The term radiation is poorly understood. Literally it refers to transmission of energy, and thus it is often applied not only to x-rays, but also to microwaves, ultrasound, diathermy, and radio waves. Of these, x-rays and gamma rays have short wavelengths with very high energy and are forms of ionizing radiation. The other four energy forms have rather long wavelengths and low energy (Brent, 1999a, 2009).
The biological effects of x-rays are caused by an electrochemical reaction that can cause tissue damage. According to Brent (1999b, 2009), x- and gamma-radiation at high doses can create biological effects and reproductive risks in the fetus:
Deterministic effects, which may cause congenital malformations, fetal-growth restriction, mental retardation, and abortion
Stochastic effects—randomly determined probabilities—which may cause genetic diseases and carcinogenesis.
In this sense, ionizing radiation refers to waves or particles—photons—of significant energy that can change the structure of molecules such as those in DNA, or that can create free radicals or ions capable of causing tissue damage (Hall, 1991; National Research Council, 1990). Methods of measuring the effects of x-rays are summarized in Table 41-3. The standard terms used are exposure (in air), dose (to tissue), and relative effective dose (to tissue). In the range of energies for diagnostic x-rays, the dose is now expressed in gray (Gy), and the relative effective dose is now expressed in sievert (Sv). These can be used interchangeably. For consistency, all doses discussed subsequently are expressed in contemporaneously used units of gray (1 Gy = 100 rad) or sievert (1 Sv = 100 rem). To convert, 1 Sv = 100 rem = 100 rad.
Table 41-3. Some Measures of Ionizing Radiation |Favorite Table|Download (.pdf)
Table 41-3. Some Measures of Ionizing Radiation
The number of ions produced by x-rays per kg of air
Unit: roentgen (R)
The amount of energy deposited per kg of tissue
Modern unit: gray (Gy) (1 Gy = 100 rad)
Traditional unit: rada
Relative effective dose
The amount of energy deposited per kg of tissue normalized for biological effectiveness
Modern unit: sievert (Sv) (1 Sv = 100 rem)
Traditional unit: rema
When calculating the dose of ionizing radiation such as that from x-rays, according to Wagner and colleagues (1997) several factors to be considered include:
Type of study
Type and age of equipment
Distance of target organ from radiation source
Thickness of the body part penetrated
Method or technique used for the study.
Estimates of dose to the uterus and embryo for a variety of commonly used radiographic examinations are summarized in Table 41-4. Studies of maternal body parts farthest from the uterus, such as the head, result in a very small dose of radiation scatter to the embryo or fetus. Because the size of the woman, radiographic technique, and equipment performance are variable factors, data in the table serve only as a guideline. When the radiation dose for a specific individual is required, a medical physicist should be consulted. In his most recent review, Brent (2009) recommends consulting the Health Physics Society website (www.hps.org) to view some examples of questions and answers posed by patients exposed to radiation (Click on ATE—ask the expert).
Table 41-4. Dose to the Uterus for Common Radiological Procedures |Favorite Table|Download (.pdf)
Table 41-4. Dose to the Uterus for Common Radiological Procedures
Dosea View (mGy)
AP, PA Lat
AP, PAc Latd
Deterministic Effects of Ionizing Radiation
One potential harmful effect of radiation exposure is deterministic, which may result in abortion, growth restriction, congenital malformations, microcephaly, and mental retardation. These deterministic effects are threshold effects, and the level below which they are induced is the NOAEL—no-adverse-effect level (Brent, 2009).
The harmful deterministic effects of ionizing radiation have been extensively studied for cell damage with resultant dysfunction of embryogenesis. These have been assessed in animal models, as well as Japanese atomic bomb survivors and the Oxford Survey of Childhood Cancers (Sorahan and colleagues, 1995). Additional sources have confirmed previous observations and provided more information. One is the 2003 International Commission on Radiological Protection (ICRP) publication of biological fetal effects from prenatal irradiation. Another is the BEIR VII Phase 2 report of the National Research Council (2006) that discusses health risks from exposure to low levels of ionizing radiation.
In the mouse model, the risk of lethality is highest during the preimplantation period—up to 10 days postconception. This is likely due to blastomere destruction caused by chromosomal damage (Hall, 1991). The NOAEL for lethality is 0.15 to 0.2 Gy. Genomic instability can be induced in some mouse models at levels of 0.5 Gy (50 rad), which greatly exceeds levels with diagnostic studies (International Commission on Radiological Protection, 2003).
During organogenesis, high-dose radiation—1 gray or 100 rad—is more likely to cause malformations and growth restriction, and less likely to have lethal effects in the mouse. Studies of brain development suggest that there are effects on neuronal development and a “window of cortical sensitivity” in early and midfetal periods with a threshold in the range of 0.1 to 0.3 Gy or 10 to 30 rad (International Commission on Radiological Protection, 2003).
Adverse human effects of high-dose ionizing radiation are most often quoted in atomic bomb survivors from Hiroshima and Nagasaki (Greskovich and Macklis, 2000; Otake and co-workers, 1987). The International Commission on Radiological Protection (2003) confirmed initial studies showing that the increased risk of severe mental retardation was greatest between 8 and 15 weeks (Fig. 41-2). There may be a lower threshold dose of 0.3 Gy—30 rad—a similar range of the “window of cortical sensitivity” in the mouse model discussed above. The mean decrease in intelligence quotient (IQ) scores was 25 points per Gy or 100 rad. There appears to be linear dose response, but it is not clear whether there is a threshold dose. Most estimates err on the conservative side by assuming a linear nonthreshold (LNT) hypothesis. From their review, Strzelczyk and colleagues (2007) conclude that limitations of epidemiological studies at low-level exposures, along with recent new radiobiological findings, challenge the hypothesis that any amount of radiation causes adverse effects.
Follow-up of subjects from Hiroshima and Nagasaki after the atomic bomb explosion in 1945: Subsequent severe mental retardation caused by exposure to ionizing in utero radiation at two gestational age epochs to 1 Gy—or 100 rad. Mean values and 90-percent confidence levels are estimated from dosimetry calculated by two methods—T65DR and D586—used by the Radiation Effects Research Foundation of the Japanese Ministry of Health and National Academy of Sciences of the United States. (Data from Otake and associates, 1987, with permission.)
Finally, there is no documented increased risk of mental retardation in humans less than 8 weeks' or greater than 25 weeks' gestation, even with doses exceeding 0.5 Gy or 50 rad (Committee on Biological Effects, BEIR V, 1990; International Commission on Radiological Protection, 2003).
There are also reports that describe high-dose radiation given to treat women for malignancy, menorrhagia, and uterine myomas. In one, Dekaban (1968) described 22 infants with microcephaly, mental retardation, or both, following exposure in the first half of pregnancy to an estimated 2.5 Gy or 250 rad. Malformations in other organs were not found unless they were accompanied by microcephaly, eye abnormalities, or growth restriction (Brent, 1999a).
The implications of these findings seem straightforward. From 8 to 15 weeks, the embryo is most susceptible to radiation-induced mental retardation. It has not been resolved whether this is a threshold or nonthreshold linear function of dose. The Committee on Biological Effects (1990) estimates the risk of severe mental retardation to be low as 4 percent for 0.1 Gy (10 rad) and as high as 60 percent for 1.5 Gy (150 rad). But recall that these doses are 2 to 100 times higher than those from diagnostic radiation. Importantly, cumulative doses from multiple procedures may reach the harmful range, especially at 8 to 15 weeks. At 16 to 25 weeks, the risk is less. And again, there is no proven risk before 8 weeks or after 25 weeks.
Embryofetal risks from low-dose diagnostic radiation appear to be minimal. Current evidence suggests that there are no increased risks for malformations, growth restriction, or abortion from a radiation dose of less than 0.05 Gy (5 rad). Indeed, Brent (2009) concluded that gross congenital malformations would not be increased with exposure to less than 0.2 Gy (20 rad). Because diagnostic x-rays seldom exceed 0.1 Gy (10 rad), Strzelczyk and associates (2007) concluded that these procedures are unlikely to cause deterministic effects.
Stochastic Effects of Ionizing Radiation
This refers to random, presumably unpredictable oncogenic or mutagenic effects of radiation exposure. They concern associations between fetal diagnostic radiation exposure and increased risk of childhood cancers or genetic diseases. According to Doll and Wakeford (1997), as well as the National Research Council (2006) BEIR VII Phase 2 report, excess cancers can result from in utero exposure to doses as low as 0.01 Sv or 1 rad. Stated another way by Hurwitz and colleagues (2006), the estimated risk of childhood cancer following fetal exposure to 0.03 Gy or 3 rad doubles the background risk of 1 in 600 to that of 2 in 600.
In one report, in utero radiation exposure was determined for 10 solid cancers in adults from 17 to 45 years of age. There was a dose-response relationship as previously noted at the 0.1 Sv or 10 rem threshold. Intriguingly, nine of 10 cancers were found in females (National Research Council, 2006). These likely are associated with a complex series of interactions between DNA and ionizing radiation. They also make it more problematic to predict cancer risk from low-dose radiation of less than 0.1 Sv or 10 rem. Importantly, below doses of 0.1 to 0.2 Sv, there is no convincing evidence of a carcinogenic effect (Brent, 2009; Preston and colleagues, 2008; Strzelczyk and co-workers, 2007).
In an earlier report, the Radiation Therapy Committee Task Group of the American Association of Physics in Medicine found that about 4000 pregnant women annually undergo cancer therapy in the United States (Stovall and colleagues, 1995). Their recommendations, however, stand to date. The Task Group emphasizes careful individualization of radiotherapy for the pregnant woman (see Chap. 57, Radiation Therapy). For example, in some cases, shielding of the fetus and other safeguards can be taken (Fenig and colleagues, 2001; Nuyttens and colleagues, 2002). In other cases, the fetus will be exposed to dangerous doses of radiation, and a carefully designed plan must be improvised (Prado and colleagues, 2000). One example is the model to estimate fetal dosage with maternal brain radiotherapy, and another is the model to calculate fetal dose with tangential breast irradiation developed by Mazonakis and colleagues (1999, 2003). The impact of radiotherapy on future fertility and pregnancy outcomes was recently reviewed by Wo and Viswanathan (2009) and is discussed in detail in Chapter 57, Fertility after Cancer Therapy.
To estimate fetal risk, approximate x-ray dosimetry must be known. According to the American College of Radiology (Hall, 1991), no single diagnostic procedure results in a radiation dose significant enough to threaten embryofetal well-being.
Dosimetry for standard radiographs is presented in Table 41-4. In pregnancy, the two-view chest radiograph is the most commonly used study, and fetal exposure is exceptionally small—0.0007 Gy or 0.07 mrad. With one abdominal radiograph, because the embryo or fetus is directly in the x-ray beam, the dose is higher—0.001 Gy or 100 mrad. The standard intravenous pyelogram may exceed 0.005 Gy or 500 mrad because of several films. The one-shot pyelogram described in Chapter 48, Management of Nonresponders, is useful when urolithiasis or other causes of obstruction are suspected but unproven by sonography. Most “trauma series,” such as radiographs of an extremity, skull, or rib series, deliver low doses because of the fetal distance from the target area.
Fetal indications for radiographic studies are limited. Perhaps the most common is pelvimetry with a breech presentation (see Chap. 24, Pelvimetry, and Fig. 20-4).
Fluoroscopy and Angiography
Dosimetry calculations are much more difficult with these procedures because of variations in the number of radiographs obtained, total fluoroscopy time, and fluoroscopy time in which the fetus is in the radiation field. As shown in Table 41-5, the range is quite variable. Although the Food and Drug Administration limits exposure rate for conventional fluoroscopy such as barium studies, special-purpose systems such as angiography units have potential for much higher exposure.
Table 41-5. Estimated X-Ray Doses to the Uterus/Embryo from Common Fluoroscopic Procedures |Favorite Table|Download (.pdf)
Table 41-5. Estimated X-Ray Doses to the Uterus/Embryo from Common Fluoroscopic Procedures
Dose to Uterus (mrad)
Fluoroscopic Exposure Time (sec)
Cinegraphic Exposure Time (sec)
223 (SD = 118)
49 (SD = 9)
1023 (SD = 952)
32 (SD = 7)
1186 (SD = 593)
49 (SD = 13)
Upper gastrointestinal seriesd
Endoscopy is the preferred method of gastrointestinal tract evaluation in pregnancy. Occasionally, an upper gastrointestinal series or barium enema may be done before the woman realizes that she is pregnant. Most would likely be performed during the period of preimplantation or early organogenesis.
Angiography may occasionally be necessary for serious maternal disorders, and especially for trauma. As before, the greater the distance from the embryo or fetus, the less the exposure and risk.
Most computed tomography (CT) imaging is now performed by obtaining a spiral of 360-degree images that are postprocessed in multiple planes. Of these, the axial image remains the most commonly obtained. Multidetector CT (MDCT) images are now standard for common clinical indications. The most recent detectors have 16 or 64 channels. MDCT protocols may result in increased dosimetry compared with traditional CT imaging. A number of imaging parameters have an effect on exposure (Brenner and colleagues, 2007). These include pitch, kilovoltage, tube current, collimation, number of slices, tube rotation, and total acquisition time. If a study is performed with and without contrast, the dose is doubled because twice as many images are obtained. Fetal exposure is also dependent on factors such as maternal size as well as fetal size and position. And as with plain radiography, the closer the target area is to the fetus, the greater the dosimetry.
Hurwitz and colleagues (2006) employed a 16-MDCT to calculate fetal exposure at 0 and 3 months' gestation using a phantom model (Table 41-6). Calculations were made for three commonly requested procedures in pregnant women. The pulmonary embolism protocol has the same dosimetry exposure as the ventilation-perfusion (V/Q) lung scan discussed below. Because of the pitch used, the appendicitis protocol has the highest radiation exposure, however, it is very useful clinically (Fig. 41-3). For imaging suspected urolithiasis, the MDCT scan protocol is used if sonography is nondiagnostic (Fig. 41-4). Using a similar protocol in 67 women with suspected appendicitis, Lazarus and co-workers (2007) reported sensitivity of 92 percent, specificity of 99 percent, and a negative-predictive value of 99 percent. Here dosimetry is markedly decreased compared with appendiceal imaging because of a different pitch. Using a similar protocol, White and co-workers (2007) identified urolithiasis in 13 of 20 women at an average of 26.5 weeks. Finally, abdominal tomography should be performed if indicated in the pregnant woman with severe trauma (American College of Obstetricians and Gynecologists, 1998).
Table 41-6. Estimated Radiation Dosimetry with 16-Channel Multidetector-Imaging Protocols |Favorite Table|Download (.pdf)
Table 41-6. Estimated Radiation Dosimetry with 16-Channel Multidetector-Imaging Protocols
3 Months' Gestation
CT-protocol for appendix shows an enlarged, enhancing—and thus inflamed appendix (arrow) next to the 25-week pregnancy. (Used with permission from Dr. Jeffrey H. Pruitt.)
CT-protocol imaging for urolithiasis disclosed a renal stone in the distal ureter (arrow) at its junction with the bladder. (Used with permission from Dr. Jeffrey H. Pruitt.)
Cranial CT scanning is the most commonly requested study in pregnant women. Its use in women with neurological disorders is discussed in Chapter 55 and with eclampsia in Chapter 34. Nonenhanced CT scanning is commonly used to detect acute hemorrhage within the epidural, subdural, or subarachnoid spaces.
Pelvimetry is used by some before attempting breech vaginal delivery (see Chap. 24, Pelvimetry). The fetal dose approaches 0.015 Gy or 1.5 rad, but use of a low-exposure technique may reduce this to 0.0025 Gy or 0.25 rad.
Most experience with chest CT scanning is with suspected pulmonary embolism. The most recent recommendations for its use in pregnancy from the Prospective Investigation of Pulmonary Embolism Diagnosis—PIOPED—II investigators were summarized by Stein and co-workers (2007). They found that pulmonary scintigraphy—the V/Q scan—was recommended for pregnant women by 70 percent of radiologists and chest CT angiography by 30 percent. But most agree that MDCT angiography has improved accuracy because of increasingly faster acquisition times. Others have reported a higher use-rate for CT angiography and emphasize that dosimetry is similar to that with V/Q scintigraphy (Brenner, 2007; Hurwitz, 2006; Matthews, 2006, and their many colleagues). At both Parkland Hospital and the University of Alabama Hospital at Birmingham, we use MDCT scanning initially for suspected pulmonary embolism (see Chap. 47, Computed Tomographic Pulmonary Angiography).
These studies are performed by “tagging” a radioactive element to a carrier that can be injected, inhaled, or swallowed. For example, the radioisotope technetium-99m may be tagged to red blood cells, sulfur colloid, or pertechnetate. The method used to tag the agent determines fetal radiation exposure. The amount of placental transfer is obviously important, but so is renal clearance because of fetal proximity to the maternal bladder. Measurement of radioactive technetium is based on its decay, and the units used are the curie (Ci) or the becquerel (Bq). Dosimetry is usually expressed in millicuries (mCi). As shown in Table 41-3, the effective tissue dose is expressed in sievert units (Sv). As discussed, to convert: 1 Sv = 100 rem = 100 rad.
Depending on the physical and biochemical properties of a radioisotope, an average fetal exposure can be calculated (Wagner and co-workers, 1997; Zanzonico, 2000). Commonly used radiopharmaceuticals and estimated absorbed fetal doses are given in Table 41-7. The radionuclide dose should be kept as low as possible (Adelstein, 1999). Exposures vary with gestational age and are greatest earlier in pregnancy for most radiopharmaceuticals. One exception is the later effect of 131iodine on the fetal thyroid (Wagner and associates, 1997). The International Commission on Radiological Protection (2001) has compiled dose coefficients for radionuclides. Stather and colleagues (2002) detailed the biokinetic and dosimetric models used by the Commission to estimate fetal radiation doses from maternal radionuclide exposure.
Table 41-7. Radiopharmaceuticals Used in Nuclear Medicine Studies |Favorite Table|Download (.pdf)
Table 41-7. Radiopharmaceuticals Used in Nuclear Medicine Studies
Estimated Activity Administered per Examination in Millicuries (mCi)
Dose to Uterus/Embryo per Pharmaceutical (mSv)b
20 mCi 99mTc DTPA
5 mCi 99mTc sulfur colloid
5 mCi 99mTc HIDA
20 mCi 99mTc phosphate
3 mCi 99mTc-macroaggregated albumin
10 mCi 133Xe gas
20 mCi 99mTc DTPA
Abscess or tumor
3 mCi 67Ga citrate
20 mCi 99mTc-labeled red blood cells
3 mCi 210Tl chloride
5 mCi 99mTcO4
0.3 mCi 123I (whole body)
0.1 mCi 131Id
5 mCi 99mTc sulfur colloid (1–3 mCi)
As discussed above, MDCT-angiography is being used preferentially for suspected pulmonary embolism during pregnancy. Until recently, the imaging modality was the ventilation-perfusion lungscan in this setting. It is used if CT angiography is nondiagnostic (see Chap. 47, Computed Tomographic Pulmonary Angiography). Perfusion is measured with injected 99Tc-macroaggregated albumin, and ventilation is measured with inhaled xenon-127 or xenon-133. Fetal exposure with either is negligible (Chan and colleagues, 2002; Mountford, 1997).
Thyroid scanning with iodine-123 or iodine-131 seldom is indicated in pregnancy. With trace doses used, however, fetal risk is minimal. Importantly, therapeutic radioiodine in doses to treat Graves disease or thyroid cancer may cause fetal thyroid ablation and cretinism.
The sentinel lymphoscintigram, which uses 99mTc-sulfur colloid to detect the axillary lymph node most likely to have metastases from breast cancer, is a commonly used preoperative study in nonpregnant women (Newman and Newman, 2007; Spanheimer and associates, 2009; Wang and co-workers, 2007). As shown in Table 41-7, the calculated dose is approximately 0.014 mSv or 1.4 mrad, which should not preclude its use during pregnancy.