test can be obtained for confirmation before the examination.¹⁶ Diagnostic imaging during pregnancy can involve both ionizing and nonionizing modalities as well as the use of intravenous contrast agents. There has been no significant biological effect reported with in utero exposure to ultrasound. Therefore, ultrasonography remains a safe and recommended first-line modality in the diagnosis and treatment of pregnant patients. In circumstances where sonographic findings are inconclusive, magnetic resonance imaging (MRI) is an appropriate alternative imaging technique if available and clinically applicable.¹⁷ Although concerns about potential biological effects related to the induction of local electric fields and currents from magnetic fields with MRI have been raised, there have been no documented biological harms to the developing fetus or the expectant mother from MRI performed at or below 1.5 tesla.¹⁸, ¹⁹, ²⁰

Infrequently, physicians encounter situations, particularly in the trauma settings, in which the use of ionizing imaging techniques is necessary for accurate diagnosis and treatments. In these circumstances, it is prudent to practice dose-reduction techniques when feasible to minimize the fetal dose and thereby reduce the probability of radiation-induced biological effects to the fetus. For instance, for an abdominal or pelvic radiograph, a posterior-anterior exposure results in lower fetal dose than an anterior–posterior exposure because the uterus is located in the anterior aspect of a mother's pelvis. Fetal radiation dose from a computed tomography (CT) scan depends on multiple factors such as kilovolt peak, milliamperes, and slice thickness. These parameters can be tailored for each individual examination to obtain significant reduction in fetal dose without sacrificing the necessary diagnostic image quality. For example, one can lower the milliamperes or increase the pitch with spiral CT. Furthermore, shielding should be used whenever the abdomen or pelvis is not being imaged. Internal shielding with barium sulfate has been demonstrated to be an effective fetal dose-reduction technique and is currently being used at our institution as part of a CT pulmonary embolus protocol in pregnant patients (Fig. 5).²¹

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• Figure 5. 

  27-weeks pregnant patient with right-sided pleuritic chest pain. (A) Topogram of CT angiography of the chest demonstrates the use of oral barium sulfate (arrowhead) and lead apron (open arrow) as methods of fetal shielding. (B) Axial CT image with intravenous contrast demonstrates a segmental pulmonary embolus in the right lower lobe (arrow).

According to the American College of Obstetricians and Gynecologists, radiologic treatment involving radioiodine isotopes is contraindicated during pregnancy because of the concern of potential thyroid cancer induction in the fetus.¹³, ¹⁷ In addition, if scintigraphic imaging of the thyroid is necessary, Tc 99m should be used in place of I-131.¹⁷ Mammography exposes the fetus to a negligible amount of radiation and therefore can be performed safely at any time during pregnancy.¹⁶, ²² For cancer staging in pregnant patients, MRI is the modality of choice and is preferred over positron emission tomography/CT because of the lack of safety data in human pregnancy with positron emission tomography and the radiation exposure associated with CT.¹⁹ However, the use of gadolinium in the diagnostic cancer work-up is not recommended during pregnancy because its safety has not been scientifically established.¹⁷ According to the American College of Radiology and American College of Obstetricians and Gynecologists guidelines, there is no single diagnostic x-ray procedure that results in a radiation dose significant enough to threaten the well-being of the embryo and fetus. Therefore, exposure to a single diagnostic x-ray examination during pregnancy is not a justified indication for therapeutic abortion.¹⁶, ¹⁷

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Conclusions 

In utero radiation exposure might result in potential deleterious health consequences to the developing embryo and fetus including fetal death, congenital malformations, growth retardation, and carcinogenic and mutagenic effects. The likelihood of each effect is greatly dependent on the radiation dose and the gestational age of the conceptus at the time of exposure. In general, the average fetal doses from diagnostic x-ray imaging and nuclear medicine studies are <50 mGy (5 rad) and have not been associated with any significant adverse fetal effects. However, each case should be evaluated on an individual basis, and the risks should be explained to the patient before the examination. Ultrasound and MRI should be used whenever possible as first-line imaging modalities in pregnant patients. In circumstances where ionizing radiation is essential for the diagnosis and treatment of an expectant mother, every effort should be made to minimize the fetal dose to reduce the fetal risks associated with in utero irradiation.

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References 

1. Walter H . Review of Radiologic Physics . (ed 3). Philadelphia, PA: Lippincott Williams & Wilkins; 2010;
   • View In Article
2. Bushberg JT , Seibert JA , Leidholdt EM , et al.  The Essentials Physics of Medical Imaging . (ed 2). Philadelphia, PA: Lippincott Williams & Wilkins; 2002;
   • View In Article
3. Wolbarst AB . Physics of Radiology . (ed 2). Madison, WI: Medical Physics Publishing; 2005;
   • View In Article
4. Hall EJ , Giaccia AJ . Radiobiology for the Radiologist . (ed 6). Philadelphia, PA: Lippincott Williams & Wilkins; 2006;
   • View In Article
5. Yamazaki JN , Schull WJ . Perinatal loss and neurological abnormalities among children of the atomic bomb: Nagasaki and Hiroshima revisited, 1949 to 1989 . JAMA . 1990;264:605–609
   • View In Article
   • MEDLINE
6. Brent RL . Saving lives and changing family histories: Appropriate counseling of pregnant women and men and women of reproductive age, concerning the risk of diagnostic radiation exposures during and before pregnancy . Am J Obstet Gynecol . 2009;200:4–24
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (2136 KB)
   • CrossRef
7. Schull WJ , Otake M . Cognitive function and prenatal exposure to ionizing radiation . Teratology . 1999;59:222–226
   • View In Article
   • MEDLINE
   • CrossRef
8. Schull WJ . Effects of Atomic Radiation, a Half-Century of Studies From Hiroshima and Nagasaki . New York, NY: Wiley-Liss & Sons, Inc; 1995;
   • View In Article
9. International Commission on Radiological Protection . In: Pregnancy and Medical Radiation . 84: Ottawa, Ontario, Canada: ICRP Publication; 2000;p. 1–43
   • View In Article
10. International Commission on Radiological Protection . In: Biological Effects After Prenatal Irradiation (Embryo and Fetus) . 90: Ottawa, Ontario, Canada: ICRP Publication; 2003;p. 1–200
    • View In Article
11. Radiation and pregnancy: A fact sheet for clinicians (Centers for Disease Control and Prevention publication) . http://www.bt.cdc.gov/radiation/prenatalphysician.asp
    • View In Article
12. United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) . Summary of Low-Dose Radiation Effects on Health, UN Publication M.II.IX.4 . New York, NY: UN Publications; 2011;
    • View In Article
13. Bentur Y . Ionizing and nonionizing radiation in pregnancy . In:  Koren G editors. Maternal-Fetal Toxicology . New York, NY: Marcel Dekker; 1994;p. 515
    • View In Article
14. Hurwitz LM , Yoshizumi T , Reiman RE , et al.  Radiation dose to the fetus from body MDCT during early gestation . AJR Am J Roentgenol . 2006;186:871–876
    • View In Article
    • CrossRef
15. Miller RW . Epidemiologic conclusions from radiation toxicity studies . In:  Fry RJM editors. Late Effects of Radiation: Proceedings of the Colloquium Held at the Center for Continuing Education . University of Chicago,Illinois, May 1969. London, UK: Taylor and Francis; 1970;p. 245–256
    • View In Article
16. ACR . Practice guideline for imaging pregnant or potentially pregnant adolescents and women with ionizing radiation . Reston, VA: American College of Radiology; 2008;
    • View In Article
17. ACOG Committee on Obstetric Practice . ACOG Committee Opinion, number 299, September 2004 (replaces no. 158, September 1995): Guidelines for diagnostic imaging during pregnancy . Obstet Gynecol . 2004;104:647–651
    • View In Article
    • MEDLINE
    • CrossRef
18. Duncan KR . The development of magnetic resonance imaging in obstetrics . Br J Hosp Med . 1996;55:178–181
    • View In Article
    • MEDLINE
19. Kirkinen P , Partanen K , Vainio P , et al.  MRI in obstetrics: A supplementary method for ultrasonography . Ann Med . 1996;28:131–136
    • View In Article
    • MEDLINE
    • CrossRef
20. Nicklas AH , Baker ME . Imaging strategies in the pregnant cancer patient . Semin Oncol . 2000;27:623–632
    • View In Article
    • MEDLINE
21. Yousefzadeh D , Ward M , Reft C . Internal barium shielding to minimize fetal irradiation in spiral chest CT: A phantom simulation experiment . Radiology . 2006;239:751–758
    • View In Article
    • MEDLINE
    • CrossRef
22. Sechopoulos I , Suryanarayanan S , Vedantham S , et al.  Radiation dose to organs and tissues from mammography: Monte Carlo and phantom study . Radiology . 2008;246:434–443
    • View In Article
    • CrossRef