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• W4300981898 abstract "INTRODUCTION Advanced endoscopic procedures that might be required during pregnancy include diagnostic and therapeutic endoscopic ultrasound (EUS), endoscopic retrograde cholangiopancreatography (ERCP), enteroscopy, endoscopic resection, ablation, and enteral stenting. In general, elective advanced endoscopy procedures, especially diagnostic studies, should be avoided throughout pregnancy and indications should be limited to urgent or emergent therapeutic procedures, as discussed in this section. Nonendoscopic diagnostic modalities should be sought out such as imaging tests, including ultrasound (US) or magnetic resonance imaging (MRI), and laboratory testing. ERCP AND EUS IN PREGNANCY Introduction EUS and ERCP are effective diagnostic and therapeutic tools for management of symptomatic choledocholithiasis. The incidence of gallstones in the adult US population is 20%, with gallstones and sludge reported in up to 12% and 30% of pregnant patients, respectively (1,2). The frequency of symptomatic choledocholithiasis requiring therapeutic intervention is rare and is estimated to occur in 1 in 1,200 deliveries (3). However, symptomatic choledocholithiasis may lead to complications such as cholangitis and pancreatitis with potentially increased fetal and maternal morbidity and mortality. ERCP is now considered a safe and effective intervention during pregnancy when performed by an experienced endoscopist for the proper indication and with the support of a multidisciplinary team. Pathophysiology Pregnant patients, in general, are twice more likely to develop choledocholithiasis than men. Sex-dependent increased lithogenicity is attributed to the female sex hormones (3). Thus, pregnancy, a high estrogen and progesterone state, is a major risk factor for biliary stone formation. The risk increases with the number of pregnancies and is 10 times higher in multiparous patients compared with nulliparous (4). Pregnancy-related lithogenicity related to estrogen increases cholesterol production and decreases gall bladder motility resulting in supersaturation of bile from cholesterol. Progesterone leads to decreased bile acid secretion and delayed gall bladder emptying resulting in increased gall bladder volume. These changes are compounded by increased secretion of chenodeoxycholate (hydrophobic bile acid), which decreases the solubility of cholesterol (1,5). ERCP and EUS in pregnancy: indications and timing It is imperative that the ERCP is performed for strong indications, such as choledocholithiasis, cholangitis, biliary pancreatitis (with documented stone and biliary obstruction), and bile or pancreatic duct trauma. ERCP requires the support of a multidisciplinary team, including an obstetrician/perinatologist and obstetrical anesthesiologist, and follows best practices for radiation safety. Alternative diagnostic imaging modalities, as described later in the chapter, should be used to confirm the indication before performing ERCP because of higher fetal and maternal morbidity and mortality from ERCP-related adverse events of pancreatitis, bleeding, infection, and perforation (6). Other major risks related to ERCP in pregnant patients include fetal radiation exposure, teratogenicity of intraprocedural medications, electrocautery risk to fetus, and technical challenges encountered during the procedure because of alteration in maternal anatomy from the gravid uterus. ERCP has been safely performed throughout gestation, but the optimal time is during the second trimester. ERCP during the first trimester should be avoided because of fetal radiation exposure during organogenesis and the risk of spontaneous abortion, preterm birth, and low birth weight (7–9). If the pancreatobiliary event necessitating ERCP occurs in the third trimester, then the timing of the procedure should depend on the acuity of the indication requiring urgent ERCP versus early delivery followed by ERCP in the postpartum period. Although the evidence pertaining to the best timing for ERCP is scarce, it should not be deferred in the setting of symptomatic choledocholithiasis, biliary pancreatitis, and cholangitis due to high risk of recurrent symptoms, hospitalizations, emergency department visits, and need for cesarean delivery (10,11). Radiation exposure during ERCP Radiation may have both stochastic effects and deterministic effects. Deterministic effects on organogenesis have a threshold of approximately 100 mGy and are at greatest risk of occurring between the 2nd and 15th weeks of gestation (12). According to the American College of Obstetricians and Gynecologists, “exposure to less than 5 rad [50 mGy] has not been associated with an increase in fetal anomalies, growth restriction or abortion” (13). The risk of developing cancer from radiation, although small, is a stochastic effect and is dose-independent without the threshold level (14). Multiple studies have estimated levels of radiation exposure to the fetus and have reported an average exposure between 0.01 and 5.77 mGy (15,16). The International Commission on Radiological Protection recommends monitoring fetal radiation exposure if the dose is expected to exceed 0.01 Gy (17). Although most pregnant patients are likely exposed to much lower levels, these data highlight the importance of minimizing radiation exposure in pregnancy. Fetal radiation exposure depends on several factors including gestational age, maternal size, body composition including fat and volume of amniotic fluid, maternal and fetal position, exposure techniques, and endoscopist experience (18,19). Draping the lower abdomen and pelvis reduces the exposure to the uterus, although most of the radiation exposure to the fetus comes from radiation scattered by the pregnant patient. Therefore, ancillary strategies (Table 1) to mitigate the risk of radiation exposure further should be implemented.Table 1.: Techniques to reduce radiation exposurePATIENT POSITIONING AND ELECTROCAUTERY In the first trimester, the patient can be placed in the prone position. However, in the second and third trimester, the patient should be placed in a left lateral position. The supine position should be avoided in the third trimester because of the risk of supine hypotension syndrome due to the compression of inferior vena cava and aorta from the gravid uterus (20). Bipolar cautery should be used for sphincterotomy. The grounding pad should be placed higher up on the right upper thorax or arm to prevent the conduction of electrical current through the amniotic fluid during sphincterotomy. ERCP outcomes and complications There are acceptable data on the short-term, perinatal maternal fetal outcomes (9,21–23) (Table 2). However, data on the long-term outcomes in children born after ERCP during gestation are sparse (24–26). Three published studies on long-term outcomes reported no malignancies or developmental delays (Table 3). Most of the ERCP’s were performed in the second or third trimester, and the fetal radiation exposure was estimated to be less than the threshold of 10 mGy. However, some of the ERCP's were without radiation, and the authors in 2 of 3 (22,23) studies did not specify the contact and assessment of exposure.Table 2.: ERCP short-term outcomes and complicationsTable 3.: ERCP long-term outcomesThe technical success of ERCP, risk of bleeding, infection, and perforation in pregnant patients is similar to that seen in the nonpregnant population. However, pregnancy is reported to be an independent risk factor for post-ERCP pancreatitis. A retrospective cohort study of a National Inpatient Sample of 907 pregnant and 2,721 nonpregnant patients revealed that post-ERCP pancreatitis occurred in 12% of the pregnant and 5% of the nonpregnant patients. Pregnancy was an independent risk factor with an odds ratio of 2.8 (confidence interval [CI] 2.1–3.8) (27). A similar result was found in another study, which showed that 16% of pregnant patients developed post-ERCP pancreatitis (9). Apart from the possibility of physiologic predisposition in pregnancy, several other potential mechanisms have been proposed for this higher risk: lesser frequency of placement of prophylactic pancreatic stent, nonradiation (or reduced fluoroscopy?) ERCP leading to cannulation difficulty, inability to use high-volume periprocedural resuscitation measures, and inability to use NSAIDs for prophylaxis due to the teratogenic effects. EUS and nonradiation ERCP techniques EUS is a safe and effective diagnostic test in pregnant patients with suspected choledocholithiasis. It can obviate the need for ERCP in a significant number of patients (44%–75%) (28). The same session EUS and ERCP also allow for the assessment of number of stones and confirmation of accurate biliary stent placement in a nonradiation (nonfluoroscopy?) ERCP. Apart from EUS, several other tools and techniques have been described for the performance of nonradiation ERCP. Among these, Uomo et al. (29) first described the “bile aspiration” technique in 1994. In this technique, after wire-guided cannulation, a catheter is advanced over the wire into the duct and aspiration of bile through the catheter is used to confirm selective cannulation. A variation of this technique includes visualization of bile emanating from the orifice on movement of the wire. The challenges with these techniques include inability to exclude cystic duct cannulation with wire and confirmation of ductal clearance. Therefore, some have described the safe use of cholangioscopy for the confirmation of selective ductal cannulation and clearance (23). OTHER ADVANCED ENDOSCOPIC PROCEDURES DURING PREGNANCY There are no data regarding risks during pregnancy when performing other advanced endoscopic procedures such as resection, enteral stenting, or ablation. Although there are similar risks that occur in nonpregnant individuals such as bleeding, infection, and perforation, these procedures should only be performed when deemed urgent or emergent and considered life-saving for the pregnant patient to not incur unknown harm with the consequences of the complications or their management. Cautions with fluoroscopy and cautery should be taken, as outlined in the previous section on ERCP in pregnancy. ABDOMINAL IMAGING IN PREGNANCY Before any endoscopic procedures, particularly those in which high-risk procedures such as ERCP, strong indications should be established. Diagnosis should be based on clinical history, laboratory studies, and imaging. However, careful consideration needs to be given when considering which imaging modalities are most optimal in pregnancy. Abdominal US in pregnancy US is not associated with ionizing radiation and does not require contrast injection. It is therefore the preferred primary abdominal imaging modality in pregnancy. No adverse fetal events have been reported with the use of US in pregnancy (30,31). Concerns have been raised regarding thermal effects of US, resulting from the transformation of acoustic energy to heat, on fetal tissues. The ALARA principle (i.e., as low as reasonably achievable) should therefore also apply to US imaging. Particular concern has been directed at the use of Doppler imaging, where higher US energy is applied over focal areas, leading to societal recommendations to avoid the use of pulsed Doppler in the first trimester (32). However, again, no adverse fetal events have been reported with the use of Doppler imaging in pregnancy (30). MRI IN PREGNANCY Given the significant concerns regarding the effect of ionizing radiation on the developing fetus, imaging modalities such as US and MRI are used more frequently. MRI utilization in pregnant people is increasing in the United States, with a retrospective cohort study indicating an increase in use from 1 of 1,000 pregnancies in 1996 to 11.9 of 1,000 pregnancies in 2016 (33). Concerns regarding MRI use include its potential for heating of sensitive fetal tissues, impact on hearing from fetal exposure to loud MRI acoustics, and adverse effects associated with the use of gadolinium-based contrast agents. Few data have previously been available on the impact of first trimester MRI scans. However, a large retrospective longitudinal Canadian study using healthcare databases found that MRI use in the first trimester seemed safe, with no increase noted in stillbirths, congenital anomalies, neoplasms, vision loss, or hearing loss over the median 3.6-year follow-up (34). On subgroup analysis of those exposed to MRI between 5 and 10 weeks of gestation, the study noted a higher risk of vision loss (adjusted hazards ratio 2.28, 95% CI, 1.09–4.77) (34). There remains a dearth of data on fetal risk with newer 3 T MRI systems that use higher field strengths, compared with older 1.5 T systems. However, the joint American College of Radiology and Society for Pediatric Radiology 2020 practice parameter states that currently available data do not conclusively indicate adverse effects of MRI in pregnancy at 1.5 T and at 3 T, no special consideration is recommended for any pregnancy trimester, and MRI scans may be performed assuming the risk-benefit ratio supports the study (35). By contrast, the Canadian Association of Radiologists recommend that 1.5 T is preferred, if both field strengths are available (36). Animal studies indicate that gadolinium-based contrast agents (GBCD) can cross the placental barrier and are detectable in amniotic fluid and fetal tissues. The large Canadian study found a higher rate of neonatal death after fetal exposure to GBCD (adjusted RR of 3.70, 95% CI, 1.55–8.85) (34). An increased risk was also noted for a broad outcome of any rheumatological, inflammatory, or infiltrative skin conditions after MRI with GBCD (adjusted hazard ratio of 1.36, 95% CI, 1.09–1.69) (34). The joint American College of Radiology and Society for Pediatric Radiology 2020 practice parameter cautions that MRI contrast agents should not be routinely administered; a decision should be made on a case-by-case basis based on the risk-benefit ratio (35). Computed tomography scans in pregnancy Utilization of computed tomography (CT) scans has increased exponentially in the general population over the course of the last decade. Not surprisingly, this has been mirrored by a similar increase in utilization of CT scans in pregnant patients (37). A retrospective cohort study found that CT imaging rates in the United States increased from 2 of 1,000 pregnancies in 1996 to 11.4 of 1,000 pregnancies in 2007 (33). This trend has mitigated in recent years with a drop to 9.3 of 1,000 pregnancies by 2016 (33). Common indications for abdominal CT in the pregnant population in the past studies have included suspected appendicitis for assessment after trauma and for assessment of nonspecific abdominal pain (37). Ionizing radiation is associated with deterministic effects to the fetus which are dose-dependent. There is no recognized dose threshold for the stochastic effects of ionizing radiation. Exposure of the embryo during the preimplantation stage to radiation doses exceeding 0.15 Gy may increase the risk of embryonic loss (38). After implantation, embryonic or fetal exposure to ionizing radiation at doses of <0.1 Gy has not been shown to increase the risk of deterministic effects such as congenital malformations, decreased IQ or mental disability, growth restriction, microcephaly, and stillbirth (38). Exposure to ionizing radiation in utero at doses greater than 0.5 Gy may increase the risk of cancer subsequently (38). Overall, most diagnostic CT scans performed during pregnancy do not reach these thresholds. A retrospective study estimating fetal radiation dose after abdominopelvic CT examinations over the years 1998–2005 found a mean fetal dose of 24.8 mGy (range 6.7–56 mGy) (37). Only a single examination exceeded 50 mGy (37). Low-dose CT protocols allow further reduction of fetal doses. A recent study combining dose measurements in an anthropomorphic phantom together with Monte Carlo simulations estimated the mean intrauterine doses of radiation across different stages of pregnancy. The mean intrauterine-simulated doses using low-dose abdominal pelvic CT scan protocols ranged from 4.8 to 5.8 mGy across different stages of pregnancy (39). Relatively higher doses of up to 12.6 mGy were noted with the trauma CT scan protocol. Given the low intrauterine doses achievable today, CT imaging may be performed if felt to be strongly clinically indicated and necessary. CT imaging may offer advantages, for example, in situations of life-threatening significant trauma due to its rapidity. Nevertheless, alternative modalities of imaging including abdominal US or MRI imaging should be considered and used where possible in the setting of pregnancy. When undertaken, diagnostic imaging procedures using ionizing radiation such as CT should be planned, so as to deliver the minimum possible radiation dose to the fetus, eg. using low-dose CT protocols, performing only a single series, and where possible, limiting imaging to the area of interest to avoid unnecessary fetal exposure (40). Consent should be obtained from the patient after a discussion of risks, benefits, and alternatives.BEST PRACTICE RECOMMENDATIONS ✓ Elective diagnostic and therapeutic advanced procedures should be avoided during pregnancy. ✓ Nonionizing radiation imaging, such as US, should be optimized during pregnancy. ✓ MRI can safely be performed during pregnancy and may be critical in helping to avoid additional invasive therapeutic procedures. Noncontrast studies are preferred. ✓ Despite low intrauterine doses, the CT scan can be used in pregnancy if deemed necessary. ✓ Indication for performing ERCP in pregnancy should be limited to urgent and emergent disease states, such as symptomatic choledocholithiasis, cholangitis, and biliary pancreatitis. ✓ A multidisciplinary team, including perinatologist, radiation safety officer (person responsible for implementing the radiation protection program), obstetrical anesthesiologist, and experienced endoscopist, should be included when reviewing indications and endoscopic treatments. ✓ The optimal time for advanced endoscopic procedures is during the second trimester; however, if consequences of a delayed procedure can cause harm to the patient or the fetus, then one should proceed with the use of a multidisciplinary team. ✓ Pregnant patients undergoing ERCP during their second or third trimester should be positioned in a left lateral position, and electrocautery grounding pads should be placed away from the fetus. ✓ If expertise is available, nonfluoroscopic ERCP techniques, such as cholangioscopy, should be considered to minimize fluoroscopy exposure. ✓ EUS can safely be used as a diagnostic tool to help determine whether further advanced endoscopic procedures are required or can be avoided." @default.
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