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.
Fetal outcomes not
specifically reported
Abbreviations: EGD, esophagogastroduodenoscopy; ERCP, endoscopic retrograde
cholangiopancreatography
20
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