Table 1 | Safety of anesthetic medications commonly used in gastrointestinal procedures Drug FDA category in pregnancy* Summary of literature regarding drug safety Meperidine B, but D at term Fentanyl C Propofol B Human data suggest some risk if used for prolonged periods or in high doses at full term.1 Meperidine is decreasingly used for endoscopy because repeated high dose meperidine administration can cause progressive accumulation of normeperidine, with toxicity manifested by respiratory depression and seizures.2 Meperidine is rapidly transferred across human placenta to fetus after maternal administration.3,4 It is not associated with an acute opioid withdrawal syndrome in neonates born to addicted mothers, as occurs with other opiates such as heroin. In the Collaborative Perinatal Project,5 meperidine was not teratogenic in a study of 268 mothers, but 6 of the infants exposed in utero had inguinal hernias. In a survey of Michigan Medicaid recipients,1 6 of 62 infants with first trimester in utero exposure to meperidine had major congenital defects. Maternal administration of the drug during delivery depresses neonatal respiration for several hours after birth.6 It may impair neonatal neuropsychologic functions, such as attention, for several weeks after birth.7 Children whose mothers received meperidine during labor had similar intellectual parameters at 5 years of age compared with children without in utero exposure.3 In a study of 407 pregnant women, neonatal outcome was worse in pregnant women who received meperidine during delivery compared with pregnant women who received placebo.8 Human data suggest some risk in when used in the third trimester. Fentanyl crosses the placenta to the fetus in humans. It is embryocidal but not teratogenic when administered for prolonged periods in pregnant laboratory animals.3,9 Maternal fentanyl administration during labor produced no neonatal toxicity in numerous studies.10 For example, there were no differences in newborn outcomes in a study comparing 137 women administered fentanyl during labor versus 112 women not administered narcotics during labor.10 Several individual case reports have associated fentanyl use during labor with transient respiratory depression, respiratory muscle rigidity, or opiate withdrawal in newborn infants.11 Limited human data; animal data suggest low risk. Administration of six times the maximal recommended human equivalent dose in pregnant rats or rabbits revealed no teratogenicity.12 Propofol rapidly transfers across the placenta in humans. Numerous studies involving hundreds of pregnant mothers revealed no neonatal toxicity from propofol administered during parturition.13 However, very high doses administered during parturition may transiently depress neonatal neurobehavioral function.3,14 Narcotics General anesthetics Ketamine B Limited human data; animal data suggest low risk.3 Multiple studies have demonstrated no teratogenic effects in numerous laboratory animal species when ketamine is administered during organogenesis. Ketamine rapidly crosses the placenta to the fetus in humans. Ketamine has transient oxytocic effects. Ketamine administration during delivery can transiently depress neonatal neurologic functions, especially after prolonged, high-dose administration.15 Ketamine has not been associated with teratogenicity in humans.16 D Human data suggest possible risk when used in first and third trimesters.3 Diazepam rapidly crosses the placenta to achieve levels in the fetal circulation approximately equivalent to the maternal serum levels.17 Although older studies suggested an association between maternal diazepam use and cleft palates in their offspring,18 three large studies, including a case-controlled study of 355 infants with oral clefts versus 11,073 healthy infants, have shown no such association.19 Other studies have suggested a possible association of diazepam exposure and congenital inguinal hernia, cardiac defects, pyloric stenosis, and Mobius syndrome (sixth and seventh nerve palsies).20,21 However, in a large report by the Israeli Teratogen Service,22 diazepam exposure did not cause a significant increase in the incidence of major congenital malformations. Several reports have raised a possible association between frequent, high-dose diazepam administration during pregnancy and mental retardation or other Sedatives Diazepam 1 Midazolam D neurologic defects.23 Limited human data; animal data suggest low risk. Administration of several times the maximal equivalent human dose in pregnant laboratory animals revealed no teratogenicity.12 Midazolam crosses the human placenta. Several studies suggested that maternal midazolam administration during labor transiently depresses neonatal neurobehavioral responsiveness.24,25 However, other studies have shown no such adverse effects.26 This benzodiazepine has not been associated with oral clefts.3 Reversal agents Naloxone B Probably safe on the basis of several studies in humans. Naloxone rapidly crosses the human placenta.3 Naloxone administered at up to 50 times the maximal equivalent human dose in pregnant mice or rats has not been shown to be fetotoxic.12 Intravenous administration of naloxone in 27 pregnant healthy women at 37 to 39 weeks of gestation improved the number and duration of fetal heart accelerations, without evident neonatal toxicity.27 Naloxone has been administered to reverse respiratory depression in newborn infants due to maternal narcotic overexposure during labor without toxic effects.28 Two infants developed respiratory failure and convulsions attributed to naloxone administered to their mothers during labor.29,30 Flumazenil C Limited human data; animal data suggest low risk. Administration of flumazenil to pregnant rabbits or rats at several hundred times the maximal recommended human dose revealed no teratogenicity.3,12 Transplacental transfer of flumazenil is unstudied in humans, but the transfer is likely to be small from a single bolus of the drug due to its short half-life. Three cases have been reported of successful administration of flumazenil during the third trimester without evident fetal toxicity.31 Flumazenil overdose can cause maternal seizures, particularly when administered to patients who are chronically receiving benzodiazepines. *If drug safety during pregnancy is not rated by the FDA, the semi-authoritative drug rating by Briggs et al.1 is substituted. 2 Table 2 | Summary of published studies on fetal safety of diagnostic EGD during pregnancy Reference Type of study n Maternal Outcome Fetal Outcome Modern studies Cappell et Retrospective, 83 No maternal deaths Healthy infants: 95% in al. (1996)32 case-controlled study patients vs. 94% in Debby et al. (2008)33 Retrospective, clinical series 60 One minor complication: transient pyrexia after EGD that rapidly resolved without requiring antibiotic therapy No maternal deaths after EGD or during the pregnancy. Incidence of other maternal complications not reported controls (same indications for EGD but not undergoing procedure due to pregnancy) Fetal demise and induced abortion in 2% and 5% of patients, respectively. All other mothers delivered healthy babies: 48 at full term and 8 preterm.No fetal malformations reported NA Bagis et al. (2002)34 Prospective 30 Cappell (2003)35 Review of 27 case reports 27 Quan et al. (2006)36 Case report 1 No procedural complications Delivered at term via normal spontaneous vaginal delivery 15 NA 93% healthy infants; 2 infants with poor fetal outcomes mentioned NA Studies before 1970 McCall et al. Clinical series (1961)37 Maternal endoscopic complications not reported. High rate of H. pylori infection found in patients with hyperemesis gravidarum vs. healthy pregnant controls One maternal death from metastatic cancer Castro Clinical series 43 NA (1967)38 Abbreviations: EGD, esophagogastroduodenoscopy; NA, not available. 3 22 healthy infants, 3 stillbirths unrelated to EGD, 1 very premature infant, 1 voluntary abortion Table 3 | Summary of published studies on fetal safety of therapeutic EGD for upper gastrointestinal bleeding during pregnancy Reference Type of study n Maternal outcome Fetal outcome Sclerotherapy for esophageal varices Aggarwal et Clinical series 17 10 patients with extrahepatic 6 healthy infants al. (2001)39 portal vein obstruction, and 7 delivered at full term, 2 Kochhar et al. (1999),40 and Kochhar et al. (1990)74 Clinical series 10 Cappell (2003) 35 Review of individual case reports 7 Lodato et al. (2008)41 Case report 1 Endoscopic banding of esophageal varices Dhiman et al. Case report 3 (2000)42 with noncirrhotic portal fibrosis received sclerotherapy with absolute alcohol or 1.5% sodium tetradecyl sulfate. 12 of 17 patients required multiple sclerotherapy sessions. 2 patients failed endoscopic sclerotherapy and required variceal banding Endoscopic sclerotherapy with injection of absolute alcohol injection for active variceal bleeding in 5 patients, and for prophylaxis of bleeding in 5 patients. A mean of 3 sessions were required. Hemostasis was achieved in all 5 actively bleeding patients. One procedural complication of esophageal stricture was successfully treated with a Savary dilator Successful sclerotherapy performed for actively or recently bleeding esophageal varices 2 sessions of endoscopic sclerotherapy performed for variceal bleeding associated with cryptogenic cirrhosis. Patient failed sclerotherapy and underwent successful TIPS for recurrent variceal bleeding healthy infants delivered at preterm, 3 stillbirths, 1 neonatal death, and 5 voluntary abortions 1 patient recieved 7 sessions of endoscopic sclerotherapy for esophageal varices, that had previously bled, without variceal eradication. Varices were successfully eradicated with 1 endoscopic banding session Uncomplicated delivery 1 patient with variceal bleeding due to portal vein obstruction underwent endoscopic banding of esophageal varices and endoscopic sclerotherapy of fundal varices. Varices were successfully eradicated 1 patient underwent 3 4 All 10 infants were delivered at term by normal vaginal delivery All infants were healthy Infant delivered at 26 weeks due to premature rupture of membranes. Infant died from respiratory distress 12 h after birth due to hyaline membrane pneumopathy Uneventful delivery Cappell et al. (1996)32 Single case of sclerotherapy in a case-controlled study of 83 EGDs 1 Ghidirim et al. (2008)43 Case report 1 Savage et al. (2007)44 Case report 1 Starkel et al. (1998)45 Zeeman et al. (1999)46 Case report 1 Case report 1 unsuccessful sessions of endoscopic sclerotherapy for esophageal varices. 2 subsequent sessions of variceal banding resulted in a reduction in variceal size, The patient was doing well in her 20th week of pregnancy No further bleeding after session of endoscopic sclerotherapy for recently bleeding, large esophageal varices Mother with noncirrhotic portal hypertension underwent prophylactic banding of large varices during second trimester Mother with cirrhosis from hepatitis C underwent endoscopic banding of 5 varices for variceal bleeding. Bleeding continued despite treatment and patient required TIPS, which successfully stopped variceal bleeding Successful hemostasis of variceal bleeding Mother with cirrhosis underwent 3 sessions of endoscopic variceal banding for large esophageal varices. No variceal bleeding experienced during pregnancy. Endoscopic hemostasis of actively bleeding nonvariceal upper gastrointestinal lesions Cappell et al. Single case of 1 Thermocoagulation failed to Mother at 20th week of gestation Healthy infant Healthy infant born at term Healthy baby delivered vaginally without complications Healthy infant Infant born prematurely at 33 weeks and had a prolonged (29 day) stay in neonatal ICU No medical complications Healthy premature stem an actively bleeding baby peptic ulcer and the patient required laparotomy. At surgery, the bleeding ulcer was oversewn and vagotomy and pyloroplasty were performed Debby et al. Single case of 1 Endoscopic Infant born without (2008)33 endoscopic electrocoagulation fetal malformations hemostasis successfully stopped active reported in a bleeding from a duodenal clinical series of 60 ulcer during first trimester of EGDs pregnancy Brunner et al. Case report 1 Endoscopic injection with Healthy infant (1998)47 epinephrine successfully stopped active bleeding from esophageal ulcers Macedo et al. Case report 1 Uncomplicated pregnancy NA (1995)48 following sclerotherapy for a bleeding Mallory-Weiss tear Abbreviations: EGD, esophagastroduodenoscopy; ICU, intensive care unit; TIPS, transjugular portosystemic shunt; NA, not available. (1996)32 endoscopic hemostasis in a case-controlled study of 83 EGDs 5 Table 4 | Summary of published studies on fetal safety of endoscopic therapy for achalasia during pregnancy Reference Type of study Endoscopic injection of botulinum toxin Wataganara et al. Case report (2009)49 Endoscopic balloon dilatation Aggarwal et al. Case report (1997)50 Clinical presentation Maternal and fetal outcomes Severe weight loss and malnutrition due to progressive dysphagia After uncomplicated endoscopic injection of botulinum toxin 1 cm above squamocolumnar junction, the patient rapidly gained weight from successful oral feedings. A healthy infant was delivered at 36 weeks of gestation. There was no evidence of neuromuscular blockade in the infant Dysphagia with weight loss despite pregnancy The patient rapidly gained weight after regaining her ability to swallow after endoscopic dilatation. The patient had an abortion at 7 months gestation The procedure performed at 11 weeks of gestation was uncomplicated and led to resolution of all maternal symptoms. A healthy infant was delivered vaginally at 35 weeks of gestation The patient did well with improved nutritional status and delivered a healthy infant at term Fiest et al. (1993)51 Case report Dysphagia, postprandial vomiting, and weight loss at 8 weeks of gestation Pulanic et al. (2008)52 Case report Severe malnutrition due to progressive, severe dysphagia Nonendoscopic pneumatic dilatation Clemendor et al. Case report (1969)53 Dysphagia 6 Uncomplicated pneumatic dilatation was performed at 24 weeks of gestation. The patient delivered a healthy infant at 36 weeks of gestation Table 5 | Summary of published studies on fetal safety of PEG or PEGJ during pregnancy Reference Type of study Maternal outcome Fetal outcome Godil et al. (1998)54 Case report (n=2) Healthy infants Shaheen et al. (1997)55 Case report (n=2) PEG performed in 2 pregnant women for anorexia nervosa or hyperemesis gravidaum. No procedural complications occurred and both maternal outcomes were favorable 1) PEG performed at 17 weeks gestation in a patient presenting with severe odynophagia from severe circumferential esophagitis with odynophagia. PEG removed at 24 weeks of gestation after the patient gained weight and was able to eat orally PEG Koh et al. (1993)56 Case report (n=1) Sarafov et al. (2009)57 Case report (n=1) PEGJ Pereira et al. (1998)58 Case report (n=2) Serrano et al. (1998)59 Case report (n =2) Irving et al. (2004)60 Case report (n=1) 2) PEG performed at 26 weeks of gestation in mentally retarded female presenting with myotonic muscular dystrophy with nausea and vomiting. The patient required ventilatory support subsequently during pregnancy from dystrophy-associated muscle weakness PEG performed in comatose patient after a motor vehicle accident at 13 weeks of gestation. Mother required antibiotic therapy for systemic infections PEG performed at 21 weeks of gestation because of advanced amyotrophic lateral sclerosis. PEGJ placed at 3 or 4 months of gestation for hyperemesis gravidarum in 2 patients. Mothers subsequently did well 1) PEGJ performed at week 22 of gestation for hyperemesis gravidarum. Procedure complicated by local wound infection 2) PEGJ performed at 15 weeks of gestation for hyperemesis gravidarum. Procedure complicated by jejunal tube extension migrating into stomach. Tube correctly repositioned by repeat endoscopy PEGJ placed at 17 weeks of gestation for refractory 7 Healthy, mildly underweight, infant delivered near term. Infant delivered at 30 weeks by cesarean section. Infant required intubation due to severe congenital myotonic muscular dystrophy and died 2 weeks after delivery from the dystrophy Healthy, normal weight, infant delivered by cesarean section at 37 weeks of gestation Infant delivered by cesarean section at 34 weeks of gestation. Child required artificial ventilation for 3 days after birth, but developed normally without developmental abnormalities Healthy infants were delivered at term via vaginal delivery 2 healthy, normal weight infants. Both seem to have developed normally at 24 and 27 months of age Healthy, but moderately underweight, infant delivered hyperemesis gravidarum at 35 weeks of gestation PEG placed at 11 weeks of Infant was born live, but gestation due to a coma from a severely underweight, at 27 massive stroke. Jejunal weeks of gestation. The infant extension was placed at week 24 was treated in neonatal ICU of gestation for recurrent vomiting. Mother subsequently did well Abbreviations: ICU, intensive care unit; PEG, percutaneous endoscopic gastrostomy; PEGJ, percutaneous endoscopic gastrojejunostomy Wejda et al. (2003)61 Case report (n=1) 8 Table 6 | Summary of published studies of fetal safety of therapeutic ERCP during pregnancy.* Reference Tang et al. (2009)62 Type of study Retrospective clinical series (n=65) Shelton et al. (2008)63 Retrospective clinical series (n=21) Jamidar et al. (1995)64 Retrospective clinical series (n=20, excludes 3 patients undergoing solely diagnostic ERCP) Gupta et al. (2005)65 Retrospective clinical series (n=18) Kahaleh et al. (2004)66 Retrospective clinical series (n=17) Maternal outcome ERCP therapies included sphincterotomy and biliary stent placement. Removal of CBD stones was successful in 32 of 33 patients with these stones. Maternal complications included pancreatitis in 11 patients (mild in 8 patients, moderate in 3 patients). Repeat ERCP with lithotripsy required to remove residual stone in 1 patient. 10 patients underwent cholecystectomy later in pregnancy for acute cholecystitis, or symptomatic gallstones. ERCP was perfomed using wireguided cannulation without fluoroscopy. Indications included jaundice and biliary colic, biliary pancreatitis, cholangitis, and abnormal intraoperative cholangiogram. Sphincterotomy with successful removal of stones was acheived in 14 patients. Sphincterotomy with successful removal of sludge was achieved in 7 patients. Mild post-ERCP pancreatitis occurred in 1 patient. ERCP therapies included sphincterotomy, stone extraction, stent, biliary stent placement and pancreatic stent placement.Severe pancreatitis (due to pancreatic orifice stenosis) occurred after ERCP in 1 patient. All patients underwent ERCP and sphincterotomy for CBD stones. 4 patients also had biliary stenting. Mild pancreatitis occurred after ERCP in 1 patient. A post-sphincterotomy bleed occurred in 1 patient. 3 patients required repeat ERCP with mechanical lithotripsy after delivery ERCP indications included gallstone pancreatitis, choledocholithiasis, and cholangitis. All patients underwent ERCP with sphincterotomy. Moderate pancreatitis occurred after ERCP in 1 patient. A postsphincterotomy bleed occurred in 1 patient that was managed by placement of a hemoclip. 2 9 Fetal outcome 59 known fetal outcomes: 54 healthy infants, 5 infants born preterm or with low birth weight. No fetal or perinatal deaths. No congenital malformations 17 known fetal outcomes: 16 healthy infants born at term, and 1 healthy infant born prematurely 18 known fetal outcomes: 14 healthy infants, 1 premature but otherwise healthy infant, 1 spontaneous abortion 3 months after ERCP, 1 neonatal death from maternal pancreatitis after ERCP, and 1 voluntary abortion Of 11 known fetal outcomes, all 11 infants were healthy at mean of 6 yrs follow-up Among 15 known fetal outcomes, all infants were healthy patients developed preeclampsia in their third trimester which was successfully treated medically Sharma et al. Retrospective clinical ERCP indications included Healthy infants (2008)67 series (n=11) abdominal pain with jaundice or cholangitis. All patients underwent biliary sphincterotomy with stenting. Fluoroscopy was not used for cannulation; bile was aspirated using a sphincterotome to confirm CBD cannulation. All patients rapidly improved after stenting. All patients underwent a “second-stage” ERCP after delivery. Among 10 patients with stones postpartum at ERCP, 9 were removed at ERCP and one required open surgery. Farca et al. (1997)68 Prospective clinical All patients underwent ERCPs Healthy infants series (n=10) with biliary stenting. 9 patients had uncomplicated ERCP, 1 patient had an impacted stone after ERCP that was relieved by repeat ERCP with sphincterotomy. Daas et al. (2009)69 Retrospective clinical 17 ERCPs including Healthy infants series (n=10) sphincterotomy, ballloon sweep and stent placement were perfomed. No maternal complications. Bani Hani et al. Retrospective review Indications for ERCP included 10 infants were delivered at (2009)70 (n=10) abnormal liver function tests, term with an average birthright upper quadrant pain, weight of 3.4 Kg and mean dilated common bile duct on Apgar score of 8.6 abdominal ultrasound, or jaundice. All patients underwent sphincterotomy and successful balloon stone extraction. All patients rapidly became asymptomatic following stone extraction. *Only studies of ≥10 patients included in table. Abbreviations: CBD, common bile duct; ERCP, endoscopic cholangiopancreatography 10 Table 7 | Summary of published studies of fetal safety of therapeutic ERCP during pregnancy Reference Chong et al. (2010)71 Type of study Retrospective clinical series (n=8) Al-Akeely (2003)72 Retrospective clinical series (n=8) Tham et al. (2003)73 Retrospective clinical series (n=7, excludes 8 patients undergoing solely diagnostic ERCP) Guitron-Cantu et al. (2003)74 Retrospective clinical series (n=7) Akcakaya et al. (2009)75 Retrospective clinical series (n=6) Simmons et al. (2004)76 Retrospective clinical series (n=6) Tarnasky et al. (2003)77 Letter to editor (n=6) 11 Maternal outcome ERCPs indications were obstructive jaundice, or cholangitis. ERCP interventions were stent placement, sphincterotomy, and balloon sweep. Maternal complications included 1 patient with obstructive jaundice from stent migration requiring repeat ERCP, 1 patient with pancreatitis, and 1 patient in whom labor was induced ERCP indications: were obstructive jaundice, or recurrent acute gallstone pancreatitis. ERCP with sphincterotomy performed. 6 patients had clearance of CBD after ERCP and did well. 2 patients underwent successful laparoscopic cholecystectomy during pregnancy after ERCP 6 patients had sphincterotomy and stone extraction for CBD stones. 1 complication of mild post ERCP pancreatitis occurred. 2 patients required laparoscopic cholecystectomy 1 day after ERCP 1 patient had biliary stenting for recurrent biliary colic with abnormal liver enzymes. The biliary stent was extracted after delivery All patients underwent ERCP with sphincterotomy for CBD stones. Successful stone extractions without procedural complications ERCP indications were choledocholithiasis, cholangitis, and biliary fistula. 5 patients underwent sphincterotomy with stone extraction, 1 patient underwent sphincterotomy and scoleces extraction. All ERCPs were uncomplicated except 1 where a persistent fistula was successfully treated with a biliary stent on repeat ERCP ERCP indications were cholelithiasis, jaundice and dilated CBD on ultrasound, and recurrent pancreatitis after cholecystectomy. All patients underwent sphincterotomy with balloon extraction. No post-ERCP complications occurred. 1 patient required cholecystectomy 5 weeks after ERCP ERCP indications were jaundice and biliary colic, cholangitis, and biliary pancreatitis. All patients Fetal outcome 4 vaginal births, 4 cesarean sections, 1 spontaneous abortion due to HELLP syndrome, 1 death from sudden infant death syndrome at 40 days, 1 infant with grade II meconium staining 8 healty infants delivered vaginally 5 healthy infants delivered at term. 2 ongoing pregnancies 7 healthy infants delivered at term. 6 healthy infants 2 unknown outcomes, 3 “excellent” outcomes, 1 infant delivered severely prematurely and born with pneumonia and acute respiratory distress syndrome 2 healthy infants delivered vaginally at term, 2 healthy infants delivered had sphincterotomy and balloon sweeps with removal of CBD stones. There were no ERCP complications, but one patient had 2 repeat admissions for biliary colic. Shah et al. (2005)78 Retrospective clinical series (n=6) Vandervoort et al. (1996)79 Meeting abstract (n=6) Baillie et al. (1990)80 Retrospective study (n=5) Sungler et al. (2000)81 Prospective study (n=5) Savas et al. (2003)82 Letter to editor (n=5) 12 ERCP indicated for extraction of known biliary ascariasis diagnosed by abdominal ultrasound. Endoscopic extraction of worms was successful in 4 patients. The 2 unsuccessful cases were related to duct stricture or intrahepatic stones. These 2 patients had surgery for cholecystectomy and worm extraction. Mothers subsequently apparently did well ERCP with sphincterotomy for CBD stones. No maternal complications except 1 case of mild post-ERCP pancreatitis ERCP indications included abnormal LFTs, dilated CBD, intrahepatic and CBD stones, gallstone pancreatitis with a thickened gallbladder wall, and jaundice with elevated serum amylase several months after cholecystectomy. 1 patient had a transient episode of cholestasis which resolved after 4 weeks, 1 patient did well, but developed atrophy of right lobe of liver associated with extensive choledocholithiasis 2 years later, 3 patients did well ERCP indications included obstructive jaundice and acute biliary pancreatitis. All 5 patients had CBD stones that were successfully removed after endoscopic sphincterotomy. Maternal outcomes were excellent in 3 patients. 1 patient had laparoscopic cholecystectomy performed for persistent biliary colic. 1 patient was initially asymptomatic following the procedure but recurrent severe cholecystitis occurred after 2 weeks requiring cholecystectomy for a walled-off gallbladder perforation Indications included biliary pancreatitis, and biliary obstruction. All patients underwent sphincterotomy and biliary sweep with extraction of CBD stones. No reported maternal procedure complications. All patients improved after procedure. by cesarean section at term, 1 infant delivered preterm by cesarean section due to intrauterine growth restriction, 1 unknown pregnancy outcome 5 “normal pregnancies”, 1 postoperative spontaneous abortion in a patient who underwent surgery after failed ERCP 6 healthy infants or continuing “uneventful’ pregnancy although baby not yet delivered 5 healthy infants 5 healthy infants No fetal adverse effects were observed after the procedure Abbreviations: CBD, common bile duct; ERCP, endoscopic retrograde cholangiography; LFTs, liver function tests. 13 Table 8 | Fetal safety of therapeutic ERCP during pregnancy* Reference Nesbitt et al. (1996)83 Type of study Case report (n=3) Maternal outcome ERCP for gallstone pancreatitis revealed impacted CBD stone in 1 patient that was treated with sphincterotomy and balloon sweep. The patient rapidly improved Fetal outcome 2 healthy infants delivered at term, 1 healthy infant delivered preterm at 32 weeks. ERCP for gallstone pancreatitis revealed dilated CBD and gallstones in gallbladder in 1 patient. Symptoms resolved rapidly after sphincterotomy ERCP for cholangitis revealed stones in CBD in 1 patient. Symptoms rapidly resolved after removal of stones with balloon sweep (without sphincterotomy?) Barthel et al. (1998)84 Case report (n=3) Baillie et al. (2003)85 Brief letter (n=3) Uomo et al. (1994)86 Case report (n=2) Llach et al. (1997)87 Case report (n=2) Sbeih et al. (1997)88 Case report (n=2) Berger et al. (1998)89 Letter to the editor (n=2) ERCP with sphincterotomy for gallstone pancreatitis. 1 patient developed exacerbation of gallstone pancreatitis after sphincterotomy and balloon pullthrough which rapidly resolved and the patient was discharged 4 days afterwards. No maternal complications in other 2 patients ERCP with sphincterotomy and stone removal in first trimester of pregnancy for cholangitis. No procedural complications ERCP for gallstone pancreatitis during second trimester of pregnancy. Both mothers did very well after ERCP, sphincterotomy, and stone extraction by balloon sweep-through ERCP during pregnancy for CBD stones, ascending cholangitis, and gallstone pancreatitis. Stones were successfully extracted by ERCP, sphincterotomy, and balloon sweep-through in both patients without complications. Both mothers did well ERCP for abdominal pain and obstructive jaundice with CBD dilatation. ERCP revealed CBD stones in both cases. Both patients rapidly recovered after sphincterotomy and stone extraction using balloon sweepthrough ERCP with sphincterotomy for gallstone pancreatitis. ERCP revelaed a passed CBD stone in 1 patient. Patient underwent laparoscopic cholecystectomy at 10 weeks gestation and subsequently did well. 1 patient underwent ERCP followed by sphincterotomy for stone extraction that was complicated by minor bleeding. Had stone extraction by Dormier basket. Patient subsequently did well 14 2 healthy infants delivered at term, 1 healthy infant preterm at 34 weeks 3 healthy infants delivered at term 2 healthy infants delivered at term 2 healthy infants 3 healthy infants delivered at term (one set of twins) 2 healthy infants Al Karawi et al. (1997)90 Case report (n=2) Hernandez et al. (2007)91 Retrospective clinical series (n=2) Kim et al. (1996)92 Case report in abstract form (n=2) Friedman et al. (1995)93 Case report (n=1) Eichenberg et al. (1996)94 Case report (n=1) Axelrad et al. (1994)95 Case report (n=1) Bagci et al. (2003)96 Case report (n=1) Lyilikci et al. (2007)97 Case report (n=1) Lu et al. (2004)98 Single case reported in a meta-analysis (n=1) ERCP performed for cholangitis with dilated CBD on abdominal ultrasound in 1 patient, and obstructive jaundice with dilated CBD on abdominal ultrasound in 1 patient. Stones were successfully extracted by ERCP with sphincterotomy and balloon sweep. No procedural complications reported ERCP and sphincterotomy for biliary pancreatitis. No ERCP related complications occurred during or after procedure. Both patients lost to followup after hospital discharge ERCP with sphincterotomy and stone extraction performed for abdominal pain and dilated CBD, and gallstone pancreatitis. Both patients “discharged in good condition” ERCP performed for abdominal pain and jaundice. Patient underwent successful ERCP, sphincterotomy, and stone extraction. Elective laparoscopic cholecystectomy performed 1 week later, with finding of chronic cholecystitis and single cystic duct stone. Patient subsequently did well ERCP with stone extraction performed for gallstone pancreatitis. Preterm initiation of labor successfully managed by tocolysis. Successful laparoscopic cholecystectomy performed soon after ERCP and patient discharged 3 days later ERCP performed for abdominal pain and obstructive jaundice with CBD dilatation on abdominal ultrasound.Failed cannulation of CBD at initial ERCP. Multiple CBD stones extracted after sphincterotomy and balloon sweep. Patient did well initially, but represented 3 weeks later with similar episode that was treated with ERCP and stent insertion ERCP performed for RUQ pain and jaundice 1 year after undergoing ERCP with sphincterotomy for CBD stones and subsequent cholecystectomy. ERCP performed without fluoroscopy. Sphincterotomy performed to enlarge existing sphincterotomy orifice. CBD stones extracted by balloon sweep. Patient did well ERCP performed during pregnancy for abdominal pain and jaundice, dilated CBD on abdominal ultrasound. ERCP revealed CBD stones. Treated with sphincterotomy and stone extraction. No further biliary problems during pregnancy Patient underwent successful ERCP and sphincterotomy without complications for gallstone pancreatitis and CBD stones 15 NA NA NA Healthy infant delivered at full term Healthy infant delivered “Uneventful delivery” at 39 weeks Healthy infant delivered at term Healthy infant delivered at term NA Freistuhler et al. (1999)99 Case report (n=1) Pasquale et al. (2007)100 Case report (n=1) Goldschmiedt et al. (1993)101 Case report (n=1) Binmoeller et al. (1990)102 Case report (n=1) Parada et al. (1991)103 Case report (n=1) Duseja et al. (2005)104 Letter to the editor (n=1) Zagoni et al. (1995)105 Letter to the editor (n=1) Rahmin et al. (1994)106 Letter to the editor (n=1) ERCP performed during pregnancy for pancreatitis, known gallstones, and severe cholestasis. Successful ERCP performed with sphincterotomy and removal of biliary sludge. Patient rapidly improved with normalization of liver function tests. Patient experienced impending abortion 8 days after ERCP that was successfully prevented by tocolysis ERCP with sphincterotomy and stone extraction for obstructive jaundice. Patient rapidly recovered after stone extraction. No procedural complications ERCP performed for persistent RUQ pain with abdominal ultrasound revealing a CBD stone. CBD stone successfully extracted after ERCP and sphincterotomy. Stent placed in cystic duct for residual gallbladder stones. Uncomplicated procedure. Patient rapidly improved ERCP performed for gallstone pancreatitis with a dilated CBD containing a CBD stone. Impacted CBD stone successfully removed after needle-knife sphincterotomy during ERCP. Patient rapidly recovered afterwards ERCP performed for jaundice with abdominal ultrasound demonstrating a dilated CBD containing a stone. ERCP with sphincterotomy was performed under ultrasound guidance without contrast radiography to avoid radiation exposure. Stone successfully passed after sphincterotomy. Procedure described as successful but patient outcome not reported ERCP performed for ascending cholangitis with CBD stones on abdominal ultrasound. Patient had nasobiliary drainage during ERCP without sphincterotomy for CBD decompression. ERCP repeated 15 days later for recurrent obstruction and cholangitis. Double-pigtail stent placed without sphincterotomy. Patient stable with no further attacks in 2 months of follow-up ERCP for abdominal pain and jaundice with CBD stones on abdominal ultrasound. Needle-knife sphincterotomy performed at site of bulging papilla with removal of 2 CBD stones without fluoroscopy. Patient did well ERCP performed for RUQ pain and jaundice with dilated CBD on abdominal ultrasound. Patient underwent ERCP, sphincterotomy, and stent deployment. No CBD stones reported but cholangiography was not performed to 16 Healthy infant delivered at 37 weeks Fetus is “in good health” after procedure pending delivery Healthy infant delivered by cesarean section at term NA NA Pregnancy proceeding normally at 24 weeks of gestation NA. “The remainder of her pregnancy was uneventful” minimize radiation exposure. Patient did well Martins et al. Case report (n=1) ERCP performed for recurrent gallstone Healthy, underweight (1997)107 pancreatitis presenting with nausea, infant delivered at 36 abdominal pain, and borderline weeks jaundice. Patient underwent ERCP and sphincterotomy. Patient improved and underwent cholecystectomy 15 days postpartum. Cases reported only in abstract form and excluded from analysis in the main text Garza et al. Abstract (n=48) Stone disease identified in 42 patients. 39 healthy infants, 1 (2001)108 All patients underwent sphincterotomy. elective abortion, 1 fetal Complications included 3 patients with death from glycogen pancreatitis, and 1 patient with minor storage disease, 2 post-sphincterotomy bleeding. spontaneous abortions, 2 Remaining patients did well. No patients doing well but still maternal deaths pregnant in third trimester, 3 patients lost to follow-up *case reports of ≤3 patients or of larger studies reported only as abstracts or as letters to the editor. Abbreviations: CBD, common bile duct; ERCP, endoscopic retrograde cholangiography; NA, not available; RUQ, right upper quadrant. 17 Table 9 | Summary of current recommendations for endoscopic procedures during pregnancy Procedure Diagnostic EGD Clinical studies Case-controlled retrospective study of 83 pregnancies, retrospective clinical series of 60 pregnancies, and 28 case reports Clinical series of 17 patients, clinical series of 10 patients, and 7 case reports General findings Very high rate of favorable fetal outcome (about 95% in both large studies) Recommendations EGD should be performed when strongly indicated after patient stabilization and once detailed informed consent is obtained Conflicting results of 67% vs. 100% for a good fetal outcome in the 2 clinical series Endoscopic banding of esophageal varices 8 case reports 6 favorable fetal outcomes, 1 infant born at 33 weeks of gestation but otherwise healthy, and 1 unknown fetal outcome Therapeutic endoscopic hemostasis of nonvariceal upper gastrointestinal bleeding 4 case reports 3 favorable pregnancy outcomes. 1 infant born prematurely (after emergency surgery for refractory upper gastrointestinal bleeding) Endoscopic botulinum toxin injection for achalasia 1 case report Mother did well. Healthy infant delivered at term Endoscopic balloon dilatation for achalasia 3 case reports 2 healthy infants delivered, 1 patient had late-term abortion for unstated reasons Sclerotherapy has been generally supplanted in the general population by endoscopic banding. Even though data on endoscopic banding during pregnancy are scant, endoscopic banding is apparently preferable to sclerotherapy during pregnancy on theoretical grounds of greater efficacy in nonpregnant population Despite scant data, variceal banding seems to be justified for recent variceal bleeding during pregnancy. See above recommendations under sclerotherapy Extremely limited clinical data during pregnancy. Based on extrapolating data from nonpregnant patients, therapeutic endoscopy seems to be indicated for ongoing upper gastrointestinal bleeding from a point source, and for a nonbleeding visible vessel within a peptic ulcer. Safest technique during pregnancy of (e.g. epinephrine, thermocoagulation, or electrocoagulation) is unknown Experimental therapy in pregnancy. May be considered as an alternative to surgery for pregnant mothers with severe dysphagia from achalasia that causes maternal weight loss that endangers fetal viability Experimental therapy in pregnancy. May be considered as alternative to surgery for pregnant mothers with severe dysphagia from achalasia that causes maternal weight loss that endangers fetal Sclerotherapy for esophageal varices 18 Percutaneous endoscopic gastrostomy 6 case reports 4 healthy infants, 1 infant that required artificial ventilation for 3 days after birth but subsequently developed normally, and 1 live-borne infant that died 2 weeks after delivery from a severe genetic disease Percutaneous endoscopic gastrojejunostomy 6 case reports 5 relatively healthy infants, 1 infant born alive but severely underweight at 27 weeks of gestation Video capsule endoscopy 2 case reports 2 relatively healthy infants Flexible sigmoidoscopy Case controlled study of 48 sigmoidoscopies in 46 patients, mailed survey of 13 patients, 14 case reports Therapeutic flexible sigmoidoscopy 5 case reports Colonoscopy Case-controlled study of 20 colonoscopies, clinical series of 8 patients, 11 individual case reports, and a In study of 46 patients: 38 healthy infants, 4 voluntary abortions, and 1 unknown pregnancy outcome. Poor outcomes included 1 stillbirth, 1 live-borne infant who died of prematurity, and 1 infant with cleft palate. Similar outcomes in mailed survey and case reports Partial colonoscopy to relieve uterus incarcerated by sacral promontory. Procedure successfully relieved uterine incarceration. No pregnancy losses due to procedure, but pregnancy outcomes not reported In study of 20 colonoscopies: 18 favorable fetal outcomes, 1 involuntary abortion, 1 congenital cardiac defect. In clinical series 19 viability Experimental therapy in pregnancy. Procedure should be strongly considered for hyperalimentation when fetal viability is endangered by maternal malnutrition and weight loss, and when the alternatives are central line hyperalimentation or surgical gastrostomy Experimental therapy in pregnancy. Procedure should be strongly considered for hyperalimentation when fetal viability is endangered by maternal malnutrition and weight loss, and when percutaneous endoscopic gastrostomy is not tolerated due to refractory nausea and vomiting Experimental procedure in pregnancy. May be considered for lifethreatening bleeding after nondiagnostic EGD and colonoscopy when alternatives are mesenteric angiography or abdominal surgery Flexible sigmoidoscopy justified during pregnancy when strongly indicated Experimental therapy in pregnancy that may be considered by an expert endoscopist in consultation with an obstetrician for uterine incarceration Colonoscopy should be considered for strong indications during the second trimester because the evidence is strongest for this trimester. Procedure is experimental in first and mailed survey of 13 cases of 8 colonoscopies: 6 healthy infants, 1 voluntary abortion, and 1 miscarriage 4 months after colonoscopy. Other data show similar fetal outcomes Therapeutic ERCP 46 studies involving 296 therapeutic ERCPs Endoscopic ultrasound 1 clinical series of 6 patients, 1 letter to the editor reporting 3 cases, and 2 case reports ~90% ERCP success rate. Maternal complications included pancreatitis (6.4%), postsphincterotomy bleeding (1.0%) and other(3%). Fetal outcomes included 237 healthy infants, 11 premature infants with low birth weight, 3 late spontaneous abortions, 2 infant deaths after live birth, 1 voluntary abortion. 42 unknown fetal outcomes 2 fetal deaths from recurrent maternal cholangitis or from HELLP syndrome Endoscopic spyscopy (Spy scope, Novadaq Technologies, Bonita Springs, Florida, USA) 1 clinical series of 5 patients third trimesters and should be considered when extremely strongly indicated (e.g. suspected colon cancer or colonic mass). Colonoscopy should be aborted if poorly tolerated by the mother or by the fetus as indicated by monitoring ERCP should be performed when strongly indicated for endoscopic therapy. Precautions to minimize radiation exposure are listed in Tbles 8and 9 in the main text. ERCP should not be performed during pregnancy for weak indications, such as for exclusively diagnostic ERCP Data too limited to provide firm conclusions. Consider endoscopic ultrasound when choledocholithiasis is a possible but unproven diagnosis and magnetic resonance cholangiography is an undesirable alternative Data too limited to provide firm conclusions, but this technology provides an attractive way to confirm choledochal stone removal without exposing the fetus to ionizing radiation Spy scope used during endoscopic ultrasound after ERCP, sphincterotomy and balloon stone removal. Successful application in all cases with no maternal complications. 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