Disease
Pregnancy trimester
Laboratory abnormalities
Hyperemesis gravidarum
First
Elevated AST, ALT
Intrahepatic cholestasis of pregnancy
Second and third trimester and postpartum
Elevated serum bile acids Elevated AST, ALT, Bilirubin Normal GGTP
Acute fatty liver of pregnancy
Third trimester and postpartum
Elevated AST, ALT, Bilirubin Elevated PT/INR Hypoglycemia
HELLP syndrome
Second half of pregnancy and postpartum
Elevated AST, ALT Decreased PLT Increased LDH
Preeclampsia
Third trimester and immediate postpartum
Elevated AST, ALT HTN, proteinuria
Viral hepatitis
Any trimester
Elevated AST, ALT, bilirubin
Hyperemesis gravidarum usually occurs during early pregnancy and resolves before 20 weeks gestation. Elevations in the serum transaminases occur in more than half of the cases and are typically less than 1000 IU/L with serum ALT usually higher than AST. Intrahepatic cholestasis of pregnancy is characterized by pruritus and should be considered in pregnant patients during the 2nd or 3rd trimester. High levels of serum transaminases up to 500 IU/L and serum bile acids (4–10 times normal) with a normal GGTP are the usual laboratory findings. The HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is characterized by abdominal pain and occurs during late pregnancy or shortly thereafter. Transaminase elevations can occur in the several thousand ranges but the prothrombin time is normal unless complicated by disseminated intravascular coagulation. Acute fatty liver of pregnancy also usually presents in the 3rd trimester of pregnancy. Elevation of serum transaminases up to 1000 IU/L and hepatic synthetic dysfunction, such as elevated prothrombin time and hypoglycemia in severe cases, are observed. Preeclampsia can occur in both HELLP syndrome and acute fatty liver of pregnancy, but the pathophysiology is different and sometimes it is difficult to differentiate among these conditions. Preeclampsia presents with hypertension and proteinuria and elevated transaminases signifies severe disease and usually occurs in the third trimester. Acute viral hepatitis (A, B, C) and hepatitis E (in endemic countries) should always be considered in any pregnant patient with elevated serum transaminases. A prospective study from the UK revealed liver dysfunction in 3 % of the deliveries during a 15-month period. Preeclampsia was the most common abnormality (48 %) followed by HELLP syndrome (22 %), intrahepatic cholestasis of pregnancy (16 %), hyperemesis gravidarum (8 %), and acute fatty liver of pregnancy (4 %) [13].
It is important to remember that a slight increase or decrease in some liver function tests may be seen during a normal pregnancy and may not be clinically significant. Serum protein concentrations decrease due to hemodilution in pregnancy; and therefore, serum albumin levels are significantly lower during all three trimesters. Serum alkaline phosphatase levels usually increase late in pregnancy due to production of the placental isoenzyme and an increase in the bone isoenzyme. Serum ALT, AST, and total bile acids level usually remain the same but total serum bilirubin levels decrease during pregnancy [14].
Biliary Colic
Biliary colic is characterized by recurrent postprandial episodes of abdominal pain in the epigastrium or right upper quadrant. It is caused by contraction of the gallbladder against an obstructed outlet due to a stone. The stone may fall back from the cystic duct and the pain resolves temporarily. During pregnancy, 28− 31 % of the patients may experience biliary colic [1, 2]. Almost two thirds of the patients who experience pain have stones larger than 10 mm in diameter [2]. Biliary pain is significantly more frequent among women with gallstones (5 of 17 patients, 29 %) than among women with biliary sludge (2 of 42 patients, 5 %). Disappearance of biliary sludge and stones after delivery is common and occurs in about two-thirds and one-third of women, respectively [1, 2]. Pre-pregnancy obesity and elevated serum leptin have been shown to be risk factors for development of gallbladder disease during pregnancy [3]. Biliary colic without bile duct stones is usually not associated with abnormal liver function tests.
Acute Cholecystitis
Acute cholecystitis is an inflammatory process with infection of the gallbladder as a result of cystic duct obstruction and bile stasis. The incidence of acute cholecystitis is between 1 and 8/10,000 pregnancies [8, 11]. Severe right upper quadrant pain in addition to other symptoms such as fever, tachycardia, nausea, vomiting, anorexia, and Murphy’s sign should raise the suspicion for acute cholecystitis. The diagnosis is usually confirmed with ultrasonography findings. Uncomplicated cholecystitis is not often associated with hyperbilirubinemia. However, mild elevation of serum aminotransferases and amylase, along with hyperbilirubinemia, is seen in the setting of the passage of small stones and/or sludge. Marked elevation of the liver function tests indicates the possibility of a common bile duct stone, cholangitis, or Mirizzi’s syndrome.
Acute Cholangitis
Acute cholangitis is a clinical syndrome characterized by fever, jaundice, and abdominal pain that develops as a result of stasis and infection in the biliary tract.
Laboratory tests typically reveal an elevated white blood cell count with neutrophil predominance, and a cholestatic pattern of liver test abnormalities with elevations in the serum alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), and bilirubin (primarily conjugated) concentration [15–17]. However, a pattern of acute hepatocyte necrosis can occur with aminotransferases as high as 2000 IU/L [18]. Cholangitis can be a common indication for ERCP during pregnancy.
Acute Pancreatitis
Acute pancreatitis is an acute inflammatory process of the pancreas, which is associated with severe epigastric abdominal pain, elevated serum amylase, and/or lipase three times greater than the upper limit of normal. Any significant elevation of serum pancreatic enzymes should be considered clinically relevant since serum amylase and/or lipase do not normally increase during the course of a normal pregnancy [18].
When uncertain, the diagnosis may be established by further radiologic findings such as focal or diffuse enlargement of the pancreas and/or peripancreatic inflammatory changes seen on contrast-enhanced abdominal computed tomography (CT) or magnetic resonance imaging (MRI). The incidence of acute pancreatitis during pregnancy is fortunately uncommon (< 10 in 10,000) [19]. In a 5-year study of over 46,000 pregnancies, the frequency of acute pancreatitis was 0.07 % at one institution [9]. Acute pancreatitis in pregnancy is most often associated with gallstones, which are responsible for over 70 % of the cases [8, 9, 19, 20]. Elevation in serum ALT to more than three times the upper limit of normal has been reported to be a very sensitive biomarker of biliary pancreatitis [21]. The pathogenesis of biliary pancreatitis is related to impaction or passage of a stone or crystals via the ampulla of Vater with pancreatic ductal obstruction causing activation of intra-acinar trypsinogen to trypsin. Biliary pancreatitis can occasionally be severe and associated with significant maternal morbidity [22]. Fetal loss is not uncommon (7 %) in biliary pancreatitis and is as high as 30 % when associated with recurrent pancreatitis [23, 24].
The second most common cause of acute pancreatitis during pregnancy is hypertriglyceridemia. In the third trimester, serum triglyceride levels rise three-fold, likely due to estrogen-induced increase in triglyceride synthesis [25]. Treatment of hyperlipidemic acute pancreatitis during pregnancy is mostly supportive.
What Are the Diagnostic Imaging Options?
Ultrasonography
Ultrasonography is a safe initial step for identifying gallbladder stones and sludge in pregnancy . Despite its high sensitivity for detection of cholelithiasis, it lacks sensitivity for identifying CBD stones. Dilated biliary ducts in the setting of abnormal liver function tests or pancreatitis raise the suspicion for choledocholithiasis.
Magnetic Resonance Imaging (MRI) and Magnetic Resonance Cholangiopancreatography (MRCP)
MRI and magnetic resonance cholangiopancreatography (MRCP) provide large field view images of the body with excellent soft-tissue contrast and images of the pancreatobiliary system [19]. Gallstone pancreatitis is often associated with small stones and sludge, which can be missed even by MRCP especially if located in the distal CBD and smaller than 5–6 mm [26–28]. MRCP is an accepted alternative imaging modality for pregnant women when more information is needed about the biliary system. Because no contrast is given during MRCP, there is no risk of renal injury. It is important to examine several views as different projection images may provide complementary information as shown in Fig. 19.1. Based on the American College of Radiology (ACR) guidance document for safe MR practice published in 2013, MRI is only indicated during pregnancy if the information cannot be acquired through other nonionizing diagnostic imaging studies, and the data will potentially affect the care of the patient or fetus during pregnancy [26]. There are no special considerations regarding performing MRI in the first compared to any other trimester of pregnancy.
Fig. 19.1
A 21-year-old at 8 weeks gestation was referred for evaluation of suspected biliary colic due to RUQ pain, nausea, vomiting, and increased LFTs. MRCP showed several stones in the distal bile duct that are best appreciated when examining different projected images as shown here. ERCP was performed without fluoroscopy with sphincterotomy and removal of stones
Endoscopic Ultrasonography (EUS)
Endoscopic ultrasonography is highly sensitive (89–94 %) and specific (94–95 %) for detecting CBD stones [29, 30]. EUS has high diagnostic accuracy for detecting CBD stones; however, compared to other imaging modalities it requires sedation, an expert endoscopist, and specialized equipment. Although EUS does not allow therapeutic intervention, it is generally safe and does not involve radiation exposure. Performing EUS prior to ERCP in patients with suspected CBD stones can help to avoid unnecessary ERCP and its complications in near two thirds of the patients [31, 32]. If a common bile duct stone is detected by EUS (Fig. 19.2), an ERCP with sphincterotomy can be performed during the same session [33, 34].
Fig. 19.2
A 26-year-old at 8 weeks gestation was referred for suspected choledocholithiasis based on increased ALT and dilated bile ducts on transabdominal ultrasonography. Endoscopic ultrasound showed a hyperechoic shadowing stone ( arrow) in the bile duct that was removed at the same session during ERCP
Case Continued
Abdominal ultrasonography showed cholelithiasis and moderate extrahepatic biliary duct dilation. There was no evidence of cholecystitis. A subsequent MRCP showed a dilated bile duct to 1.3 cm in diameter and multiple stones in the common bile duct. Based on the imaging findings, elevated transaminases, and her symptoms of abdominal pain and nausea, the likely diagnosis was biliary colic due to choledocholithiasis. The decision was made to proceed with ERCP.
What Are the Indications for ERCP in Pregnancy?
Choledocholithiasis and its complications are far and away the most common indication for performing ERCP during pregnancy. It is most important to understand that ERCP should only be considered when there is absolute certainty that endotherapy is necessary. The indications for performing an ERCP during pregnancy are similar but more restricted when compared to the nonpregnant state (Table 19.2). Furthermore, if possible, ERCP should be postponed until the second trimester or postpartum.
Table 19.2
Indications for ERCP during pregnancy
Urgent |
Acute cholangitis |
Biliary pancreatitis with suspected impacted stones |
Elective |
Suspected symptomatic choledocholithiasis |
Post-operative complications, e.g., bile leak |
Relapsing pancreatitis |
Pancreatic duct disruption |
Development of biliary disease during the pregnancy, especially in the first trimester, can result in maternal and fetal physiologic dysfunction leading to adverse pregnancy outcome such as preterm labor or low birth weight. It is important to identify complications of choledocholithiasis early during pregnancy and determine if there is a need for intervention as promptly as possible.
Not surprisingly, early reports of ERCP during pregnancy were performed for urgent indications . Baillie et al. reported the first case series of five patients in 1990. The indications were acute cholangitis in four and gallstone pancreatitis in one patient. All five patients delivered healthy babies at term [35]. Since then, ERCP during pregnancy is still almost always performed for biliary indications, but sometimes under more elective settings.
Historically, the care of pregnant patients with acute biliary related disease entailed conservative management with the hope of delaying intervention until after pregnancy or the second trimester when organogenesis is completed. While this still remains true, currently, urgent ERCP with sphincterotomy and clearance of bile duct stones is indicated in patients with cholangitis and in those with severe acute pancreatitis and evidence of persistent biliary obstruction. Elective ERCP with biliary sphincterotomy +/− stenting may be indicated when there is evidence of symptomatic CBD stones and cholecystectomy needs to be delayed due to the pregnancy or for less common reasons such as postoperative complications like bile leak (Fig. 19.3). Rarely, it may be reasonable to consider ERCP for management of pancreatitis that is not due to a biliary etiology. In the report by Jamidar et al., only 2 of the 23 pregnant patients underwent ERCP to treat a purely pancreatic indication including pancreas divisum and pancreatic duct stricture [36].
Fig. 19.3
A 42-year-old with a 21-week gestation underwent open cholecystectomy for gangrenous cholecystitis. Due to the persistent bile drainage via a percutaneous drain, she was referred for ERCP for treatment of a suspected bile leak. a Biliary access was obtained without use of fluoroscopy after a needle-knife access sphincterotomy over a pancreatic stent. b A bile duct stent was placed to ensure drainage. A postpartum ERCP was normal and the bile duct stent was extracted
Pre-Procedure Considerations
Informed Consent
Performing ERCP in a pregnant patient is appropriate only when there are clear indications for endotherapy. The benefits and risks of the procedure should be clarified for the patient, spouse, and any other relevant family members. The risks include not only those to the mother but also to the fetus. Complications of ERCP in general are pancreatitis, hemorrhage , perforation , infections (cholangitis, cholecystitis), cardiopulmonary complications (arrhythmia, hypoxemia, aspiration), stent-related complications (stent migration, stent occlusion, liver abscess, bile duct or pancreatic duct injury, and subsequent duct stricture), and death [37]. The fetus is sensitive to maternal hypoxia and hypotension, which can lead to fetal distress and demise. Other risks to the fetus include teratogenicity from medications and/or radiation exposure and premature birth. A full review of radiation issues will be discussed below. An informed consent for ERCP during pregnancy should include a discussion of potential risks of radiation, methods to reduce risk as well as an alternative for ERCP without any radiation. It should be clarified that ERCP without use of fluoroscopy is more difficult and therefore potentially associated with more risk from a technical aspect. Whether or not the endoscopist is comfortable with no radiation techniques (see below) should also be discussed. If patient and family are completely opposed to use of any radiation, then it is appropriate to discuss options for transfer to another expert center, if conditions allow.
Patient Positioning
Patient positioning for ERCP during pregnancy is typically different from the customary prone position used in the nonpregnant state. During pregnancy, the patient’s position for ERCP depends on the trimester of her pregnancy and whether or not fluoroscopy is planned. Maintaining a prone position may be difficult during the second and third trimester, so a left lateral position with the use of a pelvic wedge, if needed, is preferable. It is generally recommended that the patient should not be completely supine since the gravid uterus can compress the vena cava or the aorta causing maternal hypotension and decreased placental perfusion [10, 38, 39]. Nonetheless, outcome of the pregnancy was not adversely affected in a study of all patients who underwent ERCP in a supine position.[38] If ERCP is performed without any fluoroscopy, then all patients regardless of pregnancy stage can remain in the left lateral position.
Patient Monitoring
Standard American Society of Anesthesiologists (ASA) monitoring should be utilized throughout the procedure. In the setting of a viable fetus, fetal heart rhythm should be monitored continuously or at a minimum before and after general anesthesia depending on the gestational age. Before 24 weeks, Doppler can be used to document the presence of fetal heart rate before and after the procedure. Continuous fetal heart and uterine contraction monitoring before, during, and after the endoscopy should be performed for fetuses older than 24 weeks. This should be discussed and coordinated with the obstetric team who should be consulted in all cases involving pregnant patients.
Sedation
There are potential risks to the fetus from the use of specific medications for sedation (Table 19.3). None of the medications that are used for sedation during ERCP are in category A of Food and Drug Association of the United States (FDA), so category B or C drugs may be used [10]. Category B medications are considered relatively safe while category C drugs are likely safe and category D medications should be avoided unless absolutely needed with no safer alternatives. Most ERCPs are performed using a combination of benzodiazepine and opiates or propofol and opiates. Meperidine is a category B drug and does not appear teratogenic. However, meperidine can be considered as category D when used for long periods (> 36 h) in high doses at term due to concerns about accumulation of its mildly toxic metabolite, normeperidine. During routine endoscopy, the maximum suggested dose for meperidine is 75 mg. Fentanyl is a category C drug as it has embryocidal effects in rats, but appears safe in humans at low doses. Propofol is classified as category B, but its use in the first trimester has been inadequately studied [7]. Benzodiazepines, including midazolam and diazepam, are category D drugs. Midazolam has not been associated with congenital abnormalities like cleft palate malformations and is preferred over diazepam when sedation with meperidine is inadequate, but if possible it should be avoided in the first trimester due to the potential fetal harm at that time. Glucagon and lidocaine are considered category B, whereas flumazenil and simethicone are rated as category C [10].
Table 19.3
Medication Safety in ERCP during pregnancy
Medications | FDA category | Comment |
|---|---|---|
Meperidine | B | Safe in pregnancy, avoid use at term |
Propofol | B | Safe in pregnancy |
Fentanyl | C | Safe at low doses |
Morphine | C | Crosses fetal blood–brain barrier rapidly |
Naloxone | B | Use with caution, one reported case of neonatal fatality |
Flumazenil | C | Use only if clearly indicated |
Benzodiazepines (diazepam) | D | Possible association with mental retardation and congenital anomalies |
Midazolam | D | Preferred over diazepam, no reports of congenital anomalies, avoid in 1st trimester |
Glucagon | B | Safe in pregnancy |
Endotracheal intubation is generally recommended for any upper endoscopy procedure due to the potential concern for aspiration as well as to maintain the airway and for a potentially prolonged, complicated procedure. Physiologic changes during pregnancy include swelling of the oropharyngeal tissue and narrower glottis opening [43].
Antibiotics
An appropriate antibiotic should be administered in cases with evidence for acute cholangitis or cholecystitis; however, selecting the right antibiotic during pregnancy can be complicated (Table 19.4). There are potential concerns regarding the transplacental passage of antibiotics leading to possible teratogenic effects on the fetus. Initial antibiotic choice is empiric and should be subsequently modified based on the organisms found in the blood and bile cultures. Most of the penicillin derivatives (amoxicillin, ampicillin, ampicillin-sulbactam, piperacillin-tazobactam), clindamycin, erythromycin, and cephalosporins are classified as category B drugs and are safe during pregnancy [19]. Metronidazole crosses the placenta and should be avoided in the first trimester [43]. Imipenem, which belongs to carbapenem class, is a category C drug, and while animal studies showed no teratogenic risks, there are no available human data [19]. Quinolones are category C with reports of adverse effects to the fetus, therefore their use should be avoided during pregnancy.
Table 19.4
Antibiotic safety in ERCP during pregnancy
Antibiotics | FDA category | Comment |
|---|---|---|
Penicillins | B | Safe in pregnancy |
Cephalosporines | B | Safe in pregnancy |
Erythromycin | B | Safe in pregnancy |
Clindamycin | B | Safe in pregnant patients with penicillin allergy |
Ampicillin- sulbactam | B | Safe in pregnancy |
Piperacillin-tazobactam | B | Safe in pregnancy |
Metronidazole | B | Avoid in first trimester |
Quinolone | C | Avoid in pregnancy |
Imipenem | C | Avoid in pregnancy |
Tetracycline | D | Avoid in pregnancy |
Sulfonamide | C | Avoid in third trimester |
Case Continued
The decision of proceeding with ERCP was discussed with the patient’s obstetrician, and we were assured of staff availability during the procedure in case of fetal distress or pregnancy related complications. Informed consent was obtained after the risks, benefits, and alternatives of the procedure were thoroughly explained. She and her husband wished to have the ERCP performed without any fluoroscopy, if possible. Standard ASA monitors were placed with the addition of fetal heart monitoring. A labor and delivery nurse was present before, during, and after the ERCP to monitor fetal heart rate and rhythm, and to monitor for uterine contractions. Preoxygenation and rapid sequence induction was then performed followed by a standard general endotracheal anesthetic. The patient was positioned in the left lateral position.
Radiation and Pregnancy
What Are the Potential Effects of Fluoroscopy During Pregnancy?
Use of fluoroscopy and spot radiography is inherent to standard ERCP procedures. Any ERCP during pregnancy that utilizes fluoroscopy will expose the fetus to potential risks of ionizing radiation with the greatest risk during 8–15 weeks gestation. There are a number of excellent and comprehensive reviews on the topic [7, 10, 38, 39, 41, 44–46].
Related posts:
Training in Endoscopic Retrograde Cholangiopancreatography
Choledochal Cysts: Evaluation and Management
Endoscopic Ultrasound-Guided Fine-Needle Injection
Rectal Cancer and Anal Sphincter Disorders
ERCP from Soup to Nuts: Evaluation, Preparation, Execution, and Follow-Up
Pediatric Endoscopic Retrograde Cholangiopancreatography
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