SURGICAL PROCEDURES DURING PREGNANCY
LAPAROSCOPIC SURGERY DURING PREGNANCY
MAGNETIC RESONANCE IMAGING
GUIDELINES FOR DIAGNOSTIC IMAGING DURING PREGNANCY
Never penalize a woman because she is pregnant. Pregnant women are susceptible to any of the medical and surgical disorders that can affect childbearing-aged women. Some of these, especially those that are chronic, more often precede pregnancy. But, they as well as others can acutely complicate an otherwise normal pregnancy. It is difficult to accurately quantify nonobstetrical disorders that complicate pregnancy, however, some estimates can be made. For example, one managed-care population had an overall antenatal hospitalization rate of 10.1 per 100 deliveries (Gazmararian, 2002). Of these, approximately a third were for nonobstetrical conditions that included renal, pulmonary, and infectious diseases. In another study from the 2002 Nationwide Inpatient Sample, the injury hospitalization rate was found to be 4.1 women per 1000 deliveries (Kuo, 2007). Approximately 1 in every 635 pregnant women will undergo a nonobstetrical surgical procedure (Corneille, 2010; Kizer, 2011).
Many of these nonobstetrical disorders are within the purview of the obstetrician. Some, however, will warrant consultation, and still others require a multidisciplinary team. The latter may include maternal-fetal medicine specialists, internists and medical subspecialists, surgeons, anesthesiologists, and numerous other disciplines (American College of Obstetricians and Gynecologists, 2013). In these latter situations, obstetricians should have a working knowledge of the wide range of medical disorders common to childbearing-aged women. At the same time, nonobstetricians who help care for these women and their unborn fetuses should be familiar with pregnancy-induced physiological changes and special fetal considerations. Many of these normal pregnancy perturbations have clinically significant effects on various diseases and cause seemingly aberrant changes in routine laboratory values.
It should be axiomatic that a woman should never be penalized because she is pregnant. To ensure this, a number of questions should be addressed:
• What management plan would be recommended if the woman was not pregnant?
• If the proposed management is different because the woman is pregnant, can this be justified?
• What are the risks versus benefits to the mother and her fetus, and are they counter to each other?
• Can an individualized management plan be devised that balances the benefits versus risks of any alterations?
Such an approach should allow individualization of care for women with most medical and surgical disorders complicating pregnancy. Moreover, it may be especially helpful for consideration by nonobstetrical consultants.
MATERNAL PHYSIOLOGY AND LABORATORY VALUES
Pregnancy induces physiological changes in virtually all organ systems. Some are profound and may amplify or obfuscate evaluation of coexisting conditions. Coincidentally, results of numerous laboratory tests are altered, and some values would, in the nonpregnant woman, be considered abnormal. Conversely, some may appear to be within a normal range but are decidedly abnormal for the pregnant woman. The wide range of pregnancy effects on normal physiology and laboratory values are discussed in the chapters that follow as well as throughout Chapter 4 and the Appendix.
MEDICATIONS DURING PREGNANCY
It is indeed fortunate that most medications necessary to treat the most frequently encountered illnesses complicating pregnancy can be given with relative safety. That said, there are notable exceptions, which are considered in Chapter 12.
SURGICAL PROCEDURES DURING PREGNANCY
The risk of an adverse pregnancy outcome is not appreciably increased in most women who undergo an uncomplicated surgical procedure. With complications, however, risks likely will be increased. For example, perforative appendicitis with feculent peritonitis has significant maternal and perinatal morbidity and mortality rates even if surgical and anesthetic techniques are flawless. Conversely, procedure-related complications may adversely affect outcomes. For example, a woman who has uncomplicated removal of an inflamed appendix may suffer aspiration of acidic gastric contents at the time of tracheal intubation or extubation. Still, compared with nonpregnant women undergoing similar procedures, pregnant women do not appear to have excessive complications (Silvestri, 2011).
Effect of Surgery and Anesthesia on Pregnancy Outcome
The most extensive data regarding anesthetic and surgical risks to pregnancy are from the Swedish Birth Registry as described by Mazze and Källén (1989). The effects on pregnancy outcomes of 5405 nonobstetrical surgical procedures performed in 720,000 pregnant women from 1973 to 1981 were analyzed. General anesthesia was used for approximately half of these procedures and commonly involved nitrous oxide supplemented by another inhalation agent or intravenous medications. These procedures were performed in 41 percent of women in the first trimester, 35 percent in the second, and 24 percent in the third. The distribution by the type of procedure is shown in Figure 46-1. Overall, 25 percent were abdominal operations and 20 percent were gynecological or urological procedures. Laparoscopy was the most frequently performed operation, and appendectomy was the most common second-trimester procedure.
FIGURE 46-1 Proportions of surgical procedures by trimester in 3615 women. (Data from Mazze, 1989.)
Excessive perinatal morbidity associated with nonobstetrical surgery is attributable in many cases to the disease itself rather than to adverse effects of surgery and anesthesia. The Swedish Birth Registry again provides valuable data as shown in Table 46-1 (Mazze, 1989). The incidence of neonates with congenital malformations or those stillborn was not significantly different from that of nonexposed control newborns. There were, however, significantly increased incidences of low birthweight, preterm birth, and neonatal death in infants born to women who had undergone surgery. Increased neonatal deaths were largely due to preterm birth. These investigators concluded that these adverse outcomes likely were due to a synergistic effect of the illness in concert with the surgical procedures. In another study, there was an increased preterm delivery rate in 235 women undergoing adnexal mass surgery (Hong, 2006).
TABLE 46-1. Birth Outcomes in 5405 Pregnant Women Undergoing Nonobstetrical Surgery
In a follow-up study of the Swedish database, Källén and Mazze (1990) scrutinized 572 operations performed at 4 to 5 weeks’ gestation and reported a nonsignificant relationship with increased neural-tube defect rates. In a similar study from a Hungarian database, Czeizel and colleagues (1998) found no evidence that anesthetic agents were teratogenic. In a review, Kuczkowski (2006) concluded that there is no robust evidence that anesthetic agents are harmful to the fetus.
LAPAROSCOPIC SURGERY DURING PREGNANCY
Laparoscopy has become the most common first-trimester procedure used for diagnosis and management of several surgical disorders (Kuczkowski, 2007). In addition to management of ectopic pregnancy (Chap. 19, p. 385), it is used preferentially during most of pregnancy for exploration and treatment of adnexal masses (Chap. 63, p. 1226), for appendectomy (Chap. 54, p. 1079), and for cholecystectomy (Chap. 55, p. 1096). In 2011, the Guidelines Committee of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) updated its recommendations concerning laparoscopy use in pregnant women. Some of these guidelines are listed in Table 46-2.
TABLE 46-2. Some Guidelines for the Performance of Laparoscopic Surgery in Pregnancy
Indications—same as for nonpregnant women
Adnexal mass excision
Investigation of acute abdominal processes
Appendectomy, cholecystectomy, nephrectomy, adrenalectomy, splenectomy
Position: left lateral recumbent
Entry: open technique, careful Veress needle, or optical trocar; fundal height may alter insertion site selection
Trocars: direct visualization for placement; fundal height may alter insertion site selection
CO2 insufflation pressures: 10–15 mm Hg
Monitoring: capnography intraoperatively, FHR assessment pre- and postoperatively
Perioperative pneumatic compression devices and early postoperative ambulation
CO2 = carbon dioxide; FHR = fetal heart rate.
Summarized from Pearl, 2011.
Information regarding surgical approach selection in pregnant women comes from the American College of Surgeons database (Silvestri, 2011). During the 5-year period ending in 2009, almost 1300 pregnant women who had undergone either appendectomy or cholecystectomy were studied. Open appendectomy was performed in 36 percent of 857 pregnant women compared with only 17 percent of those not pregnant. Of those undergoing cholecystectomy, an open procedure was used in 10 percent of 436 pregnant women compared with 5 percent of nonpregnant women.
There are no randomized trials comparing laparoscopic with open surgery, however, most reviews report equally satisfactory outcomes (Bunyavejchevin, 2013; Fatum, 2001; Lachman, 1999). The most frequently performed procedures were cholecystectomy, adnexal surgery, and appendectomy. Laparoscopic adnexal mass surgery in pregnancy is preferred, and its relative safety is attested to by several investigators (Biscette, 2011; Hoover, 2011; Koo, 2011, 2012). At first, 26 to 28 weeks became the upper gestational-age limit recommended, but as experience has continued to accrue, many now describe laparoscopic surgery performed in the third trimester (Donkervoort, 2011; Kizer, 2011). In one report of 59 pregnant women undergoing laparoscopic cholecystectomy or appendectomy, a third were > 26 weeks pregnant (Rollins, 2004). There were no serious adverse sequelae to these procedures. There are now reports of laparoscopic splenectomy, adrenalectomy, and nephrectomy done in pregnant women (Aubrey-Bassier, 2012; Gernsheimer, 2007; Kosaka, 2006; Miller, 2012; Stroup, 2007).
Abdominal insufflation for laparoscopy causes hemodynamic changes that are similar in pregnant and nonpregnant women, and these are summarized in Table 46-3. Reedy and associates (1995) studied baboons at the human equivalent of 22 to 26 weeks’ gestation. There were no substantive physiological changes with 10 mm Hg insufflation pressures, but 20 mm Hg caused significant maternal cardiovascular and respiratory changes after 20 minutes. These included increased respiratory rate, respiratory acidosis, diminished cardiac output, and increased pulmonary artery and capillary wedge pressures.
TABLE 46-3. Physiological Effects of CO2 Insufflation of the Peritoneal Cavity
In women, cardiorespiratory changes are generally not severe if insufflation pressures are kept below 20 mm Hg. With noninvasive hemodynamic monitoring in women at midpregnancy, the cardiac index decreased 26 percent by 5 minutes of insufflation and 21 percent by 15 minutes (Steinbrook, 2001). Despite this, mean arterial pressures, systemic vascular resistance, and heart rate did not change significantly.
Because precise effects of laparoscopy in the human fetus are unknown, animal studies are informative. In early studies of pregnant ewes, various investigators reported that uteroplacental blood flow decreased when intraperitoneal insufflation pressure exceeded 15 mm Hg (Barnard, 1995; Hunter, 1995). This was the result of decreased perfusion pressure and increased placental vessel resistance (see Table 46-3). The previously cited baboon studies by Reedy and coworkers (1995) produced similar findings. Since then, other studies in sheep have corroborated these observations (O’Rourke, 2006; Reynolds, 2003).
Pregnancy outcomes in women are limited to observations. Reedy and colleagues (1997) used the updated Swedish Birth Registry database to analyze a 20-year period and more than 2 million deliveries. There were 2181 laparoscopic procedures, most of which were performed during the first trimester. Perinatal outcomes for these women were compared with those of all women in the database as well as those undergoing open surgical procedures. These investigators confirmed the earlier findings of an increased risk of low birthweight, preterm delivery, and fetal-growth restriction in pregnancies of women in both operative groups compared with controls. There were no differences, however, when outcomes of women undergoing laparoscopy versus laparotomy were compared. Similar findings were reported from an observational study of 262 women undergoing surgery for an adnexal mass (Koo, 2012).
Preparation for laparoscopy differs little from that used for laparotomy. Bowel cleansing empties the large intestine and may aid visualization. Nasogastric or orogastric decompression reduces the risk of stomach trocar puncture and aspiration. Aortocaval compression is avoided by a left-lateral tilt. Positioning of the lower extremities in boot-type stirrups maintains access to the vagina for fetal sonographic assessment or manual uterine displacement. Vaginally placed instruments that enter the cervix or uterus for uterine manipulation should not be used during pregnancy.
Most reports describe the use of general anesthesia after tracheal intubation with monitoring of end-tidal carbon dioxide—EtCO2 (Hong, 2006; Ribic-Pucelj, 2007). With controlled ventilation, EtCO2 is maintained at 30 to 35 mm Hg.
Beyond the first trimester, technical modifications of standard pelvic laparoscopic entry are required to avoid uterine puncture or laceration. Many recommend open entry techniques to avoid perforations of the uterus, pelvic vessels, and adnexa (Kizer, 2011; Koo, 2012). The abdomen is incised at or above the umbilicus, and the peritoneal cavity entered under direct visualization. At this point, the cannula is then connected to the insufflation system, and a 12-mm Hg pneumoperitoneum is created. The initial insufflation should be conducted slowly to allow for prompt assessment and reversal of any untoward pressure-related effects. Gas leakage around the cannula is managed by tightening the surrounding skin with a towel clamp. Insertion of secondary trocars into the abdomen is most safely performed under direct laparoscopic visual observation through the primary port. Single-port surgery has also been described (Dursun, 2013).
In more advanced pregnancies, direct entry through a left upper quadrant port in the midclavicular line, 2 cm beneath the costal margin, has been described (Donkervoort, 2011; Stepp, 2004). Known as Palmer point, this entry site is used in gynecological laparoscopy because visceroparietal adhesions uncommonly form here (Vilos, 2007).
This is a less commonly used alternative approach that uses a rod with intraabdominal fan-blade-shaped retractors. When opened, these allow the abdominal wall to be lifted upward. It avoids the typical laparoscopic cardiovascular changes because the pneumoperitoneum is created by retraction rather than insufflation (Phupong, 2007).
Risks inherent to any abdominal endoscopy are possibly increased slightly during pregnancy. The obvious unique complication is perforation of the pregnant uterus with either a trocar or Veress needle (Azevedo, 2009; Kizer, 2011). That said, reported complications are infrequent (Fatum, 2001; Joumblat, 2012; Koo, 2012). After a Cochrane database review, it was determined that randomized trials would be necessary to deduce comparative benefits and risks of laparoscopy versus laparotomy during pregnancy (Bunyavejchevin, 2013). Pragmatically, this seems unfeasible, and common sense should dictate the approach used.
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:
1. 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).
2. 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 46-4. Some Measures of Ionizing Radiation
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 46-5. Dose to the Uterus for Common Radiological Procedures
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.
FIGURE 46-2 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, p. 1220). 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 (p. 1220).
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 (p. 1056) 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, p. 562).
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 46-6. Estimated X-Ray Doses to the Uterus/Embryo from Common Fluoroscopic Procedures
Endoscopy is the preferred method of gastrointestinal tract evaluation in pregnancy (Chap. 54, p. 1069). 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 (p. 1187) and with eclampsia as noted in Chapter 40(p. 744). 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 (p. 954), abdominal tomography should be performed if indicated in the pregnant woman with severe trauma.
TABLE 46-7. Estimated Radiation Dosimetry with 16-Channel Multidetector Computed-Tomographic (MDCT) Imaging Protocols
FIGURE 46-3 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.)
FIGURE 46-4 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, p. 1042).
CT pelvimetry is used by some before attempting breech vaginal delivery (Chap. 28, p. 562). 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.
Nuclear Medicine Studies
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 46-8. Radiopharmaceuticals Used in Nuclear Medicine Studies
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, p. 1043). 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.
Of all of the major advances in obstetrics, the development of sonography for study of the fetus and mother certainly is one of the greater achievements. The technique has become virtually indispensable in everyday practice. The wide range of clinical uses of sonography in pregnancy is further discussed in Chapter 10 and in most other sections of this book.
MAGNETIC RESONANCE IMAGING
Magnetic resonance technology does not use ionizing radiation, and its application is cited throughout this book. Advantages include high soft-tissue contrast, ability to characterize tissue, and acquisition of images in any plane—particularly axial, sagittal, and coronal. An entire section in Chapter 10 (p. 222) is devoted to mechanisms that generate MR images.
The most recent update of the Blue Ribbon Panel on MR safety of the American College of Radiology was summarized by Kanal and colleagues (2007). The panel concluded that there are no reported harmful human effects from MR imaging. Chew and associates (2001) found no differences in blastocyst formation exposure of early murine embryos to MR imaging with 1.5 T strength. Vadeyar and coworkers (2000) noted no demonstrable fetal heart rate pattern changes during MR imaging in women. Chung (2002) has reviewed these safety issues.
Contraindications to MR imaging include internal cardiac pacemakers, neurostimulators, implanted defibrillators and infusion pumps, cochlear implants, shrapnel or other metal in biologically sensitive areas, some intracranial aneurysm clips, and any metallic foreign body in the eye. Of more than 51,000 nonpregnant patients scheduled for MR imaging, Dewey and colleagues (2007) found that only 0.4 percent had an absolute contraindication to the procedure.
Several elemental gadolinium chelates are used to create paramagnetic contrast. Some are gadopentetate, gadodiamide, gadoteridol, and gadoterate. These cross the placenta and are found in amnionic fluid. In doses approximately 10 times the human dose, gadopentetate caused slight developmental delay in rabbit fetuses. There is little experience with gadolinium in humans (Wang, 2012). In one study, De Santis and associates (2007) described 26 women given a gadolinium derivative in the first trimester without adverse fetal effects. Currently, according to Briggs and coworkers (2011), as well as the Panel, these contrast agents are not recommended unless there are overwhelming benefits.
In some cases, MR imaging may be complementary to CT, and in others, MR imaging is preferable. Maternal central nervous system abnormalities, such as brain tumors or spinal trauma, are more clearly seen with MR imaging. As discussed in Chapter 40 (p. 743), MR imaging has provided valuable insights into the pathophysiology of eclampsia and to calculate cerebrovascular blood flow in preeclampsia (Twickler, 2007; Zeeman, 2003, 2004a,b, 2009). It is invaluable in the diagnosis of neurological emergencies (Edlow, 2013). MR imaging is a superb technique to evaluate the maternal abdomen and retroperitoneal space. It is chosen by many to determine the degree and extent of placenta accreta and its variants in women who have had a prior cesarean delivery (Chap. 41, p. 806). It has been employed for detection and localization of adrenal tumors, renal lesions, gastrointestinal lesions, and pelvic masses in pregnancy. It has particular value in evaluating neoplasms of the chest, abdomen, and pelvis in pregnancy (Boyd, 2012; Oto, 2007; Tica, 2013). MR urography has been used successfully for renal urolithiasis (Mullins, 2012). MR imaging may be selected to confirm pelvic and vena caval thrombosis—a common source of pulmonary embolism in pregnant women (Fig. 46-5). As discussed in Chapter 37 (p. 688), CT and MR imaging is useful for evaluation of puerperal infections, but MR imaging provides better visualization of the bladder flap area following cesarean delivery (Brown, 1999; Twickler, 1997). MR imaging now includes evaluation of right lower quadrant pain in pregnancy, specifically appendicitis (Baron, 2012; Dewhurst, 2013; Pedrosa, 2007, 2009). Investigators have also found other disorders of the gastrointestinal tract to be easily diagnosed with MR imaging (Chap. 54, p. 1069).
FIGURE 46-5 Magnetic-resonance images of a pelvic vein thrombosis in a 15-week pregnant woman who presented with left leg pain but no symptoms of a pulmonary embolus. A. Reconstructed magnetic resonance venogram demonstrates partial chronic occlusion of the left common iliac vein (large arrow) and thrombosis and complete occlusion of the left internal iliac vein (small arrows). B. From the axial images, there is normal flow in the right (arrow) and no flow in the left internal iliac vein (curved arrow). (Image contributed by Dr. R. Douglas Sims.)
Fetal MR imaging provides a complement to sonography (De Wilde, 2005; Laifer-Narin, 2007; Sandrasegaran, 2006). According to Zaretsky and colleagues (2003a), MR imaging can be used to image almost all elements of the standard fetal anatomical survey. The most frequent fetal indications for MR imaging are evaluation of complex abnormalities of the brain, chest, and genitourinary system. Bauer (2009), Reichel (2003), Twickler (2002), Weisz (2009), and their associates have validated its use for fetal central nervous system anomalies and biometry (Fig. 46-6). Caire and coworkers (2003) reported its merits for fetal genitourinary anomalies. Hawkins and colleagues (2008) described MR imaging in 21 fetuses with renal anomalies and oligohydramnios. Zaretsky and associates (2003b) noted that fetal-weight estimation was more accurate using MR imaging than with sonography. Fast-acquisition sequencing has solved problems with fetal movement to improve imaging. The technique is termed HASTE—Half-Fourier Acquisition Single slow Turbo spin Echo, or SSFSE—Single Shot Fast Spin Echo. A more extensive discussion of fetal indications and findings of MR imaging are discussed in Chapter 10 and throughout this book.
FIGURE 46-6 Magnetic-resonance images of the brain of a 35-week fetus. A. Axial images show the normal frontal horns, cavum septum pellucidum, and cerebellum. B. Sagittal images demonstrate the normal corpus callosum, brainstem, and vermis.
GUIDELINES FOR DIAGNOSTIC IMAGING DURING PREGNANCY
The American College of Obstetricians and Gynecologists (2009) has reviewed the effects of radiographic, sonographic, and magnetic-resonance exposure during pregnancy. Its suggested guidelines are shown in Table 46-9.
TABLE 46-9. Guidelines for Diagnostic Imaging During Pregnancy
1. Women should be counseled that x-ray exposure from a single diagnostic procedure does not result in harmful fetal effects. Specifically, exposure to less than 5 rads has not been associated with an increase in fetal anomalies or pregnancy loss.
2. Concern about possible effects of high-dose ionizing radiation exposure should not prevent medically indicated diagnostic x-ray procedures from being performed on a pregnant woman. During pregnancy, other imaging procedures not associated with ionizing radiation, e.g., ultrasonography, and MRI, should be considered instead of x-rays when appropriate.
3. Ultrasonography and MRI are not associated with known adverse fetal effects.
4. Consultation with an expert in dosimetry calculation may be helpful in calculating estimated fetal dose when multiple diagnostic x-rays are performed on a pregnant patient.
5. The use of radioactive isotopes of iodine is contraindicated for therapeutic use during pregnancy.
6. Radiopaque and paramagnetic contrast agents are unlikely to cause harm and may be of diagnostic benefit, but these agents should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Summarized from the American College of Obstetricians and Gynecologists, 2009.
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