Imaging modalities that are used as adjuncts for diagnosis and therapy during pregnancy include sonography, radiography, and magnetic resonance (MR) imaging. Of these, radiography is the most problematic. Inevitably, some radiographic procedures are performed before recognition of early pregnancy, usually because of trauma or serious illness. Fortunately, most diagnostic radiographic procedures are associated with minimal fetal risks. As with drugs and medications, however, these procedures may lead to litigation if there is an adverse pregnancy outcome. And x-ray exposure may lead to a needless therapeutic abortion because of patient or physician anxiety.
Beginning 2007, the American College of Radiology (ACR) has addressed the growing concern of radiation dose in all fields of medicine. Some of the goals were to limit exposure through radiation safety practices and promote lifelong accumulated records of exposures in any given patient (Amis, 2007). Task Force recommendations included additional considerations for special radiosensitive populations, such as children and pregnant and potentially pregnant women. The Task Force also suggested that the College should encourage radiologists to record all ionizing radiation times and exposures, compare them with benchmarks, and evaluate outliers as part of ongoing quality assurance programs. At the present time at Parkland Hospital, special recommendations are made for the pregnant woman. Radiation exposure values and duration are recorded in high-exposure areas such as computed tomography (CT) and fluoroscopy. Moreover, quality assurance mechanisms are in place to monitor these parameters.
An excellent review of ionizing radiation exposure during pregnancy was performed following the recent Fukushima nuclear plant disaster in Japan (Groen, 2012). This review reinforced considerations during pregnancy that are discussed subsequently.
The term radiation is poorly understood. Literally, it refers to energy transmission and thus 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 ionizing radiation forms. The other four energy forms have rather long wavelengths and low energy (Brent, 1999b, 2009).
The biological effects of x-rays are caused by an electrochemical reaction that can damage tissue. According to Brent (1999a, 2009), x- and gamma-radiation at high doses can create two types of biological effects and reproductive risks in the fetus:
Deterministic effects—these may cause congenital malformations, fetal-growth restriction, mental retardation, and abortion. Although controversial, this so-called NOAEL—No Observed Adverse Effect Level—suggests that there is a threshold dose (0.05 gray or 5 rad) below which there is no risk. It also suggests that the threshold for gross fetal malformations is more likely to be 0.2 gray (20 rad).
Stochastic effects—these are randomly determined probabilities, which may cause genetic diseases and carcinogenesis. In this case, cancer risk is increased, and hypothetically, at even very low doses.
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 46-4. 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 grays (Gy), and the relative effective dose is now expressed in sieverts (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 46-4Some Measures of Ionizing Radiation ||Download (.pdf) TABLE 46-4 Some Measures of Ionizing Radiation
|Exposure ||Number of ions produced by x-rays per kg of air |
| ||Unit: roentgen (R) |
|Dose ||Amount of energy deposited per kg of tissue |
| ||Modern unit: gray (Gy) (1 Gy = 100 rad) |
| ||Traditional unit: rad |
|Relative effective dose ||Amount of energy deposited per kg of tissue normalized for biological effectiveness |
| ||Modern unit: sievert (Sv) (1 Sv = 100 rem) |
| ||Traditional unit: rem |
When calculating the ionizing radiation dose, such as that from x-rays, several factors to be considered include: (1) type of study, (2) type and age of equipment, (3) distance of target organ from radiation source, (4) thickness of the body part penetrated, and (5) method or technique used for the study (Wagner, 1997).
Estimates of dose to the uterus and embryo for various frequently used radiographic examinations are summarized in Table 46-5. 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. The size of the woman, radiographic technique, and equipment performance are variable factors. Thus, data in the table serve only as guidelines. When the radiation dose for a specific individual is required, a medical physicist should be consulted. 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.
TABLE 46-5Dose to the Uterus for Common Radiological Procedures ||Download (.pdf) TABLE 46-5 Dose to the Uterus for Common Radiological Procedures
|Study ||View ||Dosea per View (mGy) ||No. Filmsb ||Dose (mGy) |
|Skullc ||AP, PA, Lat ||< 0.0001 ||4.1 ||< 0.0005 |
|Chest ||AP, PAc, Latd ||< 0.0001–0.0008 ||1.5 ||0.0002–0.0007 |
|Mammogramd ||CC, Lat ||< 0.0003–0.0005 ||4.0 ||0.0007–0.002 |
|Lumbosacral spinee ||AP, Lat ||1.14–2.2 ||3.4 ||1.76–3.6 |
|Abdomene ||AP || ||1.0 ||0.8–1.63 |
|Intravenous pyelograme ||3 views || ||5.5 ||6.9–14 |
|Hipb (single) ||AP ||0.7–1.4 || || |
| ||Lat ||0.18–0.51 ||2.0 ||1–2 |
Deterministic Effects of Ionizing Radiation
One potential harmful effect of radiation exposure is deterministic, which may result in abortion, growth restriction, congenital malformations, microcephaly, or mental retardation. These deterministic effects are threshold effects, and the level below which they are induced is the NOAEL (Brent, 2009).
The harmful deterministic effects of ionizing radiation have been extensively studied for cell damage with resultant embryogenesis dysfunction. These have been assessed in animal models, as well as in Japanese atomic bomb survivors and the Oxford Survey of Childhood Cancers (Sorahan, 1995). Additional sources have confirmed previous observations and provided more information (Groen, 2012). One is the 2003 International Commission on Radiological Protection publication, which describes biological fetal effects from prenatal irradiation. Another is the Biological Effects of Ionizing Radiation—BEIR VII Phase 2 report of the National Research Council (2006), which discusses health risks from exposure to low levels of ionizing radiation.
In the mouse model, the lethality risk 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. Acute low-dose ionizing radiation appears to have no deleterious effects (Howell, 2013). Studies of brain development suggest that there are effects on neuronal development and a window of cortical sensitivity in early and midfetal periods. During this, the threshold ranges from 0.1 to 0.3 Gy or 10 to 30 rad (International Commission on Radiological Protection, 2003).
Data on adverse human effects of high-dose ionizing radiation have most often been derived from atomic bomb survivors from Hiroshima and Nagasaki (Greskovich, 2000; Otake, 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. 46-2). There may be a lower-threshold dose of 0.3 Gy—30 rad—a range similar to 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 hypothesis. From their review, Strzelczyk and coworkers (2007) conclude that limitations of epidemiological studies at low-level exposures, along with new radiobiological findings, challenge the hypothesis that any amount of radiation causes adverse effects. In one such study describing fetuses exposed to low radiation doses, Choi and colleagues (2012) did not find an increased risk for congenital anomalies.
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, that is, 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, 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 reports that have described high-dose radiation used to treat women for malignancy, menorrhagia, and uterine myomas. 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, 1999b).
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 as 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 considered maximal 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.
Embryo-fetal 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. As emphasized by Groen and coworkers (2012), 0.1 Gy is the radiation equivalent to that from more than 1000 chest x-rays!
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 age 17 to 45 years. 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, 2008; Strzelczyk, 2007).
In an earlier report, the Radiation Therapy Committee Task Group of the American Association of Physics in Medicine found that approximately 4000 pregnant women annually undergo cancer therapy in the United States (Stovall, 1995). Their recommendations, however, stand to date. The Task Group emphasizes careful individualization of radiotherapy for the pregnant woman (Chap. 63, Radiation Therapy). For example, in some cases, shielding of the fetus and other safeguards can be employed (Fenig, 2001; Nuyttens, 2002). In other instances, the fetus will be exposed to dangerous radiation doses, and a carefully designed plan must be improvised (Prado, 2000). One example is the model to estimate the fetal dose with maternal brain radiotherapy, and another is the model to calculate the fetal dose with tangential breast irradiation (Mazonakis, 1999, 2003). The impact of radiotherapy on future fertility and pregnancy outcomes was reviewed by Wo and Viswanathan (2009) and others, and this is discussed in detail in Chapter 63 (Radiation Therapy).
To estimate fetal risk, approximate x-ray dosimetry must be known. According to the American College of Radiology no single diagnostic procedure results in a radiation dose significant enough to threaten embryo-fetal well-being (Hall, 1991).
Dosimetry for standard radiographs is presented in Table 46-5. In pregnancy, the AP-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 53 (Surveillance) 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. In some countries, x-ray pelvimetry is done for a breech presentation (Chap. 28, Pelvimetry).
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 46-6, the range is variable. The Food and Drug Administration limits the exposure rate for conventional fluoroscopy such as barium studies, however, special-purpose systems such as angiography units have the potential for much higher exposure.
TABLE 46-6Estimated X-Ray Doses to the Uterus/Embryo from Common Fluoroscopic Procedures ||Download (.pdf) TABLE 46-6 Estimated X-Ray Doses to the Uterus/Embryo from Common Fluoroscopic Procedures
|Procedure ||Dose to Uterus (mGy) ||Fluoroscopic Exposure in Seconds (SD) |
|Cerebral angiographya ||< 0.1 ||— |
|Cardiac angiographyb,c ||0.65 ||223 (± 118) |
|Single-vessel PTCAb,c ||0.60 ||1023 (± 952) |
|Double-vessel PTCAb,c ||0.90 ||1186 (± 593) |
|Upper gastrointestinal seriesd ||0.56 ||136 |
|Barium swallowb,e ||0.06 ||192 |
|Barium enemab,f,g ||20–40 ||289–311 |
Endoscopy is the preferred method of gastrointestinal tract evaluation in pregnancy (Chap. 54, General Considerations). Occasionally, an upper gastrointestinal series or barium enema may be performed before a pregnancy is recognized. Most would likely be done during preimplantation or early organogenesis.
Angiography and vascular embolization may occasionally be necessary for serious maternal disorders, especially renal disease, and for trauma (Wortman, 2013). As before, the greater the distance from the embryo or fetus, the less the exposure and risk.
This is usually 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, and MDCT protocols may result in increased dosimetry compared with traditional CT imaging. A number of imaging parameters have an effect on exposure (Brenner, 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 delivered dose.
Cranial CT scanning is the most commonly requested study in pregnant women. It is used in women with neurological disorders as discussed in Chapter 60 (Central Nervous System Imaging) and with eclampsia as noted in Chapter 40 (Neuroimaging Studies). Nonenhanced CT scanning is commonly used to detect acute hemorrhage within the epidural, subdural, or subarachnoid spaces. Because of the distance from the fetus, radiation dosage is negligible (Goldberg-Stein, 2012).
Abdominal procedures are more problematic. Hurwitz and associates (2006) employed a 16-MDCT to calculate fetal exposure at 0 and 3 months’ gestation using a phantom model (Table 46-7). 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. 46-3). Using a similar protocol in 67 women with suspected appendicitis, Lazarus and coworkers (2007) reported sensitivity of 92 percent, specificity of 99 percent, and a negative-predictive value of 99 percent. Here dosimetry was markedly decreased compared with standard appendiceal imaging because of a different pitch. For suspected urolithiasis, the MDCT-scan protocol shown in Figure 46-4 is used if sonography is nondiagnostic. Using a similar protocol, White and colleagues (2007) identified urolithiasis in 13 of 20 women at an average of 26.5 weeks. Finally, and as discussed in Chapter 47 (Management of Trauma), abdominal tomography should be performed if indicated in the pregnant woman with severe trauma.
TABLE 46-7Estimated Radiation Dosimetry with 16-Channel Multidetector Computed-Tomographic (MDCT) Imaging Protocols ||Download (.pdf) TABLE 46-7 Estimated Radiation Dosimetry with 16-Channel Multidetector Computed-Tomographic (MDCT) Imaging Protocols
| ||Dosimetry (mGy) |
|Protocol ||Preimplantation ||3 Months’ Gestation |
|Pulmonary embolism ||0.20–0.47 ||0.61–0.66 |
|Renal stone ||8–12 ||4–7 |
|Appendix ||15–17 ||20–40 |
Computed-tomographic protocol for appendix shows an enlarged, enhancing—and thus inflamed—appendix (arrow) next to the 25-week pregnancy. (Image contributed by Dr. Jeffrey H. Pruitt.)
Computed-tomographic protocol imaging for urolithiasis disclosed a renal stone in the distal ureter (arrow) at its junction with the bladder. (Image contributed by Dr. Jeffrey H. Pruitt.)
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 associates (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. And scintigraphy is still recommended by the American Thoracic Society in pregnant women with a normal chest x-ray (Leung, 2012). 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). At Parkland and UT Southwestern University Hospitals, we prefer MDCT scanning initially for suspected pulmonary embolism (Chap. 52, Diagnosis).
CT pelvimetry is used by some before attempting breech vaginal delivery (Chap. 28, 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.
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 46-4, the effective tissue dose is expressed in sievert units (Sv) with conversion as discussed: 1 Sv = 100 rem = 100 rad.
Depending on the physical and biochemical properties of a radioisotope, an average fetal exposure can be calculated (Wagner, 1997; Zanzonico, 2000). Commonly used radiopharmaceuticals and estimated absorbed fetal doses are given in Table 46-8. 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 iodine-131 on the fetal thyroid (Wagner, 1997). The International Commission on Radiological Protection (2001) has compiled dose coefficients for radionuclides. Stather and coworkers (2002) detailed the biokinetic and dosimetric models used by the Commission to estimate fetal radiation doses from maternal radionuclide exposure.
TABLE 46-8Radiopharmaceuticals Used in Nuclear Medicine Studies ||Download (.pdf) TABLE 46-8 Radiopharmaceuticals Used in Nuclear Medicine Studies
|Study ||Estimated Activity Administered per Examination (mCi)a ||Weeks’ Gestationb ||Dose to Uterus/Embryo (mSv)c |
|Brain ||20 mCi 99mTc DTPA ||< 12 ||8.8 |
| || ||12 ||7c |
|Hepatobiliary ||5 mCi 99mTc sulfur colloid ||12 ||0.45 |
| ||5 mCi 99mTc HIDA || ||1.5 |
|Bone ||20 mCi 99mTc phosphate ||< 12 ||4.6 |
|Pulmonary || || || |
| Perfusion ||3 mCi 99mTc-macroaggregated albumin ||Any ||0.45–0.57 (combined) |
| Ventilation ||10 mCi 133Xe gas || || |
|Renal ||20 mCi 99mTc DTPA ||< 12 ||8.8 |
|Abscess or tumor ||3 mCi 67Ga citrate ||< 12 ||7.5 |
|Cardiovascular ||20 mCi 99mTc-labeled red blood cells ||< 12 ||5 |
| ||3 mCi 210Tl chloride ||< 12 ||11 |
| || ||12 ||6.4 |
| || ||24 ||5.2 |
| || ||36 ||3 |
|Thyroid ||5 mCi 99mTcO4 ||< 8 ||2.4 |
| ||0.3 mCi 123I (whole body)d ||1.5–6 ||0.10 |
| ||0.1 mCi 131I || || |
| ||Whole body ||2–6 ||0.15 |
| ||Whole body ||7–9 ||0.88 |
| ||Whole body ||12–13 ||1.6 |
| ||Whole body ||20 ||3 |
| ||Thyroid-fetal ||11 ||720 |
| ||Thyroid-fetal ||12–13 ||1300 |
| ||Thyroid-fetal ||20 ||5900 |
|Sentinel lymphoscintigram ||5 mCi 99mTc sulfur colloid (1–3 mCi) || ||5 |
As discussed above, MDCT-angiography is being used preferentially for suspected pulmonary embolism during pregnancy. Until recently, the imaging modality was the ventilation-perfusion lung scan in this setting. It is used if CT angiography is nondiagnostic (Chap. 52, Ventilation–Perfusion Scintigraphy—Lung Scan). 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, 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, 2007; Spanheimer, 2009; Wang, 2007). As shown in Table 46-8, the calculated dose is approximately 0.014 mSv or 1.4 mrad, which should not preclude its use during pregnancy.